U.S. patent application number 10/377555 was filed with the patent office on 2003-09-11 for infant formula and methods of improving infant stool patterns.
Invention is credited to Benson, John D., Halter, Robin J., Kuchan, Matthew A., Masor, Marc L., Ponder, Debra L..
Application Number | 20030171433 10/377555 |
Document ID | / |
Family ID | 27391006 |
Filed Date | 2003-09-11 |
United States Patent
Application |
20030171433 |
Kind Code |
A1 |
Kuchan, Matthew A. ; et
al. |
September 11, 2003 |
Infant formula and methods of improving infant stool patterns
Abstract
The invention is directed to an improved infant formula
containing a lipid blend that softens the firmer stools associated
with typical infant formula. A specific formula in accordance with
the invention comprises carbohydrates, proteins, vitamins and
minerals and a lipid mixture of high oleic safflower oil, soy oil
and coconut oil at specific levels and ratios. The invention also
discloses novel mixtures of fatty acids that provides infant stool
patterns more closely resembling the breast-fed infant.
Inventors: |
Kuchan, Matthew A.;
(Gahanna, OH) ; Masor, Marc L.; (Worthington,
OH) ; Ponder, Debra L.; (Atlanta, GA) ;
Halter, Robin J.; (Columbus, OH) ; Benson, John
D.; (Powell, OH) |
Correspondence
Address: |
ROSS PRODUCTS DIVISION OF ABBOTT LABORATORIES
DEPARTMENT 108140-DS/1
625 CLEVELAND AVENUE
COLUMBUS
OH
43215-1724
US
|
Family ID: |
27391006 |
Appl. No.: |
10/377555 |
Filed: |
February 28, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10377555 |
Feb 28, 2003 |
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09789035 |
Feb 20, 2001 |
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09789035 |
Feb 20, 2001 |
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09498593 |
Feb 4, 2000 |
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6248784 |
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09498593 |
Feb 4, 2000 |
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08812626 |
Mar 7, 1997 |
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6136858 |
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08812626 |
Mar 7, 1997 |
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08585221 |
Jan 11, 1996 |
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5700590 |
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08585221 |
Jan 11, 1996 |
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08178687 |
Jan 10, 1994 |
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5492899 |
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Current U.S.
Class: |
514/560 |
Current CPC
Class: |
A61K 31/70 20130101;
A61K 45/06 20130101; A61K 31/7088 20130101; A61K 2300/00 20130101;
A23D 9/00 20130101; A23L 33/40 20160801; A61K 45/06 20130101; Y10S
426/801 20130101; A61K 31/7088 20130101; A23L 33/13 20160801; A61K
31/7088 20130101; A23L 33/115 20160801; Y10S 514/866 20130101; A61K
31/70 20130101 |
Class at
Publication: |
514/560 |
International
Class: |
A61K 031/20 |
Claims
We claim:
1. An improved fat composition for consumption by humans
characterized by a fatty acid profile comprising: a) 9.5-21 weight
% lauric acid; b) up to 10 weight % palmitic acid; and c) 34-48
weight % oleic acid.
2. The fat composition of claim 1 comprising: a) 104-17.1 weight %
lauric acid; b) 7.0-8.0 weight % palmitic acid; and c) 37.0-45.2
weight % oleic acid.
3. The fat composition of claim 2 comprising: a) 10.4-15 weight %
lauric acid; b) 7.5-8.0 weight % palmitic acid; and c) 37.6-43.0
weight % oleic acid.
4. The fat composition of claim 3 comprising: a) about 14.2 weight
% lauric acid; b) 7.7 weight % palmitic acid; and c) about 40.0
weight % oleic acid.
5. The fat composition of claim 1 wherein said fat composition
comprises, based on the weight of the total fat: a) 35-55 weight %
high oleic safflower oil; b) 20-40 weight % soy oil; and c) 20-45
weight % coconut oil.
6. The fat composition of claim 5 comprising: a) 38-50 weight %
high oleic safflower oil; b) 26l-40 weight % soy oil; c) 22-36
weight % coconut oil.
7. The fat composition of claim 6 comprising: a) about 42 weight %
high oleic safflower oil; b) about 28 weight % soy oil; and c)
about 30 weight % coconut oil.
8. An enteral formula comprising: a) a source of amino nitrogen; b)
a source of carbohydrate; and c) a fit composition according to
claim 1.
9. The formula of claim 8 wherein said fat comprises: a) 10.4-17.1
weight % lauric acid; b) 7.0-8.0 weight % palmitic acid; and c)
37.0-45.2 weight % oleic acid.
10. The formula of claim 8 wherein said fat comprises: a) 10.4-15
weight % lauric acid; b) 7.5-8.0 weight % paimitic acid; and c)
37.6-43.0 weight % oleic acid.
11. The formula of claim 8 wherein said fat comprises: a) about
14.2 weight % lauric acid; b) about 7.7 weight % palmitic acid; and
c) about 40.0 weight % oleic acid.
12. The formula of claim 3 wherein said fat comprises: a) 35-55
weight % high oleic safflower oil; b) 20-40 weight % soy oil; and
c) 20-45 weight % coconut oil.
13. The formula of claim 12 wherein said fat comprises: a) 38-50
weight % high oleic safflower oil; b) 26-40 weight % soy oil; c)
22-36 weight % coconut oil.
14. The formula of claim 13 wherein said fat comprises: a) about 42
weight % high oleic safflower oil; b) about 28 weight % soy oil;
and c) about 30 weight % coconut oil.
15. The formula of claim 8 wherein said formula is in the form of a
powder intended to be reconstituted, a concentrate intended to be
reconstituted or a ready-to-feed liquid.
16. The formula of claim 15 which is in ready-to-feed form and
which comprises: a) amino nitrogen source being of a concentration
of between 10 and 35 grams per liter of formula; b) carbohydrates
being of a concentration of between 60 and 100 grams per liter of
formula; and c) fat composition being of a concentration of between
20 and 45 grams per liter of formula.
17. A method of improving the stool pattern of a formula-fed infant
comprising feeding said infant a formula comprising a fat
composition according to claim 1.
18. The method of claim 17 wherein said fat composition comprises:
a) 10.4-17.1 weight % lauric acid; b) 7.0-8.0 weight % paimitic
acid; and c) 37.0-45.2 weight % oleic acid.
19. The method of claim 18 wherein said fat composition comprises:
a) 10.4-15 weight % lauric acid; b) 7.5-8.0 weight % paimitic acid;
and c) 37.6-43.0 weight % oleic acid.
20. The method of claim 18 wherein said fat composition comprises:
a) about 14.2 weight % lauric acid; b) about 7.7 weight % palmitic
acid; and c) about 40.0 weight % oleic acid.
21. The method of claim 18 wherein said fat composition comprises:
a) 35-55 weight % high oleic safflower oil; b) 20-40 weight % soy
oil; and c) 20-45 weight % coconut oil.
