Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
  • A61K35/56—Materials from animals other than mammals
  • A61K35/63—Arthropods
  • A61K35/64—Insects, e.g. bees, wasps or fleas
  • A61K35/644—Beeswax; Propolis; Royal jelly; Honey
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/12—Ketones
  • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/77—Sapindaceae (Soapberry family), e.g. lychee or soapberry
• • 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
• • 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 a new therapeutic composition comprising a derivative of galvinoxyl alone or possibly associated with propolis, to a process for the preparation of said composition, and to the use of this composition as an antiviral means, in a manner general vis-à-vis lipoprotein enveloped viruses (abbreviated LEV), and in particular vis-à-vis herpes viruses and their analogues that are part of the set of LEVs.
• LEV vis-à-vis lipoprotein enveloped viruses
• herpes viruses and their analogues that are part of the set of LEVs.
• Propolis is a gummy substance that is recovered in hives. Specifically, it is a substance that bees collect on certain plants, including poplar bud scales and alders, collect and use to seal hives cracks, fix the rays and varnish the walls. In the field of beekeeping, propolis is known as the antibiotic or disinfectant means of the hive preventing the proliferation of bacteria and mold.
• Crude propolis generally contains resins and balsamic substances (approximately 55-50% by weight), beeswax (approximately 30-35% by weight), ethereal oils (approximately 10% by weight) and pollen (approximately 5% by weight), see in particular EP-A-0 061 508 (page 2, lines 1-28), EP-A-0 109 993 (page 1, lines 24-26) and EMSCHNEIDEWIND et al, Die Pharmazie 34, 103, (1979). EP-A-0 061 508 (page 3, lines 6-7) and EP-A-0 109 993 are known in particular.
• EBV Epstein Barr Virus
• HSVi herpes simplex virus type 1
• HSV 2 herpes simplex virus type 2
• HSViR herpes simplex type 1 resistant to acyclovir [reference antiviral with the structural formula of 2-amino-1,9-dihydro-9 - [(2-hydroxyethoxy) methyl] -6H purine-6 one]
• LEV lipoprotein envelope virus
• ZV Zoster virus
• a galvinoxyl derivative can be used as an antiviral medium for lipoprotein enveloped viruses (LEVs), and in particular vis-à-vis 'herpes.
• LUVs lipoprotein enveloped viruses
• the present invention more particularly relates to a galvinoxyl derivative chemically named "2,6-di-t-Butyl- (3,5-di-t-butyl-4-oxo-2,5-cyclohexadien-1-ylidene "p-tolylhydroxy" and represented by the following formula:
• LUVs lipoprotein enveloped viruses
• galvinoxyl derivative for convenience, 2,6-di-t-Butyl- (3,5-di-t-butyl-4-oxo-2,5-cyclohexadien-1-ylidene) -p-tolylhydroxy compound as defined herein above will simply be referred to as "galvinoxyl derivative" in the present application.
• the galvinoxyl derivative as defined above is more particularly used in the treatment of diseases caused by the herpes HSVi, HSV 2 and / or HSViR strains.
• the galvinoxyl derivative as defined above is associated with propolis.
• the present invention also relates to a pharmaceutical composition characterized in that it comprises a galvinoxyl derivative as defined above.
• composition as defined above further comprises propolis.
• said composition comprises from 100 to 650 parts by weight of the galvinoxyl derivative for one part by weight of propolis.
• composition of the invention as defined above is used in the treatment of diseases caused by lipoprotein-enveloped viruses (LEV), and more particularly in the treatment of diseases caused by herpes HSVi, HSV 2 strains. and / or HSViR.
• LUV lipoprotein-enveloped viruses
• composition as defined above comprises the galvinoxyl derivative in combination with one or more excipients suitable for oral, injectable or local administration.
• composition may further comprise propolis.
• such a composition will be particularly advantageous vis-à-vis herpes and herpes-like diseases. It has indeed been found that such a composition is particularly effective in the treatment of herpes simplex type 1 and type 2, especially diseases caused by the HSVi and HSViR strains, which are transmissible by contact between mucous membranes. on the one hand, and diseases caused by the HSV 2 strains, which are sexually transmitted and include, in particular, venereal growths, on the other hand.
