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WO2007035123A1 - Antimutagene - Google Patents

Antimutagene Download PDF

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Publication number
WO2007035123A1
WO2007035123A1 PCT/RU2005/000480 RU2005000480W WO2007035123A1 WO 2007035123 A1 WO2007035123 A1 WO 2007035123A1 RU 2005000480 W RU2005000480 W RU 2005000480W WO 2007035123 A1 WO2007035123 A1 WO 2007035123A1
Authority
WO
WIPO (PCT)
Prior art keywords
effect
antimutagenic
dose
cytogenetic
mutagen
Prior art date
Application number
PCT/RU2005/000480
Other languages
English (en)
Russian (ru)
Inventor
Aly Kurmanovich Zhanataev
Andrei Dimitreevich Durnev
Vladimir Vladimirovich Balakshin
Aleksey Nikolaevich Chistyakov
Original Assignee
Obschestvo S Ogranichennoi Otvetztvennostju 'berezovy Mir'
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Obschestvo S Ogranichennoi Otvetztvennostju 'berezovy Mir' filed Critical Obschestvo S Ogranichennoi Otvetztvennostju 'berezovy Mir'
Priority to PCT/RU2005/000480 priority Critical patent/WO2007035123A1/fr
Publication of WO2007035123A1 publication Critical patent/WO2007035123A1/fr

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Classifications

    • 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)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/01Hydrocarbons
    • A61K31/015Hydrocarbons carbocyclic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to medicine, namely, to 5 the search for new and effective agents with antimutagenic activity.
  • antimutagens are chemical, physical and biological factors that reduce the frequency of mutations and thereby protect the gene.
  • An active search for chemical antimutagens is carried out in two directions: the study of synthetic chemical compounds for the presence of antimutagenic properties (1) and research on products of natural origin on this subject.
  • a new field in the study of natural products is the analysis of the antimutagenic properties of food additives of plant origin (BAA) (3-7).
  • BAA food additives of plant origin
  • a prerequisite for such studies is the presence in many dietary supplements of such properties as anti-inflammatory, sedative, restorative while there are no undesirable side effects when used.
  • the objective of the invention is to find a new promising zo antimutagen of natural origin.
  • birch bark extract white part of birch bark
  • antimutagenic properties The inventors have found that birch bark extract (white part of birch bark) has antimutagenic properties.
  • betulin has recently been a substance that attracts widespread attention.
  • Birch bark extract can be obtained by various known methods. So, in accordance with documents SU 382657 and SU 2172178, extraction is carried out using alcohol. In accordance with 20 patent RU 2192879, owned by the applicant, birch bark extraction is carried out with toluene, with obtaining as a final product a dry crystalline substance, the main component of which (up to 97%) is betulin - triterpene diatomic alcohol.
  • the method is based on visual registration of chromosomal lesions in bone marrow cells of small laboratory rodents.
  • Birch bark extract (hereinafter BE) was administered orally in an aqueous suspension of Tween-80 at doses of 50, 150 and 450 mg / kg.
  • Mutagens cyclophosphamide at the rate of 20 mg / kg and dioxidine at a dose of 200 mg / kg were administered intraperitoneally in the form of aqueous solutions.
  • Three modes of treatment of animals were used: a single co-administration of BE with a mutagen, a preliminary five-day introduction of BE, providing for its combined use with mutagen on the last day of treatment of animals, and also a daily 5-day co-administration of BE with a mutagen.
  • Cytogenetic preparations were prepared 24 hours after a single or, in the case of repeated administrations, the last administration of the drug.
  • the animals were injected with colchicine (Segva, Germany) at a rate of 2.5 mg / kg 2.5 hours before slaughter in order to
  • the suspension was again centrifuged, the supernatant was removed, the precipitate was resuspended in 0.5 ml of the newly added fixative and applied to wet pre-defatted and cooled glasses, which were dried in a flame of a 5 alcohol burner.
  • Staining was performed with azure-eosin.
  • the composition of the dye included: 5 parts of azure (0.1%), 2 parts of eosin (0.1%), 10 parts of distilled water.
  • a Zeiss Standart-20 microscope, 10 X 100 was used for cytogenetic analysis. Cytogenetic analysis took into account cells with achromatic spaces (geps), single and paired fragments of chromosomes, chromosomes and mosomes (more than 5 chromosomal lesions in the cell). Evaluation of antimutagenic activity was performed by comparing the total number of cells with heps and structural damage.
  • the obtained value is statistically significantly different from the value of the positive control and corresponds to a 53% decrease in the cytogenetic effect of dioxidine.
  • BE at a dose of 150 mg / kg led to an increase in the antimutagenic effect to 61%; 5 total 4.0 ⁇ 0.9% of damaged metaphases were recorded.
  • BE in the maximum dose used 450 mg / kg also had a significant antimutagenic effect. However, in quantitative terms, the effect was less pronounced and amounted to only 33%.
  • Table Ns1 presents the results of experiments on the effect of a single administration of BE on the cytogenetic effects of this mutagen.
  • Table Ns1 presents the results of experiments on the effect of a single administration of BE on the cytogenetic effects of this mutagen.
  • the protective effect of BE increased and amounted to 63%.
  • the drug showed the maximum antimutagenic effect - complete suppression of the damaging effect of the mutagen: the obtained indicator is 2.6 ⁇ 0.7% of aberrant metaphases b statistically from the value characterizing the spontaneous mutation level (1.6 ⁇ 0.6%).
  • the conducted studies indicate the presence of antimutagenic activity in BE. According to the totality of the data obtained, the antimutagenic effects of BE are most pronounced under conditions of preliminary multi-day administration and when used in the dose range of 50-150 mg / kg.
  • a comparative analysis of the antimutagenic effect with respect to the damaging effect of the two used mutagens shows that formally BE is somewhat more effective when dioxidine is used as a model mutagen. However, this difference is not fundamental.
  • Birch bark extract in the dose range of 50 - 450 mg / kg has antimutagenic activity, expressed in • a decrease in the cytogenetic effects of known mutagens - cyclophosphamide and dioxidine.
  • the protective antimutagenic effect in most cases exceeds 50%, which indicates the effectiveness of the possible use of betulin and containing birch bark extract as a pharmacological means of protecting the genome.
  • Table Ns 1, Effect of a single administration of BE on the cytogenetic effects of dioxidine or cyclophosphamide in mouse bone marrow cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne la possibilité d'utilisation en tant qu'antimutagène de la bétuline contenue dans un extrait d'écorce de bouleau.
PCT/RU2005/000480 2005-09-21 2005-09-21 Antimutagene WO2007035123A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/RU2005/000480 WO2007035123A1 (fr) 2005-09-21 2005-09-21 Antimutagene

