HK1177398A - Nutritional compositions including a high protein component and exogenous nucleotides - Google Patents

Description

Nutritional composition comprising high protein component and exogenous nucleotide

Background

The present specification relates generally to health and nutrition. More particularly, the present description relates to nutritional compositions including proteins and exogenous nucleotides and methods of making and using the nutritional compositions.

There are many types of nutritional compositions currently on the market. Based on the specific ingredients of the nutritional composition, the nutritional composition may be directed to some consumer types, such as young, middle aged, elderly, athletes, and the like. Nutritional compositions may also be formulated based on a number of physiological conditions for which the nutritional composition is intended to treat or ameliorate.

Patients with malnutrition are more prone to injury during the course of health care when compared to free-living individuals. These patients typically do not consume sufficient amounts of protein. Despite the consumption of protein-containing products, prevention of wounds such as pressure ulcers is often unsuccessful. The nutritional product may be used as part of a therapy to aid in healing and closing a wound. However, the use of these nutritional products does not ensure successful and rapid healing of various types of wounds. In addition, medical conditions such as diabetes also interfere with wound healing.

It is estimated that 8-12% of all hospital patients develop pressure ulcers within the first 2 weeks after hospitalization. Even longer term care residents also develop pressure ulcers. Pressure ulcers are classified by stage into 4 types, i.e. grade I is the mildest type and grade IV is the most severe type. Their mean healing time was 4 weeks on grade I and 22 weeks on grade IV, respectively. This indicates that the nutritional options for patients with pressure ulcers are currently insufficient to support rapid healing.

SUMMARY

Nutritional compositions having a high protein content and exogenous nucleotides and methods of making and using the nutritional compositions are provided. In a general embodiment, the present specification provides a nutritional composition comprising a high protein component and one or more exogenous nucleotides.

In one embodiment, the high protein component includes one or more proteins, peptides, and amino acids and precursors and metabolites of proteins, peptides, and amino acids in an amount that provides at least about 18% of the total calories of the nutritional composition.

In one embodiment, the nutritional composition has a total volume of 300mL or less. The high protein component in the nutritional composition includes one or more proteins, peptides, and amino acids, and precursors and metabolites of proteins, peptides, and amino acids, in amounts greater than about 14 grams.

In one embodiment, the high protein component includes at least about 5 grams of protein, at least about 3 grams of bitter amino acids, and at least about 7 grams of neutral taste acids. The bitter amino acid can be arginine, phenylalanine, tyrosine, leucine, isoleucine, valine, methionine, histidine, or a combination thereof. The neutral-tasting amino acid may be glutamine, glycine, alanine, threonine, proline (praline), serine, or a combination thereof.

In one embodiment, the exogenous nucleotide is a nutritional composition in an amount of about 1 gram per 1000 calories. The exogenous nucleotide may be in monomeric form, such as 5 'adenosine monophosphate, 5' -guanosine monophosphate, 5 '-cytosine monophosphate, 5' -uracil monophosphate, 5 '-inosine monophosphate, 5' -thymine monophosphate, or a combination thereof. The exogenous nucleotide can be an intact ribonucleic acid or other nucleotide-containing compound.

In one embodiment, the nutritional composition further comprises one or more ingredients, such as non-replicating bacteria, fatty acids, triglycerides, lycium barbarum, antioxidants, vitamins, minerals, polyphenols, flavonoids, EGCg, pycnogenol, alpha-and beta-glucans, alpha-hydroxyisocaproate, aloe vera, honey, amino acids, branched chain amino acids, or combinations thereof.

In one embodiment, the nutritional composition is in an administrable form, such as pharmaceutical formulations, nutraceuticals, dietary supplements, functional foods, and beverage products.

In another embodiment, the present specification provides a method of making a nutritional composition. The method includes adding a high protein component and an exogenous nucleotide to the nutritional composition.

In an alternative embodiment, the present specification provides a method of improving wound healing in a mammal. The method includes administering to a mammal having a wound a nutritional composition including an effective amount of a high protein component and one or more exogenous nucleotides. The nutritional composition is administered to provide the exogenous nucleotides in an amount of about 0.2 g/day to about 4 g/day. The wound may be from a pressure ulcer, a surgical incision, an abrasion, or a combination thereof. The mammal may also have diabetes.

One advantage of the present description is to provide an improved nutritional composition having a high protein content and exogenous nucleotides.

Another advantage of the present description is to provide an improved method of preparing a nutritional composition.

Another advantage of the present specification is to provide a nutritional composition that accelerates or improves wound healing in mammals.

Additional features and advantages are described herein, and will be apparent from, the following detailed description of the invention.

Detailed Description

The present specification relates to nutritional compositions and methods of making and using nutritional compositions that include a high protein content and exogenous nucleotides. Embodiments of the nutritional compositions of the present disclosure may provide improved wound healing. The wound may be of any type, including a pressure ulcer, an accidental wound, a surgical incision, and the like. The need to improve wound healing is evident by the high cost of wound healing, long hospitalization and the condition experienced by patients.

The term "nutritional composition" as used herein includes, but is not limited to, complete nutritional compositions, partial or incomplete nutritional compositions, and disease or disorder specific nutritional compositions.

As used herein, "about" is preferably understood to mean a number within the range of the index value. Moreover, all numerical ranges herein should be understood to include all integers, or components within the range.

