CN103429092A - Use of nutritional compositions including lactoferrin in supporting resistance to diseases and conditions - Google Patents
Use of nutritional compositions including lactoferrin in supporting resistance to diseases and conditions Download PDFInfo
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- CN103429092A CN103429092A CN2011800627084A CN201180062708A CN103429092A CN 103429092 A CN103429092 A CN 103429092A CN 2011800627084 A CN2011800627084 A CN 2011800627084A CN 201180062708 A CN201180062708 A CN 201180062708A CN 103429092 A CN103429092 A CN 103429092A
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- lactoferrin
- alimentation composition
- 100kcal
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- disease
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- 229960003487 xylose Drugs 0.000 description 1
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- 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
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- 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
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- A23J1/00—Obtaining protein compositions for foodstuffs; Bulk opening of eggs and separation of yolks from whites
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- 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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract
The present disclosure relates to the use of nutritional compositions including lactoferrin from a non-human source in supporting resistance to diseases or conditions. The method includes administering to a human a nutritional composition comprising a fat or lipid source, a protein source and lactoferrin produced by a non-human source.
Description
Technical field
The alimentation composition field of the lactoferrin that the disclosure relates generally to have lactoferrin, particularly produced by inhuman source, infant formula (infant formulas) for example, human milk fortifier, children dietary replenishers etc.More specifically, the disclosure relates to by use the alimentation composition that comprises lactoferrin to the people, the disease that the support opposing is caused by bacterium and viral pathogen or the method for situation.
Background technology
Have at present variously for people, especially youthful dietary composition, at specific life stage, provide and supplement or basic nutrition.In general, try hard to composition and the correlation function of human milk simulating as far as possible for baby's commercial dietary composition.Have the combination of the fat constituent of the albumen of physiologically active and fusion by some of them, dietary composition is formulated as their human milk simulatings, as substitute wholly or in part.The composition that other dietary composition through being everlasting for the baby is used can comprise that the carbohydrate source, as lactose and other vitamin, mineral matter and element, thinks that they are present in human milk for being absorbed by the baby.
Lactoferrin is one of basic albumen in human milk, thinks that it is the glycoprotein with about 80 kilodalton mean molecule quantities.It is IBP, has the ability in conjunction with bimolecular iron in reversible mode, and can promote the absorption of iron in people's enteron aisle.On function, lactoferrin is regulated iron and is absorbed, and so, can and provide iron for immune response in conjunction with the free radical based on iron.
In obtaining commercial great-hearted (viable) dietary composition, because expection active in process is lost, the interpolation of lactoferrin is restricted usually.For example, in general, processing infant formula and other products, as the specific function of the temperature in human milk fortifier and various juvenile product and pH demand reduction lactoferrin, cause lactoferrin not to be included in final preparation.In addition, lactoferrin its iron binding property that usually only is considered, therefore in the situation that think that the processed condition of this character reduces, lactoferrin may be excluded outside preparation usually.
Further, as be known in the art, lacto's iron is relatively low, and every liter of breast milk contains approximately 0.3 milligram of iron.Although this amount is low, the people baby has high absorptivity, absorbs only about half of iron from breast milk.Yet, when the people baby be given have the strengthening of high-level iron for example every liter from approximately 10 milligrams during to the about prior art formula of 12 milligrams, the baby absorbs and is less than approximately total iron of 5%.Like this iron of increase level in the application prior art formula, in fact all iron binding sites can be expected and are occupied, because lactoferrin is known iron transfer albumen.
The other problem of prior art formula comprises can not provide fungistatic effect.This part is to have the lactoferrin of the binding site that is closed or damages due to use, because fungistatic effect is relevant in conjunction with the degree of iron with the lactoferrin existed in formula at least partly.
Correspondingly, it will be useful providing alimentation composition such as the infant formula that contains the lactoferrin that lactoferrin particularly produces by inhuman source, human milk fortifier, children dietary replenishers etc.In view of the people, viral respiratory infection popular in baby and children especially, the alimentation composition of the opposing viral respiratory infection that provides support will be useful especially.Preferably, even after the lactoferrin comprised in composition processes under high temperature and low pH condition, also can support disease or situation that opposing is caused by bacterium and viral pathogen.
Summary of the invention
In brief, in one embodiment, the disclosure relates to for example method of viral respiratory infection of disease or situation of supporting in the opposing people.In another embodiment, the disclosure relate in the people support opposing by least one be selected from enterotoxigenic escherichia coli (ETEC), enteropathogenic E.Coli (EPEC), haemophilus influenzae (
Haemophilus influenza), shiga toxin producing escherichia coli (STEC), enteroaggrerative E.coli (EAEC), salmonella typhimurium serotype (
Salmonella ser. Typhimurium), shigella flexneri (
Shigella flexneri), the disease that causes of the pathogen of rotavirus, norovirus, Respiratory Syncytial Virus(RSV) (RSV), adenovirus and combination thereof or the method for situation.Described method comprises uses the alimentation composition that comprises the lactoferrin that (1) fat or lipid source, (2) dietary protein origin and (3) produce by inhuman source to the people.In certain embodiments, disease or situation are viral ALRI.
