TW201532528A - Nutritional composition containing a neurologic component of kaempferol and/or fisetin and uses thereof - Google Patents

Abstract

The present disclosure generally relates to nutritional compositions that are suitable for administration to adult and pediatric subjects that include a neurologic component. The neurologic component may include a flavonoid compound, such as kaempferol, fisetin, or both, and provides beneficial health benefits such as enhanced brain development and improved memory, cognition, hand-eye coordination, and enhanced focusing. Furthermore, the neurologic component may act synergistically with other brain nutrients that may be present in the compositions.

Description

Nutrient composition containing neurological components of fulvicin and/or baicalein and application thereof Cross-reference to related applications

This application is a continuation-in-part of U.S. Application Serial No. 13/273,635, filed on Oct. 14, 2011, and U.S. Application Serial No. 13/739,787, filed on Jan. 11, 2013, the entire contents of .

The present invention relates to a nutritional composition comprising a neurological component suitable for administration to an adult and a pediatric individual. The neurological component may comprise a flavonoid compound such as luciferin, baicalein or both. The neurological component provides beneficial health benefits including improved brain development and improved memory, cognition, hand-eye coordination, and increased concentration. Furthermore, the neurological component can act synergistically with other brain nutrients that may be present in the composition.

Furthermore, the present invention relates to methods of promoting brain and nervous system health by providing a nutritional composition comprising the neurological component described herein.

The brain accounts for only 2% of the total weight, but it is an energy-consuming organ that uses up to 30% of daily calories and nutrients. (Harris, JJ et al., The Energetics of CNS White Matter. Jour . of. Neuroscience, Jan. 2012: 32(1): 356-371). Both the human brain and the nervous system begin to form and continue to develop very early in the life of the fetus until about 3 years of age. This early development can have a lifelong impact on the health of the entire brain and nervous system. Therefore, brain nutrients can be an important additive in the diet of infants, children, and pregnant and lactating women because of their ability to promote early brain development and prevent and protect the brain and nervous system from injury or disease. In addition, brain nutrients are important for adults because many nutrients promote nervous system repair and provide the health benefits of neuroprotection.

Pistachio (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopipene-4-one) is a flavonoid compound that naturally occurs in many edible plants. Among them, such as tea, broccoli, kale, kale, beans, chicory, leeks, tomatoes, strawberries and grapes, as well as plants and plant products commonly used in traditional medicine. The scutellaria is a relatively small molecule, so it can easily penetrate the blood-brain barrier to directly play a role in the brain. (Rangel-Ordonez, L., et al., Planta Med. 2010 Oct.: 76(15): 1683-90; see also Calderon-Montano, JM, et al., Mini Rev. Med. Chem. 2011 Apr; 11 ( 4): 298-344).

Baicalein (2-(3,4-dihydroxyphenyl)-3,7-dihydroxyl Iso-4-one) is a polyphenolic compound that is naturally found in fruits and vegetables such as strawberries, apples, grapes, milk thistle and onions. Baicalein is a relatively small molecule and may easily penetrate the blood-brain barrier to function directly in the brain.

Many nutrients are thought to be involved in supporting healthy brain development, and it is necessary to include neurotic components in the nutritional composition to support the health of the brain and nervous system. Saskatchewan, scutellaria and scutellaria can be used as dietary supplements, which can be formulated into compositions for infants, children and adults. More specifically, fulvicin and baicalein may be useful brain nutrients which can be advantageously formulated into compositions which are beneficial to the brain development of infants, children and adults.

Briefly, in one embodiment, the invention is directed to a nutritional composition comprising a mixture of guaranurin, baicalein or a mixture thereof.

In certain embodiments, the nutritional composition may further comprise additional brain nutrients such as docosahexaenoic acid (DHA), arachidonic acid (ARA), lutein, resveratrol, and / or cholesterol. Although not intended to be bound by theory, DHA can act synergistically with luccain and/or baicalein to promote neurogenesis and support overall brain health and development.

Furthermore, in some embodiments, the nutritional composition may optionally comprise one or any combination of the following groups: prebiotics, probiotics, iron sources, lactoferrin and/or beta -glucan sugar.

Since brain development is critical in the first year of life, in one embodiment, the nutritional composition is an infant formula or a pediatric nutritional composition. The nutritional composition described herein can be used as a drug or nutritional supplement for promoting neurological health in an individual suffering from a neurodegenerative disease and/or brain damage. Furthermore, the nutritional compositions of the present invention provide the health benefits of neuroprotection and promote the health of the overall brain and nervous system.

In some embodiments, the present invention is directed to a method for promoting health of the brain and nervous system, the method comprising providing a nutritional composition comprising a neural component to a target individual.

It is to be understood that the foregoing general description of the embodiments of the invention, This description is used to explain the principles and operation of the subject matter of the patent application. Other and further features and advantages of the present invention will be readily apparent from the <RTIgt;

Figure 1A is a phase contrast microscopy image of human adipose-derived stem cells (hADSC) (negative control group) exposed to neuronal differentiation for two hours but not treated with neuronal components. The hADSC appears to be in an undifferentiated state and has a large and flat morphology.

Figure 1B is a phase contrast microscopy image of hADSC in the presence of 20 μM DHA showing that the hADSCs differentiated into neuronal cells (positive control).

Figure 1C is a phase contrast microscopy image of hADSC in the presence of 10 micrograms/ml of luccain, which shows neuronal morphological changes and neurite outgrowth.

Figure 1D is a phase contrast microscopy image of hADSC in the presence of 1.25 micrograms/ml of luciferin and 6 [mu]M of DHA showing synergistic effects of luccain and DHA on neuronal differentiation.

Figure 2A is a phase contrast microscopy image of human adipose-derived stem cells (hADSC) (negative control group) exposed to neuronal differentiation for two hours but not treated with neuronal components. The hADSC appears to be in an undifferentiated state and has a large and flat morphology.

Figure 2B is a phase contrast microscopy image of hADSC in the presence of 20 μM DHA showing that the hADSCs differentiated into neuronal cells (positive control).

Figure 2C is a phase contrast microscopy image of hADSC in the presence of 25 μg/ml of baicalein showing neuronal morphological changes and neurite outgrowth.

Figure 2D is a phase contrast microscopy image of hADSC in the presence of 5 μg/ml of baicalein and 6 μM of DHA, which shows synergistic effects of guanosine and DHA on neuronal differentiation.

Detailed description

Referring now to the details of the embodiments of the invention, one or more examples are set forth below. The examples provided are used to explain this The nutritional composition of the invention, not a limitation. In fact, it will be apparent to those skilled in the art that the present invention may be modified and varied without departing from the scope of the invention. For example, features illustrated or described as part of one embodiment can be used with another embodiment to yield a further embodiment.

Accordingly, the present invention is intended to cover such modifications and alternatives Other objects, features, and aspects of the invention are disclosed in the following detailed description. Those of ordinary skill in the art will appreciate that the present discussion is only illustrative of exemplary embodiments and is not intended to limit the scope of the invention.

The present invention generally relates to a nutritional composition comprising a neural component, wherein the neural component may comprise guarannisin, baicalein or a mixture thereof. Furthermore, the present invention relates to methods of supporting and promoting brain and nervous system health, neurodevelopment, neuroprotection, and cognitive development by providing a nutritional composition comprising a neural component described herein.

"Nutrition composition" means a substance or blend that meets at least a portion of the nutritional needs of an individual. Throughout the present invention, the terms "nutrition", "nutritional formula", "enteral nutrition", "nutritional composition" and "nutritional supplement" are used interchangeably to refer to as liquids, powders, gels, pastes, Ingredients for solids, concentrates, suspensions or ready-to-use enteric formulations, oral formulations, infant formulas, pediatric individual formulations, children's formulas, growing milk and/or adults (such as breastfeeding or pregnant women). In a particular embodiment, the nutritional composition is for pediatric individuals, including infants and children.

The term "intestinal" means passing through the gastrointestinal tract or digestive tract or in the gastrointestinal tract or digestive tract. "Intestinal administration" includes oral feeding, intragastric feeding, pyloric administration, or any other administration into the digestive tract.

"Nerve component" refers to a compound or composition that affects neurogenesis by promoting or inhibiting neuroneogenesis. Thus, in some embodiments, the neural component promotes neonatal regeneration, while in other embodiments, the neural component inhibits or reduces neonatal regeneration.

"Pediatric individuals" include both infants and children, and herein refers to persons younger than 13 years of age. In some embodiments, a pediatric system refers to a human individual that is less than 8 years old. In other embodiments, a pediatric system refers to a human individual between about 1 and about 6 years old or between about 1 and about 3 years old. In still further embodiments, the pediatric system refers to a human individual between about 6 and about 12 years old.

"Infant" means an individual who is born within the range of not more than one year of age and includes infants of 0 to 12 months of corrected age. The term "corrected age" means the age of the baby minus the amount of time the baby is born prematurely. Therefore, if the baby is born in full term, the corrected age is the age of the baby. The term infant includes low birth weight infants, very low birth weight infants, and premature infants. "Premature baby" means a baby born before the 37th week of pregnancy. "Full term" means an infant born after the 37th week of pregnancy.

