HK1183769A - Early programming of brain function through soy protein feeding - Google Patents

Description

Early brain function planning by feeding soy protein

Background of the disclosure

The present disclosure relates to methods for improving memory and/or cognition in an infant comprising administering soy protein to the mother of the infant during pregnancy and optionally during breastfeeding. The post-partum infant may be administered soy protein directly via the nutritional formula comprising soy protein. Also disclosed are compositions comprising soy protein that can be used in the method.

The advantages of including soy protein in the diet are recognized. For example, various studies have suggested that soy protein may play a role in the prevention of menopausal symptoms, osteoporosis, certain types of cancer, and heart disease. It has also been suggested that soy protein may help reduce the level of Low Density Lipoprotein (LDL) cholesterol.

Soy-based infant formulas are also known and available from many commercial sources. These soy-based formulas are especially prepared for infants with feeding problems such as dysphoria (fullness), flatulence (gas) and spit-up (spit-up), and are also used for infants whose parents choose non-milk-based formulas as the first feeding or as a supplement to breast feeding. These soy-based formulas are particularly helpful for those infants who have allergies or sensitivities to milk proteins and those infants who have conditions where lactose from cow's milk should be avoided.

It has now surprisingly been found that an improvement in memory and/or cognition in infants can be achieved by administering soy protein during early brain development. In particular, soy protein may be administered to the mother of the infant during pregnancy and breastfeeding, as well as to the infant after delivery, for example by administering to the infant an infant comprising soy protein and/or a nutritional formula as an alternative or in addition to breastfeeding. By administering soy protein to an infant during early brain development, memory and/or cognition in the infant is improved.

Summary of the disclosure

The present disclosure relates generally to methods of improving cognition in infants. One method includes administering soy protein to a pregnant female and administering soy protein to a female during breastfeeding of an infant. Another method comprises administering soy protein to a pregnant female and administering soy protein directly to the infant after delivery.

In one embodiment, the present disclosure relates to a method of improving cognition in an infant. The method comprises administering soy protein to a pregnant female and administering soy protein to a female during breastfeeding.

In another embodiment, the present disclosure relates to a method of improving cognition in an infant. The method comprises administering soy protein to a pregnant female and administering soy protein to the infant after delivery.

It has been unexpectedly found that by administering soy protein to an infant and/or to the infant's mother during early brain development, an improvement in memory and/or cognition in the infant can be achieved. In particular, soy protein may be administered to the mother of the infant during pregnancy (i.e. pregnancy) and breastfeeding, and may also be administered directly to the infant after delivery, for example by administering to the infant an infant and/or nutritional formula comprising soy protein as an alternative or in addition to breastfeeding. After delivery, soy protein may be administered to the infant until the infant reaches at least about 12 months of age, or until the infant reaches about 1 to about 5 years of age.

Brief Description of Drawings

Fig. 1 is a graph showing the mean (± SEM) of the arrival platform latencies (seconds) for group 1 and group 2 rats in six training blocks (training blocks) in the Morris hidden platform task (Morris hidden platform task), as discussed in example 7.

Figure 2 is a graph showing the mean (± SEM) swim speed of group 1 and group 2 rats in six training plates in the muris hidden platform task, as discussed in example 7.

Figure 3 is a graph showing the mean (± SEM) pathlength of group 1 and group 2 rats in six training plates in the morris hidden platform task, as discussed in example 7.

Figure 4 is a graph showing the mean (± SEM) time that group 1 and group 2 rats spent in each quadrant of the pool during the exploratory trial 24 hours after morris hidden platform task training, as discussed in example 7.

Figure 5 is a graph showing the mean (± SEM) first entry latency of group 1 and group 2 rats in the target quadrant of the pool during the exploratory trial 24 hours after morris hidden platform task training as discussed in example 7.

Figure 6 is a graph showing the mean (± SEM) time spent by group 1 and group 2 rats in the target quadrant during the exploratory trial 48 hours after morris hidden platform task training as discussed in example 7.

Detailed description of the disclosure

The present disclosure relates to methods for improving memory and/or cognition in infants. The method comprises administering soy protein to the infant's mother during pregnancy (i.e. pregnancy) and further administering soy protein to the infant after delivery for a period of time. For example, after delivery, if the infant is breast-fed, soy protein may be administered to the infant's mother during lactation and/or soy protein may be administered directly to the infant, for example by administering to the infant an infant and/or nutritional formula comprising soy protein. Also disclosed are nutritional formulas or other compositions comprising soy protein that may be used in the methods of the present disclosure. These and other necessary or optional components or limitations of the soy protein-containing compositions and methods of the present disclosure are described in detail below.

As used herein, unless otherwise indicated, the term "infant" refers to children up to about one year of age, and includes infants from 0 to about 4 months of age, from about 4 to about 8 months of age, from about 8 to about 12 months of age, low body weight infants born at less than 2,500 grams, and preterm infants born at less than about 37 weeks of gestational age, typically from about 26 weeks to about 34 weeks of gestational age. The term "child" as used herein refers to children up to 12 years of age, and includes children from about 12 months to about 12 years of age. The term "adult" as used herein refers to an adult and children of about 12 years of age and older.

As used herein, unless otherwise indicated, the term "infant formula" refers to a nutritional formula designed for infants that contains sufficient nutrients, such as proteins, carbohydrates, lipids, vitamins, and minerals, to potentially serve as a supplemental, primary, or sole source of nutrition.

As used herein, unless otherwise specified, the term "nutritional formula" refers to a nutritional composition designed for infants, toddlers, children, adults, or a combination thereof, that contains sufficient nutrients, such as proteins, carbohydrates, lipids, vitamins, minerals, and electrolytes, to potentially serve as a supplemental, primary, or sole source of nutrition.

As used herein, unless otherwise specified, the term "ready-to-feed" refers to a liquid form nutritional formula suitable for administration, including reconstituted powders, diluted concentrates, and manufactured liquids.

All percentages, parts and ratios used herein are by weight of the total composition, unless otherwise specified. Since all such weights as they pertain to listed ingredients are based on the active level, no solvents or by-products that may be included in commercially available materials are included, unless otherwise specified.

Numerical ranges used herein are intended to include a subset of each number and sum within that range, whether or not specifically disclosed. Further, these numerical ranges should be construed as providing support for claims directed to any number or subset of numbers in that range. For example, a disclosure of 1-10 should be interpreted to support a range of 2-8, 3-7, 5-6, 1-9, 3.6-4.6, 3.5-9.9, and so forth.

All references to singular features or limitations of the present disclosure shall include the corresponding plural features or limitations and vice versa unless otherwise indicated herein or clearly implied to the contrary by the context in which the reference is made.

All combinations of method or process steps used herein can be performed in any order, unless otherwise indicated herein or otherwise clearly contradicted by context in which the referenced combination is made.

The compositions of the present disclosure may also be substantially free of any optional or selected essential ingredients or features described herein, provided that the remaining composition still contains all the required ingredients or features as described herein. In this context, and unless otherwise indicated, the term "substantially free" means that the selected composition contains less than a functional amount of optional ingredients, typically less than 0.1% by weight, and also includes zero percent by weight of such optional or selected essential ingredients.

The compositions, nutritional formulas, infant formulas, and corresponding methods of use of the present disclosure can comprise, consist of, or consist essentially of: essential components and limitations of the disclosure as described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise useful in nutritional formula applications.

Soy protein

It has surprisingly been found that memory and/or cognitive improvement in infants can be achieved by: the soy protein is administered to the pregnant female for at least about three months prior to delivery of the infant, and the soy protein is administered to the infant for at least about 4 months, or even 5 months, or even 6 months, or even 7 months, or even 8 months, or even 9 months, or even 12 months after delivery. After delivery, the soy protein may be administered to the infant's mother during breastfeeding and/or the soy protein may be administered directly to the infant, for example, by administering to the infant a soy protein-containing composition, such as an infant or nutritional formula, that includes soy protein. By administering soy protein to an infant during early brain development, for example during pregnancy and within the first 12 months after delivery, the memory and/or cognition of the infant is improved.

When the infant or nutritional formula comprising soy protein is administered directly to the infant, the infant preferably receives at least about 4 g/day of soy protein, more typically from about 4 g/day to about 40 g/day of soy protein, and preferably from about 6 g/day to about 18 g/day of soy protein.