As used herein, "complete nutrition" is preferably a nutritional product that contains sufficient types and levels of macronutrients (protein, fat and carbohydrates) and micronutrients that are the only source of nutrition sufficient for the animal to which it is administered. Patients may receive 100% of the nutritional requirements from such complete nutritional compositions.

As used herein, an "effective amount" is preferably an amount that prevents a deficiency, treats a disease or medical condition in an individual, or more generally, reduces symptoms of a disease, controls the progression of a disease, or provides a nutritional, physiological, or medical benefit to an individual. Furthermore, although the terms "individual" and "patient" are generally used herein to refer to a human, the invention is not so limited. Thus, the terms "individual" and "patient" refer to any animal, mammal, or human that has or is at risk for a medical condition that may benefit from treatment.

As used herein, "elderly" is preferably a person 65 years or older, more preferably a person 75 years or older.

As used herein, "incomplete nutrition" is preferably a nutritional product that does not contain sufficient levels of macronutrients (protein, fat and carbohydrates) or micronutrients, which are the only sources sufficient for the animal to which it is administered. Partial or incomplete nutritional compositions may be used as nutritional supplements.

As used herein, "long-term administration" is preferably continuous administration for more than 6 weeks.

As used herein, "mammal" includes, but is not limited to, rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such as sheep, pigs, cows and horses, and humans. If the term "mammal" is used, it is contemplated that it also applies to other animals that are capable of exhibiting or pre-exhibiting an effect by the mammal.

The term "patient" as used herein is preferably to be understood as including animals, especially mammals, more especially humans, which are receiving or are pre-treated as defined herein.

As used herein, "phytochemicals" or "phytonutrients" are non-nutritive compounds found in many foods. Phytochemicals are functional foods with health benefits over basic nutrition and are health promoting compounds derived from plant sources. As used herein, "phytochemicals" or "phytonutrients" refer to any chemical produced by a plant that imparts one or more health benefits to a user. The phytochemicals may be administered by any means, including topically, enterally, and/or parenterally. Non-limiting examples of phytochemicals and phytonutrients as used herein include:

1. phenolic compounds including monophenols (e.g., apigenin, carnosol, carvacrol, eperisol, Rosemarinol); flavonoids (polyphenols) including flavonols (e.g., quercetin, gingerol, kaempferol, myricetin, rutin, isorhamnetin), flavanones (e.g., hesperidin, naringenin, silybin, eriodictyol), flavonoids (e.g., apigenin, naringenin, luteolin), flavan-3-ols (e.g., catechol, (+) -catechin, (+) -gallocatechin, (+) -epicatechin, (-) -epigallocatechin gallate (EGCG), (-) -epicatechin 3-gallate, theaflavin-3-gallate, theaflavin-3' -gallate, theaflavin-3, 3' -digallate, thearubigin), anthocyanins (flavonols) and anthocyanins (e.g.: malvidin, methylcyanin, anthocyanidin, delphinidin, petunidin), isoflavones (phytoestrogens) (for example: daidzein (formononetin), genistein (biochanin A), glycitein, flavanonols, chalcones, Coumestans (phytoestrogens), and coumestrol; phenolic acids (e.g., ellagic acid, gallic acid, tannic acid, vanillin, curcumin); hydroxycinnamic acids (e.g., caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumarin); lignans (phytoestrogens), silychristin, Secoisolariciresinol, pinoresinol, and lariciresinol); p-hydroxyphenyl ethanol esters (e.g., p-hydroxyphenyl ethanol, hydroxytyrosol, olive oil stimulating aldehyde, oleanolic glycoside); stilbene compounds (e.g., resveratrol, pterostilbene, piceatannol) and punicalagin;

2. terpenes (isoprenoids), including carotenoids (tetraterpenoids), including carotenes (e.g., alpha-carotene, beta-carotene, gamma-carotene, delta-carotene, lycopene, neurosporene, phytofluene, phytoene) and xanthophylls (e.g., canthaxanthin, cryptoxanthin, zeaxanthin, astaxanthin, lutein, royal erythroxanthin); a patch (such as limonene and perillyl alcohol); saponins; a lipid, comprising: phytosterols (e.g., campesterol, beta sitosterol, gamma sitosterol, stigmasterol), tocopherols (vitamin E), and omega-3, 6, and 9 fatty acids (e.g., gamma-linolenic acid); triterpenoids (e.g., oleanolic acid, ursolic acid, betulinic acid, and tetronic acid);

3. betalains, including beta-cyanins (e.g., betanin, isobetanin, prenetanin, neobetanin); and betaxanthin (non-glycoforms) (e.g., opuntixanthin and opuntixanthin);

4 organic sulfides including dithiothioketones (isothiocyanates) (e.g., sulforaphane); and thiosulfonates (allium compounds) (e.g., allylmethyl trisulfide and diallyl sulfide), indoles, glucosinolates including indole-3-methanol; sulforaphane; 3, 3' -diindolylmethane; myrosinase glycoside; allicin; alliin; allyl isothiocyanate; piperine; cis-propanethial-S-oxide;

5. protein inhibitors, including protease inhibitors;

6. other organic acids including oxalic acid, phytic acid (inositol hexaphosphoric acid); tartaric acid; and chicken kidney tartaric acid; and

7. combinations thereof.

As used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a polypeptide" includes mixtures of two or more polypeptides and the like.

