STERILIZED LIQUID PROTEIN SUPPLEMENT INCLUDING A SOLUBILITY
ENHANCING NUTRITIONAL PROTEIN
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to and any other benefit of U.S.
Provisional Patent Application Serial No. 61/651,078, filed May 24, 2012, and
entitled "STERILIZED LIQUID PROTEIN SUPPLEMENT INCLUDING A
SOLUBILITY ENHANCING NUTRITIONAL PROTEIN," the entire disclosure of
which is incorporated by reference herein.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates to a sterilized liquid protein
supplement. More particularly, the present disclosure relates to a long term stable,
high protein-containing sterilized liquid supplement including at least one protein
source having specific solubility enhancing properties. In some embodiments, the
protein source is a hydrolyzed whey protein source, and the sterilized liquid protein
supplement includes at least 300 milligrams of protein per 1mL of supplement. The
liquid protein supplement is suitable for supplementing human milk or infant formula
and for feeding to an infant or preterm infant, or for use as an adult nutritional.
BACKGROUND OF THE DISCLOSURE
[0003] Human milk is generally recognized as an ideal feeding for most
infants due to its overall nutritional composition. It is well known and generally
accepted that human milk provides infants with unique immunologic and
developmental benefits as compared generally to commercially available infant
formulas.
[0004] For some infants, however, especially preterm infants, human milk
does not always meet the complete nutritional needs of the infant. Further many
mothers are not able to provide sufficient human milk to their infants. Under these
circumstances, infant formulas are commonly used to provide supplemental or sole
source nutrition early in life.
[0005] Although infants still generally benefit from human milk and/or
commercially available infant formulas, it is often desirable to supplement their
feedings with additional nutrients. Protein supplements have been previously used to
supplement the protein intake of infants, particularly, preterm and low birth weight
infants.
[0006] Most of the protein supplements described in the literature and
commercially available have been formulated as reconstitutable powders rather than
liquids in order to minimize the volume displacement of human milk or liquid infant
formulas by the supplement. It has recently been found, however, that liquid protein
supplements, and specifically highly concentrated liquid protein supplements, are
desirable as an alternative to powders as these liquids may have the significant benefit
of being easily commercially sterilized as they can be subjected to sufficient heat
treatment during manufacturing, including ultra high temperature (UHT) treatment,
for sterilization.
[0007] To date, however, liquid protein supplements have been typically
highly acidic, which can be problematic as the acidity of the supplement can change
its natural properties; that is, in some cases, proteins may denature, and this
denaturation may potentially impact the nutritional qualities of the supplement.
Moreover, many protein supplements are based wholly or in large part on collagen as
the protein source. Collagen, however, in some embodiments may be a less desired
protein source, and as such, supplements including collagen as a sole protein source
are not always desirable for neonate consumption.
[0008] Additionally, many liquid protein supplements available to date have
had issues with precipitation and sedimentation of the proteinaceous material that
occurs over time as the product ages, especially when the protein concentration is
greater than about 150 milligrams of protein per mL. In some cases, the undesirable
precipitation and sedimentation can begin shortly after manufacture and continue
throughout the life of the product. The precipitate and sediment generally have little
impact on the nutritional quality of the liquid protein supplement as only a small
fraction of the protein actually precipitates out of solution; however, the physical
appearance of the precipitate and sediment, which may in some cases be dark colored,
may raise concerns about the product viability and/or safety, and may significantly
impact commercial desirability. Although this problem may be controlled and
minimized to some extent by reducing the protein concentration of the liquid protein
supplement, such reduction is commercially undesirable and limits the overall
application of the liquid protein supplement as volume displacement concerns may
arise.
[0009] As such, there is a need for sterilized liquid protein supplements that
are sufficiently long term stable and that include high amounts of protein to reduce the
amount of water added to human milk or infant formula when the product is utilized.
Additionally, it would be very beneficial if the sterilized liquid protein supplements
could be made to have a more neutral pH such as to prevent protein denaturation
when added to human milk and have the milk remain a more neutral pH.
SUMMARY OF THE DISCLOSURE
[0010] The present disclosure is directed to long term stable sterilized liquid
protein supplements for use with preterm infants, infants, pediatrics and adults. The
long term stable sterilized liquid protein supplement includes at least one highly
soluble, high quality hydrolyzed protein source. Desirably, the protein source is a
hydrolyzed whey protein source that is a high quality source of essential amino acids
and highly absorbable. The protein source has a degree of hydrolysis of from about
25% to about 45%, a molecular weight median of less than 800 Daltons, and a
dipeptide and tripeptide concentration of no more than 40% by weight of the total
protein. In many embodiments the long term stable sterilized liquid protein
supplement includes at least 300 milligrams of protein per 1mL of liquid and is
highly stable such that precipitation and sedimentation are minimized or eliminated
over the shelf life of the product. In some desirable embodiments, the hydrolyzed
whey protein source may be used in combination with a hydrolyzed casein source.
The liquid protein supplement may also have a pH range of from about 3.0 to about
8.0. Many of the long term stable sterilized liquid protein supplements described
herein may be suitably prepared to be fat-free and/or carbohydrate-free, as well as
emulsifier-free and/or stabilizer-free. Methods of preparing and using the long term
stable sterilized liquid protein supplements described herein are also provided.
[001 1] The present disclosure is directed to a sterilized liquid protein
supplement comprising at least 300 mg of protein per 1 mL. The protein has a degree
of hydrolysis of from about 25% to about 45%, a molecular weight median of less
than 800 Daltons, and a dipeptide and tripeptide concentration of no more than 40%
by weight total protein, wherein the sterilized liquid protein supplement has a pH of
from about 3.0 to about 8.0.