Soy protein is administered to the infant mother during pregnancy, and in some embodiments, during breastfeeding, in the form of a soy protein-containing composition (also referred to herein as a soy protein composition), e.g., a nutritional composition. Preferably, the soy protein composition will provide at least about 3 g/day of soy protein, more typically from about 3 g/day to about 54 g/day of soy protein, and more preferably from about 8 g/day to about 18 g/day of soy protein to a pregnant woman or a breastfeeding woman. Administration of these amounts of soy protein to pregnant or breastfeeding women results in improved memory and/or cognition in the infant.

The soy protein-containing composition used in the methods of the present disclosure may comprise any suitable source of soy protein. Examples of suitable soy protein sources include, but are not limited to, soy flakes, soy protein isolate, soy protein concentrate, hydrolyzed soy protein, soy flour, soy protein fiber, soy whey, or any other protein or protein source derived from soy or mixtures thereof. Soy proteins suitable for use in the soy protein compositions of the present disclosure include extensively hydrolyzed, partially hydrolyzed, or non-hydrolyzed soy proteins or protein sources.

Commercial sources of soy protein are also well known in The nutritional arts, some non-limiting examples of which include those commercially available from Archer Daniels Midland (Decatur, Ill.) and distributed by The Solae Company (St. Louis, Mo.), under The names EXP-H0118, EXP-E-0101, SUPRO PLUS 675, SUPRO 670, SUPRO 710, SUPRO 620, SUPRO 500E, SUPRO 630, and SUPRO EX 33; and soy protein isolates of PROFAM 931, PROFAM 873 and PROFAM 891. Examples of such soy protein isolates and methods for their production are described in U.S. patent No. 7,323,200, which is incorporated herein by reference in its entirety.

  various soy protein-containing food products are also currently available. The nutrient content of some commonly available soy foods and soy ingredients is listed in table 1 below.

Watch (A) 1 : nutrient content of different soy foods and ingredients *

Soybean food	Calories (kilocalorie)	Protein (g)
			Bean paste (1 ounce)	35	2
Soya, cooked (1/2 cup)	149	14
			Soybean powder (3 Lewa cup)	441	35
Soymilk (1 cup)	140	10
			Soymilk, low-fat (1 cup)	120	8
Soybean kernel, dried roasted (1/2 cup)	387	34
			Soy protein isolate (1 oz)	94	25
A fermented soybean product (Tempen) (4) of IndonesiaOunce)	204	17
			Tofu, low fat (3 ounces)	35	6
Tofu, super hard (3 ounces)	60	6
			Textured vegetable protein (1/4 cup, dried)	59	11
GeniSoy; (35 g)	130	14

Tables are adapted from the US Department of Agriculture Handbook 8.

Nutrient

The soy protein used in the methods of the present disclosure may be incorporated into any food or beverage that may be taken by a human infant or adult or animal. Thus, in one aspect, the soy protein composition used in the methods of the present disclosure is formulated as a nutritional or infant formula. The nutritional or infant formulas of the present disclosure may contain nutrients of sufficient type and amount to meet the target dietary needs of the intended user. These nutritional or infant formulas may therefore comprise protein, carbohydrate and lipid components (both organic or non-organic), plus the soy protein discussed above. The nutritional or infant formula may also include vitamins, minerals, or other ingredients suitable for use in the nutritional formula.

When the nutritional formula is an adult formula, for example, for feeding pregnant women or breast-fed women, the protein component may constitute from about 10% to about 80% of the total caloric content of the nutritional formula; the carbohydrate component may constitute from about 10% to about 70% of the total caloric content of the nutritional formula; and the lipid component may comprise from about 5% to about 50% of the total caloric content of the nutritional formula. At least about 30% by weight of the protein component may comprise soy protein, more typically at least about 50% and up to 100% by weight of the protein component may comprise soy protein. The nutritional formula may be in liquid or powder form. These ranges are provided as examples only and are not intended to be limiting.

About 25% calorie content; the carbohydrate component may constitute from about 35% to about 50% of the total caloric content of the nutritional formula; and the lipid component may comprise from about 30% to about 60% of the total caloric content of the nutritional formula. At least about 30% by weight of the protein component may comprise soy protein, more typically at least about 50% by weight and up to 100% of the protein component may be soy protein. These ranges are provided as examples only and are not intended to be limiting. Additional suitable ranges are noted in the table below.   when the nutritional formula is a non-adult formula, such as an infant formula, the non-adult formula includes embodiments wherein the protein component may constitute about 7.5% of the nutritional formula

Nutrient	First embodiment	Second embodimentTable (A table)	Third embodiment
				Carbohydrate: % total calories	20-85	30-60	35-55
Lipid: % total calories	5-70	20-60	25-50
				Protein: % total calories	2-75	5-50	7-40

All numerical values are preceded by the term "about".

Many different sources and types of carbohydrates, lipids, proteins, minerals, and vitamins are known and may be used in the nutritional formulas of the present disclosure, provided that such nutrients are compatible with the additional ingredients in the selected formula, are safe for its intended use, and do not otherwise unduly impair product performance.

Carbohydrates suitable for use in the nutritional formulas of the present disclosure may be simple, complex, or variations or combinations thereof. Non-limiting examples of suitable carbohydrates include hydrolyzed, intact, natural and/or chemically modified corn starch, maltodextrin, glucose polymers, sucrose, corn syrup solids, rice or potato derived carbohydrates, glucose, fructose, lactose, high fructose corn syrup, and indigestible oligosaccharides such as Fructooligosaccharides (FOS), and combinations thereof.

In addition to the soy protein discussed above, non-limiting examples of proteins suitable for use in nutritional formulas include extensively hydrolyzed, partially hydrolyzed, or non-hydrolyzed proteins or protein sources, and may be derived from any known or otherwise suitable source, such as milk (e.g., casein, whey), animals (e.g., meat, fish), cereals (e.g., rice, corn), plants (e.g., soy), or combinations thereof. Proteins for use herein may also include, or be replaced in whole or in part by: free amino acids are known for use in nutritional formulas, non-limiting examples of which include tryptophan, glutamine, tyrosine, methionine, cysteine, arginine, and combinations thereof. Other (non-protein) amino acids typically added to nutritional formulas include carnitine and taurine. In some cases, the D form of the amino acid is considered nutritionally equivalent to the L form, and isomer mixtures are used to reduce costs (e.g., D, L-methionine).

Non-limiting examples of lipids suitable for use in nutritional formulas include coconut oil, soybean oil, corn oil, olive oil, safflower oil, high oleic safflower oil, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, marine oils, cottonseed oils, long chain polyunsaturated fatty acids such as arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), and combinations thereof.

In addition to these food grade oils, structured lipids (structured lipids) may be incorporated into the nutritional formula if desired. Structured lipids are known in the art. The structural lipids are mainly triacylglycerols, which comprise a mixture of medium-and long-chain fatty acids on the same glycerol core. Structural lipids are also described in U.S. patent No. 6,160,007, also incorporated herein by reference.

In addition to the components described above, the nutritional formulas of the present disclosure may further comprise any of a variety of vitamins. Non-limiting examples of vitamins include vitamin a, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamin B12, niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, chromium, carnitine, inositol, salts and derivatives thereof, and combinations thereof.

The nutritional formula may further comprise any of a variety of minerals, non-limiting examples of which include calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, sodium, potassium, chloride, and combinations thereof.

The Infant Formula of the present disclosure preferably comprises nutrients according to relevant Infant Formula guidelines for the target consumer or user group, an example of which would be Infant Formula Act, 21 u.s.c. Section 350 (a).

  the nutritional formulas of the present disclosure include those embodiments that contain the carbohydrate, lipid, and protein concentrations set forth in table 2 (nutritional formula macronutrients).

TABLE 2

Nutrient	Detailed description of the preferred embodiments	g/100 kilocalorie	g/100 g Total solids	g/L (when fed)
					Carbohydrate compound	First embodiment	8-16	30-90	54-108
	Second embodiment	9-13	45-60	57-79
						Third embodiment	15-19	63-81	157-203
Lipid	First embodiment	3-8	15-42	20-54
						Second embodiment	4-6.6	20-30	27-45
	Third embodiment	2-5	8-21	20-53
					Protein	First embodiment	1-3.9	8-20.5	7-24
	Second embodiment	1.5-3.4	10-17	10-23
						Third embodiment	3.5-6.0	14.8-25.3	37-63

All numerical values are preceded by the term "about".

