CN101605470A - Obtain aseptic breast and method for compositions thereof - Google Patents
Obtain aseptic breast and method for compositions thereof Download PDFInfo
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- CN101605470A CN101605470A CNA2007800402614A CN200780040261A CN101605470A CN 101605470 A CN101605470 A CN 101605470A CN A2007800402614 A CNA2007800402614 A CN A2007800402614A CN 200780040261 A CN200780040261 A CN 200780040261A CN 101605470 A CN101605470 A CN 101605470A
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Abstract
The invention provides and a kind of breast is sterilized but the simple and effective method of not degrading or losing the Ruzhong bioactivator, and the product of producing by this method.
Description
The cross reference of related application
The application requires the U.S. Provisional Application series number No.60/841 of application on August 30th, 2006, the U.S. Provisional Application No.60/867 of application on November 29th, 371 and 2006, and 748 priority, its content are incorporated herein does reference.
Technical field
The present invention relates to the sterilize beneficial organism that keeps a great deal of simultaneously of full milk is learned material and reduced the method for biological load.The present invention also comprises the milk product that obtains by method of the present invention.
Background
Human milk has great treatment meaning in neonate who treats premature, critical illness and other hypoimmunity and children.Yet, for these critical patients, having Bacillus cercus (B.cereus) danger that obviously can survey through the donor human milk of processing, Bacillus cercus is the sitotoxin of the omnipresence found in about 4% human milk samples.Bacillus cercus bothers most, because it has the ability of the spore that formation can not be killed by the standard pasteurization.Other bacterium that relates to comprises C.perfringens (Clostridium perfringens), Cryptosporidium parvum (Cryptosporidium parvum), circle spore coccidia (Cyclospora cayatenesis), Escherichia coli (Escherichia coli), monocyte hyperplasia listeria spp (listeria monocytogenes), salmonella and staphylococcus aureus (Staphylococcus aureus).
More complicated thing is that some donors provide some " clean " batch (LOTS) (not having Bacillus cercus and other pathogen), with one of batch contaminated.When the donor that mixes eligible newborn, infect that the breast of Bacillus cercus or other pathogen is final to pollute other clean batch, cause whole mixture destroyed.Colony forming single-digit order for these bacteriums is restricted, though and these restrictions seldom reach, any mixture that exceeds these restrictions all should discard and be not useable for processing.Although it is useful detecting former breast before mixing, the concentration for preparing the protein of some product concentrates the Ruzhong all substances effectively, comprises these pathogen.Though other pathogen can be eliminated with pasteurization, the Bacillus cercus pathogen can not be eliminated with pasteurization, and therefore importantly described blended product is carrying out not having Bacillus cercus before pasteurization and the filler through identifying.Further, need be provided at the former newborn mixture that pasteurization does not have pathogen before basically, to optimize the quality and the security of product.
Summary of the invention
The invention provides a kind of method that obtains human milk compositions, described method comprises: the filter by about 100-400 micron filters full milk; Approximately 58-65 ℃ to described full milk heat treatment about 20-40 minute; Full milk is separated into skimmed milk part and fats portion; By one or more skimmed milk filter filtered and degreased breast part, obtain the skimmed milk part (being retention) of penetrant part and enrichment protein; With described fats portion be heated to about 90-120 ℃ about 1 hour, be enough to reduce the biological load of fats portion; Mix the fraction of treated fats portion and the skimmed milk part of enrichment protein, obtain human milk compositions.On the one hand, described full milk comprises the human milk of mixing.On the other hand, detect HIV, HBV in the described full milk sample, HCV and the existence of combination arbitrarily thereof before described method further is included in and filters.On the one hand, full milk is filtered again by about 200 microns filter screen.Can carry out about 30 minutes at about 63 ℃ the heat treatment that full milk carries out.On the other hand, the skimmed milk of after separating partly comprises about 0.69% fat, about 1.07% protein and about 7.14% lactose, and the fats portion of after separating comprises about 46% fat, about 2% protein and about 10% lactose.In certain aspects, described fats portion is further processed obtaining extra skimmed milk, and the skimmed milk that this is extra and described skimmed milk are partially mixed.Described method can further be included in before the filtered and degreased breast part with butterfat partly regulate described skimmed milk part with obtain fatty consistency in the skimmed milk part be the skimmed milk part protein content about 55% to about 65%.On the other hand, the skimmed milk of described enrichment protein partly comprises about 8% protein.Described method can comprise further that washing has one or more skimmed milk filter of penetrant to obtain the protein washings and described protein washings to be added in the skimmed milk part of enrichment protein.Described full milk can be a human milk.Described method can comprise further that the dairy products to deriving from described method carry out pasteurization.
The present invention also provides the human milk compositions that derives from the inventive method.On the one hand, described human milk compositions comprises the fat constituent of the protein component of about 20-70mg/ml, about 35-85mg/ml, the carbohydrate component of about 70-115mg/ml, and wherein said composition preferably comprises people IgA.
The invention provides human milk compositions, it comprises donor from former breast of body and allosome dairy compositions, and wherein said human milk compositions comprises at least approximately 2.1g/dL people lactoprotein.On the one hand, described people lactoprotein is not the protein example (for example described people lactoprotein is the human protein of non-freeze-drying) derived from freeze-drying.On the other hand, described composition comprises about 2.1g/dL-4.0g/dL people lactoprotein.On the one hand, the final human milk compositions that mixes comprises about 2.2 to about 4% human protein.
The present invention also provides a kind of kit, it comprises human milk compositions of the present invention and is used to mix described human milk compositions and the former breast of the people graduated bottle with the preparation that obtains to mix, and the preparation of wherein said mixing is compared with the former breast that does not have inventor's dairy compositions and comprised about 4 card/ounces more.
The present invention further provides a kind of method that obtains the nutrition dairy compositions, comprised the nutrient content of measuring the former breast of people; Add human milk compositions of the present invention so that the nutritive value of described former breast increases about 4 calories/ounce to described former Ruzhong.
The invention provides the method that the extra-nutrition thing is provided for the premature, comprise human milk compositions of the present invention is added the former Ruzhong of people and gives the premature with the human milk of this mixing.
Being described in detail in accompanying drawing and hereinafter setting forth of one or more embodiment of the present invention.Can apparent further feature of the present invention from invention description and accompanying drawing and accessory rights claim, purpose and advantage.
The accompanying drawing summary
Fig. 1 shows method of the present invention.
