WO2020026953A1 - Agent anti-virus de l'herpès - Google Patents

Agent anti-virus de l'herpès Download PDF

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WO2020026953A1
WO2020026953A1 PCT/JP2019/029309 JP2019029309W WO2020026953A1 WO 2020026953 A1 WO2020026953 A1 WO 2020026953A1 JP 2019029309 W JP2019029309 W JP 2019029309W WO 2020026953 A1 WO2020026953 A1 WO 2020026953A1
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monogalactosyldiacylglycerol
mgdg
herpes virus
fatty acids
day
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PCT/JP2019/029309
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English (en)
Japanese (ja)
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真菜 浅野
久野　斉
欣也 渥美
京子 林
敏男 河原
さと子 小松
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株式会社デンソー
学校法人中部大学
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Priority to JP2020533477A priority Critical patent/JP7505697B2/ja
Priority to CN201980050286.5A priority patent/CN112584850A/zh
Publication of WO2020026953A1 publication Critical patent/WO2020026953A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/03—Algae
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • 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
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/68—Protozoa, e.g. flagella, amoebas, sporozoans, plasmodium or toxoplasma
    • 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
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/748—Cyanobacteria, i.e. blue-green bacteria or blue-green algae, e.g. spirulina
    • 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
    • A61K36/02—Algae
    • 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
    • A61K36/02—Algae
    • A61K36/05—Chlorophycota or chlorophyta (green algae), e.g. Chlorella
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses

Definitions

  • the present invention relates to an anti-herpes virus agent. More specifically, the present invention relates to an anti-herpes virus agent using a substance derived from microalgae, its use, and the like.
  • This application claims the priority based on Japanese Patent Application No. 2018-143051 filed on Jul. 31, 2018, the entire content of which is incorporated by reference.
  • Herpes virus is a DNA virus having double-stranded DNA as its genome. Herpesviruses are classified into ⁇ -herpesvirinae, ⁇ -herpesvirinae and ⁇ -herpesvirinae.
  • Herpes simplex virus (HSV), which belongs to the alpha-herpesvirinae subfamily, causes various diseases in humans. Representative examples of HSV infection include herpes simplex virus type 1 (HSV-1), a pathogen herpes labialis, and herpes simplex virus type 2 (HSV-2), a genital herpes pathogen.
  • Herpes virus is characterized by latent infection (persistent infection in the body) after primary infection, reactivated by various causes (ultraviolet rays, fever, various stresses, menstruation, immunosuppression, etc.) Causes (regression). There is no fundamental cure for herpes virus infection, and individuals infected with herpes virus will experience repeated local pathology / symptoms.
  • Nucleic acid analogs and DNA synthesis inhibitors are used for the treatment of herpes virus infection (for example, see Non-Patent Documents 1 and 2), but there are many cases where a sufficient therapeutic effect cannot be obtained. The establishment of new treatment strategies is eagerly needed.
  • an object of the present invention is to provide a new means effective for treating or preventing herpes virus infection.
  • an extract (monogalactosyldiacylglycerol-containing extract) of Coccomyxa microalgae was found to have an effect of suppressing the onset of herpes virus infection and an effect of suppressing virus growth. It was also found that the effect was dramatically enhanced by the combined use of thymidine (a synergistic effect was exhibited). The same effect was observed not only in the extract but also in the dry powder (algae) of the microalgae of the genus Komikusa. Similar to the extract, the effect was significantly enhanced by the combined use of thymidine.
  • further studies revealed the structure of monogalactosyldiacylglycerol, the active ingredient in the extract. Further, further findings have been obtained which support that the utility value of the extract is extremely high.
  • the anti-herpes virus agent according to any one of [1] to [4], wherein the active ingredient is a dry powder of algal cells.
  • a composition comprising the anti-herpesvirus agent according to any one of [1] to [15].
  • the composition according to [16] which is a food or a feed.
  • Results of HSV-2 infection (genital herpes) experiment The onset courses in the case of single administration were compared.
  • Test plot # 1 control (distilled water)
  • test plot # 2 ACV (acyclovir) (1 mg / day)
  • test plot # 3 MGDG preparation (0.1 mg / day)
  • test plot # 4 MGDG preparation (1 mg / day)
  • test plot # 5 thymidine (1 mg / day)
  • test plot # 6 thymidine (5 mg / day)
  • test plot # 7 thymidine (20 mg / day).
  • Results of HSV-2 infection (genital herpes) experiment The onset course when MGDG preparation (0.1 mg administration) and thymidine were used together was compared.
  • Test plot # 1 control (distilled water), test plot # 2: ACV (acyclovir) (1 mg / day), test plot # 3: MGDG preparation (0.1 mg / day), test plot # 8: MGDG preparation (0.1 mg / day) + thymidine (1 mg / day), test group # 9: MGDG preparation (0.1 mg / day) + thymidine (5 mg / day), test group # 10: MGDG preparation (0.1 mg / day) day) + thymidine (20 mg / day).
  • Results of HSV-2 infection (genital herpes) experiment. The onset course when MGDG preparation (1 mg administration) and thymidine were used together was compared.
