Infant formula with free amino acids and nucleotides

Food or edible material: processes – compositions – and products – Products per se – or processes of preparing or treating... – Fat or oil is basic ingredient other than butter in emulsion...

Reexamination Certificate

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C426S656000, C426S801000, C426S658000, C514S045000, C514S046000

Reexamination Certificate

active

06645543

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention relates to a non-milk based hypoallergenic infant-formula for “at-risk” infants no more than one year old, who have a documented milk allergy, such as cow's milk allergy (“CMA”), and/or an allergy to protein in “soy milk”. By “non-milk based” is meant that no ingredient of the formula is derived from mammalian milk. Because typically, such infants have acquired digestive or absorption problems, the only source of protein in the formula is to be from free amino acids, and the formula is to be storable in powder form but have specified deliverability. By “specified deliverability” is meant that the powder is solubilized in an essentially homogeneous liquid form within less than 30 secs when a unit dosage amount of 32.6 gm of the powder is manually shaken with water at 35° C. in a bottle containing 240 ml (8 fl oz) of water. By “solubilized” is meant that the powder is either soluble in water or forms an emulsion in water forming a liquid having physical characteristics analogous to those of human milk.
Still more particularly, the novel formula of the invention does not otherwise mimic human milk in that nutrient powder contains no intact or antigenic proteins; when the powder is solubilized as a ready-to-feed liquid, it is required to have a viscosity less than 10 cp at 25° C. to allow flow through a tube if the formula is delivered enterally rather than taken orally. By “intact protein” is meant a tripeptide or larger molecule having a molecular weight greater than about 500 Daltons; protein hydrolysates of whey or casein contain a major proportion by weight of tripeptides or larger molecules. Hereafter the term “enterally” specifically refers to feeding through a tube such as is typically inserted into the stomach of an infant who cannot easily be fed orally; and the term “at-risk infant” is used to specify one which is no more than one year old. The age limit is critical because a child more than one year old is not seriously “at-risk” since a one-year old is typically fed other food along with formula, and is relatively tolerant to an unbalanced formula for long enough a time to allow a competent nutritionist to alleviate the effects of the misdirected or misapplied diet. A typical infant, not a prematurely born infant, who is to be fed the novel formula weighs in the range from about 2.3 kg (5 lb) to 5.5 kg (12 lb) at birth, and weighs in the range from about 4.5 kg (10 lb) to 11.5 kg (25 lb) after one year.
The problem is to provide a storable powder formula which (i) provides the entire nutrition requirement of an at-risk infant needing an energy content in the range from about 200-250 Kcal/g nitrogen, without including any intact protein, (ii) is “gut-healing”, that is, effective to heal damage already inflicted on the infant's digestive system, and (iii) yet meets the deliverability requirements specified. The problem is solved with a formula having a tailored distribution of amino acids and nucleotides which in combination with a source of unsaturated fats and relatively short chain carbohydrates and other ingredients, provide all the vitamin and mineral needs of the infant, yet prevent GI problems. A nucleotide consists of a nucleoside combined with phosphoric acid; a nucleoside is a compound made of a sugar and a purine or pyrimidine base, especially one obtained by hydrolysis of a nucleic acid, such as adenosine. The term “nucleotide” is used herein as an equivalent of “nucleoside” in that the form in which the compound is present is not critical so long as the specified number of “nucleotide equivalents” are used. A “nucleotide equivalent” refers to the nucleotide content present in any one or more of the following forms: ribo-nucleosides, ribo-nucleotides, RNA, phosphate esters and d-ribose adducts of one with another; the various forms of nucleotides are determined, calculated and expressed as the monophosphate esters.
Unless there is reason to suspect an infant will be allergic to mammalian milk, such as cow's milk, and/or to the protein in “soy milk”, as for instance when an older sibling suffered from the allergy, a typical infant acquires cow's milk-induced enteropathy or enterocolitis, commonly referred to as “damaged gut”, and becomes at-risk under several circumstances. The condition may be evident very soon if the infant is never breast-fed by its mother but is immediately fed an infant formula; the condition may be evident almost as quickly if the infant is breast-fed by its mother who drinks cow's milk or goat's milk; the condition may be evident a little later when the infant ceases to be breast-fed or the mother does not drink cow's milk, or does not drink sufficient cow's milk to impart evident signs of the condition in the infant; or the condition may be evident when the infant is breast-fed but not sufficiently well to provide all the infant's nutrition. Such evident signs of “damaged gut” include vomiting, diarrhea, and/or blood in the stool. A formula which fails to heal such damage is deemed deficient for the needs of an at-risk infant with damaged gut.
As will presently be evident, numerous infant-formulae purportedly especially formulated for infants and free of any milk-derived protein, fall far short of meeting the exigent requirements of a formula specifically directed to an infant in this particular mode of distress.
In particular, U.S. Pat. No. 5,719,133 teaches a dietary composition containing 100% free amino acids specially designed to provide a balance of amino acids for adolescents, but does not provide any nucleotides. Since the formula in the '133 patent addressed a different problem, namely one where an adolescent needed the protein content essentially free of intact protein, but was otherwise unrestricted with respect to nutrients able to provide nucleotides, the amino acids provide from 10% to 20% of the total caloric content of the formula; the lipid component provides from 20% to 35% of the total caloric content with no restriction as to its source; and the carbohydrate provides from 50% to 65% of the total caloric content with no restriction as to the chain length thereof. However, it should not be surprising that the ranges of both essential and non-essential amino acids disclosed, and the ratios of certain amino acids to others, which ranges and ratios are designed to balance the diet of an adolescent, are inappropriate for an at-risk infant. It is found that the optimum lipid content for an at-risk infant-formula provides 50% of the total caloric content, but to solubilize fat in powder form for specified deliverability required adjusting the distribution of amino acids and nucleotides. Moreover, the carbohydrate content of the '133 formula is too high, and the lipid content too low for a desirable formula for at-risk infants.
U.S. Pat. No. 5,066,500 to Gil et al teaches the use of any one or more of all nucleotides
ucleosides in a humanized milk formula for low-birth weight, premature and pre-term infants, teaches the use of cow's milk sometimes as powder milk, and “butterfat” in each example; and, for nitrogenous sources, teaches “a mixture of dairy proteins (casein or sodium and calcium caseinates and lactose free lactalbumin) and protein hydrolyzates with low molecular weight (maximum molecular weight 1,000 Daltons, average molecular weight, 500 Daltons). As carbohydrate sources, glucose polymers are employed, such as dextrinmaltose with a different grade of dextrose equivalent degree, preferably between 10 and 30 DE. Fats are employed as a mixture of animal and one or more vegetable fats to meet the essential fatty acids requirements of patients.” (see col 9, lines 45-55). There is no suggestion that the protein be provided by only a combination of essential and non-essential amino acids, and none that there may be anything critical about the choice of a spectrum of amino acids and nucleotides, each in specified ranges, which are chosen to be absorbed and utilized by an at-risk infant.
U.S. Pat. No. 4,544,559 to Gi

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