U.S. patent application number 09/848597 was filed with the patent office on 2002-04-18 for infant formula compositions and nutrition.
Invention is credited to Gaull, Gerald E..
Application Number | 20020044989 09/848597 |
Document ID | / |
Family ID | 22937158 |
Filed Date | 2002-04-18 |
United States Patent
Application |
20020044989 |
Kind Code |
A1 |
Gaull, Gerald E. |
April 18, 2002 |
Infant formula compositions and nutrition
Abstract
Compositions containing human milk proteins, including the
so-called host resistance factors of human milk, prepared by
chemically synthesizing the human milk proteins or by genetic
engineering techniques for producing recombinant human milk
proteins, are useful for supplementing or enhancing the diet of
infants, particularly very-low-birth-weight infants. The human milk
proteins include the host resistance factors (HRF) found in human
milk, such as lactoferrin (LF), lactoperoxidase (LP), lysozyme
(LZ), immunoglobulin-A (IgA), alpha-lactalbumin, alpha, beta,
kappa-caseins, and others. The compositions may also include
components other than the human milk proteins useful for improved
infant nutrition. In the utilization of the compositions of this
invention, the compositions would be administered to an infant in
at least an amount that the infant would receive if fed
substantially only fresh human milk. Also, the proportions of the
human milk proteins would preferably be present in the compositions
in about the proportions these proteins are found in human
milk.
Inventors: |
Gaull, Gerald E.; (Evanston,
IL) |
Correspondence
Address: |
MCDONNELL BOEHNEN HULBERT & BERGHOFF
300 SOUTH WACKER DRIVE
SUITE 3200
CHICAGO
IL
60606
US
|
Family ID: |
22937158 |
Appl. No.: |
09/848597 |
Filed: |
May 3, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09848597 |
May 3, 2001 |
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09428369 |
Oct 28, 1999 |
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09428369 |
Oct 28, 1999 |
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07759100 |
Sep 6, 1991 |
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07759100 |
Sep 6, 1991 |
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07247981 |
Sep 22, 1988 |
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Current U.S.
Class: |
426/2 ; 426/580;
426/585; 426/801 |
Current CPC
Class: |
Y10S 426/801 20130101;
A23L 33/19 20160801 |
Class at
Publication: |
426/2 ; 426/801;
426/580; 426/585 |
International
Class: |
A23C 011/02 |
Claims
What is claimed is:
1. A composition containing one or more nutritional, functional or
protective human milk proteins or host resistance factors of human
milk, said proteins or host resistance factors having been
manufactured by chemical synthesis or by genetic engineering
techniques for the manufacture of said proteins or host resistance
factors as recombinant human milk proteins or as recombinant host
resistance factors of human milk.
2. A composition in accordance with claim 1 wherein said host
resistance factors include secretory immunoglobulin-A, lactoferrin,
lactoperoxidase, lysozyme, alpha-lactalbumin and alpha, beta and
kappa-casein.
3. A composition in accordance with claim 1 wherein said host
resistance factors are present in said composition in about the
proportions said factors are present in human milk.
4. A composition in accordance with claim 3 wherein said
composition contains lactoferrin.
5. A composition in accordance with claim 4 wherein said
composition contains only lactoferrin as the host resistance
factor.
6. A composition in accordance with claim 3 wherein said
composition contains only lysozyme as the host resistance
factor.
7. A composition in accordance with claim 1 wherein the composition
contains one or more other components useful for human infant
nutrition but not manufactured by genetic engineering techniques
for the production of said other components as recombinant products
and wherein said other compositions are not derived from human
milk.
8. A composition in accordance with claim 3 wherein said
composition contains lactoferrin, lactoperoxidase and lysozyme.
9. A composition in accordance with claim 1 wherein said
composition is a concentrate of said nutritional, functional or
protective human milk proteins or host resistance factors of human
milk suitable, after dilution in a liquid for infant consumption,
such that, when so diluted, said human milk proteins or said host
resistance factors can be administered to or fed directly to an
infant for consumption.
10. A composition in accordance with claim 1 wherein said
composition contains said nutritional, functional or protective
human milk proteins or host resistance factors at a concentration
in the range from about 2 to about 5,000 times the concentration of
said human proteins or host resistance factors found in fresh human
milk.