  • Test plot # 1 control (distilled water), test plot # 2: ACV (acyclovir) (1 mg / day), test plot # 4: MGDG preparation (1 mg / day), test plot # 11: MGDG preparation (1 mg / day) + thymidine (1 mg / day), test plot # 12: MGDG preparation (1 mg / day) + thymidine (5 mg / day), test plot # 13: MGDG preparation (1 mg / day) day) + thymidine (20 mg / day).
  • Results of HSV-2 infection (genital herpes) experiment. The onset course was compared when the alga body (dry powder) was administered alone or when the alga body and thymidine were used in combination.
  • Test plot # 1 control (distilled water), test plot # 2: ACV (acyclovir) (1 mg / day), test plot # 14: algal (20 mg / day), test plot # 15: algal (20 mg / day) + thymidine (1 mg / day), test plot # 16: algal cells (20 mg / day) + thymidine (5 mg / day), test plot # 17: algal cells (20 mg / day) + thymidine (20 mg / day).
  • Results of HSV-2 infection (genital herpes) experiment. The survival rates and cases of onset were compared. Results of HSV-2 infection (genital herpes) experiment. Three days after infection, the amount of virus was compared. * p ⁇ 0.05 vs.
  • Test plot # 24 control (distilled water), test plot # 25: ACV (1 mg / day), test plot # 26: MGDG preparation (1 mg / day), test plot # 27: thymidine (20 mg / day) ), Test plot # 28: ACV (1 mg / day) + MGDG preparation (1 mg / day).
  • Results of HSV-2 infection (genital herpes) experiment using algal cells (dry powder) of Kokkomixa sp. Three days after infection, the amount of virus was compared. * p ⁇ 0.05, ** p ⁇ 0.01 vs. control
  • the cream containing the MGDG preparation was applied to the affected area three times daily, and the progress was observed. Effect on cold sores (patient 2: 25 year old male). The cream containing the MGDG preparation was applied to the affected area daily, and the progress was observed. Analysis result (GC / FID chromatogram) of the content component (MGDG1) of the MGDG preparation. Analysis result (GC / FID chromatogram) of the content component (MGDG2) of the MGDG preparation. Analysis result (GC / FID chromatogram) of the component (MGDG3) of the MGDG preparation. Analysis result (GC / FID chromatogram) of the content component (MGDG4) of the MGDG preparation.
  • MGDG-1 to MGDG-5 are peaks derived from the KDG strain MGDG preparation, and peaks presumed to have the same structure as these are indicated by *.
  • HPLC chromatograms of MGDG preparations of various organisms Comixa sp. KJ strain, Euglena gracilis (Euglena of life, Biozyme), spinach.
  • MGDG-1 to MGDG-5 are peaks derived from the KDG strain MGDG preparation, and peaks presumed to have the same structure as these are indicated by *.
  • An anti-herpesvirus agent is an antiviral agent that targets a herpes virus.
  • the anti-herpes virus agent of the present invention can be expected to have a therapeutic or preventive effect on herpes virus infection.
  • the anti-herpes virus agent of the present invention exerts its effects through suppression of herpes virus growth in view of the results of the experiments described in the examples below.
  • herpesviruses are classified into three types of herpesvirinae ( ⁇ -herpesvirinae, ⁇ -herpesvirinae, and ⁇ -herpesvirinae).
  • Alpha herpesvirus subfamily includes herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and varicella-zoster virus (HHV-3). Megalovirus (HHV-5), human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) belong to the subfamily ⁇ -herpesvirinae, Epstein-Barr virus (HHV-4), human herpes Virus 8 (HHV-8, also known as Kaposi's sarcoma-associated herpesvirus (KSHV)) belongs.
  • a particularly preferred target of the anti-herpes virus agent of the present invention is herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2).
  • the anti-herpes virus agent of the present invention contains a substance derived from a single-cell algae as an active ingredient.
  • the unicellular algae Tebouxia algae, Ephemeroptera, Cyanobacteria, Euglena algae, etc.
  • the unicellular algae are not particularly limited.
  • Coccomyxa microalgae specific examples are Coccomixa sp.
  • microalgae of the genus Kokkomikusa are particularly preferred.
  • the microalgae of the genus Kokkomikusa are not particularly limited, but preferred examples include Kokkomikusa sp. Strain KJ or a mutant thereof, or Kokkomikusa sp.
  • MBIC11204 strain or a mutant thereof was established on June 4, 2013 by the National Institute of Technology and Evaluation, National Institute of Technology and Evaluation Biotechnology Center Patent Organism Depositary Center (NITE-IPOD) (2-5 Kazusa Kamasa, Kisarazu-shi, Chiba) No. 8120) and deposited under accession number FERM BP-22254 on 2 June 2015 under the provisions of the Putavest Treaty on June 2, 2015.
  • NITE-IPOD National Institute of Technology and Evaluation Biotechnology Center Patent Organism Depositary Center
  • FERM BP-22254 accession number
  • Kokkomixa sp. MBIC11204 strain (N1) was acquired by the Patent Organism Depositary Center (IPOD) of the National Institute of Advanced Industrial Science and Technology (IPOD) on January 18, 2006.
