Note: Descriptions are shown in the official language in which they were submitted.
1 3 ~ 2
-- 1 --
SPECIFICATION
NUTRITIONAL SUPPORT OR THERAPY FOR INDIVIDUALS AT
RISK OR UNDER TREAIMENT FOR ATHEROSCLEROTIC,
VASCULAR, CARDIOVASCULAR, AND/OR THROMBOTIC DISEASES
The present invention relates to
nutritional formulations for the support and therapy
of individuals. More specifically, the present
invention relates to nutritional compositions for
supporting and/or providing therapy to individuals at
risk and/or under treatment for atherosclerotic,
vascular, cardiovascular, or thrombotic diseases.
For some time investigators and scientists
have noted a relationship between diet and the heart
function and related systems. There has always been
an appreciation for the cardiovascular effects of
obesity and the recognition of widespread prevalence
of undernutrition in hospitalized patients with
cardiovascular derangements. Accordingly, there have
been many attempts to formulate nutritional support
for patients at risk for or exhibitin~
a~herosclerotic, vascular, cardiovascular, and/or
thrombotic diseases. Poindexter, et al, Nutrition in
Congestive Heart Failure, Nutrition In Clinical
Practice (1986) recognize that specific nutritional
deficiencies may cause, precipitate, or aggravate
acute heart failure. As Poindexter, et al, point
out, nutritional deficiencies have been significant
factors in the e~iology of heart failure in the
Orient and developing countries. It is further noted
that nutritional therapy for malnourished cardiac
patients in recent years has been considered
essential supportive therapy.
1 3 ~
-- 2 --
Patients suffering from long term
congestive heart failure have been found to suffer
from cardiac cachexia. Other effects of
protein-calorie malnutrition on the heart include
hypertension, reduced heart rate, reduction in basal
metabolic rate and oxygen consumption, atrophy of the
heart muscle mass, electrocardiogram (ECG)
abnormalities, and heart failure. Furthermore, when
congestive heart failure occurs secondary to valvular
heart disease that is treated surgically, nutritional
status has a notable effect on the suryical
outcome. Performing cardiac surgical procedures on
patients in a state of nutritional depletion can
result in increased morbidity and mortality, compared
to adequately nourished patients.
Typically, patients suffering from
congestive heart failure are underweight with poor
nutritional status. Patients with congestive heart
failure and cardiac cachexia frequently exhibit
anorexia and early satiety. Poindexter, et al, state
that this is attributed to the natural compensatory
mechanism that decreases work of the failing heart.
Furthermore, due to hepatic congestion that increases
pressure in the abdominal cavity, there is a constant
feeling of fullness. Moreover, altered taste
sensations and intolerances to food odors limit the
patient's desire to eat. Accordingly, liquid
nutritional supplements high in nutrient density are
desirable. However, as Poindexter notes, this must
be tempered with concern about the complications
caused by overzealous refeeding of malnourished
cardiac patient.
7 ~
Not only are patients with congestive heart
failure and other vascular diseases typically
underweight with poor nutritional status, but their
energy requirements are greatly in excess of a normal
individual's energy requirements. Poindexter, et al,
note that energy requirements of a patient with
congestive heart failure may be 30-50 percent in
excess of basal energy expenditure because of
increased cardiac and pulmonary energy expenditure.
Indeed, cachectic patients require additional
calories for repletion and post-operative cardiac
patients require still further increases in caloric
intake to meet energy demands. For example, the
protein requirement for a normal healthy individual
to maintain zero nitrogen balance is 0.5-l.Og/Kg.
The patient with congestive heart failure or the
post-operative cardiac patient in contrast can
require as much as 1.5-2.Og/Kg to maintain nitrogen
balance.
` Not only is nutrition important in treating
the patient with atherosclerotic, vascular,
cardiovascular, and/or thrombotic disease but it is
also important in supporting patients at risk of
acquiring these diseases. Diet can impact the onset
of these diseases in certain individuals.
Accordingly, there is a need for a
nutritional composition for supporting and
therapeutically treating individuals under treatment
for vascular, cardiovascular, or thrombotic
di~eases. Moreover, there is a need for a
nutritional composition for supporting individuals
who are at high risk of atherosclerotic, vascular,
cardiovascular, and/or thrombotic disease.