11. A composition in accordance with claim 1 wherein said
composition contains only lactoperoxidase as the host resistance
factor.
12. A composition in accordance with claim 1 wherein said
composition contains only secretory immunoglobulin-A as the host
resistance factor.
13. A composition in accordance with claim 1 wherein said
composition contains only alpha-lactalbumin as the host resistance
factor.
14. A composition in accordance with claim 1 wherein said
composition contains alpha, beta and kappa-casein as the
nutritional proteins.
15. A composition according to claim 14 wherein said composition
contains only alpha-casein as the nutritional protein.
16. A composition according to claim 14 wherein said composition
contains only beta-casein as the nutritional protein.
17. The composition according to claim 14 wherein said composition
contains only kappa-casein as the nutritional protein.
18. A method of providing an infant with daily nutrition which
approximates the nutrition with respect to selected human milk
proteins or host resistance factors provided an infant fed
substantially only on mother's milk which comprises administering
to the infant an amount of liquid containing a composition in
accordance with claim 1, the content of said liquid with respect to
one or more of the selected nutritional, functional or protective
human milk proteins or host resistance factors being substantially
equivalent to that of a similar amount or volume of fresh human
milk.
19. A method of providing an infant with daily nutrition which
approximates the nutrition with respect to selected human milk
proteins or host resistance factors provided the infant when fed
substantially only on mother's milk which comprises administering
to the infant an amount of liquid containing a composition in
accordance with claim 1, the content of said liquid with respect to
one or more of the selected nutritional, functional or protective
milk proteins, or host-resistance factors, being equivalent to that
the infant would receive when daily fed substantially only on
banked or pooled human milk.
20. A method in accordance with claims 18 or 19 wherein said liquid
administered to said infant contains said human milk proteins or
host resistance factors at a concentration in the range from about
2 to about 1000 times the concentration said human milk proteins or
host resistance factors are found in fresh human milk.
21. A method of improving the nutritional value of a synthetic
infant formula which comprises adding to said formula a composition
in accordance with claim 1.
22. A method in accordance with claim 21 wherein the amount of said
composition added to said synthetic infant formula is sufficient
such that when the infant formula is administered to an infant for
consumption the added nutritional, functional or protective human
milk proteins or host resistance factors in said synthetic infant
formula are at a concentration substantially the same as the
concentration of said human milk proteins and host resistance
factors in human milk.
23. The method of claim 22 wherein the nutritional, functional and
protective value of said synthetic infant formula is improved by
adding to said synthetic infant formula an effective amount of
recombinant human lactoferrin.
24. The method of claim 23 wherein the nutritional and protective
value of said synthetic infant formula is further improved by
adding to said synthetic infant formula an effective amount of
recombinant human lysozyme.
25. The method of claim 24 wherein the nutritional and protective
value of said synthetic infant formula is further improved by
adding to said synthetic infant formula an effective amount of
recombinant human lactoperoxidase.
26. The method of claim 25 wherein the nutritional and protective
value of said synthetic infant formula is further improved by
adding to said synthetic infant formula an effective amount of
recombinant human immunoglobulin-A.
27. The method of claim 26 wherein the nutritional value of said
synthetic infant formula is further improved by adding to said
synthetic infant formula an effective amount of recombinant human
alpha-lactalbumin.
28. The method of claim 27 wherein the nutritional value of said
synthetic infant formula is further improved by adding to said
synthetic infant formula an effective amount of recombinant human
casein.
29. A method in accordance with claim 21 wherein the amount of said
composition added to said synthetic infant formula is sufficient
such that when the infant formula is administered to an infant for
consumption the added nutritional, functional or protective human
milk proteins or host resistance factors in said synthetic infant
formula are at a concentration about substantially the same as the
concentration of said human milk proteins and host resistance
factors in human milk.
30. The method of claim 29 wherein the nutritional, functional and
protective value of said synthetic infant formula is improved by
adding to said synthetic infant formula an effective amount of
recombinant human lactoferrin.
31. The method of claim 29 wherein the nutritional and protective
value of said synthetic infant formula is improved by adding to
said synthetic infant formula an effective amount of recombinant
human lysozyme.
32. The method of claim 29 wherein the nutritional and protective
value of said synthetic infant formula is improved by adding to
said synthetic infant formula an effective amount of recombinant
human lactoperoxidase.