"Child" means an individual who is between about 12 months and about 13 years of age. In some embodiments, the child is an individual between the ages of 1 and 12. In other embodiments, the terms "child" or "child" mean between about 1 and about 6 years old, between about 1 and An individual between about 3 years old or between about 7 and about 12 years old. In other embodiments, the term "child" or "child" refers to any age range between about 12 months and about 13 years.

"Child nutrition product" means a composition that meets at least a portion of the nutritional needs of a child. Growing milk is an example of a child's nutritional product.

"Infant formula" means a composition that meets at least a portion of the nutritional needs of an infant. In the United States, the content of infant formula is governed by the federal regulations contained in Sections 100, 106 and 107 of 21 C.F.R. These regulations define the amount of nutrients, vitamins, minerals and other ingredients in an effort to mimic the nutritional and other properties of human breast milk.

The term "growth milk" refers to a broad range of nutritional compositions that are intended to be part of a diverse diet to support the normal growth and development of children between the ages of about 1 and about 6 years.

"Milk-based" means comprising at least one ingredient that has been raised or extracted from the mammary gland of a mammal. In some embodiments, the milk-based nutritional composition comprises a milk component derived from a domesticated ungulate, ruminant or other mammal or any combination thereof. Furthermore, in some embodiments, milk-based refers to the inclusion of bovine casein, whey, lactose or any combination thereof. Further, "milk-based nutritional composition" may mean any composition comprising any dairy-derived or milk-based product known in the art.

"Nutritionally complete" means a composition that is the sole source of nutrition that provides virtually all of the daily needs. Protein, minerals and/or trace elements, plus protein, carbohydrates and lipids. Specifically, a "nutritively intact" description provides the right amount of carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, semi-essential amino acids, vitamins, minerals, and energy to support the proper growth and development of an individual. Nutritional composition.

Thus, by definition, a nutritional composition that is “nutritiously intact” for premature babies will qualitatively and quantitatively provide the right amount of carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, essentials needed to grow premature babies. Amino acids, vitamins, minerals and energy.

By definition, a nutritional composition that is "nutritiously intact" for term infants will qualitatively and quantitatively provide the right amount of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, and half required for full-term growth. Essential amino acids, vitamins, minerals and energy.

By definition, a nutritionally complete nutrient composition for children will qualitatively and quantitatively provide the right amount of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, semi-essential amino acids required for the growth of children. , vitamins, minerals and energy.

When applied to nutrients, the term "essential" refers to any nutrient that the body cannot synthesize in an amount sufficient for normal growth and maintenance of health, and therefore must be supplied by the diet. The term "semi-essential" when applied to a nutrient means a nutrient that must be provided by the diet when the body is unable to obtain an appropriate amount of the precursor compound for endogenous synthesis.

"Probiotics" means microorganisms that have low or no pathogenicity that can have a beneficial effect on host health.

The term "inactivated probiotic" means a probiotic in which the metabolic activity or reproductive capacity of the probiotic organism has been reduced or destroyed. However, the cell level of "inactivated probiotics" still retains at least a portion of its biodiol-protein and DNA/RNA structures. The term "inactivated" as used herein is synonymous with "non-viable." More specifically, a non-limiting example of an inactivated probiotic is inactivated Lactobacillus rhamnosus GG ("LGG").

"Probiotic" means that it can promote the health of a host by selectively stimulating the growth and/or activity of one or a limited number of beneficial intestinal bacteria in the digestive tract, selectively reducing intestinal pathogens or beneficially affecting the health of the host. Intestinal short-chain fatty acids are sketches of non-digestible food ingredients that have a beneficial effect on the host.

" β -glucan" means all β -glucans, including specific types of β- 1,3-glucan and β- 1,3; 1,6-glucan, each being β -glucan Both sugars. Further, β -1,3; 1,6-glucan is a type of β- 1,3-glucan. Thus, the term " β- 1,3-glucan" includes β- 1,3; 1,6-glucan.

All percentages, parts and ratios used herein are by weight of the total blend, unless otherwise specified.

The nutritional compositions of the present invention may be substantially free of any of the optional or selected ingredients described herein. In this context, unless otherwise specifically indicated, the term "substantially free" means that the optional component of the selected composition may be present in an amount less than the functional amount, and the amount of such selective or selected component is generally low. It is 0.1% by weight, and also includes 0% by weight.

All references to the singular or the singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singularity singularity

All methods or combinations of processing steps used herein can be performed in any order, unless otherwise specifically indicated or specifically indicated to the contrary.

The compositions and methods of the present invention (including components thereof) may comprise elements and limitations of the embodiments described herein, consisting of or consisting essentially of the above, as described herein or for use in nutrition. Any additional or optional ingredients, components or limitations in the composition.

The term "about" as used herein shall be interpreted to mean any range within the two specified numbers. Any reference to a range shall be deemed to provide support for any subset within the scope.

The development of the brain and nervous system plays a key role in the overall health and well-being of the individual. Therefore, the nutritional composition of the present invention promotes the health of the brain and nervous system. Specifically, in some embodiments, providing a neurological component described herein promotes neural stem progenitor cell (NSPC) migration and signal transduction, increases dopamine receptor density, supports prevention of memory impairment, and reduces the number of apoptotic cells Reduce neuronal degeneration, increase overall brain metabolism and reduce oxidative stress.

Accordingly, in some embodiments, the present invention provides a nutritional composition comprising a carbohydrate source, a protein source, a fat source, and a neural component comprising guarannisin, baicalein or a mixture thereof.

In some embodiments, the scutellaria in the composition It can be present in the range of from about 0.1 mg/100 kcal to about 5 mg/100 kcal. In other embodiments, the scutellarin may be present in an amount ranging from about 0.1 mg/100 kcal to about 3 mg/100 kcal, or from about 0.3 mg/100 kcal to about 2 mg/100 kcal.

In some embodiments, baicalein may be present in the composition in an amount ranging from about 3 mg/100 kcal to about 200 mg/100 kcal. In other embodiments, the amount of baicalein may range from about 3 mg/100 kcal to about 100 mg/100 kcal, and in other embodiments, the amount of baicalein may be present. 3 mg / 100 kcal to about 25 mg / 100 kcal range.

In some embodiments, the nutrient composition comprising a neural component is a nutritionally complete formulation suitable for supporting normal growth and also contributing to brain development. In certain other embodiments, the composition and concentration of nutrients in the neural component are designed to mimic a level of health for early human development.

The nutrients of the neural component contained in the nutritional composition may include functional equivalents, sources, metabolites and/or precursors of the nutrient. Nutrients of such neurological components can be developed naturally, synthetically or through genetic engineering operations of organisms and/or plants, whether such sources are now known or later developed.

Any natural source of guaranurin or baicalein may be used. Preferably, the nutrient source of the neural component should be a food grade derived from food or plants, or made by microorganisms. In addition, the nutrient source of the neural component can be part of a complex mixture that can be utilized in the art. It is known to focus on the separation and purification techniques of derivatives or precursors of neurotrophic nutrients enriched in such mixtures.

More specifically, fulvicin can be obtained from a variety of plant sources known to be found from the scutellaria. For example, pangas may be isolated from the following groups: tea, broccoli, Delphinium, Witch hazel, grapefruit, kale, kale, beans, endive, Amaranth, tomato, strawberry, grape, Brussels sprouts, apples, capers, dill and other plant sources. Additional sources of Fructus sinensis include Allium ampeloprasum (leek), A.cepa (onion), A.schoenoprasum ( shrimp onion), Amaranthus lividus (苋), Angelica keiskei ( Tomorrow), Armoracia rusticana (horseradish), Artemisia dracunculus (tarragon), Atriplex hortensis ( Atriplex ), Brassica campestris (Chinese cabbage), B.juncea (wasabi), B.napobrassica ( cyanium ), B.oleracea (cauliflower, Brussels sprouts, greens and kale) , B.rapa (no cyanine), Bunias orientalis ( caspice ), Camellia sinensis (tea tree), Capparis spinosa (continued), Celosia argentea (cyan), Cichorium endivia (chicory), Citrus paradise ( grapefruit) ), Cnidoscolus aconitifolius and C.chayamansa (tree spinach), Coccinia grandis (cucurbitaceae red cucumber), Cucumis sativus (cucumber), Cucurbita maxima ( zucchini), Cyamopsis tetragonoloba (guar), Diplotaxis erucoides (canola), Diplotaxis Tenuifolia (wild species sesame leaves), Eruca sativa ( cress mustard), Foeniculum vulgare (fennel), Fragaria vesca (strawberry), Houttuy nia cordata (Houttuynia), Ipomoea batatas (sweet potato), Lactuca sativa (lettuce), Lepidium sativum (cress), Levisticum officinale (lovage), Lycium barbarum and L.chinense (wolfberry), Malus domestica (apple), Momordica cochinchinensis , Morinda citrifolia , Nasturtium officinale , Nepenthes gracilis , Olea europaea (olive oil), Petroselinum crispum ( cilantro) , Phaseolus vulgaris (green beans), Pistacia vera ( pistachio), Prunus persica ( peach), Raphanus sativus (radish), Ribes uva-crispa ( currant), Rubis fruticosus (blackberry), Rubus idaeus ( raspberry), Sambucus Nigra ( Sambucus), Sauropus androgynous (Star Gooseberry), Sesbania grandiflora ( Tianjing), Solanum lycopersicum (Tomato), S.nigrum (Salvia ), S.tuberosum (Potato), Spinacia oleracea (Spinach), Vaccinium erythrocarpum (Southern Cranberry), V.acrocarpon (Cranberry), V.microcarpum and V.oxycoccos ( small cranberry), Vaccinium vitis-ida Ea (Bilberry), Vicia faba (Broad Bean), Vigna unguiculata (Vigna), Vitis rotundifolia (Vine) and Vitis vinifera (Grape) and Chia Seed.

