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WO2012030764A2 - Préparation de lait maternel - Google Patents

Préparation de lait maternel Download PDF

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Publication number
WO2012030764A2
WO2012030764A2 PCT/US2011/049645 US2011049645W WO2012030764A2 WO 2012030764 A2 WO2012030764 A2 WO 2012030764A2 US 2011049645 W US2011049645 W US 2011049645W WO 2012030764 A2 WO2012030764 A2 WO 2012030764A2
Authority
WO
WIPO (PCT)
Prior art keywords
milk
human
human milk
skim
lyophilized
Prior art date
Application number
PCT/US2011/049645
Other languages
English (en)
Other versions
WO2012030764A3 (fr
Inventor
Elena M. Medo
Original Assignee
Neolac, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Neolac, Inc. filed Critical Neolac, Inc.
Publication of WO2012030764A2 publication Critical patent/WO2012030764A2/fr
Publication of WO2012030764A3 publication Critical patent/WO2012030764A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/20—Dietetic milk products not covered by groups A23C9/12 - A23C9/18
    • A23C9/206—Colostrum; Human milk
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23B—PRESERVATION OF FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES; CHEMICAL RIPENING OF FRUIT OR VEGETABLES
    • A23B11/00—Preservation of milk or dairy products
    • A23B11/10—Preservation of milk or milk preparations
    • A23B11/14—Preservation of milk or milk preparations by freezing or cooling
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C1/00—Concentration, evaporation or drying
    • A23C1/06—Concentration by freezing out the water
    • A23C1/08—Freeze-drying