Describe in detail
Such as this paper and used in claims, unless spell out in addition, singulative " ", " a kind of " and " described " comprises plural form. Therefore, for example " sample " comprise a plurality of this Plant sample, " described protein " comprises one or more protein well known by persons skilled in the art etc.
Unless otherwise indicated, then all technology used herein and scientific terminology all have its affiliated field The technical staff is known identical meanings usually. Although passable in implementing method and composition of the present invention Use and describe method similar or of equal value and material to this paper, but this paper has described method, the dress of giving an example Put and material.
The publication of discussing above and herein only is provided for showing that it is before the application's the applying date Open. Should not be construed as and admit that the present invention did not finish before described publication open.
Because its nutritional labeling and immunology benefit think always that for a long time human milk is premature and foot Moon youngster's ultimate food. Human milk is the only source of this nutrition and immunology benefit. Yet, The nutritive value of donor breast is different, and donor Ruzhong bacterium, virus and other pollutant are had Misgivings. For baby, particularly premature, desirable nutrition condition comprises breeder mother's breast. Or The person, perhaps in addition, mother can use humalactor to extrude breast and store to use subsequently. Although female Breast is fed and is had some contraindications, and these contraindications comprise the baby with galactosemia, and female The parent has the active type pulmonary tuberculosis, be HTLV I or the II positive, be given radio isotope, anti-Metabolin or chemotherapy, or drug abuse object. Infect about HIV, situation is more complicated, danger Balance between danger and the benefit is assessed by the professional person.
Although fully proved breastfeeding positive role, the initial ratio in United States Hospital Only be 64%, the lasting ratio in 6 months postpartum is about 29%. Breastfeeding replacement scheme is to make Employment donor breast replenishes the laboratory milk of human milk and independent laboratory milk. For many extremely low birth bodies Heavy baby need to strengthen the breast of extruding.
The Academy of Pediatrics Policy Statement suggestion can not or be reluctant for mother Meaning (for example social cause) provides himself baby of breast, and the human milk of storage can be a kind of suitable Optional nursing scheme. The The Human Milk Banking Association of that set up in 1985 North America (HMBANA) has announced the national guidelines of setting up and move the donor breast milk bank. These guides are with similar for the protection of those of supply in the people blood bank.
For the premature feeds usually for the specially designed commercial infant formula milk of these babies or its mother Parent's breast. Nutritional need about these babies is still being studied. Yet, many having studies confirm that Unsupplemented mother premature breast and stock's breast can not provide the q.s that satisfies these baby's needs Some nutriments (Davies, D.P., " Adequacy of expressed breast milk for early Growth of preterm infants " .ARCHIVES OF DISEASE IN CHILDHOOD, 52, p. 296-301,1997). The energy that the infant physical growth of LBW needs is estimated as about 120 card/kg/ My god, but accurate energy demand is because the effect of activity, basic energy consumption, absorption of nutrient ingredients Rate, disease and utilize energy to carry out difference in the synthetic ability of combination tissue and difference. About 50% Caloric intake be that analytic metabolism needs, activity and keep body temperature consumption. About 12.5% Energy is for the synthesis of new organization, and 25% energy is stored. Remaining 12.5% energy is drained. Premature labor Youngster's human milk is deficiency aspect specific nutrition usually. For example, premature's human milk usually lack calcium, phosphorus and Protein. Therefore, recommend when with premature BF premature, need to carry out by force this human milk Change is to satisfy better premature's nutritional need.
Similac Natural
With
Human Milk Fortifier is commercially available human milk fortifier.This hardening agent is different aspect form, composition source and energy and trophic component.In addition, these products are actually artificial synthetic.In neonatal intensive care unit (NICU), both needed liquid state also to need powdered human milk fortifier.Ideally, Zui Jia hardening agent is the people source.The newborn hardening agent that does not have available people source at present.
The secretion of liquid from female mammary gland is included in the hereinafter easy many compositions that are called breast.The breast of extruding is not that the typical case is aseptic, even contain bacterium when obtaining under aseptic condition yet.Yet, breast very rapidly by environment (air, milking device, with hand or other non-sterile object contacts, milk container or container etc.) even in microorganism and the specific disease substance as through the Ruzhong of pasteurization also rapidly the Bacillus cercus of propagation pollute.
Because its carbohydrate, protein, fat, mineral matter and vitamin are formed, breast is actually the ideal culture medium of all microorganisms, and breast is rotten at short notice.The newborn delayed slightly bacterial growth of refrigeration, its shelf-life can prolong several days.
Except the bacterium such as lactic acid bacteria that make the lactic acid corruption, people's pathogenic bacteria particularly constitutes a big problem.These bacteriums comprise that Salmonella (Salmonella), campylobacter (Campylobacter), listeria spp belong to the various pathogenicity bacterial strains of (Listeria) and staphylococcus (Staphylococci), these bacterial strains can occur in the Ruzhong without pasteurization especially, perhaps comprise clostridium (Clostridia) or bacillus bacterial classification, can in 62-74 ℃ pasteurization, survive owing to its heat resistant spore.
Typically, the method sterilization that breast is handled by being called UHT is promptly 120-145 ℃ of heat treatment several seconds.Except " taste that boils ", extreme heating causes the forfeiture of BA by the thermal denaturation of for example protein.This protein comprises the valuable immune active ingredient that the Ruzhong exists, and comprises for example immunoglobulin (Ig) and other immunity excitor substance, and other key protein, as lactoferrin, lactoperoxidase, growth factor etc.For example, the colostrum of biological activity has illustrated and can be used for gastrointestinal disorder etc.
In addition, can make bacterium discharge toxin by heat activation.For example, the endotoxin of Gram-negative bacteria is not destroyed by pasteurization.In the UHT sterilization, killing of Gram-negative bacteria can make endotoxin increase 6-7 doubly (Motter, J., Neth.Milk Dairy Journal, Vol.41,137-145,1987).
The method of handling full milk at present causes useful biologically active proteins matter and other molecule to reduce.For example, freeze-drying, high-temperature process etc. reduce biologically active proteins matter, lipid and other species by for example degraded and sex change.In addition, when using the heating-up temperature that reduces in pasteurization, the result provides biological load to increase and therefore increased the dairy products of consumer's risk.Some filtration step that uses at present reduces protein content and is used to leach lactose plus salts.
The present invention provides human milk fortifier for the extra nutriment of needs with the premature who supports its growth.The present invention comprises the hardening agent of deriving by the human milk of method acquisition of the present invention.In some respects, the supplementary that described human milk fortifier/human milk is derived can add in the human milk, thereby replenishes the level of protein, fat, vitamin and mineral matter.The present invention further provides the method that additional nutritive value is provided with the premature of growth for the extra nutriment of needs.