~ 3 ~
The present invention provides a nutritional
composition for supporting and/or providing therapy to
individuals at risk or under treatment for vascular,
cardiovascular, or thrombotic diseases. The formulation
can be administered either as an enteral product or
parenterally.
Various aspects of this invention are as follows:
A nutritional composition for individuals under
treatment for or at risk of atherosclerotic, vascular,
cardiovascular, and/or thrombotic disease comprising:
a nutritionally effecti.ve amount of a
protein source;
a nut-itionally effective amount of a
carbohydrate source;
a nutritionally effective amount of
medium chain fatty acids; and
a nutritionally effective amount of at
least one lipid selected from the group
consisting of: gamma-linolenic acid;
sterodonic acid; and marine oil.
An enteral composition comprising:
a protein source representing
; approximately 15 to about 25% of the caloric
source of the composition, the protein source
including essential, conditionally essential,
and nonessential amino acids, branched-chain
amino acids, and a high biological value
protein;
a carbohydrate source representing
approximately 40% to about 75% of the caloric
source of the composition; and
a lipid component representing
approximately 10% to about 40% of the caloric
source of the composition, the lipid component
including medium chain fatty acids and at
least one lipid selected from the group
~ ~ ~ 5, ~
consisting of: gamma-linolenic acid;
eicosapentaenoic acid; docosahexaenoic acid;
linolenic acid and sterodonic acid.
A parenteral regimen for cardiac therapy
comprising:
a therapeutically effective amount of an
injectable lipid emulsion including a
triacylglycerol oil having at least one of the
lipids selected from the group consisting of
eicosapentaenoic acid, gamma-linolenic acid
and sterodonic acid, and a phospholipid chosen
from the group consisting of egg phospholipid
or soybean phospholipid, and glycerol and
water;
a therapeutically effective amount of an
injectable solution of glucose and xylitol;
a therapeutically effective amount of
L-carnitine;
a therapeutically effective amount of an
injectable solution of branched-chain amino
acids; and
a therapeutically effective amount of an
injectable solution of amino acids.
As an enteral product, the formulation comprises a
protein source, a carbohydrate source, a fat source, and
electrolytes~ The protein source preferably includes a
high biological value protein, an amino acid solution,
branched-chain amino acids, and carnitine. The amino
acid solution is designed to provide the essential,
conditionally essential, and non-essential amino acids
necessary for efficacious protein metabolism in the face
of cardiovascular or thrombotic disease states. The
nutritional composition also contains a carbohydrate
source. The carbohydrate source preferably includes
xylitol and glucose base carbohydrate.
1 3 ~
4b
The lipid component of the nutritional composition
comprises long chain triglycerides and medium chain
fatty acids. The long chain triglycerides encompass
triglycerides containing fatty acids of 11 to 26 carbons
in length. The medium chain fatty acids preferably in
the present invention are those that are 6 to 10 carbons
in length.
Preferably, the long chain triglycerides comprise
marine oils and/or gamma-linolenic acid (GLA) and
sterodonic acid. Preferably, the marine oils include
linolenic acid and large amounts of two other members of
the omega three family: eicosapentaenoic acid ~EPA) and
docosahexaenoic acid
A
~31~
-- 5
(DHA). These fatty acids are incorporated into cell
membranes and serum and give rise to metabolites of
the omega-three metabolic pathways. Preferably the
long chain triglycerides comprise from approximately
50% to about 25% of the lipid component and the
medium chain fatty acids comprises from approximately
75~ to about 50% of the lipid component. If GLA is
utilized with marine oil preferably approximately
three times as much marine oil is used as GLA.
Preferably the protein source comprises
approximately 15 to about 25% of the caloric source
of the enteral nutritional composition. Most
preferably the protein source comprises approximately
20% of the caloric source of the enteral nutritional
composition. Preferably, the carbohydrate source
comprises approximately 40% to about 75% of the
caloric source of the enteral nutritional
composition. Most preferably, the carbohydrate
source comprises approximately 50% of the caloric
source of the enteral nutritional composition.
Preferably the lipid compQnent comprises
approximately 10% to about 40% of the caloric source
of the enteral nutritional composition. Most
preferably the lipid component comprises
approximately 30~ of the caloric source of the
enteral nutritional composition.