As used herein, a "prebiotic" is preferably a food substance that selectively promotes the growth of beneficial bacteria or inhibits the growth of pathogenic bacteria in the intestine. They are not activated or adsorbed on the GI tract of the person ingesting them in the stomach and/or upper intestine, but they are fermented by the gastrointestinal microflora and/or probiotics. Prebiotics are exemplified by Glenn r.gibson and Marcel b.roberfroid in the Dietary Modulation of the human colloid Microbiota: introducing the Concept of biocides, J.Nutr.1995125: 1401, and 1412. Examples of prebiotics include gum arabic, alpha glucan, arabinogalactan, beta glucan, fructooligosaccharides, galactooligosaccharides, galactomannans, gentiooligosaccharides, oligoglucosides, guar gum, inulin, isomaltooligosaccharides, lactofructooligosaccharides, lactulose, fructans, maltodextrins, partially hydrolyzed guar gum, pectic oligosaccharides, retrograded starch, soy oligosaccharides, sugar alcohols, xylooligosaccharides, or combinations thereof.

As used herein, a probiotic microorganism (hereinafter "probiotic") is preferably a microorganism (live, including semi-live or weakened and/or non-replicating), metabolite, microbial cell preparation or microbial cell component which, when administered in sufficient amounts, imparts health to a host, and more particularly, exerts a beneficial effect on the host by improving its intestinal microbial balance, thereby producing an effect on host health or wellness (Salminen S, Ouwend A. Benno Y. et al, "Probiotics: how short the defined" Trends Food Sci. Technol. 1999: 10107-10). Generally, these microorganisms are believed to inhibit or affect the growth and/or metabolism of pathogenic bacteria in the gut. Probiotics may also activate the immune function of the host. Thus, there are many ways to include probiotics into food products. Non-limiting examples of probiotics include aerococcus, aspergillus, bacteroides, bifidobacterium, candida, clostridium, debaryomyces, enterococcus, clostridium, lactobacillus, lactococcus, leuconostoc, melissococcus, micrococcus, mucor, oenococcus, pediococcus, penicillium, peptostreptococcus, pichia, propionibacterium, pseudothecium, rhizopus, saccharomyces, staphylococcus, streptococcus, bacteroides, wissmanship, or combinations thereof.

In a general embodiment, the present description provides a nutritional composition comprising a high protein component and one or more exogenous nucleotides. The combination of the high protein component and one or more exogenous nucleotides may provide synergistic benefits to accelerate or improve wound healing in mammals. The term "mammal" as used herein refers to a human (e.g., a child, an adult) or an animal.

Nucleotides are key to low molecular weight biomolecules for biochemical processes. Sources include re-synthesis, recovery by salvage mechanisms, and dietary intake. Although endogenous production serves as the primary source of nucleotides, there is evidence that exogenous sources are important in rapidly proliferating cells in the immune and gastrointestinal systems, where they may become conditionally essential. Exogenous nucleotides can support the optimal growth and function of timely metabolic living cells of cellular injury, and their supplementation can improve clinical outcomes in critically ill and immunosuppressed patients.

The exogenous nucleotides can be in monomeric and polymeric forms as part of the nutritional composition. Nucleotides are subunits of deoxyribonucleic acid ("DNA") or ribonucleic acid ("RNA"). It is an organic compound composed of nitrogenous bases, phosphate molecules, and sugar molecules (deoxyribose in DNA and ribose in RNA). The nucleotide monomers (single units) are linked to each other in a polymer or long chain. The exogenous nucleotides in the embodiments of the present description are particularly provided by dietary supplementation.

The exogenous nucleotide can be in a monomeric form, such as 5 'adenosine monophosphate ("5' -AMP"), 5 '-guanosine monophosphate ("5' -GMP"), 5 '-cytosine monophosphate ("5' -CMP"), 5 '-uracil monophosphate ("5' -UMP"), 5 '-inosine monophosphate ("5' -IMP"), 5 '-thymine monophosphate ("5' -TMP"), or a combination thereof. The exogenous nucleotide can also be in the form of a polymer, such as an intact RNA. There are a variety of sources of polymer forms, such as yeast RNA. In one embodiment, the amount of exogenous nucleotides is about 1 gram per 1000 calories of the nutritional composition.

In one embodiment, the high protein component includes one or more proteins, peptides, and amino acids and precursors and metabolites of proteins, peptides, and amino acids in an amount to provide at least about 18% of the total calories of the nutritional composition.

In one embodiment, the nutritional composition has a total volume of 300mL or less. The high protein component of the nutritional composition includes at least one protein, peptide, and amino acid and precursors and metabolites of proteins, peptides, and amino acids in an amount greater than about 14 grams.

In one embodiment, the high protein component includes at least about 5 grams of protein, at least about 3 grams of one or more bitter tasting amino acids, and at least about 7 grams of one or more neutral tasting acids. The bitter amino acid can be arginine, phenylalanine, tyrosine, leucine, isoleucine, valine, methionine, histidine, or a combination thereof. The neutral taste acid may be glutamine, glycine, alanine, threonine, proline, serine, or a combination thereof.