The nutritional formulas of the present disclosure include embodiments comprising one or more of the following per 100 kcal of reconstituted formula: vitamin A (about 250 to about 1250 IU), vitamin D (about 40 to about 150 IU), vitamin K (greater than about 4 mcg), vitamin E (at least about 0.3 IU), vitamin C (at least about 8 mg), thiamine (at least about 8 mcg), vitamin B12 (at least about 0.15 mcg), nicotinic acid (at least about 250 mcg), folic acid (at least about 4 mcg), pantothenic acid (at least about 300 mcg), biotin (at least about 1.5 mcg), choline (at least about 7 mg), and inositol (at least about 4 mg).

The nutritional formulas of the present disclosure include embodiments comprising one or more of the following per 100 kcal of reconstituted formula: calcium (at least about 50 mg), phosphorus (at least about 25 mg), magnesium (at least about 6 mg), iron (at least about 0.15 mg), iodine (at least about 5 mcg), zinc (at least about 0.5 mg), copper (at least about 60 mcg), manganese (at least about 5 mcg), sodium (about 20 to about 60 mg), potassium (about 80 to about 200 mg), and chloride (about 55 to about 150 mg).

Optional ingredients

The soy protein compositions of the present disclosure may further comprise other optional components that may modify the physical, chemical, aesthetic, or processing characteristics of the composition, or serve as pharmaceutical or additional nutritional components when used in a target population. Many such optional ingredients are known or suitable for use in other ingredients of food and nutritional products, including infant formulas, and may also be used in the soy protein compositions of the present disclosure, provided that such optional materials are compatible with the essential materials described herein, are safe for their intended use, and do not otherwise unduly impair product performance.

Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifiers, buffers, pigments, flavoring agents, nucleotides and nucleosides, additional probiotics, additional prebiotics, lactoferrin and related derivatives, thickeners and stabilizers, and the like.

Product form

The soy protein composition of the present disclosure may be prepared in any product form suitable for administration to humans, including liquid or powdered complete nutrients, liquid or powdered supplements (e.g., supplements that may be mixed with a beverage), reconstitutable powders, ready-to-feed liquids, solid matrix nutrients, liquid or powdered human milk fortifiers, beverages, nutritional snacks (e.g., multiple smaller nutritional product formulations in a single package), nutritional bars (treats or meal replacers), and dilutable liquid concentrates, among other forms, all of which are well known in the nutritional formula art.

The soy protein composition may be formulated to include only soy protein or a source thereof as described herein, or alternatively, may be combined with optional ingredients to form a number of different product forms. The soy protein compositions of the present disclosure are preferably formulated as nutritional compositions, and may include liquid or powdered nutrients or infant formulas, liquid or powdered human milk fortifiers, or solid matrix nutrients, among other forms.

When formulated as a nutritional composition, the soy protein composition of the invention can potentially provide a sole, primary, or supplemental source of nutrition for an individual. In this context, the only source of nutrition is one that can be administered one or more times per day to potentially provide the individual with all or substantially all of the fat, protein, carbohydrate, minerals, and vitamins required per day or during the intended administration period. A supplemental nutritional source is defined herein as a dietary source that does not provide a potentially unique source of nutrition for an individual.

The soy protein composition of the present disclosure may have any caloric density suitable for the target or intended patient population, i.e., pregnant women or breastfed women or infants, or provide such a density upon reconstitution of a powder embodiment or upon dilution of a liquid concentrate embodiment. For example, the most common calorie densities for infant formula embodiments of the present disclosure are typically at least about 19 kcal/fluid ounce (660 kcal/liter), more typically about 20 kcal/fluid ounce (675-. Typically, 22-24 kcal/fluid ounce formulas are more commonly used in premature or low weight infants, and 20-21 kcal/fluid ounce (675-. Non-infant and adult nutritional formulas may have any caloric density suitable for the target or intended population.

In one embodiment, the soy protein composition is formulated for direct administration to an infant and may be, for example, an infant formula. Examples of components suitable for inclusion in infant formulas are described above. Soy protein based infant formulas are also available from many commercial sources.

In some embodiments, the soy protein composition is administered to the infant until the infant reaches an age of about 1 year to about 5 years. In these embodiments, a soy protein-based nutritional formula suitable for young children may be administered as the infant grows.

In another embodiment, the soy protein composition may be a soy protein-based liquid or powdered human milk fortifier which, when combined with human milk, may be administered to an infant in accordance with the methods of the present disclosure to provide soy protein to the infant.

The soy protein composition may also be formulated for administration to pregnant women or breastfed women in accordance with the methods of the present disclosure. In a particular embodiment, the soy protein composition is an adult nutritional formula. Examples of suitable components for inclusion in the nutritional formula are described above. Commercially available soy protein compositions suitable for administration by pregnant or breastfed women according to the methods of the present disclosure are available from a number of commercial sources.

For the nutritional powder embodiments of the present disclosure, whether formulated for administration to an infant or to a pregnant or breast-fed woman, such powders are typically in the form of a flowable or substantially flowable granular composition, or at least a granular composition that can be easily scooped and measured with a spoon or similar other device, wherein the composition can be easily reconstituted by the intended user with a suitable aqueous fluid, typically water, to form a liquid nutritional formula for immediate oral or enteral use. In this context, "immediately" use generally means within about 48 hours, most generally within about 24 hours, preferably just after reconstitution. These powder embodiments include spray-dried, agglomerated, dry-mixed, or other known or otherwise effective particulate forms. The amount of nutritional powder required to produce a volume suitable for use as a serving may vary.

The nutritional formulas of the present disclosure may be packaged and sealed in single-use or multi-use containers and then stored at ambient conditions for up to about 36 months or longer, more typically from about 12 to about 24 months. For multiple use containers, these packages may be opened and then covered for reuse by the end user, provided that the covered package is then stored under ambient conditions (e.g., to avoid extreme temperatures), and the contents are used within about one month or so.

In a particular embodiment, soy protein may be incorporated into a solid matrix nutritional and administered to a pregnant woman or a breastfed woman in accordance with the methods of the present disclosure. Such solid matrix nutrients comprise a soy protein source, optionally an additional protein source, a fat source, a carbohydrate source, vitamins and minerals in amounts sufficient to supplement the normal diet of a pregnant or breast-fed woman. Such amounts are well known to those skilled in the art and can be readily calculated in the preparation of such products and include those set forth above for nutritional formulas.

Typically, a 60 gram nutritional bar (230 calories) for a pregnant female will contain 6 grams total fat (24% calories), 9 grams protein (16% calories), 35 grams carbohydrate (60% calories), and appropriate amounts of vitamins and minerals.

Typically, a 50 gram nutritional bar (220 calories) for breast-fed women will contain 6 grams total fat (24% calories), 8 grams protein (14% calories), 34 grams carbohydrate (62% calories), and appropriate amounts of vitamins and minerals.

Solid matrix nutritionals may also desirably include coatings, flavors, and/or colors to provide an attractive appearance and an acceptable taste to the nutritional composition for oral consumption. For example, the nutritional bar of example 6 was coated with a sugar-free white candy coating. Examples of suitable coatings generally include compound candy coatings, milk chocolate coatings, sugar coatings, shellac, sugar-free compound candy coatings, sugar-free sugar coatings, and sugar-free shellac. Examples of useful flavorings for solid matrix nutritionals generally include, for example, chocolate, butter pecan, strawberry, cherry, orange, peanut butter, whole wheat flour, and lemon.

The solid matrix nutritional may also desirably include ingredients that add texture to enhance the mouthfeel of the solid matrix nutritional. For example, crispy rice was added in example 6 at about 6.4 wt/wt% of the nutritional bar. Examples of other suitable ingredients to which texture may generally be added include nuts, soy chunks, toasted oats and fruit pieces.

