EP2658389A1 - Verwendung von nährstoffzusammensetzungen mit lactoferrin zur unterstützung der resistenz gegenüber krankheiten und leiden - Google Patents

Verwendung von nährstoffzusammensetzungen mit lactoferrin zur unterstützung der resistenz gegenüber krankheiten und leiden

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Publication number
EP2658389A1
EP2658389A1 EP11810939.6A EP11810939A EP2658389A1 EP 2658389 A1 EP2658389 A1 EP 2658389A1 EP 11810939 A EP11810939 A EP 11810939A EP 2658389 A1 EP2658389 A1 EP 2658389A1
Authority
EP
European Patent Office
Prior art keywords
lactoferrin
human
kcal
nutritional composition
coli
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP11810939.6A
Other languages
English (en)
French (fr)
Inventor
Anja Wittke
Cecilia MUNOZ
Dattatreya Banavara
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
MJN US Holdings LLC
Original Assignee
MJN US Holdings LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US12/980,825 external-priority patent/US20120172288A1/en
Priority claimed from US12/980,833 external-priority patent/US20120171164A1/en
Application filed by MJN US Holdings LLC filed Critical MJN US Holdings LLC
Publication of EP2658389A1 publication Critical patent/EP2658389A1/de
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23J—PROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
    • A23J1/00—Obtaining protein compositions for foodstuffs; Bulk opening of eggs and separation of yolks from whites
    • A23J1/20—Obtaining protein compositions for foodstuffs; Bulk opening of eggs and separation of yolks from whites from milk, e.g. casein; from whey
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20—Milk; Whey; Colostrum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This disclosure relates generally to the field of nutritional
  • compositions such as infant formulas, human milk fortifiers, children's dietary supplements, and the like, having lactoferrin, in particular, lactoferrin produced by a non-human source. More particularly, the disclosure relates to a method of supporting resistance to a disease or condition caused by bacterial and viral pathogens by administering to a human nutritional compositions including lactoferrin.
  • compositions for humans there are currently a variety of dietary compositions for humans, especially young humans, to provide supplemental or primary nutrition at certain stages in life.
  • commercial dietary compositions for infants seek to mimic to the extent possible the composition and associated functionality of human milk.
  • proteins some of which have physiological activity, and blended fat ingredients
  • dietary compositions are formulated such that they simulate human milk for use as a complete or partial substitute.
  • Other ingredients often utilized in dietary compositions for infants may include a carbohydrate source such as lactose as well as other vitamins, minerals and elements believed to be present in human milk for the absorption by the infant.
  • Lactoferrin is one of the primary proteins in human milk and is considered a glycoprotein having an average molecular weight of approximately 80 kilodaltons. It is an iron binding protein having the capacity to bind two molecules of iron in a reversible fashion and can facilitate the uptake of iron within the intestines for the human. Functionally, lactoferrin regulates iron absorption and as such can bind iron-based free radicals as well as donate iron for an immunological response.
  • lactoferrin In obtaining a commercially viable dietary composition, the addition of lactoferrin has generally been limited due to predicted losses of activity during processing. For example, generally, the temperature and pH requirements in processing infant formulas and other products such as human milk fortifiers and various children's products reduce specific functions of the lactoferrin, causing lactoferrin not to be included within a final formulation. In addition, lactoferrin is often considered only for its iron binding qualities; thus, lactoferrin may generally be excluded from a formulation where such properties are thought to be diminished by processing conditions.
  • human breast milk is relatively low in iron, containing about 0.3 milligrams of iron per liter of breast milk. While this quantity is low, human infants have high absorption rate, absorbing about half of the iron from the breast milk.
  • human infants are given prior art formulas with high levels of iron fortification, for example, of from about 10 mg to about 12 milligrams per liter, the infants absorb less than about 5% of the total iron. With such increased levels of iron within the prior art formulas, virtually all of the lactoferrin iron binding sites would be expected to be occupied, as lactoferrin is a known iron transport protein.
  • Additional complications of the prior art formulas include the inability of providing a bacteriostatic effect. This is partially due to the use of lactoferrin with blocked or damaged binding sites, as the bacteriostatic effect is at least partially related to the degree of binding to iron of the lactoferrin present within the formula.
  • composition such as an infant formula, human milk fortifier, children's dietary supplement, and the like, which contains lactoferrin, in particular, lactoferrin from a non-human source.
