WO2022054904A1 - Food composition, pharmaceutical composition, quasi drug composition, cosmetic composition and sundry article for preventing or treating covid-19 - Google Patents

Food composition, pharmaceutical composition, quasi drug composition, cosmetic composition and sundry article for preventing or treating covid-19 Download PDF

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WO2022054904A1
WO2022054904A1 PCT/JP2021/033292 JP2021033292W WO2022054904A1 WO 2022054904 A1 WO2022054904 A1 WO 2022054904A1 JP 2021033292 W JP2021033292 W JP 2021033292W WO 2022054904 A1 WO2022054904 A1 WO 2022054904A1
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composition
pharmaceutically acceptable
extract
prophylactic
quasi
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PCT/JP2021/033292
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French (fr)
Japanese (ja)
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明秀 梁
敬 宮川
武志 森田
智子 國吉
金緯 楊
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公立大学法人横浜市立大学
株式会社常磐植物化学研究所
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Publication of WO2022054904A1 publication Critical patent/WO2022054904A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/12Ketones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/438The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/74Rubiaceae (Madder family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/906Zingiberaceae (Ginger family)
    • A61K36/9068Zingiber, e.g. garden ginger
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9794Liliopsida [monocotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00Make-up preparations; Body powders; Preparations for removing make-up
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/02Preparations for cleaning the hair
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/06Preparations for styling the hair, e.g. by temporary shaping or colouring

Definitions

  • the present invention relates to food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods for the prevention or treatment of new coronavirus infections.
  • the new coronavirus infection (COVID-19) was confirmed in Wuhan City, Hubei province, China in December 2019, and the infection has spread all over the world.
  • the causative new coronavirus (SARS-CoV-2) is a type of coronavirus and is a plus-strand RNA virus belonging to the coronavirus subfamily of the coronaviridae family.
  • coronaviruses include the Severe Respiratory Syndrome (SARS) virus that prevailed mainly in Asia in 2003 and the Middle East Respiratory Syndrome (MERS) virus that has spread in the Middle East since 2012. ..
  • SARS Severe Respiratory Syndrome
  • MERS Middle East Respiratory Syndrome
  • the main symptoms of the new coronavirus infection are fever, general malaise, and respiratory symptoms.
  • Non-Patent Documents 1 and 2 there is a report using the molecular docking method for the interaction between naturally occurring components and the new coronavirus (SARS-CoV-2) protein, and epigallocatechin gallate, anthocyanidins, curcumin, etc. may have antiviral effects. It is shown as being (Non-Patent Documents 1 and 2).
  • the present invention is a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic product for the prevention or treatment of a new type of coronavirus infection containing a natural product which is highly safe and whose raw material is easily available.
  • the purpose is to provide compositions and miscellaneous goods.
  • the inventor of the present invention relates to a prophylactic or therapeutic agent for a new type of coronavirus infection, which is a highly safe natural product and can be widely used in foods, pharmaceuticals, quasi-drugs, cosmetics, and miscellaneous goods.
  • a prophylactic or therapeutic agent for a new type of coronavirus infection which is a highly safe natural product and can be widely used in foods, pharmaceuticals, quasi-drugs, cosmetics, and miscellaneous goods.
  • the present invention relates to cat's claw extract, ginger extract, Pteropodine and its quasi-drugs, Isopteropodine and its quasi-drugs, 6-Gingerol and its quasi-drugs ether.
  • a composition, a cosmetic composition or a quasi-drug are examples of a cosmetic composition or a quasi-drug.
  • the present invention is as follows. That is, the prophylactic or therapeutic agent for the new coronavirus infection according to one aspect of the present invention contains a cat's claw (Uncaria tomentosa) extract, and is preferably blended with this as an active ingredient.
  • a cat's claw Uncaria tomentosa
  • agent in a preventive agent or a therapeutic agent is a term used as an auxiliary term, and “agent” is used as a meaning of a substance having a pharmacological function, but this does not necessarily mean a pharmaceutical composition (drug).
  • This preventive agent and therapeutic agent can be used as an active ingredient in food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, or miscellaneous goods.
  • the prophylactic or therapeutic agent for a new type of coronavirus infection contains a ginger (Zingiber office) extract, and is preferably blended with this as an active ingredient. ..
  • the prophylactic or therapeutic agent for a new type coronavirus infection contains at least one of Pteropodine and a pharmaceutically acceptable salt thereof, and is preferable. Is compounded as an active ingredient.
  • the prophylactic or therapeutic agent for a new type of coronavirus infection contains at least one of Isopteropodyne and a pharmaceutically acceptable salt, which is preferably used. It is compounded as an active ingredient.
  • the prophylactic or therapeutic agent for the new coronavirus infection contains at least one of 6-Gingerol and a pharmaceutically acceptable ether, and is preferable. This is blended as an active ingredient.
  • the pharmaceutical composition for preventing or treating a new type of coronavirus infection contains at least one of 6-shogaol and a pharmaceutically acceptable ether. This is preferably blended as an active ingredient.
  • compositions As described above, according to the present invention, food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetics for the prevention or treatment of new coronavirus infections containing natural products that are highly safe and easily available as raw materials are used.
  • Compositions and miscellaneous goods can be provided.
  • the present invention is a naturally derived extract or compound, and since it is excellent in safety, it is suitable for use in foods, pharmaceuticals, quasi-drugs, cosmetics, and miscellaneous goods.
  • the prophylactic or therapeutic agents for the novel coronavirus infection of the present invention include cat's claw extract, ginger extract, Pteropodine and its pharmaceutically acceptable salt, Isopteropodine and its pharmaceutically acceptable salt, 6-Gingerol. And its pharmaceutically acceptable ether, and at least one of 6-shogaol and its pharmaceutically acceptable ether, preferably containing at least one of these as an active ingredient. It also contains other ingredients as needed.
  • each plant extract includes an extract of an extraction raw material, a dried product obtained by drying a diluted solution of the extract, or a crude product or a purified product thereof.
  • the site where the extraction raw material is used is not limited as long as the above effects can be obtained, but it is preferable to use bark for the cat's claw extract and rhizome for the ginger extract.
  • the extraction method of the above plant extract is not particularly limited, and can be carried out according to a method well known to those skilled in the art.
  • the extraction solvent water, an alcohol solvent, and an organic solvent such as acetone, esters, polyhydric alcohols, and ethers can be used. These solvents may be used alone or in combination. Among these, it is preferable to use ethanol, and it is more preferable to use hydrous ethanol having an ethanol content of 10% to 95% (v / v).
  • the amount of the extraction solvent, the extraction temperature, the extraction time and the extraction method are not limited as long as the present composition exhibiting the above effects can be obtained.
  • the amount of the extraction solvent is preferably 1 to 100 parts by weight with respect to the dry weight of the raw material.
  • the extraction temperature is preferably 4 to 90 ° C.
  • the extraction time is preferably 30 minutes to 1 week.
  • the extraction method can be any method such as stirring extraction, immersion extraction, countercurrent extraction, ultrasonic extraction, and supercritical extraction.
  • the above-mentioned extract is a filtrate itself obtained by filtering the obtained extract, a concentrated solution obtained by concentrating the filtrate, a dried product obtained by drying the concentrated solution, and a crude or purified product thereof. May be good.
  • the concentration method and the drying method can be performed by any method. Excipients such as dextrin may be added if necessary. Purification can be carried out according to means known to those skilled in the art, such as synthetic adsorption resin, activated carbon, ion exchange resin, column chromatography, and recrystallization.
  • Pteropodine, Isopteropodyne, 6-Gingerol, and 6-Shogaol can also be produced by organically synthesizing, but are preferably derived from plants. These compounds are obtained by extracting from plants, and the extract is recovered by filtration, centrifugation, etc., and then purified by treatment such as concentration, adsorption, separation, elution, solvent removal, etc. It is preferable to have. Examples of plants used for extraction include cat's claw (Uncaria tomentosa) and ginger (Zingiber office). The synthesis method is not particularly limited, and a conventionally known method can be used.
  • the structure of the compound obtained by synthesis or purification can be identified according to means known to those of skill in the art. For example, proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), mass analysis (MS), elemental analysis, infrared spectroscopy (IR), ultraviolet spectroscopy (UV). ), The melting point measurement method, etc. may be used alone or in combination.
  • the above compound can also be obtained by extracting and purifying cat's claw (Uncaria tomentosa) and ginger (Zingiber office), the above cat's claw extract and ginger extract are preventive agents or treatments for new coronavirus infections. It is considered that it can also be used as an agent.
  • the "pharmaceutically acceptable salt” is typically a salt produced by the reaction of the above-mentioned compound with an acid or a base
  • the "pharmaceutically acceptable ether” is typical. Refers to an ether produced by the reaction of the above compound with an alcohol, an alkoxide, or an organic halogen compound, which can maintain the effect of the above-mentioned compound for prevention or treatment of a new type coronavirus infection.
  • it is suitable for blending in the food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, and miscellaneous goods of the present invention described below.
  • the food composition is not particularly limited and may be appropriately selected depending on the intended purpose.
  • beverages such as soft beverages, carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages; candy, candy, chewables, jelly. , Gum, chocolate and other confectionery; various forms of health foods such as granules, tablets, capsules, drinks, functional foods and nutritional supplements.
  • the pharmaceutical composition is not particularly limited and can be appropriately selected according to the purpose, and examples thereof include tablets, capsules, drinks, and troches.
  • the quasi-drug composition is not particularly limited and may be appropriately selected according to the purpose.
  • disinfectants, masks, hand gels, medicated soaps, mouthwashes, bath salts, medicated toothpaste and the like can be used. Can be mentioned.
  • the cosmetic composition is not particularly limited and may be appropriately selected according to the purpose, and examples thereof include cosmetics, cosmetics, creams, milky lotions, hair styling products, hair washing products, and finishing cosmetics.
  • the miscellaneous goods are not particularly limited and may be appropriately selected according to the purpose.
  • disinfectant for example, disinfectant, mask, gloves, face shield, hand gel, spray, wet tissue, air purifier, aroma oil, etc.
  • soap and toothpaste examples include soap and toothpaste.
  • the food composition for the prevention or treatment of the new coronavirus infection, the pharmaceutical composition, the quasi-drug composition, the cosmetic composition, and the miscellaneous goods are suitably applied to humans, but each of them is used. It can also be applied to animals other than humans as long as the effect is obtained.
  • food compositions, pharmaceutical compositions, and pharmaceuticals for the prevention or treatment of new coronavirus infections containing natural products or compounds derived from natural products, which are highly safe and easily available as raw materials, are contained. It is possible to provide quasi-drug compositions, cosmetic compositions, and miscellaneous goods.
  • Example 1 Infection suppression effect of new coronavirus- Using the compounds of Production Examples 1 to 4 as samples, the infection-suppressing effect of the new coronavirus was evaluated by the following test method.
  • the IC50s of Production Examples 2 to 4 were calculated using the cell viability of VeroE6 / TMPRSS2 cells as an index.
  • Example 2 Virus infection was visualized by immunostaining with an antibody against SARS-CoV-2 Nprotein.
  • Blocking One TM Blocking One TM .
  • Immunostaining was carried out using SARS-CoV-2 Nucleocapsid Protein antibody (1: 100 dilution, Novus NB100-56576) for 1 hour at room temperature, followed by Alexa 568-labele anti-rabbit antibody (1: 100 dilution, Ther). Staining was performed at room temperature for 1 hour. Cell nuclei were stained with Prolong Gold Antifade Mount with DAPI (Thermo).
  • Example 3 We investigated whether the infection-suppressing effect on SARS-CoV-2 acts on cell invasion or after cell invasion.
  • CellTiter-Glo TM was added 48 hours after infection and cell viability was measured.
  • Coronavirus synthesizes a peptide having a function by synthesizing a polyprotein, cleaving it at three sites with a papain-like enzyme, and then cleaving it at 11 sites with a 3CL protease.
  • a test system that can detect the cleavage reaction of polyprotein by protease by the Western Brod method, the inhibitory effect of protease on cleavage of polyprotein was investigated.
  • a peptide having an amino acid sequence cleaved by the new coronavirus SARS-CoV-23C L protease and 3CL protease (FLAG-TSITSAVLQ ⁇ SGFRKMAFP-GST-biotin) was synthesized using a wheat cell-free protein synthesis system. Add the synthesized protease and substrate, and Production Examples 2 and 3 at a final concentration of 500 ⁇ M, react at 37 ° C. for 3 hours, perform SDS-PAGE using 13% polyacrylamide gel, transfer to PVDF membrane, and blocking One. Blocking treatment was performed by TM at room temperature for 15 minutes. Then, detection was performed using anti-streptavidin-HRP antibody (1: 5000 dilution).
  • the present invention relates to cat's claw extract, ginger extract, Pteropodine and its quasi-drug salt, Isopteropodine and its quasi-drug salt, 6-Gingerol and its pharmaceutically acceptable ether, and the like.