22. The method of claim 18 wherein said fat composition comprises:
a) 38-50 weight % high oleic safflower oil; b) 26-40 weight % soy
oil; c) 22-36 weight % coconut oil.
23. The method of claim 18 wherein said fat composition comprises:
a) about 42 weight % high oleic safflower oil; b) about 28 weight %
soy oil; and c) about 30 weight % coconut oil.
24. A method for reducing the incidence of constipation associated
with ingestion of infant formula, said method comprising feeding
said infant a formula comprising a fat composition according to
claim 1.
25. The method of claim 24 wherein said fat composition comprises:
a) 10.4-17.1 weight % lauric acid; b) 7.0-8.0 weight % palmitic
acid; and c) 37.0-45.2 weight % oleic acid.
26. The method of claim 24 wherein said fat composition comprises:
a). 10.4-15weight % lauric acid; b) 7.5-8.0 weight % palmitic acid;
and c) 37.6-43.0 weight % oleic acid.
27. The method of claim 24 wherein said fat composition comprises:
a) about 14.2 weight % lauric acid; b) about 7.7 weight % palmitic
acid; and c) about 40.0 weight % oleic acid.
28. An infant formula which comprises a source of amino nitrogen,
carbohydrates and fat, the improvement characterized in a fat
composition comprising: a) 10.4-15.4 weight % lauric acid; b)
7.5-8.0 weight % palmitic acid; and c) 37.6-43.0 weight % oleic
acid; and wherein said fat composition is derived from a mixture of
oils selected from the group consisting of high oleic safflower,
high oleic sunflower, soy, coconut, safflower, and palm kernel.
29. A method of improving the stool pattern of a formula-fed infant
comprising feeding said infant a nutritionally complete composition
containing fatty acids, which, based upon the total weight of fatty
acid content comprises: a) 10.4-15.0 % lauric acid b) up to 10%
palmitic acid; and c) 37.6-43.0 % oleic acid; and wherein said
fatty acids are derived from a mixture of high oleic safflower oil,
soy oil and coconut oil.
Description
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent
application Ser. No. 08/585,221 filed Jan. 11, 1996; which is a
continuation-in-part of U.S. patent application Ser. No. 08/178,687
filed Jan. 10, 1994 now U.S. Pat. No. 5,492,899 issued Feb. 20,
1996. The complete teachings of U.S. Pat. No. 5,492,899 are
incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The invention relates to an improved enteral nutritional
formula and more particularly to infant formulas which contain a
lipid fraction possessing a fatty acid profile resulting in more
desirable infant stool patterns compared to stool patterns
associated with conventional infant formula. More specifically,
this invention relates to a blend of high oleic safflower oil,
and/or high oleic sunflower oil, soy oil and coconut oil (or a
blend of fats that have a similar fatty acid profile to the
inventive blend) that has been found effective in producing stool
patterns in infants that are similar to those of the breast-fed
infant.
BACKGROUND OF THE INVENTION
[0003] The composition of human milk serves as a valuable reference
for improving infant formula However, human milk contains living
cells, hormones, active enzymes, immunoglobulins and components
with unique molecular structures that cannot be replicated in
infant formula Unlike human milk infant formula must remain stable
on the shelf for up to thirty-six (36) months. These fundamental
differences between human milk and infant formula often mandate
differences in the composition to achieve similar clinical
outcome.
[0004] The study of human milk components has stimulated many
investigations into what constituents may be added to an improved
infant formula. Greater knowledge of the composition of human milk
affords the opportunity to design infant formulas that are closer
in composition to human milk. However, it becomes increasingly
apparent that infant formula can never exactly duplicate human
milk. Many constituents in human milk are bioactive and because of
synergies among these components, there is little reason to believe
that the same compound would have the same bioactvity in infant
formula The likelihood of this possibility is further diminished
when the impact of heat treatment for sterilization and long-term
storage of the formula is considered. The present invention is
based, in part, on the concept of providing a formula which matches
the performance of breast milk in stool consistency parameters
without attempting to duplicate exactly the delicate balance of
human milk components.
[0005] The composition of human milk differs appreciably from that
of other species and much attention has been paid to the various
components. Several investigators have reported on the nucleotide
content of milk from humans (Janas, L M et al: The Nucleotide
Profile of Human Milk. Pediatr. Res. 16:659-662(1982) and Gil et
al.: Acid-soluble Nucleotides of Human Milk at Different Stages of
Lactation. Journal of Dairy Research (1982), 49, 301-307). Numerous
publications have also discussed various lipid, oil or fat blends
for use in an artificial nutritional for human infants. As the
result of investigations regarding the use of nucleotides in infant
formula, the inventors of the present application discovered that a
particular blend of oils resulted in infant stool patterns that are
similar to those of the breast fed infant.
[0006] Formula tolerance is generally assessed by gastrointestinal
symptoms (e.g., emesis, stool patterns and gas) as well as
behavioral characteristics (e.g., acceptance of formula, fussing
and crying). Concerns regarding poor tolerance are frequently
reported as a reason for formula switching within the first two
months of life. (Forsythe B W C, McCarthy P L, Leventhal J M:
Problems of early infancy, formula changes., and mother's beliefs
about their infants. J. Pediatr. 1985; 106:1012-1017). Stool
patterns are known to differ between formula-fed and breast-fed
infants, (Weaver L T, Ewing G. Taylor, L C: The Bowel Habit of
Milk-Fed infants. J. Pediatr. Gastroenterol Nutr. 1988; 7:568-571),
as well as between infants fed various formulas (Hyams, J S, Treem
W R, Etienne N L, et al.: Effect of infant formula on stool
characteristics of young infants. Pediatrics 19951 50:54).
[0007] The Hyams et al. publication, supra, also reports that
certain infant formulas typically cause a significantly greater
percentage of firm stools compared to the breast-fed infant which
may be perceived by the parent or care giver as unacceptable. This
publication also indicated that milk-based, iron-fortified formulas
resulted in a significantly lower percentage of watery stools. S.
J. Fomon in Nutrition of Normal Infants (L. Craven ed.) Mosby: St.
Louis, Mo., at page 250 states that "Many physicians appear to be
convinced that infants fed iron-fortified formulas are prone to
fussiness . . . and constipation." It is this problem and/or
perception that the present invention addresses. Quinlan et al. in
Pediatr Gastroenteral Nutr., Vol. 20, No. 1 (1995) concludes that
"Constipation" and "hard stools" are associated with formula
feeding of both term and pre-term infants and, in the latter, can
lead to life threatening complications."
[0008] Numerous investigators have reported that fatty acid
profiles similar to human milk are important to the human infant.