  • lactoferrin in particular, lactoferrin from a non-human source.
  • the lactoferrin included in the compositions is able to support resistance to a disease or condition caused by bacterial and viral pathogens even after processing under conditions of high temperature and low pH.
  • the disclosure is directed to a method of supporting resistance to a disease or condition, such as viral respiratory tract infection, in a human.
  • a disease or condition such as viral respiratory tract infection
  • the disclosure is directed to a method of supporting resistance in a human to a disease or condition caused by at least one pathogen selected from the group consisting of Enterotoxigenic E. coli (ETEC), Enteropathogenic E. coli (EPEC), Haemophilus influenza, Shigatoxin producing E. coli (STEC), Enteroaggregative E. coli (EAEC), Salmonella ser.
  • the method includes administering to a human a nutritional composition comprising (1) a fat or lipid source, (2) a protein source, and (3) lactoferrin produced by a non-human source.
  • the disease or condition is a viral, lower respiratory tract infection.
  • the nutritional composition comprises:
  • the nutritional compositions may further comprise about 0.1 g/100 kcal to about 1 g/100 kcal of a prebiotic composition, such as a prebiotic composition comprising polydextrose and/or galactooligosaccharide. More preferably, the nutritional composition comprises about 0.3 g/100 kcal to about 0.7 g/100 kcal of a prebiotic composition which comprises a combination of polydextrose and
  • the disclosure is directed to a method of supporting resistance to a disease or condition in a human caused by at least one pathogen selected from the group consisting of ETEC, EPEC, Shigatoxin producing E. coli, EAEC, Salmonella ser. Typhimurium, Shigella flexneri or combinations thereof.
  • the lactoferrin is non-human lactoferrin and/or human lactoferrin produced by a genetically modified organism.
  • the lactoferrin used is such that an effective amount of a nutritional composition containing lactoferrin may be administered to the individual to support resistance to a disease or condition caused by a viral or bacterial pathogen, even if, during processing, the nutritional composition has been exposed to pH and temperature fluctuations typical of certain processing conditions like pasteurization.
  • the present disclosure provides a method of supporting resistance to a disease or condition, such as viral respiratory tract infection, in a human caused by a bacterial or viral pathogen by administering to the human nutritional compositions that comprises a lipid or fat source, a protein source, and lactoferrin from a non-human source.
  • a disease or condition such as viral respiratory tract infection
  • lactoferrin produced by a non-human source and “lactoferrin from a non-human source” means lactoferrin produced by or obtained from a source other than human breast milk.
  • lactoferrin for use in the present disclosure includes human lactoferrin produced by a genetically modified organism as well as non-human lactoferrin.
  • organ refers to any contiguous living system, such as animal, plant, fungus or micro-organism.
  • non-human lactoferrin refers to lactoferrin having an amino acid sequence that is different than the amino acid sequence of human lactoferrin.
  • Lactoferrins are single chain polypeptides of about 80 kD containing 1
  • lactoferrin comprises two homologous lobes, called the N- and C-lobes, referring to the N-terminal and C- terminal part of the molecule, respectively.
  • Each lobe further consists of two sub- lobes or domains, which form a cleft where the ferric ion (Fe 3+ ) is tightly bound in synergistic cooperation with a (bi)carbonate anion. These domains are called Nl, N2, Cl and C2, respectively.
  • the N-terminus of lactoferrin has strong cationic peptide regions that are responsible for a number of important binding
  • Lactoferrin has a very high isoelectric point ( ⁇ pl 9) and its cationic nature plays a major role in its ability to defend against bacterial, viral, and fungal pathogens.
  • ⁇ pl 9 isoelectric point
  • the N-terminal residues 1- 47 of human lactoferrin (1-48 of bovine lactoferrin) are critical to the iron- independent biological activities of lactoferrin.
  • residues 2 to 5 (RRRR) and 28 to 31 (RKVR) are arginine-rich cationic domains in the N- terminus especially critical to the antimicrobial activities of lactoferrin.
  • a similar region in the N-terminus is found in bovine lactoferrin (residues 17 to 42;
  • lactoferrins from different host species may vary in their amino acid sequences though commonly possess a relatively high isoelectric point with positively charged amino acids at the end terminal region of the internal lobe.