The parenteral regimen for the composition
for providing nutritional support or therapy for
individuals at risk or under therapy for
atherosclerotic, vascular, cardiovascular, and/or
thrombotic disease is preferably modular. However,
the parenteral regimen can be delivered modularly or
premixed. As a modular regimen the parenteral
~ 3 ~ hd
product includes an injectable solution of: a lipid
emulsion; a carbohydrate; carnitine; branched-chain
amino acids; and amino acids.
Preferably, the lip;ld emulsion for
injection includes approximately 5 to about 20% of a
triacylglycerol oil containinq approximately 5 to
about 80% eicosapentaenoic acid (EPA) and/or
approximately 5 to about 80% gamma-linolenic acid
(GLA) and approximately 3 to about 25% sterodonic
acid (6, 9, 12, 15-otadecateraenoic acid), with
approximately 0.4 to about 1.6% egg or soy bean
phospholipid and approximately 2.25% of glycerol or
other physiologically acceptable tonicity agent,
adjusted to physiological pH with sodium hydroxide.
The remaining component(s) of the lipid emulsion is
either water or water with medium chain
triglycerides.
The present invention provides a
nutritional composition that affords a rational,
scientific diet or supplement for individuals at high
risk or under treatment for atherosclerotic,
tvascular, cardiovascular, and/or thrombotic
diseases. The formulation is designed to slow the
progression of these diseases, and prevent the onset
of acute episodes that can result in the death of
such patients. To this end, the present invention
provides a composition that includes nutritional
substrates that have been shown to effect various
biochemical and physiological parameters of vascular,
cardiovascular and blood systems. The formulation
can be administered either as an enteral product or
parenterally.
1 3 ~ ~3 ~
-- 7 --
As an enteral product, the formulation
comprises a protein source, a carbohydrate source, a
fat source, and preferably electrolytes. The protein
source preferably includes a high biological value
protein, an amino acid solution, branched-chain amino
acids, and carnitine. The high biological value
protein cbmprises the base component. Although any
high biological value protein can be utilized
preferably the high biological value protein is
lactalbumin or soy protein. Whole protein or
hydrolysates can be utilized.
The amino acid solution is designed to
provide the essential, conditionally essential, and
non-essential amino acids necessary for efficacious
protein metabolism in the face of cardiovascular or
thrombotic disease states. The amino acid solution
preferably includes: L-Arginine; L-Leucine;
L-Isoleucine; L-Lysine; L-Valine; L-Phenylalanine;
L-Histidine; L-Threonine; L-Methionine; L-Tryptophan;
L-Alanine; L-Proline; L-Serine; L-Tyrosine; and amino
acetic acid. An example of an amino acid solution
formulation that will function satisfactorily is
TRAVASOLR marketed by Travenol Laboratories,
Deerfield, Illinois. Of course, depending upon
requirements not all of the amino acids must be
included in the solution. Of course, other nutrients
such as, for example, biologically available sources
of ~aurine and cysteine can be added. Preferably the
arginine:lysine ratio is between approximately about
0.7 1 to 1.25:1. Most preferably the ratio is
approximately l:l. Clinical and experimental
evidence has shown that an arginine:lysine ratio of 1
1 3 ~
to 1 is associated with lower plasma cholosterol
levels.
The amino acid and base protein, i.e., high
biological value protein, is combined with
branched-chain amino acids to achieve a final
concentration of approximate:Ly 45 to 55 percent
branched-chain amino acids (w/w). Most preferably
the final concentration of branched-chain amino acids
is 50 percent of total protein and amino acid
content. The branched-chain amino acid mixture that
function satisfactorily is that capable of
maintaining essential intake of all three
branched-chain amino acids to meet nutritional
requirements. The branched-chain amino acids
Isoleucine, Leucine, and valine are preferably
included in a 1:1:1 molar ratio. An example of such
a branched-chain amino acid formula is BR~NCHAMINR
marketed by Travenol Laboratories, Deerfield,
Illinois. Observations on rats and dogs demonstrate
that these cardiac muscles depend more on
branched-chain amino acids than on all other amino
acids. As previously stated, other amino acids can
be utilized; for e~ample, in neonates and infants it
may be desirable to include taurine.
Preferably glycine should be supplemented
to the protein source, if necessary, to obtain levels
typically found in soy protein. It has been found
that higher levels of plasma glycine are associated
with lowered levels of plasma cholesterol.