  • NITE-IPOD National Institute of Technology and Evaluation Biotechnology Center
  • Mutants of the strain K. sp. KJ and the strains of strain S. cocoa M. sp. MBIC11204 can be irradiated with ultraviolet rays, X-rays, ⁇ -rays, etc. Editing, etc.).
  • the method for obtaining the mutant, the characteristics, and the like are not particularly limited.
  • the method for cultivating Microalgae of the genus Kokkomushi is not particularly limited.
  • the medium for cultivating the microalgae of the genus Kokkomikusa may be any of those commonly used for culturing microalgae.For example, various nutrients, trace metal salts, known media for freshwater microalgae containing vitamins, etc. Any medium for marine microalgae can be used. Examples of the medium include AF6 medium.
  • the composition of AF6 medium (per 100 ml) is as follows.
  • the nutrients include nitrogen sources such as NaNO 3 , KNO 3 , NH 4 Cl and urea, and phosphorus sources such as K 2 HPO 4 , KH 2 PO 4 and sodium glycerophosphate.
  • the trace metals include iron, magnesium, manganese, calcium, zinc and the like, and the vitamins include vitamin B1, vitamin B12 and the like.
  • stirring may be performed while supplying carbon dioxide under aeration conditions.
  • the cells are cultured by irradiating with a fluorescent lamp for 12 hours, irradiating with light and dark cycles such as 12 hours of dark conditions, or irradiating with continuous light.
  • the culture condition is not particularly limited as long as it does not adversely affect the growth of the microalgae of the genus Kompani.
  • the pH of the culture solution is 3 to 9, and the culture temperature is 10 to 35 ° C.
  • a monogalactosyldiacylglycerol-containing extract of a single-cell algae particularly preferably a microalga belonging to the genus Kokkomikusa
  • an alga body or a dry powder thereof second embodiment
  • Monogalactosyldiacylglycerol-containing extract In one embodiment of the present invention, a monogalactosyldiacylglycerol-containing extract of a single-cell algae (particularly preferably, a microalga belonging to the genus Kokkomikusa) is used as an active ingredient.
  • the extraction method is not particularly limited as long as an extract containing monogalactosyldiacylglycerol can be obtained. For example, ethanol extraction can be adopted as the extraction method.
  • a product obtained by purifying after ethanol extraction and increasing the content of monogalactosyldiacylglycerol is used as "monogalactosyldiacylglycerol-containing extract of unicellular algae (particularly preferably microalgae belonging to the genus Kokkomikusa)".
  • Examples of the purification method include column chromatography using a filler such as silica gel and alumina, gel filtration chromatography, and concentration.
  • the collected algal cells may be subjected to a drying treatment and / or a crushing treatment.
  • a dried alga body, a dried and crushed alga body (typically, a dry powder), or a crushed alga body may be prepared, and an extraction operation may be performed using the prepared alga body.
  • a single-cell algae that has been processed in advance (for example, a dried alga body, its powder / powder, or a tablet (which may contain an excipient, etc.)) is obtained and subjected to an extraction operation.
  • You may.
  • processed products of Chlorella vulgaris, Nannochloropsis oculata, Arthrospira platensis (spirulina), Euglena gracilis and the like are commercially available.
  • the content of monogalactosyldiacylglycerol in the active ingredient is not particularly limited as long as the extract shows anti-herpesvirus activity, and is, for example, 70% (w / v) to 99% (w / v), preferably 80% (w / v). w / v) to 99% (w / v), more preferably 90% (w / v) to 99% (w / v), even more preferably 95% (w / v) to 99% (w / v). (Specific examples are 96% (w / v), 97% (w / v), and 98% (w / v)).
  • Monogalactosyldiacylglycerol is one of glyceroglycolipids and is known as a component of the chloroplast thylakoid membrane of plants.
  • Monogalactosyldiacylglycerol has a skeleton in which galactose is ⁇ -linked to glycerol.
  • the anti-herpesvirus agent of the present invention contains monogalactosyldiacylglycerol as a main component.
  • monogalactosyldiacylglycerol examples include (1) constituent fatty acids C16: 3 and C18: 3 monogalactosyldiacylglycerol, and (2) constituent fatty acids C16: 2.
  • constituent fatty acids are C18: 3 and C18: 3 monogalactosyldiacylglycerol
  • constituent fatty acids are C16: 2 and C18: 2 monogalactosyldiacylglycerol
  • the constituent fatty acids are C18: 3 and C18: 2 monogalactosyldiacylglycerol
  • the constituent fatty acids are C16: 1 and C18: 2 monogalactosyldiacylglycerol.
  • the constituent fatty acids C18: 3 of (1) above are preferably C18: 3 (n- 3), at least one of the constituent fatty acids C18: 3 of the above (3) is preferably C18: 3 (n-3), and the constituent fatty acids C18: 2 of the above (4) are preferably C18: 2 (n -6), and the constituent fatty acid C18: 3 of the above (5) is preferably C18: 3 (n-3), and the C18: 2 is preferably C18: 2 (n-6).
  • the anti-herpesvirus agent of the present invention contains two or more monogalactosyldiacylglycerols having different structures.
  • the combination, content ratio, and the like are not particularly limited.
  • the anti-herpes virus agent of the present invention is preferably two or more of the above (1) to (6), more preferably three or more of the above (1) to (6), still more preferably the above ( It contains four or more of the above (1) to (6), more preferably five or more of the above (1) to (6), and still more preferably all of the above (1) to (6).