  • Suitable lactoferrins for use in the present disclosure include those having at least 48% homology with the amino acid sequence AVGEQELRKCNQWSGL at the HLf (349-364) fragment.
  • the lactoferrin has at least 65% homology with the amino acid sequence AVGEQELRKCNQWSGL at the HLf (349- 364) fragment, and, in embodiments, at least 75% homology.
  • non- human lactoferrins acceptable for use in the present disclosure include, without limitation, bovine lactoferrin, porcine lactoferrin, equine lactoferrin, buffalo lactoferrin, goat lactoferrin, murine lactoferrin and camel lactoferrin.
  • Lactoferrin for use in the present disclosure may be, for example, isolated from the milk of a non-human animal or produced by a genetically modified organism.
  • a process for producing bovine lactoferrin in high purity includes three steps. Raw milk material is first contacted with a weakly acidic cationic exchanger to absorb lactoferrin followed by the second step where washing takes place to remove nonabsorbed substances. A desorbing step follows where lactoferrin is removed to produce purified bovine lactoferrin.
  • Other methods may include steps as described in U.S. Patent Nos. 7,368,141, 5,849,885, 5,919,913 and 5,861,491, the disclosures of which are all incorporated by reference in their entirety.
  • a benefit of lactoferrin is its ability to support resistance to a disease or condition caused by certain bacterial and viral pathogens, including ETEC, EPEC, Haemophilus influenza, STEC, EAEC, Salmonella ser. Typhimurium, Shigella flexneri,
  • lactoferrin is present in the nutritional
  • compositions in an amount of at least about 10 mg/100 kCal, especially when the nutritional composition is intended for use by children.
  • the upper limit for lactoferrin is about 240 mg/100 kCal.
  • lactoferrin is present in the nutritional composition in an amount of from about 70 mg to about 220 mg/100 kCal; in yet another embodiment, lactoferrin is present in an amount of about 90 mg to about 190 mg/100 kCal.
  • Nutritional compositions for infants can include lactoferrin in the quantities of from about 0.5 mg to about 1.5 mg per milliliter of formula. In nutritional compositions replacing human milk, lactoferrin may be present in quantities of from about 0.6 mg to about 1.3 mg per milliliter of formula.
  • the nutritional compositions support resistance to a viral respiratory tract infection.
  • the disclosure is directed to a method of supporting resistance to a viral, lower respiratory tract disclosure.
  • the disclosure is directed to a method of supporting resistance to a respiratory syncytial virus infection.
  • the nutritional compositions of the disclosure may be used to support immune development to better enable the body to fight viral respiratory tract infections, either preventing such infections or reducing their severity.
  • the nutritional composition is administered prophylactically to a human who does not have a disease or condition such as viral respiratory tract infection and/or a disease or condition caused by at least one pathogen selected from the group consisting of ETEC, EPEC, Haemophilus influenza, STEC, EAEC, Salmonella ser. Typhimurium, Shigella flexneri,
  • a disease or condition such as viral respiratory tract infection and/or a disease or condition caused by at least one pathogen selected from the group consisting of ETEC, EPEC, Haemophilus influenza, STEC, EAEC, Salmonella ser. Typhimurium, Shigella flexneri,
  • the human to whom the nutritional composition is administered has viral respiratory tract infection or a disease or condition caused by the at least one pathogen when the nutritional composition is administered.
  • the human to whom the nutritional composition is administered is an infant or a child.
  • infant is generally defined as a human from birth to 12 months of age.
  • child and children are defined as humans over the age of 12 months to about 12 years old.
  • the lactoferrin in the nutritional compositions has the same or similar activity against the disease or condition to that of lactoferrin in free form.
  • the activity of the lactoferrin is not significantly diminished by inclusion in the nutritional composition.
  • the lactoferrin included in the compositions is able to support resistance to a disease or condition caused by bacterial and viral pathogens even after processing under conditions of high temperature and low pH.
  • the lactoferrin used is non-human lactoferrin.
  • bovine lactoferrin maintains certain bactericidal activity even if exposed to a low pH (i.e., below 7, and even as low as about 4.6 or lower) and/or high temperatures (i.e., above about 65°C, and as high as about 120°C), conditions which would be expected to destroy or severely limit the stability or activity of human lactoferrin.