Representative of those numerous publications are: 1) Gil et al.,
changes in the Fatty acid Profiles of Plasma Lipid Fractions
Induced by Dietary Nucleotides in Infants Born at Term, Eur. J. of
C. Nutrition, (1988) 42, 473-481; 2) E.P. 0129,990; 3) E.P.
0376,628; 4) U.S. Pat. No. 4,670,285; 5) U.S. Pat. No. 3,231,385;
6) U.S. Pat. No. 4,544,559; 7) U.S. Pat. No. 4,758,553; and 8) U.S.
Pat. No. 4,994,442. These investigators have failed to discover
that a blend of lipid sources, which is essentially free of
palmitic acid which may comprise a blend of high oleic safflower
oil, soy oil and coconut oil, is beneficial in overcoming certain
shortcomings associated with infant formula;
SUMMARY OF THE INVENTION
[0009] Previous investigations have attempted to duplicate the
fatty acid profile of human milk in an effort to improve infant
formula In contrast, the present invention is based upon discovery
that a particular fatty acid profile for the lipid not closely
related to the profile of human milk, will result in a stool
pattern similar to breast fed infants while also supplying basic
nutritional requirements. Such a lipid profile can be achieved, for
example, through a blend of oils.
[0010] The enteral formula of the instant invention provides a
positive advantage to the infant. The clinical studies which were
conducted and reported herein evidence the unexpected advantages of
the instant invention. An additional aspect of the present
invention is the overall balance of nutrient interactions and
bio-availability, which provide an improved nutritional product.
Another aspect of the present invention relates to an infant
formula which meets the requirements of the Infant Formula Act and
to methods for reducing the incidence of objectionable stool
characteristics associated with conventional infant formula.
Further, the present invention is directed to a novel blend of oils
Which provide a fatty acid profile that is beneficial in human
nutrition.
[0011] Thus, the invention provides, in one aspect an improved fat
composition for consumption by humans characterized by a fatty acid
profile comprising 9.5-21 weight % lauric acid, up to 10 weight %
palmitic acid and 34-48 weight % oleic acid. In another aspect, the
invention provides an enteral formula comprising protein,
carbohydrate and a fat composition as described above.
[0012] Yet another aspect of the invention provides a method of
improving the stool pattern of a formula-fed infant and a method
for reducing the incidence of constipation associated with
ingestion of infant formula comprising feeding the infant a formula
comprising a fat blend as described above. More specifically, the
inventive method comprises feeding an infant a nutritionally
complete formula comprising a weight ratio of lauric acid to
palmitic acid to oleic acid that ranges from 4:3:8 to 1:0.5:3 with
a preferred ratio at 2:1:6.
[0013] Even more specifically, this invention relates to an infant
formula which comprises a source of amino nitrogen, carbohydrates
and fat, the improvement characterized in a fat composition
comprising 10.4-15.4 weight % lauric acid, 7.5-8.0 weight %
palmitic acid and 37.643.0 weight % oleic acid and wherein the fat
composition is derived from a mixture of oils selected from the
group consisting of high oleic safflower oil, high oleic sunflower,
soy, coconut, safflower and palm kernel oil.
[0014] Further, this invention discloses a method of improving the
stool pattern of a formula-fed infant comprising feeding the infant
a nutritionally complete composition containing fatty acids, which,
based upon the total weight of fatty acid content comprises
10.4-15.0% lauric acid, 7.5-8.0% palmitic acid and 37.6-43.0% oleic
acid and wherein the fatty acids are derived from a mixture of high
oleic safflower oil, soy oil and coconut oil.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] The term "fatty acid profile" as used herein means the total
fatty acid content of the fat, oil, emulsifiers and other
components used to create an enteral nutritional as determined by
convention analysis. Unless specified otherwise, all percentages
are weight percents of total fatty acid content Those skilled in
the art will appreciate that sometimes the levels of fatty acids
are reported as grams of fatty acid per 100 grams of fat.
[0016] In one embodiment, the invention relates to an enteral
formula, said formula comprising: 1) protein, said protein being of
a concentration of between 10 and 35 grams per liter of formula; 2)
carbohydrates, said carbohydrates being of a concentration of
between 70 and I 10 grams per liter of formula; and 3) fat, said
fat having a fatty acid profile comprising 9.5-21 weight percent
lauric acid, up to 10 weight % palmitic acid and 34-48 weight %
oleic acid. The enteral formula according to this invention
provides a source of carbohydrates selected from sucrose, corn
syrup, glucose polymers and other carbohydrate sources. The formula
may also contain dietary fiber. The teachings of U.S. Pat. No.
5,021,245 are incorporated herein by reference.
[0017] (a) In another embodiment, the fat blend further comprises
2.7-3.1 weight % stearic acid, 17-29 weight % linoleic acid and
1.7-3.2 weight % linolenic acid. The fat blend having the recited
fatty acid profile can be achieved through a blend of high oleic
safflower oil, soy oil and coconut oil. In general, any appropriate
source of fatty acids, such as oils, fats, phospholipids,
emulsifiers, tissue extracts, single cell oils, recombinant plants,
transgenic plants and animals and animals and the like, can be used
in this invention, provided less than 10% by weight of total fatter
acids is paixnitic acid. In an additional embodiment of this
invention the weight ratio of linoleic acid to palmitic acid always
exceeds 2:1. A further aspect of the invention resides in the
discovery of a fatty acid profile for an enteral formula that
possesses up to 10 weight % palmitic acid and a weight ratio of
lauric acid to palmitic acid to oleic acid of from 3:1:7 to
1.2:1:4.3. The most preferred ratio is about 1.8:1:5.2.
[0018] An enteral formula in accordance with the invention may also
comprise a nutritionally adequate source of amino nitrogen,
carbohydrates, fats, minerals and vitamins, wherein the fat
composition consists essentially of 35-55% by weight high oleic
safflower oil; 20-40% by weight soy oil; and 20-45% by weight of
coconut oil.
[0019] The enteral formulas of the invention may be in the form of
a ready-to-feed product, a powder or a concentrate. Dilution or
reconstitution instructions supplied by the manufacturer should be
followed. Those skilled in the art can determine from the
instruction conversion factors that would convert the values of
such as 10-35 grams per liter of formula for the ready-to-feed
product to values applicable to the powdered and concentrate
forms.
[0020] As used herein, the term "high oleic safflower oil" (HOSO)
means the oil derived from the seeds of a hybrid safflower plant,
Carthamus tinctorius. Safflower oil is an edible oil which
typically has a high content of linoleic acid. Hybrids of this
plant have been developed which produce a seed oil which has an
elevated level of oleic acid. It is the oil that is derived from
the seeds of these hybrids which have been found, useful in the
present invention. Virtually interchangeable with HOSO is high
oleic sunflower oil. Like HOSO, high oleic sunflower oil contains
an elevated level of oleic acid. When used herein, the term "HOSO"
includes its sunflower relative.
[0021] As used herein, the term "soy oil" (SO) means the fat
fraction obtained from the seeds of the legume, Soja mar.
