The mixture of higher primary aliphatic alcohols, its preparation and pharmaceutical compositions based on it |
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IPC classes for russian patent The mixture of higher primary aliphatic alcohols, its preparation and pharmaceutical compositions based on it (RU 2163229):
                          
 The method of purification of crude alcohol and device for its implementation / 2158726
The invention relates to a method of purification of crude alcohol used in pharmaceutical, food and other industries
 The method of receiving beaupreau / 2111950
The invention relates to a method for producing high molecular weight unsaturated alcohols of beaupreau, which are used for the production of biologically active substances and drugs
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The invention relates to methods of cleaning isopropyl alcohol, sulfuric acid obtained by hydration of propylene
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The invention relates to the field of technology organic chemistry, and in particular to methods of cleaning ethyl synthetic industrial alcohol from impurities of aldehydes and ketones
Method of separating methanol from mixtures with hydrocarbons4or5 / 2101273
The invention relates to a method of separating methanol from mixtures with hydrocarbons4or5
 Method of extraction of butanol, butyl acetate and water from a mixture of / 2058284
The invention relates to chemical technology, and in particular to methods of separation hardly separated commercial mixtures containing butanol, butyl acetate and impurities, e.g., biological, such as antibiotic products of inactivation, pigments, and can be used in chemical, pharmaceutical, paint and other industries
 Derivatives of n-(3-piperidinylcarbonyl)-beta-alanine as antagonists of platelet activating factor (fop), the production method, pharmaceutical composition and method of treatment / 2161155
The invention relates to a derived
 -alanine and its pharmaceutically acceptable salts
 Trombotsitopeiiya chimeric immunoglobulin and methods of its use / 2158135
The invention relates to medicine, namely to trombozitopatiam the chimeric immunoglobulins and their application
 Derivatives of oxazolidine, the method of production thereof, and pharmaceutical composition / 2155762
The invention relates to compounds of formula I:
 < / BR>where X denotes O, S, NH or NA; Y represents substituted with R2aziridinyl, azetidinone, pyrolidine, piperidinyl, hexahydroazepin or pieperazinove the rest; R1indicates  or < / BR>R2represents CrH2r-COOR3; R3denotes H, A or Ar; A denotes alkyl with 1-6 C-atoms; B denotes H, a, cycloalkyl with 3-7 C atoms, Ar-CkH2kor aydinbey the rest; Ar denotes unsubstituted or mono - or twice substituted with A, Cl, Br, I, NO2, CN, OA, OH, NH2, NHA and/or NA2phenyl or benzyl residue; "k" denotes 1, 2, 3 or 4; "m" and "r" each, independently of one another, denote 0, 1, 2, 3 or 4; and "n" represents 2, 3 or 4, and their physiologically acceptable salts  Tincture of echinacea purpurea l., means on the basis of echinacea purpurea l. and method of production thereof / 2163138
The invention relates to medicine, namely to receive funds vegetable origin as immunomodulatory, antimicrobial, anti-inflammatory and antiviral agents that have nonspecific antimicrobial, antiviral, anti-inflammatory and sedative effect
 A tool that improves efficiency and prevents the decrease of immunity / 2163137
The invention relates to medicines based on plant raw materials that can be used in the form of infusions and decoctions for the treatment of human
 A means of normalizing the motility of the biliary tract and the digestive tract / 2163136
The invention relates to medicine, namely to receive funds vegetable origin
The method of producing drug for treating diseases of the musculoskeletal system / 2163135
The invention relates to medicine
Biologically active food supplement for the prevention and rehabilitation of cardiovascular system / 2163134
The invention relates to medicine, in particular biologically active additives (BAA) for food, and is intended for therapeutic and preventive effects on cardiovascular system
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(57) Abstract: Describes a new mixture of higher primary aliphatic alcohols WITH24- C34containing, wt.%: 1-tetracosane 0,5 - 1,0, 1-hexacosanol 5,5 - 8,5, 1-heptacosane 2,0 - 3,5, 1-octacosanol 60,0 - 70,0, 1-nonacosanol 0,4 - 1,2, 1-triacontanol 10,0 - 15,0, 1-dotriacontanol 4,0 - 6,0, 1-tetratriacontane of 0.4 to 2.0. The mixture can be used for the treatment of hypercholesterolemia and complications of atherosclerosis, such as increased platelet aggregation, ischemia and thrombosis, and warns caused by medicine stomach ulcers and improves sexual activity in males. This is the emergence of new properties of the mixture. Also described its preparation and pharmaceutical compositions based on it. 3 S. and 11 C.p. f-crystals, 19 ill., 20 table. This invention relates to a mixture of higher primary aliphatic alcohols containing alcohols of from 24 to 34 carbon atoms, and more specifically, alcohols with straight-chain 24, 26, 27, 28, 29, 30, 32 and 34 carbon atoms. In European patent application 0488928 describes the mixture of higher primary aliphatic alcohols from 24 to 34 carbon atoms, which may be used as active constituent parts of pharmaceutical Phnom behavior in animals and humans. In accordance with the present invention the mixture of higher primary aliphatic alcohols from 24 to 34 carbon atoms (from this point referred to M. R. A. A.) in a relatively narrow proportions reveals new properties, such as protivotromboznoe, antithrombotic and/or anti-ischemic and anti formation induced by drugs ulceration, and therefore, this particular mixture can be used as an active ingredient of pharmaceutical preparations manufactured for these purposes. The objective of the invention was to create a M. R. A. A. from 24 to 34 carbon atoms for pharmaceutical products, as well as in the separation and purification of this mixture from the wax of sugar cane as raw and cleaned up. Action to reduce the level of lipids wax of sugar cane has been demonstrated in rats (Fukuda, Effects of suger cane wax on serum Liver Lipids on rats; Chemical Abstracts, 106, 17, 137413 p) and mice (Sho H. et al. (1984) Effects of Okinawan sugar cane wax and fatty alcohols on serum and Liver Lipids in the rats; J. Nutri Vitaminol 30(6) 553-559). First of all examined the effects of the wax of sugar cane in the lipids of serum and liver in male Wistar rats fed a diet with a high content of vegetable and glno the level of serum triglycerides in rats fed vegetable or animal fats, but only the latter was significantly decreased cholesterol levels with no effect on the lipids in the liver. Hence, the authors conclude that the wax of sugar cane hypolipidemic action. On the other hand, Sho N. et. al. (1984) studied the effects of wax Okinawan sugar cane on the content of lipids in serum and liver of rats that had received a diet containing 0.5% of this wax, and they found a significant decrease in the content of cholesterol in serum and liver. However, we detected no significant changes in cholesterol levels when using fatty alcohols from the same wax in the diet of animals. Thus, they rejected the fact that the properties of the lower levels of these lipids wax belong to these spirits. However, several years later, Shimura, S., Hagesawa T., Takano S. and T. Susuki (1987: Studies on the effect of octaconasol on the motor endurance in mice; Nutrition Reports Int. 36, 1029-1038) studied the impact of octacosanol in mice, urged to high physical activity that received a diet enriched with octacosanol. They found that octacosanol isolated from sugar cane wax, significantly reduced the content as triglidae and triglycerides. They concluded that octacosanol isolated from sugar cane wax, showed properties of