In one embodiment, alimentation composition comprises:
A. the fat of about 7g/100kal or lipid are originated at the most, and more preferably from about 3g/100kcal is to fat or the lipid source of about 7g/100kcal;
B. the dietary protein origin of about 5g/100kcal at the most, more preferably from about 1g/100kcal is to the dietary protein origin of about 5g/100kcal; With
C. at least about the lactoferrin of 10mg/100kCal, more preferably from about 70mg is to the lactoferrin of about 220mg/100kCal, and most preferably from about 90mg to the lactoferrin of about 190mg/100kCal.Optionally, in certain embodiments, alimentation composition can further comprise the prebiotic compositions of about 0.1g/100kcal to about 1g/100kcal, for example comprises the prebiotic compositions of polydextrose and/or galactooligosaccharide.More preferably, alimentation composition comprises the prebiotic compositions that about 0.3g/100kcal comprises polydextrose and galactooligosaccharide combination to about 0.7g/100kcal.In certain embodiments, the disclosure relates in the people and to support opposing to be selected from disease that the pathogen of ETEC, EPEC, shiga toxin producing escherichia coli, EAEC, salmonella typhimurium serotype, shigella flexneri or its combination causes or the method for situation by least one.
Preferably, lactoferrin is non-human lactoferrin and/or passes through the biogenic human lactoferrin of genetic modification.In an especially preferred embodiment, the lactoferrin used makes the alimentation composition containing lactoferrin of effective dose can be applied to individual disease or situation to support that opposing is caused by virus or bacterial pathogens, even in process, alimentation composition once was exposed to some processing conditions as typical pH and temperature fluctuation in pasteurization.
Specific embodiments
In one embodiment, the disclosure provides by using to the people and has comprised lipid or adipose-derived, dietary protein origin and, from the alimentation composition of the lactoferrin in inhuman source, the disease in the people who supports opposing to be caused by bacterium or viral pathogen or situation be the method for viral respiratory infection for example.
As used herein, " lactoferrin produced by inhuman source " and " from the lactoferrin in inhuman source " refer to the lactoferrin that is produced or obtained by the source outside the lacto separately.For example, the lactoferrin that the disclosure is used comprises by the biogenic human lactoferrin of genetic modification and non-human milk ferritin.Term as used herein " biology " refers to the system of any continuous existence, for example animal, plant, fungi or microorganism.Term as used herein " non-human milk ferritin " refers to have the lactoferrin of the amino acid sequence of the amino acid sequence that is different from human lactoferrin.
Lactoferrin is about 80kD, the single chain polypeptide that contains 1-4 glycan according to species.The 3D structure of different plant species lactoferrin is very similar, but not identical.The leaf that each lactoferrin comprises two homologies, be called N-and C-leaf, refers to respectively N-end and the C-end portion of molecule.Every leaf further is comprised of two inferior leaves or domain, and they form the iron ion (Fe of place, ，Zai crack, crack
3+) with carbonic acid (bicarbonate radical) anion synergy, combine closely.These domains are called N1, N2, C1 and C2.The N end of lactoferrin has strong cation peptide zone, and it is responsible for many important binding characteristics.Lactoferrin has very high isoelectric point (～pI9), and its cationic property is brought into play Main Function in it resists the ability of bacterium, virus and fungal pathogens.The residual base cluster of several cationic amino acids is arranged in the N of lactoferrin stub area, the BA of mediation lactoferrin to wide scope microorganism.For example, the 1-48 of the N terminal residue 1-47(bovine lactoferrin of human lactoferrin) BA for the iron dependent/non-dependent of lactoferrin is crucial.In human lactoferrin, residue 2 is to 5(RRRR) and 28 to 31(RKVR) be to be rich in arginic cationic structural territory in the N end, to the antimicrobial acivity of lactoferrin, be especially crucial.In bovine lactoferrin, found zone similarity in the N end (residue 17 to 42, FKCRRWQWRMKKLGAPSITCVRRAFA).
As at publication Biochemistry and Cell Biology, described in " the Perspectives on Interactions Between Lactoferrin and Bacteria " occurred in pp 275-281 (2006), lactoferrin from the different hosts species, its amino acid sequence may be different, although they have relatively high isoelectric point jointly in the stub area of internal lobe with positively charged amino acid.Comprising and HLf(349-364 for suitable lactoferrin of the present disclosure) the amino acid sequence AVGEQELRKCNQWSGL at fragment place has those of at least 48% homology.In some embodiments, lactoferrin and HLf(349-364) the amino acid sequence AVGEQELRKCNQWSGL at fragment place has at least 65% homology, and in some embodiments, at least 75% homology.For example, can be accepted for non-human milk ferritin of the present disclosure and include but not limited to, bovine lactoferrin, pig lactoferrin, horse lactoferrin, buffalo's milk ferritin, goat dairy ferritin, mouse lactoferrin and bactrian camel milk ferritin.
Can for example from non-human animal's milk, separate for lactoferrin of the present disclosure, or produce by the biology of genetic modification.For example, in integral body is incorporated to the U.S. Patent number 4,791,193 of this paper by reference, Okonogi etc. disclose the method for production bovine lactoferrin in high purity.Usually, disclosed method comprises 3 steps.Raw material milk at first with weak-acid kation exchanger Contact-sorption lactoferrin, be then second step, wherein clean the material of removing non-absorption.Follow by desorption procedure, wherein lactoferrin is removed to the bovine lactoferrin that produces purifying.Other method can comprise as at U.S. Patent number 7,368, the step of describing in 141,5,849,885,5,919,913 and 5,861,491, their disclosure all by reference integral body be incorporated to.
The benefit of lactoferrin, as for some embodiment of the present disclosure, be that it supports disease that opposing is caused by some bacterium and viral pathogen or the ability of situation, described pathogen comprises ETEC, EPEC, haemophilus influenzae, STEC, EAEC, salmonella typhimurium serotype, shigella flexneri, rotavirus, norovirus, RSV, adenovirus and combination thereof.