Typically, the oil fraction of the soya seed undergoes a number of
refining, bleaching and deodorization steps resulting in the
commercial commodity. Soy oil generally contains relatively high
levels of linoleic fatty acid and to a lesser extent, linolenic
fatty acid.
[0022] As used herein, the term "coconut oil" (CO) means the oil
obtained from copra, which is dried coconut meat. This oil is
distinguished from HOSO and SO by its high content of saturated,
short-chain and medium chain fatty acids. Palm kernel oil is very
similar in fatty acid profile to CO. When used herein, the term,
"CO" includes its palm kernel relative.
[0023] As used herein, the terms "stool pattern" and "constipation"
relate to kinds of defecation that an individual experiences as a
result of nutritional intake. To "improve the stool pattern of a
formula-fed infant" means to reduce the actual or perceived
difference between the feces consistency of breast-fed infants and
those fed a conventional infant formula. As reported above, the
consumption of typical infant formula results in infant stools that
are firmer/harder than the stools resulting from the consumption of
human milk. Human milk is considered the "gold standard" by parents
and professional care givers alike. As set forth in Table IV below,
infants fed breast milk have stools that can be described as
between watery (rank of 1) and slightly above loose/mushy (rank of
2). In the five point scale used to evaluate stool consistency
whereby; watery=1, loose/mushy=2, soft=3, formed=4 and hard=5, a
difference of 0.3 to 0.4 accompanied by a shift in stool category
(i.e., soft to formed) is considered significant. Constipation in
adults is considered as a difficult, incomplete, or infrequent
evacuation of the bowels. In infants, the term is similar to
adults, but uses the breast-fed infant for comparison. Further,
this condition is a matter of an actual or perceived condition by
the parent or care giver. The breast-fed infant typically has a
higher number of stools per day (from about 2.5 to 3.5 per day) and
has stools of a looser or watery consistency compared to
formula-fed infants Thus, for both terms, "improving the stool
pattern" and "reducing the incidence of constipation", means
defecation consistency that more closely resembles the breast-fed
infant and a stool of a looser consistency.
[0024] The formulas of the invention may take the form of a
powdered product, a concentrate or a ready-to feed product Those
skilled in the art will readily appreciate what each form of the
product will consist of. In similar fashion, the skilled artisan
will understand that reconstitution: of the powder and concentrate
should follow the instructions of the product manufacturer. As
contemplated herein, reconstitution should be accomplished with
water and not milk, fruit juices or other liquids that contain
protein, carbohydrates or fats.
[0025] One aspect of this invention resides in the discovery that
particular blends of commodity oils result in a fat composition
that possesses a special mixture of fatty acids. The fatty acid
profile (predominant) of the commodity oils: soy, coconut,
safflower, high oleic safflower, high oleic sunflower, palm kernel
and palm olein, are set forth in the following Chart I in an effort
to further define and characterize these oils.
1CHART I Fatty Acid Profile of Commodity Oils High Oleic Fatty Acid
Saf- Sun- Palm Palm weight % Soy Coconut flower HOSO flower Kernel
Olein 12:0 -- 47.1 -- 0.1 -- 49.6 0.6 lauric 14:0 0.1 18.5 0.1 0.1
-- 16 1.1 myristic 16:0 10.6 9.1 6.5 4.7 4.0 8.0 32.7 palmitic 18:0
4.0 2.8 2.4 2.2 4.0 2.4 3.5 stearic 18:1n9 23.2 6.8 13.1 74.5 80.0
13.7 48.1 oleic 18:2n6 53.7 1.9 77.7 16.7 10.0 2.0 13.2 linoleic
18:3n3 7.6 0.1 -- 0.4 0.1 -- 0.5 linolenic
[0026] The fatty acid profile of this invention is compared to
Enfamil.RTM. with Iron, (manufactured by the Mead Johnson Division
of Bristol-Meyers, New York, N.Y.); Similac.RTM. with Iron
(manufactured by the Ross Products Division of Abbott Laboratories,
Abbott Park, Ill.) and human milk in the following Chart II:
2CHART II Fatty Acid Profiles of Infant Formulas, the Invention and
Human Milk Fatty Acid weight % Enfamil* Similac* Invention Human
Milk* 12:0 8.4 18.0 9.5-21 1.4-6.5 lauric 14:0 3.9 7.3 3.8-8.4
3.8-10.2 myristic 16:0 22.1 9.5 up to 10 19.8-24.0 palmitic 18:0
4.7 3.5 2.7-3.1 7.1-9.0 stearic 18:1n9 36.7 16.7 34-48 30.7-38.0
oleic 18:2n6 18.1 32.9 17-29 5.7-17.0 linoleic 18:3n3 1.7 4.0
1.7-3.2 0.1-1.8 linolenic *analyzed
[0027] The following Chart III sets forth the fatty acid profile of
various embodiments of the present invention.
3 CHART III Fatty Acid weight % Preferred More Preferred Most
Preferred 12:0 10.4-17.0 10.4-15.0 14.2 lauric 14:0 4.2-6.7 4.2-6.0
5.6 myristic 16:0 7.0-8.0 7.5-8.0 7.7 palmitic 18:0 2.8-3.1 2.9-3.1
2.9 stearic 18:1n9 37.0-45.2 37.6-43.0 40.0 oleic 18:2n6 21.0-28.2
22.0-28.0 22.6 linoleic 18:3n3 2.2-3.2 2.3-3.2 2.3 linolenic
[0028] The preferred fatty acid profile as set out above can be
accomplished through a blend of 38-50 weight % HOSO, 26-40 weight %
SO and 22-36 weight % CO. The more preferred fatty acid profile can
be accomplished through a blend of 41-44 weight % HOSO, 27-32
weight % SO, and 27-32 weight % CO. The most preferred fatty acid
profile can be accomplished through a blend of 42 weight % HOSO, 28
weight % SO and 30 weight % CO.
[0029] Clearly, certain embodiments of the inventive lipid blend
are distinguished from commercial fat blends and human milk in the
content of lauric, linoleic and palmitic fatty acids. The inventive
lipid blend isalso distinguished from the prior art formula in the
weight ratio of oleic to palmitic fatty acids.
[0030] One aspect of the present invention resides in the discovery
that an infant formula, to attain stool patterns closer to
breast-fed infants, should contain a fat component that is less
than 10% by weight palmitic acid. An additional aspect of the
inventive oil blend is that the weight ratio of palmitic acid to
palmitic acid should always exceed 2:1. In an additional
refinement, the weight ratio of oleic to palmitic should always
exceed 4:1. A further aspect of the invention resides in the
discovery that the fatty acid profile of an infant formula should
have a weight ratio of lauric acid to palmitic acid to oleic acid
of from 3:1:7 to 1.2:1:4.3. A more preferred ratio is about
1.8:1:5.2.