33. The method of claim 29 wherein the nutritional and protective
value of said synthetic infant formula is improved by adding to
said synthetic infant formula an effective amount of recombinant
human immunoglobulin-A.
34. The method of claim 29 wherein the nutritional value of said
synthetic infant formula is improved by adding to said synthetic
infant formula an effective amount of recombinant human
alpha-lactalbumin.
35. The method of claim 29 wherein the nutritional value of said
synthetic infant formula is further improved by adding to said
synthetic infant formula an effective amount of recombinant human
casein.
36. The method of claim 35 wherein said recombinant human casein is
alpha-casein.
37. The method of claim 35 wherein said recombinant human casein is
beta-casein.
38. The method of claim 35 wherein said recombinant human casein is
kappa-casein.
39. A method in accordance with claim 18 wherein the amount of said
composition added is sufficient to bring the concentration of the
human milk proteins or host resistance factors in said synthetic
formula by the addition of said composition to about the
concentration of said human milk proteins or said host resistance
factors as found in human milk when said synthetic infant formula
is administered to an infant for consumption.
Description
RELATED APPLICATIONS
[0001] The present application is a Continuation-in-Part (CIP) of
Application U.S. Ser. No. 07/247,981 filed on Sep. 22, 1988 which
is hereby expressly abandoned.
FIELD OF THE INVENTION
[0002] This invention relates to infant nutrition and in one
embodiment it is particularly applicable to the enhancement or
improvement of synthetic infant formulas. Another embodiment of
this invention is concerned with improving the nutrition of
very-low-birth-weight infants.
BACKGROUND OF THE INVENTION
[0003] It has been considered for a long time by nutritionists that
the best food or nutrition supplied to an infant is its own
mother's milk; i.e. fresh human milk. It is recognized, however,
that many situations arise wherein the infant cannot be fed
mother's milk and as a result synthetic infant milk formulas,
predominantly based on cow's milk, have been prepared and used to
nourish an infant. However, since it is generally believed that
human milk provides superior nutrition for infants, much effort has
been made to improve synthetic infant milk formulas to more closely
simulate mother's milk. For example, U.S. Pat. No. 4,303,692 (1981)
discloses a synthetic infant milk formula which includes taurine at
a level substantially equivalent to that found in human milk. In
the manufacture of synthetic infant formula based on cow's milk,
the taurine content of the cow's milk is low and may be diluted
during the manufacture of the synthetic infant formula with the
result that the produced synthetic infant formula contains a very
low level of taurine. This was corrected, as disclosed in U.S. Pat.
No. 4,303,692, by the addition of taurine to synthetic infant
formula to bring its taurine content up to the level taurine is
present in human milk. However, there are still many other
components of fresh human milk which are not found in synthetic
infant milk formulas, either cow milk-based formulas or soy
protein-based formulas, which can and have usefully been added to
synthetic infant formulas to provide an improved product for infant
nutrition.
[0004] The protein and non-protein composition of the human milk
and cow milk is described and set forth in the article by N. C. R.
Raiha entitled "Nutritional Proteins in Milk and the Protein
Requirement of Normal Infants", which appeared in the publication
Feeding the Normal Infant-Supplement, Pediatrics pp. 136-141
(1985), published by the American Academy of Pediatrics. Among
those proteins in human milk are listed alpha-lactalbumin,
lactoferrin, serum albumin, lysozyme, the immunoglobulins, mainly
IgA and other proteins as well.
[0005] In the article by B. A. Friend et al. entitled "Newer
Advances in Human Milk Substitutes for Infant Feeding" appearing in
Journal of Applied Nutrition, Vol. 35, No. 2, (1983), pp. 88-115,
there is disclosed in some detail the composition of human milk
compared with cow milk, evaporated milk formula, conventional
synthetic infant milk formula based on cow milk and a synthetic
protein milk-free formula. Additionally, there are comparisons made
between the protein and non-protein nitrogen components in human
milk and in cow milk including the various caseins which are to be
found in human milk, viz. alpha-casein, beta-casein and
kappa-casein. It is mentioned therein that human milk has a higher
proportion of alpha-lactalbumin but no beta-lactoglobulin and that
the host resistance factors or anti-microbial proteins of human
milk, viz, lactoferrin, lysozyme and secretory IgA, account for 75%
of the protein in human colostrum as compared with 39% in mature
human milk and less than 0.1% in cow's milk. This article also
lists those host resistance factors present in human milk but
absent in cow milk, viz. lymphocytes, macrophages, and secretory
IgA. Lactoferrin is present in a relatively high amount in human
milk but in only a low amount in cow milk, whereas lactoperoxidase
is present in a relatively low amount in human milk but in a high
amount in cow milk. Lysozyme and bifidus-stimulating factors are to
be found in a significant amount in human milk but only in trace
amounts in cow milk. Similarly complement (C1-C9) is to be found in
human milk but has not been positively identified in cow milk. The
vitamin binding proteins are found in high amounts in human milk
but in low amounts in cow milk.