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Abstract

The purpose of the present invention is to provide a food composition, a pharmaceutical composition, a quasi drug composition, a cosmetic composition and a sundry article, each being for preventing or treating COVID-19. A food composition, a pharmaceutical composition, a quasi drug composition, a cosmetic composition and a sundry article, each being for preventing or treating COVID-19 and comprising at least one member selected from among a cat's claw extract, a ginger extract, pteropodine and a pharmaceutically acceptable salt thereof, isopteropodine and a pharmaceutically acceptable salt thereof, 6-gingerol and a pharmaceutically acceptable ether thereof and 6-shogaol and a pharmaceutically acceptable ether thereof.

Description

新型コロナウイルス感染症の予防又は治療用の食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、及び雑貨Food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods for the prevention or treatment of new coronavirus infections.
本発明は、新型コロナウイルス感染症の予防又は治療用の食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、及び雑貨に関する。 The present invention relates to food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods for the prevention or treatment of new coronavirus infections.
新型コロナウイルス感染症(COVID-19)は、中国湖北省武漢市で2019年12月に感染者が確認され、世界各地に感染が拡大している。原因となる新型コロナウイルス(SARS-CoV-2)はコロナウイルスの一種で、コロナウイルス科のコロナウイルス亜科に属するプラス鎖RNAウイルスである。コロナウイルスは一般的な風邪の原因のほか、2003年にアジアを中心に流行した重症呼吸器症候群(SARS)や2012年以降中東地域で広がっている中東呼吸器症候群(MERS)のウイルスも含まれる。新型コロナウイルス感染症の主な症状は発熱や全身倦怠感、呼吸器症状で、約8割は軽症のまま治癒するが、約2割は肺炎症状が悪化し、約5%は人工呼吸管理などが必要な重症例となるとされ、容態が急激に悪化する例も報告されている。重症化の要因として、免疫細胞からの過剰なサイトカイン放出であるサイトカインストームによって過剰な免疫反応が起き、肺などの臓器が障害されることが考えられている。 The new coronavirus infection (COVID-19) was confirmed in Wuhan City, Hubei Province, China in December 2019, and the infection has spread all over the world. The causative new coronavirus (SARS-CoV-2) is a type of coronavirus and is a plus-strand RNA virus belonging to the coronavirus subfamily of the coronaviridae family. In addition to the common causes of colds, coronaviruses include the Severe Respiratory Syndrome (SARS) virus that prevailed mainly in Asia in 2003 and the Middle East Respiratory Syndrome (MERS) virus that has spread in the Middle East since 2012. .. The main symptoms of the new coronavirus infection are fever, general malaise, and respiratory symptoms. About 80% of them are cured with mild symptoms, but about 20% have worsening pneumonia and about 5% have artificial respiration management. It is said that this is a serious case that requires, and there have been reports of cases in which the condition deteriorates sharply. As a factor of aggravation, it is considered that an excessive immune reaction occurs due to a cytokine storm, which is an excessive release of cytokines from immune cells, and an organ such as a lung is damaged.
 また、本件出願日現在、新型コロナウイルス感染症に対する特異的な治療薬は存在せず、既存薬の転用に留まっている。抗エボラウイルス薬レムデシビルが重症の新型コロナウイルス感染者の治療期間を短縮する効果などが確認され、日本国内で特例承認を受けている。しかしながら、投薬の対象は原則として重症患者であるほか、腎機能障害や肝機能障害の頻度が高いとされるなど安全性に懸念がある。さらに、レムデシビルは供給量が限定されているという課題もある。また、ステロイド薬であるデキサメタゾンも重症例の死亡を減少させたとの報告があり、新型コロナウイルス感染症に対する治療薬として国内で2例目の承認となったが、米国NIHの治療ガイドラインでは重症患者への使用を推奨しており、軽症者に対する治療法は確立されていない。その他の治療薬は適応外使用となり、有効性や安全性については検証途中で不明瞭である。また、一般的にウイルスの感染予防手段として効果的なワクチン接種については、臨床試験が開始されているワクチンもあるものの、実用化には至っていない。こうした現状から、新型コロナウイルスに効果があり、なおかつ安全性が高く安定的に供給できる予防剤や治療剤の開発は喫緊の課題である。 In addition, as of the filing date of this case, there is no specific therapeutic drug for the new coronavirus infection, and the existing drug is only diverted. It has been confirmed that the anti-Ebola virus drug remdesivir has the effect of shortening the treatment period for patients infected with the severe new coronavirus, and has received special approval in Japan. However, as a general rule, the subjects of medication are severely ill patients, and there are concerns about safety, such as the high frequency of renal dysfunction and hepatic dysfunction. Another problem is that the supply of remdesivir is limited. In addition, it has been reported that dexamethasone, a steroid drug, also reduced the number of deaths in severe cases, and it was approved as the second treatment drug for new coronavirus infection in Japan. It is recommended for use in, and no cure has been established for mildly ill patients. Other therapeutic agents are off-label use, and their efficacy and safety are unclear during verification. In addition, although there are vaccines for which clinical trials have been started for vaccination that is generally effective as a means of preventing virus infection, it has not been put into practical use. Under these circumstances, it is an urgent task to develop preventive and therapeutic agents that are effective against the new coronavirus, are highly safe, and can be stably supplied.
 一方、天然由来成分と新型コロナウイルス(SARS-CoV-2)タンパク質の相互作用について、分子ドッキング法を用いた報告があり、エピガロカテキンガレートやアントシアニジン、クルクミンなどが抗ウイルス作用を有する可能性があるとして示されている(非特許文献1、2)。 On the other hand, there is a report using the molecular docking method for the interaction between naturally occurring components and the new coronavirus (SARS-CoV-2) protein, and epigallocatechin gallate, anthocyanidins, curcumin, etc. may have antiviral effects. It is shown as being (Non-Patent Documents 1 and 2).
 しかしながら、これらはコンピューターによるシミュレーションの結果であり、細胞や動物レベルで効果の実証はされていない。上記の通り、現時点で使用されている治療薬は安全性に懸念が残り、供給量も限られるため、こうした課題を解決できる安全性の高い、原料の入手が容易な天然物を利用した予防又は治療用食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、及び雑貨等の提供が望まれている。 However, these are the results of computer simulations, and their effects have not been demonstrated at the cellular or animal level. As mentioned above, there are still concerns about the safety of the therapeutic agents currently used, and the supply is limited. Therefore, prevention or prevention using natural products with high safety and easy availability of raw materials can solve these problems. It is desired to provide therapeutic food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, miscellaneous goods and the like.
 本発明は、上記した従来における問題を解決し、以下の目的を達成することを課題とする。即ち、本発明は、安全性が高く、原料の入手が容易な天然物を含有成分とする新型コロナウイルス感染症の予防又は治療用食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、及び雑貨を提供することを目的とする。 It is an object of the present invention to solve the above-mentioned conventional problems and to achieve the following objects. That is, the present invention is a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic product for the prevention or treatment of a new type of coronavirus infection containing a natural product which is highly safe and whose raw material is easily available. The purpose is to provide compositions and miscellaneous goods.
 上記課題を解決するため、安全性の高い天然物であって、食品、医薬品、医薬部外品、化粧品、雑貨に広く使用可能な新型コロナウイルス感染症の予防剤又は治療剤について、本発明者らが鋭意検討を重ねた結果、本発明に至った。 In order to solve the above problems, the inventor of the present invention relates to a prophylactic or therapeutic agent for a new type of coronavirus infection, which is a highly safe natural product and can be widely used in foods, pharmaceuticals, quasi-drugs, cosmetics, and miscellaneous goods. As a result of repeated diligent studies, the present invention was reached.
 すなわち、本発明は、キャッツクロー抽出物、ショウガ抽出物、Pteropodine及びその薬学的に許容される塩、Isopteropodine及びその薬学的に許容される塩、6-Gingerol及びその薬学的に許容されるエーテル、並びに、6-Shogaol及びその薬学的に許容されるエーテルの少なくともいずれかを含む、好ましくは有効成分として含む新型コロナウイルスに対する予防又は治療の効果を有する食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物又は雑貨である。これまでにキャッツクロー抽出物、ショウガ抽出物、Pteropodine、Isopteropodine、6-Gingerol、6-Shogaolの新型コロナウイルスに対する効果は全く知られておらず、本発明者らの鋭意研究による新知見である。 That is, the present invention relates to cat's claw extract, ginger extract, Pteropodine and its quasi-drugs, Isopteropodine and its quasi-drugs, 6-Gingerol and its quasi-drugs ether. In addition, food compositions, pharmaceutical compositions, quasi-drugs having prophylactic or therapeutic effects against the new coronavirus, preferably containing at least one of 6-Gingerol and its pharmaceutically acceptable ethers, preferably as an active ingredient. A composition, a cosmetic composition or a quasi-drug. So far, the effects of cat's claw extract, ginger extract, Pteropodine, Isopteropodine, 6-Gingerol, and 6-Shogalol on the new coronavirus have not been known at all, and it is a new finding by the present inventors.