[0031] This invention also relates to a method of reducing the
incidence of constipation associated with ingestion of infant
formula, said method comprising feeding an infant a nutritionally
complete formula comprising: 1) protein; 2) fat, said fat being of
a concentration of between 20 and 45 grams per liter of formula;
and wherein said fat has a fatty acid profile having a weight ratio
of lauric acid to palmitic acid to oleic acid of from 4:3:8 to
1:0.5:3. In a more preferred embodiment the weight ratio is
2:1:6.
[0032] From another perspective, the present invention reduces the
incidence of constipation through the enteral administration of a
fat blend wherein the fat comprises a fatty acid profile with less
than 10% by weight of paltnitic acid. More specifically, there is
disclosed is a method of improving the stool pattern of a
formula-fed infant, comprising feeding to the infant a formula
comprising high oleic safflower oil, soy oil and coconut oil.
[0033] An antioxidant system can be used in conjunction with the
invention which consists of .beta.-carotene, R,R,R,
.alpha.-tocopherol and selenium. The level of R,R,R,
.alpha.-tocopherol can range from 10 to 30 IU per liter of formula.
The level of .beta.-carotene can range from 375 to 575 .mu.g per
liter of infant formula and the level of selenium can range from 14
to 32 mcg per liter of formula. The selenium used in this aspect of
the invention may be delivered in the form of selenate. The
teachings of U.S. Pat. No. 5,221,545 are herein incorporated by
reference.
[0034] In actual use, the formula of this invention may be consumed
by any human. More specifically, the novel fat composition of this
invention may be incorporated into a formula which is in compliance
with accepted levels of vitamins, minerals, micro-components and
the like. The amount consumed does not differ from that associated
with the normal consumption of commercially available infant
formula. The caloric density (i.e., kcals/ml) and caloric
distribution (i.e., the relative proportion of calories from fat,
protein and carbohydrate) are not critical to this invention but
are generally comparable to conventional formulas. As is well know
to those skilled in the art, these factors can vary with the
intended use of the formula For example, pre-term, term and toddler
infants have somewhat differing caloric density requirements. Also,
formulas for specific disease states (e.g., diabetes, pulmonary
deficiency and. immuno-comprised) will have differing caloric
distributions. Those skilled in the art are aware of these
differences and will readily adapt the present invention to meet
those special needs.
[0035] A representative formula for the enteral nutritional product
of the invention is set forth in Table I.
4TABLE I A Representative Formula According To The Invention
NUTRIENT CONCENTRATION Protein 13.0-20 g/L Protein Source CSM.sup.1
55-75%* 7.15-15 g/L WPC.sup.2 25-45% 3.25-9.0 g/L Lipid 30-40 g/L
HOSO 35-55%** SO 20-40% CO 20-45% Carbohydrate Lactose 70-110 g/L
*% by weight of total protein **% of weight of total lipid
.sup.1condensed skim milk .sup.2whey protein concentrate
[0036] The pediatric nutritional formula of this invention is
generally prepared using the following method. An appropriate
quantity of protein is dispersed in sufficient water or oil to
solubilize or suspend it, thereby forming a protein
solution/suspension. Typically this protein source would be intact
milk proteins and/or hydrolyzed milk proteins. In general, any
known source of amino nitrogen can be used in this invention.
Representative sources of amino nitrogen include bovine milk
proteins, vegetable proteins, free amino acids, recombinant
proteins, hydrolyzed proteins and mixtures thereof. A carbohydrate
source such as one or more of corn syrup solids, lactose,
maltodextrins and sucrose is dissolved in water, thereby forming a
carbohydrate solution. A source of dietary fiber, such as soy
polysaccharide may also be added. Appropriate minerals are
dissolved in water, the carbohydrate solution or oil, so as to form
a mineral solution.
[0037] Once formed, the three solutions (protein, carbohydrate and
mineral) are combined in appropriate quantities with oils and oil
soluble vitamins. As used herein, the terms "oils", "fats",
"phospholipids", "lipids", "lard", and "extracts" means a source of
fatty acids that may be provided in the form of glycerides,
phospholipids, free fatty acids, the methyl-esters of fatty acids
and the like. An additional source of fatty acids is derived from
emulsifiers that contain fatty acids. Representative of such
emulsifiers, are the di-acetyl mono-glyceride esters of tartaric
acid. This resulting solution is then heat processed and
homogenized. Following processing, water soluble vitamins, iron,
choline and other nutrients are added and then nucleotides may be
added. The solution is then diluted with water to the appropriate
caloric density, approximately 670-725 kcal per liter for term
infant formula. The formula is then dispensed into containers and
retorted to obtain commercial sterility or packaged aseptically
using commercially available techniques and equipment. As prepared,
the formula contains appropriate nutrients in compliance with the
Infant Formula Act as of the date of this application. It should
also be recognized that the formula of this invention can be
prepared for use in powdered form or as a concentrated liquid.
[0038] The invention will be better understood in view of the
following examples, which are illustrative only and should not be
construed as limiting the invention.
EXAMPLE I
[0039] Preparation Of Enteral Formula
[0040] The following is a representative preparation of an enteral
nutritional formula containing the inventive lipid blend. On a
commercial scale, two formulas according to the invention were
prepared having the compositions set forth in Table II. The two
formula are as close as possible to being identical except for the
nucleotide component. These two formulas were then clinically
evaluated against human milk for a variety of parameters, including
infant stool patterns.
5TABLE II Composition Of Study Feedings (Per Liter) NUTRIENT
CONTROL NUC Protein, g 14.0 14.4 Fat, g 36.5 38.3 Carbohydrate, g
77.1 75.5 Calcium, mg 544.4 532.5 Phosphorous, mg 295.0 316.2
Magnesium, mg 73.5 77.7 Sodium, mg 170.1 179.2 Potassium, mg 931
948.6 Chloride, mg 487.7 493.2 Iron, mg 14.0 14.0 Zinc, mg 5.1 5.1
Copper, mcg 608 608 Iodine, mcg 61 61 Manganese, mcg 34 34 Vitamin
A, IU 2930 2970 Vitamin D, IU 405 405 Vitamin E, IU 24.6 24.8
Vitamin K, mcg 54 54 Vitamin C, mg 170 172 .beta.-Carotene, mcg 450
450 Selenium, mcg 23 23 Thiamin, mcg 1350 1360 Riboflavin, mcg 1014
1014 Pyridoxine, mcg 480 480 Vitamin B.sub.12, mcg 1.7 1.7 Niacin,
mcg 7095 7095 Folic Acid, mcg 101 101 Pantothenic acid, mcg 3041
3041 Biotin, mcg 30 30 Taurine, mg 45 45 Choline, mg 108 108
Inositol, mg 32 32 Energy, Kcal 676 676 CMP, mg 2.72* 31.2 UMP, mg
4.19* 17.7 AMP, mg 0.57* 9.8 GMP, mg 0.45* 14.4 *inherent to the
source of protein.