Other specific examples of product forms of the soy protein composition suitable for administration to pregnant or breast-fed women in accordance with the methods of the present disclosure include most any conventional or otherwise known food product form, such as confectionary products, cereals, food dressings (e.g., spreads, powders, sauces, jams, jellies, coffee creamers (or sweeteners), pasta, baking or cooking materials (e.g., flour, fats or oils, butter or margarine, breading or baking mixes), salted or seasoned snacks (e.g., extruded, baked, fried), beverages (e.g., coffee, juices, carbonated beverages, non-carbonated beverages, tea, ice cream-based beverages), snacks or meal replacement bars, smoothies, breakfast cereals, cheese, gum products (gummy products); breakfast, snack foods, and combinations thereof, Salted or non-salted crispy snacks (e.g. chips, crackers, pretzels), sauces (dips), baked goods (e.g. biscuits (cookies)), cakes, pies, pastries, bread, bagels, fried shredded bread slices, sauces, dry mixes (e.g. mixes for muffins, biscuits, waffles, pancakes, beverages), frozen desserts (e.g. ice cream, ice lollies, fudge-lollies, crushed ice, frozen yogurt), pasta, processed meat (e.g. american hot dogs (corn), hamburgers, hot dogs, sausages, pepperonions), pizza, puddings, flavored or non-flavored gelatins, refrigerated (e.g. biscuits, bread, brownies), milk or soy-based delicacies, yogurt or yogurt-based drinks, frozen yogurt, soy milk, soup, vegetable-based holders (burgers), And popcorn-based snacks.

Manufacturing method

The soy protein compositions of the present disclosure may be prepared by any known or otherwise effective technique suitable for preparing and formulating nutritional formulas or similar other products, which may vary depending on variables such as the selected product form of the desired composition, e.g., nutritional liquids or nutritional bars; combining the components; packaging and container selection; and so on. Such techniques and variations for any given composition are readily determined and applied by one of ordinary skill in the nutritional formulation or manufacturing arts.

The nutritional formulas of the present disclosure, including some of the exemplary formulas described below, can thus be prepared by any of a variety of known or otherwise effective formulations or manufacturing methods. These methods most generally involve initially forming an aqueous slurry containing carbohydrates, proteins, lipids, stabilizers or other formulation aids, vitamins, minerals, or combinations thereof. The slurry was emulsified, pasteurized, homogenized and cooled. Various other solutions, mixtures, or other materials may be added to the resulting emulsion before, during, or after further processing. This emulsion can then be further diluted, heat treated and packaged to form a ready-to-feed or concentrated liquid, or it can be heat treated and subsequently processed and packaged as a reconstitutable powder, e.g., spray-dried, dry-mixed, agglomerated reconstitutable powder.

Other suitable methods for preparing nutritional formulas are described, for example, in U.S. Pat. No. 6,365,218 (Borschel, et al), U.S. Pat. No. 6,589,576 (Borschel, et al), U.S. Pat. No. 6,306,908 (Carlson, et al), U.S. patent application 20030118703A 1 (Nguyen, et al), which descriptions are incorporated herein by reference.

The solid matrix nutritional composition may be manufactured using cold extrusion techniques as are known in the art. To prepare such compositions, generally all powdered components will be dry blended together. Such ingredients typically include proteins, vitamin premixes, specific carbohydrates, and the like. The fat soluble components are then blended together and mixed with the powdered premix above. Finally any liquid components are subsequently mixed into the composition to form a plastic-like composition or dough.

The above process is expected to produce plastic masses (plastic masses) which can then be shaped by a procedure called cold forming or extrusion without further physical or chemical changes. In this process, the plastic mass is forced through a die under relatively low pressure to impart the desired shape, and the resulting exudate is then cut at the appropriate location to produce the desired weight of the product.

The agglomerates may for example be forced through a die of small cross-section to form a ribbon, which is carried on a belt moving at a predetermined speed under a guillotine-type cutter operating at regular intervals. In this case, the cutter typically consists of a sharp blade adjusted so that it cuts through the ribbon but not through the underlying belt, but may also consist of a wire. In both cases, the principle is the same; the cutting process occurs at intervals that allow the moving ribbon to be cut into pieces of equal weight and size. Typically, this is achieved by timing the cutting stroke and maintaining the belt speed at a suitable level, but there is also a computer controlled version of this mechanism which provides greater versatility. Alternatively, the mass may be forced through a die of large cross-section and subsequently cut into slices at the die level by an oscillating knife or wire, which fall onto the moving belt and are thus transported away. The mass may also be extruded as a sheet stock which is subsequently cut into a suitable shape with a stamp type cutter, such as a cookie type cutter. Finally, the mass may also be forced into a chamber on a rotating die equipped with an eccentric cam, which forces the material thus formed out of the chamber at some point in the rotation of the cylindrical die.

After forming, the formed product is moved by a conveyor belt or other type of material conveyor to an area where it can be further processed or simply packaged. In general, nutritional bars of the type described may be enrobed with a material, which may be chocolate, a compound chocolate coating, or some other type of coating material. The coating material generally consists of fat which is solid at room temperature but liquid at temperatures above, for example, 31 ℃, together with other materials which impart organoleptic properties. The coating is thus applied to the rod while molten, by allowing the rod to pass through a falling curtain (falling curtain) of liquid coating, while passing the rod over a plate or roller which allows the coating to be applied to the lower surface of the rod, and blowing off the excess coating by means of air jets. Finally, the enrobed bars pass through a cooling tunnel where a stream of refrigerated air removes heat and causes the coating to solidify.

Solid matrix nutritional embodiments for use herein can also be made by baking applications or heat extrusion to produce solid product forms such as cereals, biscuits, crackers, and similar other product forms. One knowledgeable in the field of nutritional manufacturing can choose from a number of known or otherwise available manufacturing methods to produce a desired end product.

Numerous types of packaging are readily available and known to those of skill in the art. Desirable packaging characteristics include: effective protection against impact, light and heat; easy to open; and an effective seal for storage stability.

Application method

The soy protein compositions of the present disclosure may be administered to an infant during at least about the first 12 months after delivery, as well as to the infant's mother during pregnancy and/or breastfeeding, to improve memory and/or cognition of the infant. In particular, it has been found that memory and/or cognitive improvement in infants can be achieved by: for example, soy protein in the form of a soy protein composition of the present disclosure is administered to a pregnant female for at least about three months prior to delivery of the infant, and after delivery, soy protein is administered to the infant for at least about 12 months, and in some embodiments, until the infant reaches an age of about 1 to about 5 years. For example, soy protein may be administered to the mother of an infant during pregnancy and breastfeeding, and may be administered directly to the infant after delivery by administering to the infant a soy protein-containing composition, such as an infant or nutritional formula comprising soy protein. By administering soy protein to an infant during early brain development, for example to the infant's mother during pregnancy and breastfeeding, and/or within the first 12 months after delivery, the memory and/or cognition of the infant is improved.

Accordingly, in one embodiment, the present disclosure relates to a method of improving memory in an infant. The method comprises administering soy protein to the pregnant female for at least about three months prior to delivery of the infant, and administering soy protein to the infant for at least about 12 months after delivery. The improvement in memory may be, for example, an improvement in hippocampus-dependent tasks, such as spatial memory and related forms of learning and memory. The improvement in memory can be measured using any suitable technique known in the art, such as the morris water maze.

In another embodiment, the present disclosure relates to a method of improving cognition in an infant. The method comprises administering soy protein to the pregnant female for at least about three months prior to delivery of the infant, and administering soy protein to the infant for at least about 12 months after delivery.

The terms "cognitive" and "cognitive function" are used herein interchangeably and refer to a series of functions: intelligence (fluid, crystalline state), creativity (creating and opening new ideas, perceiving new relationships), memory (encoding, storing, extracting), executive function (handling novelty things, planning and implementation, monitoring behavior, alertness, suppression of task-independent information), cognitive resources (speed of information processing, working memory capacity, attentiveness), etc. The improvement in cognition may include improvement or enhancement of cognitive development. The term "cognitive development" as used herein refers to the development of cognition (cognitive function) over time. The quality of cognition (cognitive function) in humans can be assessed by tests that measure cognitive performance. As cognition (cognitive function) of a growing infant or child develops over time with brain development, the cognitive performance of a given infant or child over time is measured, providing a measure of cognitive development. For example, for children aged 6-9 years, cognitive development is generally recognized by: sudden increases in information processing capacity and/or executive function, and frontal lobe (related to executive function) development of the brain. These growth spikes can also occur at other times during childhood, such as 0-2 years of age and middle children (mid-teens).

Development of the central nervous system is a complex and persistent process that is initiated early in pregnancy when the neural canal begins to develop. Several neurological processes develop more actively during the third trimester of pregnancy, such as axonal and dendritic sprouting (sprouting), synapse formation, glial cell proliferation, and the acetylcholine (acetylcholinergic) system. Some of these processes continue to develop after birth, are more active during the first year of life, and slow down later in life. Myelination occurs during the first year of life after birth.