[0006] It is seen, therefore, that if a synthetic infant milk
formula is prepared based on cow's milk, it would be difficult, if
not impossible, to more closely simulate the protein composition of
human milk. To this end, i.e. more closely to simulate human milk,
it is necessary that there be added to or incorporated in cow
milk-based synthetic infant milk formulas, soy protein or
meat-based synthetic infant formulas, those components which are
present in human milk but are substantially absent from cow milk
and the like. This is especially true in that in addition to their
nutritional value, per se, many of the proteins of human milk have
functional and/or protective value as well which cannot be
duplicated in synthetic infant formulas based on bovine or soy
proteins.
[0007] Accordingly, it is an object of this invention to provide a
synthetic infant milk formula which more closely simulates the
composition of fresh human milk.
[0008] It is another object of this invention to provide protein
components or compositions useful for enhancing or improving the
nutritional and functional or protective value of synthetic infant
milk formulas and also banked or pooled human milk.
[0009] It is yet another object of this invention to provide
compositions useful for incorporation into the diet of an infant so
as to enhance and improve the nutritional and functional or
protective value of the diet.
[0010] Still another object of this invention is to provide
techniques and routines for improving the diet and feeding of
infants, particularly very-low-birth-weight infants.
[0011] How these and other objects of this invention are achieved
will become apparent in the light of the accompanying disclosure.
With respect to the disclosure of this invention, the disclosures
of all the publications cited herein, including U.S. Pat. No.
4,303,692, are herein incorporated and made part of this
disclosure.
SUMMARY OF THE INVENTION
[0012] Compositions containing human milk proteins, including the
so-called host resistance factors (HRF) of human milk, are useful
and are employed to enhance and improve the nutritional value of an
infant's diet by including such compositions in the infant diet.
These compositions can be incorporated in human milk, either
pooled, banked or the mother's own; in synthetic infant milk
formulas based on cow's milk or soy protein, or can be supplied
directly to the infant.
[0013] In the practices of this invention the nutritional,
functional, or protective human milk proteins, including the
so-called host resistance factors (HRF) of human milk, are prepared
by chemically synthesizing the same or by employing genetic
engineering techniques for producing the nutritional, functional
and/or protective human milk proteins including the host resistance
factors, as recombinant human milk proteins or recombinant host
resistance factors. These human milk proteins including the host
resistance factors, because of their complexity and/or
functionality, are preferably made by DNA genetic engineering
techniques as recombinant human milk proteins or recombinant host
resistance factors.
[0014] Suitable recombinant, nutritional and/or functional human
milk proteins and recombinant host resistance factors of human milk
upon which this invention is based include recombinant lactoferrin
(LF), recombinant lactoperoxidase (LP), recombinant lysozyme (LZ),
recombinant immunoglobulin-A (IgA), recombinant alpha-lactalbumin,
recombinant bifidus-stimulating factors, recombinant
vitamin-binding proteins, recombinant mineral binding proteins and
others. Desirably, these chemically synthesized or recombinant
nutritional and/or functional human milk proteins or host
resistance factors would be incorporated in amounts and
proportions, when employed to enhance the value of the synthetic
infant milk formula, so that the resulting formula contains these
incorporated materials in an amount and/or proportion that these
materials are normally found in fresh human milk. Also,
compositions of this invention could be provided so as to contain
these human milk proteins and host resistance factors in
concentrated amounts, that are much greater than that found on a
similar weight or volume basis of fresh human milk, e.g. in the
range of 2 to 1000-5000 times the concentration, with the result
that these concentrated compositions could be added to a relatively
large volume of synthetic infant milk formula so as to bring up the
concentration of these added compounds to a value similar to or
greater than those found in fresh human milk.