[0041] In this Example, a 7711 Kg batch of each formula was
prepared. In a similar fashion, the CON formula differed from NUC
in that the nucleotides were omitted. The list of ingredients and
amounts are found in Table III.
6TABLE III Ingredients And Amounts For NUC Formula INGREDIENT
AMOUNT High Oleic Safflower Oil 120.2 Kg Coconut Oil 85.7 Kg Soy
Oil 80.3 Kg Lecithin 2.92 Kg Mono-and diglyceride 2.92 Kg Oil
Soluble Vit, Premix 0.365 Kg .beta.-carotene 0.0137 Kg Carrageenan
1.43 Kg Whey Protein Concentrate 61.2 Kg Lactose 476.3 Kg Potassium
Citrate 4.6 Kg Magnesium Chloride 0.735 Kg Low Heat Condensed Skim
Milk 821 Kg Calcium Carbonate 3.36 Kg Ferrous sulfate 0.450 Kg
Water Soluble Vitamin Premix Trace 1.11 Kg Minerals/Taurine Choline
Chloride 0.600 Kg Adenosine 5'monophosphate 0.113 Kg Guanosine
5'monophosphate-Na2 0.197 Kg Cytidine 5'monophosphate 0.259 Kg
Uridine 5'monophosphate-Na2 0.216 Kg Ascorbic Acid 1.78 Kg 45% KOH
2.36 Kg Total Yield 7711 Kg
[0042] The first step in the preparation of formulas is the
preparation of the oil blend. To an appropriately sized blend tank
with agitation and heating soy oil, coconut oil and high oleic
safflower oil were added. The mixture was heated to
73.8-79.4.degree. C. The lecithin and mono-and diglycerides
(Myverol 18-06) were added to the blend tank with agitation. The
oil soluble vitamin premix was added with agitation. The premix
container was rinsed with the oil blend and transferred back to the
blend tank to ensure complete delivery of the vitamin premix. The
.beta.-carotene was added to the oil blend and the mixture agitated
until the components were well dispersed. The .beta.-carotene
container was rinsed with the oil blend and the contents returned
to the blend tank to ensure complete delivery of the
.beta.-carotene solution. Lastly, the carrageenan was added to the
oil blend and the mixture was agitated and held at 54.0-60.degree.
C. until used.
[0043] The carbohydrate, mineral and CSM (condensed skim milk)
protein slurry was prepared next. To water heated to 68-73.degree.
C. the lactose was added and the mixture agitated until the lactose
was well dissolved. Potassium citrate was then added followed by
potassium chloride, sodium chloride and magnesium chloride. The
condensed skim milk (CSM) and tri-calcium phosphate were then added
and the mixture was agitated and held at 54-60.degree. C. until
used.
[0044] The protein-in-water (PIW) slurry was then prepared. The
whey protein concentrate was added to water at 54-60.degree. C.
under mild agitation. The PIW slurry was held under mild agitation
until needed. Also contemplated in this invention is the use of
protein-in-fat (PIF) slurries, wherein an appropriate amount of
protein is admixed with all or a portion of the oil (fat)
component.
[0045] The PIW slurry was then added to the prepared oil blend. The
required amount of the carbohydrate, mineral and CSM slurry was
then added to the oil blend. The pH of the mixture was then
determined and if below specification, it was adjusted using KOH to
a pH of 6.75 to 6.85. The mixture was then held at 54-60.degree. C.
under agitation for at least 15 minutes.
[0046] The mixture was then heated to 68-74.degree. C. and
deaerated under vacuum. The mixture was then emulsified through a
single stage homogenizer at 6.21 to 7.58 MPa. After emulsification,
the mixture was heated to 120-122.degree. C. for 10 seconds and
then 149-150.degree. C. for 5 seconds. The mixture was then passed
through a flash cooler to reduce the temperature to 120-122.degree.
C. and then through a plate cooler to reduce the temperature to
71-79.degree. C. The mixture was then passed through a two stage
homogenizer at 26.89 to 28.27 MPa and 2.76 to 4.14 MPa. The mixture
was held at 73 to 83.degree. C. for 16 seconds and then cooled to 1
to 7.degree. C. At this point, samples are taken for
microbiological and analytical testing. The mixture was held under
agitation.
[0047] A calcium carbonate solution may be prepared for use in
adjusting the calcium level of the mixture if outside of
specification.
[0048] A vitamin stock solution was prepared. To water heated at 37
to 66.degree. C. was added potassium citrate and ferrous sulfate.
The vitamin premix was then added and the mixture agitated. The
choline chloride was added and then the required amount of this
vitamin mixture was added to the batch.
[0049] The nucleotide solution was then prepared. The following
nucleotides were added to water with mild agitation in the
following order: AMP, GMP, CMP, UMP. Agitation was continued for
about 10 minutes to dissolve the nucleotides. The nucleotide
solution was then added to the batch.
[0050] Lastly, an ascorbic acid solution was prepared and added
slowly to the batch with agitation for at least 10 minutes. Final
dilution with water to meet specified levels of solids and caloric
density was completed. The batch was then packaged in 0.9 Kg (32
ounce) metal cans and sterilized using conventional technology.
EXAMPLE II
[0051] Clinical Study Of Enteral Formula
[0052] The initial purpose of this clinical investigation was to
determine the effect of a nucleotide-fortified formula according to
the present invention on the development of the neonatal immune
system as measured by the antibody response to childhood vaccines.
This clinical investigation, also demonstrates that the inventive
oil blend (HOSO, SO and CO) provided an infant stool pattern that
closely resembles the breast-fed infant.
[0053] This was a 12-month, randomized, controlled, blinded,
multi-site trial of term infants. Infants enrolled into the study
received human milk (HM) or one of two clinically labeled formulas:
1) control formula (CON); or 2) CON formula supplemented with
nucleotides (NUC). The analyzed composition of each formula is set
forth in Table II. A total of 311 infants completed the study (107
CON, 101 NUC and 103 HM). Infants followed the immunization
schedule recommended by the American Academy of Pediatrics with
single lots of Hib TITER.RTM. Hemophilus influenzae type B
conjugate vaccine (Diphtheria CRM 197 and tetanus protein conjugate
sold by Lederle, Inc.) and Diphtheria and Tetanus Toxoids and
Pertussis Vaccine Adsorbed, sold by Lederle, Inc. Infants were full
term with a gestations age of 38-42 weeks, at or above the 5.sup.th
percentile for weight, length and head circumference and were
enrolled between 2 and 10 days of age. All subjects were healthy
with no indication of systemic disease and did not receive any
medications, mineral or vitamin supplements.
[0054] The primary outcome variable investigated was vaccine
response at 6, 7 and 12 months of age. Outcome variables also
included intake, anthropometry, and indicia of tolerance (stool
characteristics and incidence of spit-up).
