Note: Descriptions are shown in the official language in which they were submitted.
~2~
This invention relates to an edible fat product
for incorporation into an infant food formula.
In recent years, effort has been directed at
producing a milk-based infant formula which is similar to
human milk. For example, Canadian Patent No. 927,187
discloses a dietary product which may be added to com-
mercially available cow's milk. ~he dietary product is
intended to adapt the cow's milk to the requirements o~
human nursing and to make the cow's milk similar to
human milk. The lipid component of the dietary product
is preferably a mixture of ve~etable oil with soy lec-
ithin and eventually with milk fats.
Canadian Patent No. 927,188 discloses an edible
fat composition intended to resemble that of human milk
fat. The composition comprises various proportions of
oleic oil; oleo oil; a seed oil comprising one or more
of soybean oil, corn oil, peanut oil, sunflower seed oil
and cottonseed oil; coconut oil and/or babassu oil; and
soy lecithin.
The dietary products and fatty acid compositions
disclosed in the above patents relied upon edible oils,
50y lecithin and/or milk fats to form the lipid component.
However, these oils do not contain the C20 and C22, ~-6
and ~-3 ~atty acids which are present in human milk.
Accordingly, these dietary preparations do not provide a
~2~71)~3
balance of fatty acids that are similar in composition
to that of human milk.
I
It is now known that the composition of dietary
fat is a major determinant of tissue composition during
the formative stage in the growth and development of an
organ. Recently, the fatty acid content of fetal tis-
sues was utilized to estimate essential fatty acid ac-
cretion during intrauterine growth ~Clandinin et al,
Early Human Development, 1981, 5 : 355-366). This study
calculated that intrauterine synthesis of adipose organs
utilized some 285 mg. per day of C20 and C22, ~-6 fatty
acids and some 47.4 mg. per day of C22, ~L3 fatty acids.
It was found that an adequate intake of mothers own milk
would provide from 90 mg. to 130 mg. of -C20 and C22, ~-6
lS fatty acids per day and 55-75 mg. of C20 and C22, ~-3
fatty acids per day. An earlier study (Clandinin et al,
Early Human Development, 1980, 4 , 121-129) investigated
fatty acid components of infant brain during the last
trimester of development in the fetus. Marked subst-
antial accretion of C20 4, ~-6 and C22 6 r
occurred.
In view of the above studies, dietary formulas
for the premature or pre-term infant should contain C20
and C22, ~6 fatty acids and C20 and C22, ~-3 fatty acids
to promote healthv orcwth-noXmal~Y Occu~ring intrauterine. In
~244~0~
-4
view of the second study referred to, such fatty acids
have particular significance for the synthesis of struc-
tural lipids in brain tissue. Howeverr this study did not
suggest any means of determining the quantities of these
fatty acids required in such a formula.
In the first study referred to above, fatty acid
analysis oE human milk at day 16 of lactation was utili-
zed to estimate for the first time the pre-term infants'
daily intake of C20 and C22, ~-6 and ~-3 fatty acids. ~he
study indicated that significant amounts of these fatty
acids are normally received by the infant fed human milk.
.
Past studies have not resolved the nutritional
biochemical question of how much and which essential fatty
acids should be provided in a dietary formula to premature
infants to ensure normal synthesis of nerve tissues. Such
tissues would normally contain high levels of long-chain
metabolites of essential fatty acids as basic structural
material. In particular, it is important that the quant-
C20 and C22, ~-6 and ~-3 fatty a id
limited to appropriate ranges in a dietary formula. Tn-
sufficient supply of these fatty acids would curb brain
development. Over-feeding of these fatty acids could
distort normal prostaglandin metabolism and thus have
adverse-effects on the infant's physiolo~y. For example, providing
boo much of these fatty acids could result in over-~roduction of
prostaglandins in the gut, which could lead to a hyperactive gut
and diarrhè~:
~4~08
--5--
Studies on the composition of human milk have
identified further substances not found in many cows milk-
based formulas. Recently, it has been shown that human
milk contains physiologically active concentrations of
prostaglandins, specifically prosta~landin E2, pros-
taglandin F2~ ~ and the metabolite of prost3glandin I2
namely 6--keto prostaglandin Fl~, . These prostaglandins
and their metabolites are present in human milk at all
stages of lactation and change in concentration during
lactation in a manner analogous to the development of
the infant'~s capacity to absorb nutrients. For example,
in approximately the first three weeks of infant life,
the level of these prostaglandins and their metabolites
increases in human milk as does the infantls capacity to
absorb nutrients.