a decrease in the levels of lipids, which is in contradiction with previous results Sho N. et al. (1984) mentioned above. Similarly, antilipemics effects were further attributed to hexacosanol, other higher primary aliphatic alcohol, although, as reported, were required very high doses to obtain such results (10-30 mg/kg/ day) (Hagiwara J. 1987: Antilipaemic agents containing hexacosanol used to treat hypertension, arteriosclerosis, diabetes mellitus, heart disease and obesity; J. P. A. 62 099323). There are various commercial available lepidophyma drugs that are effective, safe and well-tolerated, but most of them cause various adverse side effects. As lepidosperma therapy should be carried out constantly, this aspect is very important. For example, gemfibrozil (gemfibrozil) reduces triglycerides in serum, increases HDL-C (high density lipoprotein) and causes a slight reduction in serum cholesterol, but there were several inherent medication negative effects. Thus, the mentioned effects on the gastrointestinal tract, takrouna, blurred vision, impotence, decreased libido, and abnormal liver function, such as an increase of transaminases, LDH, CPK, and alkaline phosphatase, were treated with gemfibrozil patients. Also it should not be used in patients with renal insufficiency. Probucol (probucol) is another lipidemias medicine with antioxidant properties, which causes a slight decrease in the level of serum cholesterol and LDL-C (low density lipoprotein). However, the lack of lipidemias action is that it reduces the content of fractions of HDL-C. in Addition, there were several negative effects such as gastrointestinal disorders in approximately 10% of treated, as well as about significant changes in the electrocardiogram. Other frequently used lepidosirenidae drugs are cholestyramine (cholestiramine) and holestipol (cholestipol). These drugs are effective medicines of the first stage, reducing cholesterol, severely reducing serum cholesterol and LDL, but tend to increase the levels of triglycerides. These drugs caused few gastrointestinal symptoms, mainly constipation.Tami, easy to receive, and require a dosage of from 12 to 20 g/day to achieve the desired effect. In addition, the described adverse chemical interaction with other drugs, such as digitoxin. Lovastatin is the first of the "statin" drugs acting as inhibitors of Gmcla-reductase (hydroxymethylcytosine-coenzym A-reductase) and are thus effectively reducing the level of serum cholesterol and LDL-C, it is also moderately increases HDL-C and reduces triglycerides. Know about some adverse effects of this medication. So, the main negative effects include myopathy, slight or moderate increase in the activity of CPK and persistent increases in serum transaminases, which is often reversible after discontinuation of treatment. Myopathy occurs mainly in patients receiving concomitant therapy with immunosuppressive drugs, such as gemfibrozil or Niacin (niacin). In addition, it was also reported such adverse effects like skin rash, itching, headache and severe lesions of the muscles in sensitive patients, leading to Milito, patients treated with lovastatin. Moreover, it is also soo is. Similarly, simvastatin and pravastatin are other "statins", acting through the same mechanisms as lovastatin, and demonstrate a similar effect in reducing cholesterol. Adverse effects reported by these patients, similar to those reported in patients treated with lovastatin, but as you say, a little lower. Patients treated with simvastatin and pravastatin, shows an increase in transaminases and CPK, and patients reported constipation, flatulence, nausea, headache, fatigue, skin rashes and myo. In European patent application 0488928 describes the mixture of higher primary aliphatic alcohols from 24 to 34 carbon atoms with the quantitative ratio of the alcohols that can be used for the treatment of hypercholesterolemia, hyperlipoproteinemias type II and stimulate sexual behavior in animals and humans. Table 1 shows the qualitative and quantitative composition of the mixture M. R. A. A., derived from the wax of sugar cane in accordance with this invention. Table 1: the Main qualitative and quantitative composition M. R. A. A., used in medicinesComponents - Quantitative is Aksana - 50,0-80,0 1-Nonacosanol - 0,5-3,0 1-Triacontanol - 6,0-20,0 1-Dotriacontanol - 1,0-10,0 1-Tetratriacontane - 0,0-2,5 The specific mixture of alcohols, proposed in the present invention, shows the quantitative and qualitative composition of its components, as described in table 2. Table 2: Specific qualitative and quantitative composition M. R. A. A., proposed in the present invention Components ratio in the mixture, %: 1-Tetracosane - 0,5-1,0 1-Hexacosanol - 6,0-8,0 1-Heptacosane is 2.5 - 3.5 1-Octacosanol - 60,0-70,0 1-Nonacosanol - 0,5-1,0 1-Triacontanol - 10,0-15,0 1-Dotriacontanol - 4,5-6,0 1-Tetratriacontane - 0,5-2,0 This composition is unexpectedly reveals new effects, such as antithrombotics, antithrombotic and/or anti-ischemic, anti-ulcers induced by drugs, as well as a protective effect in myocardial ischemia. This special blend also demonstrates the same properties reported for the mixture described in European patent application 0488928. M. R. A. A. according to the invention shows pharmacological interaction with ASA (acetylsalicylic acid) drug most commonly used for the treatment of the economic and antiischemic properties M. R. A. A. and ASC. M. R. A. A. according to the invention significantly reduces stomach ulcers caused by aspirin, ethanol, indomethacin, substance C4880 (Sigma) and other drugs that cause stomach ulcers in people receiving treatment. It is known that the gastric ulcer caused by alcohol, mainly associated with increased Da, as a physiological factor, whereas ulcers caused C4880 mainly serotonergic mechanisms are involved, although the role The and his eigenes cannot be excluded. On the other hand, a stomach ulcer, caused by the ASC, is associated with suppression of the synthesis of prostaglandins (series E), called the ASC, as they have a cytoprotective effect on gastric mucosa. It was shown that the ratio The to Pg 12 of the gastric mucosa plays an important role as an endogenous mechanism of its integrity. On the other hand, describes the treatment of some lepidophaite drugs reduces the tendency to hyperaggregation platelets, often observed in patients with hyperlipidemia, and experimental data showed antiagregatnoe effect mediated by these substances. However, only some holesterinoponizhayuschim drugs exhibit this property. As was explained, atedo, complex carbohydrates, blood and blood products, fibrous tissue and calcium deposits, often associated with medial changes. Thus, this definition is atherosclerosis as a multifactorial process that includes not only hyperlipidemia as a risk factor. Thus, among the factors contributing to the development of atherosclerosis, platelet aggregation has a very important place. Produce granules of platelets contain activates arachidonic acid, which is metabolized in circular endoperoxide. These latter mainly transformed into cyclic endoperoxide and, in the end, turning into thromboxane A2 (Tha), a strong vasoconstrictor and platelet aggregation substance. Platelet aggregation can be caused by various substances such as collagen, ADP and epinephrine, among others. Thus, in various experimental models in vivo, ex vivo or in vitro to determine the effectiveness of the alleged antithrombolytic drugs used for their effects on platelet aggregation caused by these substances. These tests are also used to determine platelet aggregation in healthy volunteers and from bol is diabetes, additional area. From these tests the most commonly used platelet aggregation induced by collagen. So, for example, collagen, injected leads to reversible intravascular platelet aggregation in vivo, and aggregates of platelets come into the vascular microcirculation, gradually