HUP9904491A2 - Compositions of plant carbohydrates as dietary supplements - Google Patents

Abstract

Dietary supplement comprises a nutritionally effective amount of \-1 saccharide in monomeric, oligomeric or polymeric and derivatised or underivatised form selected from galactose, glucose, mannose, N-acetylneuraminic acid, fucose, N-acetylgalactosamine, N-acetylglucosamine, xylose, arabinose, glucuronic acid, galacturonic acid, iduronic acid, arabinogalactan and acetylated mannose, provided that (i) when mannose is present alone, it is in monomeric form, and (ii) when acetylated mannose is present alone, it is in monomeric form.

Description

A preparation consisting of vegetable carbohydrates as a food supplement

The invention relates to dietary and nutritional additives that promote the maintenance of good health. More particularly, the invention relates to carbohydrates as food additives that are essential for the production of glycoproteins with the correct structure and thus proper function.

The term mucus was first used in the 1700s. In 1805, Bostok found that mucus was composed of proteins that were different from albumin and gelatin. In 1865, Eichwald showed that mucins contained carbohydrate groups. In 1877, Hoppe-Seyler discovered that mucins were high in sialic acid. In 1882, Landwehr showed that plant gums, which are a type of mucin, contain more than one monosaccharide. With the advent of modern methods, these monosaccharides were isolated and characterized. In 1888, Harmarsten showed that the saccharides in mucin were covalently linked. Harmarsten was the first to use the term glycoprotein. Fischer and Leuchs discovered in 1902 that mucus has a high concentration of mannose. Hayworth discovered N-acetylglucosamine in 1939 and Bierry discovered galactose in 1930. Meyer discovered fucose in 1958 (Gottschalk, Glycoproteins, 1972).

89337-9304A-SZÖ/Km0

- 2 Proteins were originally thought to be the primary communication channels for molecules in the body. The biotechnology revolution first attempted to develop new protein-based drugs, which are made up of different combinations of amino acids. However, since amino acids are linked together only through amide bonds, the possibilities for secondary configurations in proteins are limited. In fact, only one secondary configuration is possible per dipeptide.

However, there are many more functions in the body than can be attributed to the molecular configurations of proteins. Several years ago, theoretical mathematicians calculated the number of possible configurations of proteins and found that another, as yet unknown mechanism is responsible for carrying out the body's communication functions. It is known that this mechanism involves carbohydrates.

Unlike simple proteins, the much more complex carbohydrate molecule is capable of multiple molecular configurations, for example, a hexose has six chiral centers, each of which can occur in two isomeric forms, and each of which contains a hydroxyl group on the binding side towards the other molecule. Thus, while only 24 oligopeptide configurations are possible for four amino acids, more than 100,000 different oligosaccharide configurations are possible for four sugars [Stryer et al., Biochemistry, 477 (1995)].

Scientists have shown that glycoproteins play a key role in cell communication. Many cytokines, or cell messengers, do not function properly without a glycoside group attached to them. The body hydrolyzes the complex

- 3 polysaccharides, such as plant carbohydrates, are broken down into various monosaccharides and then into oligosaccharides, which are used by the body to build glycoproteins, these glycoproteins are necessary for cytokines for cell communication and thus ensure good health.

With the development of analytical methods and the development of more advanced computers, glycoproteins have been better characterized since the 1960s. In the 1980s, the mechanisms of glycoprotein synthesis in the endoplasmic reticulum and Golgi were determined. The actual oligosaccharide conformations of many glycoproteins are now known.

As a result of the increased interest in glycobiology, it has been established that cell surface carbohydrates are involved in cell adhesion and thus in cell-cell interactions. In fact, three new mechanisms have been found. According to the first, studies in the field of glycoproteins and glycolipids have demonstrated the presence of carbohydrates that are unique to certain cell types. This theory is crucial for the understanding of cell surface carbohydrates as cell type-specific recognition molecules.

A second theory is based on new information about lectins; lectins are sugar-binding proteins. In the 1970s, it was thought that glycoproteins could be easily removed from the blood by removing their branched sialic acid, N-acetylneuraminic acid. Further studies have shown that this

- 4 rapid clearance is caused by asialoglycoproteins that recognize terminal galactose and bind to lectins. After it was established that animal cells contain lectins, a large number of lectins were characterized and a characteristic section in the amino acid sequences responsible for carbohydrate recognition domains was discovered. This discovery was of great importance in understanding the carbohydrate-binding capacity in cell-cell interactions. Thus, cell communication was recognized at the molecular level.

The third theory was based on the isolation and characterization of glycosyltransferases that form carbohydrates. According to this theory, carbohydrate groups are usually built up one after the other, and each reaction is carried out by a glycosyltransferase that creates only one specific bond. With the development of molecular biology, scientists were able to manipulate carbohydrate expression and study glycoprotein function.

Recent studies have shown that oligosaccharides, which are unique to leukocytes, act as ligands for adhesion molecules on the endothelium and platelets. When these adhesion molecules, known as selectins, were cloned, they were found to contain carbohydrate-recognition domains. Thus, studies on cell-type-specific carbohydrates and animal lectins confirmed each other. These studies preceded the finding that lymphocyte-endothelial interactions depend on carbohydrates.

- 5 Based on the above, studies were directed towards the synthesis of active ingredients that correct the deformity of glycoproteins on the cell surface. When the silalyl-Le ^x carbohydrate ligand was identified, pharmaceutical companies quickly synthesized it for therapeutic purposes. This research direction became increasingly easier as the enzymatic synthesis of carbohydrates became possible due to the availability of glycosyl transferases generated by cloned cDNAs [Fukuda et al., Glycobiology, (1994)].

The synthesis of all proteins and glycoproteins is regulated by somatic genes embedded in the chromosomes of cells. The coding information expressed in nucleic acids (DNA) controls all cellular functions, including general body defense, regeneration, remodeling, and healing. Although the necessary information is contained in DNA, cellular components cannot be assembled correctly without the desired building blocks. As mentioned above, cytokines play a key role in the intracellular instructions that ultimately enable the body to carry out its vital functions. However, many cytokines do not function properly without a glycosyl group attached to them.