より具体的に、本発明は以下のとおりである。すなわち、本発明の一観点に係る新型コロナウイルス感染症の予防剤又は治療剤は、キャッツクロー(Uncaria tomentosa)抽出物を含有するものであり、好ましくはこれを有効成分として配合するものである。ここで予防剤、治療剤における「剤」は、助数詞として用いる用語であって、薬理的な機能を有するものの意味として「剤」を用いているが、これは必ずしも医薬品組成物(薬剤)を意味するものではなく、この予防剤、治療剤は、その有効成分として、食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、又は、雑貨中に利用されうるものである。 More specifically, the present invention is as follows. That is, the prophylactic or therapeutic agent for the new coronavirus infection according to one aspect of the present invention contains a cat's claw (Uncaria tomentosa) extract, and is preferably blended with this as an active ingredient. Here, "agent" in a preventive agent or a therapeutic agent is a term used as an auxiliary term, and "agent" is used as a meaning of a substance having a pharmacological function, but this does not necessarily mean a pharmaceutical composition (drug). This preventive agent and therapeutic agent can be used as an active ingredient in food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, or miscellaneous goods.
 また、本発明の他の一観点に係る新型コロナウイルス感染症の予防剤又は治療剤は、ショウガ(Zingiber officinale)抽出物を含有するものであり、好ましくはこれを有効成分として配合するものである。 Further, the prophylactic or therapeutic agent for a new type of coronavirus infection according to another aspect of the present invention contains a ginger (Zingiber office) extract, and is preferably blended with this as an active ingredient. ..
 また、本発明の他の一観点に係る新型コロナウイルス感染症の予防剤又は治療剤は、Pteropodine、及び、その薬学的に許容される塩の少なくともいずれかを含有するものであり、好ましくはこれを有効成分として配合するものである。 Further, the prophylactic or therapeutic agent for a new type coronavirus infection according to another aspect of the present invention contains at least one of Pteropodine and a pharmaceutically acceptable salt thereof, and is preferable. Is compounded as an active ingredient.
 また、本発明の他の一観点に係る新型コロナウイルス感染症の予防剤又は治療剤は、Isopteropodine、及び、薬学的に許容される塩の少なくともいずれかを含有するものであり、好ましくはこれを有効成分として配合するものである。 In addition, the prophylactic or therapeutic agent for a new type of coronavirus infection according to another aspect of the present invention contains at least one of Isopteropodyne and a pharmaceutically acceptable salt, which is preferably used. It is compounded as an active ingredient.
 また、本発明の他の一観点に係る新型コロナウイルス感染症の予防剤又は治療剤は、6-Gingerol、及び、薬学的に許容されるエーテルの少なくともいずれかを含有するものであり、好ましくはこれを有効成分として配合するものである。 Further, the prophylactic or therapeutic agent for the new coronavirus infection according to another aspect of the present invention contains at least one of 6-Gingerol and a pharmaceutically acceptable ether, and is preferable. This is blended as an active ingredient.
 また、本発明の他の一観点に係る新型コロナウイルス感染症の予防又は治療用医薬品組成物は、6-Shogaol、及び、薬学的に許容されるエーテルの少なくともいずれかを含有するものであり、好ましくはこれを有効成分として配合するものである。 In addition, the pharmaceutical composition for preventing or treating a new type of coronavirus infection according to another aspect of the present invention contains at least one of 6-shogaol and a pharmaceutically acceptable ether. This is preferably blended as an active ingredient.
 以上、本発明により、安全性が高く、原料の入手が容易な天然物を含有成分とする新型コロナウイルス感染症の予防又は治療用食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、及び雑貨を提供することができる。本発明は天然由来抽出物、又は化合物であり、安全性に優れるため、食品、医薬品、医薬部外品、化粧品、雑貨に配合、又は添加して用いるのに好適なものである。 As described above, according to the present invention, food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetics for the prevention or treatment of new coronavirus infections containing natural products that are highly safe and easily available as raw materials are used. Compositions and miscellaneous goods can be provided. The present invention is a naturally derived extract or compound, and since it is excellent in safety, it is suitable for use in foods, pharmaceuticals, quasi-drugs, cosmetics, and miscellaneous goods.
実施例における図に関する簡単な説明は以下のようである。
製造例1~製造例4の新型コロナウイルスの感染抑制効果を示す図である。 SARS-CoV-2 Nproteinに対する抗体を用いた免疫染色の結果を示す図である。 SARS-CoV-2に対する感染抑制効果の確認に関するグラフである。 プロテアーゼによるポリプロテインの切断への阻害作用に関する結果を示す図である。
A brief description of the figures in the examples is as follows.
It is a figure which shows the infection suppression effect of the new type coronavirus of Production Examples 1 to 4. It is a figure which shows the result of the immunostaining using the antibody against SARS-CoV-2 Nprotein. It is a graph regarding the confirmation of the infection suppression effect on SARS-CoV-2. It is a figure which shows the result about the inhibitory effect on the cleavage of a polyprotein by a protease.
 以下、本発明の実施形態について詳細に説明する。本発明は多くの異なる形態による実施が可能であり、以下に示す実施形態や実施例の具体的例示にのみ限定されるわけではない。 Hereinafter, embodiments of the present invention will be described in detail. The present invention can be implemented in many different embodiments and is not limited to the specific examples of the embodiments and examples shown below.
 本発明の新型コロナウイルス感染症の予防剤又は治療剤は、キャッツクロー抽出物、ショウガ抽出物、Pteropodine及びその薬学的に許容される塩、Isopteropodine及びその薬学的に許容される塩、6-Gingerol及びその薬学的に許容されるエーテル、並びに、6-Shogaol及びその薬学的に許容されるエーテルの少なくともいずれかを含有するものであり、好ましくはこれらの少なくともいずれかを有効成分として含有してなり、更に必要に応じてその他の成分を含有してなる。 The prophylactic or therapeutic agents for the novel coronavirus infection of the present invention include cat's claw extract, ginger extract, Pteropodine and its pharmaceutically acceptable salt, Isopteropodine and its pharmaceutically acceptable salt, 6-Gingerol. And its pharmaceutically acceptable ether, and at least one of 6-shogaol and its pharmaceutically acceptable ether, preferably containing at least one of these as an active ingredient. It also contains other ingredients as needed.
 前記キャッツクロー抽出物、ショウガ抽出物は、植物の抽出に一般的に用いられている方法により容易に得ることができる。なお、各植物抽出物には、抽出原料の抽出液、該抽出液の希釈液を乾燥して得られる乾燥物、又はこれらの粗精製物もしくは精製物のいずれもが含まれる。また、抽出原料の使用部位は、上記効果を得ることができる限りにおいて限定されるものではないが、キャッツクロー抽出物は樹皮、ショウガ抽出物は根茎を用いるのが好ましい。 The cat's claw extract and ginger extract can be easily obtained by a method generally used for extracting plants. In addition, each plant extract includes an extract of an extraction raw material, a dried product obtained by drying a diluted solution of the extract, or a crude product or a purified product thereof. The site where the extraction raw material is used is not limited as long as the above effects can be obtained, but it is preferable to use bark for the cat's claw extract and rhizome for the ginger extract.
 また、上記の植物抽出物の抽出方法は特に制限されず、当業者に周知の方法にしたがって行うことができる。抽出溶媒としては、水、アルコール系溶媒、およびアセトン、エステル類、多価アルコール類、エーテル類等の有機溶媒を用いることができる。これらの溶媒は単独で使用してもよいし、組み合わせて使用してもよい。これらの中でもエタノールを用いることが好ましく、エタノール含量が10%~95%(v/v)の含水エタノールを用いることがより好ましい。抽出溶媒の量、抽出温度、抽出時間および抽出方法は、上記効果を発揮する本組成物を得ることができる限りにおいて限定されるものではない。抽出溶媒の量は原料の乾燥重量に対して、1~100重量部が好ましい。抽出温度は4~90℃が好ましい。抽出時間は30分~1週間が好ましい。抽出方法は攪拌抽出、浸漬抽出、向流抽出、超音波抽出、超臨界抽出などの任意の方法で行うことができる。 Further, the extraction method of the above plant extract is not particularly limited, and can be carried out according to a method well known to those skilled in the art. As the extraction solvent, water, an alcohol solvent, and an organic solvent such as acetone, esters, polyhydric alcohols, and ethers can be used. These solvents may be used alone or in combination. Among these, it is preferable to use ethanol, and it is more preferable to use hydrous ethanol having an ethanol content of 10% to 95% (v / v). The amount of the extraction solvent, the extraction temperature, the extraction time and the extraction method are not limited as long as the present composition exhibiting the above effects can be obtained. The amount of the extraction solvent is preferably 1 to 100 parts by weight with respect to the dry weight of the raw material. The extraction temperature is preferably 4 to 90 ° C. The extraction time is preferably 30 minutes to 1 week. The extraction method can be any method such as stirring extraction, immersion extraction, countercurrent extraction, ultrasonic extraction, and supercritical extraction.