reducing the number of circulating platelets and simultaneously increasing the concentration of MDA (malondialdehyde) plasma. In addition, in some species the injection of collagen causes deaths due to thrombosis. On these models antithrombotic medications usually prevent the reduction in the number of platelets and increased concentrations of MDA, as well as the deaths caused by collagen. Some drugs, showing the anti-platelet aggregation, applicable to the treatment of thrombotic diseases, myocardial infarction and angina, but not all of them demonstrate these advantages. On the other hand, there are antithrombotic drugs, which mainly act by political processes that affect blood clotting, but not on platelet aggregation, such as streptokinase and urokinase. As ischemic cardiovascular zabolevanija, usually experience the effects of individual drugs on these complications. So, theoretically, medicine, showing properties to reduce cholesterol, which can prevent these complications by exposure to other phenomena that are included in these processes, should be useful for the treatment of these patients. Similarly, reduced levels Tha was associated not only with antithrombotic and antithrombotic actions, but also with anti-ischemic effects. Pharmacological screening antiischemic drugs usually assess their impacts caused by global ischemia of the brain. So, was described protective effect of various drugs on cerebral ischemia in rats for some nonsteroidal anti-inflammatory drugs (spit), which inhibit the reaction catalyzed by cyclooxygenase, as well as specific inhibitors thrombogenicity and analogues of prostacyclin (Pg12) (Borzeix M. G. and J. Cahn, 1988; Effects of new chemically merabolically stable prostacyclin analogues on early consequences of a transient cerebral oligemia in rats; Prostaglandins 35, 5, 653-664). Also often used in other experimental models such as total ischemia, experimentally induced in Mongolian gerbils. Acetylsalicylic acid (ASA) are the two the mental models and in humans. This medication is most commonly used for the treatment of acute myocardial infarction and ischemia, as well as for the prevention of thromboembolic disorders. Effects ASC confirmed the well-known suppression of her cyclooxygenase, a key enzyme in arachidonic acid metabolism. So, ASC induces significant and remarkable reduction of the levels of thromboxane A2 (Tha) in the serum of a substance as recognized, is involved in the pathophysiology of vascular endothelium, and this explains the above-mentioned effects ASC. However, since the suppression of the ASC is manifested at the level of cyclooxygenase, reduced not only the levels The, but also the levels of prostacyclin (Pg12), substances with pharmacological properties, shown opposite Thw. On the other hand, taking into account that ASA inhibits the synthesis of prostaglandins (series E), it induces lesions of the stomach, because it prevents the cytoprotective action of prostaglandins. This is the basis of the main adverse side effects reported to the ASC, that is, gastritis, stomach ulcers and related disorders. The preferred composition of the specific higher primary alifaticheskii the initial qualitative and quantitative composition M. R. A. A. used in medicines Components of Relative quantity in the mixture, %: 1-Tetracosane - 0,8+/-0,1 1-Hexacosanol - 6,7+/-0,3 1-Heptacosane - 3,0+/-0,3 1-Octacosanol - 65,6+/-3,4 1-Nonacosanol - 0,7+/-0,1 1-Triacontanol to 12.5+/and-0.6 1-Dotriacontanol - 5,0+/-0,4 1-Tetratriacontane - 0,8+/-0,1 Pharmaceutical drugs with this particular mixture of higher primary aliphatic alcohols can be administered to humans and animals. Daily dosage M. R. A. A., derived from the wax of sugar cane, which will be used for the treatment of various diseases, is set in the range between 1 and 100 mg per day, preferably about 3-20 mg M N. R. A. A., may, for example, be administered orally or parenterally. The preferred method of administration is oral film-coated tablets, as well as granules or capsules. Pharmaceutical preparations containing as active ingredient from 0.5 to 15.0 wt.% M. R. A. A. This dose is obtained by mixing M N. R. A. A. with various fillers, such as agglutinating substance, dezintegriruetsja substances, sliding, lubricants or fillers. These fillers include lactose, cucurbitales cellulose, titanium dioxide, a special talc for tablets and polyethylene glycol. A mixture of acetylsalicylic acid with M N.R. A. A., the object of the present invention, which will be demonstrated in the examples, exhibits synergism with their pharmacological interaction associated with them antithrombocyte, antithrombotic and anti-ischemic properties, if the ratio between them is in the range from 20:1 to 1:20, especially with such a ratio as 10: 1 to 1:10. The wax of sugar cane and its natural source, the sludge, is always of interest, not only because of their industrial applicability, but also because of their chemical composition. The amount of wax in sugar cane varies between 0.1% and 0.3%, depending on its type. During the agricultural process only 40% of the amount of the wax is dissolved in the juice, the remaining material is lost from pressed sugar cane. Of these 40%, 94% of this amount is absorbed by the slurry, which is obtained from the crude wax. This wax is composed of esters, aldehydes, ketones, carbohydrates, fatty acids and free alcohols, and the amount of each depends on the variety and origin of plants sugar cane and technology the software products of sugar cane, have been studied by several authors, with the aim of determining from the structure and main properties. Getting different groups of compounds of all kinds of wax, reported (J. A. Lamberton et al., 1959; Australian Journal of Chemistry 13, 261-268 and Horn A. and J. S. Martic; 1957; Jornal of Science Food and Agriculture, 10, 571), suggests a method of producing fatty alcohols from the cuticular wax of sugar cane-based homogeneous saponification with alcoholic potassium hydroxide solution followed by etherification of unsaponifiable material and further molecular distillation. Also reported another method of separation of a mixture of alcohols using high-performance speakers with a high vacuum. Distillation of wax with a high vacuum target chemical separation of carbonyl compounds and extraction of the remaining wax when using petroleum ether. The solvent is evaporated and the remaining content azetiliruetsa for further selection using chromatography on aluminium oxide. In the end, using alkaline hydrolysis produces alcohols and then precrystallization from ethanol, showing a melting point in the range from 80 to 82oC. Process for obtaining a mixture of higher aliphatic dog, followed by extraction of mixtures of alcohols with fluid in sub - and supercritical state at a temperature in the range of 25-100oC, using appropriate solvents, and it is shown that depending on the solubility at low temperature and pressure changes can be selective extraction. According to this technology, applied to the wax of sugar cane, you can receive a 5% mixture of alcohols C20-C36. In another project (Inada, S., Furukawa, K., Masui, T., Honda, K., Ogasawara J. and Tsubikamoto G.; 1986; Process for recovering primary normal aliphatic higher alcohols. J. P. 60-119514) proposed a very similar extraction applied to the wax, which is based on the liquids in sub - and supercritical States of CO2with ethylene. Separation of organic compounds from their mixtures by means of fluids in sub - and supercritical conditions is also described. From the analytical point of view, all these methods are valuable, but the implementation on a large scale is hampered by the use of column chromatography and molecular distillation, all of which are uneconomic technologies. The technology of the present invention is based on the saponification process in a homogeneous phase, sugar cane wax, previously melted concentrated solutions of