It has been known in man that prostaglandins
affect functions related to nutrient absorption. Thus, in
the human a variety of physiological functions are affected
in the gut by prostaglandins e.g. gastric acid and mucous
secretion, smooth muscle contraction , local circulation,
nutrient transport and absorption.
However, the presence of prostaalandins and their
metabolites in human milk has not been previously recognized.
Consequently the potential of prostaglandins and their
metabolites in milk to influence gastrointestinal physiology
7~
in newborn infants, and thus the rates of nutrient absorp-
tion for infants fed human milk, has not been appreciated.
The present invention provides information on
the range of prostaglandin content that would stimulate
S benefits to infants fed semi-synthetic or milk based
infant formulas.
An object of the present invention is to pro-
vide a stable liquid infant formula with an improved
fatty acid composition having suitable shelf life.
A further object of the present invention is
to provide an edible fat product for incorporation in a
formula suitable for pre-term infants which will contain
appropriate levels of the C20 and C22, ~-6 and ~ 3 fatty acids
to promote normal brain development and healthy growth.
_ ~5 A further object of the present invention is to
pro~ide an improved infant formula containins prostaglandins
and a metabolite.
According to one aspect of the invention, an
edible fat product is provided for incorporation in a
formula suitahle for feeding infants. The product
comprises at least one ~f the following:
(a) at least one member of the group of C2o,u~-6
fatty acids and C22, ~-6 fatty acids, wherein the total of
said C20,~ -6 and said C22, ~-6 fatty acids is about
0.13-5.6% by weight of all fatty acids in the product;
lZ4~L708
tb) at least one member of the group of C2o~u~-3
fatty acids and C22,UJ_3 fatty acids, wherein the total of
said C20, ~-3 and said C22,~_3 fatty acids is about n.013-3.33%
by weight of all fatty acids in the product.
According to a further aspect of the invention,
a formula is provided which is suitable for feeding infants.
The formula comprises at least one of the following:
(a) at least one member of the group of C20,
~ -6 fatty acids and C22, ~ -6 fatty acids, wherein the
C20, 6 and said C22,U~-6 fatty a id
about 5-100 mg. per 100 mls. of the formula;
(b) at least one member of the group of C20,
~L3 fatty acids and C22, ~-3 fatty acids, wherein the total
of said C20, ~-3 and said C22,~-3 fatty acids is about
0.5-60 mg. per 100 mls. of the formula.
According to a further aspect of the invention,
a formula is provided which is suitable for feeding infants.
The formula comprises at least one of the following:
(a) prostaglandin E2 in a concentration of
about 50 -1000 nanograms per 100 mls. of the formula;
(b) 6-keto prostaglandin Fl~ in a concentration
of about 20-300 nanograms per 100 mls. of the formula;
(c~ prostaglandin F2~ in a concentration of
about 25-300 nanograms per 100 mls of the formula.
-8- 12~4~08
The milk of more than fifty mothers of full-
ter~ infants and pre-term infants were sampled between
day 4 and day 150 of lactation. Each mother was sampled
over 10 different days of lactation, ~nd on s~ecific days was
sampled 6 times over 24 hours. From analysis of the
samples, the fatty acid composition of human milX by
weight was determined (Table ~). The amount of each
of the fatty acids in Table 1 is expressed as a percentage
of the total of the fatty acids in the milk by weight~
n In Table 2, the concentration of various
fatty acids is expressed in mg. per 100 mls of human
milk.