Term " premature labor ", " not mature " and " LBW (LBW) ", the baby was used interchangeably, and was meant the baby that the babies that are less than 37 week births pregnant age and/or birth weight are lower than 2500gm.Premature's needs are urgent especially.(for＜1500g) the baby, the death rate before 1 years old is 25% for ELBW.For under-weight (＜2500g) for the baby, 1 annual death rate is 2%; (＞2500g) baby's the death rate still is significantly higher than 0.25% to normal birth weight.
Special concern be NEC (NEC), this is a kind of serious gastrointestinal disease of unknown etiology in the neonate.NEC is characterised in that the mucous membrane of part small intestine or strides mucosal necrosis.The very little ill baby of birth is for the susceptible of NEC before mature.The cumulative incidence of disease of NEC partly is because due to high-risk premature's the survival rate improvement.
On the one hand, the invention provides the method that obtains and process the human milk of a donor or one group of donor.Method of the present invention is included in and reduces the process that biological load keeps nutritive value simultaneously in the goods of reinforcement.Common described method comprises that discriminated union permits the measure of suitable donor.The donor typical case is the donor of being recommended by its doctor in charge.Except other reason, help like this to guarantee that donor is not long-term ill individuality.The method and system of allowance and set of monitoring breast and distribution is at U.S. Patent application No.11/526, and 127 (it is for referencial use to incorporate this paper into its full content) are middle to be described.
Screen and carry out biological sample and handle by interview.At virus (for example HIV 1 and 2, HTLV I and II, HBV and HCV) and syphilis and other protokaryon pathogen (for example Bacillus cercus) screening biological sample, abandon detecting positive beneficence.
When screening, find it is that positive any potential sample is all removed from handle sample, and this donor is removed from further donations.The another kind of measure of taking comprises at drug abuse situation detection donor sample or newborn mixture.
Donor can regularly be permitted again.For example, require per four months of donor to screen by the scheme identical with its initial allowance qualification.The donor of not permitting again or not being allowed postpones breast is provided, and is permitted fully until it again.In some cases, if prove that by permitting results of screening more then this donor is forever postponed.In the latter's situation, all from stock, remove and destroy by all remaining breasts that this donor provides.
The donor of permitting can be in Notified body (for example newborn storehouse office) donations, and perhaps the typical case extrudes breast at home.On the one hand, newborn storehouse or directly provide articles for use to take home for the donor of permitting by Dairy Processing merchant (Ru Ku and add industry and commerce can be identical or different entity).The articles for use typical case comprises the computer-readable code (for example bar code label) on the container and can further comprise milker.Donor can be extruded and freezing breast at home then, and is preferably freezing at-20 ℃.On the one hand, as long as the blood testing satisfaction as a result afterwards in donor Ruzhong heart 10-14 days of in the end visiting can receive the donor breast,, then arrange donor and extrude breast at the center or be allowed to condition at collection breast in the family if this result is satisfied.Detect the situation of breast and container, and check bar code information according to database.If satisfied, this unit is placed donor Ru Ku center or processing center household freezer (20 ℃), until preparing further detection and handling.
On the other hand, breast is extruded in its family by donor, rather than collects in newborn library facilities, and method of the present invention comprises the newborn sample of each donor mark in addition, to guarantee that breast is really from the donor of registration.This process identification technology is (sees for example incorporate this paper International Application PCT/US2006/36827 for referencial use into described) known in the art.Can store (for example at-20 ℃) and quarantine to breast until receiving testing result.In above-mentioned steps, discard any underproof newborn sample.The same with blood donations center, closely control to all security informations of donor, comprise the acquisition of blood testing data.
(for example detecting by risk factor) breast of the allowance of collecting is handled by carrying out sterilising filtration and/or pasteurization (perhaps reducing other method of biological load) alone or in combination.On the one hand, by big micron (for example approximately 100-400 micron), be typically about 200 microns filter or strainer filtering.The full milk of filtration is heat-treated (100, see Fig. 1) to prepare separation, full milk is heated about 30 minutes (for example about 20-60 minute) at about 63 ℃ (for example about 50-80 ℃).On the one hand, the full milk temperature raise in acceptable time and surpasses 70 ℃ (HTST) before this step made and filters.For example, specify the content that is used for special producing dairy products container in batches to thaw, and in heat insulation processing jar, mix at 65 ℃.This jar has the continuous temperature supervising device and contains the sheath of circulation glycol coolant.With glycol-cooled to 2-8 ℃ being used for mixed process, and without vortex or make breast form foam and stir tank mixer, because vortex or make breast form foam can to destroy important protein matter composition.Can analyze the biological load of the newborn sample of mixing.
On the other hand, the full milk preparation in the processing jar is connected with high temperature, short time (HTST) pasteurizer by platinum cure silicone rubber pipe.After pasteurization, collect breast and place second processing jar also cooling.Can use other Pasteurisation process (for example pasteurization (vat pasteurization) in the groove), this technology is known in the art.For example, in groove, in the pasteurization, the breast in the jar is heated to minimum 62.5 ℃, and kept about 30 minutes in this temperature.Air on the breast is higher than 5 ℃ of newborn temperature through being steam heated to.On the other hand, both carry out HTST and also carried out pasteurization in the groove.
(as shown in Figure 1) on the other hand, as described herein with 100 heating 110 of people's full milk.Full milk with heating is separated into skimmed milk and butterfat (i.e. fat) 120 then.Is skimmed milk by conventional method such as centrifugal process with newborn degreasing.On the one hand, fat is removed divalent ion (for example calcium ion etc.) with not comprising separating of skimmed milk.On the one hand, the breast that mixes is injected sedimentator with from all the other Ruzhong fractionation of fatty (butterfat), simultaneously skimmed milk is moved in second processing jar (keeping 2-8 ℃) until the optional filtration step that carries out.After centrifugal, butterfat flows in the little rustless steel container.On the one hand, then this butterfat is carried out pasteurization, quantitative subsequently heat, protein and fat content.On the other hand, after finishing separation, determine volume, protein and the fat content of described butterfat, this butterfat of a part is added back in the described skimmed milk to reach heat, protein and the fat content that helps to filter or produce specific products.Can add mineral matter to the Ruzhong in pasteurization and/or before or after filtering.