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/RU2005/000480 WO2007035123A1 (fr) 2005-09-21 2005-09-21 Antimutagene

Publications (1)

Publication Number Publication Date
WO2007035123A1 true WO2007035123A1 (fr) 2007-03-29

Family

ID=37889089

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU2005/000480 WO2007035123A1 (fr) 2005-09-21 2005-09-21 Antimutagene

Country Status (1)

Country Link
WO (1) WO2007035123A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998034603A1 (fr) * 1997-02-11 1998-08-13 Regents Of The University Of Minnesota Utilisation de la betuline et d'analogues dans le traitement de l'infection par herpesvirus
RU2183965C1 (ru) * 2001-06-27 2002-06-27 Сироткин Геннадий Владимирович Способ профилактики и лечения алкогольной интоксикации
RU2254032C2 (ru) * 2003-08-14 2005-06-20 Закрытое акционерное общество "СНС-фарма" Композиция биологически активных веществ
RU2258528C1 (ru) * 2004-05-28 2005-08-20 Государственное учреждение системы высшего и послевузовского профессионального образования "Сибирский государственный медицинский университет" (ГУ СВ ПО СибГМУ) Лекарственное средство, обладающее антимутагенным действием

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998034603A1 (fr) * 1997-02-11 1998-08-13 Regents Of The University Of Minnesota Utilisation de la betuline et d'analogues dans le traitement de l'infection par herpesvirus
RU2183965C1 (ru) * 2001-06-27 2002-06-27 Сироткин Геннадий Владимирович Способ профилактики и лечения алкогольной интоксикации
RU2254032C2 (ru) * 2003-08-14 2005-06-20 Закрытое акционерное общество "СНС-фарма" Композиция биологически активных веществ
RU2258528C1 (ru) * 2004-05-28 2005-08-20 Государственное учреждение системы высшего и послевузовского профессионального образования "Сибирский государственный медицинский университет" (ГУ СВ ПО СибГМУ) Лекарственное средство, обладающее антимутагенным действием

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
VASILINKO J.K. ET AL., EXPERIMENTALNAYA I KLINICHESKAYA FARMAKOLOGYA, vol. 56, no. 4, 1993, pages 53 - 55 *

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