  • the anti-herpesvirus agent of a particularly preferred embodiment contains the monogalactosyldiacylglycerol (5) alone or in combination with one or more of (1), (2) to (4) and (6). Will be done.
  • an anti-herpesvirus agent comprising one or more monogalactosyldiacylglycerols as an active ingredient selected from the group consisting of the above (1) to (6).
  • the combination, content ratio, and the like are not particularly limited.
  • the monogalactosyldiacylglycerol (MGDG5) of (5) showed particularly high activity. Therefore, in a particularly preferred embodiment, the monogalactosyldiacylglycerol (5) is at least one of the active ingredients.
  • monogalactosyldiacylglycerol containing various fatty acids fatty acids are shown below.
  • monogalactosyldiacylglycerols including known monogalactosyldiacylglycerols, will generally be able to exert anti-herpesvirus activity.
  • an alga or a dry powder thereof is used as an active ingredient instead of an extract from the alga.
  • the dry powder can be prepared by subjecting the collected algal cells to a drying treatment and a crushing (crushing) treatment.
  • a drying treatment for example, drum drying, spray drying, freeze drying and the like can be employed.
  • a bead crusher, a homogenizer, a French press, a mixer / blender, a fine crusher, or the like can be used.
  • the order of the drying treatment and the crushing treatment does not matter.
  • a drying and crushing process may be performed simultaneously using an apparatus having drying and crushing functions.
  • the particle size of the dry powder is not particularly limited.
  • thymidine is used in combination with the above-mentioned active ingredient (monogalactosyldiacylglycerol-containing extract of microalga belonging to the genus Kokkomikusa, alga body, and dry powder of alga body).
  • the anti-herpesvirus agent of this embodiment contains, as active ingredients, a monogalactosyldiacylglycerol-containing extract of a microalga belonging to the genus Kokkomixa, an alga body or a dry powder of an alga body, and thymidine.
  • Thymidine By using thymidine in combination, a synergistic effect is exerted, and an anti-herpes virus agent having high anti-herpes virus activity (ie, enhanced therapeutic / prophylactic effect against herpes virus infection) is obtained.
  • Thymidine (CAS No. 50-89-5) is one of DNA nucleosides and has a structure in which deoxyribose is connected to a pyrimidine base, thymine.
  • the amount of thymidine used in combination is not particularly limited.However, when using a monogalactosyldiacylglycerol-containing extract of microalgae belonging to the genus Kokkomikusa as the active ingredient, the amount of the active ingredient and thymidine is in a weight ratio, for example, 1 : 1 to 1: 500, preferably 1:10 to 1: 200. On the other hand, when an alga body of a microalga belonging to the genus Kokkomikusa or a dry powder thereof is used as the active ingredient, the amount of the active ingredient and thymidine is in a weight ratio (however, in the case of an alga body, the dry weight is used). For example, 100: 1 to 1:10, preferably 20: 1 to 1: 1.
  • the anti-herpes virus agent of this embodiment will be provided as a combination preparation obtained by mixing the above-mentioned active ingredient and thymidine.
  • the anti-herpes virus agent of this embodiment can be provided in the form of a kit comprising the first component containing the active ingredient and the second component containing thymidine. In this case, the first component and the second component are used simultaneously.
  • Simultaneous here does not require strict synchronism, and the subject of application is the active ingredient of the first component (monogalactosyldiacylglycerol-containing extract of microalga belonging to the genus Kokkomikusa, alga, drying of alga)
  • the “simultaneous” condition is satisfied as long as a state in which the powder) and the active ingredient (thymidine) of the second component coexist is formed, and the synergistic effect of the combined use of thymidine is exhibited.
  • a medicament when constituted by using the anti-herpesvirus agent of the present invention, for example, it is administered to a subject to be treated or prevented (typically a human) after mixing both components, After administration, the other may be administered immediately.
  • the administration of one may be followed by administration of the other with a predetermined time difference. In this case, it is preferable to set the time difference as short as possible.
  • the other is administered within one hour (preferably within 30 minutes) after administration of one.
  • anti-herpes virus agent of the present invention can be typically used as a composition containing the same for anti-herpes virus infection control.
  • compositions here are pharmaceuticals, foods, feeds.
  • the anti-herpesvirus agent of the present invention is used.
  • HSV-1 herpes labialis, herpes stomatitis, corneal herpes, herpes simplex encephalitis, etc.
  • HSV-2 genital (genital) herpes, neonatal herpes
  • Myelitis Myelitis, etc.
  • the medicament of the present invention can exert a therapeutic effect or a preventive effect on herpes virus infection (these two effects are collectively referred to as “pharmaceutical effect”).
  • the medicinal effects include (1) prevention, suppression or delay of the onset of herpes virus infection, (2) alleviation of symptoms or accompanying symptoms characteristic of herpes virus infection (mildness), (3) It includes prevention, suppression or delay of deterioration of symptoms or accompanying symptoms characteristic of herpervirus infection, and the like. It should be noted that since the therapeutic effect and the preventive effect are partially overlapping concepts, it may be difficult to distinguish them clearly and the benefits of doing so are small.