In one embodiment, lactoferrin exists with the amount at least about 10mg/100kCal in alimentation composition, especially when described alimentation composition intention is applied by children.In certain embodiments, the upper limit of lactoferrin is about 240mg/100kCal.In another embodiment, when alimentation composition is infant formula, lactoferrin exists with the amount from about 70mg to about 220mg/100kCal in alimentation composition; In another embodiment, lactoferrin exists to the amount of about 190mg/100kCal with about 90mg.Alimentation composition for the baby can comprise the lactoferrin from every milliliter of about 0.5mg of formula to the amount of about 1.5mg.In the alimentation composition that substitutes human milk, lactoferrin can be from every milliliter of about 0.6mg of formula to the approximately amount existence of 1.3 mg.
As described in, in one embodiment, alimentation composition support opposing viral respiratory infection.People, particularly baby and children Yi Fasheng viral respiratory infection.Viral ALRI, especially those by Respiratory Syncytial Virus(RSV), caused those, can be debatable especially.In fact, Respiratory Syncytial Virus(RSV) is the main cause that baby and children are in hospital, and for example can cause, and bronchitis, pneumonia and long-term complications are for example stridulated.Therefore, in a preferred embodiment, the disclosure relates to the method for supporting the opposing virus lower respiratory tract infection.In still another preferred embodiment, the disclosure relates to the method for supporting the opposing respiratory syncytial virus infection.For example, alimentation composition of the present disclosure can be used for supporting immunity to grow, and makes better body antagonism viral respiratory infection, or prevents this infection or reduce their order of severity.
In certain embodiments, alimentation composition prophylactically is applied to and does not have for example viral respiratory infection and/or be selected from disease that the pathogen of ETEC, EPEC, haemophilus influenzae, STEC, EAEC, salmonella typhimurium serotype, shigella flexneri, rotavirus, norovirus, RSV, adenovirus and combination thereof causes or the people of situation by least one of disease or situation.In other embodiments, be applied the people of alimentation composition when alimentation composition is applied, there is viral respiratory infection or the disease caused by least one pathogen or situation.
Preferably, the people that alimentation composition is applied is baby or children.As used herein, term " baby " is normally defined the people from birth to 12 months ages." children " and " children " are defined as the age and surpass 12 months to about 12 years old large people.
Preferably, the lactoferrin in alimentation composition has with the activity of the lactoferrin of free form same or similarly active to disease or situation.In other words, preferably, the activity of lactoferrin does not reduce significantly by being included in alimentation composition.Even after the lactoferrin also comprised in preferred composition is processed under high temperature and low pH condition, also can support disease or situation that opposing is caused by bacterium and viral pathogen.In an embodiment of the present disclosure, lactoferrin used is the non-human milk ferritin.
For example, surprisingly, even bovine lactoferrin is exposed to stability or the active condition that can expect destruction or seriously limit human lactoferrin and hangs down pH(lower than 7, and even low by according to appointment 4.6 or lower) and/or high temperature (higher than approximately 65 ℃, and height 120 ℃ according to appointment) also keep some bactericidal activity.These low pH and/or hot conditions can be expected during some processing scheme of the alimentation composition of type described herein, for example pasteurization.Yet, although bovine lactoferrin has with human lactoferrin and has the approximately amino acid composition of 70% sequence homology, and stable and keep active under human lactoferrin becomes the condition of unstable or inactivation, bovine lactoferrin has bactericidal activity to the bacterial pathogens of not expecting of finding in people's enteron aisle.
In some embodiments, alimentation composition of the present disclosure can be infant formula.Term " infant formula " is applicable to by meet the liquid of infant nutrition demand or the composition of powder type as the human milk substitute.In the U.S., the content of infant formula is by 21 C.F.R. § § 100,106 and the federal regulations listed for 107 times regulation.These rules have defined macronutrient, vitamin, mineral matter and other composition level, to make great efforts nutrition and other character of simulation lacto.In an independent embodiment, nutrition product can be human milk fortifier, means that it is to add human milk to increase the composition of human milk nutritive value.As human milk fortifier, disclosed composition can be powder or liquid form.In another embodiment, disclosed nutrition product can be the child nutrition composition.
Alimentation composition of the present disclosure can provide minimum, part or all of nutritional support.Alimentation composition can be nutritious supplementary pharmaceutical or dietary substitute.In some embodiments, alimentation composition can be used together with food or other alimentation composition.In the present embodiment, alimentation composition can mix mutually with food or other alimentation composition before the object picked-up, or can before or after pickuping food or alimentation composition, be administered to object.Alimentation composition can be applied to the preemie who accepts infant formula, human milk, human milk fortifier or its combination.For purpose of the present disclosure, " preemie " is less than the baby who is born after gestation in 37 weeks, and " full-term newborn infant " is the baby of birth after at least 37 all gestation.
Alimentation composition can but need not be comprehensive nutrition.The technical staff will recognize that " comprehensive nutrition " depends on many factors and change, and include but not limited to that age, clinical condition and the meals of the object of applicable this term are taken in.Usually, " comprehensive nutrition " refers to that alimentation composition of the present disclosure provides normal growth required enough all carbohydrate, lipid, essential fatty acid, protein, essential amino acid, conditionally essential amino acid, vitamin, mineral matter and energy.As for nutraceutical, term " essential " can not be synthetic with the amount that is enough to be used in normal growth and keeps fit by body and any nutrients that must supplement by diet thereby refer to.As for nutraceutical, term " condition must " refer to body can not get enough precursor compounds for occur must be supplementary by diet under endogenous condition when synthetic nutrients.