hydroxides of alkali and alkaline earth metals, especially hydroxides met the walkie-talkie solutions of hydroxides should be such that that the ratio by weight of the corresponding hydroxide by weight of wax, which can be recycled, should be more than 5%, especially 8 to 25% and more particularly from 15 to 25%. The process of saponification takes place within a period of 30 minutes and more specifically within 2 to 5 hours. The solid obtained at this stage, shown in the apparatus for extraction in the system solid-liquid, where M N. R. A. A. selectively extracted relevant organic solvents selected among the ketones of 3 to 8 carbon atoms, alcohols of from 1 to 5 carbon atoms, hydrocarbons of from 6 to 9 carbon atoms, halogenated, as well as from aromatic, such as benzene and its derivatives, including mixtures thereof. Some of the solvents used in this invention are the following: acetone, methyl ethyl ketone, pentanone, hexanone, heptanone, 2-methylpentane, ethanol, methanol, 2-propanol, butanol, tertbutanol, pentane, hexane, heptane, octane, chloroform, 1,2-dichloroethane, dichloromethane, trichloroethane, 1,2,3-trichloropropane, benzene, toluene, phenol, p-metalcolor and others. Extraction is carried out in the course of time, varying from 5 to 10 hours. Then the product consistently crystal is as clean M N. R. A. A. reached about 80 to 98%, more particularly from 90 to 98%. M. R. A. A., thus obtained, formed by alcohols comprising from 22 to 38 carbon atoms. This substance is a mixture of not quite white with a melting temperature between 76,5 and 84,5oC. For analysis M. R. A. A. by gas chromatography on a capillary column made of quartz glass, these alcohols are transformed into derivatives with N-methyl-N-tetramethylsilane was-trifurcated (MSTFA). The technology of obtaining M N. R. A. A. from the wax of sugar cane has some advantages in comparison with other reported previously. One of those benefits is associated with a short period of receipt. Another advantage of this invention is connected with the practical output (about 30% by weight), which can be obtained for alcohols of the wax of sugar cane, compared with the results previously described Sho et al., who announces the release of lower than 5%. Another advantage of the proposed technology related to the degree of purity of M. R. A. A., which can be obtained (about 98%) and significantly higher than that reported in previously published works. Thus, the method proposed in this is, published Inada et al. (JP 60-119514) and Hagiwara Y. (JP 62-87537). And finally, in the overall picture of the characteristics of M. R. A. A. its a very good safety and tolerability are important advantages in comparison with medicines of modern science. Thus, the results obtained in the study of acute, sub-chronic and chronic actions conducted on rodents, rabbits, dogs of the Beagle and the monkeys did not reveal toxicity of the drug. Also not shown any mutagenic action of this drug or that he has a teratogenic effect in rats and rabbits. Introduction M. R. A. A. during the period of formation of two generations of animals had no effect neither on fetal development, nor on the reproductive capacity of rats. Finally, 24-month Carcinogenicity study conducted in rats also showed no toxicity and carcinogenic action of the M. R. A. A. Short-term and long-term clinical trials have also confirmed the excellent safety and tolerability. The objects and purposes of the present invention will be described in detail in the following examples. These examples will not limit the amount specified image is 0oC by adding 200 g of potassium hydroxide dissolved in 150 ml of water. This process was maintained for 5 h with stirring. M. R. A. A. were extracted from the solid residue, obtained by the process for 12 h in the system of extraction, solid-liquid, using heptane as solvent. The extract obtained is cooled at room temperature, resulting in M N.R. A. A. crystallizes and precrystallization of methyl ethyl ketone. Up to 285 g of this mixture of alcohols was obtained with purity up to 94,70%. The melting point of the mixture is in the range from 80,5 82,5 tooC. table 4 shows the qualitative and quantitative composition M. R. A. A., obtained using this technique. Table 4: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-Tetracosane - 0,81 1-Hexacosanol - 7,00 1-Heptacosane - 2,81 1-Octacosanol - 65,09 1-Nonacosanol - 0,67 1-Triacontanol - 12,43 1-Dotriacontanol - of 5.05 1-Tetratriacontane - 0,84 Unidentifiable component - 5,30 In the same way, depending on the type of sugar cane wax mixture may Soder 1-Nonacosanol - 0,5-3,0 1-Triacontanol - 6,0-20,0 1-Dotriacontanol - 1,0-10,0 and perhaps 1-Tetratriacontane - 0,0-2,5 a total of 100 wt.% when the purity of about 80 to 98%. The same results can be obtained using acetone, hexane and/or diethylether as solvent. Example 2 Taken 2 kg (two) of the crude wax from sugar cane to melt at 85-100oC, to which is added 300 g of sodium hydroxide dissolved in 200 ml of water, the saponification process was continued for 4 hours while stirring. Extraction M. R. A. A. was carried out using chloroform as the solvent for 10-hour period on a typical system, extraction, solid-liquid, the extract obtained is cooled at room temperature, the obtained solid residue precrystallization from methanol and finally from a mixture of chloroform/ethyl ketone. Received M. SC.R. A. A. (405 g) with a purity of up to 92,52%. Melting point M. R. A. A. is within 79-80,5oC. table 5 shows the qualitative and quantitative composition M. R. A. A., obtained using this technique. Table 5: Qualitative and quantitative composition of the Sabbath. 1-Hexacosanol - 6,84 1-Heptacosane - is 3.08 1-Octacosanol - 62,92 1-Nonacosanol - 0,80 1-Triacontanol - 12,66 1-Dotriacontanol - 4,65 1-Tetratriacontane - 0,70 Unidentifiable component of 7.48 In the same way, depending on the type of sugar cane wax mixture may contain, %: 1-Tetracosane - 0,5 - 1,0, especially 0,8 0,1 1-Hexacosanol - 5,5 - 8,5, especially 6,7 0,3 1-Heptacosane - 2,0 - 3,5, especially 3,0 0,3 1-Octacosanol - 60,0 - 70,0, especially 65,6 3,4 1-Nonacosanol - 0,4 - 1,2, especially 0,7 0,1 1-Triacontanol - 10,0 - 15,0, especially 12,5 0,6 1-Dotriacontanol - 4,0 - 6,0, especially 5,0 0,4 1-Tetratriacontane - 0,4 - 2, especially 0,8 0,1 A total of 100 wt.% when the purity of about 80 to 98%. The same results can be obtained using acetone, hexane and/or diethylether as solvent. Example 3 Twelve kg of calcium hydroxide dissolved in 7 l of water are added to 50 kg of purified sugar cane wax, previously melted at 100-120oC. The saponification process is continued for a period of 7.5 h under stirring. M. R. A. A. extracted, using ethanol as a solvent for 12 hours in which the temperature value, then this solid precrystallizer of chloroform, and obtained M. SC.R. A. A. (13.7 kg) with purity 93,77%. The melting point of the mixture is in the range from 80,0 82,0 tooC. table 6 shows the qualitative and quantitative composition obtained M. SC.R. A. A. when using this technique. Table 6: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-tetracosane - 0,71 1-hexacosanol - 6,88 1-heptacosane - 3,06 1-octacosanol - 64,70 1-nonacosanol - 0,62 1-triacontanol - 12,01 1-dotriacontanol - 5,09 1-tetratriacontane - 0,90 Unidentifiable component - 6,23 Example 4 8.6 kg of calcium hydroxide dissolved in 4.5 l of water was added to 50 kg of the crude sugar cane wax, previously melted at 100-120oC. the saponification Process was carried out with constant stirring for 3 h M N.R. A. A. was extracted with dichloromethane as a solvent for 12 hours in the apparatus for extraction in the system solid-liquid. The resulting product is left to cool at room temperature, and the resulting hard substance precrystallization M. R. A. A. makes 78.5-80,5oC. table 7 shows the quantitative and qualitative composition M. R. A. A., obtained by this method. Table 