Definitions

  • This disclosure is related to human milk products, compositions ana methods of making and using such
  • compositions are provided.
  • the disclosure provides sterile human milk protein compositions.
  • the sterile human milk protein composition is prepared by a method comprising sterile filtering skim human milk through at least two successively smaller submicron filters to obtain a human milk protein composition; lyophilizing the human milk protein composition; and applying a viral inactivation step and/or a sterilizing process to the lyophilized human milk protein composition.
  • the skim human milk is obtained by gravity separation for 24-36 hours or by
  • the skim human milk is clarified prior to filtration through at least one clarifying filter.
  • the clarifying filters comprise a micron filter or diatomaceous earth.
  • the at least one clarifying filters comprises two clarifying filters. In this
  • a second clarifying filter is a submicron filter.
  • the at least two submicron filters are between about 0.5 and 0.2 micron filters.
  • the viral sterilizing step comprises heat treatment.
  • the viral sterilizing step comprises gamma irradiation.
  • the lyophilized product comprises proteins that upon
  • the lyophilized product comprises at least 50% of the skim milk's lysozyme content. In yet another embodiment, the lyophilized product comprises at least 40% of the skim milk's IgA content. In yet another embodiment, the lyophilized product comprises at least 80% of the skim milk's lactoferrin content. In one embodiment, the lyophilized human milk product comprises a storage life of about 6 months or more and comprises biologically active proteins when reconstituted. In yet another embodiment, following sterile filtration the skim human milk comprises about 20-50 mg/ml protein.
  • the skim human milk comprises about 1900-2400 pg/ml lactoferrin, about 12-18 pg/ml lysozyme and/or about 1-3 mg/ml human IgA.
  • the human skim milk is non-pasteurized prior to or during filtration.
  • the disclosure also provides a sterile lyophilized human milk product obtained from non-pasteurized human milk comprising biologically active human IgA, human lactoferrin, and human lysozyme proteins .
  • Figure i shows a flow process of the disclosure.
  • Figure 2A-C depicts general schematics of systems of the disclosure for carrying out the method of Figure 1.
  • ia shows a system up through an individual vial filling step, prior to lyophilization and sterilization of the lyophilized product;
  • b includes another example of filter sizes usable in the disclosure as well as demonstrating the lyophilization;
  • c shows an example utilizing a
  • compositions the exemplary methods, devices and materials are described herein.
  • Preterm infants have poor or underdeveloped immune systems and immature digestive systems. Because of this, such preterm infants have increased total caloric and specific nutrient needs (when generally compared with term infants) . Furthermore, it is well recognized the human milk contains not only the nutritional/caloric needs , but also provides important biological molecules for immune resistance and development . Thus, providing a proper balance of caloric and biologically important materials is an important factor in their growth and development .
  • the disclosure provides human milk compositions and methods of making and using such compositions for feeding to infants, e.g. , premature infants .
  • the compositions of the disclosure are derived from human milk and thus comprise human milk proteins; however, unlike pasteurization
  • Pasteurization processes merely reduce biological risks by neat treatment and are typically characterized as having a reduced bioburden for about 30 days.
  • the products and methods of the disclosure reduced biological contaminants (bacterial and viral) and in many instances can be considered "sterile" having a bioburden that does not result in any contamination or microbial degradation of nutrient or microbial growth for at least 60 days.
  • the disclosure provides a sterile human milk protein lyophiiized composition comprising about 4-5 mg of human milk protein per Decaliter when reconstituted in sterile water.
  • the disclosure provides lyophiiized or
  • reconstituted human milk protein compositions e.g.,
  • compositions that include human oligosaccharides, peptides, and other small molecules and methods of making and using such compositions .
  • the compositions contain various levels of nutritional components and can be used in feeding of or administration to preterm, and. full term infants, as well as children and. adults with various disorders and/or diseases.
  • the compositions are generated by clarifying human skim milk followed, by micron and submicron filtration, lyophilization and viral heat treatment.
  • the resulting product comprises sterile human milk proteins in a lyophiiized form.
  • the lyophiiized proteins can be reconstituted in sterile water or in a mother's milk before feeding to her baby.
  • the lyophiiized product is reconstituted to provide about 3.5-5.0 grams of protein per decaliter ⁇ e.g., 4.0-4.8, 4.2-4.6, 4.3-4.5 grams per decaliter) .
  • human milk is obtained, including pooled human milk.
  • the human milk is then separated into cream and skim through various methods including gravitational separation or through centrif ligation .
  • the skim portion of the milk often includes large products that can clog a filter during filtration.
  • the methods of the disclosure comprises a clarification process to remove large particulars .
  • Such methods car; include passing the skim milk through diatomaceous earth or a large micron filter (e.g., about 5-10 microns ⁇ .
  • the clarification process may comprise one or more passages of the skim through a micron filter or diatomaceous earth (or a combination thereof) .
  • the resulting clarified skim can then be stored by freezing or immediately further sterile filter.
  • the sterile filtration of the clarified skim can be performed through one or more filters having the same or graduated filter sizes.
  • the clarified skim can be filtered through a 0.45 micron filter, followed by a second, 0.2 micron filter.
  • the clarified, skim can be filtered through one or more 0.2 micro filters or one or more 0.45 micron filters or a combination thereof.
  • the resulting sterile filtered skim milk has a reduced bioburden and can be bacterial free.
  • the resulting sterile filtered skim milk can then be freed-dried or lyophilized to provide a iyophilized sterile milk protein composition.
  • lyophilized sterile milk composition can then be heat treated to eliminate viral contaminants providing a sterile human milk protein composition.
  • the lyophilized product may be stored for 6 months or more without degradation or
  • the lyophilized composition can be readily reconstituted in sterile water or may be reconstituted in human milk [e.g., a mother' s own milk) to increase the protein content of the mother' s milk. It may be desireabie to add the lyophilized product to bovine milk or a mixture of human and non-human milk formulations .