また上記の抽出物は、得られた抽出液を濾過し得られた濾液そのもの、濾液を濃縮した濃縮液、濃縮液を乾燥して得られる乾燥物、これらの粗精製物又は精製物であってもよい。濃縮方法、乾燥方法は任意の方法で行うことができる。必要な場合にはデキストリンなどの賦形剤を入れてもよい。精製を行う場合は、合成吸着樹脂、活性炭、イオン交換樹脂、カラムクロマトグラフィー、再結晶など当業者に既知の手段に従って行うことができる。 Further, the above-mentioned extract is a filtrate itself obtained by filtering the obtained extract, a concentrated solution obtained by concentrating the filtrate, a dried product obtained by drying the concentrated solution, and a crude or purified product thereof. May be good. The concentration method and the drying method can be performed by any method. Excipients such as dextrin may be added if necessary. Purification can be carried out according to means known to those skilled in the art, such as synthetic adsorption resin, activated carbon, ion exchange resin, column chromatography, and recrystallization.
 Pteropodine、Isopteropodine、6-Gingerol、6-Shogaolは有機化学的に合成することによっても製造することが可能であるが、植物由来のものであることが好ましい。これらの化合物は植物から抽出することによって得られ、更にこれをろ過や遠心分離等で抽出液を回収し、これに濃縮、吸着、分離、溶出、溶媒除去などの処理をして精製したものであることが好ましい。抽出に使われる植物は、キャッツクロー(Uncaria tomentosa)、ショウガ(Zingiber officinale)が例として挙げられる。なお、合成方法は特に限定されるものではなく、従来公知の方法を利用することができる。 Pteropodine, Isopteropodyne, 6-Gingerol, and 6-Shogaol can also be produced by organically synthesizing, but are preferably derived from plants. These compounds are obtained by extracting from plants, and the extract is recovered by filtration, centrifugation, etc., and then purified by treatment such as concentration, adsorption, separation, elution, solvent removal, etc. It is preferable to have. Examples of plants used for extraction include cat's claw (Uncaria tomentosa) and ginger (Zingiber office). The synthesis method is not particularly limited, and a conventionally known method can be used.
合成または精製により得られた化合物の構造は、当業者に既知の手段に従って同定することができる。例えば、プロトン核磁気共鳴分光法(1H-NMR)、カーボン核磁気共鳴分光法(13C-NMR)、質量分析法(MS)、元素分析法、赤外分光法(IR)、紫外分光法(UV)、融点測定法などを単独で、または組み合わせて使用してもよい。 The structure of the compound obtained by synthesis or purification can be identified according to means known to those of skill in the art. For example, proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), mass analysis (MS), elemental analysis, infrared spectroscopy (IR), ultraviolet spectroscopy (UV). ), The melting point measurement method, etc. may be used alone or in combination.
上記化合物は、キャッツクロー(Uncaria tomentosa)やショウガ(Zingiber officinale)を抽出精製することによっても得られるものであるから、上記キャッツクロー抽出物やショウガ抽出物は新型コロナウイルス感染症の予防剤又は治療剤としても使用できるものと考えられる。 Since the above compound can also be obtained by extracting and purifying cat's claw (Uncaria tomentosa) and ginger (Zingiber office), the above cat's claw extract and ginger extract are preventive agents or treatments for new coronavirus infections. It is considered that it can also be used as an agent.
 また、上記化合物において、「薬学的に許容される塩」は、典型的には上記化合物と酸又は塩基との反応によって生じる塩であって、「薬学的に許容されるエーテル」は、典型的には上記化合物とアルコール、アルコキシド、有機ハロゲン化合物との反応によって生じるエーテルであって、上記化合物の新型コロナウイルス感染症の予防又は治療の効果を維持することができるものをいう。 Further, in the above-mentioned compound, the "pharmaceutically acceptable salt" is typically a salt produced by the reaction of the above-mentioned compound with an acid or a base, and the "pharmaceutically acceptable ether" is typical. Refers to an ether produced by the reaction of the above compound with an alcohol, an alkoxide, or an organic halogen compound, which can maintain the effect of the above-mentioned compound for prevention or treatment of a new type coronavirus infection.
 キャッツクロー抽出物、ショウガ抽出物、Pteropodine及びその薬学的に許容される塩、Isopteropodin及びその薬学的に許容される塩e、6-Gingerol及びその薬学的に許容されるエーテル、並びに、6-Shogaol及びその薬学的に許容されるエーテルは、優れた新型コロナウイルス感染症の予防及び治療効果を有する。特に、以下に説明する本発明の食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、雑貨に配合するのに好適である。 Cat's claw extract, ginger extract, Pteropodine and its pharmaceutically acceptable salt, Isopotapodin and its pharmaceutically acceptable salt e, 6-Gingerol and its pharmaceutically acceptable ether, and 6-Shogalol. And its pharmaceutically acceptable ethers have excellent prophylactic and therapeutic effects on new coronavirus infections. In particular, it is suitable for blending in the food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, and miscellaneous goods of the present invention described below.
 食品組成物としては、特に制限はなく、目的に応じて適宜選定することができるが、例えば、清涼飲料、炭酸飲料、栄養飲料、果実飲料、乳酸飲料等の飲料;飴、キャンディー、チュアブル、ゼリー、ガム、チョコレート等の菓子類;顆粒剤、錠剤、カプセル剤、ドリンク剤など種々の形態の健康食品、機能性表示食品や栄養補助食品が挙げられる。 The food composition is not particularly limited and may be appropriately selected depending on the intended purpose. For example, beverages such as soft beverages, carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages; candy, candy, chewables, jelly. , Gum, chocolate and other confectionery; various forms of health foods such as granules, tablets, capsules, drinks, functional foods and nutritional supplements.
 医薬品組成物としては、特に制限はなく、目的に応じて適宜選定することができるが、例えば、錠剤、カプセル剤、ドリンク剤、トローチなどが挙げられる。 The pharmaceutical composition is not particularly limited and can be appropriately selected according to the purpose, and examples thereof include tablets, capsules, drinks, and troches.
 医薬部外品組成物としては、特に制限はなく、目的に応じて適宜選定することができるが、例えば、消毒液、マスク、ハンドジェル、薬用石けん、うがい薬、入浴剤、薬用歯みがき粉などが挙げられる。 The quasi-drug composition is not particularly limited and may be appropriately selected according to the purpose. For example, disinfectants, masks, hand gels, medicated soaps, mouthwashes, bath salts, medicated toothpaste and the like can be used. Can be mentioned.
 化粧品組成物としては、特に制限はなく、目的に応じて適宜選定することができるが、例えば、化粧水、化粧液、クリーム、乳液、整髪料、洗髪料、仕上げ用化粧品などが挙げられる。 The cosmetic composition is not particularly limited and may be appropriately selected according to the purpose, and examples thereof include cosmetics, cosmetics, creams, milky lotions, hair styling products, hair washing products, and finishing cosmetics.
 また、雑貨としては、特に制限はなく、目的に応じて適宜選定することができるが、例えば、消毒液、マスク、手袋、フェイスシールド、ハンドジェル、スプレー、ウエットティッシュ、空気清浄器、アロマオイル、石けん、歯みがき粉などが挙げられる。 The miscellaneous goods are not particularly limited and may be appropriately selected according to the purpose. For example, disinfectant, mask, gloves, face shield, hand gel, spray, wet tissue, air purifier, aroma oil, etc. Examples include soap and toothpaste.
 なお、新型コロナウイルス感染症の予防又は治療用食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、雑貨は、ヒトに対して好適に適用されるものであるが、それぞれの作用効果が得られる限り、ヒト以外の動物に対して適用することもできる。 The food composition for the prevention or treatment of the new coronavirus infection, the pharmaceutical composition, the quasi-drug composition, the cosmetic composition, and the miscellaneous goods are suitably applied to humans, but each of them is used. It can also be applied to animals other than humans as long as the effect is obtained.
 以上、本実施形態により、安全性が高く、原料の入手が容易な天然物又は天然物由来の化合物を含有成分とする新型コロナウイルス感染症の予防又は治療用食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、雑貨を提供することができる。 As described above, according to the present embodiment, food compositions, pharmaceutical compositions, and pharmaceuticals for the prevention or treatment of new coronavirus infections containing natural products or compounds derived from natural products, which are highly safe and easily available as raw materials, are contained. It is possible to provide quasi-drug compositions, cosmetic compositions, and miscellaneous goods.
以下、本発明の実施例を説明するが、本発明は、これらの実施例に何ら限定されるものではない。 Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples.
(製造例1)
―Pteropodineの単離精製―
株式会社常磐植物化学研究所製のキャッツクロー(Uncaria tomentosa)抽出物を硫酸酸性条件下で加熱抽出する。pHを中性に調整後、等量のメタノール/クロロホルム混液を加えて、液-液分配を行った後、シリカゲルを用いたカラム精製を行った。Pteropodineが多く含まれる画分を濃縮・乾燥させ、再度シリカゲルを充填したカラムに吸着させ、ヘキサン/酢酸エチル混液を用いて溶出させた後、再結晶化し、Pteropodineを得た。構造は化学式(1)に示す。
Figure JPOXMLDOC01-appb-C000001