  • Pharmaceutical formulation can be carried out according to a conventional method.
  • other pharmaceutically acceptable components eg, carriers, excipients, disintegrants, buffers, emulsifiers, suspensions, soothing agents, stabilizers, preservatives, preservatives, physiological Saline, etc.
  • an excipient lactose, starch, sorbitol, D-mannitol, sucrose and the like can be used.
  • a disintegrant starch, carboxymethyl cellulose, calcium carbonate and the like can be used. Phosphates, citrates, acetates and the like can be used as buffers.
  • As the emulsifier gum arabic, sodium alginate, tragacanth and the like can be used.
  • glycerin monostearate, aluminum monostearate, methyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, sodium lauryl sulfate, and the like can be used.
  • Benzyl alcohol, chlorobutanol, sorbitol and the like can be used as a soothing agent.
  • propylene glycol, ascorbic acid, or the like can be used.
  • phenol, benzalkonium chloride, benzyl alcohol, chlorobutanol, methyl paraben and the like can be used.
  • benzalkonium chloride, paraoxybenzoic acid, chlorobutanol and the like can be used.
  • the dosage form in the case of formulating is not particularly limited.
  • dosage forms include tablets, powders, fine granules, granules, capsules, syrups, injections, and external preparations (ointments, creams, lotions, solutions, gels, cataplasms, plasters, tapes) , Aerosols, etc.) and suppositories.
  • the drug is administered orally or parenterally (local injection into the affected area, intravenous, intraarterial, subcutaneous, intradermal, intramuscular or intraperitoneal injection, transdermal, transnasal, transmucosal, etc.) Applied to the subject.
  • Systemic administration and local administration are also adapted to the subject. These administration routes are not mutually exclusive, and arbitrarily selected two or more can be used in combination.
  • the medicament of the present invention contains an active ingredient in an amount necessary for obtaining the expected effect (ie, a therapeutically or prophylactically effective amount).
  • the amount of the active ingredient in the medicament of the present invention generally varies depending on the dosage form, but the amount of the active ingredient is set, for example, in the range of about 0.1% by weight to about 99% by weight to achieve a desired dose.
  • the dosage of the medicament of the present invention is set so as to obtain the expected effect.
  • symptoms, the age, sex, and weight of the patient are generally considered. Those skilled in the art can determine an appropriate dose in consideration of these matters.
  • the dosage can be set so that the daily amount of the active ingredient is 1 mg to 20 mg, preferably 2 mg to 10 mg for an adult (body weight: about 60 kg).
  • the administration schedule may be, for example, once to several times a day, once every two days, or once every three days. In preparing the administration schedule, the condition of the patient, the duration of the effect of the active ingredient, and the like can be considered.
  • the present application is to administer a therapeutic or prophylactically effective amount of a medicament containing the anti-herpes virus agent of the present invention to a subject suffering from or possibly suffering from herpes virus infection.
  • a method for treating or preventing a herpes virus infection characterized by the following.
  • the target of treatment or prevention is typically a human, but a mammal other than a human (eg, monkey, cow, pig, horse, goat, sheep, dog, cat, rabbit, etc.), bird (chicken, quail, turkey) , Geese, ducks, ostriches, ducks, parakeets, birds, etc.).
  • one of the utilization forms of the anti-herpes virus agent of the present invention is a food or feed containing the anti-herpes virus agent of the present invention.
  • the food of the present invention include general foods (cereals, vegetables, meat, various processed foods, confectionery and desserts, milk, soft drinks, fruit juice drinks, coffee drinks, vegetable juice drinks, alcoholic drinks, etc.), nutritional supplements ( Supplements, nutritional drinks, etc.), food additives, pet food for pets, and dietary supplements for pets.
  • dietary supplements or food additives they can be provided in the form of powders, granules, tablets, pastes, liquids and the like.
  • feed of the present invention examples are feed (eg, feed for livestock and poultry) and pet food.
  • the food or feed of the present invention preferably contains an active ingredient in an amount that can be expected to have a therapeutic or preventive effect.
  • the amount to be added can be determined in consideration of the condition, age, sex, weight, and the like of the person to whom it is used.
  • the collected algal cells were dried with a drum dryer and pulverized with a fine pulverizer to obtain a powder (dry powder of algal cells).
  • 1 l of ethanol was added to 100 g of the dry powder for dispersion, and the mixture was allowed to stand in a dark place for 3 days. After standing, the mixture was filtered to separate into a primary filtrate and a residue. To this residue, 1 l of ethanol was added and dispersed in the same manner as described above, allowed to stand for 3 days, and then filtered again to separate a secondary filtrate and a residue. This filtration operation was repeated once to obtain a tertiary filtrate and a residue.
  • the primary filtrate, the secondary filtrate, and the tertiary filtrate were mixed, ethanol was distilled off using an evaporator, and the residue was dried under reduced pressure to obtain an ethanol extract DE.
  • the DE was subjected to DIAION HP-20 (manufactured by Mitsubishi Chemical Corporation, 3.5 ⁇ 57 cm) column chromatography. Elution was performed with H 2 O, 50% ethanol (EtOH), EtOH and acetone in that order, and each eluted fraction was dried at room temperature under reduced pressure (DE1, 400.9 mg; DE2, 310.3 mg; DE3, 2.25 g; DE4, 4.86 g).
