Composition comprising soy protein, dietary fibres and a...

Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from leguminosae

Reexamination Certificate

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C424S439000

Reexamination Certificate

active

06630178

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to soy protein, phytoestrogens and dietary fibres and compositions thereof suitable for preventing, alleviating and/or treating cardiovascular diseases such as arteriosclerosis, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, hypertension and related cardiovascular diseases. In particular a composition according to the present invention has improved effects in lowering levels of total serum cholesterol and LDL-cholesterol. A composition according to the present invention is also particularly useful in reducing the accumulation of cholesterol in the arterial wall of subjects at high risk for developing cardiovascular disease or already suffering from a cardiovascular disease such as atherosclerosis. A composition according to the present invention is also useful for lowering serum levels of total cholesterol and/or LDL-cholesterol and/or triglycerides and/or homocystein and/or for increasing serum levels of HDL-cholesterol and/or for improving the HDL/LDL-ratio in subjects at risk for developing cardiovascular diseases and in subjects already suffering from an arteriosclerotic condition such as e.g. atherosclerosis or a related cardiovascular disease. The present invention also relates to the use of these compositions in the manufacture of a medicament for treating a subject suffering from cardiovascular diseases, more particularly arteriosclerosis, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, hypertension and/or related cardiovascular diseases. The present invention also concerns use of a composition according to the present invention in the prevention and/or treatment of said diseases and disorders and for lowering serum levels of total cholesterol and/or LDL-cholesterol and/or triglycerides and/or serum levels of homocystein in subjects. In addition, the present invention also provides methods for preventing and/or treating and/or prophylactically treating and/or alleviating by therapy said diseases and disorders.
BACKGROUND OF THE INVENTION
Lipid metabolism involves biosynthesis and degradation of e.g. fatty acids, triglycerides and cholesterol. Ingested triglycerides are hydrolysed in the small intestine and hydrolysis products are absorbed by the intestinal mucosa. Due to the relative insolubility of dietary lipids in water, lipid digestion and absorption is facilitated by the action of detergent substances such as bile acids secreted from the gallbladder. Bile acids are essential for lipid digestion and absorption through the intestinal mucosa.
Triglycerides and cholesterol synthesized in the liver are transported in the bloodstream to peripheral tissues by transport proteins called lipoproteins. Lipoproteins are tiny vesicles coated by apoproteins, phospholipids and free cholesterol and with an interior consisting of the more hydrophobic lipids, cholesteryl esters and triglycerides. Apoproteins and lipoproteins are primarily synthesized in the liver. The lipoproteins are capable of performing an apoprotein mediated binding to a receptor on the surface of a cell into which the entire lipoprotein particle is taken up and further metabolised.
Several different families of lipoproteins have been characterized and are traditionally classified by their density as determined by centrifugation. A standard lipoprotein classification scheme may include in increasing order of density, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
VLDL contains approximately 60 to 65 percent triglycerides and 5 to 10 percent cholesterol, lecithin and protein. They are relatively large and function in the transport of triglycerides from the liver to tissue. LDL contains approximately 40 to 50 percent cholesterol and 10 to 15 percent triglycerides, lecithin and protein. They are somewhat smaller than VLDL and also function in the transport of cholesterol from the liver to tissue. HDL contains roughly 75 percent lecithin and protein, while the rest is made up of cholesterol and a small amount of triglycerides. They function in the transport of cholesterol from tissue to the liver and, as such, have the opposite function of LDL. Cholesterol esters cannot readily traverse cellular membranes and are taken up by cells in a receptor-mediated process. Once bound to the LDL-receptor, the LDL-particle is internalised by means of endocytosis, and cholesterol and fatty acids are released and further metabolised.
Ongoing investigations of the LDL-receptor-mediated internalization of cholesterol have generated a better understanding of the relationship between dietary cholesterol, plasma cholesterol levels, and the condition of artherosclerosis. It is believed that the white blood cells that accumulate cholesterol at sites of arterial injury contain a receptor termed a scavenger receptor. Like the LDL-receptor, this scavenger receptor acts by the mechanism of endocytosis and mediates internalization of various extracellular materials. However, the scavenger receptor is indiscriminatory and takes up many different types of extracellular materials including oxidized-LDL-particles containing cholesterol. In contrast to the LDL-receptor, the scavenger receptor is not down-regulated by a high concentration of cholesterol in the cell.
In addition to the above-mentioned lipoproteins, the organism also contains a type of lipoproteins called chylomicrons. Chylomicrons contain 90 to 95 percent triglycerides and only a small amount of cholesterol, lecithin and protein, and they function in the transport of triglycerides from the small intestine to e.g. muscles, liver and heart.
The metabolism of cholesterol in the human organism is closely linked to the synthesis, transport and degradation of triglycerides. Cholesterol is an essential lipid component in all mammalian cells. It is used to regulate the fluidity of cellular membranes and serves as a precursor for certain hormones, vitamin D and bile acids. Cholesterol is synthesized in the liver and is transported with the blood to peripheral tissues by lipoproteins. The liver has a dual function in the metabolism of cholesterol since it is capable of both synthesizing cholesterol and converting surplus cholesterol into bile acids. It is also capable of excreting cholesterol into the bile.
Bile acids have ampholytic characteristics and contain both hydrophobic and hydrophilic surfaces. This ampholytic character facilitates a bile acid mediated emulsification of lipids into micelles. The formation of micelles allows digestive attacks by water-soluble enzymes and facilitates lipid absorption through the mucosal cells of the intestine. Bile acids are secreted from the liver and stored in the gallbladder before being passed through the bile duct and into the intestine. Biosynthesis of bile acids represents a major metabolic fate of cholesterol and accounts for more than half of the approximately 800 mg cholesterol that is normally metabolised per day in a normal adult. Even though bile acids in an amount of 400 mg are synthesized each day, significantly more than this amount is secreted into the intestine. Most of the bile acids that are secreted into the upper small intestine are absorbed in the lower small intestine and are recycled to the liver. The process of enterohepatic circulation may amount to as much as 20 to 30 g of bile acids per day. In contrast, daily elimination of bile acids in the faeces amounts to just 0.5 g or less.
Cholesterol acts on three different levels of regulation of its own synthesis. Firstly, it suppresses endogenous cholesterol synthesis by inhibiting HMG-CoA reductase. Secondly, it activates acyl-CoA:cholesterol acyltransferase (ACAT) which is involved in the synthesis of cholesterol esters from cholesterol and fatty acids bound to acyl-CoA. Thirdly, cholesterol regulates synthesis of the LDL-receptor. Accordingly, a decreased synthesis of LDL-receptors will ensure that a cell in which a sufficient amount of cholesterol is already present does not take up cholesterol. This m

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