Table 1 lists some of the known physiological functions performed by glycoproteins. Table 2 lists some of the specific known functions performed by the branches and chains of the oligosaccharide.

Table 1. Known functions performed by glycoproteins

Function Glycoproteins structural molecule collagen lubricant and protectant mucins transport molecule transferrin, ceruoloplasmin immunological molecule immunoglobulins, histocompatibility antigens hormone chorionic gonadotropin, thyroid stimulating hormone (TSH) enzyme different, such as alkali metal phosphatase cell connection recognition solution cell-cell (e.g. sperm- song -oocyte), various proteins involved in virus-cell, bacteria-cell and hormone-cell interactions With different carbohydrates some lectins

ongoing interaction

Table 2 Some known functions of oligosaccharide chains in glycoproteins * Modified physicochemical properties such as solubility, viscosity, charge and protein denaturation.

- 7 * Protection against proteolysis inside and outside the cell.

* Facilitating the proteolytic processing of precursor proteins into smaller products.

* They are involved in biological activity, such as human chorionic gonadotropin (hCG).

* Facilitating the incorporation of proteins into membranes, intracellular protein migration, and protein secretion and excretion.

* Effect on embryonic development and differentiation.

* Effect exerted by metabolism.

* Effect on metastasis sites selected by cancer cells.

In summary, glycoproteins with the correct structure and thus functioning properly regulate and influence various cellular processes.

Despite the recognition of the importance of glycoproteins in cell-cell communication and the importance of carbohydrates in the formation of glycoproteins, and despite the fact that diet is the main source of carbohydrates, the fields of glycobiology and nutrition have not been studied together. Current nutrition textbooks explain in detail the importance of essential vitamins, minerals, proteins (amino acids), and fats, but sugars are considered only as a source of energy [Shils et al.: Modern Nutrition in Health and Disease (1994)], not as a complete

- 8 essential materials for the production of glycoproteins necessary for achieving health. For example, Shils et al. describe that the basic sources of carbohydrates in the diet are: 1) corn, rice, wheat and potatoes, which provide starch containing glucose, 2) sugar cane and beet sugar, which provide fructose and glucose, and 3) milk, which provides galactose and glucose [Shils et al.: Modern Nutrition in Health and Disease (1994)].

In contrast, Harper in Biochemistry (Murrey et al., 1996) lists eight monosaccharides and Principles of Biochemistry, II, (Zubay et al., 1995) lists eleven monosaccharides that are commonly found in the oligosaccharide chains of cellular glycoproteins. Thus, there are approximately 200 monosaccharides found in nature, of which the 11 are thought to be most important for maintaining mammalian health.

The eleven saccharides mentioned are: galactose, glucose, mannose, N-acetylneuraminic acid, fucose, N-acetylgalactosamine, N-acetylglucosamine and xylose [Murray et al.; Herper: Biochemistry (1996)], as well as iduronic acid, arabinose and glucuronic acid [Zubey et al.: Principles of Biochemistry, Volume II (1995)]. The structures of these carbohydrates are described in Stryer's Biochemistry (Stryer, 1995) and the Merck Index (12th edition, 1996).

Recognizing the above, attempts are still being made, albeit with limited success, to synthetically attach glucosyl groups to cytokines and other proteins. NIH has established projects to develop methods that

- 9 lyes can synthesize glycomoieties that are currently missing from genetically engineered proteins. However, these synthetic cytokines have been disappointing. Several questions have arisen, and scientists must first determine 1) how to synthesize the glycomoieties, 2) how to attach the glycomoieties to the protein, and 3) how to deliver the right glycoproteins in the right concentrations to the right places in the body to ensure proper health.

People of various cultures have used plants and herbs for centuries to treat various diseases in mammals. In particular, poultices, teas, powders, pastes, extracts, plant and herb parts, plant or herb extracts, solutions, creams, ointments, tablets have been used. It is also known that the earth's agricultural areas have been depleted of essential minerals necessary for life, and thus the widespread use of vitamins, minerals and nutritional supplements has become necessary. A recent discovery emphasizes the importance of plant chemicals (phytochemicals), which occur in ripe fruits and vegetables, but not in other plants. In order to add the necessary, but not yet defined, phytonutrients and phytonutrients to the diet, some companies have begun to make nutritional supplements from freeze-dried ripe plants and herbs.

- 10 Nutritionists have developed hundreds of nutritional supplements to provide essential components of nutrition and promote good health in mammals. However, the industry is also plagued by false claims of products to treat physiological disorders and modern agricultural practices that prioritize quantity over nutritional value, resulting in products with lower nutritional value and lacking essential nutritional components.

Despite the enormous number of nutritional supplement products available on store shelves, the nutritional needs of people are still not being met. Many of these commercially available nutritional supplements do not provide any significant nutritional benefits. The inventors of the present invention believe that the known products have one or more of the following disadvantages: a) they do not contain the appropriate nutritional product(s); b) the nutritional products may not be well absorbed by the individual consuming them.

Thus, while scientists are beginning to recognize that other phytochemicals are necessary for maintaining health and that other plants and herbs have been recognized for their effectiveness in treating disease, our invention has not yet been described. There is a need for non-pharmaceutical dietary supplements that provide essential glycoproteins

- They contain 11 saccharides, which promote good health in mammals.

The subject of our invention is a nutritional supplement that promotes good health by providing mammals with essential saccharides that are the building blocks of glycoproteins.

The inventors of the present invention have found that when these essential saccharides are introduced into the diet of mammals in the form of a food supplement containing the saccharides, they promote good health. Without wishing to limit the mechanism of action, it is likely that these essential saccharides are absorbed by the mammalian body and can thus be utilized in the formation of glycoproteins. By introducing the essential saccharides in this way, the mammalian body does not have to use unnecessary energy to break down these essential saccharides, and thus the energy can be used for other physiological needs, such as strengthening the immune system, to prevent, combat and/or improve various physiological disorders.