Baicalein can be supplied from many plant sources, including fruits and vegetables such as strawberries, apples, grapes, milk thistle and onions. Astragalus Found in the core dicotyledonous plants (Eudicotyledons), such as trees and shrubs in the Fabaceae, such as Acacia greggii and Acacia berlandieri, Parrot frondosa, Acacia (USA) Gleditsia triacanthos, a member of the lacquer family, such as the species of Quebracho Colorado and sumac, including sumacs. Baicalin can also be provided by Cork tree (Callitropsis nootkatensis).

Synergism can be observed when luciferin or baicalein is combined with other brain nutrients. Other brain nutrients that may be included in the compositions of the present invention include DHA, ARA, lutein, resveratrol, and cholesterol DHA. In a particular embodiment, the inclusion of guarannisin and baicalein and DHA in the compositions of the present invention provides a beneficial synergistic effect on neuroneogenesis and promotes the development and health of the brain and nervous system.

Additionally, the neural component can be added to or incorporated into the nutritional composition by any of the methods well known in the art. In some embodiments, a neural component can be added to the nutritional composition to supplement the nutritional composition. For example, in one embodiment, the neural component can be added to a commercially available infant formula. For example, Enfalac, Enfamil®, Enfamil® Premature Formula, Enfamil® with Iron, Enfamil® LIPIL®, Lactofree®, Nutramigen®, Pregestimil® and ProSobee® (available from Glenview, Ill., USA) A suitable amount of nerve component is used in the practice of the invention.

In other embodiments, the neural component can be used to replace another nutrient source that does not contain the nutrients of the neural component. For example, a certain amount of a fat source that does not contain the neural component can be replaced with another fat source that contains the nutrients of the neural component. In still other embodiments, the source of the component that is typically added to the nutritional composition can be altered such that the selected source provides both the component that is typically added to the nutritional composition and the neurogenic component. Nutrients of matter.

In some embodiments, the neural component can be included in a prenatal dietary supplement. The neural component can be incorporated into the prenatal dietary supplement by any method known in the art. Prenatal administration of this neurological component can directly affect the development of the fetus and embryo. Since brain development begins early in prenatal life, the inclusion of neural components in prenatal dietary supplements promotes brain development and neurological renewal in pediatric individuals still in the womb.

Conveniently, commercially available prenatal dietary supplements and/or prenatal nutritional products can be used. For example, a suitable amount of neural component can be used in the implementation of the present invention in Expecta® Supplement (available from Glenview, Ill., USA).

The prenatal dietary supplement can be administered in one or more doses per day. In some embodiments, the prenatal dietary supplement is administered in two doses per day. In a separate embodiment, the prenatal dietary supplement is administered in three doses per day. The prenatal dietary supplement can be administered to pregnant or lactating women.

Any orally acceptable dosage form is contemplated by the present invention. Examples of such dosage forms include, but are not limited to, pills, tablets, capsules, Soft capsules, liquids, liquid concentrates, powders, elixirs, solutions, suspensions, emulsions, lozenges, beads, cachets, and combinations thereof. Alternatively, the prenatal dietary supplement of the present invention can be added to a more complete nutritional product. In this embodiment, the nutritional product may contain protein, fat and carbohydrate components and may be used to supplement the diet or may be the sole source of nutrition.

In some embodiments, the nutritional composition comprises at least one source of carbohydrates. The carbohydrate source can be any user skilled in the art, such as lactose, glucose, fructose, corn syrup solids, maltodextrin, sucrose, starch, rice syrup solids, and the like. The amount of carbohydrate component in the nutritional composition can generally vary from about 5 grams per 100 kilocalories to about 25 grams per 100 kilocalories. In some embodiments, the amount of carbohydrate is between about 6 grams per 100 kilocalories and about 22 grams per 100 kilocalories. In other embodiments, the amount of carbohydrate is between about 12 grams per 100 kilocalories and about 14 grams per 100 kilocalories. In some embodiments, corn syrup solids are preferred. Furthermore, hydrolyzed, partially hydrolyzed and/or highly hydrolyzed carbohydrates may be preferred to be incorporated into the nutritional composition as they are readily digestible. In particular, hydrolyzed carbohydrates are less likely to contain allergenic surface binding sites.

Non-limiting examples of carbohydrate materials suitable for use in the present invention include hydrolyzed or intact, natural or chemically modified waxy or non-waxy forms from corn, tapioca, rice or potato. starch. Non-limiting examples of suitable carbohydrates include various types known as hydrolyzed corn starch, maltodextrin, maltose, corn sugar Pulp, dextrose, corn syrup solids, hydrolyzed starch of glucose and various other glucose polymers, and combinations thereof. Non-limiting examples of other suitable carbohydrates include those commonly referred to as sucrose, lactose, fructose, high fructose corn syrup, indigestible oligosaccharides (such as oligosaccharides), and combinations thereof.

Furthermore, the nutritional composition of the invention may comprise at least one source of protein. The protein source can be any protein source used in the art, such as skim milk, whey protein, casein, soy protein, hydrolyzed protein, amino acid, and the like. Sources of cow's milk protein useful in the practice of the invention include, but are not limited to, milk protein powder, milk protein concentrate, milk protein isolate, skim milk solids, skim milk, skim milk, whey protein, whey protein isolate, milk Albumin concentrate, sweet whey, acid whey, casein, acid casein, caseinate (such as sodium caseinate, calcium caseinate, calcium caseinate), soy protein and any of them combination.

In a particular embodiment of the nutritional composition, the protein-derived whey: casein ratio is similar to that found in human breast milk. In one embodiment, the protein source comprises from about 40% to about 85% whey protein and from about 15% to about 60% casein.

In some embodiments, the nutritional composition comprises from about 1 gram to about 7 grams of protein source per 100 kilocalories. In other embodiments, the nutritional composition comprises from about 3.5 grams to about 4.5 grams of protein per 100 kilocalories.

In some embodiments, the protein of the nutritional composition is provided as a complete protein. In other embodiments, the protein The system is provided in two forms, intact protein and hydrolyzed protein (degree of hydrolysis of about 4% to 10%). In certain other embodiments, the protein has a higher degree of hydrolysis. In still other embodiments, the protein source comprises an amino acid. In yet another embodiment, the protein source can be supplemented with a peptide comprising glutamine. In another embodiment, the protein component comprises a highly hydrolyzed protein. In yet another embodiment, the protein component of the nutritional composition consists essentially of highly hydrolyzed protein to minimize the occurrence of food allergies.

In some embodiments, the protein component of the nutritional composition comprises a partially or highly hydrolyzed protein, such as a protein from cow's milk. The protein can be enzymatically treated to break down some or most of the proteins that cause adverse symptoms in order to reduce allergic reactions, intolerance and sensitization. Again, the protein can be hydrolyzed by any method known in the art.

In some embodiments, the nutritional composition of the invention is substantially free of intact protein. In this context, the term "substantially free" means that the preferred embodiment herein contains a concentration of intact protein that is sufficiently low to render the formulation hypoallergenic. The nutritional composition according to the present invention is substantially free of intact protein, and thus the degree of hyposensitivity is determined by the American Academy of Pediatrics policy statement of August 2000, which defines a hypoallergenic formula as: In a prospective, randomized, double-blind, placebo-controlled trial of this formulation in infants or children diagnosed with milk allergy, the hypoallergenic formula showed no 90 at 95% confidence level in appropriate clinical studies. % of infants or children who have been diagnosed with milk allergy have a reaction.

In some embodiments, the nutritional composition may be protein free and contain free amino acids as a protein equivalent source. In some embodiments, the amino acid may include, but is not limited to, histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine , sulphate, tryptophan, lysine, alanine, arginine, aspartame, aspartic acid, glutamic acid, glutamine, glycine, lysine, serine Carnitine, taurine and mixtures of them. In some embodiments, the amino acid can be a branched amino acid. In certain other embodiments, a small amino acid peptide can be included as a protein component of the nutritional composition. Such small amino acid peptides can be naturally occurring or synthetic. The amount of free amino acid in the nutritional composition can vary from about 1 g/100 kcal to about 5 g/100 kcal.

The nutritional composition may also comprise a source of fat. Suitable fat or lipid sources for use in the nutritional compositions of the present invention can be any of those known or used in the art, including, but not limited to, animal sources such as milk fat, butter, butter fat, egg yolk lipids; marine sources, Such as fish oil, marine oil, single cell oil; vegetable and vegetable oils, such as corn oil, canola oil, sunflower oil, soybean oil, palm oil, coconut oil, high oleic sunflower oil, evening primrose oil, rapeseed oil, olive oil , linseed (linseed) oil, cottonseed oil, high oleic safflower oil, palm oil stearin, palm kernel oil, wheat germ oil; medium chain triglyceride oil and fatty acid emulsions and esters; and their Any combination.