  • the acetone fraction (DE4) was subjected to silica gel column (3 ⁇ 42 cm) chromatography.
  • DE4D2 silica gel column (1.5 x 35 cm) chromatography, CHCl 3 -MeOH-H 2 0 DE4D2A by eluting with (10: 1: 0.1) and (15.6 mg) DE4D2B a (686.5 mg) Obtained.
  • DE4D2B was subjected to LH-20 column (Sigma-Aldrich) chromatography using chloroform (CHCl 3 ) -MeOH (3: 1) as a solvent system to obtain DE4D2Bl (11.6 mg) and DE4D2B2 (652.3 mg). Obtained.
  • HSV-2 infection genital herpes
  • HSV-1 infection skin herpes
  • skin herpes Effects of MGDG preparation of Algae sp. MBIC11204 strain and algal cells
  • the efficacy of the MGDG preparation and the alga body (dry powder) of Kokkomixa sp. MBIC11204 strain against HSV-2 infection and HSV-1 infection was evaluated. Changes in efficacy when used in combination with thymidine were also investigated.
  • HSV-2 UW268 strain
  • HSV-1 HSV-1
  • BALB / c mice (6 weeks old, female) were injected subcutaneously with medroxyprogesterone 17-acetate (3 mg / mouse) 6 days before and 1 day before virus inoculation I do.
  • medroxyprogesterone 17-acetate (3 mg / mouse) 6 days before and 1 day before virus inoculation I do.
  • Test plot # 1 control (distilled water)
  • Test plot # 2 ACV (acyclovir) (1 mg / day)
  • Test plot # 3 MGDG preparation (0.1 mg / day)
  • Test plot # 4 MGDG preparation (1 mg / day)
  • Test plot # 5 thymidine (1 mg / day)
  • Test plot # 6 thymidine (5 mg / day)
  • Test plot # 7 thymidine (20 mg / day)
  • Test plot # 8 MGDG preparation (0.1 mg / day) + thymidine (1 mg / day)
  • Test plot # 9 MGDG preparation (0.1 mg / day) + thymidine (5 mg / day)
  • Test plot # 10 MGDG preparation (0.1 mg / day) + thymidine (20 mg / day)
  • Test plot # 11 MGDG preparation (1 mg / day) + thymidine (1 mg / day)
  • Test plot # 12 MGDG preparation (1 mg / day) + thymidine (1 mg /
  • Test plot # 19 control (PBS) (application)
  • Test plot # 20 5% ACV (application)
  • Test plot # 21 5% MGDG preparation (application)
  • Test plot # 22 5% thymidine (applied)
  • Test plot # 23 5% MGDG preparation + 5% thymidine (applied)
  • Test plot # 24 control (distilled water)
  • Test plot # 25 ACV (1 mg / day)
  • Test plot # 26 MGDG preparation (1 mg / day)
  • Test plot # 27 thymidine (20 mg / day)
  • Test plot # 28 thymidine (20 mg / day) + MGDG preparation (1 mg / day)
  • Inject HSV-1 (2 ⁇ 10 5 PFU / 50 ⁇ l / mouse) into the depilated area with a microsyringe.
  • (4) Record the onset degree (lesion score) of herpes symptoms (appearing in a band) and death cases over 14 days.
  • HSV-2 genital herpes model (1) Onset and survival rate (Figs. 1 to 5) The MGDG preparation administered alone significantly suppressed the onset in the 0.1 mg and 1 mg / day administration groups (# 3, # 4) (FIG. 1), and there were no deaths (FIG. 5). Thymidine dose-dependently suppressed the onset and mortality, and a remarkable therapeutic effect was observed particularly in the 20 mg / day administration group (# 7) (FIGS. 1 and 5).
  • the MGDG preparation administered alone showed a stronger virus growth inhibitory effect as the virus inoculation amount was lower, and a sufficient effect was obtained even at 0.1 mg / day.
  • thymidine 1 mg, 5 mg
  • there was no difference in the effect due to the difference in the amount of virus inoculated and a marked suppression effect was observed in the 20 mg / day administration group.
  • the MGDG preparation and thymidine were used in combination, a remarkable combination effect was observed at a low inoculation dose, and a remarkable effect was observed even when a small amount of the MGDG preparation ⁇ 0.1 mg ⁇ + ⁇ thymidine ⁇ 1 mg / day was administered.
  • Dry powder when administered alone, was less effective than the MGDG preparation, but inhibited virus growth. When the amount of virus inoculated was reduced, a remarkable growth inhibitory effect was observed when used in combination with thymidine.
  • x-axis concentration of thymidine / IC 50 of thymidine in the absence of MGDG preparation (1.2 ⁇ g / ml)
  • y-axis IC 50 (12 ⁇ g / ml ) of MGDG preparation in IC 50 / thymidine absence of MGDG preparation in thymidine presence of a fixed concentration
  • x-axis concentration of MGDG preparation / IC 50 of thymidine in the absence of MGDG preparation (12 ⁇ g / ml)
  • y-axis IC thymidine in the presence of MGDG preparations constant concentration 50 / MGDG preparation IC 50 of MGDG preparation in the absence (1.2 ug / ml)
  • IC 50 value was calculated from the average of two measurements.
