U.S. patent application number 16/782336 was filed with the patent office on 2020-06-18 for tube feed formulations and methods for using same.
The applicant listed for this patent is Societe des Produits Nestle S.A.. Invention is credited to Jennifer Mager, Zamzam Fariba Roughead, Heidi Storm, James Scott Teresi.
Application Number | 20200188455 16/782336 |
Document ID | / |
Family ID | 45441512 |
Filed Date | 2020-06-18 |
United States Patent
Application |
20200188455 |
Kind Code |
A1 |
Mager; Jennifer ; et
al. |
June 18, 2020 |
TUBE FEED FORMULATIONS AND METHODS FOR USING SAME
Abstract
Nutritional compositions that mimic whole foods and methods of
using the nutritional compositions are provided. The nutritional
compositions may include an increased number and variety of fruits
and vegetables, an increased variety of macronutrient sources and
an increased amount of other components that are found in whole
foods. The nutritional compositions may also include
ethnicity-specific meals and organic ingredients and provide
emotional appeal to the patient and/or the patient's caregiver.
Methods of administering such nutritional compositions to patients
in need of same are also provided.
Inventors: |
Mager; Jennifer; (St. Paul,
MN) ; Roughead; Zamzam Fariba; (Plymouth, MN)
; Storm; Heidi; (Branchburg, NJ) ; Teresi; James
Scott; (Caldwell, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Societe des Produits Nestle S.A. |
Vevey |
|
CH |
|
|
Family ID: |
45441512 |
Appl. No.: |
16/782336 |
Filed: |
February 5, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15349336 |
Nov 11, 2016 |
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16782336 |
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14966800 |
Dec 11, 2015 |
9538779 |
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15349336 |
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13805939 |
Apr 3, 2013 |
9282758 |
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PCT/US2011/042160 |
Jun 28, 2011 |
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14966800 |
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61451272 |
Mar 10, 2011 |
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61359184 |
Jun 28, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A23L 33/40 20160801;
A61K 31/165 20130101; A23L 33/17 20160801; A61K 35/745 20130101;
A23V 2002/00 20130101; A23L 33/16 20160801; A61K 31/202 20130101;
A61K 9/0053 20130101; A61P 3/00 20180101; A61K 38/02 20130101; A61K
33/00 20130101; A61P 3/02 20180101; B65B 2230/02 20130101; A23L
33/10 20160801; A23L 33/115 20160801; A61K 31/20 20130101; A61P
1/14 20180101; A61J 15/00 20130101; A61K 35/747 20130101; A23L
33/15 20160801; A61K 35/744 20130101; A61K 31/70 20130101; A23L
33/125 20160801 |
International
Class: |
A61K 35/747 20060101
A61K035/747; A61K 35/745 20060101 A61K035/745; A61K 35/744 20060101
A61K035/744; A61K 31/165 20060101 A61K031/165; A23L 33/10 20060101
A23L033/10; A61K 33/00 20060101 A61K033/00; A61K 31/202 20060101
A61K031/202; A61K 9/00 20060101 A61K009/00; A23L 33/15 20060101
A23L033/15; A23L 33/125 20060101 A23L033/125; A23L 33/16 20060101
A23L033/16; A23L 33/115 20060101 A23L033/115; A23L 33/17 20060101
A23L033/17; A23L 33/00 20060101 A23L033/00; A61K 38/02 20060101
A61K038/02; A61K 31/70 20060101 A61K031/70; A61K 31/20 20060101
A61K031/20; A61J 15/00 20060101 A61J015/00 |
Claims
1-20. (canceled)
21. A tube feed formulation having a caloric density from about 1.0
kcal/mL to 2.0 kcal/mL and an osmolality up to 800 mOsm/kg water
and consisting of organic ingredients comprising at least five
different whole food components comprising a source of
carbohydrates comprising rice, the at least five different whole
food components further comprising at least one fruit or vegetable
selected from the group consisting of potato, pear, blueberry, and
mixtures thereof; the organic ingredients further comprising a
source of protein comprising at least one of pea protein or rice
protein; the organic ingredients further comprising a source of
fat.
22. The tube feed formulation of claim 21, wherein the at least
five different whole food components comprise potato, pear and
blueberry.