In one embodiment, the nutritional composition may contain one or more probiotics. Any probiotic known in the art can be accepted in this embodiment. In a particular embodiment, the probiotic may be selected from any of the following groups: Lactobacillus species, Lactobacillus rhamnosus GG (ATCC No. 53103), double Bifidobacterium species, Bifidobacterium longum BB 536 (BL999, ATCC: BAA-999), Bifidobacterium longum AH1206 (NCIMB: 41382), Bifidobacterium breve AH1205 ( Bifidobacterium breve AH1205) ) (NCIMB: 41387), Bifidobacterium infantis 35624 (NCIMB: 41003) and Bifidobacterium animalis subsp. lactis BB-12 (DSM No. 10140) or Any combination of the same.

If included in the composition, the amount of the probiotic may vary from about 1 x 10 ⁴ to about 1.5 x 10 ¹⁰ cfu of probiotic bacteria per 100 kcal, more preferably from about 1 x 10 ⁶ to about 100 kcal. 1 × 10 ⁹ cfu of probiotics. In certain other embodiments, the amount of the probiotic may vary from about 1 × 10 ⁷ cfu / 100 kcal to about 1 × 10 ⁸ cfu / 100 kcal between changes.

In one embodiment, the probiotic may be viable or non-viable. The term "viable" as used herein refers to a living microorganism. The term "unviable" or "non-viable probiotic" refers to probiotic microorganisms that are not viable, their cellular components, and/or their metabolites. Such non-viable probiotics may have been overheated or otherwise inactivated, but their ability to beneficially affect the health of the host. Probiotics useful in the present invention may be naturally occurring, synthetic or permeabilized Developed by genetic engineering operations of organisms, whether such new sources are known now or later developed.

In certain embodiments, the nutritional composition may also contain one or more prebiotics (also known as probiotic sources). Prebiotics can stimulate the growth and/or activity of ingested probiotic microorganisms, selectively reduce pathogens found in the gut and beneficially affect the profile of the short-chain fatty acids in the gut. Such probiotics can be developed for naturally occurring, synthetic or genetic engineering operations through organisms and/or plants, whether such new sources are now known or later developed. The probiotics which can be used in the present invention may include oligosaccharides, polysaccharides, and other probiotics containing fructose, xylose, soybean, galactose, glucose, and mannose.

More specifically, the probiotics which can be used in the present invention may include polydextrose, polydextrose powder, lactulose, lactulose oligosaccharide, raffinose, grape oligosaccharide, inulin, fructooligosaccharide, and different Malto-oligosaccharides, soybean oligosaccharides, lactulose oligosaccharides, xylooligosaccharides, chitooligosaccharides, mannooligosaccharides, arabinooligosaccharides, citric acid oligosaccharides, fuco-oligosaccharides, galactooligosaccharides and Gentio-oligosaccharide. In some embodiments, the total amount of probiotics present in the nutritional composition can range from about 0.1 grams per 100 kilocalories to about 1 gram per 100 kilocalories. In certain embodiments, the total amount of probiotics present in the nutritional composition can range from about 0.3 grams per 100 kilocalories to about 0.7 grams per 100 kilocalories. Further, the nutritional composition may comprise a probiotic component comprising polydextrose ("PDX") and/or galactooligosaccharide ("GOS"). In some embodiments, the probiotic component comprises at least 20% GOS, PDX, or a mixture thereof.

If PDX is used in the probiotic composition, in one embodiment, the amount of PDX in the nutritional composition can range from about 0.1 g/100 kcal to about 1 g/100 kcal. In another embodiment, the amount of polydextrose can range from about 0.2 grams per 100 kilocalories to about 0.6 grams per 100 kilocalories. In still other embodiments, the amount of PDX in the nutritional composition can range from about 0.1 mg/100 kcal to about 0.5 mg/100 kcal, or about 0.3 mg/100 kcal.

If GOS is used in the probiotic composition, in one embodiment, the amount of GOS in the nutritional composition can range from about 0.1 g/100 kcal to about 1 g/100 kcal. In another embodiment, the amount of GOS in the nutritional composition can range from about 0.2 grams per 100 kilocalories to about 0.5 grams per 100 kilocalories. In other embodiments, the amount of GOS in the nutritional composition may range from about 0.1 mg/100 kcal to about 1.0 mg/100 kcal, or from about 0.1 mg/100 kcal to about 0.5 mg/100 kcal. .

In a special embodiment of this nutritional composition, PDX is administered with GOS. In this embodiment, the PDX:GOS ratio of the PDX and GOS to be administered may be about 9:1 to 1:9. In another embodiment, the PDX:GOS ratio can be from about 5:1 to 1:5. In still another embodiment, the PDX:GOS ratio can be about 1:3 and 3:1. In a particular implementation, the PDX to GOS ratio can be about 5:5. In another particular embodiment, the PDX to GOS ratio can be about 8:2.

In a particular embodiment, the nutritional composition is supplemented by a total amount of at least about 0.2 mg/100 kcal, or about 0.2 mg/100. From kilocalories to about 1.5 mg / 100 kcal GOS and PDX. In some embodiments, the nutritional composition can comprise a total of from about 0.6 to about 0.8 mg/100 kcal of GOS and PDX.

As indicated, the disclosed nutritional composition can comprise a beta -glucan source. Glucans are polysaccharides, in particular polymers of glucose, which are naturally occurring and can be found in the cell walls of bacteria, yeasts, fungi and plants. Beta glucan ( beta -glucan) is itself a distinct subset of glucose polymers consisting of a chain of glucose monomers linked together via beta -type glycosidic linkages to form complex carbohydrates.

The β- 1,3-glucan is a carbohydrate polymer purified from, for example, yeast, mushroom, bacteria, algae or grain. (Stone BA, Clarke AE. Chemistry and Biology of (1-3)-Beta-Glucans. London: Portland Press Ltd; 1993.) The chemical structure of β- 1,3-glucan depends on the β -1, The source of 3-glucan. Furthermore, various physical and chemical parameters such as solubility, primary structure, molecular weight and branching have a role in the biological activity of β- 1,3-glucan (Yadomae T., Structure and biological activities of fungal beta-1,3- glucans.Yakugaku Zasshi.2000; 120:413-431.)

β -1,3- glucan with or without β -1,6- glucose side chain of natural polysaccharide, which can be found in a variety of plants, yeast, fungi and the cell walls of bacteria. β -1,3; 1,6- glucans are those comprising glucose units linked with the (1,3), which has (1,6) connected to the side chain position. β -1,3; 1,6- glucan is a group share common structure (including by linear backbone of glucose units linked β -1,3 bonds of which with β -1,6 linked via extending from the backbone The glucose branch of the heterogeneous glucose polymer. Although this is the basic structure of the currently described beta -glucan class, there may be some variations. For example, certain yeast beta -glucans have other beta (1,3) branching regions extending from the beta (1,6) branch, which further increases the complexity of their individual structures.

The β -glucan derived from baker's yeast ( Saccharomyces cerevisiae ) consists of a chain of D-glucose molecules linked at positions 1 and 3 having a glucose side chain attached at positions 1 and 6. Derived from the yeast beta] - glucans are insoluble in a general linear structure having a glucose unit, the fiber-glucose, β -1,3 backbone having this structure, the length is usually interspersed β 6-8 glucose units of -1,6 side chain. More specifically, the β -glucan derived from baker's yeast is poly-(1,6) -β -D-glucopyranosyl-(1,3) -β -D-glucopyranose.

In addition, β -glucan is well tolerated and does not produce or cause excessive gas, abdominal distension, bloating or diarrhea in pediatric individuals. Adding beta -glucan to a nutritional composition for a pediatric individual, such as an infant formula, growing milk, or other child nutritional product, will improve the individual's immune response by increasing resistance to invading pathogens, thereby maintaining or improving Overall health.

In some embodiments, the amount of beta -glucan in the nutritional composition is between about 3 mg/100 kcal and about 17 mg/100 kcal. In another embodiment, the amount of beta -glucan is between about 6 mg/100 kcal and about 17 mg/100 kcal.

In some embodiments, the nutritional composition can comprise β -1,3; 1,6-glucan. The β- 1,3; 1,6-glucan is derived from baker's yeast. The nutritional composition may comprise whole glucan particles β -glucan, microparticle β -glucan, PGG-glucan (poly-1,6- β -D-glucopyranosyl-1,3- β -D-glucopyranose) or any mixture of them.

The nutritional composition of the present invention may comprise lactoferrin. Lactoferrin is a single-chain polypeptide of about 80 kD and contains 1-4 glucans depending on the species. The 3-D structure of lactoferrin from different species is very similar but not identical. Each lactoferrin contains two homologous lobules, termed N- and C-lobules, which refer to the N-terminal and C-terminal portions of the molecule, respectively. Each leaflet is further composed of two cotyledons or domains forming a fracture in which the ferric ion (Fe3+) is tightly bonded and cooperates with the (hydrogen) anion of carbonic acid. These domains are called N1, N2, C1, and C2, respectively. The N-terminus of lactoferrin has a strong cationic peptide region responsible for some important binding properties. Lactoferrin has a very high isoelectric point (~pI9) and its cationic nature plays a major role in its ability to defend against bacterial, viral and fungal pathogens. There are several cationic amino acid residue clusters in the N-terminal region of lactoferrin that mediate the biological activity of the lactoferrin against a variety of microorganisms.