As noted above, soy protein is administered to the infant mother during pregnancy in accordance with the methods of the present disclosure. The soy protein is administered to the pregnant woman for at least about 4 weeks prior to delivery of the infant, preferably at least about 6 weeks prior to delivery, more preferably at least about 3 months prior to delivery, preferably at least about one third of pregnancy, or at least about 6 months prior to delivery, and more preferably for the duration of pregnancy. The soy protein may be administered to the pregnant female in the form of a nutritional composition, such as described herein. The soy protein may be administered to the pregnant female according to any suitable dosing regimen, for example once a week, once a day, and/or multiple times a day. In one embodiment, the soy protein is preferably administered to the pregnant female on a daily basis. Preferably, the soy protein composition provides at least about 3 g/day of soy protein, more typically from about 3 g/day to about 54 g/day of soy protein, and more typically from about 8 g/day to about 18 g/day of soy protein to the pregnant female.

After delivery, soy protein is administered to the infant for at least about 3 months, preferably at least about 6 months, and more preferably until the infant reaches about 12 months of age. In some embodiments, soy protein may be administered to an infant until the infant reaches an age of about 1 year to about 5 years. The soy protein may be administered to the infant after delivery by administering a soy protein containing composition, such as an infant or nutritional formula, comprising soy protein. After delivery, soy protein may also be administered to the infant's mother during lactation and breastfeeding of the infant.

In embodiments wherein soy protein is administered to a breastfeeding mother, it is preferred that soy protein is administered to the breastfeeding woman for the duration of breastfeeding, i.e., until weaning. The soy protein may be administered to a breastfed woman in the form of a nutritional composition, such as described herein. The soy protein may be administered to a breastfed woman according to any suitable dosing regimen, for example once a week, once a day, and/or multiple times a day. In one embodiment, the soy protein is preferably administered to a breastfed woman on a daily basis. Preferably, the soy protein composition provides at least about 3 g/day of soy protein, more typically from about 3 g/day to about 54 g/day of soy protein, and more typically from about 8 g/day to about 18 g/day of soy protein to a breastfed woman.

It should be understood that not all women are breastfeeding their infants, and not all women who are breastfeeding their infants are breastfed at least about 3 months, or at least about 6 months or 12 months after delivery. Thus, in some embodiments, soy protein is administered to an infant after delivery, for example by administering to the infant an infant and/or nutritional formula comprising soy protein. In one embodiment, the infant formula comprising soy protein is administered to the infant in addition to breast feeding, e.g., as a supplement to breast feeding and/or at least about 3 months post weaning, or until the infant reaches an age of at least about 12 months. In some embodiments, the soy protein is administered to the infant until the infant reaches an age of about 1 year to about 5 years. In this embodiment, a suitable nutritional formulation may be reformulated to include soy protein and administered to children. In another embodiment, the infant is administered an infant and/or nutritional formula comprising soy protein as the sole source of soy protein (i.e., without prior or concurrent breast feeding) immediately after delivery until the infant reaches at least about 12 months of age, or until the infant reaches from about 1 to about 5 years of age.

It will be preferred to provide the infant with at least about 4 g/day soy protein, more typically from about 4 g/day to about 40 g/day soy protein, and more typically from about 6 g/day to about 18 g/day soy protein.

Examples

The following examples further describe and demonstrate specific embodiments within the scope of the present disclosure. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present disclosure, as many variations thereof are possible without departing from the spirit and scope of the disclosure. All exemplified amounts are weight percentages based on the total weight of the composition, unless otherwise indicated.

Each of the exemplified compositions is fed to humans to provide unique, primary, or supplemental nutrition. Each composition contains soy protein and may be used in the methods of the present disclosure to improve memory and/or cognition in the infant.

Examples 1

The following examples illustrate nutritional powder embodiments of soy-based infant formulas that may be administered to infants in accordance with the methods of the present disclosure. The ingredients used to make 100 kg nutritional powder infant formula are shown in the table below.

Powdered infant formulas are prepared by first dispersing carbohydrates (sucrose solids) and minerals into water with suitable heat and agitation to form a carbohydrate-mineral slurry. The soy protein isolate, along with any oil soluble vitamins, emulsifiers, and antioxidants, is then dispersed into a vegetable oil (soy, coconut, high oleic safflower) with suitable heat and agitation to form a protein-oil slurry. The resulting slurry is then blended with corn syrup and the resulting pH adjusted to between 6.0 and 7.0 with a suitable alkaline solution. The final total solids content of the resulting blend was 45-50.5%. The blend was then emulsified at 100-400 psi, subjected to High Temperature Steam Treatment (HTST) at 160-170F, and then homogenized using a 2-stage homogenization process at a pressure of 900-1300 psi/400 psi. Water soluble materials such as water soluble vitamins, methionine and trace minerals are then added to the homogenized mixture, which is then subjected to Ultra High Temperature (UHT) treatment at 220-. The heat treated mixture was then cooled to 160-.

Examples 2

The following examples illustrate ready-to-feed liquid nutritional soy-based infant formulas that may be administered to infants in accordance with the methods of the present disclosure. The ingredients used to make 100 kg of ready-to-feed infant formula are shown in the table below.

A ready-to-feed nutritional infant formula is prepared by first dispersing carbohydrates (sucrose solids) and minerals into water with suitable heat and agitation to form a carbohydrate-mineral slurry. The soy protein isolate, along with any oil soluble vitamins, emulsifiers, and antioxidants, is then dispersed into a vegetable oil (soy, coconut, high oleic safflower) with suitable heat and agitation to form a protein-oil slurry. The resulting slurry is then blended with corn syrup and the resulting pH adjusted to between 6.0 and 7.0 with a suitable alkaline solution. The final total solids content of the resulting blend is 20-30%. The blend was then emulsified at 100-500 psi, subjected to High Temperature Steam Treatment (HTST) at 143-154 deg.C, and then homogenized using a 2-stage homogenization process at a pressure of 3000-4000 psi/500 psi. Water soluble materials such as water soluble vitamins, methionine and trace minerals are then added to the homogenized mixture. The mixture was diluted with water to a solids content of 12-13%, packaged and sealed into suitable containers, and subsequently sterilized at 115-126 ℃.

Examples 3

The following examples illustrate human milk fortifier powders added to human milk that may be administered to infants in accordance with the methods of the present disclosure. The ingredients used to make 8,172 kg of powdered human milk fortifier are shown in the table below.

Composition (I)	The amount of 8,172 kg of fortifier is prepared
		Ingredient water	16,205 L
Corn syrup solids	1603 kg
		Magnesium chloride	96.2 kg
Potassium citrate	223.8 kg
		Citric acid sodium salt	6.6 kg
Sodium chloride	15.4 kg
		MCT oil	801 kg
Lecithin	16.6 kg
		Vitamin A	2.36 kg
Vitamin D	359.3 g
		Vitamin K	27.5 g
Tocopheryl acetate	15.8 kg
		Calcium carbonate	33.1 kg
Tricalcium phosphate	646 kg
		Soy protein concentrate	1506 kg
Defatted milk powder	3307 kg
		Potassium citrate	257.2 g
Ferrous sulfate	3.7 kg
		Zinc sulfate	11.1 kg
Copper sulfate	1.84 kg
		Manganese sulfate	0.320 kg
Sodium selenate	0.001 kg
		Nicotinamide	0.98 kg
Riboflavin	1.14 kg
		Calcium pantothenate	4.08 kg
Pyridoxine hydrochloride	0.655 kg
		m-inositol	9.55 kg
Biotin	0.0727 kg
		Folic acid	0.0775 kg
Cyanocobalamin	0.0016 kg
		Ascorbic acid	153.5 kg

。

A carbohydrate/mineral slurry was prepared by heating 2,763 litres of ingredient water to 54 ℃ -62 ℃. With agitation, the indicated amounts of corn syrup solids, magnesium chloride, sodium citrate, potassium citrate, ultra micronized tricalcium phosphate, and calcium carbonate were added to the heated water. The slurry was kept at 54-62 ℃ under agitation for no longer than six hours until it was blended with other slurries.

An oil blend was prepared by heating the indicated amount of MCT oil to 32-37 ℃ with agitation. The emulsifier is then added with agitation and allowed to dissolve. Vitamin A, D, K and vitamin E were then added to the slurry with agitation. The finished oil slurry was kept at a temperature of 26-48 ℃ under moderate agitation for a period of no more than six hours until it was blended with other slurries.