(Manufacturing Example 1)
-Isolation and purification of Pteropodine-
A cat's claw (Uncaria tomentosa) extract manufactured by Tokiwa Phytochemical Research Institute Co., Ltd. is heat-extracted under sulfuric acid acidic conditions. After adjusting the pH to neutral, an equal amount of methanol / chloroform mixed solution was added, liquid-liquid partitioning was performed, and then column purification using silica gel was performed. The fraction containing a large amount of Pteropodine was concentrated and dried, adsorbed again on a column packed with silica gel, eluted with a hexane / ethyl acetate mixed solution, and then recrystallized to obtain Pteropodine. The structure is shown in the chemical formula (1).
Figure JPOXMLDOC01-appb-C000001
<1H-NMR(500MHz,CDCl3)>
δ1.40(3H,d,J=6.1Hz,18-CH3)、1.51(1H,m,14β-H)、1.59(1H,m,20-H)、1.72(1H,ddd,J=12.1Hz,J=4.3Hz,J=4.3Hz,14α-H)、1.99(1H,m,6α-H)、2.32(1H,dd,J=12.1Hz,J=3.8Hz,21α-H)、2.36(1H,dd,J=12.1Hz,J=4.3Hz,3-H)、2.36(1H,m,5α-H)、2.40(1H,ddd,J=13.0Hz,J=12.5Hz,6β-H)、2.44(1H,ddd,J=12.1Hz,J=4.7Hz,J=4.3Hz,15-H)、3.30(1H,ddd,J=13.0Hz,J=8.5Hz,J=2.9Hz,5β-H)、3.32(1H,dd,J=12.1Hz,J=2.0Hz,21β-H)、3.60(3H,s,23-OCH3)、4.55(1H,qd,J=10.5Hz,J=6.1Hz,19-H)、6.87(1H,d,J=7.6Hz,12-H)、7.04(1H,ddd,J=7.6Hz,J=7.3Hz,J=1.0Hz,10-H)、7.18(1H,ddd,J=7.6Hz,J=7.6Hz,J=1.2Hz,11-H)、7.20(1H,d,J=7.3Hz,9-H)、7.41(1H,s,17-H)、8.52(1H,brs,NH)
<1H-NMR (500MHz, CDCl3)>
δ1.40 (3H, d, J = 6.1Hz, 18-CH3), 1.51 (1H, m, 14β-H), 1.59 (1H, m, 20-H), 1.72 (1H) , Ddd, J = 12.1Hz, J = 4.3Hz, J = 4.3Hz, 14α-H), 1.99 (1H, m, 6α-H), 2.32 (1H, dd, J = 12) .1Hz, J = 3.8Hz, 21α-H) 2.36 (1H, dd, J = 12.1Hz, J = 4.3Hz, 3-H) 2.36 (1H, m, 5α-H) ), 2.40 (1H, ddd, J = 13.0Hz, J = 12.5Hz, 6β-H), 2.44 (1H, ddd, J = 12.1Hz, J = 4.7Hz, J = 4) .3Hz, 15-H), 3.30 (1H, ddd, J = 13.0Hz, J = 8.5Hz, J = 2.9Hz, 5β-H), 3.32 (1H, dd, J = 12) .1Hz, J = 2.0Hz, 21β-H) 3.60 (3H, s, 23-OCH3), 4.55 (1H, qd, J = 10.5Hz, J = 6.1Hz, 19-H ), 6.87 (1H, d, J = 7.6Hz, 12-H), 7.04 (1H, ddd, J = 7.6Hz, J = 7.3Hz, J = 1.0Hz, 10-H. ), 7.18 (1H, ddd, J = 7.6Hz, J = 7.6Hz, J = 1.2Hz, 11-H), 7.20 (1H, d, J = 7.3Hz, 9-H). ), 7.41 (1H, s, 17-H), 8.52 (1H, brs, NH)
(製造例2)
―Isopteropodineの単離精製―
株式会社常磐植物化学研究所製のキャッツクロー(Uncaria tomentosa)抽出物を硫酸酸性条件下で加熱抽出する。pHを中性に調整後、等量のメタノール/クロロホルム混液を加えて、液-液分配を行った後、シリカゲルを用いたカラム精製を行った。ヘキサン/酢酸エチル溶出画分を濃縮・乾燥させた後、再度シリカゲルを用いたカラム精製を行った。ヘキサン/酢酸エチル混液を用いて溶出させた後、再結晶化し、Isopteropodineを得た。構造は化学式(2)に示す。
Figure JPOXMLDOC01-appb-C000002
(Manufacturing Example 2)
-Isolation and purification of Isopateropodine-
A cat's claw (Uncaria tomentosa) extract manufactured by Tokiwa Phytochemical Research Institute Co., Ltd. is heat-extracted under sulfuric acid acidic conditions. After adjusting the pH to neutral, an equal amount of methanol / chloroform mixed solution was added, liquid-liquid partitioning was performed, and then column purification using silica gel was performed. After concentrating and drying the hexane / ethyl acetate elution fraction, column purification using silica gel was performed again. After elution with a hexane / ethyl acetate mixed solution, it was recrystallized to obtain Isopteropodine. The structure is shown in the chemical formula (2).
Figure JPOXMLDOC01-appb-C000002
<1H-NMR(500MHz,CDCl3)>
δ0.88(1H,ddd,J=11.7Hz,J=11.7Hz,J=11.7Hz,14β-H)、1.41(3H,d,J=6.2Hz,18-CH3)、1.59(1H,m,20-H)、1.62(1H,ddd,J=11.7Hz,J=2.8Hz,J=2.8Hz,14α-H)、2.00(1H,ddd,J=11.9Hz,J=7.6Hz,J=7.6Hz,6α-H)、2.39(1H,ddd,J=11.9Hz,J=7.6Hz,J=2.4Hz,6β-H)、2.42(1H,dd,J=11.9Hz,J=3.8Hz,21-α)、2.46(1H,ddd,J=7.6Hz,J=7.6Hz,J=7.6Hz,5α-H)、2.51(1H,ddd,J=11.7Hz,J=2.8Hz,J=2.8Hz,15-H)、2.57(1H,dd,J=11.7Hz,J=2.8Hz,3-H)、3.22(1H,ddd,J=7.6Hz,J=7.6Hz,J=2.4Hz,5β-H)、3.29(1H,dd,J=11.9Hz,J=1.8Hz,21β-H)、3.60(3H,s,23-OCH3)、4.36(1H,qd,J=10.4Hz,J=6.2Hz,19-H)、6.89(1H,d,J=7.7Hz,12-H)、7.02(1H,ddd,J=7.7Hz,J=7.7Hz,J=1.1Hz,10-H)、7.19(1H,ddd,J=7.7Hz,J=7.7Hz,J=1.3Hz,11-H)、7.27(1H,d,J=7.7Hz,9-H)、7.41(1H,s,17-H)、8.42(1H,brs,NH)
<1H-NMR (500MHz, CDCl3)>
δ0.88 (1H, ddd, J = 11.7Hz, J = 11.7Hz, J = 11.7Hz, 14β-H), 1.41 (3H, d, J = 6.2Hz, 18-CH3), 1.59 (1H, m, 20-H), 1.62 (1H, ddd, J = 11.7Hz, J = 2.8Hz, J = 2.8Hz, 14α-H), 2.00 (1H, ddd, J = 11.9Hz, J = 7.6Hz, J = 7.6Hz, 6α-H) 2.39 (1H, ddd, J = 11.9Hz, J = 7.6Hz, J = 2.4Hz , 6β-H), 2.42 (1H, dd, J = 11.9Hz, J = 3.8Hz, 21-α), 2.46 (1H, ddd, J = 7.6Hz, J = 7.6Hz) , J = 7.6Hz, 5α-H), 2.51 (1H, ddd, J = 11.7Hz, J = 2.8Hz, J = 2.8Hz, 15-H), 2.57 (1H, dd) , J = 11.7Hz, J = 2.8Hz, 3-H), 3.22 (1H, ddd, J = 7.6Hz, J = 7.6Hz, J = 2.4Hz, 5β-H), 3 .29 (1H, dd, J = 11.9Hz, J = 1.8Hz, 21β-H) 3.60 (3H, s, 23-OCH3) 4.36 (1H, qd, J = 10.4Hz) , J = 6.2Hz, 19-H), 6.89 (1H, d, J = 7.7Hz, 12-H), 7.02 (1H, ddd, J = 7.7Hz, J = 7.7Hz) , J = 1.1Hz, 10-H), 7.19 (1H, ddd, J = 7.7Hz, J = 7.7Hz, J = 1.3Hz, 11-H), 7.27 (1H, d) , J = 7.7Hz, 9-H), 7.41 (1H, s, 17-H), 8.42 (1H, brs, NH)
(製造例3)
―6-Gingerolの単離精製―
乾燥させたショウガ(Zingiber officinale)粉砕物にメタノールを加えて抽出し、濃縮した後、濃縮液に水とジエチルエーテルを加えて、液-液分配を行った。ジエチルエーテル層を濃縮した後、シリカゲルを用いたカラム精製を行った。ヘキサン、ヘキサン/酢酸エチル混液、メタノールで溶出させた後、6-Gingerolが多く含まれる画分を濃縮し、さらに逆相高速液体クロマトグラフィー(ODS)を用い75%メタノールで精製を行い、6-Gingerolを得た。構造は化学式(3)に示す。
Figure JPOXMLDOC01-appb-C000003
(Manufacturing Example 3)
―6-Isolation and purification of Gingerol―
Methanol was added to the dried ginger (Zingiber officinale) pulverized product for extraction, and after concentration, water and diethyl ether were added to the concentrated solution for liquid-liquid partitioning. After concentrating the diethyl ether layer, column purification using silica gel was performed. After elution with hexane, a mixed solution of hexane / ethyl acetate, and methanol, the fraction containing a large amount of 6-Gingerol is concentrated, and further purified with 75% methanol using reverse phase high performance liquid chromatography (ODS), 6-. Obtained Gingerol. The structure is shown in the chemical formula (3).
Figure JPOXMLDOC01-appb-C000003
<1H-NMR(500MHz,CDCl3)>
δ0.89(3H,t,J=7.0Hz,10-CH3)、1.30(6H,m,7-2H,8-2H,9-2H)、1.38-1.49(2H,m,6-2H)、2.48(1H,dd,J=17.5Hz,J=9.0Hz,4-H)、2.57(1H,dd,J=17.5Hz,J=2.0Hz,4-H)、2.73(2H,m,2-2H)、2.84(2H,m,1-2H)、3.87(3H,s,3’-OCH3)、4.02(1H,m,5-H)、6.66(1H,dd,J=8.0Hz,J=2.0Hz,6’-H)、6.68(1H,d,J=2.0Hz,2’-H)、6.82(1H,d,J=8.0Hz,5’-H)
<1H-NMR (500MHz, CDCl3)>
δ0.89 (3H, t, J = 7.0Hz, 10-CH3), 1.30 (6H, m, 7-2H, 8-2H, 9-2H), 1.38-1.49 (2H, m, 6-2H), 2.48 (1H, dd, J = 17.5Hz, J = 9.0Hz, 4-H), 2.57 (1H, dd, J = 17.5Hz, J = 2. 0Hz, 4-H), 2.73 (2H, m, 2-2H), 2.84 (2H, m, 1-2H), 3.87 (3H, s, 3'-OCH3), 4.02 (1H, m, 5-H), 6.66 (1H, dd, J = 8.0Hz, J = 2.0Hz, 6'-H), 6.68 (1H, d, J = 2.0Hz, 2'-H), 6.82 (1H, d, J = 8.0Hz, 5'-H)
(製造例4)
―6-Shogaolの単離精製―
乾燥させたショウガ(Zingiber officinale)粉砕物にメタノールを加えて抽出し、濃縮した後、濃縮液に水とジエチルエーテルを加えて、液-液分配を行った。ジエチルエーテル層を濃縮した後、シリカゲルを用いたカラム精製を行った。ヘキサン、ヘキサン/酢酸エチル混液、メタノールで溶出させた後、6-Shogaolが多く含まれる画分を濃縮し、さらに逆相高速液体クロマトグラフィー(ODS)を用い35%アセトニトリルで精製を行い、6-Shogaolを得た。構造は化学式(4)に示す。
Figure JPOXMLDOC01-appb-C000004
(Manufacturing Example 4)
―6-Isolation and purification of Shogaol―
Methanol was added to the dried ginger (Zingiber officinale) pulverized product for extraction, and after concentration, water and diethyl ether were added to the concentrated solution for liquid-liquid partitioning. After concentrating the diethyl ether layer, column purification using silica gel was performed. After elution with hexane, a mixed solution of hexane / ethyl acetate, and methanol, the fraction containing a large amount of 6-shogaol is concentrated, and further purified with 35% acetonitrile using reverse phase high performance liquid chromatography (ODS), 6-. Shogaol was obtained. The structure is shown in the chemical formula (4).
Figure JPOXMLDOC01-appb-C000004
<1H-NMR(600MHz,CDCl3)>
δ0.89(3H,t,J=8.7Hz,10-CH3)、1.30(4H,m,8-2H,9-2H),1.45(2H,m,7-2H)、2.19(1H,ddd,J=16.2Hz,J=10.8Hz,J=1.8Hz,6-H)、2.85(4H,m,1-2H,2-2H)、3.87(3H,s,3’-OCH3)、6.09(1H,br d,J=19.2Hz,4-H),6.68(1H,dd,J=9.6Hz,2.4Hz,6’-H)、6.71(1H,d,J=2.4Hz,2’-H)、6.80(1H,m,5-H)、6.83(1H,d,J=9.6Hz,5’-H)