Our invention thus does not have the disadvantages of the prior art solutions. One object of our invention is the use of various carbohydrate preparations, such as glyconutrients or glyconutrients, as a nutritional supplement, whereby the diet of mammals is provided with sugars that are essential for glycoprotein and/or glycolipid production, and thus promotes good health. According to one embodiment, the invention provides a

- 12 refers to a food supplement containing a specified amount of at least one of the eleven essential carbohydrates required for the production of properly structured and thus properly functioning glycoproteins and/or glycolipids in mammals. While some of the eleven sugars mentioned are readily available from normal foods, others are rarely available.

Accordingly, a first object of the present invention is to provide a nutritional supplement for the production of saccharide products which are essential components of glycoproteins found in mammals, said nutritional supplement comprising a nutritionally effective amount of at least one saccharide in monomeric, oligomeric or polymeric or derivatized or native form, which may be:

galactose, glucose, mannose, N-acetylneuraminic acid, fucose, N-acetylgalactosamine, N-acetylglucosamine, xylose, arabinose, glucuronic acid, galacturonic acid, iduronic acid, arabinogalactan, acetylated mannose, glucosamine and galactosamine.

In another embodiment of the invention, the food supplement comprises a nutritionally effective amount of at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten or at least eleven saccharides in monomeric, oligomeric or polymeric, derivatized or native form, which may be as listed above. Since some of these saccharides contain

- 13 talmaz ionizable groups, our invention also includes the known non-toxic salt forms thereof.

Monomeric, oligomeric, polymeric, derivatized, or native forms of saccharides can be obtained from a variety of sources. These include gum tragacanth, guar gum, corn flour, rice flour, sugar cane, beet sugar, potato, milk, agar, algin, locust bean gum, horseradish, karaya gum, seed gums, larch extract, aloe vera extract, ghatti gum, starch, cellulose, degraded cellulose, fructose, high fructose corn syrup, pectin, chitin, acacia, gum arabic, alginic acid, carrageenan, dextran, xanthan gum, chondroitin sulfate, sucrose, acetylated polymannose, maltose, glucan, lentinan, mannan, levan, hemicellulose, inulin, fructan and lactose.

Further embodiments of our invention may include phytochemicals and phytonutrients derived from ripe and freeze-dried plants or vegetables, dioscorea complex, herbal extracts, herbal tonics, β-sitosterols, melatonin, soy lecithin, vitamins or minerals.

In another embodiment of the invention, the composition comprises a pre-ripened form of at least one of the eleven essential carbohydrates. Pre-ripening comprises one or all of the following steps: 1) physical ripening, such as shearing or sonication; 2) chemical ripening, such as enzymatic ripening and acid or base treatment.

- 14 hydrolysis; and 3) biological ripening with microbes, such as bacteria, fungi or molds.

A further aspect of the invention is a nutritional supplement for the treatment of alcohol-dependent mammals, comprising a nutritionally effective amount of natural and/or synthetic monomeric, oligomeric and/or polymeric forms of acetylated mannose, gum ghatti, gum tragacanth, glucosamine, wheat starch and arabinogalactan. In a specific embodiment, the nutritional supplement reduces alcohol craving in alcohol-dependent mammals when administered the supplement. In a further specific embodiment, the nutritional supplement improves the general behavior of the alcohol-dependent mammal by reducing depression, irritability or improving cognition, energy and positive outlook.

A further aspect of the invention is a nutritional supplement for reducing unwanted side effects in mammals when the mammals are administered a biologically active substance that causes side effects, the nutritional supplement comprising a nutritionally effective amount of natural and/or synthetic monomeric, oligomeric and/or polymeric acetylated mannose, gum ghatti, gum tragacanth, glucosamine, wheat starch and arabinogalactan. In a specific embodiment, the nutritional supplement reduces unwanted side effects of drugs acting on the central nervous system. In a more specific embodiment, the nutritional supplement reduces the undesirable side effects of drugs acting on the central nervous system.

- 15 undesirable side effects caused by methylphenidate in mammals treated with methylphenidate.

The mammalian body hydrolyzes or metabolizes complex polysaccharides, such as plant carbohydrates, into various monosaccharides, which are then converted into oligosaccharides, which are used by the body to build glycoproteins that are necessary for cytokines for cell communication.

The term “phytochemical” refers to molecules synthesized by plants that are found in complex organic matrices in food, plant tissues, and that are minimally altered from their naturally occurring forms during processing. The term “nutrient” refers to non-toxic nutrients derived from plants, minerals, or animal materials that have health-promoting effects and that can be used as a dietary supplement to improve the quality of nutrition in a balanced overall diet. Nutrients include both glyconutrients and phytonutrients.

The terms “glyconutrient” or “glyconutrient” refer to complex carbohydrates, saccharides or simple sugars that are synthesized in nature and are necessary for the biochemical synthesis of various types of communication, as well as signaling molecules that are free from interstitial cell fluids and are active in cell-cell communication (e.g. cytokines, growth factors, etc.), or to molecular configurations that

- 16 which contain highly specific molecular activities of cell membranes (receptor sites, ion transport channels, antigen recognition, etc.).

The term “phytonutrient” or “phytonutrient” refers to molecules synthesized in products that are only present in plants and that are produced by them for the protection of plant cells. Phytonutrients primarily have antioxidant free radical scavenging and vital micronutrient activity. The molecules thus introduced through dietary supplementation are found in mature plant tissues, with the highest concentrations in the seed coat and fruit tissues surrounding the seed. When these molecules are delivered to mammalian tissues with the diet, they are effective in optimizing the biochemistry, immunology, and physiology of the cell microenvironment.

The term “dioscorea complex” refers to an extract of the Dioscorea species (Mexican yam) which provides a natural precursor nutrient, diosgenin, which is a complex, six-ring cyclic molecule containing a molecular building block (perhydrocyclopentanophenanthrene) that is involved in the natural synthesis of adrenal and gonadal hormones in mammals. The presence of this complex molecule in the diet can help to establish optimal hormone balance while maintaining normal physiological control mechanisms. This dietary supplement component is suitable for improving the metabolic regulation of virtually every cell in the body.