The lactoferrin used in the present invention can be, for example, isolated from the milk of a non-human animal or made by genetically engineered organisms. In some embodiments, the oral electrolyte solution described herein may comprise non-human lactoferrin, non-human lactoferrin produced by genetically engineered organisms, and/or human milk made from genetically engineered organisms. Ferritin.

Suitable non-human lactoferrin for use in the present invention includes, but It is not limited to those having at least 48% homology to the amino acid sequence of human lactoferrin. For example, the amino acid composition of bovine lactoferrin ("bLF") has about 70% sequence homology to the amino acid composition of human lactoferrin. In some embodiments, the non-human lactoferrin has at least 65% homology to human lactoferrin and, in some embodiments, at least 75% homology. Non-human lactoferrin acceptable for use in the present invention, including, but not limited to, bovine lactoferrin, porcine lactoferrin, equine lactoferrin, buffalo lactoferrin, goat lactoferrin, rat lactoferrin, and camelloferrin .

In some embodiments, the nutritional composition of the invention comprises non-human lactoferrin, such as bLF. bLF is a glycoprotein belonging to the iron transporter or transfer family. It is isolated from cow's milk and bLF is a component of whey in milk. There is a known difference between the amino acid sequence in human lactoferrin and bLF, the glycosylation pattern, and the ability to bind to iron. In addition, multiple and a series of processing steps involved in the separation of bLF from milk can affect the physicochemical properties of the bLF preparation produced. It has been reported that human lactoferrin and bLF also differ in their ability to bind to the lactoferrin receptor found in the human small intestine.

Although not wishing to be bound by this theory or any other theory, it is believed that bLF isolated from whole milk has the original combined lipopolysaccharide (LPS) which is less than those derived from whole milk powder. . In addition, it is believed that bLF with a low somatic cell count has less original binding LPS. The bLF with fewer original binding LPSs has more available binding sites on the surface. This is believed to help bind bLF to the proper location and disrupt the infection process.

bLF suitable for use in the present invention can be made by any method known in the art. Okonogi et al. disclose a method for making high purity bovine lactoferrin, for example, in U.S. Patent No. 4,791,193, the disclosure of which is incorporated herein by reference. In general, the disclosed process includes three steps. The raw milk material is first contacted with a weakly acidic cation exchanger to absorb lactoferrin, and a second step is performed in which cleaning is performed to remove the unabsorbed material. This is followed by a desorption step in which lactoferrin is removed to produce purified bovine lactoferrin. Other methods may include the steps described in U.S. Patent Nos. 7,368, 141, 5, 849, 885, 5, 919, 913, and 5, 861, 491, the entire disclosures of each of which are incorporated herein by reference.

The lactoferrin used in certain embodiments may be any lactoferrin isolated from whole milk and/or having a low somatic cell count, wherein "low somatic cell number" refers to a somatic cell count of less than 20 Million cells / ml. For example, suitable lactoferrin can be obtained from Tatua Cooperative Dairy Co., Ltd. of Morrinsville, New Zealand, Friesland Campina Domo of Amersfoort, The Netherlands, or Fonterra Cooperative Group Ltd. of Auckland, New Zealand.

Surprisingly, the lactoferrin contained in the present invention, even when exposed to low pH values that are expected to disrupt or severely limit the stability or activity of human lactoferrin (i.e., below about 7, or even as low as about 4.6) The relevant activity can be maintained at or below the elevated temperature and/or at elevated temperatures (i.e., above about 65 ° C and up to about 120 ° C). These low pH and/or high temperatures are expected during certain treatment regimes for the type of nutrient composition described herein. Conditions (such as Pasteur's sterilization method). Thus, even after treatment, lactoferrin has bactericidal activity against adverse bacterial pathogens found in the human gut. In some embodiments, the nutritional composition can comprise an amount of lactoferrin from about 25 mg/100 ml to about 150 mg/100 ml. In other embodiments, the lactoferrin is present in an amount from about 60 mg/100 ml to about 120 mg/100 ml. In still other embodiments, the lactoferrin is present in an amount from about 85 mg/100 ml to about 110 mg/100 ml.

The nutritional composition of the present invention may also contain a source of long chain polyunsaturated fatty acids ("LCPUFA"). Suitable LCPUFAs include, but are not limited to, DHA, eicosapentaenoic acid ("EPA"), ARA, linoleic acid (18:2 n-6) in the n-6 pathway, gamma -linolenic acid (18:3) N-6), dihomo-γ-linolenic acid (20:3 n-6), α-linolenic acid (18:3 n-3), stearidonic acid (18:4 n-3), two Decaenoic acid (20:4 n-3), eicosapentaenoic acid (20:5 n-3) and docosapentaenoic acid (22:6 n-3).

Advantageously, the amount of LCPUFA in the nutritional composition is at least about 5 mg/100 kcal and may vary from about 5 mg/100 kcal to about 100 mg/100 kcal, more preferably about 10 MG/100 kcal to approx. 50 mg/100 kcal.

Sources of LCPUFA include dairy products like eggs and butter; marine oils such as salmon, mackerel, sardines, mackerel and many other fish; certain animal fats, lard, tallow and microbial oils (such as fungi and algae oils), or Any other LCPUFA from which it can be used and used for nutritional composition Source (enhanced or unreinforced). The LCPUFA can be part of a complex mixture that can be obtained by a separation technique known in the art that enriches the derivatives or precursors of LCPUFA and LCPUFA in such mixtures.

The LCPUFA can be provided in the nutritional composition in the form of a free fatty acid ester; a monoglyceride, a diglyceride, and a triglyceride; a phosphoglyceride, including lecithin; and/or a mixture thereof. Furthermore, the LCPUFA can be provided in the nutritional composition in the form of a phospholipid, especially a phospholipid choline.

In one embodiment, particularly if the nutritional composition is an infant formula, the nutritional composition is supplemented by both DHA and ARA. In this embodiment, the weight ratio of the ARA:DHA can be from about 1:3 to about 9:1. In a particular embodiment, the ratio of ARA:DHA is from about 1:2 to about 4:1.

Advantageously, in some embodiments, the DHA of the nutritional composition is present in an amount of at least about 17 mg/100 kcal and may range from about 5 mg/100 kcal to about 75 mg/100 kcal. Change between. In some embodiments, the DHA is present in an amount from about 10 mg/100 kcal to about 50 mg/100 kcal.

The nutritional composition can be supplemented with an oil containing DHA and/or ARA using standard techniques known in the art. For example, DHA and ARA can be added to the composition by substituting an equivalent amount of an oil typically present in the composition, such as high oleic sunflower oil. Another example is a total lipid that is typically present in a composition that does not contain DHA and ARA via substitution. The remainder of the fat blend is used to add the oil containing DHA and ARA to the composition.

If DHA and/or ARA are used, the source of the DHA and/or ARA can be any source known in the art, such as marine oil, fish oil, single cell oil, egg yolk lipids, and brain lipids. In some embodiments, the DHA and ARA are derived from single cell Martek oil, DHASCO®, and ARASCO® or a variety of variations thereof. The DHA and ARA may be in a natural form with the proviso that the remainder of the LCPUFA source does not cause any substantial deleterious effects on the infant. Alternatively, purified forms of DHA and ARA can be used.

In one embodiment, the source of the DHA and ARA is a single cell oil as taught in U.S. Patent Nos. 5,374,567, 5, 550, 156, and 5, 397, 591, the disclosures of each of which are incorporated herein by reference. However, the invention is not limited to this type of oil.

In addition, some embodiments of the nutritional composition can mimic certain characteristics of human breast milk. However, in order to meet the specific nutritional needs of some individuals, the nutritional composition may contain more nutrients than human milk. For example, the nutritional composition may comprise more DHA than human breast milk. The increased DHA content of the nutritional composition can compensate for the nutritional deficiencies of the existing DHA.

In some embodiments, the nutritional compositions of the invention described herein may also comprise an effective amount of iron. The iron may be in the form of iron encapsulated in a capsule, such as ferrous fumarate encapsulated in a capsule or ferrous sulfate encapsulated in a capsule, or in the form of a less active iron, such as pyrophosphate Iron or iron orthophosphate.

In some embodiments, the nutritional composition of the present invention further comprises lutein. Lutein as used herein, unless otherwise specifically indicated, refers to one or more of the following groups: free lutein, lutein ester, lutein salt or others having associations as described herein or otherwise indicated Structure of lutein derivatives. In some embodiments, the lutein is present in an amount from about 0.343 mg/100 kcal to about 6.0 mg/100 kcal. In still other embodiments, the lutein is present in an amount from about 1.0 mg/100 kcal to about 4.0 mg/100 kcal.

Sources of lutein useful in the present invention include, but are not limited to, carotenoid-rich plant sources including, but not limited to, kiwi, grape, citrus, tomato, watermelon, papaya, and other red fruits, or dark green vegetables, Such as kale, spinach, green radish, kale, radish lettuce, broccoli, zucchini, peas and brussels sprouts, spinach and carrots. In addition, sources of lutein include other plants and any other source from which lutein can be obtained and used in nutritional compositions (enhanced or unfortified). The lutein can be part of a complex mixture which can be obtained by techniques known in the art for enriching the derivatives or precursors of lutein and lutein in such mixtures.

