The use of phospholipid complexes of extracts of vitis vinifera as protivoateroskleroticheskim agents
The invention relates to medicine. The proposed use of phospholipid complexes of oligomeric proanthocyanidins for therapeutic and prophylactic treatment of atherosclerosis and treatment of atherosclerosis. The invention prevents the formation of atherosclerotic plaques. 2 S. and 3 C.p. f-crystals, 1 table. The invention relates to the use of phospholipid complexes of oligomeric proanthocyanidins containing from 2 to 7 catechin units extracted from Vitis vinifera, for the preparation of drugs for the treatment and prevention of atherosclerosis and myocardial infarction and brain.Extracts of Vitis vinifera already known and used in the treatment of cardiovascular disorders associated with venous insufficiency, for treating disorders permeability and resistance of the capillaries and scarring. These extracts, which can be obtained from the seeds of plants, as described in GB-A-1541469 or in FR-A-2092743 are a mixture of polyphenols such as epicatechin and its polymerization products, partially esterified by Gallic acid on the C-3 hydroxyl monomer. Phospholipid complexes of extracts of Vitis vinifera described in U.S. patent US-4963527 and currently commercially available PAYE in accordance with US-4963527, upon systemic administration, preferably oral, display a marked protivoateroskleroticheskim activity for both animals and humans.More defined, found that phospholipid complexes of oligomeric proanthocyanidins containing from 2 to 7 catechin units extracted from Vitis vinifera, prevent or reduce the formation of atherosclerotic plaques dose-dependent manner.Such activity was detected in rabbits, which were kept on a diet with a high content of cholesterol, in order to induce atherosclerotic lesions, similar lesions in humans, on the vascular level, particularly in the aortic arch, abdominal aorta, carotid arteries and cerebral vessels. In these models the above-mentioned phospholipid complexes change the state of the macro - and microscopic blood vessels, reducing, compared with untreated animals, as the number of atherosclerotic plaques and the severity of the process affects the beneficial effect on blood vessels and tissue. In another model of atherosclerosis, created with the purpose of studying the possibilities for protection of the brain, which was surgically reduced vascular lumen of the internal carotid artery of the rabbit, despite the introduction of hyperhaline vascular walls, and increased life expectancy of animals. In addition, patients suffering from atherosclerosis, see reducing obstruction of the carotid artery due to atherosclerotic plaques, and improved blood flow in the carotid artery, measured by Doppler ultrasound echography.Phospholipid complexes of proanthocyanidins extracted from Vitis vinifera, can be used in appropriate oral compositions, such as tablets, soft and hard gelatin capsules at doses ranging from 50 to 500 mg two to three times a day, depending on the severity of the disease that is being treated. Preparation of pharmaceutical compositions can be effected in accordance with conventional techniques and excipients.The following examples illustrate the invention in more detail.Example 1 3 groups, each with 8 new Zealand rabbits were treated as follows: Group 1: Control, normal diet Group 2): a Diet high in cholesterol (0.2% cholesterol) Group 3: a Diet high cholesterol + phospholipid complex of extracts of Vitis vinifera (0.2% cholesterol + 2% Leucoselect).After 8 weeks, during which measured the levels of cholesterol, LDL/VLDL (glipizide, animals slaughtered.Estimated number, size and distribution of atherosclerotic lesions in the thoracic aorta and abdominal aorta.Strips of aorta fixed and stained with Sudan IV for visualization of lesions and evaluation of cholesterol vessels and content of oxidized cholesterol by gas chromatography. The results presented in the table demonstrate that the processing of phospholipid complexes of extracts of Vitis vinifera statistically reduces atherosclerotic lesions, induced by a diet high in cholesterol.Example 2 Capsules containing 500 mg of phospholipid complex of extracts of Vitis vinifera Composition: Complex extract of Vitis vinifera with soy phosphatidylcholine - 200 mg Lactose - 57 mg Modified starch 40 mg
Magnesium stearate - 3.0 mg
Complex extract of Vitis vinifera with soy phosphatidylcholine 250 mg
Microcrystalline cellulose - 118 mg
Precipitated silica 3 mg
Magnesium stearate 4 mg
Anionic polymer of methacrylic acid and its esters - 12 mg
Talc - 8 mg
Magnesium carbonate - 8 mg
Corn starch 5 mg
Arabian gum - 159 mg
Partially hydrogenated vegetable oil 100 mg
Soy lecithin - 5 MND
1. The use of phospholipid complexes of oligomeric proanthocyanidins containing from 2 to 7 catechin units extracted from Vitis vinifera, as an active ingredient for the manufacture of drugs for therapeutic and prophylactic treatment of atherosclerosis.2. Application under item 1, where a single dose of the drug ranges from 50 to 500 mg of active ingredient.3. Application under item 1 or 2, where the drug is administered orally.4. Application under item 3, where the medicinal product is presented in the form of soft or hard gelatin capsules or tablets.5. A method of treating atherosclerosis, which involves the administration to a patient an effective amount of phospholipid complex extract of Vitis vinifera.