[0015] One advantage of employing chemical synthesis or genetic
engineering techniques for the manufacture of nutritional and/or
functional human proteins and the host resistance factors of human
milk, is the resulting produced materials would be free of the AIDS
or human immunodeficiency virus (HIV), such as HIV-I, HIV-II and
other viruses including but not limited to cytomegalic inclusion
virus. In the past, the human milk proteins, particularly the
so-called host resistance factors, have been recovered or produced
from fresh human milk. Since these resulting produced materials are
often pooled or are produced from pooled human milk, there is a
danger that the resulting produced and recovered human milk
proteins, including the host resistance factors could contain HIV
if one of the contributors to the pooled human milk or the pooled
human milk proteins had AIDS or was injected with HIV. This is not
a reasonable possibility when the nutritional and/or functional
human milk proteins, including the so-called host resistance
factors, are produced as recombinant human milk proteins or
recombinant host resistance factors employing genetic engineering
techniques. Similarly, if these human milk proteins or host
resistance factors are manufactured by chemical synthesis which,
because of the complexity of these materials, would be difficult to
do, these materials produced by chemical synthesis would also be
free of HIV.
DETAILED DESCRIPTION OF THE INVENTION
[0016] A host resistance factor which is particularly suitable for
manufacture by recombinant DNA techniques in accordance with this
invention is human lysozyme as found in human milk. Human lysozyme,
as indicated hereinabove, is found in human milk and serves, among
other things, to protect the infant from bacterial infection. In
fact, it has even been proposed to employ human lysozyme derived
from human milk to enrich synthetic cow milk-based formula so that
the lysozyme-enriched cow-based infant formula more closely
approximates human milk with respect to lysozyme content and
activity, see the article by B. Haneberg et al. entitled "Lysozymes
in Feces from Infants and Children" which appeared in Acta Paediatr
Scand. 63:588-594 (1974).
[0017] Also, with respect to the utilization of lysozyme in infant
formula so as to enhance the biological value of infant formulas
based on cow's milk, reference is made to the article by T. Sh.
Sharmanov et al. entitled "Multicomponent Additive for Infant
Formula Enriched with Essential and Protective Factors", Kazakhstan
Division of the Institute of Nutrition, USSR Academy of Medical
Science, Alma-Ata, published in Vopr. Pitan 1986, #3, pp. 59-62
(1986).
[0018] Of special interest with respect to the preparation or
production of human lysozyme by genetic engineering DNA techniques
for the production of a recombinant human lysozyme, reference is
hereby made to EPO Application 181,634, published Jun. 21, 1986.
This European patent publication discloses DNA genetic engineering
techniques employing the gene for human lysozyme including a method
of preparing a vector containing the gene, the transformation of
cells with the vector containing the lysozyme gene and the
culturing of the transformed cells for the production and recovery
of the resulting produced recombinant human lysozyme. It is
disclosed that the recombinant human lysozyme thus produced had
functional applications for anti-inflammation, hemostatic, tissue
regeneration and anti-tumor. It also discloses other applications
for use of human lysozyme in an eye wash as an anti-inflammation
enzyme and as a food antiseptic. Human lysozyme has advantages over
non-human lysozyme, such as egg white lysozyme, since it does not
have side effects due to the body's immune response when used for
medical purposes. This European patent publication clearly teaches
the production of recombinant human lysozyme, a product useful in
the practices of this invention.
[0019] Another compound of special interest in recombinant form as
produced by DNA genetic engineering techniques for use in
compositions in the practices of this invention is human
lactotransferrin or human lactoferrin which is found in human milk
and which has been characterized and identified as a glycoprotein.
Specifically, the polypeptide chain of human lactoferrin has been
identified and found to possess two glycosylation sites to which
glycans are linked through an
N-(-aspartyl)-N-acetylglucosaminylamine bond and which are
structurally heterogeneous. Accordingly, the make-up and structure
of human lactotransferrin is known.