[0012] The present disclosure is further specifically directed to a sterilized
liquid protein supplement comprising at least 300 mg of whey protein per 1 mL. The
whey protein has a degree of hydrolysis of from about 25% to about 45%, a molecular
weight median of less than 800 Daltons, and a dipeptide and tripeptide concentration
of no more than 40% by weight total protein. The sterilized liquid protein supplement
has a pH of from about 5.0 to about 7.0.
[0013] The present disclosure is further specifically directed to a sterilized
liquid protein supplement comprising at least 330 mg of protein per 1mL and having
a pH of from about 3.0 to about 8.0. The protein comprises a whey protein
hydrolysate wherein the whey protein hydrolysate, when prepared as a 37.5% by
weight solution in water and filtered through a 0.45 mih filter, produces a filtrate
having at least 98% by weight protein recovery.
[0014] The present disclosure is further specifically directed to a
supplemented human milk comprising human milk and a sterilized liquid protein
supplement comprising at least 300 mg of protein per 1 mL. The protein has a degree
of hydrolysis of from about 25% to about 45%, a molecular weight median of less
than 800 Daltons, and a dipeptide and tripeptide concentration of no more than 40%
by weight total protein. The sterilized liquid protein supplement has a pH of from
about 3.0 to about 8.0.
[0015] The present disclosure is further specifically directed to a sterilized
liquid protein supplement comprising at least 300 mg of protein per 1mL and
comprising a first protein and a second protein. The first protein is a whey protein
hydrolysate having a degree of hydrolysis of from about 25% to about 45%, a
molecular weight median of less than 800 Daltons, and a dipeptide and tripeptide
concentration of no more than 40% by weight total protein. The second protein is a
casein hydrolysate. The sterilized liquid protein supplement has a pH of from about
3.0 to about 8.0.
[0016] The present disclosure is further specifically directed to a sterilized
liquid protein supplement comprising at least 300 mg of protein per 1 mL. The
protein has a degree of hydrolysis of from about 25% to about 45%, a molecular
weight median of less than 800 Daltons, and a dipeptide and tripeptide concentration
of no more than 40% by weight total protein. The sterilized liquid protein supplement
has a pH of from about 3.0 to about 8.0.
[00 1 ] It has been unexpectedly found that stable sterilized liquid protein
supplements can advantageously be prepared as solutions, including clear solutions,
having a high concentration of protein, and in particular, having a high concentration
of hydrolyzed protein, when formulated using a protein source with a specific
combination of attributes. Specifically, when a protein utilized has a certain degree of
hydrolysis, molecular weight median, and dipeptide and tripeptide concentration, a
liquid protein supplement can be prepared including at least 300 milligrams of protein
per 1mL of liquid protein supplement and, in some embodiments, up to 333
milligrams of protein per 1mL liquid. By utilizing the highly soluble protein as
described herein, the liquid protein supplements can be sufficiently concentrated so as
to not unacceptably dilute the other components of human milk or other infant
formulas and be sufficiently shelf stable.
[00 18] Additionally, by using the highly soluble protein as defined herein in
the liquid protein supplement, the solubility of critical amino acids, including the
solubility of L-tyrosine, can be significantly improved further improving the overall
nutritional value of the product. Also, because the protein as defined herein is highly
soluble and stable, the shelf life and overall stability of the liquid protein supplement
is significantly improved such that the product is stable and highly resistant to
precipitation/sedimentation/crystallization for long periods of time.
[0019] Additionally, the more neutral pH levels of the sterilized liquid
protein supplements described herein may prevent denaturation of the proteins in
human milk or other infant formulas to be supplemented with the liquid protein
supplement, thereby allowing for sufficient protein supplementation to infants,
particularly preterm and low birth weight infants. Further, the pH levels allow the
sterilized liquid protein supplements to be added to human milk without the need for
adjusting the pH of the final liquid product.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0020] The present disclosure is generally directed to sterilized liquid
protein supplements, methods of preparing the sterilized liquid protein supplements,
and methods of using the sterilized liquid protein supplements. The sterilized liquid
protein supplements of the present disclosure generally comprise a protein source, and
in particular a hydrolyzed protein source, that is highly soluble in water such that a
long term stable liquid protein supplement including, in many embodiments, at least
300 milligrams of protein per mL of supplement can be produced. The protein source
utilized has a specifically defined degree of hydrolysis, molecular weight median, and
dipeptide and tripeptide concentration that has been discovered to provide a highly
soluble protein. In some embodiments, the sterilized liquid protein supplements are
substantially clear liquid protein supplements being substantially free of carbohydrate
and fat and may also be substantially free of emulsifiers and/or stabilizers. In addition
to providing for a more stable liquid high protein supplement with a reduced amount
of precipitation and sedimentation the protein source provides a high quality source of
amino acids and is highly absorbable. In many embodiments the hydrolyzed protein
source is a hydrolyzed whey protein source.
[0021] The sterilized long term stable liquid protein supplements described
herein provide for an improved, easy to use high protein nutritional supplement that is
sterile, long term stable, and easily mixable with human breast milk and/or infant
formula to improve the nutritional quality of the resulting liquid with minimum
volume displacement. These protein-dense supplements provide the commercial
advantage of a sterile liquid as compared to conventional powder forms and have,
through the use of a specifically defined protein source, overcome traditional hurdles
related to the formation of precipitation, sedimentation, and off-color over time
typically associated with high protein liquids. In some embodiments, the sterile liquid
protein supplements may further include additional components including vitamins,
minerals, and the like.