- 17 The term “herbal extract” refers to phytochemicals that are produced in plant tissues and that can be extracted with water, polar solvents, or petroleum solvents and that have some beneficial or medicinal properties. Most herbal extracts can be toxic, especially in concentrated form, but are generally safe when used as a traditional herbal remedy in teas, poultices, or as a poultice to treat disease or maintain good health. The term “herbal body tonic” refers to substances that the inventors have found to reduce and reverse the damage to elastic tissues and collagen fibers caused by aging and the sun by preserving skin elasticity and thus effectively reducing or eliminating the development of wrinkles, sagging, hyperpigmentation, and reversing the development of other undesirable elements.

The carbohydrates present in the food supplement of the invention are found in a wide range of natural and synthetic sources. These include shrubs, trees, plants, yeasts, fungi, molds, gums, resins, starch and cellulose derivatives and natural mucilage sources. Natural sources include, for example: (a) shrub and tree exudates, which include acacia, karaya, tragacanth or ghatti; (b) marine gums, which include agar, algin or carrageenan; (c) seed gums, which include guar, locust bean or horsetail; (d) plant extracts, which contain pectin or acetylated polymannose.

- 18 mazn; (e) starch and cellulose derivatives, such as hetastarch, carboxymethylcellulose, ethylcellulose, hydroxypropylmethylcellulose, methylcellulose, oxidized cellulose; and microbial gums, such as dextran, xanthan [Tyler et al. (1981)]. It is noted, however, that the composition of the invention is not limited to sources from which the said carbohydrates can be obtained.

The saccharides used according to the invention can occur in nature as mono-, oligo- and polysaccharides. The compositions according to the invention can therefore contain the saccharides in monomeric, oligomeric and polymeric forms. The following Table 3 lists some natural sources of the saccharides according to the invention.

Table 3

Carbohydrate source: gum tragacanth, guar gum, rice or grain flour

LAREX B-1000 (Larch extract) MANAPOL™ (aloe vera extract) ghatti gum

The corresponding saccharide(s) are galacturonic acid and sialic acid mannose and galactose (1:2 molar ratio) glucose poly arabinog acylated mannose-based polymer arabinose, galactose, mannose, xylose, glucuronic acid (10:6:2:1:2 molar ratio)

- 19 Carbohydrate source starch pectin chondroitin sulfate chitin acacia, gum arabic alginic acid carrageenan dextran xanthan gum

The corresponding saccharide(s) are glucose galacturonic acid N-acetylgalactosamine N-acetylglucosamine arabinose, galactose, glucuronic acid mannosyluronic acid, gulosyluronic acid galactose, 3,6-anhydrogalactose glucose glucose, mannose, glucuronic acid

The saccharides listed above are generally present in natural amounts in the carbohydrate sources given, which corresponds to the molar ratio of saccharides in ghatti gum and guar gum. The relative amounts or proportions of saccharides in carbohydrates can be readily determined by conventional extraction or analytical methods or by reference to known literature.

The term "carbohydrate" is used interchangeably with the terms "saccharide", "polysaccharide", "oligosaccharide" and "sugar", all of which are well-known carbohydrate chemistry terms. Although the compositions of the invention contain at least one of the eleven basic saccharides, it is noted that the saccharides may be mono-, oligo- and/or polysaccharides, for example, a composition containing tragacanth and guar gum contains galacturonic acid, sialic acid, mannose and

- Contains 20 galactoses. Thus, by changing the amount of a given gum in the food supplement, the amount of the corresponding saccharide can also be changed.

Although the present invention includes the eleven basic saccharides mentioned above, it is noted that other saccharides, nutritive compounds or biologically active or inert compounds may also be present in the dietary supplement of the present invention. Such nutritive compounds include one or more of the following: phytonutrients, dioscorea complex, plant extracts, herbal extracts, plant parts, herbal components, vitamins and minerals. These nutritive compounds may be added to the dietary supplement of the present invention, or they may be administered separately to the mammal receiving the dietary supplement. For example, a patient receiving a glyconutrient-containing dosage form of the present invention may receive the same phytonutrient either in the same dosage form or in a separate dosage form. Inert compounds may include flavoring agents, fillers, lubricants, buffers, gels, binders, excipients, carriers, and/or other compounds that aid in the formulation or administration of the dietary supplement of the invention. Glyconutrient-containing dietary supplements of the invention containing additional compounds, agents, or other materials may be obtained directly from MANNATECH™ (Coppell, TX).

Dioscorea complex can be extracted from Ayus herb (Japan). If the food supplement according to the invention

- 21 dioscorea complex, the proportion of which relative to the total basic saccharides is about 0.0001/99.9999 about 50/50%. In a specific embodiment, the amount of dioscorea complex relative to the total basic saccharides is about 0.01-70/90, 99-30 - about 10-40/90-60 or about 20/80.

Phytonutrients are available from a variety of sources, including Cap-Tab (United States of America) or can be added by freeze-drying and grinding ripe fruits and/or vegetables into a powder, which is then added to the food supplement of the invention. Such fruits and vegetables include the well-known fruits and vegetables, in particular broccoli, Brussels sprouts, cabbage, carrots, cauliflower, garlic, kale, onions, papaya, pineapple, tomatoes and turnips. These phytonutrients can be formulated into powder complexes or capsules, or can be used in a gelatin base or natural fruit juice, optionally with the addition of flavorings. When the phytonutrient is used in the nutritional supplement of the invention, the amount of total phytonutrients relative to total glyconutrients is from about 0.001/99.999 to about 99.99/0.01% by weight. The term phyto-1 refers to a nutritional supplement comprising glyco-1 (Example 5) and freeze-dried raw fruit or vegetable. In a specific embodiment, the amount of phytonutrient relative to total glyconutrients is from about 20-99/80-1 to about 50-95/50-5.