< / BR>where W and X are both carbon, T is nitrogen, U represents CR1where R1represents hydrogen, or alkyl containing 1-8 carbon atoms, R represents-N(CH2R5)-SO2Z, Q represents -(C=O)-NHOH, with
< / BR>is a benzene ring, or is a heteroaryl ring of 5 to 6 atoms in the cycle, which may contain 0-2 heteroatoms selected from nitrogen, oxygen and sulfur, in addition to the heteroatom of nitrogen, denoted as W, where benzene or heteroaryl ring may optionally contain one or two substituent R1where permissible; Z is phenyl, which is optionally substituted by phenyl, alkyl with 1-8 carbon atoms, or a group OR2; R1represents halogen, alkyl with 1-8 carbon atoms, alkenyl with 2-6 carbon atoms, perfluoroalkyl from 1 to 4 carbon atoms, phenyl, optionally substituted by 1-2 groups OR2group-NO2group -(CH2)nZ, where Z is a phenyl which allows an alkyl with 1-8 carbon atoms, phenyl, optionally substituted with halogen, or heteroaryl radical containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; R5represents hydrogen, alkyl with 1-8 carbon atoms, phenyl, or heteroaryl containing 5 to 6 atoms in the cycle, including 1-2 heteroatoms selected from nitrogen, oxygen and sulfur; or their pharmaceutically acceptable salts
< / BR>or
< / BR>where R is SH, benzyl or phenyl, optionally substituted by a hydroxy-group or a lower alkoxygroup, or a group of the formula
< / BR>R1is hydrogen or halogen; X represents -(CH2)n-; -CH(R2)(CH2)n-; -CH2O(CH2)n-; CH2NH-; benzyl, -C(R2)=CH-; CH2CH (OH)- or thiazol-2,5-diyl; Y represents-S -; (CH2)n; -O-; -NH-; -N (R2)-; -CH=CH-; -NHC(O)NH-; -N(R2)C(O)N(R2)-; -N[CH2WITH6H3(OCH3)2]-; -N(CH2WITH6H5)-; -N(CH2WITH6H5)C(O)N(CH2WITH6H5)-; -N(alkoxyalkyl)-; -N(cyclooctylmethyl)-; 2,6-pyridyl; 2,5-furanyl; 2,5-thienyl; 1,2-cyclohexyl; 1,3-cyclohexyl; 1,4-cyclohexyl; 1,2-naphthyl; 1,4-naphthyl; 1,5-naphthyl; 1,6-naphthyl or diphenylene; 1,2-phenylene; 1,3-phenylene or 1,4-phenylene, where phenylenebis group optionally substituted by 1-4 substituents selected from the group comprising halogen, lower alkyl, lower alkoxygroup, the hydroxy-group, carboxypropyl, -COO-lower thiazolyl, 2-oxo[1,2,3,5] oxadiazolyl, 5-thioxo[1,2,4]oxadiazolyl and 5-tert-butylsulfonyl[1,2,4] oxadiazolyl; X' represents -(CH2)n-; (CH2)nCH(R2)-; -(CH2)nOCH2-; -NHCH2-; benzyl, -CH= C(R2)-; -CH(OH)CH2or thiazol-2,5-diyl; R2denotes lower alkyl, lower alkoxygroup or benzyl and n = 0-3, their pharmaceutically acceptable salts, mono - and diesters, except (R)-1-[(R)- and (R)-1-[(S)-3-mercapto-2-methylpropionyl] pyrrolidin-2-carboxylic acid; medicinal product with amyloidoses activity, and the method of obtaining these derivatives
FIELD: medicine, cardiology, phytotherapy, pharmacy.
SUBSTANCE: invention relates to the field in development of an agent of vegetable origin used for improvement of the functional state and prophylaxis of organic alterations in cardiovascular system, in particular, atherosclerosis. The biologically active supplement used for prophylaxis of cardiovascular diseases, in particular, atherosclerosis comprises clover dry extract, haw-thorn flowers powder, ascorbic and nicotinic acids, and accessory substances taken in the definite ratio. The biologically active supplement is made in the form of tablet or capsule. No adverse responses observed in intake of the supplement. The blood cholesterol level was reduced to the normal value in 68% of patients and reducing morbidity with acute respiratory-viral infections has been noticed. In patients with ischemic heart disease with cholesterolemia the improvement of the state is noted on the background of conventional therapy: the moderate reducing the arterial pressure value in its elevation, improved in the state of health, enhanced working capacity, reduced retrosternal pains, ear noise, vertigo, headache.
EFFECT: valuable medicinal properties of supplement.