7: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-tetracosane - 0,75 1-hexacosanol - 7,00 1-heptacosane - 3,14 1-octacosanol - 63,60 1-nonacosanol - 0,62 1-triacontanol - a 12.03 1-dotriacontanol - 4,99 1-tetratriacontane - 0,78 Unidentifiable component - 7,09 Example 5 Taken twenty (20) kg refined sugar cane wax, previously melted at a temperature of 100-110oC, with the addition of 3.7 kg of potassium hydroxide dissolved in 3.0 l of water. The saponification process lasted 5 hours, performed with constant stirring. Extraction M. R. A. A. produced by the apparatus for extraction of socket (Soxhlet) using methyl ethyl ketone as a solvent for 14 hours. Extracted material is cooled at room temperature. He further precrystallization from a mixture of hexane:chloroform 1:1. Was obtained M. SC.R. A. A. (3.8 kg) with purity, component 92,56%. Melting point M. R. A. A. in point is using this technique. Table 8: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-tetracosane - 0,85 1-hexacosanol - 6,56 1-heptacosane - 3,10 1-octacosanol - 63,10 1-nonacosanol - 0,72 1-triacontanol - 12,18 1-dotriacontanol - 5,31 1-tetratriacontane - 0,74 Unidentifiable component - 7,44 Example 6 One kg of the crude sugar cane wax melted beforehand at 100oC by adding 250 g of calcium hydroxide. The saponification process is performed with constant stirring for 2 h M N.R. A. A. extracted using 2-propanol as a solvent for 12 hours in the apparatus for extraction in the system solid-liquid. The resulting product is cooled at room temperature, after which precrystallizer using heptane. M. R. A. A. (165 g) was obtained with a purity of 93,63%. The melting point of this M. R. A. A. varies from 80,0 up 81,5oC. table 9 shows the qualitative and quantitative composition M. R. A. A. obtained using this technique. Table 9: Qualitative and quantitative composition obtained M. SC.R. A. A. heptacosane - 3,18 1-octacosanol - 64,13 1-nonacosanol - 0,69 1-triacontanol - 12,54 1-dotriacontanol - 4,93 1-tetratriacontane - 0,80 Unidentifiable component - 6,37 Example 7 Two (2) kg of purified wax of sugar cane was pre-melted at 110oC, then adding 400 g of sodium hydroxide dissolved in 200 ml of water. This process is maintained for 3 hours with constant stirring. Extraction M. R. A. A. is performed using toluene as solvent in the apparatus for extraction in the system solid-liquid for 6 hours, and it re-precrystallizer using methanol as solvent. M. R. A. A. (389 g) was obtained with purity, component 95,10%. The melting point of the mixture is between 81,0 and 83,0oC. table 10 shows the qualitative and quantitative composition M. R. A. A., obtained using this method. Table 10: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-tetracosane - 0,80 1-hexacosanol - 7,00 1-heptacosane - 2,82 1-octacosanol - 64,54 1-nonacosanol - 0,72 1-Tr is 4,40 Example 7a 1000 g of purified sugar cane wax was melted at 100-110oC, then adding 200 g of sodium hydroxide dissolved in 150 ml of water. This process is maintained for 5 hours with constant stirring. Extraction M. R. A. A. is performed using acetone or ethanol as solvent in the apparatus for extraction in the system solid-liquid for 9 hours. The extract obtained was cooled at room temperature, and M. N. R. A. A. crystallizes and precrystallizer in ethyl ether. M. R. A. A. (305 g) was obtained with purity, component 95,60%. The melting point of the mixture is between 81,5 and 82.5oC. Table 10A shows the qualitative and quantitative composition M. R. A. A., obtained using this method. Table 10a: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-tetracosane - 0,80 1-hexacosanol - 7,00 1-heptacosane - 2,73 1-octacosanol - 65,14 1-nonacosanol - 0,70 1-triacontanol - of 13.05 1-dotriacontanol - 5,28 1-tetratriacontane - 0,90 Unidentifiable component - 4,40 Premixed potassium, dissolved in 200 ml of water. The saponification process runs for 2 hours with constant stirring. Extraction M. R. A. A. is carried out using chloroform or diethyl ether as the solvent for 10 hours in the system extraction solid-liquid. After that, the extract is cooled at room temperature, and M. N. R. A. A. precrystallizer in ethanol and finally in hexane. M. R. A. A. (410 g) was obtained with purity, component 93,79%, melting point M. R. A. A. is between 81 and 82oC. table 10B shows the qualitative and quantitative composition obtained M. SC.R. A. A. Table 10B: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-tetracosane - 0,70 1-hexacosanol - 6,84 1-heptacosane - is 3.08 1-octacosanol - 64,27 1-nonacosanol - 0,80 1-triacontanol - was 12.75 1-dotriacontanol - 4,65 1-tetratriacontane - 0,7 Unidentifiable component - 6,21 Example 8 Five (5) kg of purified wax of sugar cane were treated with 1 kg of potassium hydroxide dissolved in 500 ml of water, after melting it at 120oC. This process prot is as a solvent in the extraction system solid-liquid for 5 hours After that, the extract is cooled at room temperature, whereby M. R. A. A. crystallized using toluene as solvent. M. R. A. A. (1490 g) was obtained with purity, component 92,20%. Melting point M. R. A. A. is between 79,5 and 81,0oC. table 11 shows the qualitative and quantitative composition M. R. A. A. obtained using this method. Table 11: Qualitative and quantitative composition obtained M. SC.R. A. A. Component - the Percentage of each alcohol, %: 1-tetracosane - 0,76 1-hexacosanol - 6,58 1-heptacosane - 2,84 1-octacosanol - 62,43 1-nonacosanol - 0,71 1-triacontanol - 13,08 1-dotriacontanol - of 5.05 1-tetratriacontane - 0,75 Unidentifiable component - 7,80 Example 9 Compositions developed two different pharmaceutical preparations using this M. R. A. A. as an active constituent parts are presented in table 12. These drugs were developed based on the physical, chemical and physico-chemical properties of the active components. Preparations were made using the process of wet granulation of the active ingredient and the pharmaceutical and food & the TV and pressing. Example 10 Male new Zealand rabbits (2-3 kg) were adapted to laboratory conditions for 15 days and a random sample was divided into 4 experimental groups: control (receiving only fillers), and group 3, treated M. R. A. A. in the dose of 5, 50 and 200 mg/kg, suspended in gum acacia in water, as a filler, is injected into the stomach through a tube (1 ml/kg) for 4 weeks. The lipid profile was determined by the underlying data (the day before treatment and 4 weeks after). M. H. P. A. A., administered orally in doses of 5, 50 and 200 mg/kg for 30 days significantly reduced (Wilcoxon, p < 0.05) in dependence on the dose of total cholesterol and the levels of serum LDL (low density lipoprotein). In addition, the percentage change in the control and treated groups were statistically different (Mann Whitney U, p < 0,05), see figure 1-4. Fig. 1 shows the effect of M. H. P. A. A. on the levels of serum cholesterol, Fig. 2 - on the levels of serum LDL-C, Fig. 3 - changes in serum cholesterol and Fig. 4 - the change in serum (%) LDL-C in rabbits with normal levels of cholesterol in the blood. In this series of experiments the highest input of the op perate M. H. P. A. A. in rabbits with normal levels of cholesterol in the blood. No significant changes in levels of HDL-C (lipids high density) did not producirovanie in all four groups. Fig. 6 illustrates the effect of M. H. P. A. A. on serum triglycerides and Fig. 7 - changes in serum triglyceride levels in rabbits with normal level of cholesterol in the blood. Comparison of percentage changes in triglyceride levels in treated and control groups showed that they were also significant (Mann Whitney u, p < 0,05), but the dependence of the effect of dose was not observed. Example 11 Male new Zealand rabbits were divided by random selection into 4 groups: control group (receiving only the filler is injected into the stomach through a tube), and group 3, treated with M. R. A. A., octacosanol and hexacosanol, respectively, at doses