23. The tube feed formulation of claim 21, wherein the source of
protein comprises pea protein and rice protein.
24. The tube feed formulation of claim 21, wherein the source of
fat provides 25% to 35% of the total energy of the tube
formulation, the source of protein provides 25% to 30% of the total
energy of the tube formulation, and the source of carbohydrates
provides 45% to 65% of the total energy of the tube
formulation.
25. The tube feed formulation of claim 21, which does not contain
corn, does not contain soy, does not contain dairy protein and does
not contain lactose.
26. The tube feed formulation of claim 21, wherein the source of
fat comprises olive oil and canola oil.
27. The tube feed formulation of claim 21, wherein the organic
ingredients further comprise taurine and/or vitamins and minerals
comprising at least one of calcium, vitamin A, vitamin B1, vitamin
B2, vitamin B3, vitamin B5, vitamin B6, vitamin B9, vitamin B12,
vitamin C, vitamin D, vitamin E, vitamin K, potassium, choline,
magnesium, iron, iodine, zinc, copper, potassium, phosphorus,
selenium, chromium, biotin.
28. The tube feed formulation of claim 21, wherein the organic
ingredients further comprise at least one of an herb or a
spice.
29. A method of providing nutrition to a human, the method
comprising administering the tube feed formulation of claim 21 to
the human.
30. The method of claim 29, wherein the tube feed formulation is
administered to the human in an amount comprising at least three
servings of fruits and vegetables per day.
31. The method of claim 29, wherein the tube feed formulation is
administered to the human long-term.
32. The method of claim 29, wherein the tube feed formulation
provides complete nutrition to the human.
33. A tube feed formulation having a caloric density from about 1.0
kcal/mL to 2.0 kcal/mL and an osmolality up to 800 mOsm/kg water
and consisting of organic ingredients comprising at least six
different whole food components comprising chicken, rice and at
least one fruit or vegetable selected from the group consisting of
squash, mango, beet, spinach and mixtures thereof; the organic
ingredients further comprising pea protein; the tube feed
formulation further comprising a source of fat.
34. The tube feed formulation of claim 33, wherein the at least six
different whole food components comprise squash, mango, beet and
spinach.
35. The tube feed formulation of claim 33, wherein the source of
fat provides 25% to 35% of the total energy of the tube
formulation, the source of protein provides 25% to 30% of the total
energy of the tube formulation, and the source of carbohydrates
provides 45% to 65% of the total energy of the tube
formulation.
36. The tube feed formulation of claim 33, which does not contain
corn, does not contain soy, does not contain dairy protein and does
not contain lactose.
37. The tube feed formulation of claim 33, wherein the source of
fat comprises olive oil and canola oil.
38. The tube feed formulation of claim 33, further comprising at
least one of calcium, vitamin A, vitamin B1, vitamin B2, vitamin
B3, vitamin B5, vitamin B6, vitamin B9, vitamin B12, vitamin C,
vitamin D, vitamin E, vitamin K, potassium, choline, magnesium,
iron, iodine, zinc, copper, potassium, phosphorus, selenium,
chromium, biotin, or taurine.
39. The tube feed formulation of claim 33, further comprising at
least one of an herb or a spice.
40. A method of providing nutrition to a human, the method
comprising administering the tube feed formulation of claim 33 to
the human.
41. The method of claim 40, wherein the tube feed formulation is
administered to the human in an amount comprising at least three
servings of fruits and vegetables per day.
42. The method of claim 40, wherein the tube feed formulation is
administered to the human long-term.
43. The method of claim 40, wherein the tube feed formulation
provides complete nutrition to the human.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S.
application Ser. No. 15/349,336 filed Nov. 11, 2016, which is a
continuation of U.S. application Ser. No. 14/966,800 filed Dec. 11,
2015 which issued as U.S. Pat. No. 9,538,779, which is a
continuation of U.S. application Ser. No. 13/805,939 filed Apr. 3,
2013 which issued as U.S. Pat. No. 9,282,758, which is a National
Stage of International App. No. PCT/US2011/042160 filed Jun. 28,
2011, which claims priority to U.S. Provisional Patent App. No.
61/451,272 filed Mar. 10, 2011 and U.S. Provisional Patent App. No.