  • the methods featured herein can be used to process donor milk, e.g., about 50-1800 liters of raw human milk.
  • the raw milk may be pre-screened for biological contaminants or the donors screened for various risk factors or infections .
  • Methods of screening a subject are very similar to those used for screening donors of blood for blood supplies.
  • a donor may be screened for substance abuse, viral infections ⁇ e.g., HIV, hCMV, Hepatitis A, B, or C and the like) .
  • the donor may also be screened for
  • the donor may also be qualified based upon recent travel activities (e.g. , to certain foreign countries), sexual behavior, and drug use.
  • subjects may be screened for milk content (e.g., fat or protein content) .
  • milk content e.g., fat or protein content
  • it may be desirable to collect milk from subjects that express high protein, low fat milk.
  • whole milk is meant milk from which no fat has been removed.
  • silk milk is meant milk from which at least 75% of fat has been removed.
  • premature infants are used interchangeably and refer to infants born less than 37 weeks gestational age and/or with brrth weights less than 2500 gm.
  • full term infant is used to refer to infants born after 37 weeks gestational age and/or with birth weights greater than 2500 gm.
  • bioburden microbiological
  • contaminants and pathogens that can be present in milk, e.g. , viruses, bacteria, moid, fungus and the like.
  • Fig. 1 shows one embodiment of a method of
  • donor milk can be carefully analyzed for both identification purposes and to avoid contamination .
  • the donor milk may be frozen or unfrozen, pooled or unpooled . If the donor milk is frozen, the donor milk is thawed. The thawed donor milk may be pooled following thawing or may be pooled prior to freezing.
  • the raw milk is then separated into skim and cream. The separation of the skim from the cream may be performed by any number of methods known in the art including, but not limited to, gravitational separation or by centrifugation. Because directly applying the skim to sterile filters will cause rapid clogging of the filter system, the skim milk is first clarified before sterile filtration.
  • the clarification of the skim may be performed by passing the skim through diatomaceous earth or through large pore filters (e.g., from 5 micron to 50 micron filters) .
  • the clarification step may comprise a combination of filters or filters and diatomaceous earth.
  • a first clarification filter may comprise a 45 micron filter followed by a 20 micron and a 5 micron filter. It will be recognized that any filter size in between and. inclusive of 5 and. 50 microns can be used.
  • the permeate from the clarification step is then processed through one or more sterile filters .
  • the sterile filters are about 0.2 microns to 0.45 microns.
  • the permeate from the clarification step is filtered through one or more graduated sterile filters (e.g., a 0.45 micron filter and then a 0.2 micron filter) .
  • the permeate from the sterile filtration can then be combined with other permeates from different sterile fiiurations batches .
  • the resulting permeates are freeze- dried/lyophiiized to provide a dry human milk protein composition.
  • the iyophilized/freeze-dried composition can then be further sterilized by a viral heat activation step or by gamma irradiation or other techniques known in the art .
  • the resulting lyophilized/ ' freeze-dried product can be easily stored in sterile containers for at least 6 months or more .
  • the lyophilized/freeze-dried product can be reconstituted in bovine milk, human milk (e.g., milk from the mother of the baby to be fed) , or sterile solutions ⁇ e.g. , water) .
  • the reconstituting fluid can be further supplemented with vitamins, minerals, oligosaccharides, fatty acids and other nutritional factors .
  • the lyophilized/ ' freeze-dried product can be easily stored in sterile containers for at least 6 months or more .
  • the lyophilized/freeze-dried product can be reconstituted in bovine milk, human milk (e.g., milk from the mother of the baby to be fed) , or sterile solutions ⁇ e.g. , water) .
  • the reconstituting fluid can be further supplemented with vitamins, minerals, oligosaccharides
  • lyophilized product is reconstituted to a final concentration of about 4.0-5.0 mg/DL of protein.
  • the reconstituted milk protein is fed to a neonate from 2-8 times per day or as necessary or desired.
  • human breast milk was centrifuged at 10, 000 x g for 30 minutes and passed through 25 pm filter paper to remove large particles .
  • 1200 mL were passed through a Sartoclean GF 3 + 0.6 um filter (Sartorius 5605304 F7--SS ) which reached a final pressure 12.0 psi .
  • the entire 1200 mL were then passed through a Sartoclean GF 0.8 + 0.65 urn filter (Sartorius 5605305G7--SS) without any backpressure.
  • the filters can be ceramic filters .
  • Figure 2A-C depicts general schematics of systems of the disclosure for obtaining human milk protein in a sterile composition.
  • kits comprising a lyophilized/ freeze-dried human milk protein composition in a vral or other storage container; a syringe or other container for holding a reconstituting liquid.
  • the vials and liquid containers may be in a unit dose form.
  • the reconstituting liquid may comprise additional nutritional factors or therapeutics .
  • a variation that can be used would include a shaker water bath . Care should be taken to mix the thawing milk to equilibrate the temperatures and prevent overheating of the milk. The milk was refrigerated after thawing before it was processed any further.
  • Protec® RF0.5 glass microfiber filter was used. Rapidly thawed 24 hour and 36 hour decanted milk pre-filtered by the DM.G5 was readily filtered, at 10 psi. Twice as much
  • a 30" RF0.5 filter is capable of filtering up to 5400 L of 24 hour milk, provides for
  • a filtration scheme that uses a pump set at 3 LPM and tubing system capable of producing up to 20 psi upstream pressure is able to filter the 200 L batch through the 30" DeitaMaxTM DMG5 and the 30" Protec ⁇ RF0.5 if the milk is thawed quickly. This allows up to 5 psi differential pressure for the first filter and 10 psi differential pressure for the second filter with 5 psi pressure to spare.
  • the milk can be collected in a bag or other sterile
  • the final sterile filtration uses about seven 30" EverLUXTM STW0.2 filters for the 20G L batch and the addition of addition filters should be considered for larger batches (e.g., eight ⁇ 233 L) or nine (272L) etc.) .
  • Each 10" STW0.2 filter module can filter approximately 9.7 L. With nine cartridges in a single housing, a flow rate of -1.9 LPM may be possible at 10 psi. Seven cartridges allow -1,5 LPM. A separate pump or pressure source should be used for the final filtration .
  • each capsule will have a flow rate of about 200 ml/mi.n ,
  • Table 1 demonstrates that the filtration provides a sterile composition comprising at least 45% or more of the initial starting human milk proteins listed above