of 5 mg/kg Profile of lipid parameters in serum were determined at baseline and after 30 days of treatment. M. R. A. A. significantly reduced total cholesterol and LDL-C. In addition, levels of cholesterol, LDL-C and triglyceride levels in rabbits treated with M. R. A. A., were significantly lower than levels in the control group. However, changes to the profile ical values of the differences, as shown in table 13. Example 12 After the 5-week period of diet forty-five outpatients whose parameters cholesterol and LDL-C were not sufficiently regulated diet, received tablets containing 5 mg M N. R. A. A. (twice a day, lunch and dinner), or placebo for 6 weeks. During this period of active treatment remained the diet regime. The levels of lipid profile was determined in the initial moment (the end of the period only the diet), also after 4 and 6 weeks after initiation of therapy. M. R. A. A. significantly reduced the level of total cholesterol in serum on 16,23% and LDL-With - 21,33%. Also were significantly reduced up to 17,67% 22,28%, respectively, the relationship of indicators of cholesterol to HDL-C and LDL-C to HDL-C (p < 0.05 definition of Wilcoxon for paired data). In all patients, the levels of both total cholesterol and LDL-C after 6 weeks after treatment were below baseline levels. Changes in other fractions of the lipid profile were insignificant, the results are shown in tables 14 and 15. Example 13 The group of patients with hyperlipoproteinemia type II received tablets containing 15 mg of the drug after 8 nagelneue and 8 weeks after therapy. The main results are summarized in table 16. The Product M N.R. A. A. significantly reduced total cholesterol by 16,44% and LDL-C in 23,51%. Fig. 8 shows the effect of M N.R. A. A. the profile of lipid parameters in patients with hyperlipoproteinemia type II, with changes of parameters cholesterol, LDL-C and HDL-C are average values and changes of triglycerides in the form of median values. HDL-C was increased by 6.40%, while the performance of triglycerides and APNP-C was reduced by 7,80% 10,83%, respectively, but these changes were not statistically significant. Table 17 shows the changes in the relationship of LDL-C to HDL-C and cholesterol to HDL-C, they were significantly reduced by 29,07% 23,72%, respectively. Example 14 First of all, we investigated the effect of M. H. P. A. A. on a induced by ADP and collagen platelet aggregation in rats. A group of male rats Sprague-Dawley weighing 250-350 g were divided by random selection into two experimental groups. M. H. P. A. A. is administered orally in suspension in the carrier from an aqueous solution of gum acacia by intragastric administration through a feeding tube for 4 weeks. The study included the following groups: control group (received the of robotito rats were anestesiologi pairs of ether. The abdominal cavity was opened, and blood (5 ml) were collected from the Vena cava and mixed with 3.8% sodium citrate (1 volume of citrate to 9 blood). Platelet-rich plasma (CCP) was obtained by centrifugation of blood. Poor platelet plasma (BTP) were obtained using centrifugation aliquot samples OTP when 330xg within 15 minutes. Platelet aggregation was caused by ADP and collagen was measured using aggregometry of Payton as described (L. McGregor, Morazain R. and Renaud, S.,; 1980; Effect of dietary Linoleic acid on platelet functions in the rat; Trombosis Res. 20, 499). Statistical comparison of the results obtained in treated and control groups was carried out using neparitetnogo U determine by Mann-Whitney. In rats treated with M. R. A. A. at a dose of 25 mg/kg for 4 weeks, showed a significant inhibition of platelet aggregation ex vivo, with the use of submaximal doses of ADP and collagen. Fig. 9 shows platelet aggregation in rats caused by ADP, while introducing them M. R. A. A. within 1 month, and Fig. 10 - induced collagen platelet aggregation in rats, which were injected M. R. A. A. within 1 month (p < < 0,05, U definition by Mann-Whitney, 15 cm % transmittance). The Introduction Of M. R. A. A. rats orally for 4 weeks Snet as protivotromboznoe medicine. Example 15 To characterize the effect of M. R. A. A. on platelet aggregation ex vivo in rats, there were some studies course antiaggregating action on platelets. With this aim, rats, Sprague-Dawley both sexes weighing 250-350 g were divided into 4 experimental groups: one control group and 3 groups of animals treated with single doses of M. R. A. A. 25, 50 and 200 mg/kg, respectively. In addition, we studied the effect on platelet aggregation after 2, 6 and 24 hours after a dose of 200 mg/kg M. R. A. A. prepared as described in example 14, and is administered orally as a single dose two hours before the experiment. Control animals received the same volume of media. All animals were deprived of food but had free access to water for 20 hours before the experiment. All animals were anestesiologi ether and then took samples of blood from the Vena cava and mixed with 3.8% sodium citrate (9 volumes of blood to 1 anticoagulant). The blood was centrifuged at 250 g for 10 minutes to obtain platelet-rich plasma (OTP). After separation of the OTP remainder was centrifuged at 1300 g for 15 minutes to obtain platelet-poor plasma (BTP). The levels of platelet aggregation was measured after calibration of the instrument at 0% light transmittance for OTP and 100% for BTP. Curves aggregation was recorded for 5 min Fig. 11 shows the effect of M N.R. A. A. the called ADP platelet aggregation in platelet-rich plasma of rats, p < < 0,05 (test U Mann-Whitney). The results are expressed in percentage of maximal aggregation (%). Groups were compared using the U test of Mann-Whitney (p < < 0,05). M. R. A. A. (50 and 200 mg/kg), administered 2 hours before sampling of blood, suppressed induced ADP platelet aggregation, whereas lower doses (25 mg/kg) did not give significant changes in responses to ADP. The highest dose of M. R. A. A. (200 mg/kg) was selected to study the flow over time antitromboticos steps. Fig. 12 shows the effect on the induced ADP platelet aggregation at a concentration of 2 µmol/l, p < < 0,01. Although after 2 h platelet aggregation was significantly suppressed after 6 h the suppression had only borderline significance (p = 0,06), whereas at 24 h, no statistical difference was not received. The results show that oral administration of policosanol rats two hours prior to the selection of the.R. A. A. at a dose of 50 and 200 mg/kg The overwhelming effect of M. R. A. A. on induced ADP aggregation is reversible, as 6 hours after treatment in the dose of 200 mg/kg, the inhibition of platelet aggregation was only of borderline significance, and 24 hours after treatment revealed a lack of effectiveness, showing that M N.R. A. A. does not cause permanent changes in the cells. Example 16 Studied the effect of M N.R. A. A. on intravascular platelet aggregation in rats and induced collagen destruction mice. Rats male Sprague-Dawley weighing 250-300 g and female mice of 57BL6 weighing 20-35 g was distributed to a random sample in the different experimental groups. M. R. A. A. prepared as described in example 14, at the same time, ASA was dissolved in 5% NaHCO3. Drugs administered orally through a feeding tube in the stomach two hours before the examination. Animals received no food for 16 hours before oral drug administration. Rats were given 1 ml/100 g body weight, and mice 0.5 ml/20 g of body weight of the control animals received equivalent volumes of media. In the study of intravascular platelet aggregation in rats used 4 groups of experimental animals. 