From the above analysis, it was observed that
the total concentration of C20 and Cz2, ~-6 fatty acids
in any of the samples was at least 5 mg. per 100 mls of
human milk. Similarly, the lower limit to the total
concentration of C20 and C22, u~3 fatty acids for all
of the samples was about 0.5 mg. per 100 mls of human
milk. These lo~er limits were used as a starting point
2~ for determining the ranges of the w 6 and ~-3 fatty acids
in the infant formula (as indicated below).
In order to provide an appropriate source of
structural lipids for use in new tissue synthesis and as
an energy substrate, each 100 mls of infant formula
25: should contain about 2. 8 + 1. 0 grams total of fatty acid.
124~70~3
g
TABLE 1: Patty Acid Composltion ~f Human ~llk
Fatty Acid ~% w/w)Human Milk
Short chain 2.0 ~ 0.6
Medium chain 11 + 1.7
C16:0 20 ' 2.4
Cl~:l 3.2 ~ 0.3
Cla:0 5.8 ~ 0.7
C18:1, w-g 38 + 2.9
C18:2~ W-6 12 + 4.3
Cl8~3, ~-3 0.9 1 0.4
C20:4- ~-6 0.5 ~ O l
C20 and C22 ~-61.0 + 0.2
C2~:5' 0.125 t 0,04
C22:6' 0,36 + 0.032
C22, ~ -3 0.52 + 0.063
C20 and C22 ~-30.7 ~ 0.2
C20 0, C22 0, C24:00.5 + 0.1
Other fatty acids~ 4.4
1) Mean ~ SDx for n - 16
12~4'708
--10--
TABLE 2: Fatty Acid Intake Provided by Human Milk
~ I
Fatty AcidFatty Acid Intake ~ g/100 mls)
Short Chain3 216 +24
Cl4:0 214 +24
C16:0 465 ~25
C18:0 147 +17
c2o o 5.2 + 1.3
C22:0 2.5 + 0.5
C24:0 0.4 + 0.2
C18:2~ 288 l60
C18:3~ ~-6 0.8 + 0.4
C20:2, ~-6 9.8 + 2
C20:3, ~-6 9.4 + 1.4
C20:4, ~-6 13.9 + 0.8
C22:3, ~-6 1.8 ~ 0.3
C22:4, ~-6 3.4 + 0.3
- C22:5, ~-6 1.7 + 0.3
Total ~-6 328 +63
C18:3, ~-3 28.5 + 5.9
cls:4~ ~-3 7.6 + 1.3
C20:4, ~-3 1.5 + 0.5
C20:5, ~-3 3.2 + 0.8
C22:5, ~-3 3.4 + 0.3
C22:6~ ~-3 9.1 ~ 0.8
Total ~_ 3 53.4 + 6.4
C14:1 2 + 0.4
C16 1 81.~ +43-5
~ 8 1 gO8 +43.5
C24:1 2.2 + 0.5
Total Fatty Acid2558 +133
Values (x + SE-2 ) are given for mothers delivering an infant after
28-32 weeks of gestation.
2The level of energy intake used for calculation was 120 kcal/kg body
weight/day based on ~ 1300 gms body weight.
3Includes fatty acids from CB to C12.
LZ~470~3
If 3.8 grams total of fatty acid are incorporated into
the infant formula, then in order to have a concentration
of at least about S mg. total of the C20 and C22, ~-6
fatty acids per 100 mls of the formula, these fatty acids
must comprise at least about 0.13% by weight of all the
fatty acid incorporated in the formula. Similarly, in
order to have a concentration of at least about 0.5 mg.
total of the C20 and C22, ~-3 fatty acids per 100 mls of
for~ula when 3.8 grams total of fatty acid are incorp-
orated into the formula, at least about 0.013~ by weight
of the total fatty acid incorporated should be these ~-3
fatty acids.