" full milk " is meant the breast of the degrease that therefrom do not eliminate." skimmed milk " is meant the full milk of having removed all or part of fat content.Therefore recognize that " skimmed milk " comprises " low fat milk " this variant, wherein removed all basically fat contents." butterfat " or " fats portion " is meant the part of the full milk that separates with skimmed milk.Typically, butterfat comprises long-chain, medium chain and SCFA, and concentration is higher than the respective concentration of the skimmed milk that derives from same article.
According to an embodiment, the milipore filter that is used for the filtered and degreased breast has prescribed level to be passed through greater than any material of 40kDa to prevent molecular weight.Material except this includes but not limited to: lactoprotein and butter oil.Perhaps, also can use and prevent that molecular weight is greater than 1-40kDa and the milipore filter that passes through of any material of any scope therein.Typically, can use the filter membrane that comprises 0.45 μ m or littler (for example 0.2 μ m).Typically, use 0.2 μ m filter membrane.In some embodiments, can use gradient to filter (for example at first use 0.45 μ m to filter, next uses 0.3 μ m to filter and filters perhaps any combination of these filter types again with 0.2 μ m).The separation of fat from skimmed milk makes and is easy to filter.Can sterilize by known method, for example filter or tangential flow filtration, use appropriate depth filter or film filter to carry out.
Following lactoprotein can be caught (molecular weight indicates) by milipore filter in bracket: lactalbumin (～14kDa), casein (～23kDa), lactoglobulin (～37kDa), albumin (～65kDa) and immunoglobulin (Ig) (＞100kDa).
Can utilize the 3.5kDa or the milipore filter of low-molecular-weight cutoff value more, for example derive from AdvancedMembrane Technology respectively, San Diego, Calif and Dow Denmark, Naskov, Denmark.Also can use the milipore filter of making by ceramic material.Ceramic filter has the advantage that surpasses synthetic filter.Ceramic filter can be used the circulation steam sterilization.
Typically use the barometric gradient that strides across milipore filter so that filter.Typically, regulate the filtering traffic of passing through this film of described barometric gradient to keep wishing.On the one hand, at first milipore filter is started with a spot of breast, and discard penetrant, begin afterwards to filter.Be sure oing to start by this way filter is useful for filter efficiency.
After pasteurization, dairy products are carried out sterile processing.After being cooled to, can detecting nutrient content, protein content, specific factor, and be adjusted to the level of hope through the breast of pasteurization greater than 2 ℃ to about 8 ℃.On the one hand, measure nutrient content, protein content, the specific factor of the skimmed milk/retention of enrichment, and be adjusted to the level of hope, for example the energy content of butterfat to obtain to wish by adding pasteurization.This product is pumped in the filling element and delivers in syringe or the bottle with branch from processing jar.Detect the virus and the germ contamination situation of finished product, pack afterwards and send.
Method and composition of the present invention has kept the key protein of hope and the activity of vitamin, has reduced biological load simultaneously.Different phase during breast is machined to finished product detects the situation that exists of various organisms.The organism of using in the affirmation research of determining pollution condition comprises bacterium: Escherichia coli, staphylococcus aureus (S.aureus) and Streptococcusagalactiae (S.agalactiae), and virus: human immunodeficiency virus (HIV), hepatitis A virus (HAV), bovine viral diarrhea virus (BVDV) and pseudorabies virus (PSR), the latter is as the mark of CMV.Known HIV and HAV are the potential pollutants of human milk, and therefore selected as correlated virus.Known HCV (HCV) also is the potential pollutant of human milk.Use method of the present invention, the results are as follows:
Table 1: the Log of the organism of detection
10Drop-out value
These viral log drop-out values are not represented the maximum drop-out value that can reach by method of the present invention.Interested especially is the killing of recovery virus (resilient virus) hepatitis A virus (HAV) that is not subjected to the little no lipid envelope of pasteurization condition (62.5 ± 1.0 ℃, the 15 minutes) influence that dairy industry tradition uses.In addition, although staphylococcus aureus has suitable resistance for heat treatment, this organism of processing by the inventive method illustrates reduction～15log.
The present invention also provides the hardening agent composition.Described hardening agent composition is as described herein by collecting and filtration and/or pasteurization step obtain.Hardening agent of the present invention comprises important lactoprotein and biological factor.
Human milk comprises about 100000 kinds of different biological factor: protein, lipid, carbohydrate, vitamin and trace mineral.Key component comprise monomeric immunoglobulin A (IgA) and dimer secretory IgA (s[IgA]
2), lysozyme and lactoferrin.Therefore, help to guarantee that the Pasteurisation process of dairy products security should also preserve these potential heat labile essential compositions of sufficient amount ideally.
Immunoglobulin A (IgA) and secretory IgA in the quantitative human milk samples of use sandwich ELISA method (s[IgA]
2).After use Prolacta HTST method is carried out pasteurization, compare with respective value in the untreated human milk samples, that IgA concentration on average reduces is about 27% (for example from about 7% to about 47%), and the secretory IgA level on average reduces by 17% (for example from about 7% to about 27%).
Lysozyme activity is determined by the microtitre determination method, uses micrococcus lysodeikticus (Micrococcuslysodeikticus) suspension as substrate.Lysozyme activity is about 22000IU/mL in the human milk after pasteurization, is 57% (for example from about 47% to about 67% or more) of the former Ruzhong of people initial activity (39000IU/MI).
Lactoferrin concentration is determined by elisa technique.Using the lactoferrin content of method of the present invention human milk after pasteurization is about 0.033g/100mL, is about 14% (for example about 4-24%) of the former Ruzhong of people initial concentration (0.24g/100mL).
Carry out the vitamin analysis by the HPLC program of confirming.Vitamin A after the pasteurization, vitamin C and α-, γ-and the Delta-Tocopherol level remain unchanged.Vitamin B6 content is reduced to about 7.8 μ g/100mL slightly in the human milk, is about 89% of initial concentration 8.8 μ g/100mL.These results are shown in the table 2.
Table 2: pasteurization is to the effect of people's milk composition
The protein component of dairy compositions of the present invention and hardening agent provides protein source.Protein is the synthetic necessary of growth, enzyme and hormone, and substitutes the protein of losing from skin and urine and ight soil.These metabolic processes have determined need be in the relative quantity of total protein in the food of feeding and specific amino acids.The adaptability of the amount of protein and type is determined by absorption and maintenance, blood plasma amino acid, some blood analyte and the metabolic response of measuring growth, nitrogen in the infant feeding.Special advantage part of the present invention is to have people IgA albumen, lysozyme and lactoferrin in described composition.