[0022] In addition, the specified protein sources described herein, and
specifically the specified whey protein hydrolysates, may be a biologically active
addition to adult nutritional products and adult nutritional supplements, including
diabetic adult nutritional products and supplements and muscle health adult nutritional
products and supplements.
[0023] These and other optional elements or limitations of the sterilized
liquid protein supplements and methods of the present disclosure are described in
detail hereinafter.
[0024] The terms "substantially clear liquid" or "substantially clear sterilized
liquid protein supplement" as used herein, unless otherwise specified, are used
interchangeably and refer to non-emulsified or similar other liquids having a visibly
clear or translucent appearance, which liquid may and typically will have a thin or
watery texture with a consistency similar to that of a clear juice and most typically
having a viscosity of less than 25 centipoises as determined by a Brookfield
viscometer at 22°C using a # 1 spindle at 60 rpm.
[0025] The terms "sterile", "sterilized" and "sterilization" as used herein,
unless otherwise specified, refer to the reduction in transmissible agents such as fungi,
bacteria, viruses, spore forms, and so forth, in food or on food grade surfaces to the
extent necessary to render such foods suitable for human consumption. Sterilization
processes may include various techniques involving the application of heat, peroxide
or other chemicals, irradiation, high pressure, filtration, or combinations or variations
thereof.
[0026] The term "retort packaging" and "retort sterilizing" are used
interchangeably herein, and unless otherwise specified, refer to the common practice
of filling a container, most typically a metal can or other similar package, with a
liquid protein supplement and then subjecting the liquid-filled package to the
necessary heat sterilization step, to form a sterilized, retort packaged, liquid protein
supplement.
[0027] The term "total solids", unless otherwise specified herein refers to all
material components of the compositions of the present disclosure, less water.
[0028] The term "hypoallergenic" as used herein means that the sterilized
liquid protein supplement has a decreased tendency to provoke an allergic reaction in
a user, such as a preterm or term infant, as compared to non-hypoallergenic liquid
supplements. More particularly, the sterilized liquid protein supplement is
hypoallergenic when there is 95% confidence that 90% of allergic infants would not
react to the supplement in a double-blind, placebo-controlled (DBPC) study. An
example of a suitable DBPC study is described in Kleinman, et al. "Use of infant
formulas in infants with cow milk allergy: a review and recommendations," Pediatr
Allergy Immunol 1991, 4 : 146-155.
[0029] The term "stable" as used herein means that the sterilized liquid
protein supplement is resistant to separation and precipitation for a time period after
manufacture of at least three months, and desirably at least six months and desirably
at least one year.
[0030] All percentages, parts and ratios as used herein, are by weight of the
total composition, unless otherwise specified. All such weights as they pertain to
listed ingredients are based on the active level and, therefore, do not include solvents
or by-products that may be included in commercially available materials, unless
otherwise specified.
[003 1] Numerical ranges as used herein are intended to include every
number and subset of numbers within that range, whether specifically disclosed or
not. Further, these numerical ranges should be construed as providing support for a
claim directed to any number or subset of numbers in that range. For example, a
disclosure of from 1 to 10 should be construed as supporting a range of from 2 to 8,
from 3 to 7, from 5 to 6, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth.
[0032] All references to singular characteristics or limitations of the present
disclosure shall include the corresponding plural characteristic or limitation, and vice
versa, unless otherwise specified or clearly implied to the contrary by the context in
which the reference is made.
[0033] All combinations of method or process steps as used herein can be
performed in any order, unless otherwise specified or clearly implied to the contrary
by the context in which the referenced combination is made.
[0034] The various embodiments of the sterilized liquid protein supplements
of the present disclosure may also be substantially free of any optional or selected
ingredient or feature described herein, provided that the remaining sterilized liquid
protein supplement still contains all of the required ingredients or features as
described herein. In this context, and unless otherwise specified, the term
"substantially free" means that the selected sterilized liquid protein supplement
contains less than a functional amount of the optional ingredient, typically less than
5% by weight, including less than 4% by weight, including less than 3% by weight,
including less than 2% by weight, including less than 1% by weight, including less
than 0.5% by weight, including less than 0.1% by weight, and also including zero
percent by weight of such optional or selected ingredient.
[0035] The sterilized liquid protein supplements and corresponding
manufacturing methods of the present disclosure can comprise, consist of, or consist
essentially of the essential elements and limitations of the disclosure as described
herein, as well as any additional or optional ingredients, components, or limitations
described herein or otherwise useful in the sterilized liquid protein supplement.
Product Form
[0036] The sterilized liquid protein supplements of the present disclosure
including the highly soluble protein source may be used as a supplemental source of
nutrition and may optionally be in the form of clear or substantially clear liquids. The
sterilized liquid protein supplements are suitable for use as human milk fortifiers,
infant liquid nutritionals, and/or preterm liquid nutritionals, as well as adult
nutritionals and adult supplements. When used as adult nutritionals and/or adult
supplements, the sterilized liquid protein supplements will generally include at least
one, or two, or three or more additional protein sources, and may also include at least
one of fat and carbohydrate.
[0037] The sterilized liquid protein supplements of the present disclosure are
generally thin liquids comprising a highly soluble protein source as described below.