It was determined that when the total of the
C20 and C22, ~-6 fatty acids was between abou-t 5 mg. to
100 mg. and the total of the C20 and C22, ~-3 fatty acids
was between about 0.5 mg. to 60 mg., per 100 mls of
infant fonm~a, these ranges separately or in ccmbination could be
achieved without unduly distorting the balance of the fatt~ acid
ca$~nents which it was atte~pted to formLlate. That is,~these
?n ranges are consistent with physiologically acceptable
concentrations of the fatty acids. In order to achieve
a concentration of 100 mg. total of the C20 and C22, w-6
fatty acids per 100 mls. of formula when 1.8 grams of
total fatty acid are incorporated in the formula, about
5.6~ by weight of the fatty acid incorporated should be
these ~-6 fatty acids. Similarly, to achieve a total
of 60 mg. of the C20 and C22, ~-3 fatty acids per 100 mls
of infant formula, if 1.8 grams total fatty acid is in-
-12~ 7~
corporated in~o the formula, then about 3.33~ by weight
of the fatty acid incorporated should be these ~-3 fatty
acids.
Accordingly, the total of the C20, ~-6 fatty
acids and the C22, ~-6 fatty acids is about 0.13 - 5.6
by weight of all fatty acids in the fat product. The
total of the C20, ~-3 fatty acids and the C22, ~3 fatty
acids is about 0.013 - 3.33~ by weight of all fatty acids
in the fat product.
lC Preferred ranges may be selected which more
closely reflect the biological variation in fatty acid
concentrations present in human milk. Thus, preferably,
each 100 mls. of the formula contains a total of about
0.5-40 mg. of said C22, ~-3 fatty acids.
More preferably, each 100 mls. of the formula
contains about 15-70 mg. total of said C2o,~-6 and said
C22, ~-6 fatty acids, about 2-25 mg. total of said
C20, ~-3 and said C22, ~-3 fatty acids, and about
2-25 mg~ total of said C22,~ -3 fatty acids.
Studies have sugaested that the human fetus
utili7es large quantities of C20 4, ~-6 and C22,~ -3
(primarily C22 6, ~-3) fatty acids for synthesis of
human brain. Studies have further suggested that C20 5,
~-3 fatty acids are a precurser for Series 3 Prostaglan-
dins, and for C~2 5,w -3 and C22 6, w-3 which are normal
components of neural tissues In order that the nutritional
support of the pre-term infant should provide for feeding of these
co~x~ents, each 100 mls. of the formMla preferably oontains a total
~;~447~3
-13-
of about 5-80 mg. of the C20 4, ~ -6 fatty acids, about
1-40 mg- of the C22 6~ ~~3 fatty acids, and about 0.5-
15 mg. of the C20 5, ~-3 fatty acids. These ranges are
consistent with physiologically acceptable concentrations
of the fatty acids. More preferably, each 100 mls. of the
formula contains a total of about 10-70 mg. of the C20 ~,
W-6 fatty acids, about 5-22 mg. of the C22 6~ ~~3 fatty
acids, and about 2-8 mg. of the C20 5, ~-3 fatty acids.
I'hese ranges more closely reflect the biological variation
in fatty acid concentrations present in human milk.
Preferred percentage ranges can then be calculated
from the last three paragraphs. Thus, preferably the
total of the C22 ~-3 fatty acids is about 0.013-2.22% by
weight of all fatty acids in the fat product incorporated
in the formula.
More preferably, the total of said C20, ~-6
and said C~2~W -6 fatty acids is about 0.39~3.9% by
weight of all fatty acids in the fat product, the total of
said C20, ~-3 and said C22, ~-3 fatty acids i~ about
0.05-1.39~ by weight o~ all fatty acids in the product,
and the total of said C22, ~-3 fatty acids is about 0.05-
1.39% by weight of all fatty acids in the product.
Similarly, the total of the C~0 4, ~-6 fatty
-14-
12~7C~3
acids is preerably about 0.13 - ~.44%, the total of
the C22 6' ~~3 fatty acids is preferably about 0.02 -
2.22~, and the total of the C20 5, ~3 fatty acids is
preferably about O.Ol - 0.83~, by weight of all fatty
acids in the fat product. More preferably, the total of
the C20 ~, ~-6 fatty acids is about 0.26 - 3.9%, the
total of the C22 6, u~3 fatty acids is about 0~13 - 1.22%,
and the total of the C20 5, ~-3 fatty acids is about
0.05 - 0.44%, by weight of all fatty acids in the fat
product. These ~ercenta~e rangeswere determined using the
preferred milligram ranges given on the last two panes.