<1H-NMR (600MHz, CDCl3)>
δ0.89 (3H, t, J = 8.7Hz, 10-CH3), 1.30 (4H, m, 8-2H, 9-2H), 1.45 (2H, m, 7-2H), 2 .19 (1H, ddd, J = 16.2Hz, J = 10.8Hz, J = 1.8Hz, 6-H) 2.85 (4H, m, 1-2H, 2-2H), 3.87 (3H, s, 3'-OCH3), 6.09 (1H, br d, J = 19.2Hz, 4-H), 6.68 (1H, dd, J = 9.6Hz, 2.4Hz, 6) '-H), 6.71 (1H, d, J = 2.4Hz, 2'-H), 6.80 (1H, m, 5-H), 6.83 (1H, d, J = 9. 6Hz, 5'-H)
(実施例1)
―新型コロナウイルスの感染抑制効果―
 製造例1~製造例4の化合物を試料として用い、下記の試験法により、新型コロナウイルスの感染抑制効果を評価した。
(Example 1)
-Infection suppression effect of new coronavirus-
Using the compounds of Production Examples 1 to 4 as samples, the infection-suppressing effect of the new coronavirus was evaluated by the following test method.
 10μMの最終濃度でVeroE6/TMPRSS2細胞培地に添加し、37℃、3時間培養した。その後、新型コロナウイルスSARS-CoV-2(MOI=0.05)を添加し、細胞に感染させた。さらに37℃、48時間培養し、CellTiter-GloTMを加えて細胞生存率を測定した。
 ポジコンとしては、新型コロナウイルスの肺細胞への感染を抑制できると報告されているカモスタット(Camostat)とナファモスタット(Nafamostat)を用いた。
The cells were added to VeroE6 / TMPRSS2 cell medium at a final concentration of 10 μM and cultured at 37 ° C. for 3 hours. Then, the new coronavirus SARS-CoV-2 (MOI = 0.05) was added to infect the cells. The cells were further cultured at 37 ° C. for 48 hours, CellTiter-Glo TM was added, and the cell viability was measured.
As the positive control, camostat and nafamostat, which are reported to be able to suppress the infection of the lung cells of the new coronavirus, were used.
 図1の結果から、製造例1~製造例4の化合物は、ポジコンのカモスタット(Camostat)とナファモスタット(Nafamostat)より、新型コロナウイルスに対する高い感染抑制作用を有することが確認できた。 From the results shown in FIG. 1, it was confirmed that the compounds of Production Examples 1 to 4 had a higher infection-suppressing effect on the new coronavirus than the positiveon camostat and nafamostat.
 なお、VeroE6/TMPRSS2細胞の細胞生存率を指標として製造例2~4のIC50を算出した。
Figure JPOXMLDOC01-appb-T000005
The IC50s of Production Examples 2 to 4 were calculated using the cell viability of VeroE6 / TMPRSS2 cells as an index.
Figure JPOXMLDOC01-appb-T000005
(実施例2)
 SARS-CoV-2 Nproteinに対する抗体を用いた免疫染色を行うことでウイルスの感染を視覚化した。
最終濃度10μM、25μM、50μMで製造例2、製造例3をVeroE6/TMPRSS2細胞の培地へ加え、37℃で3時間培養した後、新型コロナウイルスSARS-CoV-2(MOI=0.05)を添加し、細胞に感染させた。さらに37℃、24時間培養し、4%パラホルムアルデヒドで細胞を固定した。透過処理としてTritonX-100を加え、室温で15分処理を行った。その後Blocking OneTMにて室温で15分ブロッキング処理を行った。免疫染色はSARS-CoV-2 Nucleocapsid Protein antibody(1:100希釈,Novus NB100―56576)を用いて1時間室温で反応させ、その後Alexa 568―labele anti―rabbitantibody(1:100希釈, Thermo)を用いて1時間室温で染色を行った。細胞の核はProlong Gold Antifade Mount with DAPI (Thermo)を用いて染色を行った。
(Example 2)
Virus infection was visualized by immunostaining with an antibody against SARS-CoV-2 Nprotein.
Production Example 2 and Production Example 3 were added to the medium of VeroE6 / TMPRSS2 cells at final concentrations of 10 μM, 25 μM, and 50 μM, cultured at 37 ° C. for 3 hours, and then the new coronavirus SARS-CoV-2 (MOI = 0.05) was added. It was added and infected the cells. Further, the cells were cultured at 37 ° C. for 24 hours, and the cells were fixed with 4% paraformaldehyde. Triton X-100 was added as a permeation treatment, and the treatment was carried out at room temperature for 15 minutes. After that, blocking treatment was performed at room temperature for 15 minutes with Blocking One TM . Immunostaining was carried out using SARS-CoV-2 Nucleocapsid Protein antibody (1: 100 dilution, Novus NB100-56576) for 1 hour at room temperature, followed by Alexa 568-labele anti-rabbit antibody (1: 100 dilution, Ther). Staining was performed at room temperature for 1 hour. Cell nuclei were stained with Prolong Gold Antifade Mount with DAPI (Thermo).
 図2の結果から、製造例2と3を添加した場合はいずれも濃度依存的に感染細胞の減少が観察された。 From the results shown in FIG. 2, when Production Examples 2 and 3 were added, a decrease in infected cells was observed in each of them in a concentration-dependent manner.
(実施例3)
 SARS-CoV-2に対する感染抑制効果は細胞侵入と細胞侵入後のどちらに作用するかを検討した。
最終濃度50μMの製造例2と3を以下の条件でVeroE6/TMPRSS2細胞の培地へ加えた。Full timeの条件では新型コロナウイルスSARS-CoV-2(MOI=0.05)感染3時間前から培地へ加え、感染2時間後の洗浄後も培地に製造例2と3が50μMで存在するようにした。Entryの条件では新型コロナウイルスSARS-CoV-2(MOI=0.05)感染3時間前から培地へ加え、感染2時間後の洗浄後まで培地に製造例2と3が存在するようにした。Post-entryの条件では新型コロナウイルスSARS-CoV-2(MOI=0.05)感染2時間後の洗浄後から感染48時間後の検出まで製造例2と3が存在するようにした。検出は感染48時間後にCellTiter-GloTMを加えて細胞生存率を測定した。
Figure JPOXMLDOC01-appb-T000006
(Example 3)
We investigated whether the infection-suppressing effect on SARS-CoV-2 acts on cell invasion or after cell invasion.
Production Examples 2 and 3 having a final concentration of 50 μM were added to the medium of VeroE6 / TMPRSS2 cells under the following conditions. Under the conditions of Full time, the new coronavirus SARS-CoV-2 (MOI = 0.05) was added to the medium 3 hours before infection, and Production Examples 2 and 3 were present in the medium at 50 μM even after washing 2 hours after infection. I made it. Under the conditions of Entry, production examples 2 and 3 were added to the medium from 3 hours before infection with the new coronavirus SARS-CoV-2 (MOI = 0.05), and production examples 2 and 3 were present in the medium until after washing 2 hours after infection. Under the conditions of Post-entry, Production Examples 2 and 3 were allowed to exist from after washing 2 hours after infection with the new coronavirus SARS-CoV-2 (MOI = 0.05) to detection 48 hours after infection. For detection, CellTiter-Glo TM was added 48 hours after infection and cell viability was measured.
Figure JPOXMLDOC01-appb-T000006
図3の結果から、製造例2と3はいずれも細胞侵入後に作用することが確認された。 From the results shown in FIG. 3, it was confirmed that both Production Examples 2 and 3 act after cell invasion.
(実施例4)
 コロナウイルスはポリプロテインが合成後、パパイン様酵素により三箇所切断後、3CL プロテアーゼによって11箇所切断されることで、機能を持ったペプチドを合成する。
 プロテアーゼによるポリプロテインの切断反応をウエスタンブロッド法で検出できる試験系を用い、プロテアーゼによるポリプロテインの切断への阻害作用を検討した。
 コムギ無細胞タンパク質合成系を用いて、新型コロナウイルスSARS-CoV-23C Lプロテアーゼと、3CLプロテアーゼによって切断されるアミノ酸配列を持つペプチド(FLAG-TSITSAVLQ^SGFRKMAFP-GST-biotin)を合成した。合成したプロテアーゼと基質、さらに最終濃度500μMで製造例2と3を加え、37℃で3時間反応させ、13%ポリアクリルアミドゲルを用いてのSDS-PAGEを行いPVDFメンブレンへと転写し、Blocking OneTMにて室温で15分ブロッキング処理を行った。その後anti-streptavidin-HRP antibody(1:5000希釈)を用いて検出を行なった。
(Example 4)
Coronavirus synthesizes a peptide having a function by synthesizing a polyprotein, cleaving it at three sites with a papain-like enzyme, and then cleaving it at 11 sites with a 3CL protease.
Using a test system that can detect the cleavage reaction of polyprotein by protease by the Western Brod method, the inhibitory effect of protease on cleavage of polyprotein was investigated.
A peptide having an amino acid sequence cleaved by the new coronavirus SARS-CoV-23C L protease and 3CL protease (FLAG-TSITSAVLQ ^ SGFRKMAFP-GST-biotin) was synthesized using a wheat cell-free protein synthesis system. Add the synthesized protease and substrate, and Production Examples 2 and 3 at a final concentration of 500 μM, react at 37 ° C. for 3 hours, perform SDS-PAGE using 13% polyacrylamide gel, transfer to PVDF membrane, and blocking One. Blocking treatment was performed by TM at room temperature for 15 minutes. Then, detection was performed using anti-streptavidin-HRP antibody (1: 5000 dilution).
 図4の結果から、製造例2と3はいずれもプロテアーゼによるポリプロテインの切断を阻害した。 From the results shown in FIG. 4, both Production Examples 2 and 3 inhibited the cleavage of polyprotein by protease.
本発明は、キャッツクロー抽出物、ショウガ抽出物、Pteropodine及びその薬学的に許容される塩、Isopteropodine及びその薬学的に許容される塩、6-Gingerol及びその薬学的に許容されるエーテル、並びに、6-Shogaol及びその薬学的に許容されるエーテルの少なくともいずれかを有効成分として配合した食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、雑貨として産業上の利用可能性がある。 The present invention relates to cat's claw extract, ginger extract, Pteropodine and its quasi-drug salt, Isopteropodine and its quasi-drug salt, 6-Gingerol and its pharmaceutically acceptable ether, and the like. Industrial availability as a food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, miscellaneous goods containing at least one of 6-Gingerol and its pharmaceutically acceptable ether as an active ingredient. be.