The sterilized liquid protein supplements may be, in some embodiments, substantially
fat free and substantially carbohydrate free; that is, the supplements are devoid of
added fat and carbohydrate except for that fat and carbohydrate inherent to the raw
materials or added fat or carbohydrate at low concentrations to aid in the manufacture
of the sterilized liquid protein supplement. In this context, the term "fat free" and/or
"carbohydrate free" means that the sterilized liquid protein supplement typically
contains less than 1.0%, more typically less than 0.5%, and more typically less than
0.1%, including zero percent, fat and/or carbohydrate by weight of the sterilized
liquid protein supplement. Additionally as noted above, in some embodiments the
sterilized liquid protein supplements may be emulsifier-free and/or stabilizer-free.
[0038] The sterilized liquid protein supplements of the present disclosure
have a solids content of at least 10%, including from 10% to about 50%, further
including from 10% to about 40%, and further including from about 15% to about
35% . The sterilized liquid protein supplements are liquids that are capable of being
poured directly from a package containing them into human milk, other infant feeding
formula, or a combination thereof, to produce a liquid suitable for feeding to infants,
including preterm infants.
[0039] To provide improved stability and shelf-life, it is generally desirable
that the sterilized liquid protein supplements of the present disclosure include
insoluble solids at a concentration of less than 5 grams per 100 grams of the sterilized
liquid protein supplement, including an insoluble solids content of from about 0.5
grams to less than 5 grams per 100 grams of the sterilized liquid protein supplement,
or even an insoluble solids concentration of 0 grams per 100 grams of the sterilized
liquid protein supplement. Having a low insoluble solids content may result in less
precipitation of the solids out of solution (i.e., plugging/fouling) and an improved
appearance of the sterilized liquid protein supplements which, as noted above, may be
clear or substantially clear in some embodiments.
[0040] The sterilized liquid protein supplements may be and typically are
shelf-stable. The sterilized liquid protein supplements typically contain up to 95% by
weight of water, including from about 50%> to 95%, also including from about 60%> to
about 90%, and also including from about 70%> to about 85%, of water by weight of
the sterilized liquid protein supplement.
[0041] The sterilized liquid protein supplements may have a variety of
product densities, but most typically have a density greater than 1.040 g/mL,
including from about 1.06 g/mL to about 1.12 g/mL, and also including from about
1.085 g/mL to about 1.10 g/mL.
[0042] The sterilized liquid protein supplements are generally formulated to
have a caloric density of at least 0.4 kcal/mL, including at least 0.8 kcal/mL, including
from 0.4 kcal/mL to about 1.2 kcal/mL, including from about 0.6 kcal/mL to about
1.1 kcal/mL, and including from about 0.8 kcal/mL to about 0.94 kcal/mL.
[0043] The sterilized liquid protein supplements are further formulated to
have a pH sufficient to reduce or inhibit microbial growth, particularly growth of C.
sakazakii, Clostridium botulinum, Salmonella spp., Staphylococcus aureus, and
Escherichia coli, as well as many food spoilage microorganisms known in the art.
Preferably, the sterilized liquid protein supplements are prepared to have a pH ranging
from about 3.0 to about 8.0, but are most advantageously in a pH range of from about
5.0 to about 7.0, and including from about 5.5 to about 6.5.
Macronutrients
[0044] The sterilized liquid protein supplements of the present disclosure
include a highly soluble protein component as described herein. The sterilized liquid
protein supplements may include macronutrients of sufficient types and amounts that,
when used in combination with human milk or other infant feeding formula, help
meet the nutritional needs of the user, especially the premature infant.
Protein Source
[0045] The sterilized liquid protein supplements of the present disclosure
include a highly soluble protein source that is a high quality source of essential amino
acids and highly absorbable. In some embodiments, the highly soluble protein source
may be a protein hydrolysate, including a whey protein hydrolysate. These highly
soluble protein sources enable the preparation of stabilized liquid protein supplements
that can increase the delivery of nutrients and amino acids, and L-tyrosine
specifically. In some embodiments of the present disclosure, the aqueous solubility of
L-tyrosine may be 2.6 times greater with the highly soluble protein as described
herein as compared to L-tyrosine in water only.
[0046] The highly soluble protein source has a narrowly specified degree of
hydrolysis that, in combination with the other protein attributes described herein,
impacts the overall solubility of the protein. The degree of hydrolysis is the extent to
which peptide bonds are broken by a hydrolysis method. The degree of protein
hydrolysis for purposes of characterizing a hydrolyzed protein component of some
embodiments described herein is easily determined by one of ordinary skill in the
formulation arts by quantifying the amino nitrogen to total nitrogen ratio (AN/TN) of
the protein component of the selected formulation. The amino nitrogen component is
quantified by a USP titration method or by a published colorimetric method (e.g.,
TNBS or OPA colorimetry) for determining amino nitrogen content, while the total
nitrogen component is determined by the Tecator Kjeldahl method, all of which are
well known methods to one of ordinary skill in the analytical chemistry art.
[0047] The degree of hydrolysis of the highly soluble protein source is from
about 25% to about 45%, including from about 25% to about 40%, including from
about 25% to about 38%, including from about 27% to about 38%, including from
about 2 9% to about 37%, including from about 30% to about 35%, including from
about 30% to about 34%, and including about 32%. In some embodiments, the
degree of hydrolysis may be 20%, or even 25%, or even 27%, or even 29%, or even
30%, or even 31% or even 32%.