61/359,184 filed Jun. 28, 2010, the entire contents of which are
incorporated herein by reference.
SUMMARY
[0002] Nutritional compositions including whole foods are provided.
Methods of using the nutritional compositions are also provided. In
a general embodiment, the present disclosure provides a nutritional
composition (e.g., oral nutritional supplements, tube feed
formulations, etc.) including at least five different processed
whole food components; a source of protein, a source of fat, a
source of carbohydrate, and a source of vitamins and minerals.
[0003] In an embodiment, the five different processed whole food
components may include 4 servings of fruits/vegetables and 1
serving of an animal source.
[0004] In an embodiment, the nutritional composition includes at
least six or seven different whole food components.
[0005] In an embodiment, the whole food components are selected
from the group consisting of a processed fruit, a processed
vegetable, a processed meat, a processed grain, or combinations
thereof. In an embodiment, the whole food components need not be
processed.
[0006] In an embodiment, the nutritional composition further
includes at least one of an herb, a spice and a flavoring.
[0007] In an embodiment, the protein is selected from the group
consisting of dairy based proteins, plant based proteins, animal
based proteins, artificial proteins, or combinations thereof.
[0008] In an embodiment, the dairy based proteins are selected from
the group consisting of casein, caseinates, casein hydrolysates,
whey, whey hydrolysates, milk protein concentrate, milk protein
isolate, or combinations thereof
[0009] In an embodiment, the plant based proteins are selected from
the group consisting of soy protein, pea protein, canola protein,
wheat and fractionated wheat proteins, corn proteins, zein
proteins, rice proteins, oat proteins, potato proteins, peanut
proteins, proteins derived from beans, lentils, buckwheat, pulses,
or combinations thereof
[0010] In an embodiment, the animal based proteins are selected
from the group consisting of beef, poultry, fish, lamb, seafood,
pork, egg, or combinations thereof
[0011] In an embodiment, the nutritional composition further
includes phospholipids.
[0012] In an embodiment, the nutritional composition further
includes a prebiotic selected from the group consisting of acacia
gum, alpha glucan, arabinogalactans, beta glucan, dextrans,
fructooligosaccharides, fucosyllactose, galactooligosaccharides,
galactomannans, gentiooligosaccharides, glucooligosaccharides, guar
gum, inulin, isomaltooligosaccharides, lactoneotetraose,
lactosucrose, lactulose, levan, maltodextrins, milk
oligosaccharides, partially hydrolyzed guar gum,
pecticoligosaccharides, resistant starches, retrograded starch,
sialooligosaccharides, sialyllactose, soyoligosaccharides, sugar
alcohols, xylooligosaccharides, their hydrolysates, or combinations
thereof.
[0013] In an embodiment, the nutritional composition further
includes a probiotic selected from the group consisting of
probiotics include Aerococcus, Aspergillus, Bacteroides,
Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus,
Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc,
Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus,
Penicillium, Peptostrepococcus, Pichia, Propionibacterium,
Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus,
Streptococcus, Torulopsis, Weissella, or combinations thereof.
[0014] In an embodiment, the nutritional composition further
includes an amino acid selected from the group consisting of
alanine, arginine, asparagine, aspartate, citrulline, cysteine,
glutamate, glutamine, glycine, histidine, hydroxyproline,
hydroxyserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine,
lysine, methionine, phenylalanine, proline, serine, taurine,
threonine, tryptophan, tyrosine, valine, or combinations
thereof.
[0015] In an embodiment, the nutritional composition further
includes a source of .omega.-3 fatty acids selected from the group
consisting of .alpha.-linolenic acid, docosahexaenoic acid,
eicosapentaenoic acid, or combinations thereof. The source of
.omega.-3 fatty acids may be selected from the group consisting of
fish oil, poultry, eggs, flax seed, walnuts, almonds, algae, krill,
modified plants, or combinations thereof.
[0016] In an embodiment, the nutritional composition further
includes a nucleotide. The nucleotide may be selected from the
group consisting of a subunit of deoxyribonucleic acid, a subunit
of ribonucleic acid, a polymeric form of deoxyribonucleic acid, a
polymeric form of ribonucleic acid, yeast extract forms, or
combinations thereof.