  • a low pH i.e., below 7, and even as low as about 4.6 or lower
  • high temperatures i.e., above about 65°C, and as high as about 120°C
  • bovine lactoferrin has an the amino acid composition which has about a 70% sequence homology to that of human lactoferrin, and is stable and remains active under conditions under which human lactoferrin becomes unstable or inactive
  • bovine lactoferrin has bactericidal activity against undesirable bacterial pathogens found in the human gut.
  • the nutritional composition may be an infant formula.
  • infant formula applies to a composition in liquid or powdered form that satisfies the nutrient requirements of an infant by being a substitute for human milk.
  • the content of an infant formula is dictated by the federal regulations set forth at 21 C.F.R. ⁇ 100, 106 and 107. These regulations define macronutrient, vitamin, mineral, and other ingredient levels in an effort to simulate the nutritional and other properties of human breast milk.
  • the nutritional product may be a human milk fortifier, meaning it is a composition which is added to human milk in order to enhance the nutritional value of human milk.
  • the disclosed composition may be in powder or liquid form.
  • the disclosed nutritional product may be a children's nutritional composition.
  • the nutritional composition of the disclosure may provide minimal, partial, or total nutritional support.
  • the nutritional composition may be a nutritional supplement or a meal replacement.
  • the nutritional composition may be administered in conjunction with a food or another nutritional composition.
  • the nutritional composition can either be intermixed with the food or other nutritional composition prior to ingestion by the subject or can be administered to the subject either before or after ingestion of a food or nutritional composition.
  • the nutritional composition may be administered to preterm infants receiving infant formula, breast milk, a human milk fortifier, or combinations thereof.
  • a "preterm infant” is an infant born after less than 37 weeks gestation
  • a "full term infant” is an infant born after at least 37 weeks gestation.
  • the nutritional compositions may, but need not, be nutritionally complete.
  • nutritionally complete means that the nutritional composition of the present disclosure provides adequate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy required for normal growth.
  • essential refers to any nutrient which cannot be synthesized by the body in amounts sufficient for normal growth and to maintain health and which therefore must be supplied by the diet.
  • conditionally essential as applied to nutrients means that the nutrient must be supplied by the diet under conditions when adequate amounts of the precursor compound is unavailable to the body for endogenous synthesis to occur.
  • composition which is "nutritionally complete” for the preterm infant will, by definition, provide qualitatively and quantitatively adequate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy required for growth of the preterm infant.
  • the composition which is "nutritionally complete” for the full term infant will, by definition, provide qualitatively and quantitatively adequate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy required for growth of the full term infant.
  • composition which is "nutritionally complete” for a child will, by definition, provide qualitatively and quantitatively adequate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy required for growth of a child.
  • the nutritional composition may be provided in any form known in the art, including a powder, a gel, a suspension, a paste, a solid, a liquid, a liquid concentrate, or a ready-to-use product.
  • the nutritional composition is an infant formula, especially an infant formula adapted for use as sole source nutrition for an infant.
  • the nutritional product disclosed herein may be administered enterally.
  • enteral means through or within the gastrointestinal, or digestive, tract, and “enteral administration” includes oral feeding, intragastric feeding, transpyloric administration, or any other introduction into the digestive tract.
  • Suitable fat or lipid sources for practicing the present disclosure may be any known or used in the art, including but not limited to, animal sources, e.g., milk fat, butter, butter fat, egg yolk lipid; marine sources, such as fish oils, marine oils, single cell oils; vegetable and plant oils, such as corn oil, canola oil, sunflower oil, soybean oil, palmolein, coconut oil, high oleic sunflower oil, evening primrose oil, rapeseed oil, olive oil, flaxseed (linseed) oil, cottonseed oil, high oleic safflower oil, palm stearin, palm kernel oil, wheat germ oil; medium chain triglyceride oils and emulsions and esters of fatty acids; and any combinations thereof.
  • animal sources e.g., milk fat, butter, butter fat, egg yolk lipid
  • marine sources such as fish oils, marine oils, single cell oils
  • vegetable and plant oils such as corn oil, canola oil, sunflower oil, soybean oil, palmolein, coconut oil
  • the protein source included in the nutritional composition comprises bovine milk proteins.
  • Bovine milk protein sources useful in practicing the present disclosure include, but are not limited to, milk protein powders, milk protein concentrates, milk protein isolates, nonfat milk solids, nonfat milk, nonfat dry milk, whey protein, whey protein isolates, whey protein concentrates, sweet whey, acid whey, casein, acid casein, caseinate (e.g. sodium caseinate, sodium calcium caseinate, calcium caseinate) and any combinations thereof.