Lutein for use in the present invention includes any known natural or synthetic source for oral nutrition, including infant formula, or other acceptable source. The lutein source may be provided as an individual component or in combination with other substances or sources, including, for example, a multivitamin premix, a mixed carotenoid premix, a pure lutein source, and an infant formula. The source of the inherent lutein component. The lutein concentration and ratio as described herein can be calculated based on both the added and intrinsic lutein source. In one embodiment, the nutritional composition is an infant formula comprising at least about 10%, 25%, more preferably from about 50% to about 95% by weight of the total lutein. . In other embodiments, the nutritional composition is an infant formula, preferably comprising at least about 85% (by weight of total lutein) of intrinsic lutein.

In certain embodiments, the nutritional composition can comprise zeaxanthin. In some embodiments, the zeaxanthin may be present in an amount from about 0.143 mg/100 kcal to about 4.0 mg/100 kcal. In other embodiments, the zeaxanthin may be present in an amount from about 0.50 mg/100 kcal to about 3.0 mg/100 kcal. In still other embodiments, the zeaxanthin may be present in an amount from about 1.5 mg/100 kcal to about 2.5 mg/100 kcal. Zeaxanthin suitable for inclusion in the nutritional composition includes, but is not limited to, meso-zeaxanthin (3R, 3'S) and other stereoisomers such as (3R, 3R') and (3S, 3'S) . In some embodiments, the nutritional composition can comprise lutein and zeaxanthin. The ratio of lutein to zeaxanthin may range from 95:5 to 5:95.

Cholesterol may also be present in the nutritional composition of the present invention. In some embodiments, the cholesterol is present in an amount from about 1 mg/100 kcal to about 100 mg/100 kcal. In other embodiments, the cholesterol in the nutritional composition is present in an amount from about 5 mg/100 kcal to about 25 mg/100 kcal. In other embodiments, the cholesterol is present in an amount from about 15 mg/100 kcal to about 40 mg/100 kcal. And other implementations The cholesterol in the nutritional composition is present in an amount from about 50 mg/100 kcal to about 75 mg/100 kcal.

In one embodiment, the source of cholesterol for use in the present invention includes, but is not limited to, milk, other dairy products, eggs, meat, tallow, poultry, fish, shellfish, and any other cholesterol from which it can be obtained and used in nutritional compositions. Source (enhanced or unreinforced). Sources of cholesterol also include precursors such as squalene, lanosterol, dimethyl sterol, methosterol, 7-enecholylol (lathosterol) and 24-dehydrocholesterol (desmosterol). Cholesterol can be part of a complex mixture that can be obtained by techniques known in the art for enriching the cholesterol or cholesterol derivatives or precursors in such mixtures.

In some embodiments, the nutritional composition of the invention comprises resveratrol. Resveratrol can be present in an amount from about 5 mg/100 kcal to about 120 mg/100 kcal. In other embodiments, resveratrol can be present in an amount from about 9 mg/100 kcal to about 60 mg/100 kcal.

Sources of resveratrol for use in the present invention include, but are not limited to, plant-derived extracts including, but not limited to, apple extract and grape seed extract. Further, non-limiting examples of plants rich in resveratrol suitable for use in the nutritional composition of the present invention include: berries (arabberry, grape, mulberry, blueberry, lingonberry, blackcurrant, wild cherry) Raspberry, blackberry, raspberry, cherry, red currant, cranberry, crowberry, cloudberry, wortleberry, rowanberry, purple corn, purple potato, purple carrot, red sweet potato, Red cabbage, eggplant. Chalk Resin can be part of a complex mixture which can be obtained by techniques known in the art for enriching the derivatives or precursors of resveratrol and resveratrol in such mixtures.

Without wishing to be bound by any particular theory, the combination of DHA, lutein, resveratrol and/or cholesterol and neural components may have additive and/or synergistic health benefits to the brain and nervous system. In certain embodiments, the nutritional composition comprising DHA, lutein, cholesterol, milk fat, and/or resveratrol and a mixture thereof can act synergistically with the nutrients of the neural component to promote neural cell tissue The nerves are new.

The nutritional compositions of the present invention can be provided in any form known in the art, such as powders, gels, suspensions, pastes, solids, liquids, liquid concentrates, reconstitutable milk powder substitutes or ready-to-use products. In certain embodiments, the nutritional composition can comprise a nutritional supplement, a child nutritional product, an infant formula, a human milk fortifier, a growing milk, or any other nutritional composition designed for use in an infant or pediatric individual. The nutritional composition of the present invention includes, for example, oral ingestion, substances which promote health, including, for example, foods, beverages, tablets, capsules, and powders. Furthermore, the nutritional composition of the present invention can be standardized to a specific calorie content, which may be provided in the form of a ready-to-use product or may be provided in a concentrated form. In some embodiments, the nutritional composition is in the form of a powder having a particle size in the range of 5 microns to 1500 microns, more preferably in the range of 10 microns to 300 microns.

If the nutritional composition is in the form of an immediate use product, the nutritional composition may have a permeation weight molar concentration of between about 100 and about 1100. The milliosmoles are between the molar concentration/kg of water, more typically from about 200 to about 700 milliosmoles per kilogram of water per kilogram of water.

In certain embodiments, the nutritional composition is hypoallergenic. In other embodiments, the nutritional composition is a Kosher-compliant food (or kosher) and/or a Muslim-compliant food (halal). In still further embodiments, the nutritional composition contains components that are not genetically engineered. In one embodiment, the nutritional blend is free of sucrose. The nutritional composition may also be free of lactose. In other embodiments, the nutritional composition does not contain any medium chain triglyceride oil. In some embodiments, no carrageenan is present in the composition. In other embodiments, the nutritional composition does not contain all of the gum.

The nutritional composition of the present invention is not limited to compositions comprising the nutrients specifically listed herein. Any nutrient can be delivered as part of the composition to meet the nutritional needs of the individual and/or to optimize the nutritional status of the individual.

Further, in some embodiments, the nutritional composition is nutritionally intact, containing suitable types and amounts of lipids, carbohydrates, proteins, vitamins, and minerals to be the sole source of nutrition for the individual. Specifically, the nutritional composition optionally comprises any number of proteins, peptides, amino acids, fatty acids, probiotics and/or their metabolic by-products, prebiotics, carbohydrates, and any nutrients available to the individual. And other nutrients or other compounds that are physiologically beneficial. Further, the nutritional composition of the present invention may comprise a fragrance, a flavor enhancer, a sweetener, a pigment, a vitamin, a mineral, a therapeutic ingredient, a functional food ingredient, a food ingredient, and a Work ingredients or a combination of them.

The nutritional composition of the present invention can be standardized to a specific calorie content, which can be provided in the form of a product to be used immediately, or it can be provided in a concentrated form.

In some embodiments, the nutritional composition of the invention is a growing milk. Growing milk is a fortified milk-based drink intended for children over 1 year old (usually 1-3 years old, 4-6 years old, or 1-6 years old). It is not a medical food and does not want to be used as a meal replacement or supplement to address special nutritional deficiencies. Conversely, the design of the growing milk is intended as a supplement to a variety of diets to provide children with a continuous daily intake of all essential vitamins and minerals, large amounts of nutrients plus additional functional dietary ingredients (such as those with claims) Additional protection for non-essential nutrients that promote health traits.

The exact composition of the nutritional composition according to the present invention may vary from market to market based on local regulations and dietary intake information for the desired population. In some embodiments, the nutritional composition according to the present invention is derived from a milk protein source (such as whole fat or skimmed milk), plus sugars and sweeteners added to achieve the desired organoleptic properties, and added Made up of vitamins and minerals. The fat composition is usually derived from a milk raw material. The target of total protein can be set to match the value of human milk, milk or lower. The goal of total carbohydrates is usually set to provide as little added sugar as possible (such as sucrose or fructose) to achieve an acceptable taste. Usually, the amount of vitamin A, calcium and vitamin D added is in line with the nutritional contribution of regional milk. In addition, in some embodiments, the amount of vitamins and minerals added may be One serving provides approximately 20% dietary reference intake (DRI) or 20% daily demand (DV). Furthermore, the nutritional values of different markets may vary depending on the nutritional needs, raw material contributions and regional regulations of the identified desired population.

One or more sufficient amounts of vitamins and/or minerals may also be added to the nutritional composition to provide the individual's daily nutritional needs. One of ordinary skill in the art will appreciate that the demand for vitamins and minerals will vary depending on, for example, the age of the child. For example, infants' vitamin and mineral needs may differ from children between the ages of 1 and 13. Thus, this embodiment does not intend to limit the nutritional composition to a particular age group, but rather to provide an acceptable range of vitamin and mineral ingredients.

