Fructan containing composition for the prevention and...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

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C514S054000, C536S123120, C426S658000

Reexamination Certificate

active

06500805

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to the use of certain fructans, preferably certain inulins, for the manufacture of a composition for the prevention and/or treatment of colon cancer in non-bovine mammals.
The present invention also relates to the use of compositions comprising certain fructans, preferably certain inulins, for the prevention and/or treatment of colon cancer in non-bovine mammals, and to a method of prevention and/or treatment of colon cancer in non-bovine mammals.
BACKGROUND OF THE INVENTION
Cancer in mammals is a disease which is already known from Ancient Times. Nowadays cancer, particularly lung, breast and colon cancer, has become one of the major causes of death of non-bovine mammals, in particular of humans, in the industrialised world.
The cancer disease is known to proceed in several steps, including genesis of cells of modified genome and functionality resulting in the formation of malignant cells; uncontrolled local proliferation of the malignant cells and invasion of adjacent normal body structures; and metastasis. During metastasis malignant cells are spread in a body cavity and/or throughout the body via the blood stream and/or the lymph, with invasion of various normal body structures. The invasion of the normal body structures results in their malfunctioning and/or destruction, eventually leading to the death of the affected mammal.
Various factors which can provoke carcinogenesis and cancer have already been identified, including certain viral infections, exposure to ionising radiation, exposure to certain mineral fibres, exposure to chemical mutagens, and improper diet.
As a result thereof various preventive measures have been introduced which have shown to be successful in preventing or reducing the occurrence of certain cancers.
Furthermore, various surgical and chemotherapeutical methods have been developed for the treatment of cancer. According to the type of cancer, the stage of the disease and the particulars of the affected mammal, these methods have been shown effective to a more or lesser degree.
Many reliable animal models for the study of the genesis and evolution of various cancers are available at present, enabling the evaluation of the preventive and curative properties of miscellaneous chemicals and dietary products.
Epidemiological studies in combination with studies on animal models have lead to the identification of dietary fibres as an important factor in the prevention and inhibition of certain cancers in mammals.
Dietary fibres are commonly defined as components of plant cells which are resistant to hydrolysis by the alimentary enzymes of man. Dietary fibres comprise cellulose, hemicellulose, polysaccharides, pectin, gums, waxes and lignin. According to this definition, fructans, which are soluble and edible polysaccharides, are dietary fibres. Fructans are composed of chains of carbohydrates which consist mostly of fructose units and in which fructosyl-fructose linkages constitute the majority of the linkages. Fructans commonly occur as polydisperse carbohydrates. They occur in plants, but they also can originate from bacterial activity and they can be synthesised enzymatically as well. All these fructans present typical dietary fibre properties; they are embraced by the present invention and are referred to herein as fructan(s).
Fructans are well known compounds including levan and inulin carbohydrates. Levans are D-fructans generally consisting of chains of fructose units which are essentially connected to each other by &bgr;(2-6) linkages. Inulins are also D-fructans generally consisting of chains of fructose units but which are essentially connected to each other by &bgr;(2-1) linkages. Most of the inulin chains terminate in one glucose unit.
Levans may occur as linear chain carbohydrates but they are mostly composed of branched fructose chains, whereas inulins are generally composed of linear chain carbohydrates but they may also occur as chains of fructose units which are branched to a larger or lesser extent. Levans and inulins which are suitable according to the present invention include linear and branched chain carbohydrates, as well as mixtures of said linear and branched chain carbohydrates.
Inulins occur in many plants and crops and can occur at concentrations of about 10 to 20% on fresh weight in chicory, dahlia tubers and Jerusalem artichoke. They can be isolated from these plants, purified, and optionally refined to remove impurities and undesired fractions of carbohydrates, at industrial scale, according to well known techniques.
Inulins can be represented by the general formulae GF
n
and F
m
wherein G represents a glucose unit, F represents a fructose unit, n represents the number of fructose units linked to the terminal glucose unit, and m represents the number of fructose units linked to each other in the carbohydrate chain. The number of saccharide units (fructose and glucose units) in one fructan molecule, i.e. the values n+1 and m in the above formulae, are commonly referred to as the degree of polymerisation and represented as (DP). Often the parameter average degree of polymerisation ({overscore (DP)}) is used too, which is the value corresponding to the total number of saccharide units divided by the total number of saccharide molecules present in a given (poly)saccharide composition.
Inulin from plant origin is a polydisperse composition of fructose chains with a degree of polymerisation (DP) ranging from 2 to about 100, whereas inulin from bacterial origin usually has a higher degree of polymerisation.
Fructans, including inulins of general formulae GF
n
and F
m
, with a lower degree of polymerisation, usually defined as a (DP)<10, are commonly named oligofructoses and are referred to herein accordingly.
Inulin is commercially available. For example, inulin from chicory is available as RAFTILINE® from ORAFTI, (Tienen, Belgium), in various grades. Typical RAFTILINE® grades are, for example , ST, ST-Gel and GR (which have an average degree of polymerisation ({overscore (DP)}) of 10 and contain in total about 8% by weight glucose, fructose and sucrose), LS (which has also an average degree of polymerisation of 10 but which contains in total less than 1% by weight glucose, fructose and sucrose), and HP (high performance inulin) and HP-Gel (which have an average degree of polymerisation of ≧23, commonly about 25, and are essentially free of glucose, fructose and sucrose).
Oligofructoses are usually obtained by partial, acidic or enzymatic hydrolysis of inulins and can also be obtained by enzymatic synthesis from sucrose , according to techniques which are well-known in the art. Oligofructoses are commercially available. Several grades of oligofructose are, for example, available from ORAFTI, (Tienen, Belgium), as RAFTILOSE®, e.g. RAFTILOSE® P95 which contains about 95% by weight oligofructoses with a degree of polymerisation ranging from 2 to 7 and about 5% by weight in total of glucose, fructose and sucrose.
STATE OF THE ART
Dietary fibres, in particular fructans, are known to have effects on various physiological functions and mechanisms in mammals.
In non-bovine mammals, these fibres are almost not metabolised in the mouth, the stomach and the small intestine, and they thus almost quantitatively enter the large intestine where they are completely fermented by the colonic microflora. This phenomenon results in various beneficial health effects in non-bovine mammals such as, for example, a reduction of the intestinal transit time, a decrease of the intestinal pH, a bifidus stimulating activity in the colon, an increase of the stool weight (bulking) and stool frequency.
Fructans, particularly inulin, are also known to have a beneficial effect on lipid metabolism , including a lowering effect on blood cholesterol and on serum triglycerides, and an increasing effect on the HDL/LDL ratio.
P. D. Cooper et al., Molecul. Immunol., 23 (8), 895, (1986), describe the activation of the alternative pathway of complement by gamma-inulin (a specific polymorphic form of dahlia in

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