A protein slurry in water was prepared by heating 9,053 litres of ingredient water to 48-60 ℃. With agitation, specified amounts of soy protein concentrate and skim milk powder were added to the heated water. The finished protein slurry in water is not maintained but is blended directly with the other slurry.

The protein slurry, oil blend and carbohydrate/mineral slurry in water are blended together with agitation and the resulting blend is maintained at a temperature of 51 ℃ to 60 ℃. After waiting at least five minutes with agitation, the pH of the final blend was adjusted to 6.45 to 6.80 with 1N KOH. The total solids content of the final blend was 30%. After the pH check, the final blend was kept for no longer than two hours.

After waiting a period of not less than five minutes and not more than two hours, the blend was degassed, heat treated at high temperature for a short period of time and homogenized as follows: degassing the blend at 10 to 15 inches Hg; the blend was emulsified in a single homogenizer at 900-; passing the blend through a sheet/coil heater and heating the mixture to 71 ℃ to 82 ℃; homogenizing the blend in a dual homogenizer at 3900 to 4100/400 to 600 psig; passing the blend through a 16 second holding tube at a temperature of 73 ℃ to 85 ℃; cooling the blend to a temperature of 1 ℃ to 7 ℃; and storing the blend at a temperature of 1 ℃ to 7 ℃.

After the above steps have been completed, appropriate analytical tests for quality control are performed. Based on the analytical results of the quality control tests, batch corrections are made, if necessary. The final blend total solids is 29% to 31%.

The water-soluble vitamin solution, ascorbic acid solution and trace mineral solution are prepared separately and added to the processed blend.

An ascorbic acid solution was prepared by adding the required amount of ascorbic acid to 2,453 liters of 10 ℃ to 37 ℃ water with stirring.

A mineral solution was prepared by heating 321 liters of ingredient water to 37-65 ℃. The required amounts of potassium citrate and ferrous sulfate were added with stirring. Agitation was allowed until the solution was clear green. The required amount of zinc sulfate, copper sulfate, manganese sulfate and sodium selenate are added into the green mineral solution. Stir for a minimum of five minutes.

A water-soluble vitamin solution was prepared by heating 530 liters of ingredient water to 37-65 ℃. The required amounts of nicotinamide, riboflavin, calcium pantothenate, pyridoxine hydrochloride, thiamine hydrochloride, m-inositol, biotin, folic acid, and cyanocobalamin were added to the heated water.

All of the ascorbic acid solution, mineral solution, and water-soluble vitamin solution were then added to the blended slurry with agitation.

The final mixture was preheated to 71-82 ℃ by a plate heater before entering the equilibration tank (purge tank). The mixture leaves the equilibration tank and passes through a steam jet ejector where it is heated to 88-93 ℃. The mixture was fed to a steam-flash chamber where it was cooled to 71-82 ℃ and then pumped through an in-line 200 microfilter before the high pressure pump and into a dryer. The dryer settings were as follows: the nozzle pressure was 3000-.

To control bulk density, dispersability, particle size, moisture, and physical stability, the specific spray nozzle, nozzle pressure, drying temperature, and fine reinjection parameters may be varied depending on the drying conditions of the day. From the dryer the powder enters a powder cooler where it is cooled to below 43 ℃. The cooled powder is stored in suitable containers until filled into individual packages.

Examples 4

The following example illustrates a vanilla flavored liquid nutritional product containing soy protein that may be administered to a pregnant woman or a breastfed woman in accordance with the methods of the present disclosure. The ingredients used to make 454 kg (1,000 pounds) of the nutritional product are shown in the table below.

Composition (I)	Amount/454 kg	Amount (pounds)/1000 pounds
			Water (W)	347 kg	765
Maltodextrin	35.6 kg	78.5
			Sucrose	32.2 kg	70.9
Soy protein isolate	28 kg	61.7
			High oleic safflower oil	1.76 kg	3.87
Canola oil	1.76 kg	3.87
			Potassium citrate	1.77 kg	3.90
Magnesium phosphate	1.27 kg	2.80
			Vanilla spice	0.91 kg	2.00
Cellulose gel	0.91 kg	2.00
			Corn oil	0.88 kg	1.94
Calcium citrate	0.45 kg	1.00
			Choline chloride	240 g	0.529
Citric acid sodium salt	227 g	0.500
			Soybean lecithin	197 g	0.435
UTM/TM premix	163 g	0.359
			Ascorbic acid	148 g	0.326
Carrageenan	68 g	0.150
			Vitamin DEK premix	44 g	0.0970
Vitamin premix	29 g	0.0639
			30% beta-carotene	3.7 g	0.00816
Vitamin A palmitate premix	1.6 g	0.00364
			Potassium iodide	233 mg	0.000515

。

Liquid nutritional products are manufactured by preparing three slurries, which are blended together, heat treated, standardized, packaged and sterilized.

Specifically, a carbohydrate/mineral slurry is prepared by combining a specified amount of cellulose gel with a desired amount of water under high agitation. The mixture is heated to a temperature of about 140 ° F to about 150 ° F with agitation. The cellulose gel is dissolved before the addition of the minerals. The following minerals were then added in the order listed under high agitation: potassium citrate, sodium citrate and UTM/TM premix. The slurry was held under agitation for a minimum of 5 minutes. The remaining minerals were added under high agitation in the order listed: potassium iodide and magnesium phosphate. Next, maltodextrin was added to the slurry under high agitation and allowed to dissolve. Sugar was then added under high agitation and allowed to dissolve. The finished carbohydrate/mineral slurry is maintained under high agitation at a temperature of about 140 ° F to about 150 ° F for no longer than twelve hours until it is blended with other slurries.

The high oleic safflower oil, corn oil and canola oil are combined and heated to a temperature of from about 130 ° F to about 140 ° F with agitation. The emulsifier (soy lecithin) was then added with agitation and allowed to dissolve. The vitamin D, E, K premix, vitamin a palmitate and 30% beta-carotene were then added to the slurry with agitation. The stabilizer is added to the slurry with agitation and allowed to disperse. The finished oil slurry is maintained under moderate agitation at a temperature of about 130 ° F to about 140 ° F for a period of no more than twelve hours until it is blended with other slurries.

A 10-12% protein slurry in water is prepared by first adding soy protein isolate to the desired amount of water under high agitation. The slurry is heated to a temperature of about 85 ° F to about 95 ° F with agitation and held for a minimum of 15 minutes. The slurry temperature is then increased to a temperature of about 115 ° F to about 125 ° F and held for a minimum of 5 minutes. The slurry temperature is then increased to a temperature of about 145 ° F to about 155 ° F. Cocoa powder can be dispersed in a protein slurry for chocolate flavored products. The finished protein slurry in water is maintained at a temperature of about 145 ° F to about 155 ° F with moderate agitation for a period of no more than two hours until it is blended with other slurries.

The protein slurry and oil slurry in water are blended together with agitation, and the resulting blend is maintained at a temperature of about 140 ° F to about 150 ° F. After waiting at least five minutes, the carbohydrate/mineral slurry is added to the blend from the previous step with agitation, and the resulting blend is maintained at a temperature of about 140 ° F to about 150 ° F. The total solids content of the final blend was about 25%. The blend pH was brought to about 6.8 to about 7.0 with 1N KOH.

After waiting a period of not less than five minutes and not more than two hours, the blend was degassed, ultra-high temperature treated and homogenized as follows: degassing the blend at 10 to 15 inches Hg; preheating the blend to 155-165 ℃ F. by passing it through a plate/coil heat exchanger; emulsifying the blend at 900-; passing the blend through a sheet/coil heater and heating the mixture to about 250 ° F to about 255 ° F; ultra-high temperature heating the blend to a temperature of about 298 ° F to about 302 ° F with a hold time of about 5 seconds; reducing the temperature of the blend to about 250 ° F to about 255 ° F by passing the blend through a flash cooler; reducing the temperature of the blend to about 160 ° F to about 170 ° F by passing it through a plate/coil heat exchanger; homogenizing the blend at about 3900 to about 4100/about 400 to about 600 psig; passing the blend through a holding tube at a temperature of about 165 ° F to about 175 ° F for at least 16 seconds; cooling the blend to a temperature of about 340 ° F to about 45 ° F by passing the blend through a heat exchanger; and storing the blend at a temperature of from about 34 ° F to about 45 ° F with agitation.