By limiting, the composition that is " comprehensive nutrition " for the preemie will provide the preemie the enough all carbohydrate on required quantitative and qualitative analysis of growing, lipid, essential fatty acid, protein, essential amino acid, conditionally essential amino acid, vitamin, mineral matter and energy.By limiting, the composition that is " comprehensive nutrition " for full-term newborn infant will provide the full-term newborn infant enough all carbohydrate on required quantitative and qualitative analysis of growing, lipid, essential fatty acid, protein, essential amino acid, conditionally essential amino acid, vitamin, mineral matter and energy.By limiting, the composition that is " comprehensive nutrition " for children will provide all carbohydrate enough on the required quantitative and qualitative analysis of children growth, lipid, essential fatty acid, protein, essential amino acid, conditionally essential amino acid, vitamin, mineral matter and energy.
Alimentation composition can provide with any form known in the art, comprises powder, gel, suspension, cream (paste), solid, liquid, liquid concentrate or off-the-shelf.In a preferred embodiment, alimentation composition is infant formula, especially is suitable for use as the infant formula of the unique nutrient source of baby.
In preferred embodiments, nutrition product disclosed herein can be used through enteron aisle.As described herein, " through enteron aisle " refers to by intestines and stomach or alimentary canal or in intestines and stomach or alimentary canal, and " through enteron aisle, using " comprises feeding in oral feeding, stomach, uses or to any other importing in alimentary canal through pylorus.
Can be any known or source of using, this area for implementing suitable fat of the present disclosure or lipid source, include but not limited to, animal origin, butterfat for example, butter, cream, yolk lipid; Marine source, fish oil for example, marine oil (marine oils), single cell oil; Vegetables and vegetable oil, corn oil for example, Canola Oil, sunflower oil, soybean oil, palm olein, coconut oil, high oleic sunflower oil, evening primrose oil, rapeseed oil, olive oil, linseed (linseed) oil, cottonseed oil, high oleic safflower oil, palm stearin (palm stearin), palm-kernel oil, wheat-germ oil; The ester of medium chain triglyceride oil and emulsion and aliphatic acid, and any combination.
In certain embodiments, the dietary protein origin comprised in alimentation composition comprises milk protein.Can be used for implementing milk protein of the present disclosure source and include but not limited to, lactoprotein powder, lactoprotein concentrate, the lactoprotein separator, Non-fat milk solids, defatted milk, skimmed milk power, lactalbumin, lactalbumin isolate, whey protein concentrate, sweet whey, yogurt is clear, casein, acid casein, caseinate is (as casein sodium, casein sodium calcium, calcium caseinate) and any combination.
In one embodiment, albumen provides with intact proteins.In other embodiments, albumen provides in the about combination of the partially hydrolysed protein between 4% and 10% with intact proteins and hydrolysis degree.In another embodiment, dietary protein origin can supplement to contain glutamine peptide.
In a specific embodiments of the present disclosure, dietary protein origin comprises whey and casein, and whey is similar to the ratio of finding in caseic ratio and lacto.For example, in certain embodiments, whey and caseic weight ratio are from about 20% whey: 80% casein is to about 80% whey: 20% casein.
In an embodiment of the present disclosure, alimentation composition can comprise one or more probios.Term " probio " refers to have low pathogenicity or without pathogenicity, to the microorganism of host health performance beneficial effect.As long as it realizes the result of intention, any probio known in the art is all acceptable in the present embodiment.In a specific embodiment, probio can be selected from lactobacillus (
Lactobacillus) species, Lactobacillus rhamnosus GG(
Lactobacillus rhamnosus GG), Bifidobacterium (
Bifidobacterium) species, bifidobacterium breve (
Bifidobacterium brevis), bifidobacterium longum (
Bifidobacterium longum), and bifidobacterium animalis subspecies BB-12(
Bifidobacterium animalis subsp. lactisBB-12).
If be included in composition, the amount of probio can be from every kg body weight every day approximately 10
4To approximately 10
10Individual CFU (cfu) changes.In another embodiment, the amount of probio can be from every kg body weight every day approximately 10
6To approximately 10
9Individual CFU changes.In another embodiment, the amount of probio can be that every kg body weight every day is at least about 10
6Individual CFU.And disclosed composition can also comprise probio conditioned medium composition.
In one embodiment, one or more in probio are great-hearted.In another embodiment, one or more in probio are unvital.As described herein, term " great-hearted " refers to viable microbial.Term " unvital " or " unvital probio " refer to probiotic micro-organisms, its cell component and its metabolin of non-work.These unvital probios can be gone out by heat kill or otherwise deactivation, but keep the ability of beneficial effect host health.It can be natural generation, synthetic being used for probio of the present disclosure or, by the biological exploitation of genetic manipulation, no matter these new sources are current known or exploitation afterwards.
In an embodiment of the present disclosure, alimentation composition can comprise the prebiotic compositions that comprises one or more prebioticses.As described herein, term " prebiotics " refers to by the growth of a kind of in the selective stimulating colon or a limited number of bacterium that can improve host health and/or activity and beneficial effect host's indigestible COF." prebiotic compositions " is the composition that comprises one or more prebioticses.These prebioticses can be natural generation, that synthesize or, by genetic manipulation biology and/or plant exploitation, no matter these new sources are known or exploitation afterwards at present.In certain embodiments, the prebiotics comprised in disclosure composition comprises U.S. Patent number 7,572, those of instruction in 474, and the disclosure of this patent is incorporated to this paper by reference.