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  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Dairy Products (AREA)

Abstract

La présente invention porte sur des produits à base de lait maternel, sur des compositions et sur des procédés de fabrication et d'utilisation de telles compositions.
PCT/US2011/049645 2010-08-30 2011-08-30 Préparation de lait maternel WO2012030764A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US37806410P 2010-08-30 2010-08-30
US61/378,064 2010-08-30

Publications (2)

Publication Number Publication Date
WO2012030764A2 true WO2012030764A2 (fr) 2012-03-08
WO2012030764A3 WO2012030764A3 (fr) 2012-06-07

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017117409A1 (fr) * 2015-12-30 2017-07-06 Prolacta Bioscience, Inc. Produits de lait humain utiles en soins pré- et post-opératoires
US10820604B2 (en) 2011-08-03 2020-11-03 Prolacta Bioscience, Inc. Microfiltration of human milk to reduce bacterial contamination
WO2020243790A1 (fr) * 2019-06-05 2020-12-10 Australian Breast Milk Bank Pty Ltd Procédé et récipient pour produire une composition en poudre comprenant du lait maternel humain
US11419342B2 (en) 2013-03-13 2022-08-23 Prolacta Bioscience, Inc. High fat human milk products
EP3996514A4 (fr) * 2019-07-09 2023-07-12 Aquero Canada Ltd. Compositions, procédés de production, stérilisation et utilisations bénéfiques pour la santé de lait lyophilisé
US12070044B2 (en) 2019-02-22 2024-08-27 Aquero Canada Ltd. Fortified milk compositions and their processes of preparation
US12152058B2 (en) 2020-01-14 2024-11-26 Babylat Ag Apparatus and method for obtaining protein-enriched fractions from breast milk