The terms "protein", "peptide", "oligopeptide" or "polypeptide" as used herein are preferably to be understood as referring to any composition comprising a single amino acid (monomer), two or more amino acids linked to each other by peptide bonds (dipeptide, tripeptide or polypeptide), collagen, a precursor, homologue, analogue, mimetic, salt, prodrug, metabolite or fragment thereof or a combination thereof. For clarity, any of the above terms may be used interchangeably unless otherwise specified. It will be understood that polypeptides (or peptides or proteins or oligopeptides) typically comprise amino acids other than the 20 naturally occurring amino acids, and that many amino acids, including terminal amino acids, on a given polypeptide may be modified by natural means such as glycosylation and other post-translational modifications or by chemical modification techniques well known in the art. Among the known modifications of polypeptides that may be present in the present specification, include, but are not limited to, acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of a flavonoid or heme moiety, covalent attachment of a polynucleotide or polynucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphatidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, covalent cross-linking formation, cystine formation, pyroglutamate formation, formylation, gamma-carboxylation, saccharification, glycosylation, glycosylphosphatidylinositol ("GPI") membrane anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to polypeptides such as arginylation and ubiquitination. The term "protein" also includes "artificial proteins," which refer to linear or nonlinear polypeptides composed of repeating units of peptides. Non-limiting examples of proteins include diet-based proteins and plant-based proteins. Dairy-based proteins include casein, caseinates (e.g., all forms including sodium caseinate, calcium caseinate, potassium caseinate), whey (e.g., all forms including concentrate, isolate, demineralization), concentrated milk proteins, and milk protein isolates. Plant-based proteins include soy protein (e.g., all forms, including concentrates and isolates), pea protein (e.g., all forms, including concentrates and isolates), canola protein (e.g., all forms, including concentrates and isolates), other plant proteins commercially available as wheat and fractionated wheat proteins, corn and its fractions including zein, rice, oats, potato, peanut, green bean, mung bean, and any protein derived from legumes, lentils, and legumes.

Other examples of proteins may be derived from animal sources (e.g., meat meal, organic meats, and meat extracts), marine sources (e.g., fish meal, fish muscle, and all forms of marine meal and muscle), and microbial sources (e.g., single cell proteins and variants).

All the above-mentioned proteins can be used as intact proteins or hydrolysates. The hydrolysate can have a low to high degree of hydrolysis. Peptides resulting from hydrolysis may include large or small peptides or a range of peptide sizes.

Free amino acids may be used instead of or in addition to proteins to provide the essential amino acids. Dipeptides are also commercially available and can provide the essential amino acids.

Non-limiting examples of peptides can be in a range of size classes, including small (e.g., di-and tri-peptides that do not require additional fragmentation for intestinal absorption), medium (e.g., oligopeptides, which are 4-10 amino acids in length), large (e.g., > 10 amino acids, but less than small proteins-molecular weight 1,000-5,000), and very large (e.g., proteins with molecular weight greater than 5,000, but which cannot be absorbed).

Additional components may be used with the exogenous nucleotide and the protein component to improve wound healing. In one embodiment, the nutritional composition further comprises one or more ingredients, such as non-replicating bacteria, fatty acids, triglycerides, lycium barbarum, antioxidants, vitamins, minerals, polyphenols, flavonoids, EGCg, pycnogenol, alpha-and beta-glucans, alpha-hydroxycaproic acid salts, aloe vera, honey, amino acids, branched chain amino acids, or combinations thereof.

The specific components and their functions are described in more detail below:

non-replicating bacteria (e.g., inactivated bacteria) -support immune function.

Arginine-proline precursor through ornithine, nitric oxide precursor for vasodilation and immune function stimulated by T-cells.

Glutamine-arginine precursor through citrulline; the activity of lymphokine-activated killer cells ("LAK") is glutamine-dependent.

Fatty acids and triglycerides-regulate inflammation and cell membrane and skin components.

Matrimony vineA bioavailable form of wolfberry berries for use in immune responsiveness.

Copper-macrophage function and immune cell proliferation in response to challenge.

Zinc-an essential cofactor required for the optimal innate immune response, protein synthesis, cell division and immune function.

Vitamin C-depletion upon stress; collagen synthesis, interferon stimulation, maintenance of the redox integrity of cellular and intracellular matrix components.

Vitamin a-is important for modulating antibody responses and B-cell differentiation into IgG expressing cells, and is also required for skin maintenance and collagen crosslinking.

Beta-carotene-vitamin a precursor, as beneficial as vitamin a + antioxidant activity.

Vitamin E-lipid soluble antioxidants stabilize cell membranes and lipids to prevent oxidative damage to immune cells.

Selenium-a selenium-containing protein component that increases cellular immune responses, early peaks of T cell proliferation, and increased T helper cells by producing interferon.

Polyphenols-inhibit the inflammatory cytokine interleukin-1 and reduce prostaglandin E2 production.

Flavonoids-stimulate or inhibit protein phosphorylation and thereby modulate immune cell function.

EGCg-a catechol with protective effect on dendritic cells that can probe the wound site, reducing the production of the inflammatory mediators IL-6 and COX-2.

Pycnogenol-improves T-cell and B-cell function and stimulates IL-2 and natural killer T-cell activity.

Alpha-and/or beta-glucans-immune cell stimulators of the innate and adaptive immune system by direct binding to macrophages.

AHCC- (methylated α -glucan) -specifically modified α -glucan.

Aloe-inhibits inflammatory cytokines TNF-alpha and IL-1 beta.

Honey-penetration and pH effects to prevent infection and immune stimulation.

Branched chain amino acids-protein antibodies ("abs") that readily oxidize and thereby complement immune cells to synthesize proteins, such as B-cells.