The protein source also preferably includes
L-carnitine. The L-carnitine is added to achieve a
final concentration of approximately 15 to 40 mg/g of
total protein. Most preEerably the final
~3~ ~ d~
concentration of L-carnitine is 25 mg/g of total
protein. Many publications have shown that damaged
cardiac muscle functions better when supplemented
with L-carnitine.
The nutritional composition also contains a
carbohydrate source. The carbohydrate source
preferably includes xylitol and a glucose-based
carbohydrate. In a preferred embodiment the
carbohydrate source includes maltodextrin and
xylitol. The glucose substrate and xylitol are
preferably present in a 1:1 ratio by weight. The
carbohydrate source can also include ribose. In a
preferred embodiment, the composition contains
maltrodextrin, xylitol, and ribose in a preffered
15 ratio of approximately 1:1:.066 by weight. In
another embodiment, the composition contains
maltrodextrin and xylitol preferably in a ratio of
approximately l:l by weight
The use of carbohydrates such as xylitol or
ribose in nutritional support of individuals
susceptible to and/or under treatment for
cardiovascular disease is based upon the unique
pathways for the metabolism of these compounds.
Xylitol is a naturally occurring intermediate in the
glucuronic acid-xylulose cycle, and may also be
metabolized through the generation of the
intermediate compound xylulose to form ribose.
Accordingly, the administration or ingestion of the
xylitol, xylulose, and/or ribose provides conversions
of these intermediates to glucose. By providing a
glucose-based carbohydrate source, i.e.,
maltodextrin, conversion of these compounds to
glucose is minimized. The administration of a l to l
1 3 ~
-- 10 --
ratio of glucose substrates with xylitol and ribose
represents an effective means to maximize glucose
production with minimal insulin elevation, while
enhancing adenine nucleotide synthesis for this
patient population.
The effect of ribose on cardiac function
and ischemic events may be related to several
specific functions of the compound. Administration
of ribose to cardiac tissue following oxygen
deprivation has been demonstrated to result in a 90%
increase in the de novo synthesis of myocardial
adenine nucleotides, as well as in the elevation of
5-phosphoribosyl-1-pyrophosphate (PRPP) specific pool
in myocardial tissue. Continuous infusion of ribose
has been demonstrated to result in a 13-fold increase
in myocardial adenine nucleotide synthesis. Such
elevations have further been demonstrated to reduce
the occurrence of cell lesions in the myocardium.
It has been suggested that cellular
depletion of compartmentalized ATP may be primarily
responsible for the pathological effects of the
ischemic event, through an imbalance between
subcellular phosphocreatine and compartmentalized
ATP~ ATP may also serve as a modulator of myocardial
cell function, responsible for potassium exchange and
calcium:sodium exchange. These reactions require
higher concentrations of ATP then those required for
the PRPP pool alone. Demonstration of a marked
effect of ribose administration on protection against
isoproterenol-induced myocardial cell damage further
supports the hypothesis for a role in cellular
depletion of adenine nucleotides in the progression
of cardiac necrosis.
9 3 ~ r~ ~
-- 11 --
The lipid component of the nutritional
composition comprises long chain triglycerides and
medium chain fatty acids. Preferably, the long chain
triglycerides comprise "marine oils" and/or
gamma-linolenic acid of 11 to 26 carbons in length.
These fatty acids can be both saturated and
unsaturated in nature. It has been shown that
monounsaturated fatty acids are effective in lowering
plasma cholesterol. Accordingly, preferably
monounsaturated fatty acids are utilized as a
component of these lipid substrates.
The medium chain fatty acids preferable in
the present invention are those that are 6 to 10
carbons in length. These medium chain fatty acids
are a superior energy source for the cardiac muscle
cells. The fatty acids can be provided to patients
as free fatty acids, mono-, di- or triglycerides.
Medium chain fatty acids are chemically unique in
that in the absence of cytoplasmic medium chain fatty
acyl CoA synthetase they are able to pass through the
inner mitochondrial membrane unhindered. Medium
chain fatty acyl CoA synthetase does exist in the
mitochondria and activates the fatty acids once they
have crossed the inner membrane. These activated
fatty acids are then rapidly metabolized.