The peroentage ranges were calculated as des~ribed above
for the total C20 and C22, ~-6 an~ ~-3 pero~ntage ranges,
In order to achieve fatty acid compositions within
l~ the above specified ranges, the edible fat product is pre-
ferably a blend of egg yolk lipid and at least one member
of the group of coconut oil and soyabean oil. Preferably
the egg yolk lipid in the blend is about 75-95 parts by
weight, and the total of the coconut oil and the soyabean oil
in the blend is about 5-25 parts by weight. Alternately, the
fatty acids may be derived from phospholipids of red blood
cell membranes. Most preferably, the fatty acids are derived
from a blend of about 5-25 parts coconut oil and about 75-95
parts egg yolk lipid by weight, or a fat source o~ similax
composition. The approximate fatty acid composition of coconut
oil and egg yolk lipid is shown in Table 3.
. . .
-
12~47~)8
TABLE ~: Fatty Acid Composition of Natural Fats ~tilized in the
Lipid Formulation
_ ~
Fatty Acids_(% W~ ~Coconut Oil Egg Yolk Lipid
Short chain 14.1
Medium chain 60.1 0.36
Cl6 0 8.2 26.1
C16:1 0.4 3.32
Cl~:0 3.0 lQ.2
C18~ ~9 5-7 37.1
1;~ C18:2, ~-6 1.8 10.7
C16:3. ~~3 - 0.35 -
20:4' 6 1.5~2.8
C20 and C22, ~ -6 1.5-3.96
C20 5, ~ -3 0-0.095
~- C22:6' 3 0.5-0.85
C22, -3 0.5-1.1
C20 and C22, ~ -3
C20:0- C22:0~ C24:0 0;9 0.1
Other fatty acids 5.8 5.25
-16- ~2~
The values in Table 3 indicate ranges for
the concentrations of C20 and C22, uL6 and ~-3 fatty
acids in the egg yolk lipid. It will be appreciated that
the concentrations of fatty acids in the egg yolk lipid
will vary somewhat depending on the source of the egg
yolk.
Table 4 shows the approximate fatty acid
composition of one blend of about lO parts of coconut
oil and 90 parts of egg yolk lipid. From a comparison
of Tables l and 4, it will be seen that using this blend
of egg yolk lipid and coconut oil, the fatty acid com-
position achieved is relatively similar to that of human
milk. ThiC shows an advantage of usina a blendpartly derived
rom egg yolk lipid, or a source of fatty acids of similar
composition to egg yolk lipid. However, it will be ap-
preciated that other sources of the fatty acids can be
used.
A further advantage to using egg yolk lipid as
a source of fatty acids is that the C20 and C22, ~-6
and ~3 fatty acids are then derived from a natural fat.
~oreover, the edible fat product of this invention has
beneficial effects on the synthesis of brain tissue, and
on the absorption of calcium, and is absorbed in the gut
at a high rate. Therefore the fat product is especially
suited for incorporation into an infant formula partic-
ularly adapted for total nutritional support of the
human infant.
-17- ~2~7~
\
TABLE 4: Approximate Fatty Acid Composition of a blend of
Coconut Oil and Egg Yolk Lipid
Fatty Acid t% wLw )Fat Blend
Short chain 1.4
Medium chain 6.3
C16:0 24.3
C16:1 3.1
C18:0 9 3
C18:1' ~9 34.0
C18:2' 6 9.8
C18:3' 3 0.32
C20:4' 6 1.35-2.52
C20 and C22,~ -6 1.35-3.56
C20:5' 3 0-0.086
C22 6, ~-3 - 0.45-0.77
C22,~-3 0.45-0.99
C20 and C22, ~-3 0.45-0.81
C20:0' C22:0' C24:~ 0.2
Other fatty acids 5.5
20 1) Approximately 10 parts coconut oil and 90 parts egg yolk
lipid.
-18-
Preferably the fat product of this invention
is incorporated into an aqueous infant formula further
comprising a sugar, non-fat milk, water and optionally
a protein source.