- 22 There are a number of plant and herb extracts that are expected or proven to have nutritional value that promote good health and that can be incorporated into or used with the food supplement of the invention. Such plant and herb extracts can be obtained by known extraction methods by extracting substances, compounds or agents from plants or herbs. In a specific embodiment, the food supplement of the invention contains extracts of the following plants or herbs: broccoli, Brussels sprouts, cabbage, carrots, cauliflower, garlic, kale, onion, papaya, pineapple, tomato, asparagus, mushrooms, parsnips, radishes and turnips. In the food supplement of the invention, the total amount of plant or herb extract (expressed as dry solids) relative to the total glyconutrients is about 0.001-75/99.999-25 to about 10-90/90-10 wt%.

A number of vitamins and minerals may be present in the nutritional supplement of the invention. Although some vitamins and minerals are of synthetic origin, they have nutritional value, the nutritional supplement particularly contains nutritionally effective amounts of non-toxic vitamins and minerals, which are obtained primarily from natural sources. PROFILE™ is the brand name of the vitamin and mineral supplement shown in the examples. This product, which can be manufactured from MANNATECH™ (Coppell, TX), contains nutritionally effective amounts of the following vitamins and minerals: a) A, B1, B12, B2, B6, b

- 23 vitamins a-carotene, bioflavonoids, biotin, C, choline, D, E, folic acid, inositol, K, niacinamide, para-aminobenzoic acid and pantothenic acid; and b) minerals calcium, copper, GTF chromium, iodine, iron, magnesium, manganese, molybdenum, potassium, selenium, silicon, vanadium and zinc. These vitamins and minerals are used in nutritionally acceptable non-toxic forms.

A “nutritional effective amount” means an amount that produces a beneficial nutritional effect or response in a mammal. For example, the nutritional response to vitamin and mineral supplements may vary from mammal to mammal, and the nutritionally effective amount of the vitamin and mineral will vary accordingly. For example, while one mammal may require certain vitamins and minerals in specific amounts, another mammal may require those vitamins and minerals in different amounts.

Other compounds, agents and nutrients in the food supplement according to the invention may include, for example, cellulose, calcium carbonate, kola nuts, kola nut extract, pap cheese, Atlantic kelp, cayenne pepper, silicon dioxide, stearic acid, amino acids, glycine, lysine, glutamic acid, arginine, calcium carbonate, orchilic substances, boron citrate, chromium picolinate, essential fibers, essential oils, essential plant substances, essential enteric ecological substances, flora growth promoters, essential fatty acids, live probiotic flora, proteins and enzymes.

- 24 The nutritional supplement of the invention can be prepared and administered to mammals as a powder, reconstitutable powder, liquid/solid suspension, liquid, capsule, tablet, capsule, solution and cream. It is known to those skilled in the art that the nutritional supplements of the invention can be formulated in a form suitable for irrigation, for ocular administration, for otic administration, for rectal, sublingual, transdermal, buccal, vaginal or dermal administration. thus, other dosage forms may also be used, such as chewable candy, concentrates, drops, elixirs, emulsions, films, gels, granules, chewing gum, jellies, oils, pastes, lozenges, pellets, shampoos, rinses, soaps, sponges, suppositories, wipes, syrups, chewable gelatin forms and chewable tablets.

Since people have different dietary habits, the food supplement of the invention can be administered in a wide range of dosage amounts and the dosage units can be formulated within wide limits. For example, for people whose diet is deficient in nine to eleven essential saccharides, the food supplement contains these nine saccharides in a nutritionally effective amount. For people who bioabsorb essential saccharides extremely efficiently, the food supplement contains a smaller amount of essential saccharides.

- 25 It is noted that the dosage form of the nutritional supplement will depend on the disease or disorder of the mammal, such as someone suffering from chronic fatigue or fibromyalgia will generally receive a different dosage amount than an alcoholic trying to quit drinking alcohol. The appropriate dosage amount of the nutritional supplement can be readily determined from the response of the individual, i.e., general health and response to a specific dosage amount of the supplement. If the glyconutrient supplement is administered to the mammal along with another agent, such as a phytonutrient, plant extract, herbal extract and/or dioscorea complex, the appropriate amounts of the supplement and the various agents can be readily determined from the response of the individual, i.e., general health and response to specific doses of the various substances.

The nutritional supplement of the invention may be administered simultaneously or sequentially in a single dosage form or in a combination of dosage forms. It is possible and likely that the nutritional supplement of the invention will immediately result in a general improvement in health, such improvement may take days, weeks or months. Regardless, the glyconutrient nutritional supplement of the invention will result in a favorable nutritional response in the mammal consuming it.

The food supplement according to the invention can be administered simultaneously with at least one phytonutrient, herbal extract, plant extract or dioscorea complex.

- 26 or consecutively. The case where the food supplement is administered simultaneously with at least one phytonutrient, herbal extract, plant extract or dioscorea complex is illustrated in the following examples.

In the examples shown, the food supplement according to the invention was administered as a powder-containing capsule. In the case where the food supplement also contained a phytonutrient, it was administered, for example, in the form of a caplet or gelatin. If the food supplement contained a dioscorea complex, the composition was administered, for example, as a caplet or capsule. In the case where the food supplement contained a phytonutrient, a dioscorea complex and a herbal extract, it could be administered as a caplet.

Depending on the size and contents of the capsule or caplet, the dietary supplement is dosed as follows. Dosage amounts are for a #1 size capsule and a 1000-1200 mg caplet.

Additional additive Dosage form Glyco-1 2 capsules, 4x daily Phyto-1 1 caplet, once daily With Glyco-1 Dioscorea Complex 1 caplet, 4x daily PROFILE™ 1 tablet, 3x daily

Based on the studies, we varied the supplement dosage based on the individual's response to an initial dosage amount.

- 27 the amount of the supplement. For example, if the average health of the individual did not improve with the use of an initial dose, the dosage of the supplement was adjusted one or more times. The actual dosage amount last given for a particular individual depended largely on the individual's dietary response. The supplement and other supplements were generally administered in an amount of about 1 to about 12 capsules (or caplets or tablets)/day.