[0048] In addition to the specified degree of hydrolysis, the highly soluble
protein source has a specified molecular weight median to enhance the solubility of
the protein source in the sterilized liquid protein supplement. The molecular weight
median of the highly soluble protein is less than 800 Daltons, including less than 750
Daltons, including less than 725 Daltons, including less than 700 Daltons, including
less than 675 Daltons, including less than 650 Daltons, including less than 625
Daltons, including less than 600 Daltons, including less than 575 Daltons, including
less than 570 Daltons, including less than 565 Daltons, including less than 560
Daltons, including about 550 Daltons. In some embodiments, the molecular weight
median of the highly soluble protein is from about 550 Daltons to about 800 Daltons,
including from about 550 Daltons to about 700 Daltons, including from about 550
Daltons to about 650 Daltons, and including from about 550 Daltons to about 600
Daltons.
[0049] In addition to the specified degree of hydrolysis and specified
molecular weight median, the highly soluble protein source has a specified dipeptide
and tripeptide concentration to enhance the solubility of the protein source in the
sterilized liquid protein supplement. The dipeptide and tripeptide concentration of the
highly soluble protein source is no more than 40% by weight total protein, including
no more than 35% by weight total protein, including no more than 32% by weight
total protein, including no more than 30% by weight total protein, including no more
than 28% by weight total protein, including no more than 27% by weight total protein,
including about 26% by weight total protein. In some embodiments, the degree of
hydrolysis is from about 26% to about 40%, including from about 26% to about 35%,
including from about 26% to about 30%, and including from about 26% to about
28%.
[0050] The sterilized liquid protein supplements of the present disclosure
include much higher concentrations of protein as compared to conventional liquid
protein supplements as noted herein as the highly soluble proteins allow for increased
protein concentrations that remain stable over long periods of time. The sterilized
liquid protein supplement in accordance with the present disclosure includes at least
300 mg protein per mL, including at least 310 mg protein per mL, including at least
315 mg protein per mL, including at least 320 mg protein per mL, including at least
325 mg protein per mL, including at least 330 mg protein per mL, and including about
333 mg protein per mL. In some embodiments, the sterilized liquid protein
supplements include at least 200 mg protein per mL, including at least 220 mg protein
per mL, including at least 240 mg protein per mL, including at least 250 mg protein
per mL, including at least 275 mg protein per mL, and including at least 295 mg
protein per mL. In other embodiments, the sterilized liquid protein supplements
include from about 200 to about 330 mg protein per mL, including from about 225 to
about 330 mg protein per mL, including from about 250 to about 330 mg protein per
mL, and including from about 275 to about 330 mg protein per mL. This protein may
come from one, two, three or more sources.
[005 1] In one embodiment of the present disclosure, highly soluble proteins
suitable for use in the sterilized liquid protein supplements of the present disclosure
may be identified by utilizing a protein recovery test using a suitably sized filter, such
as a suitably sized PTFE filter. In this embodiment, a protein containing aqueous
solution is first prepared by introducing 37.5 g of a protein source into 62.5 g of room
temperature water (to give a total of 100.0 g, so that the concentration of the protein
source is 37.5% by weight) and stirring the protein in water solution for thirty minutes
at room temperature. An aliquot of this stirred protein containing aqueous solution is
then syringe-filtered through a 0.45 micron membrane and the filtrate is tested for
protein concentration (e.g., by high performance liquid chromatography or by some
other suitable quantitative analytical technique). A protein suitable for use in the
liquid protein supplements of the present disclosure will have at least 98% by weight
of the total protein in the filtrate and have a visible light transmittance, as measured at
860 nm vs. purified water, of at least 99%. Proteins or protein sources that meet these
requirements are highly soluble proteins as discussed herein and may suitably be used
in the sterilized liquid protein supplements of the present disclosure.
[0052] One particularly suitable protein hydrolysate source for use in the
liquid protein supplements of the present disclosure is Tatua W4015 whey protein
hydrolysate (Morrinsville, New Zealand), which is approximately 80% protein by
weight and has a degree of hydrolysis of about 32%, a molecular weight median of
about 550 Daltons, and a dipeptide and tripeptide concentration of about 26% by
weight total protein. This particularly suitable protein source can be the sole protein
source in the sterilized liquid protein supplement, or may be used in combination with
one or more other protein sources.
[0053] As noted above, it has been unexpectedly found that the free Ltyrosine
solubility in water is substantially increased in accordance with the present
disclosure; that is, it has been found that a 2.6 fold enhancement of the solubility of
free L-tyrosine occurs in a 37.5% (w/w) aqueous solution of Tatua W4015 whey
protein hydrolysate as compared to the solubility of free L-tyrosine in water (Tatua
W4015 whey protein concentrate has a free L-tyrosine concentration of 1300 mg/L,
which is 2.6 times than the aqueous solubility of free L-tyrosine of 500 mg/L.)
[0054] In addition to the highly soluble protein source as described herein,
the sterilized liquid protein supplement may, in some embodiments, include an
additional protein source. The additional protein source may include any number of
hydrolyzed, including extensively hydrolyzed, and/or intact protein or elemental
ingredients. Suitable examples of hydrolyzed or non-hydrolyzed (intact) proteins can
be derived from any known or otherwise suitable source such as milk (e.g., casein,
whey, lactose-free milk protein isolates), animal (e.g., meat, fish), cereal (e.g., rice,
corn), vegetable (e.g., soy, pea, bean), or combinations thereof. One particularly
suitable additional protein source is a casein hydrolysate, such as Dellac CE90HM
casein hydrolysate (Friesland Campina, Deltown Specialties Division, Delhi NY.)
Vitamins and Minerals
[0055] The sterilized liquid protein supplements of the present disclosure
may further comprise any of a variety of vitamins, non-limiting examples of which
include vitamin A, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridoxine,
vitamin B12 , niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol,
salts and derivatives thereof, and combinations thereof. In some desirable
embodiments, the sterilized liquid protein supplements further include water soluble
vitamins such as vitamin B12 , niacin, folic acid, biotin, pantothenic acid, and vitamin
C.