Leucine-the most potent branched chain amino acid of proteins used to stimulate and maintain immune cell proliferation and muscle anabolism.

alpha-HICA- (alpha-hydroxyisocaproic acid) can improve anabolic leucine metabolites.

In one embodiment, the nutritional composition further comprises one or more amino acids. Non-limiting examples of amino acids include alanine, arginine, asparagine, aspartic acid, citrulline, cysteine, glutamic acid, glutamine, glycine, histidine, hydroxyproline, hydroxyserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, and valine, and combinations thereof.

The term "antioxidant" as used herein is preferably understood to include any one or more of a variety of substances (e.g., beta carotene (vitamin a precursor), vitamin C, vitamin E, and selenium) that inhibit oxidation or reactions promoted by reactive oxygen species ("ROS") and other radical and non-radical species. In addition, antioxidants are molecules that can slow or prevent the oxidation of other molecules. Non-limiting examples of antioxidants for use herein include carotenoids, coenzyme Q10 ("CoQ 10"), flavonoids, glutathione, wolfberry (lycium barbarum), hesperidines, lycium barbarum, lignans, lutein, lycopene, polyphenols, selenium, vitamin a, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and combinations thereof.

The term "vitamin" as used herein is preferably to be understood as including any of the various fat-soluble or water-soluble organic substances which are necessary for the growth and activity of the body in minute amounts and which are naturally obtained from plant and animal food or are prepared synthetically (non-limiting examples include vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin or nicotinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal or pyridoxamine or pyridoxine hydrochloride), vitamin B7 (biotin), vitamin B9 (folic acid) and vitamin B12 (the various cobalamines; cyanocobalamines in vitamin supplements in general), vitamin C, vitamin D, vitamin E, vitamin K (including vitamin K1 and vitamin K2), provitamines, derivatives, analogues Calcium, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin, vanadium and zinc.

The terms "treat," "treating," and "ameliorating," as used herein, are preferably prophylactic or preventative treatment (prevention and/or slowing of the development of the targeted pathological condition or disorder) and curative, or ameliorating a disease treatment, including curative measures to cure, slow down, alleviate symptoms of, and/or prevent the development of the diagnosed pathological condition or disorder; and treating patients at risk of or suspected of having an infectious disease and patients who are ill or have been diagnosed as having a disease or medical condition. The term does not necessarily mean that the individual is treated to complete recovery. The term "treating" also refers to maintaining and/or promoting the health of an individual who is not suffering from a disease, but is suspected of developing an unhealthy condition such as nitrogen imbalance or muscle loss. The terms "treat," "treatment," and "ameliorating" are also intended to include enhancing, or otherwise facilitating, one or more primary prophylactic or therapeutic measures. The terms "treat," "treating," and "ameliorating" are also intended to include dietary management of a disease or disorder or dietary management to prevent or prevent a disease or disorder.

As used herein, a "tube feed" is preferably a complete or incomplete nutritional product that is administered to the gastrointestinal system of an animal in a non-oral administration, including, but not limited to, nasogastric tubes, orogastric tubes, gastric tubes, jejunostomy ("J-tubes"), percutaneous endoscopic gastrostomy ("PEG"), orifices such as chest wall orifices providing access to the stomach, jejunum entry, and other suitable entries.

In another embodiment, the present specification provides a method of making a nutritional composition. The method comprises adding a high protein component and one or more exogenous nucleotides to the nutritional composition in an amount effective to, for example, accelerate or improve wound healing in a mammal. The nutritional composition may be in an administrable form, such as a pharmaceutical formulation, nutraceutical, dietary supplement, functional food, beverage product, or a combination thereof.

In an alternative embodiment, the present specification provides a method of improving wound healing in a mammal. The method comprises administering to a mammal having a wound a nutritional composition comprising an effective amount of a high protein component and an exogenous nucleotide. The nutritional composition is administered to provide the exogenous nucleotide in an amount of about 0.2 g/day to about 4 g/day. The wound may be from a pressure ulcer, a surgical incision, an abrasion, or a combination thereof. The mammal may also have diabetes.

In an alternative embodiment, the present specification provides a method of ameliorating pressure ulcers in a mammal using the same procedures as described above.

Other optional ingredients may be added to make a sufficiently palatable nutritional composition. Any suitable amount of optional ingredients may be added.

Examples

The following examples illustrate various embodiments of the present specification, by way of example and not by way of limitation.

Example 1

Table 1: complete feed product suitable for pressure ulcer control diet

Composition (I)	Measurement of	Function(s)
			Caseinate salts	75g (20% energy)	High quality protein
Mediterranean flower oil	50g (30% energy)	Fatty acid source and energy
			Maltodextrin	188g (50% energy)	Carbohydrate and energy source
Yeast extract	2.5g	RNA/nucleotide Source
			Yeast premix	2.5g
Mineral premix	1.0g
			Emulsifier	1.5g
Water (W)	1290g
			Optional ingredients		As otherwise mentioned

Example 2

Table 2: 1-day feeding dietary formula for controlling pressure ulcers

Composition (I)	Measurement of	Function(s)
			Casein sodium salt	55g	High quality protein
Calcium caseinate	17g	High quality protein
			Palm kernel oil	20g	Medium chain triglycerides
Fish oil	16.7g	N-3 fatty acids for reducing inflammation
			Sunflower oil	5.0g	Fatty acids and energy
Maltodextrin	200g	Carbohydrate and energy source
			Yeast extract	2.26g	RNA/nucleotide Source
Arginine	18.75g	Support of T-cell function