The nutritional composition may optionally include, but is not limited to, one or more of the following vitamins or derivatives thereof: vitamin B ₁ (thiamine, thiamine pyrophosphate, TPP, thiamine triphosphate, TTP, hydrochloric acid) Thiamine, thiamine monophosphate), vitamin B ₂ (riboflavin, flavin mononucleotide, FMN, flavin adenine dinucleotide, FAD, lacoflavin, egg yolk Ovoflavin), vitamin B ₃ (niacin, nicotinic acid, nicotinamide, niacinamide, nicotinamide adenine dinucleotide, NAD, nicotinic acid mononucleotide, NicMN, pyridine-3-carboxylic acid), vitamin B ₃ precursor tryptophan, vitamin B ₆ (pyridoxine, pyridoxal, pyridoxamine, pyridoxine hydrochloride) Pantothenic acid (pantothenate, panthenol), folate (folic acid, folacin, pteroylglutamic acid), vitamin B ₁₂ (cobalamin, mecobalamin, deoxyadenosine cobalt Amine, cyanocobalamin, hydroxocobalamin, adenosine cobalamin), biotin, vitamin C (ascorbic acid), vitamin A (retinol, retinyl acetate, retinyl palmitate , retinyl esters with other long-chain fatty acids, retinal, retinoic acid, retinol esters, vitamin D (calciferol, cholecalciferol, vitamin D ₃ , 1,25-dihydroxyvitamin D) , vitamin E (α - tocopherol acetate, [alpha] - tocopheryl succinate, [alpha] - tocopherol, nicotinic acid, [alpha] - tocopherol, [alpha] - tocopherol), vitamin K (vitamin K _1, phylloquinone, naphthoquinone, Vitamin K ₂ , menaquinone-7, vitamin K ₃ , menaquinone-4, menadione, menaquinone-8, menaquinone-8H, menaquinone-9, carbaryl醌-9H, menaquinone-10, menaquinone-11, menaquinone-12, menaquinone-13), choline, inositol, beta -carotene and any combination thereof.

In embodiments in which a child nutritional product, such as a growing milk, is provided, the composition may optionally include, but is not limited to, one or more of the following minerals or derivatives thereof: boron, calcium, calcium acetate, gluconic acid Calcium, calcium chloride, calcium lactate, calcium phosphate, calcium sulfate, chloride, chromium, chromium chloride, chromium picolinate, copper, copper sulfate, copper gluconate, cupric sulfate, fluoride , iron, carbonyl iron, ferric iron, ferrous fumarate, iron orthophosphate, ground iron, polysaccharide iron, iodide, iodine, magnesium, magnesium carbonate, magnesium hydroxide, magnesium oxide, magnesium stearate, magnesium sulfate , manganese, molybdenum, phosphorus, potassium, potassium phosphate, potassium iodide, potassium chloride, potassium acetate, selenium, sulfur, sodium, sodium docusate, sodium chloride, sodium selenate, sodium molybdate, zinc, zinc oxide, sulfuric acid Zinc and a mixture of them. Non-limiting exemplary derivatives of mineral compounds include salts of any mineral compound, Base salts, esters and chelates.

Minerals may be added in the form of salts such as calcium phosphate, calcium glycerate phosphate, sodium citrate, potassium chloride, potassium phosphate, magnesium phosphate, ferrous sulfate, zinc sulfate, copper sulfate, manganese sulfate and sodium selenite. Growing milk or other children's nutritional composition. Additional vitamins and minerals may be added as known in the art.

In one embodiment, the amount of vitamins A, C, and E, zinc, iron, iodine, selenium, and choline that may be included in the nutritional composition of each child is about the maximum dietary recommendation for any given country. 10 to about 50%, or about 10 to about 50% of the average dietary recommendation for the national group. In another embodiment, the amount of vitamin B available to each child's nutritional composition is about 10 to 30% of the maximum dietary recommendation for any given country, or the average dietary recommendation for the national group. About 10 to 30%. In yet another embodiment, the amount of vitamin D, calcium, magnesium, phosphorus, and potassium in the nutritional product of the child can be equivalent to the average amount found in the dairy product. In other embodiments, the amount of other nutrients present in the nutritional composition of each child may be about 20% of the maximum dietary recommendation for any given country, or about the average dietary recommendation for the national group. 20%.

The nutritional composition of the present invention may optionally include one or more of the following flavoring agents including, but not limited to, flavored extracts, volatile oils, cocoa powder or chocolate flavorings, peanut butter flavorings, biscuit chips, vanilla or any commercially available product. Flavoring agent. Examples of useful flavoring agents include, but are not limited to, pure fennel extract, imitation banana extract, imitation cherry extract, chocolate Extract, pure lemon extract, pure orange extract, pure mint extract, honey, imitation pineapple extract, imitation rum extract, imitation strawberry extract, grape or grape seed extract, apple extract, more Orange extract or vanilla extract; or volatile oils such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, cinnamon oil, clove oil or peppermint oil; peanut butter, chocolate flavoring A mixture of vanilla biscuit chips, butterscotch, toffee and a mixture of them. The amount of flavoring can vary widely depending on the flavoring agent used. The type and amount of flavoring agent can be selected as known to those skilled in the art.

The nutritional composition of the present invention may optionally include one or more emulsifiers which may be added thereto to stabilize the final product. Examples of suitable emulsifiers include, but are not limited to, lecithin (e.g., from eggs, or soy, or any other plant and animal source), alpha -lactalbumin and/or monoglycerides and diglycerides, and the like. a mixture. Other emulsifiers will be apparent to those skilled in the art, and the selection of a suitable emulsifier will depend, in part, on the blend and the final product.

The nutritional composition of the present invention may optionally comprise one or more preservatives which may also be added thereto to extend the shelf life of the product. Suitable preservatives include, but are not limited to, potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate, calcium EDTA disodium, and mixtures thereof.

The nutritional composition of the present invention may optionally include one or more stabilizers. Suitable stabilizers for practicing the nutritional compositions of the present invention include, but are not limited to, gum arabic, ghatti gum, karaya gum, tragacanth, agar, red algae gum. (furcellaran), guar gum, gellan gum, locust bean gum, pectin, low methoxy pectin, gelatin, microcrystalline cellulose, CMC (carboxymethyl cellulose sodium), methyl fiber , hydroxypropyl methylcellulose, hydroxypropylcellulose, DATEM (diglycerides and diglycerides, diterpene tartrate), dextran, carrageenan, CITREM and their mixture.

The invention further provides methods for promoting the health of the brain and nervous system by providing a nutritional composition comprising the neural components described herein to a subject individual. Without being bound by any particular theory, it is believed that providing a nutritional composition comprising a neural component will support neuronal regeneration.

In some embodiments, the target individual can be a pediatric individual. Furthermore, in one embodiment, the nutritional composition provided to the pediatric individual can be an infant formula. The neural components added to the infant formula can be selected from a particular source, and their concentrations can be adjusted to maximize health benefits. In another embodiment of the method, the nutritional composition comprising the neural component for the pediatric individual is a growing milk.

In another embodiment, the nutritional composition can be provided to a subject who is already suffering, is currently suffering, or is likely to have brain and/or nervous system damage or disease in the future. For example, in one embodiment, the nutritional composition can be provided to a subject individual who has been diagnosed with Alzheimer's disease or another degenerative brain disorder.

In yet another embodiment, the neurotrophic nutritional composition can be provided to any target individual to promote neuroprotection. again In other embodiments, the method is directed to promoting neonatal regeneration by providing a nutritional composition comprising a neural component to a pregnant or lactating mother. In addition, the nutritional composition comprising the neural components described herein provides a supplemental source of neurotrophic nutrition to the target individual.

The methods of the invention for providing the nutritional compositions described herein can be administered to the target individual of these methods with increasing neurotrophic and health benefits. The method content for providing the nutritional composition described herein for a particular neurological disease or for administration to a particular target individual is not limited, and conversely, when suitable for administration of the nutritional composition described herein, it may further serve as Example.

Example

The examples provided are intended to illustrate the neuronal effects of nutrients contained in the neural components of the nutritional compositions described herein. Briefly, the examples provided describe the neurogenic capacity of scutellarin and baicalein for hADSC. These examples should not be construed as limiting the nutritional composition of the present invention, but rather as an illustration. The specification and examples of the invention are intended to be illustrative only, and the scope and spirit of the invention is indicated by the scope of the claims. The steps described in U.S. Patent Application Serial No. 13/408,485, issued toK., et al. in.

Example 1

This example describes the neurogenic effect of guarannisin on hADSC compared to hADSC cultured in the presence of DHA (positive control group) and no oudunin and DHA (negative control group). Panaxanthin (Cat. No. 60010) was purchased from Sigma-Aldrich and diluted to 95 mg/ml in 95% ethanol to produce a clear pale yellow viscous solution which was then stored in - 20 ° C.

Since California Carlsbad, Invitrogen® company (also referred Life Technology Inc.) later hADSC 100 mm culture dishes and grown to near confluence monolayer, the culture dishes containing the Complete MesenPro RS ^TM growth medium with supplements and L- Maintenance medium consisting of glutamine (also from Invitrogen®). The process of culturing, passage and inoculation of hADSC is described below. Then, the cells were removed and re-seeded at a density of 0.5-1 x 10 ⁴ cells/ml on a 24-well plate with poly-L-ornithine and bovine plasma fibronectin coating. The medium is the same as the above maintenance medium. Three days after the inoculation, the medium was changed to a neuronal differentiation medium.