[0056] The sterilized liquid protein supplements may also further comprise
any of a variety of minerals known or otherwise suitable for use in infant or other
nutritional formulas, non-limiting examples of which include phosphorus,
magnesium, calcium, zinc, manganese, copper, iodine, sodium, potassium, chloride,
selenium, and combinations thereof.
Other Optional Ingredients
[0057] The sterilized liquid protein supplements of the present disclosure
may further optionally comprise other ingredients that may modify the physical,
chemical, aesthetic or processing characteristics of the compositions or serve as
pharmaceutical or additional nutritional components when used in the targeted
population. Many such optional ingredients are known for use in food and nutritional
products, including infant formulas, and may also be used in the sterilized liquid
protein supplements of the present disclosure, provided that such optional materials
are compatible with the materials described herein, are safe and effective for their
intended use, and do not otherwise unduly impair product performance.
[0058] Non-limiting examples of such optional ingredients include
preservatives, anti-oxidants, various pharmaceuticals, buffers, carotenoids, colorants,
flavors, nucleotides and nucleosides, thickening agents, prebiotics, probiotics, sialic
acid-containing materials, and other excipients or processing aids.
Method o f Manufacturing
[0059] The sterilized liquid protein supplements of the present disclosure
may generally be prepared using the following method: suspending a highly soluble
protein source in an aqueous solution using agitation to form a protein component
suspension or solution mixture having a protein component concentration greater than
30% by weight; diluting the suspension or solution mixture with water to form a
diluted mixture having a protein component concentration of from about 25% to about
30% by weight; heating the diluted mixture with agitation; cooling the heated
mixture; homogenizing the cooled mixture and holding the homogenized mixture at a
cooled temperature for a period; further cooling the homogenized mixture; and
diluting the cooled homogenized mixture with water to form a cooled homogenized
mixture comprising more than 10 grams per 100 mL protein component. The
homogenized mixture may then be filled into a suitable bottle or container and
sterilized.
[0060] In one or more other desirable embodiments, the sterilized liquid
protein supplement is prepared by first suspending a highly soluble protein source in
an aqueous solution using agitation to form a protein suspension mixture having a
protein concentration of greater than 30% by weight, including from about 35% to
about 65%o by weight, including from about 35% to about 57% by weight, and
including from about 45% to about 50% by weight. All or at least a portion of the
protein source may be a highly soluble whey protein hydrolysate. In one
embodiment, the protein source is solely a whey protein hydrolysate and is suspended
in water at a temperature of from about 120°F to about 180°F to make the protein
suspension mixture. The whey protein hydrolysate is added with sufficient agitation
to disperse the protein and keep insoluble amino acids/peptides in suspension. While
maintaining both the temperature and agitation, additional water is then added to
further dilute the suspension mixture to a protein concentration of from about 25% to
about 40% by weight, including about 37.5% by weight.
[0061] The diluted protein suspension mixture is then heated with agitation
to a temperature of from about 150°F to about 210°F, including from about 165°F to
about 175°F and treated at from 0 to about 500 psig, including from 0 to about 300
psig.
[0062] The treated mixture is then again heated using a two-step heating
process. In a first heating step, the treated mixture is heated using, for example, an
ultra high temperature (UHT) treatment to a temperature of from about 240°F to about
260°F, including from about 248°F to about 252°F. A second heating step is then
conducted using steam injection UHT to heat the mixture to a temperature of from
about 275°F to about 305°F, including from about 300°F to about 302°F. The
mixture is held at this second heat temperature for a period of about from about 1
second to about 5 seconds.
[0063] The heated mixture can then be cooled to a temperature of from
about 150°F to about 200°F. In some embodiments, the cooling step is a twostep/
stepwise cooling process to prevent precipitation of solids in the mixture. For
example, the heated mixture can first be cooled to a temperature of from about 225°F
to about 265°F, including from about 248°F to about 252°F, and then the mixture can
further be cooled to a temperature of from about 150°F to about 200°F, including
from about 160°F to about 170°F to remove steam and water. Any known method of
cooling can be used to cool the heated mixture. One suitable method includes flash
cooling.
[0064] The cooled mixture is then homogenized at from 0 to about 500 psig,
including from 0 to about 300 psig and held at a temperature of from about 150°F to
about 200°F for a period of from about 10 seconds to about 20 seconds.
[0065] The homogenized mixture is then cooled to a temperature of less than
100°F, desirably a temperature of from about 30°F to about 45°F, including from
about 34°F to about 45°F. Finally, the cooled homogenized mixture is diluted with
water to form a sterilized liquid protein supplement having a target protein component
content, such as a protein component content of more than 10 grams per 100 mL of
final sterilized liquid protein supplement, including more than 1 grams per 100 mL
of sterilized liquid protein supplement, and including more than 14 grams per 100 mL
of sterilized liquid protein supplement. In some embodiments, the protein component
concentration may be from about 14 grams to about 33 grams per 100 mL of sterilized
liquid protein supplement, including from about 18 grams to about 33 grams per 100
mL of sterilized liquid protein supplement, including from about 20 grams to about 33
grams per 100 mL of sterilized liquid protein supplement, including from about 25
grams to about 33 grams per 100 mL of sterilized liquid protein supplement, including
from about 28 grams to about 33 grams per 100 mL of sterilized liquid protein
supplement, and including from about 30 grams to about 33 grams per 100 mL of
sterilized liquid protein supplement. In one desirable embodiment, the protein
component concentration may be from about 30 grams to about 33 grams of protein
per 100 mL of final sterilized liquid protein supplement.