Although nonessential, should recognize that human milk compositions of the present invention can take place with non-natural or allos/heterogeneous composition modification or additional these compositions.For example, protein content can be regulated or be modified by the nitrogenous source that use is suitable for people picked-up.This protein is well known to those skilled in the art, and can be easy to select when this composition of preparation.The example of the suitable protein composition that can add comprises casein, whey, condensed skim milk (condensed skim milk), no fat breast, soybean, pea, rice, corn, protein hydrolysate, free amino acid, contains protein source of calcium and composition thereof in having the colloidal suspension liquid of protein.
Another composition of dairy compositions of the present invention comprises adipose-derived.Fat is LBW baby's energy source normally, not only because of its high heat density but also because of its hyposmosis activity in solution.And, although nonessential, can replenish fat constituent for dairy compositions of the present invention.This allos/heterogeneous fat constituent comprises the coconut oil (medium chain triglyceride, MCT oil) of high oil red caul-fat, soybean oil, fractionation, high oily sunflower oil, corn oil, rapeseed oil, coconut oil, palm oil and palm-kernel oil, offshore oil (marine oil), cottonseed oil and specific aliphatic acid such as DHA (DHA) and arachidonic acid.
DHA is a kind of omega-3 fatty acid.DHA is 20 carbon o-3 PUFA of enrichment in human milk.Yet human milk DHA content is according to mother's diet and obviously different.If the fish of the edible high DHA of mother, then higher DHA level is contained in its Ruzhong usually; If mother is edible fishes seldom, then its Ruzhong DHA level is lower.Therefore, human milk can need additional DHA to accept the DHA of capacity to guarantee the premature.Replenish DHA typical case and follow additional arachidonic acid.The U.S. Patent No. 5,492,938 of Kyle etc. described from dinoflagellate the method that obtains DHA with and application in pharmaceutical composition and dietary supplement.
Carbohydrate is another composition of the present composition.Carbohydrate provides the energy source that can be easy to utilize, and helps to grow and has reduced and organized catabolism to cause underfed quick growth baby's danger.In the infant formula Ruzhong based on breast of human milk and standard, main carbohydrate is a lactose.The LBW baby may not fully digest lactose, because lactase activity is grown yet fully in third trimester of pregnancy (36-40 week) fetus enteron aisle.On the other hand, sucrase active reaches maximum in pregnant 32 weeks, and the glucoamylase (glucosoamylase) of digestible starch syrup dry powder (glucose polymer) is active in the same twice that increases apace with lactase activity in pregnant late period (third trimester).Can be human milk compositions carbohydrate supplementation of the present invention.The example that can be used for the carbohydrate of supplementary copy inventor dairy compositions comprises but non-cornstarch, maltodextrin, glucose polymer, sucrose, corn syrup, corn syrup solids, rice syrup, glucose, fructose, lactose, high-fructose corn syrup and heavy oligosaccharides such as the FOS (FOS) that is limited to hydrolysis.
Vitamin and mineral matter are important for baby's normal nutrition and growth.Premature or LBW baby need electrolyte such as sodium, potassium and chlorine to keep growth and acid-base balance.These electrolytical enough picked-ups also are to substitute from urine, ight soil and required from the electrolyte of skin forfeiture.Calcium, phosphorus and magnesium are that the normal bone mineralising is required.For the bone growth, in feeding food, must there be these mineral matters of q.s.
Trace mineral is relevant with cell division, immunologic function and growth.Therefore, infant physical growth and growth need provide the trace mineral of capacity for it.Important trace mineral comprises copper, magnesium and iron (it is synthetic most important for hemoglobin, myoglobins and iron enzyme).Zinc be for growth, the activity of plurality of enzymes and DNA, RNA and protein synthetic required.Copper is active required for several important enzymes.Manganese be for the growth of bone and cartilage required, and most important in polysaccharide and glycoprotein synthetic.Therefore, can be human milk of the present invention and hardening agent composition replenishing vitamins and mineral matter.
Vitamin A is to be growth, cell differentiation, vision and the necessary a kind of liposoluble vitamin of immune system.Vitamin D plays an important role for the absorption of calcium and the growth of bone, and is less for the inhalation effects of phosphorus.Vitamin E (tocopherol) prevents the peroxidating of polyunsaturated fatty acid in the cell, therefore prevents tissue damage.Folic acid plays an important role in amino acid and nucleotide metabolism.Be illustrated among the LBW baby of low folic acid picked-up, serum folic acid concentration drops to after 2 ages in week and is lower than normal level.In addition, some B family vitamins low concentration in premature's breast milk exists.
As mentioned above, the needs of the changeability of human milk vitamin and mineral concentration and premature increase require minimum reinforcement to accept the vitamin and the mineral matter of q.s to guarantee developmental baby.The vitamin that replenishes in human milk compositions of the present invention and hardening agent and the example of mineral matter comprise vitamin A, vitamin B1, vitamin B2, vitamin B6, cobalamin, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, nicotinic acid, m-inositol, calcium, phosphorus, magnesium, zinc, manganese, copper, sodium, potassium, chlorine, iron and selenium.Also need to replenish other nutriment: chromium, molybdenum, iodine, taurine, carnitine and choline.
The invention provides composition, it comprises 67Kcal/dL (20 calories every ounce) full milk product, 80Kcal/dL (24 calories every ounce) full milk product and human milk fortifier.Described newborn hardening agent composition comprises about 20-70mg/ml protein, about 35-85mg/ml fat, about 70-115mg/ml carbohydrate and contains people IgA.Use method of the present invention can obtain the composition of various heats.The example of described composition is 24 calories of dairy compositions and hardening agent dairy compositions.