[0017] In an embodiment, the nutritional composition further
includes a phytonutrient that is isolated from food or is present
as part of the whole food component provided in the tube feed
formula (fruits, vegetables, grains). These may be flavanoids,
carotenoids, allied phenolic compounds, polyphenolic compounds,
terpenoids, alkaloids, sulphur-containing compounds, or
combinations thereof.
[0018] In an embodiment, the nutritional composition further
includes ingredients with antioxidant activities selected from the
group consisting of herbs/spices/flavorings (garlic, cinnamon,
ginseng, turmeric, curcumin, rosemary, mint, lemongrass, ginkgo,
ginger, tea, vanilla extract), polyphenols, carotenoids,
flavonoids, lignan, lutein, lycopene coenzyme Q10 ("CoQ10"),
glutathione Goji (wolfberry), lactowolfberry, hesperidine,
selenium, vitamin A, vitamin E, or combinations thereof.
[0019] In an embodiment, the vitamins are selected from the group
consisting of vitamin A, vitamin B1 (thiamine), vitamin B2
(riboflavin), vitamin B3 (niacin or niacinamide), vitamin B5
(pantothenic acid), vitamin B6 (pyridoxine, pyridoxal, or
pyridoxamine, or pyridoxine hydrochloride), vitamin B7 (biotin),
vitamin B9 (folic acid), and vitamin B12 (various cobalamins;
commonly cyanocobalamin in vitamin supplements), vitamin C, vitamin
D, vitamin E, vitamin K, folic acid, biotin, choline, or
combinations thereof
[0020] In an embodiment, the minerals are selected from the group
consisting of boron, calcium, chromium, copper, iodine, iron,
magnesium, manganese, molybdenum, nickel, phosphorus, potassium,
selenium, silicon, tin, vanadium, zinc, or combinations
thereof.
[0021] In an embodiment, the nutritional composition further
includes a nutrient source that is typically consumed by
individuals in a specific region of the world. For example, the
nutrient source may be a fruit, a vegetable, protein, an herb, a
spice, a flavoring, or combinations thereof.
[0022] In an embodiment, the nutritional composition includes
pediatric-friendly food blends, or foods that parents would
consider "normal" for kids consuming an oral diet. Popular branded
foods include, for example, Cheerios.RTM., Juicy Juice.RTM.,
Campbell's Alphabet Soup.TM., chicken nuggets, strawberry
shortcake, bananas, apple sauce, etc.
[0023] In an embodiment, the whole food components (e.g., fruit,
vegetable, grain), vitamins, minerals, proteins, fats, and/or
carbohydrates are organic. In one embodiment, the protein source
may be raised with natural farming practices including free range
(chicken), lamb and grass grazing (beef).
[0024] In an embodiment, the nutritional composition includes a
source of fiber or a blend of different types of fiber. The fiber
blend may contain a mixture of soluble and insoluble fibers.
Soluble fibers may include, for example, fructooligosaccharides,
acacia gum, inulin, etc. Insoluble fibers may include, for example,
pea outer fiber.
[0025] In another embodiment, the nutritional composition includes
a processed whole food, at least seven different sources of
macronutrients selected from the group consisting of protein,
carbohydrate, fat, or combinations thereof, and a source of
vitamins or minerals. The sources of macronutrients may be selected
from fats, carbohydrates and proteins.
[0026] In an embodiment, the at least seven different sources of
macronutrients include at least one protein, at least one
carbohydrate and at least one fat.
[0027] In an embodiment, the at least seven different sources of
macronutrients include at least three different protein
sources.
[0028] In an embodiment, the at least seven different sources of
macronutrients include at least three different carbohydrate
sources.
[0029] In an embodiment, the at least seven different sources of
macronutrients include at least three different fat sources.
[0030] In yet another embodiment, a method of improving the overall
health of a patient having an underlying medical condition is
provided. The method includes administering to a patient having an
underlying medical condition a nutritional composition having at
least five different whole food components; a source of protein, a
source of fat, carbohydrate, and a source of vitamins and
minerals.
[0031] In an embodiment, the nutritional composition includes at
least six or seven different whole food components.