[0066] Once diluted to its final protein component concentration, the liquid
protein is commercially sterilized for long term shelf stability, commonly by either
retort or aseptic processing/packaging. The retort packaging can be accomplished
using any of a variety of techniques well known to those of ordinary skill in the art, so
long as the heat treatment is sufficient (i.e., about 125°C for about 20-30 minutes) to
achieve long term shelf stability of the sterilized liquid protein supplement.
Alternatively, the aseptic processing/packaging can be accomplished by using any of
a variety of techniques well known to those skilled in the art so long as the heat
treatment (i.e., about 145°C for 5 seconds) and packaging conditions are sufficient to
achieve and maintain commercial sterility.
Method of Use
[0067] The sterilized liquid protein supplement of the present disclosure
may be used in combination with human milk or other suitable infant formula, or a
combination of both, wherein the resulting fortified human milk or fortified infant
formula or combination of both has an osmolality suitable for oral administration to
an infant, including a preterm infant. The osmolality of human milk is generally
about 286 mOsm/kg water; the osmolality of the combination of sterilized liquid
protein supplement and human milk (or infant formula) will most typically be less
than 500 mOsm/kg water, more typically from about 300 mOsm/kg water to about
400 mOsm/kg water. In some embodiments, the osmolality of the combination of
sterilized liquid protein supplement and human milk is from about 285 mOsm/kg
water to about 315 mOsm/kg water, and desirably about 298 mOsm/kg water.
[0068] The sterilized liquid protein supplements of the present disclosure
may be added directly to human milk or infant formula or both in a volume to volume
ratio of from about 1mL sterilized liquid protein supplement to 100 mL of human
milk or formula to about 5 mL sterilized liquid protein supplement to 100 mL of
human milk or formula, and including about 3 mL sterilized liquid protein supplement
to 100 mL of human milk or formula. The ratio is ultimately selected based primarily
upon the ingredients and concentration of the sterilized liquid protein supplement and
in view of the particular nutritional needs of the infant. The sterilized liquid protein
supplements may be added directly to every feeding or to a sufficient number of
feedings (e.g., once or twice daily) to provide optimal nutrition in view of the
particular nutritional needs of the infant.
[0069] Human milk or other infant feeding formula, after fortification with
the sterilized liquid protein supplement, will most typically have a caloric density
ranging from about 11 kcal/fl oz (0.4 kcal/mL) to about 35 kcal/fl oz (1.2 kcal/mL),
including from about 19 kcal/fl oz (0.64 kcal/mL) to about 30.0 kcal/fl oz (1.0
kcal/mL) with the 22-26.7 kcal/fl oz formulations (0.74-0.90 kcal/mL) being more
useful in preterm infants, and the 19-21 kcal/fl oz (0.64-0.71 kcal/mL) formulations
more useful for term infants.
[0070] The methods of the present disclosure therefore include a method of
providing nutrition to infants, especially preterm infants, said method comprising the
addition of the liquid protein supplement to human milk or other infant feeding
formula, followed by the administration of the fortified human milk or feeding
formula to the infant.
EXAMPLES
[0071] The following examples illustrate specific embodiments and/or
features of the sterilized liquid protein supplements of the present disclosure. The
examples are given solely for the purpose of illustration and are not to be construed as
limitations of the present disclosure, as many variations thereof are possible without
departing from the spirit and scope of the disclosure. All exemplified amounts are
weight percentages based upon the total weight of the formulation, unless otherwise
specified.
Example 1
[0072] In this Example, a sterilized liquid protein supplement including a
single protein component of a whey protein hydrolysate is prepared using the methods
of the present disclosure. The whey protein hydrolysate is Tatua W4015 whey protein
hydrolysate.
[0073] Specifically, the whey protein hydrolysate is suspended in water at a
temperature of from about 120°F to about 180°F to make a protein suspension
mixture having a protein component concentration of about 47.5% by weight. The
whey protein hydrolysate is added with sufficient agitation to disperse the protein and
keep insoluble amino acids/peptides in suspension. While maintaining both the
temperature and agitation, additional water is then added to further dilute the protein
suspension mixture to a protein concentration of about 37.5% by weight. The diluted
mixture is then heated to a temperature of from about 165°F to about 175°F and is
treated at from 0 to about 300 psig. The treated mixture is then again heated using a
two-step heating process. In the first heating step, the treated mixture is heated using
an ultra high temperature (UHT) treatment to a temperature of from about 248°F to
about 252°F. A second heating step is then conducted using steam injection UHT to
heat the mixture to a temperature of from about 300°F to about 302°F. The treated
mixture is held at this temperature for a period of about 5 seconds.
[0074] The heated mixture is then flash cooled to a temperature of from
about 248°F to about 252°F to remove steam and water. The mixture is then further
cooled to a temperature of from about 160°F to about 170°F. The cooled mixture is
then homogenized at from 0 to about 300 psig and held at a temperature of from about
165°F to about 185°F for a period of about 16 seconds.
[0075] The homogenized mixture is then cooled to a temperature of from
about 34°F to about 45°F. Finally, the cooled homogenized mixture is diluted with
water to form a liquid protein supplement having a target protein component content
of about 33.3 grams hydrolyzed whey per 100 mL liquid protein supplement.
[0076] The sterilized liquid protein supplement is then filled into a container
and retort sterilized to produce the final product.