It is known that there is a biochemical individuality of mammals and that different amounts of active ingredients or food are required to achieve the desired health-improving effect [Williams, R.: Nutrition Against Disease (1971)]. The amounts of the aforementioned foods initially used as dietary supplements are related to an agreed health status. The nutritional response of mammals to dietary supplements and the determination of whether or not an increase in dosage is warranted depends on energy levels, stiffness, pain, discomfort, poor sleep, fatigue relief, and emotional state. The reduction of health complaints and the reduction or elimination of the aforementioned parameters can serve as a guideline for reducing glyconutrient intake. A complicating factor regarding the amount of glyconutrients needed to achieve a beneficial effect may be that each individual has a different quantitative need for nutrients. These differences may be of genetic origin, may occur due to biochemical balance,

- 28 disease states, age-related physiology, previous and current general nutrition, individual dietary habits and the nutritional content of the food. The desired response or improvement in health is achieved when the missing nutrient or nutrients are appropriately dosed in the nutritional supplement. The human body protects, repairs, regenerates, regulates and heals itself through gene control, and the nutrient provides the repeated sources necessary for this task. The nutritional supplement of the invention does not contain the glyconutrients commonly found in the urban or suburban food chain and is thus a much more favorable source of known but as yet unidentified nutrients that are necessary for optimal biochemistry and physiology.

Example 1

A suitable composition according to the invention is prepared as follows. Tragacanth gum (100 kg) as a source of galacturonic acid and sialic acid (N-acetylneuraminic acid) is introduced into a stainless steel ribbon mixer and guar gum (10 kg) as a source of mannose and galactose is introduced into the stainless steel ribbon mixer. The mixture of tragacanth gum and guar gum is mixed for 5 minutes. Then 250 g of Aerosil 380™ (silica gel) is added as a flow agent, then 200 kg of rice flour is added as a gluten-free gluten filler and glucose source. The mixture is then mixed for 15 minutes. Finally, 100 g of calcium stearate is added to the mixture as a lubricant and the resulting mixture is mixed for a further 3 minutes to produce a powder. The resulting powder is then filled into size 1 gelatin capsules, the capsules

- 29 fill weight is 250 mg. A Model 8 (Elanco) capsule filling machine is used to fill the capsules.

Example 2

Another suitable composition of the invention is prepared as follows.

25 kg each of galactose, glucose, mannose, N-acetylneuraminic acid, fucose, N-acetylgalactosamine, N-acetylglucosamine and xylose are introduced into a stainless steel ribbon mixer and the mixture is mixed for 5 minutes. The materials mentioned are products of Florida Food Products, Aldrich Chemical Company and Sigma Chemical. Then 250 g of Aerosil 380™ (silica gel) is introduced as a flow agent, followed by 200 kg of rice flour as a gluten-free filler and glucose source. The resulting mixture is mixed for 15 minutes. Finally, 100 g of calcium stearate is added as a lubricant and the mixture is mixed for another 3 minutes to produce a powder. The resulting powder is filled into size 1 gelatin capsules with a fill weight of 250 g, using a Model 8 (Elanco) capsule filling machine.

Example 3

A further suitable composition according to the invention is prepared according to Example 2. The final composition of the composition in % by weight is as follows:

% by weight Component Approximate density 20 Gum Tragacanth T/3 0.71 g/ml 20 Gum Ghatti No. 1 0.79 mg/l 40 arabinogalactan 0.20 g/ml

- 30 20 MANAPOL® 0.12 q/ml total components 0.30 g/ml

Gum tragacanth T/3 and Gum Ghatti No. 1 are products of AEP Colloids of Ballston Spa, New York. Arabinogalactan is obtained from redwood and is a product of North American Pharmacal of Norwalk, Connecticut. MANAPOL® is a freeze-dried aloe vera extract and is a product of Carrington Laboratories (Irving, Texas).

Example 4

Quantification

Determination of the sugar content of the composition according to the invention

The carbohydrates were products of Aldrich Chemical Company, Milwaukee, Wisconsin.

The eluent is deionized (DI) water, with a resistance of > 17 MOhm.

The sample is prepared as follows: 2 ml of 2 N hydrogen fluoride is added to 10 mg of the sample to be analyzed in a 10 ml test tube with a screw cap and TEFLON lining. The sample is then incubated at 120 °C for 1 hour to hydrolyze the product to monosaccharides. The excess reagent is removed in a stream of air and the sample is resuspended in 1 ml of DI water.

High-performance liquid chromatography analysis: AOAC Official Methods of Analysis 977.20.

Example 5

The food supplement is prepared on an industrial scale according to the examples given above. The preparation is designated Gliko-1 and contains the components in the amounts listed below. The amounts in % by weight are given with respect to the total weight of the preparation containing all components.

Component % by weight MANAPOL® (aloe vera extract) 10 ghatti rubber 10 tragacanth gum 10 glucosamine 10 cornstarch 12 arabinogalactan 48

The composition is formulated into topical and oral formulations.

Example 6

Reducing drug side effects in the treatment of attention deficit hyperactivity disorder

We used the Manual 4th edition (DSM-IV) to assess ADHD. One group consisted of five children whose parents did not give them methylphenidate (NO MED). The other 12 children received two different doses of methylphenidate: (a) 6 children received the normal prescribed dose (MED); and (b) 6 children received a reduced dose, i.e., an amount below the normal prescribed dose (MED RED).

In the study, DSM-IV symptoms were classified according to the ADHD scale; 18 individuals were classified on a scale of 0-3, in terms of severity. The same classification was used for oppositional defiant behavior (ODD) symptoms and conduct disorder (CD) symptoms according to DSM-IV. At each assessment, parents and teachers jointly rated the classification scale. In addition, parents also rated the General Health Inventory for their children.

After the screening tests, each individual was given the Glyco-1 glyconutrient product (1 capsule/10 pounds of body weight on the first day and 1 capsule/20 pounds of body weight on the remaining days) in their diet. In the second week, parents and teachers assessed the children using a different grading system, and the MED RED group received half the prescribed treatment. In the third week, phytonutrients (Phyto-1; 5 per day) were added to the dietary supplement. Further grading was continued in weeks 5 and 6.