Described 24 calories of full milk compositions comprise following composition: human milk, calcium glycerophosphate, potassium citrate, calcium gluconate, calcium carbonate, magnesium phosphate, sodium chloride, natrium citricum, zinc sulfate, copper sulphate and manganese sulfate.Per unit part (serving) described 24 calories of compositions (10ml) have following feature (notice that described numerical value is approximation, this area recognize these numerical value because the machine of detection method, use etc. and can be different):
Calorie 8.5
Total fatty 0.44g
Sodium 2.3mg
Potassium 6.3mg
Total carbohydrates (Carbs.) 0.79g
Sugar 0.64g
Protein 0.31g
Vitamin A 21.1IU
Vitamin C＜0.10mg
Calcium 8.0mg
Iron 13.3mcg
Phosphorus 3.8mg
Magnesium 0.74mg
Chlorine 5.0mg
Zinc 0.12mcg
Copper 17.3mcg
Manganese＜6.2mcg
Morie osmolarity～322mOsm/Kg H
2O
Described hardening agent composition comprises following composition: human milk, calcium carbonate, potassium phosphate, calcium phosphate, calcium glycerophosphate, calcium gluconate, natrium citricum, magnesium chloride, calcium chloride, magnesium phosphate, zinc sulfate, copper sulphate and manganese sulfate.The described hardening agent composition of per unit part (2ml) have following feature (notice that described numerical value is approximation, this area recognize these numerical value because the machine of detection method, use etc. and can be different):
Calorie 2.7
Total fatty 0.15g
Sodium 1.2mg
Potassium 2.3mg
Total carbohydrates 0.21g
Sugar 0.15g
Protein 0.10g
Vitamin A 5.5IU
Vitamin C＜0.02mg
Calcium 8.9mg
Iron 0.01mg
Phosphorus 3.6mg
Magnesium 0.38mg
Chlorine 0.4mg
Zinc 0.05mg
Copper 2.7mcg
Manganese＜1.3mcg
Morie osmolarity～343mOsm/Kg H
2O (when mixing) with former breast
The Morie osmolarity of human milk compositions of the present invention and hardening agent is most important for absorption, absorption and the digestion of described composition.Unsuitable Morie osmolarity can cause baby's abdominal distension and vomiting.The Morie osmolarity of human milk compositions of the present invention and hardening agent (in case mixing with former breast) typical case is lower than about 400mOsm/Kg H
2O.Typically, described Morie osmolarity is the water of the water of about 310mOsm/Kg to about 380mOsm/Kg.When being composition carbohydrate supplementation of the present invention or fat constituent, should regulate the Morie osmolarity of said composition.For example, the Morie osmolarity of the described reinforcement human milk of the type of composition (for example carbohydrate or fat) influence.Carbohydrate inversion many more, then osmotically active is high more.In addition, when with the human milk reprovision, because the diastatic further hydrolysis of human milk makes the carbohydrate source of partial hydrolysis can further improve Morie osmolarity.Those skilled in the art can easily select to cause the carbohydrate or the carbohydrate combination of Morie osmolarity of the hardening agent/human milk compositions of suitable reprovision.
Described hardening agent typically mixes with human milk to increase by 4 card/ounces.Typically this is former breast: 80: 20 mixtures of hardening agent (for example former breast of 8ml and 2ml hardening agent), show work " Plus 4 " in following table.Though the former breast and the hardening agent of any or all correlation ratios or amount all comprise in the present invention, other typical mixture comprises 70: 30 (Plus 6), 60: 40 (Plus 8) and 50: 50 (Plus 10).Table 3 shows the example of the mixture of the former breast of people (for example mother's oneself breast) combination human milk compositions of the present invention.Table 4 illustrates the heat Calculation example of the mixture of former breast of people and dairy compositions of the present invention.
Table 3
Table 4
Described hardening agent typically places 10ml syringe or 20ml bottle.Can comprise the bottle that has syringe.In the situation of syringe kits (for example syringe and bottle) or 20ml bottle, described bottle can comprise scale mark to help correct dilution.For example, can detect mother's former breast to determine the nutritive value of this former breast.Typical former breast on average comprises 1.1% protein, 4.2% fat, 7.0% lactose (sugar), and the energy of per 100 gram 72kcal is provided.Can detect the nutritive value of the former breast of mother, use hardening agent composition of the present invention to regulate then, make the former breast of mother increase by 4 card/ounces.
" UD " is meant the independent packing of the hardening agent of the hardening agent that contains the amount that is useful on dairy baby food.Preparation is used for premature's the amount typical case of human milk of reinforcement in every day 25ml to 150ml scope.Therefore, single UD is an an amount of hardening agent of strengthening the former dairy products of 8-40ml.For bigger volume, can add extra UD.Therefore, UD is former breast of the every 8ml of 2ml hardening agent or the former breast of the every 40ml of 10ml hardening agent.On the one hand, described UD comprises the 10ml syringe, and can comprise the scale mark that 2ml is enough to prepare a plurality of dairy products.
Typically, the amount of the human milk of preparation is based on the amount of the breast of 24 hours nutrition supplies that need offer the baby.For example, baby's feeding every day 150ml breast of 1500gm.If use freezing breast, then place tepidarium until thawing fully this freezing breast.In hardening agent, mix and to pay special attention to.Need mix gently avoiding destroying the butter oil ball, the destruction of butter oil ball can increase on the sidewall that butter oil sticks to the feeding container, causes significantly forfeiture of fat (energy).With the fortified milk of syringe extraction specified amount, and with being indicated.When dairy products are finished, give Baby Room with the equal portions feeding food of mark, place refrigerator so that the nursing staff conveniently takes.Typically, before feeding, the fortified milk of refrigeration is heated.For example, in dry heat laboratory cultures case, approximately heating about 15 minutes in 35-45 ℃ of scope.Make the temperature of described fortified milk reach room temperature like this.Can give the baby by a batch feeding (bolus feeding) mode or by the lasting feeding mode of syringe infusion pump with this fortified milk.If the use infusion pump is placed so that fat continues to inject syringe needle is vertical, and syringe is directly invested on the TF to reduce the potential surface area that fat and immunizing composition may adhere to.
The invention provides the human milk of non-xenogenesis and hardening agent composition and the human protein of verified promotion immunology progress and infant physical growth is provided.In addition, human milk of the present invention and hardening agent composition are the health advantages maximizations that is fully tolerated and make human milk, have solved the variability of human milk as the source of energy, protein, calcium, phosphorus, sodium and other micronutrient simultaneously.
The typical case uses independent UD specification packing when in bulk.Owing to the volume of the breast that gives the premature during feeding in every day is less, therefore prepare the reinforcement human milk of small size.Repeated to open, the worry always in hospital environment of the aseptic in the bulk container of five equilibrium and storage.Independent UD makes can add a small amount of hardening agent in human milk, but does not have the possibility of polluting the residue hardening agent.
Those skilled in the art are easy to obtain the also container of known many types.The example that can be used for the type of the container in the method and composition of the present invention comprises bottle, syringe and jar (for example metal, glass or plastic tank).
As mentioned above, the invention still further relates to the method that nutrition is provided for the premature, by will be of the present invention hardening agent add the nutrient content that reaches hope in the human milk with the former breast of mediator, and give the premature with the human milk of this reinforcement.The present invention further provides by giving the method for human milk that the premature strengthens to promote that the premature grows.