Example 2
[0077] In this Example, several exemplary sterilized liquid protein
supplements of the present disclosure are set forth.
[0078] Table 1 shows a sterilized liquid protein supplement produced
according the disclosure set forth herein including 333 mg protein per mL. Table 2
shows a sterilized liquid protein supplement produced according to the disclosure set
forth herein including 250 mg protein per mL. Table 3 shows a sterilized liquid
protein supplement produced according to the disclosure set forth herein including
200 mg protein per mL. Table 4 shows a sterilized liquid protein supplement
produced according to the disclosure set forth herein including 167 mg protein per
mL. Table 5 shows a sterilized liquid protein supplement produced according to the
disclosure set forth herein including 250 mg protein per mL, wherein the protein is a
70%/30% whey/casein mixture, which mimics human milk. Table 6 shows a protein
system suitable for use in an adult nutritional liquid directed at muscle health.
Table 1
Tatua W4015 Whey Protein Hydrolysate 375
Total 1000
Table 2
Ingredient Concentration, Kg per 1000 Kg
Water 718
Tatua W4015 Whey Protein Hydrolysate 282
Total 1000
Table 3
Ingredient Concentration, Kg per 1000 Kg
Water 775
Tatua W4015 Whey Protein Hydrolysate 225
Total 1000
Table 4
Ingredient Concentration, Kg per 1000 Kg
Water 812
Tatua, W4015 Whey Protein Hydrolysate 188
Total 1000
Table 5
Ingredient Concentration, Kg per 1000 Kg
Water 732
Tatua W4015 Whey Protein Hydrolysate 197
Dellac CE90HM Casein Protein 7 1
Hydrolysate
Total 1000
Table 6
Protein Ingredient Grams of Protein Per Liter of Nutritional
Milk Protein Concentrate 22
Sodium Caseinate 22
Soy Protein Isolate 8
Tatua W4015 Whey Protein Hydrolysate 3
WHAT IS CLAIMED IS:
1. A sterilized liquid protein supplement comprising at least 300 mg of
protein per 1 mL, the protein having a degree of hydrolysis of 25% to 45%, a
molecular weight median of less than 800 Daltons, and a dipeptide and tripeptide
concentration of no more than 40% by weight total protein, wherein the sterilized
liquid protein supplement has a pH of from 3 to 8.
2. A sterilized liquid protein supplement according to claim 1 wherein the
protein is a whey protein hydrolysate.
3. A sterilized liquid protein supplement according to claim 1 or claim 2
wherein the sterilized liquid protein supplement comprises at least 320 mg of protein
per 1mL and the protein has a degree of hydrolysis of 25% to 40%, a molecular
weight median of less than 700 Daltons, and a dipeptide and tripeptide concentration
of no more than 35% by weight total protein.
4. A sterilized liquid protein supplement according to any one of claims 1
to 3 wherein the sterilized liquid protein supplement comprises at least 330 mg of
protein per 1mL and the protein has a degree of hydrolysis of 30%> to 35%, a
molecular weight median of less than 600 Daltons, and a dipeptide and tripeptide
concentration of no more than 30% by weight total protein.
5. A sterilized liquid protein supplement according to any one of claims 1
to 4 wherein the sterilized liquid protein supplement comprises at least 330 mg of
protein per 1mL and the protein has a degree of hydrolysis of from about 30% to
about 35%, a molecular weight median of less than 575 Daltons, and a dipeptide and
tripeptide concentration of no more than 28% by weight total protein.
6. A sterilized liquid protein supplement according to any one of claims 1
to 5 wherein the sterilized liquid protein supplement comprises about 333 mg of
protein per 1mL and the protein has a degree of hydrolysis of about 32%, a molecular
weight median of about 550 Daltons, and a dipeptide and tripeptide concentration of
about 26% by weight total protein.
7. A sterilized liquid protein supplement according to any one of claims 1
to 6 wherein the sterilized liquid protein supplement is substantially free of fat and
carbohydrate.
8. A sterilized liquid protein supplement according to any one of claims
1 to 7 wherein the sterilized liquid protein supplement has a pH of 5 to 7.
9. A sterilized liquid protein supplement according to any one of claims 1
to 7, wherein the supplement comprises at least 330 mg of protein per 1mL, has a pH
of 3 to 8, the protein comprises a whey protein hydrolysate, and the whey protein
hydrolysate, when prepared as a 37.5% by weight solution in water and filtered
through a 0.45 mih filter, produces a filtrate having at least 98% by weight protein
recovery.
10. A sterilized liquid protein supplement according to any one of claims 1
and 3-9, wherein the protein comprises a combination of whey protein hydrolysate
and casein hydrolysate.
11. A sterilized liquid protein supplement comprising at least 250 mg of
protein per 1 mL, the protein having a degree of hydrolysis of 25% to 45%, a
molecular weight median of less than 800 Daltons, and a dipeptide and tripeptide
concentration of no more than 40% by weight total protein, wherein the sterilized
liquid protein supplement has a pH of 3 to 8.
12. A sterilized liquid protein supplement according to any one of claims 1
to 11 wherein the supplement is clear or substantially clear.
13. A sterilized liquid protein supplement according to any one of claims 1
to 12 in combination with human milk.
14. A method of providing nutrition to infants comprising the addition of
the sterilized liquid protein supplement according to any one of claims 1 to 12 to
human milk or infant formula to form a fortified human milk or fortified infant
formula followed by administration of the fortified human milk or fortified infant
formula to an infant.
15. A method according to claim 14 wherein the infant is a preterm infant.