The results showed that Gliko-1 did not produce any additional improvement in ADHD symptoms compared to methylphenidate alone. However, there was a statistically significant reduction in methylphenidate-induced side effects when individuals were given Gliko-1, resulting in an improvement in overall health.

Example 7: Treatment of alcoholics with Glyco-1

The Gliko-1 capsules used in this study were prepared according to Example 6. The study aimed to determine the effect of a glyconutrient-containing dietary supplement on mood and alcohol craving in alcoholics. The study was conducted as follows.

Two groups of alcoholics (Little Rock, Arkansas) were selected: three recovered alcoholics and two actual alcoholics. All met the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) criteria for alcohol dependence. The individuals in the recovered group had been abstinent for a range of 2.5 years to 6 years and 11 months. In both groups, the duration of alcohol use ranged from 15 to 30 years, and the individuals ranged in age from 33 to 62 years.

The study used a self-rating scale to measure alcohol craving, ranging from 0 to 9, and the Profile of Mood States (POMS). The POMS divided 65 symptoms into five categories: perception, depression, energy, anger/temperament, and positive attitude. The tests were conducted before glyconutrient administration and at the end of the 5-week study.

Glyconutrients were administered to each subject with their food: 1 capsule/10 pounds of body weight on the first day, then 1 capsule/20 pounds of body weight throughout the study. No other interventions were performed.

The results showed that the average initial alcohol craving decreased statistically significantly in 5 individuals. The results also showed that there was a statistically significant improvement in the measured mood state.

Example 8

Treatment of various disorders with glyconutrients

The following table presents the results when subjects were given Gliko-1 alone or in combination with one or more of the following: Fito-1, Gliko-1 with Dioscorea, and PROFILE™. Each subject received a starting dose of Gliko-1, followed by one or more of the additional supplements in the amounts indicated below:

Additional additive Dosage

Glyco-1 (A) 2 capsules, 4x daily

Phyto-1 (B) 1 caplet, 4 times a day

Glyco-1 (C) containing Dioscorea 1 caplet, 4x daily

PROFILE™(D) 1 tablet, 3x daily Topically applied hydrogel preparation containing glyconutrients “E” Oral dietary supplement containing glyconutrients “F” and herbal extracts.

In each study, we examined the development of individuals and their nutritional and general health response to a dietary supplement administered over a given interval. In those

- In 35 individuals who did not respond well to the initial dose, the dosing period was changed and their progress was further monitored. It should be noted that in all cases, Glyco-1 contained a nutritionally effective amount of essential saccharide(s) in the appropriate dose, which are necessary to promote good average health in the given individual. This means that the food supplement containing the glyconutrient according to the invention is not intended to cure the listed diseases and disorders, but rather provides the individual with the necessary glyconutrients, and thus the individual's own body heals itself.

Table 4

Disorders treated by administration of glyconutrients alone or in combination with one or more phytonutrients, dioscorea complex, vitamins or minerals

Disorder Nutrient dosed Treatment results aging or optimal health plan A, B, C, D reduced body fat; increased muscle mass and bone density; serum biochemistry moving to much healthier levels old-fashioned stroke A, B, C restored sensory and muscle control

Disorder Nutrient dosed Treatment results multiple sclerosis A, B, C restored sensory and muscle control muscular atrophy of the side A, B, C restored sensory and muscle control muscular dystrophy A, B, C restored sensory and muscle control central paralysis A, B, C restored sensory and muscle control macular degeneration A, B, C vision restoration epileptic seizure A, B, C reduction or elimination of allergic diseases and infections; improvement in coordination, learning ability, memory and appearance Down syndrome A, B, C reduction or elimination of allergic diseases and infections; improvement in coordination, learning ability, memory and appearance systemic concentrated immunodeficiency syndrome A, B, C restoring antibody T-cell function Tay-Sachs A, B, C recovery of lost functions

Disorder Nutrient dosed Treatment results retinitis pigmentosa A, B, C restoration of vision color blindness A, B, C color vision Huntington's disease A, B, C restore or repair lost functions Alzheimer's disease A, B, C restore or repair lost functions Parkinson's disease A, B, C restore or repair lost functions inflammatory polyneuropathy A, B, C restore or repair lost functions closed head trauma syndrome A, B, C restore or repair lost functions spinal cord injury A, B, C restore or repair lost functions ulcerative colitis A, B, C healed ulcer Crohn's disease A, B, C healed ulcer schizophrenia A, B, C improvement of functions depression A, B, C improvement of functions anxiety reactions A, B, C improvement of functions compulsive disorders A, B, C improvement of functions nervous muscle twitching A, B, C improvement of functions Restless Leg Syndrome A, B, C improvement of functions

Disorder Nutrient dosed Treatment results Tourette's syndrome A, B, C improvement of functions autism A, B, C improvement of functions Wegener's granulomatosis A, B, C tissue repair Lupus Erythematosus A, B healing wounds rheumatoid arthritis A, B symptom relief thyroiditis A, B normalization of antinuclear antibodies Myasthenia gravis A, B normalization of antinuclear antibodies Diabetes mellitus A, B normalization of glucose and Hgb AIC levels; restoration of kidney function; healing of ulcers; elimination of infections; normalization of high lipid levels; reduced amounts of insulin and glycomedics osteoporosis A, B reduced pain, increased bone density alcoholism The reduce appetite cocaine The reduce appetite

Disorder Nutrient dosed Treatment results atherosclerosis A, B reduced total cholesterol, LDL and triglycerides, increased HDL; improved patency of blood vessels and improved arrhythmia spontaneous myocarditis (probably viral) A, B increased ejection function; restoration of pulse; increased Coxsackie virus antibody levels; reversal of heart failure rheumatoid arthritis A, B eliminating pain, stiffness, fever and swelling; restoring movement, strength and endurance degenerative arthritis A, B eliminating pain, stiffness, fever and swelling; restoring movement, strength and endurance traumatic arthritis A, B eliminating pain, stiffness, fever and swelling; restoring movement, strength and endurance juvenile arthritis A, B eliminating pain, stiffness, fever and swelling; restoring movement, strength and endurance