  • the proteins are provided as intact proteins. In other embodiments, the proteins are provided as a combination of both intact proteins and partially hydro lyzed proteins, with a degree of hydrolysis of between about 4% and 10%. In yet another embodiment, the protein source may be supplemented with glutamine- containing peptides.
  • the protein source comprises whey and casein proteins and the ratio of whey to casein proteins ratio is similar to that found in human breast milk.
  • the weight ratio of whey to casein proteins is from about 20% whey:80% casein to about 80% whey: 20% casein
  • the nutritional composition may contain one or more probiotics.
  • probiotic means a microorganism with low or no pathogenicity that exerts beneficial effects on the health of the host. Any probiotic known in the art may be acceptable for use in the present disclosure provided it achieves the intended result.
  • the probiotic may be selected from Lactobacillus species, Lactobacillus rhamnosus GG,
  • Bifidobacterium species Bifidobacterium longum, Bifidobacterium brevis, and Bifidobacterium animalis subsp. lactis BB-12.
  • the amount of the probiotic may vary from about 10 4 to about 10 10 colony forming units (cfu) per kg body weight per day. In another embodiment, the amount of the probiotic may vary from about 10 6 to about 10 9 cfu per kg body weight per day. In yet another embodiment, the amount of the probiotic may be at least about 10 6 cfu per kg body weight per day. Moreover, the disclosed composition may also include probiotic-conditioned media
  • one or more of the probiotics is viable. In another embodiment, one or more of the probiotics is non-viable.
  • viable refers to live microorganisms.
  • non-viable or non-viable probiotic means non-living probiotic microorganisms, their cellular components and metabolites thereof. Such non-viable probiotics may have been heat-killed or otherwise inactivated but retain the ability to favorably influence the health of the host.
  • the probiotics useful in the present disclosure may be naturally-occurring, synthetic or developed through the genetic manipulation of organisms, whether such new source is now known or later developed.
  • the nutritional compositions may include a prebiotic composition comprising one or more prebiotics.
  • prebiotic means a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon that can improve the health of the host.
  • prebiotic composition is a composition that comprises one or more prebiotics.
  • prebiotics may be naturally-occurring, synthetic, or developed through the genetic manipulation of organisms and/or plants, whether such new source is now known or developed later.
  • the prebiotic included in the compositions of the present disclosure include those taught by U.S. Patent No.
  • Prebiotics for use in the present disclosure may be naturally-occurring, synthetic, or developed through the genetic manipulation of organisms and/or plants, whether such new source is now known or developed later.
  • Prebiotics useful in the present disclosure may include oligosaccharides, polysaccharides, and other prebiotics that contain fructose, xylose, soya, galactose, glucose and mannose.
  • prebiotics useful in the present disclosure may include lactulose, lactosucrose, raffinose, gluco-oligosaccharide, inulin, polydextrose, polydextrose powder, galactooligo saccharide, fructo-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharides, lactosucrose, xylo-oligosacchairde, chito-oligosaccharide, manno-oligosaccharide, aribino-oligosaccharide, siallyl-oligosaccharide, fuco- oligosaccharide, and gentio-oligosaccharides.
  • the nutritional preferably, lactosucrose, raffinose, gluco-oligosaccharide, inulin, polydextrose, polydextrose powder, galactooligo saccharide, fructo-oligosaccharide, isomal
  • compositions comprise polydextrose (PDX) and/or galactooligosaccaharide (GOS).
  • PDX polydextrose
  • GOS galactooligosaccaharide
  • the nutritional compositions comprise one or more additional prebiotics.
  • the total amount of prebiotics present in the nutritional composition may be from about 0.1 g/100 kcal to about 1 g/100 kcal. More preferably, the total amount of prebiotics present in the nutritional composition may be from about 0.3 g/100 kcal to about 0.7 g/100 kcal. At least 20% of the prebiotics should comprise galactooligosaccharide and/or polydextrose.
  • the amount of polydextrose in the nutritional composition may, in an embodiment, be within the range of from about 0.1 g/100 kcal to about 1 g/100 kcal. In another embodiment, the amount of polydextrose in the nutritional compositions is within the range of from about 0.2 g/100 to about 0.6 g/100 kcal.