Can be natural generation, that synthesize or develop by genetic manipulation biology and/or plant for prebiotics of the present disclosure, no matter these new sources be known or exploitation afterwards at present.Can comprise oligosaccharides, glycan, and other prebiotics that comprises fructose, wood sugar, soybean, galactolipin, glucose and mannose for prebiotics of the present disclosure.More specifically, can comprise lactulose, lactosucrose, gossypose for prebiotics of the present disclosure, Portugal's oligosaccharides, inulin, polydextrose, polydextrose powder, galactooligosaccharide, FOS, oligoisomaltose, soyabean oligosaccharides, lactosucrose, xylo-oligosaccharide, chitosan oligosaccharide, Oligomeric manna sugar, low araban, low poly sialic acid sugar, oligomeric fucose, and oligomeric dragon gallbladder sugar.Preferably, alimentation composition comprises polydextrose (PDX) and/or galactooligosaccharide (GOS).Optionally, except polydextrose and/or galactooligosaccharide, alimentation composition also comprises one or more additional prebioticses.
If be included in alimentation composition, the total amount of the prebiotics existed in alimentation composition can be from about 0.1g/100kcal to about 1g/100kcal.The total amount of the prebiotics more preferably, existed in alimentation composition can be from about 0.3 g/100kcal to about 0.7 g/100kcal.At least 20% prebiotics should comprise galactooligosaccharide and/or polydextrose.
If polydextrose is for prebiotic compositions, in one embodiment, in alimentation composition, the amount of polydextrose can be the scope of about 0.1g/100kcal to about 1g/100kcal.In another embodiment, the amount of the polydextrose in alimentation composition is in the scope from about 0.2 g/100kcal to about 0.6 g/100kcal.
If galactooligosaccharide is for prebiotic compositions, in one embodiment, in alimentation composition, the amount of galactooligosaccharide can be from about 0.1g/100kcal to about 1g/100kcal.In another embodiment, the amount of the galactooligosaccharide in alimentation composition is from about 0.2 g/100kcal to about 0.5 g/100kcal.In certain embodiments, in prebiotic compositions, the ratio of polydextrose and galactooligosaccharide is that about 9:1 is to about 1:9.
In some embodiments, nutritional preparation of the present disclosure can further comprise long-chain polyunsaturated fatty acid (LCPUFAs) source.Preferably, the source of LCPUFAs comprises DHA (DHA).Other suitable LCPUFAs includes, but are not limited to α-linoleic acid, gamma-linoleic acid, linoleic acid, leukotrienes, eicosapentaenoic acid (EPA) and arachidonic acid (ARA).
In one embodiment, alimentation composition supplement with DHA and ARA the two.In this embodiment, the weight ratio of ARA:DHA can be from about 1:3 to about 9:1.In one embodiment of the invention, the weight ratio of ARA:DHA is that about 1:2 is to about 4:1.
In alimentation composition, the amount of long-chain polyunsaturated fatty acid can change 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.
Alimentation composition can be used standard technique known in the art to supplement with the oil containing DHA and ARA.For example, DHA and ARA can by replace normal presence in composition etc. gauging for example high oleic sunflower oil add composition.As another example, the oil that contains DHA and ARA can add composition by the equivalent remainder (rest) of replacing total fat blend of normal presence in the composition that does not contain DHA and ARA.
If use, the source of DHA and ARA can be any source known in the art, marine oil for example, fish oil, single cell oil, yolk lipid and cephalopin.In some embodiments, DHA and ARA derive from respectively unicellular Martek oil, DHASCO and ARASCO, or its variant.DHA and ARA can be native forms, and prerequisite is that the remainder in LCPUFA source does not cause harmful effect of any essence to the baby.Alternatively, DHA and ARA can be with the form application of refining.
In an embodiment of the present disclosure, the source of DHA and ARA is U.S. Patent number 5,374, the single cell oil of instruction in 567,5,550,156 and 5,397,591, and the disclosure of these patents integral body by reference is incorporated to this paper.But the disclosure is not limited in these oil.
In certain embodiments, alimentation composition comprises the iron from about 0.5mg/100kcal to about 5mg/100kcal, comprises the iron be attached on lactoferrin.
Embodiment
The embodiment that provides the following examples to explain alimentation composition of the present disclosure, but it should not be construed as any restriction of the present disclosure.The consideration of the enforcement based on to specification or alimentation composition disclosed herein or method, other embodiment within this paper claim scope it will be apparent to those skilled in the art that.The meant for illustration book only is thought of as exemplary together with embodiment, the scope of the present disclosure and spirit are shown by claims.
Embodiment 1
The present embodiment example lactoferrin and infant formula are in vitro to causing diarrhoeic Escherichia coli (diarrengic
E. coli) impact of strain growth.
Acquisition is from each DEC population (enterotoxigenic escherichia coli (ETEC), enteropathogenic E.Coli (EPEC), shiga toxin producing escherichia coli (STEC), enteroaggrerative E.coli (EAEC)) 15 clinical diarrhoeic Escherichia coli (diarrheageanic that cause
E. coli,DEC) bacterial strain.As discussed previously, bacterial strain separates from the Peruvian cohort study from the children with diarrhoea, and identifies and cause diarrhoeic Escherichia coli (diaheagenic by PCR in real time
E. coli) population.In addition, also obtain clinical isolates and 15 shigella flexneri separators of 15 salmonella typhimurium serotypes.
All clinical strains and standard laboratory control strain are grown over 24 hours in the McConkey agar medium at 37 ℃.For the vigor analysis, bacterial strain is grown 18 hours in lysogenicity meat soup at 37 ℃.Then bacterial strain cleans twice in PBS, and at centrifugal 5 min of 4500 * g.Only the bacterium of mid-log phase is used.
Prepare 0,0.6,1,2,4,6,8 and 10 mg/ml lactoferrin mother liquors and 0,0.6,1,2,4,6, the 8 and 10 mg/ml infant formula mother liquor containing 2.1 g/100 kcal lactoproteins and 1.8 mg/100 kcal iron in distilled water.