After the above steps have been completed, appropriate analytical tests for quality control are performed. Based on the analytical results of the quality control test, an appropriate amount of water was added to the batch with agitation for dilution to about 22% total solids.

The vitamin solution and flavor solution are prepared separately and added to the processed blend.

A vitamin solution was prepared by adding the following ingredients to the required amount of water with stirring: ascorbic acid, a water-soluble vitamin premix and choline chloride. The vitamin solution pH was adjusted to about 6 to about 10 with 45% KOH. The vitamin slurry is then added to the blended slurry with stirring.

Perfume solutions are prepared by adding natural and artificial perfumes to an appropriate amount of water with stirring. The fragrance slurry was then added to the blended slurry with stirring.

The product pH is adjusted to achieve optimal product stability. The finished product is then placed in a suitable container and terminally sterilized.

Examples 5

The following examples illustrate orange juice and carrot juice soy beverages which may be administered to pregnant women or breast-fed women in accordance with the methods of the present disclosure. The ingredients used to make 6.8 kg of beverage are shown in the table below.

Composition (I)	Measurement of
		Water (W)	5.2 kg
Soy protein	332 g
		Orange juice (65 Brix)	309 g
Carrot juice (70 Brix)	194.4 g
		Pectin	18 g
Solid cane juice	488 g (488 g)
		Canola oil	3.35 g
Ascorbic acid	2.22 g
		Vitamin DEK premix	0.66 g
Vitamin premix	0.44 g
		Vitamin A palmitate	0.07 g

。

Beverages are made by preparing three slurries that are blended together, heat treated, standardized and aseptically packaged. Specifically, a carbohydrate/mineral slurry is prepared by combining a specified amount of pectin with a desired amount of water under high agitation. The mixture is heated to a temperature of about 140 ° F to about 150 ° F with agitation. The slurry was held under agitation for a minimum of 5 minutes. The cane juice solids were added under high agitation and allowed to dissolve. The finished carbohydrate/mineral slurry is maintained under high agitation at a temperature of about 140 ° F to about 150 ° F for no longer than twelve hours until it is blended with other slurries.

The oil blend is prepared by combining and heating canola oils to a temperature of about 130 ° F to about 140 ° F with agitation. The vitamin D, E, K premix and vitamin a palmitate were then added to the slurry with agitation. The finished oil slurry is maintained under moderate agitation at a temperature of about 130 ° F to about 140 ° F for a period of no more than twelve hours until it is blended with other slurries.

A 10-12% protein slurry in water is prepared by first adding soy protein to the required amount of water under high agitation. The slurry is heated to a temperature of about 85 ° F to about 95 ° F with agitation and held for a minimum of 15 minutes. The desired amounts of orange juice concentrate and carrot juice are added with agitation. The finished protein slurry in water is maintained at a temperature of about 145 ° F to about 155 ° F with moderate agitation for a period of no more than two hours until it is blended with other slurries.

The protein slurry and oil slurry in water are blended together with agitation, and the resulting blend is maintained at a temperature of about 140 ° F to about 150 ° F. After waiting at least five minutes, the carbohydrate slurry is added to the blend from the previous step with agitation, and the resulting blend is maintained at a temperature of about 140 ° F to about 150 ° F.

After waiting a period of not less than five minutes and not more than two hours, the blend is degassed at 10-15 inches Hg, preheated to 155-165F by a plate/coil heat exchanger, emulsified at 900-1100 psig, passed through a plate/coil heater and heated to about 250F to about 255F, heated to a temperature of about 298F to about 302F, having a hold time of about 5 seconds, reduced to about 250F to about 255F by passing through a flash cooler, reduced to a temperature of about 160F to about 170F by passing through a plate/coil heat exchanger, homogenized at about 3900 to about 4100/about 400 to about 600 psig, slurried at a temperature of about 165F to about 175F for at least 16 seconds through a holding tube, cooled to a temperature of about 34F to about 45F by passing through a heat exchanger, and stored at a temperature of about 34F to about 45F with agitation.

After the above steps have been completed, appropriate analytical tests for quality control are performed. Based on the analytical results of the quality control test, an appropriate amount of water was added to the batch with agitation for dilution to the preferred total solids.

The vitamin solution was prepared separately and added to the processed blend.

A vitamin solution was prepared by adding the following ingredients to the required amount of water with stirring: ascorbic acid and a water-soluble vitamin premix. The vitamin solution pH was adjusted to about 6 to about 10 with 45% KOH. The vitamin slurry is then added to the blended slurry with stirring.

The final blend pH was adjusted to 4.0 with 10% malic (citric) acid and 10% citric acid solutions. The finished product is then aseptically filled into suitable containers.

Examples 6

The following example illustrates a lemon flavored nutritional bar that may be administered to a pregnant female or a breastfeeding female in accordance with the methods of the present disclosure. The ingredients used to make the 1 kg bar are shown in the table below.

Composition (I)	Quantity-1 kg of
		Candy coating	190 g of
Soy protein	162.3 g
		Honey	143.5 g
Maltodextrin	107.9 g
		High fructose corn syrup	91.5 g
Rice cracker (rice crisps)	63.5 g
		Soybean polysaccharide	49.1 g
Glycerol	46.3 g
		Vitamin/mineral premix	28.2 g
High oleic safflower oil	27.9 g
		Fructo-oligosaccharide	21.2 g
Encapsulated guar gum	16.5 g
		Microcrystalline cellulose	13.3 g
Mustard flower (canola)	11.7 g
		Lemon flavor	10.1 g
Fructose	7.8 g
		Citric acid	3.3 g
m-inositol	2.9 g
		Soybean lecithin	2.8 g
Alpha-tocopherol acetate	911 mg

。

The stick core was prepared by mixing the intervening blend in two stages, adding a liquid preblend followed by canola oil. The intervening blend was prepared by mixing the desired amounts of soy protein, fructooligosaccharide, m-inositol and soy polysaccharide in a ribbon blender for 10 minutes. The required amounts of the following ingredients were added to a ribbon blender: microcrystalline cellulose, citric acid and maltodextrin, and mixed for an additional 20 minutes. 25 kg of blend was taken from the bottom of the mixer and added back through the top of the mixer and mixed for an additional 5 minutes. The dry blend was stored in a drum.

The required amounts of the above pre-blend were added to the dough mixer along with the required amounts of lemon flavor, vitamin/mineral premix, alpha-tocopherol acetate, microencapsulated guar gum and crunchy rice and mixed by the dough mixer for 200 strokes (strokes).

A liquid preblend was prepared by adding the required amounts of high fructose corn syrup, honey, glycerol, crystalline fructose, high oleic safflower oil and bleached lecithin to a Hobart Mixer (Hobart Mixer) for 5 minutes.

All liquid pre-blend was added to the intervening blend in the dough mixer in the first 60 strokes. The total mixing time was set to 500 strokes. When 100 strokes of 150 are left, the desired amount of canola oil is added to the dough mixer.

The combined materials are transferred from the dough mixer to an extruder. The extruder was adjusted to produce 33.3 grams to 37.3 grams of rod cores with a target weight of 35.3 grams. The extruded rod cores were transported through a cooling tunnel set to a target range of 8-12 ℃.

The rod cores were coated with a candy coating prepared as follows. The coating is melted at a temperature range between 46-48 ℃. Temperatures in the melter are not allowed to exceed 50 ℃. Once melted, the coating was held at 46-48 ℃ for 30 minutes to ensure that all unstable crystals were destroyed.

The extruded rod cores are conveyed through a enrober. The coating is applied to the bar at a temperature range of between about 41-48 ℃. The coating temperature in the enrober is not allowed to exceed 50 ℃. The target percent coating was 16.3% and 19% was the maximum coating percent.

After the enrober, the coated rods were transported through a cooling tunnel set at 10 ℃ in the range of 8-13 ℃. The rod passes through a metal detector before wrapping. The cooled sticks are packaged in a foil wrapper.

Examples 7

In this example, an animal model was used to test the effect of administering soy protein to pregnant or breast-fed women on memory and cognition in the offspring.

Test subject

Sprague Dawley (SD) rats (n = 6) allowed to become pregnant were given a diet containing soy protein as the sole protein source (17.5 g soy protein per 100 g feed) or a similar diet containing casein as the sole protein source (control) ad libitum from the third week of gestation until weaning.

