WO2007035123A1 - Antimutagene - Google Patents
Antimutagene Download PDFInfo
- 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
Links
- 239000002592 antimutagenic agent Substances 0.000 title claims description 7
- 235000018185 Betula X alpestris Nutrition 0.000 claims abstract description 13
- 235000018212 Betula X uliginosa Nutrition 0.000 claims abstract description 13
- JYDNKGUBLIKNAM-UHFFFAOYSA-N Oxyallobutulin Natural products C1CC(=O)C(C)(C)C2CCC3(C)C4(C)CCC5(CO)CCC(C(=C)C)C5C4CCC3C21C JYDNKGUBLIKNAM-UHFFFAOYSA-N 0.000 claims abstract description 12
- FVWJYYTZTCVBKE-ROUWMTJPSA-N betulin Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(CO)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C FVWJYYTZTCVBKE-ROUWMTJPSA-N 0.000 claims abstract description 12
- MVIRREHRVZLANQ-UHFFFAOYSA-N betulin Natural products CC(=O)OC1CCC2(C)C(CCC3(C)C2CC=C4C5C(CCC5(CO)CCC34C)C(=C)C)C1(C)C MVIRREHRVZLANQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 230000002790 anti-mutagenic effect Effects 0.000 description 27
- 239000003471 mutagenic agent Substances 0.000 description 22
- 231100000707 mutagenic chemical Toxicity 0.000 description 22
- 230000002559 cytogenic effect Effects 0.000 description 18
- 230000003505 mutagenic effect Effects 0.000 description 18
- 229960004397 cyclophosphamide Drugs 0.000 description 13
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 12
- 230000031864 metaphase Effects 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 230000001594 aberrant effect Effects 0.000 description 8
- 210000002798 bone marrow cell Anatomy 0.000 description 7
- 239000013641 positive control Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000011260 co-administration Methods 0.000 description 5
- 230000000254 damaging effect Effects 0.000 description 5
- 208000031404 Chromosome Aberrations Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 231100000005 chromosome aberration Toxicity 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 231100000244 chromosomal damage Toxicity 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000834 fixative Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010028400 Mutagenic effect Diseases 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 231100000243 mutagenic effect Toxicity 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003307 slaughter Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108091060290 Chromatid Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000219095 Vitis Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000004410 anthocyanin Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002072 anti-mutant effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002962 chemical mutagen Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004756 chromatid Anatomy 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002443 hepatoprotective effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000000815 hypotonic solution Substances 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000004560 pineal gland Anatomy 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000011514 vinification Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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)
-
- 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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs 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.
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)
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 |
-
2005
- 2005-09-21 WO PCT/RU2005/000480 patent/WO2007035123A1/fr active Application Filing
Patent Citations (4)
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)
Title |
---|
VASILINKO J.K. ET AL., EXPERIMENTALNAYA I KLINICHESKAYA FARMAKOLOGYA, vol. 56, no. 4, 1993, pages 53 - 55 * |
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