Containing about 2 * 10
8The clinical strains culture of logarithmic phase cell is inoculated into containing in 96 orifice plates of 1% bactopeptone.Every plate is also inoculated infant formula or lactoferrin mother liquor by Microdilution, makes every kind of bacterial strain be able to 0,0.6,1,2,4,6,8 or 10 mg/ml lactoferrins or infant formula are tested.By the serial culture of 10 times of dilutions, plate is hatched and every 30 minutes monitoring growth kineticses at 37 ℃.Then monitoring growth in spectrophotometer and/or ELISA reader.After hatching 18-20 hour, the MIC of each bacterial strain is recorded as the least concentration that causes complete bacteriostatic infant formula or lactoferrin.
Also tested lactoferrin and the infant formula Cooperative Analysis to the activity of each bacterial strain, and measured as described above the impact of lactoferrin/infant formula combination on bacterial growth.For these Cooperative Analysis, the result based on MIC research and growth kinetics, determine separately the concentration of lactoferrin and infant formula to every kind of reagent.
Embodiment 2
The present embodiment example lactoferrin and infant formula are in vitro on causing the impact of diarrhoeic Escherichia coli bacterial strain on human intestinal epithelial's cell adhesion.
The layer of minute joining of Hep2 cell is (in 24 orifice plates about 5 * 10
4Cells/well) with the enterotoxigenic escherichia coli of describing in embodiment 1, enteropathogenic E.Coli, shiga toxin producing escherichia coli, enteroaggrerative E.coli, salmonella typhimurium serotype or shigella flexneri separator, infect.Then will containing or containing the infant formula of 10mg/ml lactoferrin, do not add wherein, make the ratio that bacterium is 100:1 to the concentration of infant formula.Then, the Hep2 cellular layer of infection is at 37 ℃, 5% CO
2In hatch 4 hours.Then the powerful Hep2 cell that cleans is to remove the non-bacterium of sticking.Cell is fixed with 70% methyl alcohol, with 10% Jim Sa solution-dyed, and checks under the microscope.In addition, carry out fluorescence actin decoration method (FAS) analysis for enterotoxigenic escherichia coli, shiga toxin producing escherichia coli, shigella flexneri and salmonella typhimurium serotype as previous report.
Embodiment 3
The present embodiment example lactoferrin and infant formula supporting situation that opposing is caused by bacterial pathogens or the effect in disease in vitro.
Obtain the female Balb/c Strains of Mouse of 6 to 8 week age, body weight 20 to 24g, health, and be divided into experimental group and control group.Then experimental group raises the infant formula containing 75 or 165 mg/ml lactoferrins with 200 μ l before infection, and control group is raised with 200 μ l infant formulas before infection.Adjust the amount of the infant formula use, the amount that mouse is accepted is equivalent to mg/kg and 1333 mg/kg lactoferrins every days 600.Then mouse uses 300 μ L 10
8The salmonella typhimurium serotype of CFU (cfu), 200 μ L 10
8The citric acid bacillus of cfu (
Citrobacter rodentium) (mouse model of EPEC) or 200 μ L 10
8The cfu shigella flexneri infects.For infecting and processing front inoculation, use the tube feed pin.After infection, mouse is accepted respectively arbitrarily containing the infant formula of 75 or 165 mg/ml lactoferrins or infant formula 7 days separately.Again, adjust the amount of the infant formula use, the amount that mouse is accepted is equivalent to mg/kg and 1333 mg/kg lactoferrins every days 600.After infection, monitor the death rate, body weight and clinical sign (perpendicular hair, bow-backed attitude and motion reduce) in all mouse every day, monitor 7 days.Within 15 minutes, determine the incidence of clinical sign by the behavior of the mouse of each infection relatively.After infection the 10th day, mouse was condemned to death, and carried out cardiac puncture and obtained the blood culture.For histopathological analysis, extract organ (colon, liver and spleen).By group being divided set, blindly with the virologist who prevents prejudice, the inflammation in organ and degree of necrosis are studied.
Embodiment 4
The present embodiment example lactoferrin and infant formula supporting situation that opposing is caused by viral pathogen or the effect in disease in vitro.
Carry out embodiment 3 as above-mentioned, except mouse is infected by (Calicivus) strain of rotavirus, norovirus, astrovirus, adenovirus and calicivirus rather than bacterial isolates.Mouse is as above-mentioned monitored and research.
Embodiment 5
The present embodiment explaination is according to an embodiment of nutrition product of the present disclosure.
Embodiment 6
The present embodiment explaination is according to another embodiment of nutrition product of the present disclosure.
Embodiment 7
The present embodiment has been explained and can be used for the embodiment of preparation according to the composition of disclosure nutrition product.
Embodiment 8
The present embodiment has been explained and can be used for preparation another embodiment according to the composition of disclosure nutrition product.
Preferably, this alimentation composition is applied to the people and supports the disease or the situation that are caused by bacterium or viral pathogen in the opposing people, comprises viral respiratory infection.
All lists of references that this specification is quoted, include but not limited to that all papers, publication, patent, patent application, speech, text, report, manuscript, handbook, books, network deliver thing, journal article, periodical etc., this by reference integral body be incorporated to this specification.Discussion to this paper list of references is only the viewpoint of making in order to sum up its author, is not to admit that any list of references forms prior art.The applicant retains the accuracy of the list of references that query quotes and the right of correlation.