Vitamin premix	2.5g
			Mineral premix	1.0g
Emulsifier	1.5g
			Water (W)	1243g
Optional ingredients	52g	As otherwise mentioned

Example 3

Table 3: high protein oral nutritional supplement product, 8 fluid ounces

Composition (I)	Measurement of	Function(s)
			Concentrated milk protein	15g	High quality protein
Oil blends	6g	Fatty acids and energy
			Sucrose	13g	Carbohydrate and energy source
Corn syrup solids	18.9g	Carbohydrates and sweeteners
			Mineral substance	2.5g
Yeast extract	1.0g	RNA/nucleotide Source
			Vitamin preparation	1.0g
Water (W)	200g
			Optional ingredients		As otherwise mentioned

Example 4

Table 4: protein and nucleotide oral modular nutritional products for wound healing

Composition (I)	Measurement of	Function(s)
			Whey protein isolate	6g	High quality protein
Yeast extract	2g	RNA/nucleotide Source
			Citric acid	1g	Acidifying agent
Vitamin premix	0.1g
			Mineral premix	0.2g

Optional ingredients

0.4g

As otherwise mentioned

Example 5

Table 5: amino acid and nucleotide modular oral nutritional products for wound healing

Composition (I)	Measurement of	Function(s)
			L-arginine	4g	High quality protein
Yeast extract	2g	RNA/nucleotide Source
			Citric acid	2g	Acidifying agent
Malic acid	1g	Acidifying agent
			Vitamin premix	0.1g
Mineral premix	0.2g
			Optional ingredients	0.4g	As otherwise mentioned

The nutritional product is preferably understood to also comprise any number of optional further ingredients, including common food additives, such as one or more acidulants, further thickeners, buffers or agents for pH adjustment, chelating agents, colorants, emulsifiers, excipients, flavors, minerals, osmotic agents, pharmaceutically acceptable carriers, preservatives, stabilizers, sugars, sweeteners, texturizers and/or vitamins. Any suitable amount of optional ingredients may be added.

In a preferred embodiment, the nutritional composition comprises a high protein component and exogenous nucleotides. In another embodiment, the high protein component includes at least one of proteins, peptides, and amino acids and precursors and metabolites of proteins, peptides, and amino acids in an amount to provide a nutritional composition of at least about 18% of the total calories. In another embodiment, the nutritional composition has a total volume of less than 300mL, wherein the high protein component includes at least one protein, peptide, and amino acid and precursors and metabolites of the protein, peptide, and amino acid in an amount greater than about 14 grams. In another embodiment, the high protein component includes at least about 5 grams protein, at least about 3 grams bitter amino acids, and at least about 7 grams neutral taste acids. In another embodiment, the bitter amino acid is selected from the group consisting of arginine, phenylalanine, tyrosine, leucine, isoleucine, valine, methionine, histidine and combinations thereof; in another embodiment, the neutral-tasting amino acid is selected from the group consisting of glutamine, glycine, alanine, threonine, proline, serine, and combinations thereof. In another embodiment, the exogenous nucleotide is in an amount of about 1 gram per 1000 calories of the nutritional composition. In another embodiment, the exogenous nucleotide is in a monomeric form selected from the group consisting of 5 'adenosine monophosphate, 5' -guanosine monophosphate, 5 '-cytosine monophosphate, 5' -uracil monophosphate, 5 '-inosine monophosphate, 5' -thymine monophosphate, and combinations thereof. In another embodiment, the exogenous nucleotide is an intact ribonucleic acid and/or other form comprising a nucleotide. In a preferred embodiment, the nutritional composition further comprises an ingredient selected from the group consisting of non-replicating bacteria, fatty acids, triglycerides, lycium barbarum, antioxidants, vitamins, minerals, polyphenols, flavonoids, EGCg, pycnogenol, alpha-and beta-glucans, alpha-hydroxyisocaproate, aloe vera, honey, amino acids, branched chain amino acids, and combinations thereof.

In a preferred embodiment, the nutritional composition is in an administrable form selected from the group consisting of pharmaceutical preparations, nutraceuticals, dietary supplements, functional foods and beverage products.

In a preferred embodiment, the nutritional composition further comprises an antioxidant. In another embodiment, the antioxidant is selected from carotenoids, coenzyme Q10 ("CoQ 10"), flavonoids, glutathione, lycium barbarum (lycium barbarum), hesperidine, lycium barbarum, lignans, lutein, lycopene, polyphenols, selenium, vitamin a, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, or combinations thereof.

In a preferred embodiment, the nutritional composition further comprises a carbohydrate.

In a preferred embodiment, the nutritional composition further comprises fat.

In a preferred embodiment, the nutritional composition further comprises fish oil. In another embodiment, the fish oil is selected from docosahexaenoic acid ("DHA") and eicosapentaenoic acid ("EPA").

In a preferred embodiment, the nutritional composition further comprises minerals. In another embodiment, the mineral is selected from the group consisting of boron, calcium, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin, vanadium, zinc, and combinations thereof.

In a preferred embodiment, the nutritional composition further comprises a plant nutrient. In another embodiment, the phytonutrient is selected from the group consisting of flavonoids and homologous phenolic and polyphenolic compounds, terpenoids (including carotenoids) and alkaloids (including curcumin, limonin and quercetin) and combinations thereof.