Can use method of the present invention that the breast that derives from people or ox is processed.On the one hand, described breast comprises colostrum.Typically, described colostrum suitably dilution (for example with water 1: 1) in sterilized water.
Breast by method acquisition of the present invention is substantially the same with former breast, but comprises biological load or the pathogen-free domestic such as the Bacillus cercus of reduction.The aseptic milk product of gained comprises BA (for example comprising protein and antibody compositions), however bacterium, fungi and the spore do not found in former Ruzhong.
The skimmed milk that obtains does not partly have bacterium, fungi and spore.Then the skimmed milk that filters is stored separately or made up once more with fats portion after filtering.In the situation that skimmed milk is stored separately, can before edible, itself and fats portion be made up once more subsequently.Perhaps, edible this skimmed milk part.The breast of described skimmed milk and/or combination once more can long term storage, preferably stores being lower than under the room temperature, more preferably 4 ℃ of storages.
The further illustration of following embodiment the present invention, but unrestricted the present invention's meaning.
Embodiment
In the Class100000 clean room, handle, in the Class10000 clean room, carry out filling.Mix the donor breast, sample thief carries out risk factor and determines (for example carrying out PCR pollutes and infect to determine HIV, HBV, HCV).Filter the donor breast to remove piece and big predetermined substance by 200 micron screen.
Then the full milk that filters is handled 16 seconds (for example HTST) about 63 ℃ of heat treated 30 minutes or at about 73 ℃.This heat treatment is used to reduce biological load and the breast of separation is prepared in preparation.The breast of the heating of this filtration is separated into skimmed milk and fat (butterfat).The skimmed milk that carries out after separation and the analysis of butterfat comprise: (a) skimmed milk-about 0.69% fat, about 1.07% protein, about 7.14% lactose; (b) butterfat-about 46% fat, about 2% protein, about 10% lactose.
Remove about 50% butterfat and separate once more by separator.This step produces more skimmed milk, will increase protein output.Product from the non-skimmed milk side of separator is a butter, and it can be retained and be used for other technology.
Butterfat or fats portion are added in the skimmed milk to regulate described skim milk content with better ultrafiltration.For example, fat need be about 55% to about 65% of protein content in the described skimmed milk.A purpose of ultrafiltration step is to remove too much water and condensing protein.The filter that is used for ultrafiltration has about 40kDa cutoff value.Water is considered to penetrant.The skimmed milk of collecting after the ultrafiltration is analyzed, and it has about 8% protein.Can use penetrant to carry out filter wash or back washing (post wash) to be recovered in any protein that is trapped in during the ultrafiltration step on the filter.The back washings is added in the skimmed milk that concentrates so that protein content is about 7.2%.
After adding, after the washings, butterfat is added in the skimmed milk that concentrates, so that calorie increases to correct target.In this, product has about 9.2% fat, about 6.3% protein and about 10.5% lactose.Sample to Final Bulk carries out the mineral matter analysis.This is the mineral matter in measuring big batch.Described Final Bulk is freezing under-20 ℃ or lower temperature.When the mineral matter result sends the laboratory back to, Final Bulk is thawed.Based on initial content of mineral substances among the Final Bulk, calculate if any the amount of any extra mineral matter that will add.Final objective is about: (a) for the large quantities of products of content low in calories (Prolact for example
TM+ 4, be also referred to as Plus 4; Perhaps Prolact
TM+ 6, be also referred to as Plus 6), calcium-471.6mg/dL, phosphorus-225.2mg/dL, sodium-75mg/dL, potassium-208.1mg/dL, magnesium-24.4mg/dL, chloro-69.1mg/dL, zinc-3.1mg/dL, copper-0.1mg/dL and manganese-9.2 μ g/dL; (b) for Prolact
TM+ 8, be also referred to as Plus 8 and Prolact
TM+ 10, be also referred to as Plus 10, calcium-235.8mg/dL, phosphorus-112.6mg/dL, sodium-37.5mg/dL, potassium-104mg/dL, magnesium-12.2mg/dL, chloro-34.6mg/dL, zinc-1.6mg/dL, copper-0.05mg/dL and manganese-4.6 μ g/dL.Final Bulk is heated to 50 ℃, and mineral matter is mixed among the FinalBulk.
After mixed mineral matter, this product is carried out pasteurization in jar.This jar outside adds sheath and uses the ethylene glycol of heat to heat this jar (the product temperature is about 67 ℃, and air themperature is higher than the product temperature, is about 70 ℃), with product through pasteurization 30 minutes.Use the ethylene glycol of cooling in adding the jar of sheath, to make the product temperature be reduced to about 5 ℃.But then with this product as required five equilibrium advance in the container of can.For example, can specification comprises: Prolact
TM+ 4 10mL, Prolact
TM+ 4 20mL, Prolact
TM+ 615mL, Prolact
TM+ 6 30mL, Prolact
TM+ 8 20mL, Prolact
TM+ 8 40mL, Prolact
TM+ 10 25mL and Prolact
TM+ 10 50mL.When carrying out filling, can get bottle at random and detect nutritive value and biological load.Can detect following pathogen: total aerobic counting＜10 CFUs/mL, Bacillus cercus-1 CFU/mL, Escherichia coli-1 CFU/mL, coliform (Coliform)-1 CFU/mL, pseudomonad-1 CFU/mL, salmonella-1 CFU/mL, staphylococcus-1 CFU/mL, yeast-1 CFU/mL, mould-1 CFU/mL.The product that produces by said method can comprise following content: for (a) Prolact+4 and Prolact+6, (i) total calorie is that about 1.35Cal/mL is to about 1.55Cal/mL, (ii) protein is that about 5.5g/dL is to about 6.5g/dL, (iii) fat is that about 8.5g/dL is to about 9.5g/dL, (iv) calcium is about 417.6mg/dL, (v) chlorine is about 69.1mg/dL, (vi) copper is about 0.1mg/dL, (vii) magnesium is about 24.4mg/dL, (viii) manganese is about 9.2 μ g/dL, (ix) phosphorus is about 225.2mg/dL, (x) potassium is about 208.1mg/dL, (xi) sodium be about 75mg/dL and (xii) zinc be about 3.1mg/dL; (b) for Prolact+8 and Prolact+10, (i) total calorie is that about 1.35Cal/mL is to about 1.55Cal/mL, (ii) protein is that about 5.5g/dL is to about 6.5g/dL, (iii) fat is that about 8.5g/dL is to about 9.5g/dL, (iv) calcium is about 208.8mg/dL, (v) chlorine is about 34.6mg/dL, (vi) copper is about 0.05mg/dL, (vii) magnesium is about 12.2mg/dL, (viii) manganese is about 4.6 μ g/dL, (ix) phosphorus is about 112.6mg/dL, and (x) potassium is about 104.1mg/dL, (xi) sodium be about 37.5mg/dL and (xii) zinc be about 1.6mg/dL.