  • the IC 50 values of MGDG preparation is 12 ⁇ g / ml
  • IC 50 of thymidine was 1.2 ug / ml (Table 1).
  • HSV-2 infection (genital herpes) experiment (Effect of Kokkomikusa sp. KJ strain) It was verified that the strain KJ was similar to HSV-2 infectious disease, as was the case with S. spp. MBIC11204.
  • changes in efficacy when combined with thymidine (0.5 mg / day) were examined.
  • Test plot # 1 control (distilled water)
  • Test plot # 2 ACV (1 mg / day)
  • Test plot # 3 Algae (dry powder) (5 mg / day)
  • Test plot # 4 Algae (dry powder) (5 mg / day) + thymidine (0.5 mg / day)
  • Test plot # 5 Algae (dry powder) (10 mg / day)
  • (3) Local inoculation of HSV-2 (UW268 strain) (1 ⁇ 10 3 PFU / 20 ⁇ l / mouse).
  • (5) Record the onset of herpes symptoms (lesion score) and deaths over 14 days.
  • the HUT medium shown in FIG. 15 may be used in the usual manner (using the same culture conditions as those of the above-mentioned strain of Kokkomixa sp. KJ). May be).
  • Dried powder of each alga body can be obtained by drying the alga body collected from the culture solution by centrifugal separation with a drum dryer and pulverizing with a pulverizer.
  • An MGDG preparation of each algae can be obtained from the dried powder by the same extraction operation as in the case of Kokkomixa sp. KJ.
  • the obtained MGDG preparations were used for the following examinations: Commercially available spinach (Spinacia oleracea) was also finely dried and freeze-dried. The MGDG preparation was obtained by crushing with a crusher and extracting MGDG.
  • Tables 2 and 3 show the fatty acid composition ratio of each sample by the area percentage method.
  • Table 3 summarizes the calculation results excluding C6: 0 and unknown components 1 and 2 (Unknown 1 and 2).
  • the area ratio of the two components is extremely biased at 3: 1.
  • the combinations of fatty acid residues are (C18: 2 (other than n-6) and C18: 2 (other than n-6)) and (C18: 2 (other than n-6) and C18: 3 n3)
  • "-" Represents non-detection.
  • the constituent fatty acids are C16: 3 and C18: 3 (n-3) monogalactosyldiacylglycerol (MGDG1), and (2) the constituent fatty acids are C16: 2 and C18: 2.
  • MGDG2 Monogalactosyldiacylglycerol
  • MGDG3 monogalactosyldiacylglycerol
  • MGDG4 monogalactosyldiacylglycerol
  • MGDG5 monogalactosyldiacylglycerol
  • MGDG1 to MGDG5 The virucidal activity of each MGDG (MGDG1 to MGDG5) constituting the MGDG preparation was compared.
  • Methodhod> (1) The MGDG preparation derived from Kokkomixa sp. KJ strain was subjected to HPLC, and each peak was collected to obtain five kinds of purified MGDG (MGDG1, MGDG2, MGDG3, MGDG4, MGDG5). In addition, MGDG preparations (containing MGDG1 to MGDG5) before fractionation were prepared as Mix products.
  • each sample was mixed with each virus solution (2 ⁇ 10 5 PFU / ml) to a final concentration of 50 ⁇ g / ml, and allowed to stand at 37 ° C. for 60 minutes. Table 5 shows the viruses and host cells used.
  • (3) After diluting the mixed solution of (2) with a MEM medium containing no fetal bovine serum, a plaque assay medium was overlaid and cultured at 37 ° C. for 2 to 3 days.
  • the cells were fixed and stained with neutral red solution, and the number of plaques was measured under a microscope. Using the number of appearances of the virus when no sample was added as a reference (100%), the virus remaining rate of each sample was calculated. The virucidal performance of each sample was evaluated from the virus residual rate.
  • HPLC measurement results are shown in FIGS.
  • the vertical axis of the chromatogram is normalized so that the peak maximum value in each sample is 1.
  • -At least 5 peaks were detected in the MGJ preparation of the KJ strain.
  • the MGDG preparations of each organism other than the KJ strain at least one peak whose retention time was the same as or very close to that of the MGJ preparation of the KJ strain was detected. It is presumed that the peak having the same retention time has the same chemical structure as MGDG derived from the KJ strain.
  • -Virucidal activity against HSV-2, IFV and FCV is observed in five peaks derived from the KJ strain MGDG preparation (Experiment 9; Fig. 23).
  • the MGDG preparation of each organism other than the KJ strain has at least one peak corresponding to the five peaks derived from the KJ strain MGDG preparation, it is presumed to have virusicidal activity as well. You. That is, these MGDG preparations can be expected to have the same effects as those of the KJ strain MGDG preparation.
  • the fifth peak of the KDG strain MGDG preparation is known to have high virucidal activity against HSV-2 and IFV (FIG. 23).
  • the anti-herpes virus agent of the present invention contains a substance derived from a unicellular algae (preferably microalgae) as an active ingredient, and can exert anti-herpes virus activity by a different mechanism of action from existing anti-herpes virus agents. Therefore, it is also suitable for use in combination with existing anti-herpes virus agents, and provides a new therapeutic strategy.