[0055] Experimental Design
[0056] At 2, 4 and 6 months of age, DPT and Hib vaccines were
administered. Parents of the infants agreed to feed the infant only
study formula until 4 to 6 months of age when table foods were
added to supplement the study formula. The HM fed group were
exclusively breast fed up to 2 months of age and a mixture of HM
and Similac.RTM. with Iron (Ross Products Division of Abbott
Laboratories) after 2 months, if necessary.
[0057] Weight, length and head circumferences Were measured at 21
days of age and at 2, 4, 5,.6 and 12 months of age. Three-day
records of formula intake, frequency of spit-up and vomiting and
the frequency, color and consistency of stools were used to assess
tolerance.
[0058] Statistical Methods
[0059] Anthropometric data were analyzed for each gender
separately. Analysis of Variance (ANOVA) was done at birth, initial
visit, 2, 4, 6, 7 and 12 months of age for weight, length and head
circumference. Stool variables were ranked and analyzed with ANOVAs
(number of stools, mean rank consistency and percent of stools with
gas or unusual odor).
[0060] Results
[0061] Substantial amounts of data were collected on Leach of the
311 infants enrolled in this clinical investigation. Below is a
summary of the information that supports the novel and unobvious
features of the instant invention.
[0062] Growth of infants was similar in all three groups. Tolerance
and intake was similar for the two formula groups. The similarity
in growth and tolerance among all infants demonstrated that both
formulas are acceptable, however, for the first time, a stool
pattern similar to HM was found.
[0063] The anthropometric measurements indicate that growth was
comparable among all infants in the study. The fact that even
before controlling for birth values there were no differences among
males for weight, length or head circumference gives assurance that
growth was acceptable among all groups.
[0064] The higher stool frequency and number of feedings per day of
HM-fed infants compared to formula-fed infants during the first 2
months is well established. Softer stools of HM-fed infants are
also common. However in this study, the difference observed was in
the NUC group at 2 months and was only a small amount. Overall, the
measures of tolerance among all groups were very similar through 4
months when half the infants were still being exclusively
breast-fed. These data demonstrate both formulas were extremely
well tolerated and are set forth in Table IV. These data also
suggest that the inventive lipid blend produced infant stool
patterns very similar to infants consuming breast milk. This is a
surprising observation as stool patterns of prior art infant
formula were always harder than the stools of infants fed breast
milk.
7TABLE IV INTAKE AND TOLERANCE MEAN (SEM).sup.1 2 MONTHS NUC CON HM
100 107 103 Feedings (#/day) 6.2 (0.1) 6.2 (0.1) 7.7 (0.2) Intake
(mL/day) 831 (19) 823 (18) ND Spit-up (% of feedings) 8 (2) 18 (2)
20 (2) Stool Frequency (#/day) 1.6 (0.1) 1.4 (0.1) 2.7 (0.2) Stool
Consistency.sup.2 2.0 (0.1) 1.9 (0.1) 1.7 (0.1) 4 MONTHS NUC CON HM
98 107 103 Feedings (#/day) 5.9 (0.1) 6.0 (0.1) 6.6 (0.2) Intake
(mL/day) 987 (33) 926 (17) ND Spit-up (% of feedings) 22 (2) 18 (2)
20 (2) Stool Frequency (#/day) 1.4 (0.1) 1.4 (0.1) 1.5 (0.1) Stool
Consistency.sup.2 2.0 (0.1) 2.1 (0.1) 2.1 (0.1) .sup.1Values in the
same row with different superscripts are significantly different: P
< 0.05 .sup.2Mean rank consistency, where 1 = water, 2 = mushy,
3 = soft, 4 = formed, 5 = hard
[0065] These data also support an additional aspect of the instant
invention--lipid sources which are less than 10% by weight palmitic
fatty acid will provide stool patterns that are similar to
breast-fed infants.
EXAMPLE III
[0066] In this experiment an investigation of protein sources and
lipid sources were evaluated. A randomized and blinded tolerance
study was conducted. Two levels of each factor were studied:
Protein: 100% nonfat milk (CSM) or 64% by weight nonfat milk plus
36% whey protein; and Lipid: soy/coconut (conventional infant
formula oil blend) or HOSO, SO and CO (inventive oil blend)..
Infants were fed commercially available Similac.RTM. with Iron
(Ross Products Division of Abbott Laboratories, Columbus, Ohio)
during a 1 week baseline period and then randomized to receive one
of eight experimental formulas for an additional two weeks. Those
eight experimental formulas consisted of two groups of four
formulas which differed in method of manufacture. For purposes of
this application, the two groups were combined and thus four
formulas are reported herein. Eight (8) sites were used to recruit
infants, each having a birthweight greater than 2.5 Kg. Primary
outcome variables were stool frequency, stool consistency and
incidence of vomit and spit up.
[0067] The analyzed composition of each formula is set forth in
Table V. The protein system was either 100% CSM (nonfat milk) or a
blend of 64% nonfat milk and 36% whey protein (WP). The lipid blend
was either 60/40% by weight soy and coconut oils (SWI, a.k.a.
Similac with Iron) or 42/30/28% high oleic safflower, coconut and
soy oils (ALT, a.k.a. Alternative Lipid Test). Similac.RTM. wiith
Iron, manufactured by the Ross Products Division of Abbott
Laboratories, Columbus, Ohio, was used as a baseline nutritional.
Formulas were packaged in clinically labeled 0.9 Kg (32 ounce) cans
and provided 67.7 kcal/100 ml (20 kcal/fl.oz). All formulas met or
exceeded levels of nutrients as recommended by the Committee on
Nutrition of the American Academy of Pediatrics and the Infant
Formula Act, 1980.
8TABLE V ANALYZED COMPOSITION OF STUDY FORMULAS (PER LITER)*
Similac .RTM. NUTRIENT CSM/SWI CSM/ALT WP/SWI WP/ALT Baseline Feed
Protein, g 14.8 14.1 14.2 13.2 14.8 Source nonfat milk nonfat milk
whey, whey, nonfat nonfat milk nonfat milk milk Fat, g 36.9 34.7
36.3 34.5 37.3 Source SWI ALT soy and HOSO, soy soy and coconut
coconut oils and coconut oils oils Carbohydrate, g 79.3 74.6 73.6
70.3 73.3 Source lactose lactose lactose lactose lactose Minerals
Calcium, mg 560 525 537 514 544 Phosphorous, mg 463 334 333 321 476
Magnesium, mg 64.3 55.1 56.2 53.7 62.6 Sodium, mg 210 176 174 171
187 Potassium, mg 821 1010 952 949 837 Chloride, mg 510 493 519 488
512 Iron, mg 13.4 14.0 13.8 13.7 12.7 Vitamins A, IU 3161 3008 3081
2860 3194 E, IU 24.2 23.1 23.6 22.1 22.3 C, mg 120 164 91 144 269
Thiamine (B.sub.1), mg 1.48 1.41 1.43 Pyridoxine (B.sub.6), mg 0.48
0.50 0.48 0.48 0.48 : - based on compendium value for ash *8
batches were prepared, however, the batches of differing
manufacturing methods were combined for this study.