After birth, a total of 18 male and female rat pups were assigned to one of 2 groups, depending on the diet their mothers received: group 1 (n =9, 3 females and 6 males) (soy protein) or group 2 (n =9, 2 females and 7 males) (control). Group 1 rats were housed by females administered a soy protein diet, and group 2 rats were housed by females administered a casein-containing control diet. Rats began weaning at postnatal day 21 (PN 21). Behavioral assessments were performed from day 27 after birth (PN 27) to day 35 after birth (PN 35).

Food and water were available ad libitum throughout the home cage from the behavioral assessment. Group 1 rats received the same soy protein diet as administered to their mothers, and group 2 (control) rats were administered a casein-containing control diet. Animals were maintained in a 12:12 hour light-dark cycle, with behavioral assessments performed during the light phase of the cycle. All experimental procedures were approved by the University of Granada Ethics Committee and followed by European Community Council Directive (86/609/EEC) 24/11/1986.

Moris hidden platform task ( PN27-PN35 ）

The Morris hidden platform task is performed at days 27-35 after birth. The pool used in this task consisted of a 150 cm diameter and 50 cm deep circular plastic bucket with a removable visible circular platform of 11 cm diameter. The temperature of the water is maintained at 24-26 ℃. The pool is conceptually divided into four quadrants, and the platform is placed in the center of one of the quadrants, about 35 cm from the pool edge. The water was stained with a non-toxic black ink so that the computerized system used to collect the data could detect white rats.

Training consists of one block per day. Each panel consisted of four trials separated by 5 minute inter-trial intervals. Each trial begins by placing the subject in water against the wall of a pool of one of four compass conditions (east, west, north or south). Each subject released from each of the four compass points once during four trials of one plate. The order is changed randomly. The animal is allowed to swim freely for 60 seconds or until it climbs onto the platform. If it does not find a platform within 60 seconds, it is put there by the experimenter. All rats spent the last 15 seconds of each trial on the platform. During the inter-trial interval, subjects were housed in groups in cages lined with electric heating pads and covered to block the pool and room view. At the end of training exploratory trials, subjects were allowed to swim freely for 60 seconds after release from a fixed starting position.

Video systems and related software allow recording of several dependent variables: escape latency, path length, velocity, time spent in the target quadrant, proximal area (proximal area), platform area crossing, and thigmotaxis (tigmotaxis).

Each subject received 6 training plates, which performed one training session per day during 6 consecutive days, and several exploratory trials without a platform, in order to assess spatial memory 24 and 48 hours after the last training plate.

Results

Latency to platform: figure 1 shows the mean (± SEM) latency for groups 1 and 2 rats to reach the hidden platform during each of the 6 training plates. Both groups display spatial learning, i.e. followingThe latency and distance to reach the hidden platform for the training program is reduced.

Bulk 2 x 6 (group x plates) mixed ANOVA analysis, in which treated groups as inter-group factors and plates as in-subject factors, revealed a significant effect of the major factor plates (F_{（ 4.64 ）}= 22.11；p<0.01), but group (F) is not disclosed_{（ 1.6 ）}= 0.21；p>0.6) or interaction group x plate (F)_{（ 4.64 ）}= 0.83；p>0.5). Post hoc analysis by LSD test showed that the latency decreased significantly and progressively in both groups starting from panel 3, reflecting spatial learning. Therefore, the average latency in plate 3 is shorter than those recorded in the first two plates (p)<0.06) and no difference (p) was seen between panels 5 and 6>0.8）。

Speed of swimming: figure 2 shows the average (± SEM) swimming speed of rats with groups 1 and 2 of training plates during training in the hidden platform task. 2 x 6 (group x plates) Mixed ANOVA analysis, in which treatment groups were used as intergroup factors and plates were used as in-subject factors, did not reveal the major factor group (F)_{（ 1.6 ）}= 0.007；p>0.9), plate (F)_{（ 5.80 ）}= 0.29；p>0.9), or interaction group x plate (F)_{（ 5.80 ）}= 0.62；p>0.6).

Path length: figure 3 shows the mean (± SEM) path lengths of rats along groups 1 and 2 of training plates during training in the hidden platform task. 2 x 6 (group x plates) mixed ANOVA analysis in which treatment groups were used as an inter-group factor and plates were used as an intra-subject factor revealed a major factor plate (F plate)_{（ 5.80 ）}= 22.06；p<0.01), but does not disclose group (F)_{（ 1.6 ）}= 1.35；p>0.2) or interaction group x plates (F)_{（ 5.80 ）}= 0.92；p>0.4). Post hoc analysis by LSD test showed a significant and progressive decrease in distance from plate 4 in both groups, reflecting spatial learning. The average distance in the slab 4 is therefore shorter than those recorded in the preceding slabs (p)<0.01) and no difference (p) was seen between panels 5 and 6>0.3）。

Exploration test ( 24 Hours) -time in each quadrant during the test: figure 4 shows the time spent in each quadrant during the exploratory trial (24 hours post-training) by the rats in each group. 2 x 6 (group x quadrant) Mixed ANOVA analysis, in which the treatment group was an intergroup factor and the quadrant was an intra-subject factor, did not reveal the major factor group (F)_{（ 1.6 ）}= 0.36；p>0.5) or interaction group x quadrant (F)_{（ 5.80 ）}= 0.74；p>0.5), but it shows quadrant (F)_{（ 3.48 ）}= 10.50；p<0.01). Post hoc analysis by LSD testing showed that all groups were in the target, opposite and counter-clockwise quadrants (p)<0.05) spending ratio clockwise quadrant (p)>0.8) more time.

Exploration test ( 24 Hour) -first entry into target quadrant latency during test: figure 5 shows the mean (± SEM) first entry latency of the quadrant in which the platform was located during the test. Better memory of platform position by group 1 is supported by the reduction in latency to reach the target quadrant during the exploration trial. ANOVA analysis of first entry latency in the target quadrant during the course of the exploratory trial revealed group (F)_{（ 1.6 ）}= 6.42；p<0.05) was observed.

Exploration test ( 48 Hours) -time in target quadrant during test: figure 6 shows the time spent in the target quadrant during the exploratory test (48 hours post-training).ANOVA analysis of time in the target quadrant during the exploratory trial revealed group (F)_{（ 1.6 ）}= 4.16; p = 0.05).

Conclusion

The above experiments demonstrate the selective enhancement of spatial memory (morris water maze-hidden platform task) in developing rats of the soybean proteome (group 1). Both group 1 and 2 rats were able to learn the hidden platform water maze task. However, rats receiving the soy protein supplemented diet (group 1) appeared to show better memory of the platform position as they reached the target quadrant before the group 2 rats during the exploration trial (24 hours). Consistently, group 1 rats spent more time in the target quadrant during the exploratory trial (48 hours post-training) than group 2 rats.

Claims (15)

1. A method of improving cognition in an infant, the method comprising administering soy protein to a pregnant female and administering soy protein to the female during breastfeeding.

2. The method of claim 1, wherein the woman is administered soy protein for at least about four weeks prior to delivery of the infant.

3. The method of claim 1, wherein the woman is administered soy protein for at least about six months prior to delivery of the infant.

4. The method of claim 1, wherein the female is administered soy protein daily during pregnancy.

5. The method of claim 1 wherein the woman is administered soy protein during breastfeeding until weaning.

6. The method of claim 5 wherein the infant is administered soy protein after weaning.

7. The method of claim 6 wherein the infant is administered soy protein after weaning up to an age of about twelve months.

8. The method of claim 1, wherein the improvement in cognition is improvement in memory.

9. The method of claim 1, wherein the female is administered from about 3 g/day to about 54 g/day of soy protein during pregnancy.

10. A method of improving cognition in an infant, the method comprising administering soy protein to a pregnant female and administering soy protein to the infant after delivery.

11. The method of claim 10, wherein the soy protein is administered to the infant after delivery via an infant formula comprising soy protein.

12. The method of claim 10, wherein the woman is administered soy protein for at least about four weeks prior to delivery of the infant.

13. The method of claim 10, wherein the infant is administered soy protein for at least about four months after delivery.

14. The method of claim 10, wherein the infant is administered soy protein to an age of about twelve months after delivery.

15. The method of claim 10, wherein the improvement in cognition is improvement in memory.