[0032] In an embodiment, the whole food components are selected
from the group consisting of a processed fruit, a processed
vegetable, a processed meat, a processed grain, a herb, spice or
flavoring, or combinations thereof
[0033] In an embodiment, the patient uses the nutritional
composition for a long-term to receive nutrients found in whole
food. The patient may be sedentary/bedridden and/or may be an older
adult. The patient may have depressed or altered immune function
and increased oxidative stress, compromised gut health, altered
glucose metabolism and lipid status, poor musculoskeletal health
(loss of bone and muscle), pressure ulcers, and chronic wounds. In
an embodiment, the patient may also have an underlying medical
condition selected from the group consisting of cerebral palsy,
failure-to-thrive, cystic fibrosis, neuromuscular disorders, brain
injury, developmental delay, or combinations thereof.
[0034] In another embodiment, a method of maintaining or improving
the overall health of a patient using a tube feeding or nutritional
composition for a long-term or having an underlying medical
condition is provided. The method includes administering to a
patient having an underlying medical condition a nutritional
composition having a processed whole food, a source of vitamins or
minerals, and at least seven different sources of macronutrients
selected from the group consisting of protein, carbohydrates, fats,
or combinations thereof.
[0035] In an embodiment, the nutritional composition contains at
least seven different sources of macronutrients with the sources
including at least one source of protein, at least one source of
carbohydrate, and at least one source of fat. The nutritional
composition may also include a source of fiber. The nutritional
composition may contain at least seven different sources of
macronutrients that may also include at least three different
proteins. The nutritional composition may contain at least seven
different sources of macronutrients that may also include at least
three different carbohydrates. The nutritional composition may
contain at least seven different sources of macronutrients that may
also include at least three different fats. The nutritional
composition may also include at least three different sources of
fiber.
[0036] In another embodiment, methods of administering nutritional
composition are provided. The methods include administering a
nutritional composition as a bolus, at three or more different
times per day. The first nutritional composition having a whole
food to a patient at a first time of a day may correspond to a
typical breakfast time, administering a second nutritional
composition having a whole food to the patient at a second time of
the day may correspond to a typical lunch time, and administering a
third nutritional composition having a whole food to the patient at
a third time of the day may correspond to a typical dinner time.
Additional bolus tube feeding may correspond to snack times. As
such, the present methods may include fourth, fifth or sixth
nutritional compositions corresponding to typical daily snack
times.
[0037] In an embodiment, the nutritional compositions are changed
to a new nutritional composition on a daily basis. The nutritional
compositions may also be changed to a new nutritional composition
on a weekly or monthly basis. The cycle of different nutritional
compositions may occur by different weeks. In these respects, for
example, the methods may provide a new first, or breakfast,
formulation each day of the week. The methods may also provide a
new second, or lunch, formulations each day of the week. In another
embodiment, the nutritional composition may be the same for each of
breakfast, lunch and dinner for a first week, and then changed to a
second formulation for each of breakfast, lunch and dinner for a
second week, etc.
[0038] In an embodiment, the first, second and third nutritional
compositions include at least one source of protein, at least one
source of carbohydrate, at least one source of fat, and at least
one type of fruit and vegetable. The protein of each of each of the
first, second and third nutritional compositions may be different.
At least one of a fruit and a vegetable of each of the first,
second and third nutritional compositions may be different.
[0039] In an embodiment, the nutritional composition may contain
food components specific to cultures/regions of the world (e.g.,
Mediterranean, Asia, South and Latin America).
[0040] In an embodiment, the amount/bolus of nutrients provided at
a single time point (resulting in a more concentrated dose) may
elicit different physiological responses compared to when provided
as a continuous feed. As an example, pulse feeding of protein
stimulates protein synthesis to a greater extent than when protein
is consumed evenly throughout the day. In an embodiment, at least
one tube feeding formulation per day may contain high amounts of
protein.
[0041] In an embodiment, increased variety of foods and/or food
components and flavors may be delivered to stimulate specific taste
receptors in the gut, thus eliciting different physiological
responses. For example, stimulation of the Umami taste receptor in
the gut increases mucous secretion and GLP-1 and GLP-2 release.
Stimulation of the bitter taste receptor in the gut increases CCK
release and delays gastric emptying. Stimulation of the sweet taste
receptor in the gut stimulates release of GLP-1 and GIP, and also
regulates the expression of glucose transporter thus enhancing gut
absorption of sugars.