Disorder Nutrient dosed Treatment results asthma The eliminating shortness of breath and wheezing and improving lung function allergies - nose, eyes, hay fever The eliminate itching, swelling and rashes silicone breast implants A, B, C reducing and eliminating symptoms environmental toxin syndrome A, B, C reducing and eliminating symptoms agent orange A, B, C reducing and eliminating symptoms Gulf War Syndrome A, B, C reducing and eliminating symptoms Hepatitis B and C A, C, D normalization of liver enzymes and symptoms influenza virus A, C, D prevention or cure; improvement of symptoms common cold A, C, D prevention or cure; improvement of symptoms AIDS A, C, D elimination of symptoms; m-RNA and HIV-1 undetectable; restored immune functions herpes A, C, D eliminating infections wart A, C, D eliminating infections human papillovirus A, C, D eliminating infections

Disorder Nutrient dosed Treatment results otitis media (persistent or recurring) A, C, D elimination of symptoms and need for antibiotics leukemia A, B, C, D correction of altered chromosomes lymphoid tumor A, B, C, D normalization of tissue biopsy sarcomas (astrocytoma tumors) A, B, C, D normalization of tissue biopsy glandular cancers, including breast, prostate, ovarian, gastrointestinal, and lung cancer A, B, C, D elimination of metastases and shrinkage of the mass to an undetectable level uterus inversion and female impotence A, B, C, D restoring psychological interest and physiological sexual function in older age diabetes-related pain, ulcers and coldness of the extremities, Raynaud's phenomenon, frostbite, snakebite and atherosclerosis A, C, E restoration of intact, healthy limbs and microvascular circulation

Disorder Nutrient dosed Treatment results skin damage caused by sun, age and radiation A, C, E reducing pigmentation, wrinkles and lost elasticity and restoring the dermis and epidermis athletic performance C, F better fitness and endurance, less fatigue, and improved recovery in young and older athletes

The present invention therefore relates to a food supplement and a food supplement for promoting and maintaining optimal good health. The invention particularly relates to carbohydrate compositions which are useful as food supplements and which are essential for the production of glycoproteins of the correct structure and thus of proper function.

Glycoproteins have been shown to play a key role in all cell communication. Many cytokines, or cellular “words,” cannot function properly without a glycosyl group attached to them. The body breaks down complex polysaccharides, such as plant carbohydrates, into various monosaccharides and then converts these into oligosaccharides, which the body builds into glycoproteins necessary for cytokine cell communication and thus for good health.

The invention can solve the problem of consuming highly refined foods, which are processed to remove many essential components from the food.

- 43 residues were removed, such as sugars required for glycoproteins to have the correct structure and function.

The above has described in detail various embodiments of our invention. A person skilled in the art can make obvious modifications based on the description presented above without departing from the essence and scope of our invention. All described embodiments can be carried out without special experimentation. The scope of our invention is described in the description and equivalent embodiments. The description does not limit the scope of our invention.

In our description, the term "a" can mean "one", "at least one", or "one or more".

Claims (9)

Patent claims 1. A food supplement for providing dietary saccharides in monomeric, oligomeric, polymeric, derivatized or native form, which saccharides are essential components of glycoproteins found in mammals, and the food supplement comprises a composition comprising a nutritionally effective amount of the following components: at least one saccharide from the following first group of saccharides: galactose, glucose, mannose, xylose and acetylated mannose; and at least one saccharide from the following second group of saccharides: N-acetylneuraminic acid, fucose, N-acetylgalactosamine, N-acetylglucosamine, arabinose, glucuronic acid, galacturonic acid, iduronic acid and arabinogalactan. 2. The food supplement according to claim 1, wherein the composition comprises at least two saccharides from the second group of saccharides. 3. The food supplement according to claim 1, wherein the composition comprises at least three saccharides from the second group of saccharides. 4. The food supplement according to claim 1, wherein the composition comprises at least four saccharides from the second group of saccharides. 5. The food supplement according to claim 1, wherein the composition comprises at least five saccharides from the second group of saccharides. 6. The food supplement of claim 1, wherein the saccharide is in oligomeric or polymeric form in at least one of the following: gum tragacanth, guar gum, corn flour, rice flour, sugar cane, beet sugar, potato, milk, agar, algin, locust bean gum, raclette, karaya gum, seed gums, red pine extract, aloe vera extract, ghatti gum, starch, cellulose, degraded cellulose, fructose, high fructose corn syrup, pectin, chitin, acacia, gum arabic, alginic acid, carrageenan, dextran, xanthan gum, chondroitin sulfate, sucrose, acetylated polymannose, maltose, glucan, lentinan, mannan, levan, hemicellulose, inulin, fructan and lactose. 7. A dietary supplement according to claim 1, comprising a nutritionally effective amount of dioscorea complex, a mixture of ripe and freeze-dried and powdered raw fruits and vegetables, xanthines and herbal body ionizers, β-sitosterol, melatonin, saccharide bioabsorption enhancers or non-toxic vitamins and minerals. 8. The dietary supplement of claim 7, wherein the mixture of ripe and freeze-dried and powdered raw fruits and plants comprises: broccoli, Brussels sprouts, cabbage, carrots, cauliflower, garlic, kale, onion, papaya, pineapple, tomato and turnip. 9. The dietary supplement according to claim 7, wherein the bioabsorption enhancing agent is soy lecithin. - 46 10. The food supplement according to claim 7, wherein the vitamin A, B1, B12, B2, B6, beta-carotene, bioflavonoids, biotin, C, choline, D, E, folic acid, inositol, K, niacinamide, para-aminobenzoic acid and pantothenic acid; and the mineral is calcium, copper, GTF, chromium, iodine, iron, magnesium, manganese, molybdenum, potassium, selenium, silicon, vanadium and zinc. The authorized person: Danubia Patent and Trademark Office Ltd. patent attorney kG