  • the amount of galactooligosaccharide in the nutritional composition may, in an embodiment, be from about 0.1 g/100 kcal to about 1 g/100 kcal. In another embodiment, the amount of galactooligosaccharide in the nutritional composition is from about 0.2 g/100 kcal to about 0.5 g/100 kcal. In certain embodiments, the ratio of polydextrose to galactooligosaccharide in the prebiotic composition is between about 9:1 and about 1:9.
  • the nutritional formulation of the disclosure may further contain a source of long chain polyunsaturated fatty acids (LCPUFAs).
  • LCPUFAs long chain polyunsaturated fatty acids
  • the source of LCPUFAs comprise docosahexanoic acid (DHA).
  • DHA docosahexanoic acid
  • suitable LCPUFAs include, but are not limited to, a-linoleic acid, ⁇ -linoleic acid, linoleic acid, linolenic acid, eicosapentanoic acid (EPA) and arachidonic acid (ARA).
  • the nutritional composition is supplemented with both DHA and ARA.
  • the weight ratio of ARA:DHA may be from about 1:3 to about 9:1. In one embodiment of the present disclosure, the weight ratio of ARA:DHA is from about 1:2 to about 4:1.
  • the amount of long chain polyunsaturated fatty acids in the nutritional composition may vary from about 5 mg/100 kcal to about 100 mg/100 kcal, more preferably from about 10 mg/100 kcal to about 50 mg/100 kcal.
  • the nutritional composition may be supplemented with oils containing
  • DHA and ARA using standard techniques known in the art.
  • DHA and ARA may be added to the composition by replacing an equivalent amount of an oil, such as high oleic sunflower oil, normally present in the composition.
  • oils containing DHA and ARA may be added to the composition
  • the source of DHA and ARA may be any source known in the art such as marine oil, fish oil, single cell oil, egg yolk lipid, and brain lipid.
  • the DHA and ARA are sourced from the single cell Martek oils, DHASCO® and ARASCO® respectively, or variations thereof.
  • the DHA and ARA can be in natural form, provided that the remainder of the LCPUFA source does not result in any substantial deleterious effect on the infant. Alternatively, the DHA and ARA can be used in refined form.
  • sources of DHA and ARA are single cell oils as taught in U.S. Pat. Nos. 5,374,567; 5,550,156; and 5,397,591, the disclosures of which are incorporated herein in their entirety by reference.
  • the nutritional compositions comprise from about 0.5 mg/100 kcal to about 5 mg/100 kcal of iron, including iron bound to lactoferrin.
  • This Example exemplifies the effect of lactoferrin and infant formula on the growth of diarrengic E. coli strains in vitro.
  • DEC clinical diarrheageanic E. coli
  • ETEC Enterotoxigenic E. coli
  • EPEC Enteropathogenic E. coli
  • STEC Shigatoxin producing E. coli
  • EAEC Enteroaggregative E. coli
  • All clinical strains and standard laboratory control strains are grown in McConkey agar medium over 24 hours at 37°C.
  • the strains are grown in lysogeny broth at 37°C for 18 hours. The strains are then washed twice in PBS and centrifugated at 4500 x g for 5 min. Only bacteria in mid-log phase is used.
  • Each plate is also inoculated, via microdilution, with the stock solution of infant formula or lactoferrin such that each strain is tested against 0, 0.6, 1, 2, 4, 6, 8 or 10 mg/ml of lactoferrin or infant formula.
  • the plates are incubated at 37°C and monitored every 30 minutes for growth kinetics by serial cultures of 10-fold dilutions. Growth is then monitored in a spectrophotometer and/or ELISA reader. After incubation for 18-20 hours, the MIC for each strain is recorded as the lowest concentration of infant formula or lactoferrin that caused complete bacterial inhibition.
  • lactoferrin/infant formula combination on bacterial growth is measured as described above.
  • concentrations of lactoferrin and infant formula are determined for each agent separately based on the results of the MIC study and growth kinetics.
  • This Example exemplifies the effect of lactoferrin and infant formula on the adherence of diarrengic E. coli strains to human intestinal epithelial cells in vitro.
  • a subconfluent layer of Hep2 cells (approximately 5 x 10 4 cells/well in a 24-well plate) is infected with the Enterotoxigenic E. coli, Enteropathogenic E. coli, Shigatoxin producing E. coli, Enteroaggregative E. coli, Salmonella ser.