Citations (4)

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US7070300B2 (en) * 2004-06-04 2006-07-04 Philips Lumileds Lighting Company, Llc Remote wavelength conversion in an illumination device
US20090250714A1 (en) * 2008-04-03 2009-10-08 Samsung Electro-Mechanics Co., Ltd. White light emitting diode and lighting apparatus using the same
US20090295265A1 (en) * 2004-12-24 2009-12-03 Kyocera Corporation Light Emitting Device and Illumination Apparatus
US7800287B2 (en) * 2006-08-29 2010-09-21 Osram Sylvania Inc. Enhanced emission from pc-LEDs using IF filters

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7070300B2 (en) * 2004-06-04 2006-07-04 Philips Lumileds Lighting Company, Llc Remote wavelength conversion in an illumination device
US20090295265A1 (en) * 2004-12-24 2009-12-03 Kyocera Corporation Light Emitting Device and Illumination Apparatus
US7800287B2 (en) * 2006-08-29 2010-09-21 Osram Sylvania Inc. Enhanced emission from pc-LEDs using IF filters
US20090250714A1 (en) * 2008-04-03 2009-10-08 Samsung Electro-Mechanics Co., Ltd. White light emitting diode and lighting apparatus using the same

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10820604B2 (en) 2011-08-03 2020-11-03 Prolacta Bioscience, Inc. Microfiltration of human milk to reduce bacterial contamination
US20200359642A1 (en) * 2011-08-03 2020-11-19 Prolacta Bioscience, Inc. Microfiltration of human milk to reduce bacterial contamination
US11805785B2 (en) 2011-08-03 2023-11-07 Prolacta Bioscience, Inc. Microfiltration of human milk to reduce bacterial contamination
US11419342B2 (en) 2013-03-13 2022-08-23 Prolacta Bioscience, Inc. High fat human milk products
US12063943B2 (en) 2013-03-13 2024-08-20 Prolacta Bioscience, Inc. High fat human milk products
US12004528B2 (en) 2015-12-30 2024-06-11 Prolacta Bioscience, Inc. Human milk products useful in pre- and post-operative care
US11344041B2 (en) 2015-12-30 2022-05-31 Prolacta Bioscience, Inc. Human milk products useful in pre- and post-operative care
JP2021176325A (ja) * 2015-12-30 2021-11-11 プロラクタ バイオサイエンス，インコーポレイテッド 術前及び術後のケアに有用なヒト乳製品
IL260327B1 (en) * 2015-12-30 2023-06-01 Prolacta Bioscience Inc Human milk products used before and after active treatment
IL260327B2 (en) * 2015-12-30 2023-10-01 Prolacta Bioscience Inc Human milk products useful in pre- and post-operative care
WO2017117409A1 (fr) * 2015-12-30 2017-07-06 Prolacta Bioscience, Inc. Produits de lait humain utiles en soins pré- et post-opératoires
JP2019505203A (ja) * 2015-12-30 2019-02-28 プロラクタ バイオサイエンス，インコーポレイテッド 術前及び術後のケアに有用なヒト乳製品
IL303044B1 (en) * 2015-12-30 2025-01-01 Prolacta Bioscience Inc Human milk products used before and after active treatment
US12070044B2 (en) 2019-02-22 2024-08-27 Aquero Canada Ltd. Fortified milk compositions and their processes of preparation
WO2020243790A1 (fr) * 2019-06-05 2020-12-10 Australian Breast Milk Bank Pty Ltd Procédé et récipient pour produire une composition en poudre comprenant du lait maternel humain
EP3996514A4 (fr) * 2019-07-09 2023-07-12 Aquero Canada Ltd. Compositions, procédés de production, stérilisation et utilisations bénéfiques pour la santé de lait lyophilisé
US12152058B2 (en) 2020-01-14 2024-11-26 Babylat Ag Apparatus and method for obtaining protein-enriched fractions from breast milk

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