  • the active ingredient of the anti-herpesvirus agent of the present invention is a single cell algae (preferably microalgae), high safety can be expected.

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Abstract

La présente invention aborde le problème de la fourniture d'un nouveau moyen qui est efficace dans le traitement ou la prévention d'une infection par le virus de l'herpès. L'invention concerne un agent anti-virus de l'herpès contenant une substance dérivée d'algues unicellulaires utilisée comme principe actif.
PCT/JP2019/029309 2018-07-31 2019-07-25 Agent anti-virus de l'herpès WO2020026953A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020019730A (ja) * 2018-07-31 2020-02-06 株式会社デンソー 抗インフルエンザ剤

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0449242A (ja) * 1990-06-15 1992-02-18 Chiba Seifun Kk 抗ヘルペス剤、動物用抗ヘルペス剤
JP2001505908A (ja) * 1996-12-09 2001-05-08 ウインストン ダンカン ケルヴィン 生物学的制御方法
JP2005247757A (ja) * 2004-03-04 2005-09-15 Nikken Sohonsha Corp 抗ウイルス剤
JP2007126383A (ja) * 2005-11-02 2007-05-24 Univ Of Tokushima 消化管粘膜保護剤、カベオリン遺伝子発現促進剤及び抗ストレス剤
JP2010529012A (ja) * 2007-06-01 2010-08-26 コミッサリア ア レネルジ アトミック モノガラクトシルジアシルグリセロール合成酵素阻害活性を有する化合物の除草剤又は殺藻剤としての使用、除草組成物及び殺藻組成物
JP2014027929A (ja) * 2012-07-06 2014-02-13 Euglena Co Ltd 生物用飼料添加剤
WO2014192940A1 (fr) * 2013-05-31 2014-12-04 味の素株式会社 Procédé de production de glucosylglycérol
JP2015015918A (ja) * 2013-07-10 2015-01-29 株式会社デンソー 新規微細藻類

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0449242A (ja) * 1990-06-15 1992-02-18 Chiba Seifun Kk 抗ヘルペス剤、動物用抗ヘルペス剤
JP2001505908A (ja) * 1996-12-09 2001-05-08 ウインストン ダンカン ケルヴィン 生物学的制御方法
JP2005247757A (ja) * 2004-03-04 2005-09-15 Nikken Sohonsha Corp 抗ウイルス剤
JP2007126383A (ja) * 2005-11-02 2007-05-24 Univ Of Tokushima 消化管粘膜保護剤、カベオリン遺伝子発現促進剤及び抗ストレス剤
JP2010529012A (ja) * 2007-06-01 2010-08-26 コミッサリア ア レネルジ アトミック モノガラクトシルジアシルグリセロール合成酵素阻害活性を有する化合物の除草剤又は殺藻剤としての使用、除草組成物及び殺藻組成物
JP2014027929A (ja) * 2012-07-06 2014-02-13 Euglena Co Ltd 生物用飼料添加剤
WO2014192940A1 (fr) * 2013-05-31 2014-12-04 味の素株式会社 Procédé de production de glucosylglycérol
JP2015015918A (ja) * 2013-07-10 2015-01-29 株式会社デンソー 新規微細藻類

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHIRASUWAN, N. ET AL.: "Anti HSV-1 activity of sulphoquinovosyl diacylglycerol isolated from Spirulina platensis", SCIENCEASIA, vol. 35, no. 2, 2009, pages 137 - 141, XP002680721, DOI: 10.2306/SCIENCEASIA1513-1874.2009.35.137 *
DE JULIAN-ORTIZ, J. V. ET AL.: "Virtual Combinatorial Syntheses and Computational Screening of New Potential Anti-Herpes Compounds", JOURNAL OF MEDICINAL CHEMISTRY, vol. 42, no. 17, 1999, pages 3308 - 3314, XP002909417, DOI: 10.1021/jm981132u *
HAYASHI, K. ET AL.: "In vitro and in vivo anti-herpes simplex virus activity of monogalactosyl diacylglyceride from Coccomyxa sp. KJ (IPOD FERM BP-22254), a green microalga", PLOS ONE, vol. 14, no. 7, 16 July 2019 (2019-07-16), pages e0219305, XP055682802 *
HERNANDEZ-CORONA, A. ET AL.: "Antiviral activity of Spirulina maxima against herpes simplex virus type 2", ANTIVIRAL RESEARCH, vol. 56, no. 3, 2002, pages 279 - 285, XP009121553, DOI: 10.1016/S0166-3542(02)00132-8 *
JANWITAYANUCHIT, W. ET AL.: "Synthesis and anti-herpes simplex viral activity of monoglycosyl diglycerides", PHYTOCHEMISTRY, vol. 64, no. 7, 2003, pages 1253 - 1264, XP004470666, DOI: 10.1016/j.phytochem.2003.09.008 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020019730A (ja) * 2018-07-31 2020-02-06 株式会社デンソー 抗インフルエンザ剤
JP7233043B2 (ja) 2018-07-31 2023-03-06 株式会社デンソー 抗インフルエンザ剤

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