Claims (7)

  1.  キャッツクロー(Uncaria tomentosa)抽出物を含有する新型コロナウイルス感染症の予防剤又は治療剤。 A prophylactic or therapeutic agent for a new type of coronavirus infection containing a cat's claw (Uncaria tomentosa) extract.
  2.  ショウガ(Zingiber officinale)抽出物を含有する新型コロナウイルス感染症の予防剤又は治療剤。 A prophylactic or therapeutic agent for a new type of coronavirus infection containing a ginger (Zingiber office) extract.
  3.  Pteropodine、及び、その薬学的に許容される塩の少なくともいずれかを含有する新型コロナウイルス感染症の予防剤又は治療剤。 A prophylactic or therapeutic agent for a new type of coronavirus infection containing at least one of Pteropodine and its pharmaceutically acceptable salt.
  4.  Isopteropodine、及び、薬学的に許容される塩の少なくともいずれかを含有する新型コロナウイルス感染症の予防剤又は治療剤。 A prophylactic or therapeutic agent for a new type of coronavirus infection containing at least one of Isopteropodine and a pharmaceutically acceptable salt.
  5.  6-Gingerol、及び、薬学的に許容されるエーテルの少なくともいずれかを含有する新型コロナウイルス感染症の予防剤又は治療剤。 A prophylactic or therapeutic agent for a new type of coronavirus infection containing at least one of 6-Gingerol and a pharmaceutically acceptable ether.
  6.  6-Shogaol、及び、薬学的に許容されるエーテルの少なくともいずれかを含有する新型コロナウイルス感染症の予防剤又は治療剤。 A prophylactic or therapeutic agent for a new type of coronavirus infection containing at least one of 6-shogaol and a pharmaceutically acceptable ether.
  7.  請求項1から6に記載の抽出物又は化合物の少なくともいずれかを含有する新型コロナウイルス感染症の予防及び治療用の食品組成物、医薬品組成物、医薬部外品組成物、化粧品組成物、又は、雑貨。 A food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, or a new coronavirus infection containing at least one of the extracts or compounds according to claims 1 to 6. ,general merchandise.
PCT/JP2021/033292 2020-09-11 2021-09-10 Food composition, pharmaceutical composition, quasi drug composition, cosmetic composition and sundry article for preventing or treating covid-19 WO2022054904A1 (en)