In contrast, long chain fatty acids, i.e.,
those fatty acids having ll to 26 carbons, due to
their chemical nature cannot cross the inner
mitochondrial membrane without being first activated
by cytoplasmic long chain fatty acyl CoA synthetase,
a rate limiting process. The long chain fatty acids
must then undergo obligatory conversion to a
r~ 2
- 12 -
carnitine transport form for entry into the
mitochondria for metabolism.
Medium chain fatty acids combine their
unique ability to cross the mitochondria membrane
with the unique biochemical milieu of the cardiac
cell. The cardiac muscle lacks cytoplasmic medium
chain acyl CoA synhetase and the ability to activate
medium chain fatty acids. Thus, medium chain fatty
acids rapidly enter the mitochondria and supply
energy in these cells directly. Long chain fatty
acids cannot do this because of their necessary
cytoplasmic activation and the slower carnitine
transport in this organ.
The long chain triglycerides preferably
comprise marine oils and/or gamma-linolenic acid
(GLA) and/or sterodonic acid. The marine oils
preferably include linolenic acid and large amounts
of two other members of the omega three family:
eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA). These fatty acids are incorporated into cell
membranes and serum lipids and give rise to
metabolites of the omega-three metabolic pathways.
GLA is an omega-6 fatty acid and is a precursor to
the l-series prostaglandins.
Preferably the long chain triglycerides
comprise from approximately 50% to about 25% of the
lipid component and the medium chain fatty acids
comprises from approximately 75% to about 50% of the
lipid component. If GLA is utilized with marine oil,
preferably approximately three times as much marine
oil is used as GLA.
All cells utilize these fatty acids to form
various prostaglandins and leukotrienes. When fatty
acids are released from cell membranes, lipoxygenase
and cyclooxygenase mediate further metabolic
activity. Although EPA is a relatively poor
substrate for lipoxygenase and cyclooxygenase, it
appears to have a high binding affinity and thereby
inhibits arachidonic acid conversion by these
enzymes. An added benefit of the omega three fatty
acid pathway lies in the physiological activity of
their cellular products (See Table I - PGI2 =
2-series prostacyclin; PGI3 = 3-series prostacyclin;
TXA2 = 2-series thromboxane; and TXA3 = 3-series
thromboxane).
TABLE I
15 Cell Fatty Acid Product Physiological
Actions
_
Endothelial Arachidonic PGI2 Lower platelet
activity:
vasodilation
Eicosapentaenoic PGI3 Lower platelet
activity:
vasodilation
Platelet Arachidonic TXA2 Platelet hyper-
activity:
vasocon-
striction
Eicosapentaenoic TXA3 Lower platelet
activity-
vasoconstric-
tion
_
13 ~ ~ ~ rs) s?
~ 14 -
In most subjects who consume such diets,
total serum cholesterol, LDL cholesterol, and
triglycerides are significant:Ly lowered, whereas HDL
cholesterol concentrations are elevated. This
pattern of change would be one thought to be less
atherogenic and the thrombogenic.
Studies conducted with human platelets
utilizing pure EPA and arachiclonic acid support the
role of the balance of EPA anci arachidonic acid as
the critical factor in controlling platelet
activators and vessel constriction.
The electrolytes component of the present
invention preferably includes sodium, potassium,
chloride, calcium, magnesium, and phosphorus.
Preferably the protein source comprises
approximately 15 to about 25~ of the caloric source
of the enteral nutritional composition. Most
preferably the protein source comprises approximately
20~ of the caloric source of the enteral nutritional
composition. Preferably, the carbohydrate source
comprises approximately 40% to about 75% of the
calori-c source of the enteral nutritional
composition. Most preferably, the carbohydrate
source comprises aproximately 50% of the caloric
source of the enteral nutritional composition.
Preferably the lipid component comprises
approximately 10~ to about 40% of the caloric source
of the enteral nutritional composition. Most
preferably the lipid component comprises
approximately 30% of the caloric source of the
enteral nutritional composition.
~L 3 1 ~
By way of examp].e, and not limitation, two
preferred enteral cardiac formulations will now be
set forth.
TABLE II
CARDIAC FORMULATION
-
Form: Liquid
Concentration: 2.0 kcal/ml
1 0
Protein Source: Lactalbumin
L-Carnitine
Enhance BCAA
Hi Arg: lys ratio
Inc. Glycine
Gm/Liter 100
~ Cal 20
.