• the derivative of galvinoxyl alone or possibly associated with propolis is used for obtaining an antiviral drug intended for use in human or veterinary therapy vis-à-vis diseases caused by viruses lipoprotein envelope, including diseases caused by strains (i) HSVI, HSV2 and HSViR and (ii) IVA, EBV and ZV.
• the antiviral composition according to the invention may be prepared according to a method known per se.
• the process for the preparation of the composition is characterized by mixing the galvinoxyl derivative alone or with propolis in a suitable aqueous or oily physiological medium at a temperature of between 15 ° C and 75 ° C.
• the weight ratio of the galvinoxyl derivative to propolis ranges from 100/1 to 650/1.
• the infectious titres are determined in the usual manner according to the method known as the limiting dilutions and compared to control samples of HSViR virus, propolis control samples and control samples of HG1 incubated under the same conditions (it has not It has not been necessary to prepare control samples of excipients since previous tests have demonstrated the lack of effect of the excipient on viruses, especially HSViR).
• the method described by RFSCHINAZI et al., Antimicrob was used. Agents Chemother. , 22 (No. 3), pages 499-507 (1982) and resumed by JC POTTAGE, ibid. 30, (No. 2), pages 215-219, (1986), taking into account the following definitions:
• Y c Y a XY b .
• a mixture of 59 g of white petrolatum, 2.99 g of sorbitan sesquioleate and 3 g of glycerol monooleate is heated to 70-75 ° C.
• the mixture is ceased to heat when the mixture has become homogeneous and then 5 g of DEG, 30 g of water at a temperature of 65 ° C. or less are added with stirring and the stirring is continued until cooling to RT.
• polyethylene glycol 1500 stearate are mixed with 13 g of glycerol monostearate, 3 g of glycerol monooleate, 10.5 g of decyl oleate, 5.5 g of capric / caprylic triglyceride and 5 g of glycerol monostearate.
• glycerol isostearate The mixture is gradually heated to 70-75 ° C and the heating is stopped as soon as the mixture has become homogeneous. 8 g of DeG are then added and the mixture is stirred slowly. 3 g of propylene glycol, 0.3 g of citral and 47 g of water are then poured into the resulting mixture.
• the propolis used in Examples 1 and 3 above is a purified propolis obtained by extraction with EtOH at 80% [ie EtOH / H 2 O mixture in a weight ratio of approximately (8/2)], as indicated above. after.
• the raw Prp is deposited by the bees on perforated plastic grates mounted on frames arranged in the hives. These grids containing the crude Prp are taken from the hives and brought to -30 ° C in a freezer so as to make the crude Prp brittle, which is then grinded with mortar.
• the milled material is extracted with 80% EtOH, 1 part by weight of crude Prp for 10 parts by volume of 80% EtOH, for 24 hours, with stirring, at RT.
• the insoluble residue is removed by filtration.
• the filtrate which is collected is evaporated under reduced pressure and gives a dry extract of light brown color. Yield: 65% by weight, based on the initial crude Prp.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Virology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Chemical & Material Sciences (AREA)
• Natural Medicines & Medicinal Plants (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Biotechnology (AREA)
• Oncology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Insects & Arthropods (AREA)
• Organic Chemistry (AREA)
• Molecular Biology (AREA)
• General Chemical & Material Sciences (AREA)
• Communicable Diseases (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Alternative & Traditional Medicine (AREA)
• Botany (AREA)
• Medical Informatics (AREA)
• Mycology (AREA)
• Animal Husbandry (AREA)
• Microbiology (AREA)
• Zoology (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)

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• 2010
  • 2010-08-10 FR FR1056523A patent/FR2963736B1/fr not_active Expired - Fee Related
• 2011
  • 2011-08-09 WO PCT/IB2011/053543 patent/WO2012020370A1/fr active Application Filing
  • 2011-08-09 EP EP11754743.0A patent/EP2603229A1/de not_active Withdrawn

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