Although preferred embodiment of the present disclosure has been used particular term, tool and method to be described, these are described only for exemplary purpose.The word used is illustrative word rather than restriction.Be appreciated that in the situation that do not depart from the spirit or scope of the present disclosure that claims are listed, those skilled in the art can be changed and change.In addition, the various aspects that are to be understood that each embodiment can be replaced whole or in part mutually.For example, although example produce the method for the commercialization sterile liquid nutritious supplementary pharmaceutical prepare according to those methods, other purposes is also expected.Therefore, the spirit and scope of claims should not be limited to the description of the preferred form that this paper comprises.
Claims (15)
1. support the method for resist the disease or situation in the people, comprise to the people and use alimentation composition, described alimentation composition comprises:
A) fat or lipid source;
B) dietary protein origin; With
C) lactoferrin produced by inhuman source, wherein said lactoferrin and HLf(349-364) the amino acid sequence AVGEQELRKCNQWSGL at fragment place has at least 48% homology.
2. the process of claim 1 wherein described disease or situation be by least one be selected from enterotoxigenic escherichia coli, enteropathogenic E.Coli, haemophilus influenzae (
Haemophilus influenza), shiga toxin producing escherichia coli, enteroaggrerative E.coli, salmonella typhimurium serotype (
Salmonella ser. Typhimurium), shigella flexneri (
Shigella flexneri), the pathogen of rotavirus, norovirus, Respiratory Syncytial Virus(RSV), adenovirus and combination thereof the disease or the situation that cause.
3. according to the process of claim 1 wherein that described disease or situation are viral respiratory infections.
4. according to the process of claim 1 wherein that described people is baby or children.
5. according to the process of claim 1 wherein that described fat or lipid source exists to the about level of 7 g/100 kcal with about 3g/100 kcal, and described dietary protein origin exists to the about level of 5 g/100 kcal with about 1 g/100 kcal.
6. according to the process of claim 1 wherein that described lactoferrin exists with the level at least about 10mg/100kcal.
7. according to the method for claim 6, wherein said lactoferrin exists to the about level of 220 mg/100kcal with about 70 mg/100kcal.
8. according to the process of claim 1 wherein that described lactoferrin is selected from the non-human milk ferritin, passes through biogenic human lactoferrin and the combination thereof of genetic modification.
9. according to the process of claim 1 wherein that described lactoferrin is stable and keeps active under human lactoferrin becomes the condition of unstable or inactivation.
10. according to the method for claim 9, wherein said alimentation composition lives through pasteurizing conditions.
11., according to the process of claim 1 wherein that described alimentation composition further comprises prebiotic compositions, described prebiotic compositions comprises the compound that is selected from galactooligosaccharide, polydextrose and combination thereof.
12. according to the process of claim 1 wherein that described alimentation composition comprises the iron of about 0.5mg/100kcal to about 5mg/100kcal, comprises the iron be attached on lactoferrin.
13. according to the process of claim 1 wherein described lactoferrin and HLf(349-364) the amino acid sequence AVGEQELRKCNQWSGL at fragment place has at least 65% homology.
14. according to the process of claim 1 wherein that described people has described disease or situation when described alimentation composition is applied.
15. according to the process of claim 1 wherein that described alimentation composition is prophylactically used, and described people does not have described disease or situation when described alimentation composition is applied.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711129504.3A CN107668721A (en) | 2010-12-29 | 2011-12-15 | Purposes of the alimentation composition comprising lactoferrin in resist the disease and situation is supported |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
| US12/980833 | 2010-12-29 | ||
| US12/980825 | 2010-12-29 | ||
| PCT/US2011/065229 WO2012091945A1 (en) | 2010-12-29 | 2011-12-15 | Use of nutritional compositions including lactoferrin in supporting resistance to diseases and conditions |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711129504.3A Division CN107668721A (en) | 2010-12-29 | 2011-12-15 | Purposes of the alimentation composition comprising lactoferrin in resist the disease and situation is supported |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103429092A true CN103429092A (en) | 2013-12-04 |
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| CN201711129504.3A Pending CN107668721A (en) | 2010-12-29 | 2011-12-15 | Purposes of the alimentation composition comprising lactoferrin in resist the disease and situation is supported |
| CN2011800627084A Pending CN103429092A (en) | 2010-12-29 | 2011-12-15 | Use of nutritional compositions including lactoferrin in supporting resistance to diseases and conditions |
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|---|---|---|---|
| CN201711129504.3A Pending CN107668721A (en) | 2010-12-29 | 2011-12-15 | Purposes of the alimentation composition comprising lactoferrin in resist the disease and situation is supported |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP2658389A1 (en) |