In a preferred embodiment, the nutritional composition further comprises a prebiotic. In another embodiment, the prebiotic is selected from the group consisting of gum arabic, alpha glucan, arabinogalactan, beta glucan, fructooligosaccharides, galactooligosaccharides, galactomannans, gentiooligosaccharides, oligoglucosides, guar gum, inulin, isomaltooligosaccharides, lactosucrose, levulose, fructans, maltodextrins, partially hydrolyzed guar gum, pectic oligosaccharides, retrograded starch, soy oligosaccharides, sugar alcohols, xylooligosaccharides, or combinations thereof.

In a preferred embodiment, the nutritional composition further comprises a probiotic. In another embodiment, the probiotic is selected from the group consisting of replication-competent and replication-free: aerococcus, aspergillus, bacteroides, bifidobacterium, candida, clostridium, debaryomyces, enterococcus, clostridium, lactobacillus, lactococcus, leuconostoc, honeybee, micrococcus, mucor, oenococcus, pediococcus, penicillium, peptostreptococcus, pichia, propionibacterium, pseudothecatula, rhizopus, saccharomyces, staphylococcus, streptococcus, torulopsis, weissella, or combinations thereof.

In a preferred embodiment, the nutritional composition further comprises vitamins. In another embodiment, the vitamin is selected from the group consisting of fat soluble or water soluble organic substances including vitamin a, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K (including vitamin K1 and vitamin K2), folic acid and biotin, provitamins, derivatives, analogs and combinations thereof.

In a preferred embodiment, the nutritional composition is fully nutritional.

In a preferred embodiment, the nutritional composition further comprises is not fully nutritional.

In a preferred embodiment, a method of preparing a nutritional composition is provided that includes adding a high protein component and an exogenous nucleotide to the nutritional composition. In another embodiment, the high protein component includes at least one of proteins, peptides, and amino acids and precursors and metabolites of proteins, peptides, and amino acids in an amount to provide a nutritional composition of at least about 18% of the total calories. In another embodiment, the nutritional composition has a total volume of less than 300mL, and wherein the high protein component includes at least one protein, peptide, and amino acid and precursors and metabolites of the protein, peptide, and amino acid in an amount greater than about 14 grams. In another embodiment, the high protein component includes at least about 5 grams protein, at least about 3 grams bitter amino acids, and at least about 7 grams neutral taste acids. In another embodiment, the nutritional composition is in an administrable form selected from the group consisting of pharmaceutical preparations, nutraceuticals, dietary supplements, functional foods, and beverage products.

In another embodiment, a method of improving wound healing or treating a wound in a mammal comprises administering to a mammal having a wound an effective amount of a high protein component and an exogenous nucleotide. In another embodiment, the nutritional composition is administered to provide the exogenous nucleotides in an amount of about 0.2 g/day to about 4 g/day. In another embodiment, the mammal is a human. In another embodiment, the mammal is an elderly human. In another embodiment, the mammal is hospitalized. In another embodiment, the mammal is in a care facility. In another embodiment, the mammal is home care. In another embodiment, the nutritional composition is tube fed. In another embodiment, the administration is chronic. In another embodiment, the administration is short-term administration. In another embodiment, the high protein component includes at least one of proteins, peptides, and amino acids and precursors and metabolites of proteins, peptides, and amino acids in an amount to provide a nutritional composition of at least about 18% of the total calories. In another embodiment, the nutritional composition has a total volume of less than 300mL, and wherein the high protein component includes at least one protein, peptide, and amino acid and precursors and metabolites of the protein, peptide, and amino acid in an amount greater than about 14 grams. In another embodiment, the high protein component includes at least about 5 grams protein, at least about 3 grams bitter amino acids, and at least about 7 grams neutral taste acids. In another embodiment, the wound is a pressure ulcer, a surgical incision, an abrasion, and combinations thereof. In another embodiment, the mammal has diabetes. In another embodiment, the mammal has renal failure. In another embodiment, the mammal has liver insufficiency or liver failure.

In a preferred embodiment, is a method of treating pressure ulcers in a mammal, the method comprising administering to a mammal having a pressure ulcer, a nutritional composition comprising an effective amount of a high protein component and an exogenous nucleotide. In another embodiment, the nutritional composition is administered to provide the exogenous nucleotides in an amount of about 0.2 g/day to about 4 g/day. In another embodiment, the high protein component includes at least one of proteins, peptides, and amino acids and precursors and metabolites of proteins, peptides, and amino acids in an amount to provide a nutritional composition of at least about 18% of the total calories. In another embodiment, the nutritional composition has a total volume of less than 300mL, and wherein the high protein component includes at least one protein, peptide, and amino acid and precursors and metabolites of the protein, peptide, and amino acid in an amount greater than about 14 grams. In another embodiment, the high protein component includes at least about 5 grams protein, at least about 3 grams bitter amino acids, and at least about 7 grams neutral taste acids. In another embodiment, the mammal has diabetes. In another embodiment, the mammal has renal failure. In another embodiment, the mammal has liver insufficiency or liver failure. In another embodiment, the mammal is a human. In another embodiment, the mammal is an elderly human. In another embodiment, the mammal is hospitalized. In another embodiment, the mammal is in a care facility. In another embodiment, the mammal is home care. In another embodiment, the nutritional composition is tube fed. In another embodiment, the administration is chronic. In another embodiment, the administration is short-term administration.