[0068] Parents were instructed to begin feeding their infants the
baseline formula immediately after enrollment and were given forms
to record the volume of each feeding, incidences of spit up and
vomiting, and stool characteristics during Days 2-7. At the Day 8
visit to the pediatrician's office, parents returned any unused
formula and were given the assigned study formula Dietary/stool
records were again completed daily during study days 9-21.
[0069] The analyses of variables were done to evaluate all main
effects and interactions. This study evaluated a number of
variables of which, only a few are presented herein. For each
variable, the effects of interest were tested using analysis of
covariates (ANCOVA) with baseline values as covariates. An
intent-to-treat analysis was carried out. All results were
considered statistically significant at the 0.05 level. Multiple
comparisons for significant effects in the ANCOVA models were
carried out by comparing least-squares means. A Bonferroni-type
adjustment was made to the individual P-values to ensure an overall
level of 0.05 for all comparisons.
9TABLE VI MEAN RANK STOOL CONSISTENCY* Factor Study Period Protein
WP Mean 2.1 CSM Mean 2.2 Lipid ALT Mean.sup.a 2.0 SWI Mean.sup.b
2.4 *= Values with unlike superscripts are significantly different
at P < 0.05 with a < b. Protein: WP = whey and nonfat milk,
CSM = nonfat milk; Fat: SWI = soy and coconut oils, ALT = high
oleic safflower, soy and coconut oils.
[0070] Stool Consistency
[0071] Mean Rank Stool Consistency, as set forth in Table VI,
clearly demonstrates that the lipid blend of this invention
produces a softening of infant stools. It was further determined
that type of protein had no measurable impact on stool
consistency.
[0072] A significant effect of lipid was observed for predominant
stool consistency. The data is reported in Table VII. The SWI lipid
blend was associated with firmer stools. The percentage of stools
of each consistency is shown in Table VII. An effect of lipid was
found in the watery, soft and formed categories of stool
consistencies with the SWI oil blend producing an overall firmer
stool.
10TABLE VII Distribution of Predominant Stool
Consistency.sup..Arrow-up bold. STUDY PERIOD Factor W L/M S F H
PROTEIN WP Mean 26 42 26 4 1 CSM Mean 25 39 27 7 3 LIPID ALT Mean
37.sup.a 37 20.sup.b 4.sup.b 2 SWI Mean 15.sup.b 44 33.sup.a
7.sup.a 1 .sup..Arrow-up bold.Values are average daily % of stools.
Values with unlike superscripts are significantly different at P
< 0.05 with a > b. W = watery, L/M = loose/mushy, S = soft, F
= formed, H = hard. Protein: WP = whey and nonfat milk, CSM =
nonfat milk; Fat: SWI = soy and coconut oils, ALT = high oleic
safflower, soy and coconut oils.
[0073] The main effect of the lipid component was on stool
consistency. This was due to a greater percentage of infants
experiencing a softer stool consistency with ALT. The results
indicate that ALT oil contributes to softer infant stools. The data
supports the conclusion that the ALT oil blend is associated with
softer, more watery stools.
EXAMPLE IV
[0074] Powdered Formula
[0075] In this experiment, powdered formulas having different oil
blends and protein sources were evaluated for their ability to
soften infant stools. As a result of the knowledge obtained from
Example IV, it was concluded that protein, as used in Example III
and this experiment, has no appreciable effect on stool
consistency. The Control formula was powdered Similac.RTM. with
Iron. The Experimental formula used a 64/36 weight % nonfat
milk/whey protein base and the inventive 42/23/30 weight %
HOSO/SO/CO blend.
[0076] A clinical study similar to those previously described, was
initiated. The two week study was completed by 30 Control-fed
infants and 27 Experimental-fed infants. After the initial baseline
feeding, stool data was collected from day 22 through day 34. The
results of the study are set forth in Table VIII.
11TABLE VIII Stool Characteristics PARAMETER CON EXP Mean Rank
Stool* 3.1.sup.a 2.1.sup.b Consistency Average Daily %** Watery
3.7.sup.b 24.2.sup.a Loose/Mushy 25.2.sup.c 45.9.sup.d Soft
40.sup.d 19.4.sup.c Formed 20.2.sup.b 8.4.sup.a Hard 10.9.sup.b
2.0.sup.a *Stool consistency ranked as watery = 1, loose/mushy = 2,
soft = 3, formed = 4, and hard = 5; categories were defined as
Watery - loose and runny; Loose/Mushy - spread over diaper, covered
with mucous; Soft - spread over diaper, pasty; Formed - has some
shape in diaper, yet moist; and Hard - well shaped and appears to
contain little water. **Calculated as % of individual's stools,
followed by deriving a mean value for all infants. .sup.a,bValues
in same row are significantly different, P < 0.01.
.sup.c,dValues in same row are significantly different, P<
0.05.
[0077] The data when analyzed as a percent of infants that reported
a predominance of stools in a given category is presented in Table
IX.
12TABLE IX Predominant Stool Consistencies % of Infants PARAMETER
CON EXP Watery 0 23 Loose/Mushy 21 46 Soft 46 27 Formed 21 4 Hard
11 0
[0078] Table VIII and IX clearly demonstrates that a significant
difference in distribution of stool patterns is achieved with the
inventive oil blend.
[0079] These recent extensive clinical studies support the results
originally reported in the parent patent application--the oil blend
of this invention provides a stool pattern that closely resembles
the stool pattern of breast-fed infants. Further, the use of the
novel oil blend of this invention addresses the reported concerns
association with conventional infant formula
[0080] Numerous additional studies have been conducted which are
only redundant to the work reported herein. This extensive and
costly research has advanced the state of the art of human
nutrition and forms the basis of the claims presented in this
application.
INDUSTRIAL CAPABILITY
[0081] The results from these experiments demonstrate that the
enteral formula of this invention is effective in producing stool
patterns that are similar to breast-fed infants and that problems
typically associated or perceived to be associated with
conventional infant formula, especially iron fortified formula, can
be alleviated through the use of the novel oil blend of this
invention. The medical community is constantly searching for
nutritional formulas that will benefit the infant. The present
invention can clearly fill that need. The manufacture of the
formula utilizes conventional equipment and may be readily
accomplished.
[0082] While the infant formula and method of making said formula
herein described constitute a preferred embodiment of this
invention, it is to be understood that the invention is not limited
to this precise formulation or method and that changes may be made
therein without departing from the scope of the invention which is
defined in the appended claims.
* * * * *