Under prerequisite without departing from the spirit and scope of the present invention, can use with different mode described herein and carry out embodiment of the present invention.Described embodiment therefore just illustration the present invention and unrestricted meaning, institute changes and equivalent all is included in the description of the invention.
Claims (31)
1. method that obtains human milk compositions comprises:
Filter full milk by about 100-400 micron filter;
About 58-65 ℃ of this full milk of heat treatment about 20-40 minute;
This full milk is separated into skimmed milk part and fats portion;
Filter this skimmed milk part to obtain the skimmed milk part of penetrant part and enrichment protein by one or more skimmed milk filter;
Heat fats portion about 1 hour at about 90-120 ℃, be enough to reduce the biological load of fats portion; And
The skimmed milk part of mixing the fraction of treated fats portion and enrichment protein is to obtain human milk compositions.
2. the process of claim 1 wherein that described full milk comprises the human milk of mixing.
3. the method for claim 1 further is included in the sample that detects described full milk before filtering whether have HIV, HBV, HCV or its any combination.
4. the process of claim 1 wherein and full milk is filtered by about 200 microns filter screen.
5. the process of claim 1 wherein to described full milk about 30 minutes of about 63 ℃ of heat treatments.
6. the process of claim 1 wherein that the skimmed milk after separating partly comprises about 0.69% fat, about 1.07% protein and about 7.14% lactose.
7. the process of claim 1 wherein that the fats portion after separating comprises about 46% fat, about 2% protein and about 10% lactose.
8. claim 1 or 7 method, wherein said fats portion is further processed to obtain extra skimmed milk.
9. the method for claim 8 is wherein partially mixed with described extra skimmed milk and described skimmed milk.
10. the method for claim 1, further be included in filter before the described skimmed milk part with fats portion regulate the skimmed milk part with obtain fatty consistency in the described skimmed milk part be described skimmed milk part protein content about 55% to about 65%.
11. the process of claim 1 wherein that the skimmed milk of described enrichment protein partly comprises about 8% protein.
12. the method for claim 1 or 11 further comprises described one or more skimmed milk filter that washing has a penetrant obtaining the protein washings, and this protein washings is added in the skimmed milk part of enrichment protein.
13. the process of claim 1 wherein that described full milk is a human milk.
14. the process of claim 1 wherein described human milk compositions is carried out pasteurization.
15. pass through the human milk compositions that the method for claim 14 obtains.
16. human milk compositions, it comprises
The protein component of about 20-70mg/ml,
The fat constituent of about 35-85mg/ml,
The carbohydrate component of about 70-115mg/ml; And
Wherein said composition comprises people IgA.
17. through the human milk compositions of the claim 16 of pasteurization, wherein said composition comprises:
The 50mg/ml protein component,
The 75mg/ml fat constituent, and
The 105mg/ml carbohydrate component.
18. through the human milk compositions of the claim 16 of pasteurization, wherein said composition comprises:
The 31mg/ml protein component,
The 44mg/ml fat constituent, and
The 79mg/ml carbohydrate component.
19. through the human milk compositions of the claim 16 of pasteurization, it further comprises and is selected from vitamin A, vitamin C, calcium, iron, phosphorus, magnesium, chlorine, zinc, copper, manganese, sodium, potassium, lysozyme, lactoferrin, vitamin B6 and the composition of combination arbitrarily thereof.
20. through the human milk compositions of the claim 16 of pasteurization, wherein said people IgA comprises secretory IgA.
21. through the human milk compositions of the claim 16 of pasteurization, wherein said IgA is about 100-600mg/ml.
22. through the human milk compositions of the claim 16 of pasteurization, wherein said IgA is about 230mg/ml.
23. through the human milk compositions of the claim 19 of pasteurization, wherein said lysozyme is 22000IU/ml.
24. through the human milk compositions of the claim 19 of pasteurization, wherein said lactoferrin is 0.33mg/ml.
25. kit, it comprises human milk compositions and a graduated bottle of claim 15 or 16, described graduated bottle is used to mix described human milk compositions and the preparation of the former breast of people to obtain to mix, and the preparation of wherein said mixing is compared with the former breast that does not contain described human milk compositions through pasteurization and comprised about 4 calories/ounce more.
26. a method that obtains the nutrition dairy compositions comprises:
Measure the nutrient content of the former breast of people,
Add human milk compositions through the claim 15 of pasteurization or 16 so that the nutritive value of described former breast improves about 4 calories/ounce to described former Ruzhong.
27. one kind for the premature provides the method for extra-nutrition thing, comprises that human milk compositions with claim 15 or 16 adds in the human milk and the mixing human milk that will obtain gives the premature.
28. a human milk compositions that comprises donor from former breast of body and allosome dairy compositions, wherein said human milk compositions comprise at least approximately 2.1g/dL human protein.
29. the human milk compositions of claim 28, wherein said human protein are the human proteins of non-freeze-drying.
30. the human milk compositions of claim 28, wherein said composition comprise about 2.1g/dL (21mg/ml) to about 3.75g/dL (37.5mg/ml) human protein.
31. the human milk compositions of claim 28, wherein said composition comprise about 2.1% to about 3.75% protein.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103002757A (en) * | 2010-05-18 | 2013-03-27 | N.V.努特里奇亚 | Preterm milk formula |
| CN109952031A (en) * | 2016-10-04 | 2019-06-28 | Imb公司 | Methods and systems for producing sterilized human milk products |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1637043A1 (en) * | 2004-09-17 | 2006-03-22 | Medela Holding AG | Human milk fortifiers and methods for their production |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP1637043A1 (en) * | 2004-09-17 | 2006-03-22 | Medela Holding AG | Human milk fortifiers and methods for their production |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103002757A (en) * | 2010-05-18 | 2013-03-27 | N.V.努特里奇亚 | Preterm milk formula |
| CN109952031A (en) * | 2016-10-04 | 2019-06-28 | Imb公司 | Methods and systems for producing sterilized human milk products |
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