Subculture of hADSC was performed when cell culture reached confluence. To pass hADSC passage, the following procedure was used: i) aspiration of Complete MesenPRO RS medium from the cells; ii) rinsing the surface area of the cell layer with Dulbecco's phosphate buffered saline (DPBS) buffer, via addition of DPBS On the side of the container opposite the adhered cell layer and shaking the container back and forth several times; iii) aspirating and discarding DPBS; iv) adding a sufficient volume of pre-warmed phenol red-free trypsin-EDTA solution to cover the cell layer, To exfoliate the cells; v) incubate at 37 ° C for about 7 minutes; vi) observe the cells under the microscope to determine if additional incubation is required; vii) add 3 ml of maintenance medium to the plate, mix the cell suspension, The suspension was added to a 15 ml centrifuge tube and centrifuged at 210 g for 5 minutes; viii) the total number of cells and the percentage of survival were determined using a hemocytometer; ix) Complete MesenPRO RS medium was added to each container so that the final culture volume was cm 0.2 to 0.5 ml; X) appropriate volume of cells was added to each vessel and incubated cells were seeded at 37 ℃, 5% CO ₂ and 90% humidity; and xi) three or four after seeding Complete medium was removed and an equal volume of medium was replaced Complete MesenPRO RS.

The passaged hADSC was inoculated to the fresh culture plate, and the surface of the culture dish was washed three times with a sterile DPBS solution, and then rinsed with sterile water several times to prepare a culture dish coating. The first layer of the coating was poly-L-ornithine prepared by the addition of from about 15 to about 20 micrograms per milliliter of poly-L-ornithine and incubated at 37 ° C for one hour. The plates were washed three times with DPBS for 15 minutes each time. The second layer of the coating is bovine plasma fibronectin. The fibronectin stock solution was diluted 1000-fold in DPBS and 500 microliters was added to each well. The plate was allowed to stand at room temperature for one hour. The last wash was performed with 500 μl of DPBS per well and the plate was used immediately.

Then, the cells were removed and re-seeded at a density of 2×10 ⁴ cells/ml (1×10 ⁴ cells/well) on a 24-well plate containing poly-L-ornithine and bovine plasma fibronectin coating. .

3 days after inoculation and triggering; the medium was changed to a serum-free neuronal differentiation medium. The plates were removed from the incubator and all procedures were performed under a laminar flow hood. The medium was completely removed from each well. Then, hADSC was washed with about 1 ml of sterile DPBS solution per well to remove excess medium. DPBS was removed and the solution was neuronal differentiation medium to serum-free replacement of the neuronal differentiation medium containing Neurobasal ^TM Medium from L- bran with an amine of the acquired company Amides Invitrogen®, 20 ng / ml of bFGF of 20 mM Micrograms per milliliter of EGF and N2 supplements.

Various concentrations of luccain in the range of 5 to 20 μg/ml were added to individual wells to be individually tested, and under a phase contrast microscope and a positive control group (20 μM DHA) at 24 hours, 48 hours, and 96 hours. ) and the negative control group (untreated) compared. This experiment was repeated three times. Panels 1A-C depict phase contrast microscopy images of a negative control group, a positive control group, and cells treated with 20 micrograms/ml of luccain. In general, if the hADSC exhibits a neuronal morphology, this result is due to the neurogenic capacity of the added neural component (in this example, luciferin).

The hADSC treated with the negative control group maintained its large, flat, and committed cell morphology, indicating no significant neurodevelopment (Fig. 1A). In the presence of 20 μM DHA, some of the hADSCs changed dramatically into neuronal cell morphology (Fig. 1B). The cytoplasm shrinks and the neurites begin to protrude. As the cell body shrinks and the reflection from the microscope light increases, halo can be observed in cells with neuronal differentiation. At 5 to 20 micro A large proportion of cells in the presence of gram/ml of luciferin are neurogenic, as seen in Figure 1C (which shows hADSC treated with 10 μg/ml of luciferin).

In order to investigate the synergy between fulvicin and other brain nutrients, hADSC was treated with fulvicin and DHA. Compared with 20 μg/ml of guaranurin alone or 20 μM of DHA, the treatment with 1.5 μg/ml of luciferin and 6 μM of DHA showed a strong neurogenic effect, thus demonstrating synergy in vitro (p. 1D map).

Example 2

This example describes the neurogenic effect of baicalein on hADSC compared to hADSC cultured in the presence of DHA (positive control group) and no DHA and fulnosine (negative control group). Baicalein (Cat. No. F4043) was purchased from Sigma-Aldrich and diluted to 95 mg/ml in 95% ethanol to produce a clear pale yellow viscous solution which was then stored at -20 °C. . The hADSCs were cultured, passaged, inoculated and treated with the negative control, DHA, baicalein or baicalein and DHA via the same procedure outlined in Example 1.

The hADSC treated with the negative control group maintained its large, flat, and developed morphology, indicating no significant neurological regeneration (Fig. 2A). In the presence of 20 μM DHA, some of the hADSCs changed dramatically into neuronal cell morphology (Fig. 1B). Cytoplasmic contraction and neurites Start to stand out. As the cell body shrinks and the reflection from the microscope light increases, halo can be observed in cells with neuronal differentiation. A large proportion of cells undergo neuroneogenesis in the presence of 5 to 50 micrograms per milliliter of baicalein, as seen in Figure 1C, which shows hADSC treated with 25 micrograms per milliliter of baicalein.

In order to investigate the synergy between baicalein and other brain nutrients, hADSC was treated with baicalein and DHA. Compared with 25 μg/ml of guaranurin alone or 20 μM of DHA, the treatment with 1.5 μg/ml of luciferin and 6 μM of DHA showed a strong neurogenic effect, thus demonstrating synergy in vitro (p. 1D map).

Example 3

Table 1 provides exemplary embodiments of the nutritional composition according to the present invention and describes the amount of each component to be included per 100 kcal. The composition contains a nerve component comprising guaranurin, baicalein or both.

All references cited in this patent specification, including but not limited to all papers, publications, patents, patent applications, The contents of presentations, texts, reports, manuscripts, manuals, books, web posts, magazine articles, journals, etc. are hereby incorporated by reference. The discussion of the references herein is for the purpose of summarizing the assertions made by the authors, and does not admit that any reference constitutes prior art. The Applicant reserves the right to challenge the accuracy and pertinence of the cited reference materials.

Although the embodiments of the present invention have been described using specific terms, devices, and methods, such description is for illustrative purposes only. The text used is a description, not a limiting text. It will be appreciated that various changes and modifications can be made by those skilled in the art without departing from the spirit and scope of the invention. In addition, it should be understood that the various aspects of the embodiments may be interchanged in whole or in part. For example, while other methods for producing commercially available sterile liquid nutritional supplements made according to those methods have been exemplified, other uses are contemplated. Therefore, the spirit and scope of the appended claims should not be limited to the description of the versions contained therein.

Claims (20)

A nutritional composition comprising: (i) a source of carbohydrates; (ii) a source of protein; (iii) a source of fat; and (iv) a neuronal component comprising guarannisin, baicalein or a combination thereof. The nutritional composition of claim 1, wherein the scutellarin is present in an amount of from about 0.1 mg/100 kcal to about 5 mg/100 kcal. The nutritional composition of claim 1, wherein the baicalein is present in an amount of from about 0.15 mg/100 kcal to about 73 mg/100 kcal. The nutritional composition of claim 1, further comprising a long-chain polyunsaturated fatty acid. The nutritional composition of claim 4, wherein the long chain polyunsaturated fatty acid comprises docosahexaenoic acid, arachidonic acid or a mixture thereof. The nutritional composition of claim 1, further comprising a prebiotic. The composition of claim 6, wherein the prebiotic comprises polydextrose and galactooligosaccharide. The composition of claim 1, further comprising a nutrient selected from the group consisting of probiotics, iron source, β- Glucan and combinations thereof. The composition of claim 1, further comprising a nutrient selected from the group consisting of lutein, cholesterol, resveratrol, and mixtures thereof. The nutritional composition of claim 1, wherein the nutritional composition is an infant formula. A nutritional composition comprising: (i) from about 6 grams to about 22 grams of carbohydrate source per 100 kcal; (ii) from about 1 gram to about 7 grams of protein source; (iii) from about 1.3 grams to about 7.2 grams of fat And (iv) a neural component comprising: (a) from about 0.1 mg to about 5 mg of luciferin; (b) from about 3 mg to about 200 mg of baicalein; or (c) (a) and a mixture of (b). The nutritional composition of claim 11, which further comprises from about 9.60 x 10 ⁵ cfu to about 3.80 x 10 ⁸ cfu of probiotic per 100 kcal. The nutritional composition of claim 11 further comprising from about 0.3 grams to about 1.2 grams of prebiotic per 100 kcal. The nutritional composition of claim 11, wherein the nutritional composition further comprises from about 4 mg to about 50 mg of docosahexaenoic acid per 100 kcal. A method for promoting the health of the brain and nervous system, comprising: The target individual is provided with a nutritive composition comprising a carbohydrate source, a protein source, a fat source, and a nerve component, wherein the neural component is a guaranurin, baicalein or a mixture thereof. The method of claim 15, wherein the target individual is a pediatric individual. The method of claim 16, wherein the nutritional composition is an infant formula. The method of claim 16, wherein the nutritional composition further comprises a long chain polyunsaturated fatty acid. The method of claim 18, wherein the long chain polyunsaturated fatty acid is docosahexaenoic acid, arachidonic acid or a combination thereof. The method of claim 16, wherein the nutritional composition further comprises at least one nutrient selected from the group consisting of probiotics, prebiotics, beta -glucan, and iron sources.