Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1993-11-22
1996-03-26
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
A61K 3156
Patent
active
055020453
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/FI91/00139 filed May 03, 1991.
A high cholesterol level in serum can be lowered effectively by altering the intestinal metabolism of lipids. In this case the aim may be to hamper the absorption of tri-glycerides, cholesterol or bile acids. It has been observed in a number of investigations that certain plant sterols, such as .beta.-sitosterol (24-ethyl-5-cholestene-3.beta.-ol) and its hardened form, .beta.-sitostanol (24-ethyl-5.alpha.-cholestane-3.beta.-ol), lower serum cholesterol levels by reducing the absorption of dietary cholesterol from the intestines (1-25). The use of plant sterols can be considered safe, since plant sterols are natural components of vegetable fats and oils. Plant sterols themselves are not absorbed from the intestines, or they are absorbed in very low concentrations. A decreased incidence of coronary disease is clearly associated with a decrease in serum cholesterol, in particular LDL cholesterol. A high serum cholesterol value is the most significant single indicator of the risk of coronary disease.
The degree of cholesterol absorption depends on a hereditary property, apoprotein E-phenotype. Apoprotein E is a protein which belongs to serum lipoproteins and takes part in the transport of cholesterol in the system (26). Of alleles associated with the synthesis of apoprotein E, i.e. the lipoprotein which affects absorption, there are known three types, e2, e3, and e4, which combine in pairs at random. Alleles are capable of forming in total six different combinations. The higher the sum of the subindices, the better absorbable the cholesterol and the higher the level of cholesterol, in particular bad LDL cholesterol, in the serum (27). e4 allele is overrepresented among the hereditary factors of Finns, so that its proportion is almost double as compared with many European populations (28). Finns are indeed exceptionally sensitive to dietary flaws and to fatty and high-cholesterol food (29).
Serum cholesterol levels can be lowered by dietary means, by paying attention to the quantity and type of the fat ingested and to the amount of cholesterol intake. In practice, however, these means do not always lead to a satisfactory end result. Other methods, suitable for the entire population, for reaching serum cholesterol levels lower than the present ones must be searched for. Increasing the fiber content of food is a method of limited effect. The cholesterol-lowering effect of soluble fiber in food is based on the binding and removal of bile acids. Since the absorption of cholesterol is of fundamental significance in the regulation of the cholesterol level in serum, it is logical to aim at developing methods by which the absorption of cholesterol can be prevented or reduced.
Pollak demonstrated that ingested plant sterol lowered the level of serum cholesterol in man (1). The same had previously been observed in experimental animals (2, 3). It has been observed in a number of investigations that large doses of plant sterols lower the levels of serum cholesterol, at best by 10-20% (4, 5). In these experiments, large amounts, up to 24 g/day, of .beta.-sitosterol in crystalline form were used (6). In certain experiments the serum cholesterol level was lowered significantly even with lower doses (7), although a small amount of soluble sitosterol administered in the form of fatty acid esters did not seem to lower serum cholesterol very effectively (8). Sitosterol preparations have in general been well tolerated in long-term use (9).
Natural plant sterols resemble cholesterol in their structure. The differences between a cholesterol molecule and a plant sterol molecule are primarily found in the structure of the side chain of the basic frame. An ordinary diet contains plant sterols 100-300 mg/day. Most of the plant sterol in the diet is .beta.-sitosterol, and approx. one-third is campesterol. Small amounts of saturated 5.alpha.-sitostanols are also present in food. Usually the campesterol concentrations in serum in particular reflect the degree of absorption of
REFERENCES:
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patent: 5270041 (1993-12-01), Eugster et al.
Chemical Abstracts, vol. 115, No. 1, 8 Jul. 1991, T. Heinemann et al., "Mechanisms of Action of Plant Sterols on Inhibition of Cholesterol Absorption: Comparison of Sitosterol and Sitostanol".
Chemical Abstracts, vol. 112, No. 7, 12 Feb. 1990, I. Ikeda et al., "Effects of Sitosterol and Sitostanol on Micellar Solubility of Cholesterol".
Chemical Abstracts, vol. 112, No. 7, 2 Feb. 1990, T. Heinemann et al., "Comparison of Sitosterol and Sitostanol on Inhibition of Intestinal Cholesterol Absorption".
Chemical Abstracts, vol. 95, No. 13, 28 Sep. 1981, I. Ikeda et al., "Antihypercholesterolemic Activity of beta-sitostanol in Rabbits".
Chemical Abstracts, vol. 88, No. 3, 16 Jan. 1978, M. Sugano et al., "A comparison of hypocholesterolemic activity of beta-sitosterol and beta-sitostanol in rats".
Int'l Search Report, dated 11 Dec. 1991 of PCT/FI91/00139.
Int'l Preliminary Exam Report, dated 4 Aug. 1993 of PCT/FI91/00139.
Copy of Written Opinion from Int'l Preliminary Exam Authority, dated 14 Apr. 1993 of PCT/FI91/00139.
Abstract, JP 44 004974, 28 Feb. 1969, "Sitosterol Fatty Acid Ester", Tsuchiya.
Miettinen Tatu
Vanhanen Hannu
Wester Ingmar
Henley III Raymond
Raision Tehtaat Oy AB
Weddington Kevin E.
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