In addition to the edible fat product, the
infant ormula preferably comprises a source of macro-
nutrient, i.e. protein and carbohydrate,and an appropriate
combination of minerals and vitamins. A typical protein
source would be electrodialysed whey or electrodialysed
skim milk or milk whey, although other protein sources
are also available and may be used~ Sugars would include
food substances such as glucose or edible lactose. The
infant formula would preferably include the following
vitamins and minerals: calcium, phosphorous, potassium,
sodium, chloride, magnesium, manganese, iron, copper,
zinc, selenium, iodine, and Vitamins A, E, D, and the
B complex. These micronutrients would be added in the
form of commonly accepted nutritional compounds in
amounts equivalent to those present in human milk on an
energy basis, i.e. on a per calorie basis. Water is
included to obtain an aqueous suspension of nutrients
pr~.iding the appropriate essential nutrient to energy
-
~4~ 8
--19-- I
balance contained within an appropriate fluid volume.
More preferably, the infant formula comprises '~I
an aqueous suspension containing in each 100 mls 2.8 +
1.0 gm. of fatty acid derived from a blend of egg yolk
lipid and coconut oil, or fat of similar fatty acid
composition so that the formula contains the C20 and
C22, ~-6 and ~-3 fatty acids within the appropriate ranges
of concentrations set out above. The infant formula in
each 100 mls. further preferably comprises 2.~ + 1.0 gm.
of protein source, 10 + 5 gm. of sugar.
Table 5 shows an example of an appropriate
nutrient composition for a ready-to-feed infant formula
suitable for pre-term infants. The fat soluble vitamins
can be dissolved in the fat blend and the remaining
formula inaredients can be dissolved in the water. The
fat blend with the dissolved vitamins and the water
solution can then be mixed and homogenizedr Adequate
amounts of other trace minerals are present in the
electrodialysed whey and non-fat milk.
The infant formula can be sterilized and
subsequently utilized on a ready-to-feed basis or stored
as a concentrate. The concentrate can be prepared by
spray dryin~ the infant formula prepared as indicated
above, and the formula can be reconstituted ~y rehyd-
rating the concentrate. Moreover, the infant formula is
~5 a stable liquid and has a suitable shelf life.
~2~L7~)8
-20-
TABLE 5: Appropriate nutrient composition of a Proposed
Formula for feeding of Preterm infants.
Amounts per 100 mls
Fatty acid (Fat blend of coconut oil,
soyabean oil and egg yolk
lipid, or fat source of
similar composition) 2.8 g
Lactose 8 g
Protein (Electrodialysed Whey and non-fat
milk) 2.1 g
Vitamin A USP units 265
Vitamin D USP units 42
Vitamin E I.U. 0.6
Vitamin Bl (Thiamine HCl) 0.07 mg
PartotheniC Acid 0.21 mg
Vitamin B2 (Riboflavin) 0.11 mg
Vitamin C (Ascorbic Acid) 5 3 ~5
Vitamin B6 (Py~idoxine HCl) o ~ J~g
Vitamin B12 (Cyanocobalamin) 0.11 mg
Niacinamide 0.53 mg
Fol~c Acid 3.2 mg
Calcium 42 mg
Phosphorus 33 m~
Sodium 15 mg
Potassium 55 mg
25- Chloride 41 mg
Mangesium 6.0 mg
Iron 0.85 mg
Copper n. 04 mg
Zinc 0.32 mg
Iodine 6.9 meq
Selenium 0.01 ~ug
Water to 100 ml volume
Choline 9 mg
Inositol 10 mg
'5 Manganese 1 ~g
`` -21- ~2~708
~able 6 shows the approximate range of prosta-
glandin content of human milk for certain prostaglandins
and a metabolite.
Appropriate ranges for the prostaglandins
and the metabolite of Table 6 can be selected which are
consistent with physiologically acceptable concentrations
of these compounds. Thus, it was determined that when
the total of the prostaglandin E2 was between about 50-
1000 nanograms, the total of the 6-keto prostaglandin Fl_~
lO was between about 20-300 nanograms, and the total of the
prostaglandin F2~ was between about 25-300 nanograms,
per lO0 mls, of infant formula, these ranges separat~ly
or in combination could be achieved without unduly dis-
torting the balance of the components which it was
attempted to formulate.