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Citations (1)

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JP2005343836A (en) * 2004-06-04 2005-12-15 Lotte Co Ltd Anti-influenza virus agent, and infection inhibiting article containing the same and food and drink

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Publication number Priority date Publication date Assignee Title
JP2005343836A (en) * 2004-06-04 2005-12-15 Lotte Co Ltd Anti-influenza virus agent, and infection inhibiting article containing the same and food and drink

Non-Patent Citations (2)

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Title
FERREIRA ANDERSON O., POLONINI HUDSON C., DIJKERS ELI C. F.: "Postulated Adjuvant Therapeutic Strategies for COVID-19", JOURNAL OF PERSONALIZED MEDICINE, vol. 10, no. 80, 5 August 2020 (2020-08-05), pages 1 - 33, XP055910588, DOI: 10.3390/jpm10030080 *
YEPES-PÉREZ ANDRES F., HERRERA-CALDERON OSCAR, SÁNCHEZ-APARICIO JOSÉ-EMILIO, TIESSLER-SALA LAURA, MARÉCHAL JEAN-DIDIER, CARDONA-G : "Investigating Potential Inhibitory Effect of Uncaria tomentosa (Cat’s Claw) against the Main Protease 3CLpro of SARS-CoV-2 by Molecular Modeling", EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE, OXFORD UNIVERSITY PRESS, US, vol. 2020, 30 September 2020 (2020-09-30), US , pages 1 - 14, XP055910590, ISSN: 1741-427X, DOI: 10.1155/2020/4932572 *

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