Carbohydrate Source: Maltodextrin
- Xylitol,
Ribose
Ratio: 1.0:1.0:.066
Gm/Liter 121,121,8
% Cal 50
Fat Source: Marine Oil (MO)
GLA, MCT
Gm/Liter MCT&LCT 57.7
MO:GLA:MCT 3:1:12
~ Cal 30
~ 3 ~
- 16 -
. .
Electrolytes:
Na/Liter 50Omg
21.8~mEq
K/Liter 1000mg
35.4mEq
Cl/Liter 1000:mg
Ca/Liter 1200mg
P/Liter 1000mg
Mg/Liter 600mg
TABLE III
CARDIAC FORMULATION
.. . .
Form: Liquid
15 . -------
Concentration: 2.0 kcal/ml
Protein Source: Lactalbumin
L-Carnitine
-~ Enhance BCAA
Hi Arg: lys ratio
- Inc. Glycine
Gm/Liter 100
% Cal 20
Carbohydrate Source: Maltodextrin
Xylitol
Ratio: 1.0:1.0
Gm/Liter 125,125
~ Cal 50
Fat Source: Marine Oil (MO)
GLA, MCT
Gm/Liter MCT&LCT 57.7
MO:GLA:MCT 3:1:12
% Cal 30
. . . _
Electrolytes:
Na/Liter 500mg
21.8mEq
K/Liter lOOOmg
35.4mEq
Cl/Liter lOOOmg
28.3rnEq
Ca/Liter 1200mg
P/Liter lOOOmg
Mg/Liter 600mg
The parenteral regimen for the composition
for providing nutritional support or therapy for
individuals at risk or under therapy for vascular,
cardiovascular, or thrombotic disease is preferably
modular. However, the parenteral regimen can be
premixed before use. The parenteral regimen solution
for injection contains: a lipid emulsion; a
carbohydrate solution; carnitine; branched-chain
amino acids; and amino acids.
Preferably, the lipid emulsion for
injection includes approximately 5 to about 20~ of a
triacylglycerol oil containing approximately 5 to
about 80% eicosapentaenoic acid (EPA) and/or
approximately 5 to about 80% gamma-linolenic acid
(GLA) and approximately 3 to about 25~ sterodonic
acid (6, 9, 12, 15-octadecatetraenoic acid), with
approximately 0.4 to about 1.6% egg or soy bean
phospholipid and approximately 2.25~ of glycerol or
other physiologically acceptable tonicity agent,
~3~?J~ 2
- 18 -
adjusted to physiological pH with sodium hydroxide.
Water or water and medium chain triglycerides
comprise the remainder of the lipid emulsion. If
medium chain triglycerides are used they comprise no
more than 30% (w/v) of the lipid emulsion.
The carbohydrate injection solution
preferably contains glucose and xylitol in an
approximately 1:1 ratio by weight. The solution can
contain in an embodiment approximately 3.3~ ~w/v)
ribose.
To the branched-chain amino acid injection
solut iOII can be added any other amino acid capable of
necessary to meet nutritional requirements. The
branched-chain amino acid injection solution c~ntains
Isoleucine, Leucine, and Valine, preferably in a
1:1:1 molar ratio.
The solution for injection of amino acids
can contain essential, non-essential, and
conditionally essential amino acids. Preferably the
solution includes: L-Arginine; L-LeuCine;
L-Isoleucine; L-Lysine; L-Valine; L-Phenylalanine;
L-Histidine; L-Threonine; L-Methionine; L-Tryptophan;
L-Alanine; L-Proline; L-Serine; L-Tyrosinei and amino
acetic acid. However, the solution can contain less
than all these amino acids, or other nutrients such
as, for example, taurine and cysteine. An example of
such an amino acid solution and the relevant
proportions of each amino acids is TRAVASOLR marketed
by Travenol Laboratories, Deerfield, Illinois.
By way of example, and not limitation,
contemplated examples will now be given.
1 3~ cj
- 19 -
Example One
This contemplated example demonstrates the
use of the parenteral cardiac formulation in
providing nutrition and therapy to a patient
suffering cardiovascular disease.