Preferably, each lO0 mls. of the formula
contains at least one of the follo~ing:
~a) a total of about 200-500 nanograms of
prostaglandin E2;
(b) a total of about 25-50 nanograms of 6-keto
prostaglandin FlX;
(c) a total of about 25-lO0 nanograms of
prostaglandin F2~.
-22- ~ ~fl~7~
TABLE 6: Approximate Content of Human Milk for Certain
Prostaglandins and a Metabolite
.~mounts (ng/lO0 mls?
Prostaglandin E2 100-800
6-Keto Prostaglandin Fl~ 25-200
Prostaglandin F2 ~ 25-200
~2'~L~7~38
-23-
The latter ranges more closely reflect the bio-
logical variation in concentrations of these compounds
present in human milk.
These compounds can be added with the fat
during preparation of the above or other infant formulas.
The co~pounds can also be added to the above or ct~r i~fant formulas
as a sterile preparate af~r the heat sterilization stage.
These prostaglandins and metabolite are
available from the Up50hn company as 0.5 mg. tablets
or 0.5 mg./cc. ampule injectible solutions. However,
preferably the compounds are added in the pure form.
Alternately the-sterile preparate can be prepared from
ampules of these or other injectible solutions.
The invention will be more fully understood by
reference to the following examples. However, these
examples are merely intended to illustrate embodiments
of the invention and are not to be construed to limit
the scope of the invention.
Examp~e I
About 2.52 grams of fatty acid extracted from
egg yolk was combined with about 0.28 grams of coconut
oil. This fat blend was thoroughly homogenized at 35DC
just before use.
It was calculated that the edible fat product
represented ~v this fat blend compris2d
-24-
-` ~2~47~8
approximately the following fatty acids (based on
the approximate fatty acid values shown below for the
egg yolk lipid used):
Fatty Acids (% w/w) Egg-Yolk Lipid Fat Blend
C20:4' 6 2~1% 1.89%
C20 and C22,W -6 2.3% 2.07%
C20:5' 3 0.1% ~ 0.09%
C22:6' 3 0.65% 0.59%
C22, ~-3 0.8% 0.72%
lO C20 and C22, 3 0.81%
Example II
~ on-fat milk of sufficient volume to result in
a final volume of lO0 mls of formula was heated to 93C
under constant agitation~ The agitation was maintained
15 during the heating process but foaming was avoided. The
non-fat milk was heated rapidly to 93C to 96C and
maintAined at this temperature for 30 - lS0 seconds.
~470~3
-25-
The heated milk was then immediately cooled
by addition of other formula ingredients in the following
order: electrodialysed whey, the fat blènd from Example
I as a freshly prepared homogenate, and lactose, vitamins
and minerals according to their concentrations in Table 5.
Sufficient electrodialysed whey was added to make up a
total of about 2.1 grams of protein, including the protein
derived from the non-fat milk. The total mlxture was
mixed at about 57C - 60C. The total mixture was
then rapidly heated to 71C, homogenized and sterilized
at a temperature of 113C for three minutes. The pre-
pared formula was rapidly cooled to room temperature and
stored as a ready-to-feed form having a solids concen-
tration of about 12.4% w/v.
By means of the concentrations for the
C20 and C22, ~-6 and ~L3 fatty acids ~iven in ~xample 1, it was
calculated that the 100 mls of infant formula comprised
the following fatty acids:
C2o 4~-6, about 52.9 mg
C20 & C22, ~-6, about 58 mg.
C20:5r ~~3, about 2.5 mg
C22:6~ ~~3~ about 16,4 mg.
C22, ~-3, about 20.2 mg.
C20 ~ C22'~ ~3~ about 22.7 mg.
-26- ~2~7~8
Preferably, the solids concentration o~ the
liquid processed is in a range from about 12 - 25% by
volume. At this solids concentration, the processing
conditions specified in Example II can be maintained.
Preferably, the infant formula in ready-to-feed form
has a solids concentration of about 12.4% ~w/v.