[0020] Recombinant lactotransferrin or lactoferrin (LF) is
particularly useful as a component in the preparation of
compositions in accordance with this invention and the use of such
compositions. The functional role of lactotransferrin in human
milk, particularly its role in iron absorption and its role in
protection against enteric infection in a newborn infant is
described in an article entitled "Lactoferrin in Human Milk: Its
Role in Iron Absorption and Protection Against Enteric Infection in
the Newborn Infant", published in Archives of Disease in Childhood,
Vol. 55, pp 417-421 (1980). This article emphasizes that human milk
is unusually rich in lactoferrin and that lactoferrin was first
reported in 1939 by the investigators, M. Sorensen et al. in an
article entitled "The Proteins in Whey", published by C. R. Lab
(Carlsberg)[Ser Chim], Vol. 23, pp. 1 55-59 (1939).
[0021] The role of a lactoferrin in human milk is the subject of
the article entitled "Iron-Binding Proteins in Milk and Resistance
to Escherichia coli Infection in Infants" by J. R. Bullen et al.,
published in the British Medical Journal, pp. 69-75 (Jan. 8, 1972).
Further, the article by J. D. Oram et al. entitled "Inhibition of
Bacteria by Lactoferrin and Other Iron-Chelating Agents", published
in Biochimica et Biophysica Acta, 170, pp. 351-365 (1968),
discloses that human lactoferrin when not fully saturated with iron
is bacteriostatic with respect to Bacillus stearothermophilus and
Bacillus subtilis, both in the presence and absence of trace
amounts of metals. Another article of interest as to the role of
lactoferrin is the article of T. M. Cox et al. entitled "Iron
Binding Proteins and Influx or Iron Across the Duodenal Brush
Border--Evidence for Specific Lactotransferrin Receptors in the
Human Intestine", Biochimica et Biophysics Acta, Vol. 588, pp.
120-128 (1979). This article discloses that lactotransferrin coats
the luminal surface of the small intestine and shows a remarkable
physio-chemical homology with other transferrins and that the
proteins may be distinguished from human serum transferrin by its
immunological properties, its glycan sequences, its conformation
and by the localization of the two iron-binding sites on the
protein.
[0022] Still another article by G. Spik et al. entitled
"Characterization and Properties of the Human and Bovine
Lactotransferrins Extracted from the Faeces of Newborn Infants",
published in Acta Paediatr Scan, 71:979-985 (1982), discloses that
when a cow's milk diet for infants is supplemented by partially or
completely iron-saturated human or bovine lactoferrin, the amount
of copro-lactotransferrin excreted depended on the origin and on
the iron saturation of the lactotransferrin. This article stated
that the lactoferrins ingested by babies are not completely
destroyed and keep their functional ability to bind iron and thus
may supplement the protective bacteriostatic effects of the
endogenous lactotransferrin in the intestinal tract.
[0023] Accordingly, in view of the above, it is obvious that much
is known about the physical and chemical structure and make-up of
human lactotransferrin and its utility when present in an infant
diet.
[0024] Further, the article by B. Reiter entitled "The Biological
Significance and Exploitation of Some of the Immune Systems in
Milk--A Review", published in Microbiologie--Aliments--Nutrition,
Vol. 2, pp. 1-20 (1984), reviews the human resistance factors or
protective proteins found in human milk including the
immunoglobulins, complements, lysozyme, lactoferrin,
lactoperoxidase and others. In this article, special attention is
given to the functional and protective roles of lysozyme in human
milk and it is disclosed that feeding lysozyme to infants increases
the immunoglobulin level in faeces (secretory IgA) compared with
the faeces of infants fed formula feed only. This article also
discloses the role of lactoferrin in inhibiting bacteria.
Lactoperoxidase is also discussed in this article and its
bactericidal effect in human milk, see also the article by J. H.
Brock entitled "Lactoferrin in Human Milk. Its Role in Iron
Absorption and Protection Against Enteric Infections in the Newborn
Infant" published in Archives of Diseases in Childhood, 55, pp.
417-421 (1980).
[0025] Of special interest is the article by G. E. Gaull et al.
entitled "Growth Modulators in Human Milk: Potential Roles",
published by Pediatrics pp. 156-160. This article mentions that
there are at least three major groups of non-cellular constituents
in human milk. These groups comprise:
[0026] 1) the so-called classical nutrients, i.e. proteins, lipids,
lactose, vitamins and the major and trace minerals;
[0027] 2) the so-called protective or human host resistance
factors, such as secretory IgA mentioned herein; and
[0028] 3) a newly recognized functional group consisting of growth
modulators which includes small molecules, such as taurine, small
hormone-like proteins, such as epidermal growth factor (EGF),
enzymes and interferons. The last mentioned growth modulators are
also protective factors. All these factors or groups are useful
when chemically synthesized or in recombinant form in compositions
in accordance with this invention.