A middle-aged male patient is admitted to
intensive care following an acute myocardial
infarction. Among the therapies administered would
be the parenteral cadiac formulation as part of a
continuous intravenous infusion. The parenteral
cardiac formula includes: a lipid emulsion
injection; a carbohydrate injectable solution;
injectable carnitine; injectable branched-chain amino
acid solution; and an injectable amino acid
solution. The lipid emulsion for injection includes
10% of a triacylglycerol oil containing 15%
eicosapentaenoic acid (EPA) and 5% gamma-linolenic
acid (GLA) and 5% sterodonic acid with 1.2% soybean
phospholipid and approximately 2.25% of glycerol and
water. The carbohydrate injection solution contains
glucose and xylitol in an approximately 1:1 ratio by
weight. The branched-chain amino acid injection
solution contains Isoleucine, Leucine, and ~aline, in
a 1:1:1 molar ratio. The amino acid solution was
TRAVASOLR. The key critical features of this
patient's clinical profile include:
cardiac ischemia with hyperreactive
platelets that can be easily triggered to
aggregate, leading to a life-threatening
secondary event involving thrombus formation
and vasoconstriction of the coronary artery
at the site of activation, increased
- 20 -
vascular tone and a predisposition to
vascular spasm.
As a result of this cardiac parenteral formulation,
the patient's cardiac muscle tissue would have
available energy and protein substrates and their
platelets would be far less reactive within hours of
the onset of I.V. administration. Furthermore, the
balance of the 2-series prostacyclins and 3 series
prostacyclin/2-series thromboxane ratio would begin
to shift in a favorable direction, leading to a
reduced risk of vascular spasm.
Example Two
This same patient, as described in example
one, recovers and is sent home to follow a strict
regimen. He has advanced atherosclerosis, the
sequellae of which include hypertensionJ elevated
serum triglycerides and LDL, VLDL, and total
cholesterol concentrations, low serum HDL cholesterol
concentration, and a very high risk of stroke,
myoGardial infarction, or other thrombotic events.
Doctors focus on dietary control of this
disease process, to supplement prescribed
medicationsa The cardiac enteral diet set forth in
Table II as a nutritional supplement provides
necessary cardiac muscle nutrition as well as the
therapeutic effects of EPA/DHA. Consumed on a daily
basis, this diet would:
1. provide specialized cardiac muscle
protein;
2. provide carbohydrate and calorie
nutrition;
3. lower serum triglyceride and LDL, VLDL,
and total cholesterol concentrations;
- 21 -
4. markedly reduce platelet reactivity,
leading to reduced incidence of thromboxane
and serotonin release by platelets
(vasoactive stimulators and platelet
activators) as well as platelet derived
growth factor release (a known atherogenic
factor);
5. lower systolic blood pressure, another
factor associated with atherogenesis.
Example Three
_ _
In this contemplated example, a patient
with cardiovascular disease requires a vascular
graft. The highest risk for graft-associated
thrombosis occurs within the first week following
graft placement. Since this is a platelet/white
blood cell-mediated event, lacing this patient on a
combined parenteral (set forth in Example One) and
enteral (Table II) cardiac formulation for 7-10 days,
while in recovery, will markedly dampen both platelet
and white blood cell reactivity as well as provide
essential nutritional support.
Following release from hospital, this
patient could continue with the daily consumption of
the parenteral and/or enteral formulation to maintain
2, a low thrombogenic potential.
Example Four
In this contemplated example, an elderly
patient following hip surgery is committed to several
weeks of bed rest. There is a recognized marked
thrombotic tendency following this procedure, partly
due to the surgery itself, and partly to the
prolonged vascular stasis resulting from the
elimination of physical activity.
1 3 ~
- 22 -
A regimen of combined enteral (Table II)
and parenteral (set forth in Example One) cardiac
formulation for a week following surgery, and a
continuation of the enteral formulation during the
remainder of the recovery period, will not only
dampen the thrombotic tendency, but also will provide
essential nutrients to support the healing process in
this elderly patient.
It should be understood that various
changes and modifications to the presently preferred
embodiments described herein will be apparent to
those skilled in the art. Such changes and
modifications can be made without departing from the
spirit and scope of the present invention and without
diminishing its attendant advantages. It is
therefore intended that such changes and
modifications be covered`by the appended claims.
