Mixture of higher primary aliphatic alcohols, its obtention from

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ortho-hydroxybenzoic acid or derivative doai

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514724, 568840, 568877, 568920, 568921, 568923, C07C 2974, A61K 31045

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056631561

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BRIEF SUMMARY
This application is a 35 U.S.C. 371 National Stage filing of PCT/EP93/00007 published as WO 94/07830 on Apr. 14 1994.
This invention is related to a mixture of higher primary aliphatic alcohols, containing alcohols of a range from 24 to 34 carbon atoms and more especially, those with straight chain of 24, 26, 27, 28, 29, 30, 32 and 34 carbon atoms.
This mixture shows a relative composition of each alcohol, that is highly reproducible batch to batch.
According with the present invention this mixture of higher primary aliphatic alcohols from 24 to 34 carbon atoms (thereafter called M.H.P.A.A.), in a relative narrow quantitative correlation, shows new properties such as antiplatelet, antithrombotic and/or anti-isquemic agents, as well as for the antagonism of drug-induced ulcers and that is why this specific mixture can be used as active ingredient of pharmaceutical formulations prepared for these purposes.
An object of the invention is to place at the public's disposal M.H.P.A.A. of 24 to 34 carbon atoms for pharmaceutical formulations.
One of the objects of this invention is to obtain, isolate and purify this, particular, mixture of higher primary aliphatic alcohols (M.H.P.A.A.) of 24 to 34 carbon atoms from the sugar cane wax, both from raw and refined wax.
Lipid-lowering effects of sugar cane wax have been demonstrated in rats (Fukuda, Effects of sugar cane wax on serum liver lipids on rats; Chemical Abstracts, 106, 17, 137413p) 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).
Firstly, effects of sugar cane wax on serum and liver lipids were investigated in male Wistar rats fed high levels of plants and animal fats. The authors found that addition of 0.5% of sugar cane wax to dietary fat reduces significantly serum triglycerides in rats fed plant or animal fats, but only in the last ones cholesterol levels decreased significantly, without affecting the content of liver lipids. Hence, authors concluded that sugar cane wax shows hypolipidemic effects.
On the other hand, Sho H. et al (1984) studied the effects of Okinawan sugar cane wax on serum and liver lipids in rats fed a diet containing 0.5% of this wax and they found a significant reduction of both serum and liver cholesterol content. Nevertheless, no significant variation in cholesterol levels were found when used fatty alcohols from the same wax in the diet of animals. Thus, they discarded that lipid-lowering properties of the wax were attributable to these alcohols.
However, some years later, Shimura S., Hagesawa T., Takano S. and Susuki T. (1987: Studies on the effect of octacosanol on the motor endurance in mice; Nutrition Reports Int. 36, 1029-1038) studied the effects of octacosanol in mice subjected to physical activity and fed octacosanol-enriched diet. They found that octacosanol isolated from sugar cane wax significantly reduced the content of both triglycerides and cholesterol in the liver, while only serum levels of triglycerides were reduced in a significant manner. They concluded that octacosanol isolated from sugar cane wax showed lipid-lowering properties, which disagrees with the previous results of Sho H. et al (1984) aforementioned.
Likewise, antilipaemic effects have been also further attributed to hexacosanol, another higher primary aliphatic alcohol, although very high doses were reported as needed to obtain such results (10-30 mg/kg/day) (Hagiwara Y. 1987: Antilipaemic agents containing hexacosanol used to treat hypertension, arteriosclerosis, diabetes mellitus, heart disease and obesity; JP A 62 099323).
There are different commercial lipid-lowering drugs considered as effective, safe and well tolerated, but most of them produce different adverse side effects. Since lipid-lowering therapy must be administered chronically, this aspect is very important.
For example, gemfibrozil reduces serum triglycerides, raises HDL-C levels and produces a mild decrease of serum cholesterol, but several drug-related adverse effects hav

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