[0029] Further, of special interest in the practice of the present
invention is the paper by R. E. McClead et al. entitled "Oral
Lactoferrin (LF) and Lactoperoxidase (LP) Decrease Mortality of
Enterotoxigenic E. coli (ETEC) Infection", presented at the
American Pediatric Society/Society of Pediatric Research--April,
1987 wherein it is concluded that supplemental feedings of
lactoferrin at concentrations comparable to that in human milk
decrease mortality from ETEC in suckling mice and that high
concentrations of LP but not of LZ are also protective. This
article speculates that infant formula containing LF and/or LP may
prevent enteric infections in the newborn.
[0030] Another article of interest in connection with the practices
of this invention is the article by S. K. Polberger et al. entitled
"Growth and Metabolic Responses in Very-Low-Birth-Weight Infants
(VLBW) Infants Fed with Ultrafiltrated Human Milk Protein Fortified
Fresh Breast Milk--A Model for Optimal Feeding of VLBW-Infants?"
also presented at the Meeting of American Pediatric Society/Society
of Pediatric Research--April 1987. This article indicates that
human milk protein obtained by ultrafiltration of human milk is
nutritionally useful when employed to fortify the mother's own
fresh human milk and that a significant correlation was found
between protein intake and growth, serum urea, plasma, prealbumin
and transferrin as well as many plasma and urine amino acids, with
the optimal nutritional protein intake from human milk protein in
VLBW--infants being between 3.0 and 3.5 g/kg/d.
[0031] Further, in another such article by B. L. Nichols et al.
entitled "Human Lactoferrin Fortification of Formulas Promotes
Thymidine Uptake into DNA of Rat Intestinal Crypt Cells" also
presented at Meeting of American Pediatric Society/Society of
Pediatric Research--April 1987, there is disclosed that cow
milk-based and soy protein-based formulas to which lactoferrin has
been added reverses the inhibition of thymidine uptake into the DNA
of rat intestinal crypt cells as compared with the same formulas
without the addition of human lactoferrin.
[0032] The above disclosures clearly indicate the advantages in
accordance with this invention of incorporating into synthetic
infant formulas that are cow milk-based and/or soy-based, one or
more of the recombinant nutritional and/or functional human milk
proteins including one or more of the recombinant host resistance
factors found in human milk. Many of the human proteins including
the host resistance factors of human milk are obtained by
ultrafiltration from pooled human milk. As noted herein, there is a
danger that the pooled human milk might be contaminated with HIV or
other dangerous viruses. This is one reason in accordance with the
practices of this invention that the nutritional and/or functional
human milk proteins including the host resistance factors of human
milk, all as described hereinabove, be prepared and produced by
chemical synthesis or by genetic engineering techniques. Such
produced human milk proteins would be free of HIV and/or other
dangerous viruses and could be produced in substantial amounts
without dependency on the availability or supply of human milk.
[0033] Moreover, in accordance with this invention, such human milk
proteins could be specially produced, such as human lysozyme and
human lactotransferrin so that, in effect, tailor-made recombinant
human milk protein compositions containing only, for example, human
lysozyme or only human lactoperoxidase or human lactoferrin or
human secretory IgA and others, or combinations thereof, could be
produced in high purity. The production of human milk proteins by
recombinant DNA techniques permits greater flexibility in the
make-up and utilization of compositions in accordance with this
invention when utilized to enhance the diet of infants,
particularly VLBW infants or to enhance the nutritional and/or
functional value of synthetic infant formulas, either cow
milk-based, soy protein-based or meat-based, as indicated
hereinabove. Instead of recombinant human milk proteins, one could
employ in the practices of this invention human milk proteins
produced by chemical synthesis where applicable or desired. Such
chemically synthesized human milk proteins, like the corresponding
recombinant proteins, would also be free of HIV and accordingly
would also be usefully employed in the practices of this
invention.
[0034] As will be apparent to those skilled in the art in the light
of the foregoing disclosures, many modifications, alterations and
substitutions are possible in the practices of this invention
without departing from the spirit or scope thereof.
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