| CN (2) | CN107668721A (en) |
| BR (1) | BR112013015458A2 (en) |
| CA (1) | CA2823018A1 (en) |
| EC (1) | ECSP13012799A (en) |
| HK (1) | HK1250608A1 (en) |
| MX (1) | MX2013005943A (en) |
| PE (1) | PE20141826A1 (en) |
| RU (1) | RU2013134133A (en) |
| SG (1) | SG190780A1 (en) |
| TW (1) | TW201306760A (en) |
| WO (1) | WO2012091945A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023185338A1 (en) * | 2022-04-01 | 2023-10-05 | 北京三元食品股份有限公司 | Fermented milk |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20122152A1 (en) | 2012-12-17 | 2014-06-18 | Progine Farmaceutici S R L | COMPOSITION FOR TOPICAL USE. |
| 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 (en) | 2014-09-05 | 2016-03-09 | Progine Farmaceutici Srl | Vaginal formulations for preventing and treating vaginal and cervico-vaginal infections |
| IT201600128713A1 (en) * | 2016-12-20 | 2018-06-20 | Frima Res Srls | COMPOSITION IN THE TREATMENT OF INFLAMMATORY ANEMIA OR FROM FLOGOSIS FROM CHRONIC DISEASE |
| 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 |
Citations (3)
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| CN101130079A (en) * | 2007-07-19 | 2008-02-27 | 浙江省中医药研究院 | Application of lactoferrin in preparing medicament for preventing and controlling disease caused by human rotavirus |
| CN101247823A (en) * | 2005-05-05 | 2008-08-20 | 布里斯托尔-迈尔斯斯奎布公司 | Use of bovine lactoferrin in the manufacture of a medicament for inhibiting the growth of bacteria |
| CN101494970A (en) * | 2005-09-28 | 2009-07-29 | 文特里亚生物科学公司 | Oral formulation for enteric disorders and/or rehydration |
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| IE61701B1 (en) | 1986-07-17 | 1994-11-30 | Morinaga Milk Industry Co Ltd | Process for producing bovine lactoferrin in high purity |
| US5407957A (en) | 1990-02-13 | 1995-04-18 | Martek Corporation | Production of docosahexaenoic acid by dinoflagellates |
| AU661297B2 (en) | 1991-01-24 | 1995-07-20 | Martek Corporation | Microbial oil mixtures and uses thereof |
| US5374567A (en) | 1993-05-20 | 1994-12-20 | The United States Of America As Represented By The Secretary Of The Navy | Operational amplifier using bipolar junction transistors in silicon-on-sapphire |
| EP0744901B1 (en) | 1994-02-16 | 2001-12-05 | Pharming Intellectual Property BV | Isolation of lactoferrin from milk |
| EP1480524B1 (en) | 2002-03-07 | 2013-04-17 | Upfront Chromatography A/S | A process of isolating lactoferrin |
| US20070191264A1 (en) * | 2005-05-05 | 2007-08-16 | Bristol-Myers Squibb Company, A Delaware Corporation | Methods for inhibiting the growth of bacteria |
| US7572474B2 (en) | 2005-06-01 | 2009-08-11 | Mead Johnson Nutrition Company | Method for simulating the functional attributes of human milk oligosaccharides in formula-fed infants |
| US20080003329A1 (en) * | 2006-06-30 | 2008-01-03 | Ricardo Rueda | Enriched infant formulas |
| WO2008047391A1 (en) * | 2006-10-17 | 2008-04-24 | S.I.F.Fr.A. Farmaceutici Srl | Nutriceutic composition comprising lactoferrin and proteasic probiotics |
| MX348901B (en) * | 2007-11-26 | 2017-07-03 | Nestec Sa | Age-tailored nutrition system for infants. |
| ITRM20080163A1 (en) * | 2008-03-26 | 2009-09-27 | Maurizio Acri | USE OF LATTOFERRINA FOR THE PREVENTION OF NEONATAL SEPSIS IN PREMATURED NEWBORNS |
| AU2010311325B2 (en) * | 2009-10-29 | 2014-11-20 | Société des Produits Nestlé S.A. | Nutritional compositions comprising lactoferrin and probiotics and kits of parts thereof |
-
2011
- 2011-12-15 WO PCT/US2011/065229 patent/WO2012091945A1/en active Application Filing
- 2011-12-15 PE PE2013001479A patent/PE20141826A1/en not_active Application Discontinuation
- 2011-12-15 EP EP11810939.6A patent/EP2658389A1/en not_active Ceased
- 2011-12-15 CN CN201711129504.3A patent/CN107668721A/en active Pending
- 2011-12-15 BR BR112013015458A patent/BR112013015458A2/en not_active IP Right Cessation
- 2011-12-15 CA CA2823018A patent/CA2823018A1/en not_active Abandoned
- 2011-12-15 MX MX2013005943A patent/MX2013005943A/en unknown
- 2011-12-15 SG SG2013035936A patent/SG190780A1/en unknown
- 2011-12-15 CN CN2011800627084A patent/CN103429092A/en active Pending
- 2011-12-15 RU RU2013134133/10A patent/RU2013134133A/en not_active Application Discontinuation
- 2011-12-22 TW TW100148027A patent/TW201306760A/en unknown
-
2013
- 2013-07-29 EC ECSP13012799 patent/ECSP13012799A/en unknown
-
2018
- 2018-08-06 HK HK18110050.6A patent/HK1250608A1/en unknown
Patent Citations (3)
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| CN101247823A (en) * | 2005-05-05 | 2008-08-20 | 布里斯托尔-迈尔斯斯奎布公司 | Use of bovine lactoferrin in the manufacture of a medicament for inhibiting the growth of bacteria |
| CN101494970A (en) * | 2005-09-28 | 2009-07-29 | 文特里亚生物科学公司 | Oral formulation for enteric disorders and/or rehydration |
| CN101130079A (en) * | 2007-07-19 | 2008-02-27 | 浙江省中医药研究院 | Application of lactoferrin in preparing medicament for preventing and controlling disease caused by human rotavirus |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023185338A1 (en) * | 2022-04-01 | 2023-10-05 | 北京三元食品股份有限公司 | Fermented milk |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107668721A (en) | 2018-02-09 |
| ECSP13012799A (en) | 2013-10-31 |
| CA2823018A1 (en) | 2012-07-05 |
| HK1250608A1 (en) | 2019-01-11 |
| PE20141826A1 (en) | 2014-12-17 |
| MX2013005943A (en) | 2013-10-01 |
| TW201306760A (en) | 2013-02-16 |
| EP2658389A1 (en) | 2013-11-06 |
| BR112013015458A2 (en) | 2016-08-09 |
| RU2013134133A (en) | 2015-02-10 |
| SG190780A1 (en) | 2013-07-31 |
| WO2012091945A1 (en) | 2012-07-05 |
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