However, it will be appreciated that a more
concentrated liquid may be prepared, provided that it
can be diluted to the desired volum~ containing-approxi-
mately 12.4% w/v solids.
Alternately, on cooling of the infant formulait may be spray dried and stored for future use without
further stabilization or treatQent of any kind. This
enables a dry concentrate of the infant formula to be
stored in a powder form. The dry concentrate can be
diluted with water at any time to the desired volume
containing approximately 12.4% w/v solids.
Example III
To the fat blend from Example I, the following
0 was added, expressed here per kilogram of fatty acid:
80 micrograms of prostaglandin E2;
10 micrograms of 6-keto prostaglandin Fl~;
10 micrograms of prostaglandin F2~.
-27- ~2~7~8
The infant formula was prepared as described in Example II.
Based on 2.8 gm. total fatty acid, it was cal-
culated that 100 mls. of the infant formula comprised the
following prostaglandins and metaholite:
prostaglandin E2, about 224 nanograms
6-keto prostaglandin F~, about 28 nanograms
prostaglandin F2~, about 2~ nanograms
It will be appreciated that the invention is
not limited to the particular embodiments described
above, since many modifications may be made by one skil-
led in the art. For example, with minor modification,
the infant formula of this invention is also appropriate
for nutritional support of term infants, for alimentary
use in states of convalescence and for use in aged subjects.
~24L~L7G18
27a
SUPPLEMENTARY DISCLOSURE
An alternate and preferred source of the
C20 and C22, ~-6 and ~-3 fatty acids is fish or
marine oil. Without limiting the foregoing, such
fish oils as Tilapia, ~lenhaden, Herring, Caplin and
mixtures thereof, can be used. The amount of fish
oil needed to achieve the desired range of the C20
and C22,~ -6 and ~ -3 fatty acids will vary according
to the particular fish oil used. ~lso, the fatty acid
composition of fish oils is subject to season differences.
The C20 and C22, ~-3 and ~ -6 fatty acids derived
from fish or marine oil are preferably blended with
an oil of vegetable origin in order to more closely
approximate the fatty acid content of human milk. Such
oils include, without limiting same, coconut oil,
soyabean oil, cocoa oil, palm oil, oreo oil, sunflower
oil, and mixtures thereof. Other suitable vegetable oils
will be evident to persons skilled in the art.
~24~4~
27b
.
ExampIe IV
In accordance with the procedur~ described in
Example I, an edible fat product was prepared by
blending together, on a weight basis, 16~ fish oil
(Tilapia), 10% cocoa oil, 13% palm oil, 10% oreo oil,
26% sunflower oil, 13% coconut oil and 12% soyabean oil.
This fat blend was then incorporated into an infant
formula, in accordance with the procedure described in
Example II. The fatty acid content of this formula is
compared to the fatty acid content of a similax formula
based on egg yolk lipid and coconùt oil in Table 7.
`~
70~3
- -- .. -
- 27c -
TA~LE 7
. . .
Fatty acid composition of formulas prepared with egg yolk
lipid and fish oil:
Fatty acids (~ w/w)with egg Yolk oilwith fish oil (TILAPIA)
short chain fatty acids 1.00 1.95
C12 0 5.69 6.46
Cl~ 0 2.62 4.55
C16 0 22.70 19.21
C16:1 3.94 2.44
C18:0 11.94 8.08
C18:1 ~9 38.97 39.30
C18:2 ~6 lI.49 12.22
C18:3 ~3 0.46 1.6&
c2o o 0.11 0.20
C20:1 ~9 0.22 0.04
C20:2 ~6 0.10
C20 3 ~6 0.07 0.02
C20:4 ~6 0.25 0.13
C22 4 ~6 0.05
C22 5 ~.6 ~ 0.03 0.06
20 and C22 ~6 0.50 0.21
C20:3 ~3 0.13
C20:4 ~3 ~ 0.12
C20:5 ~3 2.03
22:3
C22:4 ~3 0.32
C22 5 ~3 0.04 0.70
C22:6 ~' 0.07
20 and C22 ~3 0.11 3.30
J