1) control, 2, 3 and 4, polucha the Oia (30-40 mg/kg). The carotid artery was inserted cannula for sampling blood samples before and after 90 seconds after intravenous injection of 30 mg/kg in the vein of the penis. Blood (900 ál) was collected in plastic tubes containing 100 μl of a mixture of 0.7 mg/ml of indomethacin and 0.19 mg/ml EDTA. Aliquot sample was used to determine the concentration of platelets in each sample by counting by optical microscopy. The blood is then centrifuged and determined the plasma concentration of malondialdehyde (MDA) by the method with thiobarbituric acid (Satoh M, 1978; Serum Lipid peroxyde in cerebroyascular disorders determined by a new colorimetric method; Clin. Chim. Acta 90, 34-43). Changes in the number of platelets and the concentration of MDA in plasma after injection of collagen was expressed as percentage of the original values. Differences between control and treated groups was determined using the U test of Mann-Whitney. To study induced collagen destruction mice (rats?) groups in the experiment were as follows: 1) control animals receiving only the media, but the induction of death by intravenous injection of collagen, 2) animals pre-treated with M. R. A. A. at a dose of 360 mg/kg 2 hours before injection of collagen; 3) robotville treated with M. R. A. A. at a dose of 180 mg/kg) and ASA at a dose of 50 mg/kg 2 hours prior to the study. Acid-soluble collagen from the skin of calves of type III were obtained as described (Kimura Y., Kaube T. and K. Watanabe, 1985; Effect of celostagel on platelet aggregation and experimental thrombosis; Arzneim. Forsch., Orug Research 35, 1140-1148) and used at a final concentration of 2.5 mg/ml Injection of 0.1 ml/20 g) was produced via the retro-orbital plexus. This dose resulted in 60-100% of loss of control animals. Comparison of mortality rates among control and treated animals was performed with the use of precise determination of likelihood Fisher. Fig. 13 shows the effect of M N.R. A. A. on intravascular platelet aggregation in rats, p < < 0,05; p < < 0,01 (U test of Mann Whitney). M. R. A. A. significantly inhibited the decrease in the number of circulating platelets and the simultaneous increase in the concentration of MDA in the plasma caused by collagen. Fig. 14 demonstrates the effect of M. R. A. A. on caused by collagen loss C57BL6 mice, p < < 0,01 (U test Mann-Whitney). Caused by collagen loss was significantly reduced M. R. A. A. at a dose of 360 mg/kg Is protective action caused by collagen loss was observed when the dose was administered at 1 and 4 hours before the study, but these values is " collagen death of C57BL6 mice, p < < 0,05 (U test Mann-Whitney). Fig. 16 illustrates the effect of the combined introduction of M. R. A. A. and ask for induced collagen destruction mice, p < < 0,01 (the exact definition of likelihood Fisher). The Combination Of M N.R. A. A. (180 mg/kg) and ASA (50 mg/kg) also leads to a significant statistical reduction caused by collagen loss, whereas treatment with both drugs, administered separately, proved ineffective. Dose M N. R. A. A. and ASC, which were ineffective when introduced separately, were explicitly protects with a joint introduction, showing thus the synergistic antithrombotic action M. R. A. A. and ASC. Example 17 For analysis of the action of M N.R. A. A. cerebral infarction in rats, rats, male Sprague-Dawley weighing 290-330 g were distributed into the following experimental groups: 1) negative control: rats without overlap ligature receiving only the media via a stomach tube, 2) positive control: rat with the imposition of the ligature receiving the media via a stomach tube, 3) and 4) rats with the imposed ligature receiving M. R. A. A. (5 and 25 mg/kg) in the same way. The introduction of different preparations were made daily for 4 weeks. Posley, that is usually applied on this model. To call cerebral ischemia animal carefully anestesiology, and oligemia caused by bilateral ligature of the common carotid arteries. Then immediately was subcutaneously injected sodium nitroprusside (0.8 mg/250 g) to cause arterial hypotension. Banners carotid arteries were removed after 60 minutes, and the animals were observed for 72 hours and then scored. The brain was rapidly removed and placed in a drying Cabinet at 80oC for 24 hours. Determined weight as raw and dry to set the water content (edema) and used the following formula; Edema = Weight raw - dry weight / Weight raw 100 Statistical analysis of results was performed using neparitetnogo U test Mann-Whitney. M. H. P. A. A. at a dose of 25 mg/kg significantly reduced brain swelling (p < < 0,05) when administered daily for 4 weeks. This dose also reduced the degree of loss and the percentage of animals with edema, although the reduction of these other indicators did not reach significant levels. These data show that M. H. P. A. A. at a dose of 25 mg/kg significantly protects against cerebral ischemia induced experimentally in rats, as obtained a significant reduction of edema Hildren of brain edema, but this reduction did not reach significant levels (table 18). Example 18 To explore synergies between M N. R. A. A. and aspirin under the action induced in the rat brain ischemia, male rats weighing 250-300 g were divided into 5 groups: 1) negative control (rats without overlap ligatures); 2) positive control (animals imposed by the ligature receiving only the media); 3) animals receiving orally via a stomach tube 25 mg/kg / M. R. A. A.; 4) animals receiving oral ASC, dissolved in 5% sodium bicarbonate at a dose of 30 mg/kg; 5) rats, which are administered orally ASC (30 mg/kg) + M N.R. A. A. (25 mg/kg). Drugs were administered two hours before the experiment. To induce ischemia, animals carefully anestesiologi ether and the carotid artery was prepared and applied a ligature. Hypotension was then generated using subcutaneous injection of sodium nitroprusside (0.8 mg/250 g). Banners carotid arteries were removed after 60 minutes, and the animals were observed for 24 hours. They were scored, the brain was immediately removed and placed in a drying Cabinet at 80oC for 24 hours to determine water content. The results were analyzed using aparametric U TES is.N. R. A. A., neither aspirin was not significantly reduced ischemic brain when animals were injected separately in the above-mentioned doses. However, if joint application was received considerable protection. These results confirm the synergism between anti-ischemic effects M. R. A. A. and ASC. Example 19 Used Mongolian gerbils of both sexes (body weight 60-80 g) and pre-adapted to laboratory conditions for one week. M. R. A. A. was administered via a stomach tube suspended in the carrier - aqueous solution of tween-20. Animals were allocated through a random sample, the following groups: (1) positive control (animals with the imposition of the ligature receiving only media), (2) M. R. A. A. (50 mg/kg) and (3) M. N. R. A. A. (300 mg/kg). All drugs were injected two hours before induction of ischemia of the brain, the Left common carotid artery was isolated on the neck and put a double ligature of the surgical thread under ether anesthesia. The behavior of each animal was observed within 24 hours, noting the clinical symptoms of ischemia of the brain, such as a circular movement, attacks spins and grabs. It was also noted the death of animals. Statistical comparison of frequent Fig. 18 shows the effect of M N.R. A. A. on brain infarction induced in Mongolian gerbils, p < < 0,05 (U test Mann-Whitney). The results show that the treatment reduced the symptoms and significantly reduced the death of animals. It is well known that approximately 60% of Mongolian gerbils developing a neurological disease, such as behavior whirling and seizures rotation after ligation of the common carotid artery. These symptoms were related to the fact that approximately 2/3 of these animals there is inadequacy or lack of connecting routes between the basilar and carotid system. In addition, almost 80% of the animals, which are manifested clinical symptoms die within 72 hours after applying ligatures. As the severity of cerebral infarction in all areas of the brain are difficult to assess, while the death of rats, it is easy to calculate, usually this option