  • This Example exemplifies the effect of lactoferrin and infant formula in supporting resistance to conditions or diseases caused by bacterial pathogens in vivo.
  • Healthy, female Balb/c strain mice between 6 and 8 weeks of age with a weight between 20 and 24 g are obtained and separated into an experimental group and control group.
  • the experimental group is then fed 200 ⁇ of infant formula containing either 75 or 165 mg/ml of lactoferrin before infection and the control group is fed 200 ⁇ of infant formula before infection.
  • the amount of infant formula that is administered is adjusted so the amount the mice receive is equivalent to 600 mg/kg and 1333 mg/kg per day of lactoferrin.
  • the mice are then infected with 300 ⁇ 10 8 colony forming units (cfu) of Salmonella ser.
  • mice For infection and pre-treatment inoculations, a gavage needle is used. After infection, the mice receive infant formula containing either 75 or 165 mg/ml of lactoferrin or infant formula alone ad libitum, respectively for 7 days. Again, the amount of infant formula that is administered is adjusted so the amount the mice receive is equivalent to 600 mg/kg and 1333 mg/kg per day of lactoferrin. The mortality, weight and clinical signs (piloerection, hunched position, and reduced movement) is monitored daily in all mice for 7 days after infection.
  • This Example exemplifies the effect of lactoferrin and infant formula in supporting resistance to conditions or diseases caused by viral pathogens in vivo.
  • Example 3 is performed as described above, except that mice are infected with strains of Rotavirus, Norovirus, Astrovirus, Adenovirus and Calicivus instead of the bacterial strains. The mice are monitored and studied as described above.
  • This example illustrates an embodiment of a nutritional product according to the present disclosure.
  • This example illustrates another embodiment of a nutritional product according to the present disclosure.
  • This example illustrates one embodiment of ingredients that can be used to prepare the nutritional product according to the present disclosure.
  • the nutritional composition is administered to a human and supports resistance to a disease or condition in the human caused by a bacterial or viral pathogen, including viral respiratory tract infection.

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EP11810939.6A 2010-12-29 2011-12-15 Verwendung von nährstoffzusammensetzungen mit lactoferrin zur unterstützung der resistenz gegenüber krankheiten und leiden Ceased EP2658389A1 (de)

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US12/980,825 US20120172288A1 (en) 2010-12-29 2010-12-29 Use of nutritional compositions including lactoferrin in supporting resistance to diseases and conditions
US12/980,833 US20120171164A1 (en) 2010-12-29 2010-12-29 Use of nutritional compositions including lactoferrin in supporting resistance to viral respiratory tract infections
PCT/US2011/065229 WO2012091945A1 (en) 2010-12-29 2011-12-15 Use of nutritional compositions including lactoferrin in supporting resistance to diseases and conditions

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US9609888B2 (en) * 2013-07-31 2017-04-04 Mead Johnson Nutrition Company Nutritional compositions containing synergistic combination and uses thereof
US20160015068A1 (en) * 2014-07-16 2016-01-21 Mead Johnson Nutrition Company Nutritional formulas containing oil blends and uses thereof
EP2992894A1 (de) 2014-09-05 2016-03-09 Progine Farmaceutici Srl Vaginal formulierungen für die vorbeugung und behandlung von vaginal- und zervikovaginalen infektionen
IT201600128713A1 (it) * 2016-12-20 2018-06-20 Frima Res Srls Composizione nel trattamento dell'anemia infiammatoria o da flogosi da malattia cronica
WO2022091023A1 (en) * 2020-11-02 2022-05-05 Apharm Srl Combination of active ingredients, compositions containing it and their use to sustain and strengthen the immune system
CN115886073A (zh) * 2022-04-01 2023-04-04 北京三元食品股份有限公司 一种发酵乳

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CA2823018A1 (en) 2012-07-05
CN107668721A (zh) 2018-02-09
CN103429092A (zh) 2013-12-04
BR112013015458A2 (pt) 2016-08-09
HK1250608A1 (zh) 2019-01-11
WO2012091945A1 (en) 2012-07-05
RU2013134133A (ru) 2015-02-10
ECSP13012799A (es) 2013-10-31
TW201306760A (zh) 2013-02-16

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