In a preferred embodiment, is a method of treating a surgical incision in a mammal, the method comprising administering to a mammal having a pressure ulcer a nutritional composition comprising an effective amount of a high protein component and an exogenous nucleotide. In another embodiment, the nutritional composition is administered to provide the exogenous nucleotides in an amount of about 0.2 g/day to about 4 g/day. In another embodiment, the high protein component includes at least one of proteins, peptides, and amino acids and precursors and metabolites of proteins, peptides, and amino acids in an amount to provide a nutritional composition of at least about 18% of the total calories. In another embodiment, the nutritional composition has a total volume of less than 300mL, and wherein the high protein component includes at least one protein, peptide, and amino acid and precursors and metabolites of the protein, peptide, and amino acid in an amount greater than about 14 grams. In another embodiment, the high protein component includes at least about 5 grams protein, at least about 3 grams bitter amino acids, and at least about 7 grams neutral taste acids. In another embodiment, the mammal has diabetes. In another embodiment, the mammal has renal failure. In another embodiment, the mammal has liver insufficiency or liver failure. In another embodiment, the mammal is a human. In another embodiment, the mammal is an elderly human. In another embodiment, the mammal is hospitalized. In another embodiment, the mammal is in a care facility. In another embodiment, the mammal is home care. In another embodiment, the nutritional composition is tube fed. In another embodiment, the administration is chronic. In another embodiment, the administration is short-term administration.

In a preferred embodiment, wherein the method results in a reduction in healthcare spending costs. In another embodiment, the reduction in cost of healthcare spending is due to a reduction in length of hospital stay. In another embodiment, the reduction in healthcare spending costs is due to a reduction in length of time in a care facility. In another embodiment, the reduction in healthcare expenditure costs is due to a reduction in complications.

All dosage ranges contained herein are intended to include all numbers, whole or parts of the range.

It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims.

Claims (21)

1. A nutritional composition comprising a high protein component and exogenous nucleotides, wherein the high protein component comprises at least one protein, peptide, and amino acid and precursors and metabolites of the protein, peptide, and amino acid in an amount to provide the nutritional composition in at least about 18% of total calories.

2. The nutritional composition of claim 1, wherein the nutritional composition has a total volume of less than 300mL, and wherein the amount of high protein content is greater than about 14 grams.

3. The nutritional composition of claim 1, wherein the high protein component comprises at least about 5 grams of protein, at least about 3 grams of bitter tasting amino acids, and at least about 7 grams of neutral tasting acids, wherein the bitter tasting amino acids are selected from the group consisting of arginine, phenylalanine, tyrosine, leucine, isoleucine, valine, methionine, histidine, and combinations thereof; and the neutral-tasting amino acid is selected from the group consisting of glutamine, glycine, alanine, threonine, proline, serine, and combinations thereof.

4. The nutritional composition of claim 1, wherein the amount of exogenous nucleotides is about 1 gram per 1000 calories of the nutritional composition.

5. The nutritional composition of claim 1, wherein the exogenous nucleotide is a monomeric form selected from the group consisting of 5 'adenosine monophosphate, 5' -guanosine monophosphate, 5 '-cytosine monophosphate, 5' -uracil monophosphate, 5 '-inosine monophosphate, 5' -thymine monophosphate, and combinations thereof.

6. The nutritional composition of claim 1, wherein the exogenous nucleotides are intact ribonucleic acids and/or other forms comprising nucleotides.

7. The nutritional composition of claim 1, further comprising an ingredient selected from the group consisting of non-replicating bacteria, probiotics, fatty acids, triglycerides, wolfberry, antioxidants, vitamins, minerals, polyphenols, flavonoids, EGCg, pycnogenol, alpha-and beta-glucans, alpha-hydroxyisocaproate, aloe vera, honey, amino acids, branched chain amino acids, carbohydrates, fats, fish oils, phytonutrients, prebiotics, and combinations thereof.

8. A method of treating a wound or improving wound healing in a mammal, the method comprising administering to a mammal having a wound a nutritional composition comprising an effective amount of a high protein component and an exogenous nucleotide.

9. The method of claim 8, wherein the nutritional composition comprises the composition of any one of claims 1-7.

10. The method of any one of claims 8, wherein the nutritional composition is administered to provide the exogenous nucleotides in an amount of about 0.2 g/day to about 4 g/day.

11. The method of claim 8, wherein the mammal is of an aging age.

12. The method of claim 8, wherein the mammal is hospitalized, in a care facility, a nursing home, or in home care.

13. The method of claim 8, wherein the nutritional composition is tube fed.

14. The method of claim 8, wherein the mammal has at least one of diabetes, renal failure, hepatic insufficiency, or hepatic failure.

15. The method of claim 8, wherein the wound is a pressure ulcer.

16. The method of claim 8, wherein the wound is a surgical incision.

17. The method of claim 8, wherein the method results in a reduction in healthcare spending costs.

18. The method of claim 17, wherein the reduction in healthcare spending cost is due to a reduction in length of hospital stay.

19. The method of claim 17, wherein the reduction in healthcare spending cost is due to a reduction in length of time in a care facility.

20. The method of claim 17, wherein the reduction in healthcare spending cost is due to a reduction in complications.

21. The method of claim 20, wherein the complication is selected from a local infection, sepsis, delayed healing, embolism, thrombosis, iatrogenic accident, hypoxia, or a combination thereof.