is used to assess the alleged anti-ischemic drugs. Our results show that M. R. A. A. (200 mg/kg) significantly protects from total brain ischemia caused by bilateral ligature of the common carotid arteries in Mongolian gerbils. Thus showing the applicability of M. R. A. A. the and, caused by various drugs. Used rat Sprague Dawley both sexes weighing 200-220, Animals were adapted to laboratory conditions for a week, providing them with food and water ad Libitum (as you want). After 24-hour fasting rats were divided by random selection into two experimental groups. Animals from the first group were injected intraperitoneally M. R. A. A. at a dose of 25 mg/kg, in the form of a suspension in a solution of tween-20 in water. While the animals of the second group (control) received only the same volume of solvent. In each case the experimental procedure for the induction of various types of gastric ulcers caused by medication, was conducted both in the control and in the group receiving treatment (for each type of ulcer was used two groups):A) stomach Ulcers caused 4880 C (Sigma). The method performance was similar to the procedure described Awouter F. , Nemegeens C. J. E. and Jansken P. A. J. (1985: Apharmacological analysis of the rat mast cell 5-HT gastric Lesion test and the effect of ketanserin; Drug. Div. Res. 5, 303-312). This was subcutaneously injected diphenhydramine dose of 10 mg/kg over 30 minutes intravenously injected C 4880. Animals were scored after 4 hours after injection C 4880 and quickly removed the stomachs were opened them along the length of maximal curvature and washed the od magnifying glass. The results were expressed in percent of the area in which apparent defeat. In this model, pre-treatment with the drugs (M. N. R. A. A. or solvent) was carried out for 30 minutes before injection of diphenhydramine. In) Ulcer caused by alcohol. The procedure was carried out as described Zengil H., Onik E., Erean T. S. and Tarker R. K. (1987: Protective effect of ilopnost and UK 38485 against gastric mucosal damage by various stimuli; Prostaglandins Leukotrienes and Medicine 30, 61-67). For this reason, one hour after a dose of M. R. A. A. or solvent rats orally via a stomach tube was introduced 40% ethanol (1 ml/rat). Two hours later the rats were scored, and the process of quantifying gastric ulcers was performed as described. C) a stomach Ulcer, caused by the ASC: the Procedure was carried out in accordance with methods of the same authors, which were referred to in the previous paragraph. One hour after the introduction of M. R. A. A. or solvent rats orally was administered ASA (100 mg/kg). Two hours later the rats were scored, and the procedure of measurement of gastric ulcers was carried out as described. Comparison between control and treated M. R. A. A. groups were carried out using neparitetnogo U test Mann-Whitney. Fig. 19 shows the effect of M N.R. the Yala occurrence of gastric ulcers, caused 4880 C, ethanol and ASC. In addition, as can be seen in table 19, administered orally M. R. A. A. not only reduces Thw, but also increases Pg12, thus significantly reducing the ratio DV to Pg12. Lower levels Thw and increase Pg12 caused by M. R. A. A., could explain the protective effect of this mixture against stomach ulcers. Thus, there is a highly significant reductions in the ratio of KW to Pg12 when applied combined introduction M. R. A. A. and ASC. In addition, this mechanism could also explain the action of a mixture of alcohols on other stomach ulcers caused by medicines. Example 21 Forty-five outpatients of both sexes aged from 25 to 70 years with hyperlipoproteinemia type II received the M. SC.R. A. A. or placebo in pill form once a day for 6 weeks (treated patients received 5 mg/day M. R. A. A.) in terms of double-blind testing. Before and after treatment was determined by the following parameters: bleeding time, platelet count, prothrombin time, the progressive activity of anti-thrombin, the time of lysis, euglobulin fraction of plasma, platelet aggregation caused by ADP, and the concentration of malondialdehyde is m coagulation, was not affected, while there were considerable differences between the groups on platelet aggregation caused by ADP. In addition, also saw a very significant decrease in MDA (p = 0.058). 1. The mixture of higher primary aliphatic alcohols C24- C34containing, wt.%: 1-Tetracosane - 0,5 - 1,0 1-Hexacosanol - 5,5 - 8,5 1-Heptacosane - 2,0 - 3,5 1-Octacosanol - 60,0 - 70,0 1-Nonacosanol - 0,4 - 1,2 1-Triacontanol - 10,0 - 15,0 1-Dotriacontanol - 4,0 - 6,0 1-Tetratriacontane - 0,4 - 2,0 2. The mixture under item 1, characterized in that it contains, wt%: 1-Tetracosane - 0,8 0,1 1-Hexacosanol - 6,7 0,3 1-Heptacosane - 3,0 0,3 1-Octacosanol - 65,6 3,4 1-Nonacosanol - 0,7 0,1 1-Triacontanol - 12,5 0,6 1-Dotriacontanol - 5,0 0,4 1-Tetratriacontane - 0,8 0,1 3. Mix on PP.1 and 2, showing antithrombotics, antithrombotic protection and total ischemia of brain activity. 4. Mix on PP.1 and 2, showing a protective activity against gastric ulcers induced by acetylsalicylic acid. 5. The method of obtaining a mixture of higher primary aliphatic alcohols C24- C34under item 1, characterized in that the molten wax of sugar cane, precision is the ratio of hydroxide to wax 15 - 25% followed by extraction of the mixture of alcohols in the system solid - liquid solvent selected from hydrocarbon with 6 to 9 carbon atoms, ketone with 3 to 8 carbon atoms, alcohol with 1 to 5 carbon atoms, halogen derivative or toluene, and the resulting product is subjected to recrystallization of the above-mentioned solvents or mixtures thereof. 6. The method according to p. 5, characterized in that the solvent in the extraction step using a solvent selected from methyl ethyl ketone, acetone, ethanol, 2-propanol, heptane, chloroform, dichloromethane, toluene. 7. The method according to p. 5, characterized in that the use of sugar cane wax with a melting point of 90 - 150oC and saponification are for 2 to 5 h, and the extraction - 5 - 10 PM 8. The method according to p. 5, characterized in that the product obtained in the crystallization process has a melting temperature of 78.5 83oC. 9. The method according to p. 5, characterized in that as hydroxide of alkali or alkaline earth metal is used, sodium hydroxide, or potassium, or calcium. 10. Pharmaceutical composition in the form of tablets, capsules or granules on the basis of active substances and pharmaceutical excipient as is omnitele, characterized in that as the active active substance contains 0.5 to 15.0 wt.% the mixture of alcohols on PP.1 to 4. 11. The pharmaceutical composition according to p. 10, characterized in that as excipients contains lactose and/or corn starch, as agglutinating substances, sucrose, talc and/or microcrystalline cellulose, as dezintegriruetsja substances gelatin and/or croscarmellose sodium, as the lubricant is talc and/or magnesium stearate. 12. The pharmaceutical composition according to p. 10, characterized in that it contains a mixture of alcohols on PP.1 to 4 0.5 to 15 wt.% and as pharmaceutical excipient%: Lactose - 50,0 - 65,0 Cornstarch - 10 - 20 Sucrose - 3,0 - 6,0 Microcrystalline cellulose - 6,0 - 10,0 Gelatin - 1,5 - 4,0 Crosscarmellose sodium - 3,0 - 7,0 Talc - 1,0 - 3,0 Magnesium stearate - 0,5 - 2,5 and possibly other pharmaceutical excipients, for example, 0.5 to 1.5 wt.% acatitla pulp. 13. The pharmaceutical composition according to any one of paragraphs.10 to 12, wherein the daily dose is from 1 to 100 mg of the mixture on PP.1 to 4, especially from 5 to 20 mg, and is preferably orally or parenterally, as antitromboticos, ago and/or therapeutic agent for gastric ulcer. 14. Mixture comprising acetylsalicylic acid and a mixture of higher primary aliphatic alcohols in the quantitative ratio of 10 : 1 to 1 : 10, manifesting antithrombotics, antiischemic or antithrombotic activity.
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