[0042] In an embodiment, the nutritional compositions may be
delivered warm or cold. It can be theorized that differences in
food temperature may impact digestion and physiological
response.
[0043] In yet another embodiment, a tube feed package is provided.
The package includes a first component contained in the package
that is a tube feed formulation having a processed whole food, and
a second component contained in the package, the second component
being ingestible and packaged separately from the first component.
The second component may include a taste, or an aroma that may
stimulate the cephalic phase of digestion, and/or include
functional ingredients such as probiotics for oral health.
[0044] In an embodiment, the second component is a tablet, lozenge,
dissolvable strip, or chewing gum that contains a flavor and scent,
and may or may not contain a source of protein, a source of fat or
a source of carbohydrate. The tablet, lozenge, dissolvable strip or
chewing gum would simulate the experience of eating and stimulate
the cephalic response, which primes the body to absorb and use
nutrients. The second component may be compliant with a nothing per
orem ("NPO") diet. The second component may also be calorie free
and may also have a scratch and sniff component. The second
component may release a scent upon opening.
[0045] In an embodiment, the flavor of the second component
corresponds to the processed whole food of the tube feed
formulation. The flavor and/or scent of the second component may
also correspond to a nutrient source that is typically consumed by
individuals in a specific region of the world.
[0046] In an embodiment, the second component includes a functional
ingredient selected from the group consisting of probiotics,
capsaisin, a source of strong flavor, or combinations thereof. The
second component may have a strong flavor (e.g., tart, ginger, etc.
to stimulate saliva production), and contain functional ingredients
such as probiotics (to maintain healthy oral flora), and/or
ingredients that trigger the swallow reflex such as capsaicin. The
second component may be, or have a, scratch and sniff component to
enhance the aroma, and may be used when oral intake is
contraindicated (e.g., dysphagia, neurological impairment).
[0047] In an embodiment, the flavor and scent of the second
component may or may not be similar to the foods present in the
tube feeding. In another embodiment, the second component comes
with a variety of flavors for emotional appeal such that the
patient can choose what they are hungry for.
[0048] In an embodiment, the first and second components are
contained in a package having a shape of an eating utensil (e.g., a
plate) with pictures or shapes of food components found in the tube
feed formula, or combinations thereof.
[0049] An advantage of the present disclosure is to provide
improved tube feed formulations.
[0050] Another advantage of the present disclosure is to provide
improved nutritional compositions that include real or whole
foods.
[0051] Yet another advantage of the present disclosure is to
provide nutritional compositions that promote bone health.
[0052] Still yet another advantage of the present disclosure is to
provide nutritional compositions that preserve lean body mass.
[0053] Still yet another advantage of the present disclosure is to
provide nutritional compositions that preserve muscle mass.
[0054] Another advantage of the present disclosure is to provide
nutritional compositions that maintain glucose homeostasis.
[0055] Another advantage of the present disclosure is to provide
nutritional compositions that maintain normal or reduce cholesterol
or triglycerides levels.
[0056] Another advantage of the present disclosure is to provide
nutritional compositions that maintain gut health.
[0057] Another advantage of the present disclosure is to provide
nutritional compositions that help maintain healthy immune function
and reduce oxidative stress.
[0058] Another advantage of the present disclosure is to provide
nutritional compositions that support normal growth.
[0059] Another advantage of the present disclosure is to provide
nutritional compositions that treat and/or prevent chronic
diseases.
[0060] Yet another advantage of the present disclosure is to
provide nutritional compositions that treat and/or prevent pressure
ulcers.
[0061] An advantage of the present disclosure is to provide
nutritional compositions that improve the overall health of
patients on a long-term tube feeding regimen. These patients may be
sedentary, elderly, or have cystic fibrosis, quadriplegia, cerebral
palsy, and/or other neuromuscular disorders, or dysphagia.
[0062] Still yet another advantage of the present disclosure is to
provide tube feed formulations that provide emotional appeal to
patients and/or their caregivers.
[0063] Another advantage of the present disclosure is to provide
tube feed formulations that mimic a real food, oral diet.
[0064] Yet another advantage of the present disclosure is to
provide methods of administering tube feed formulations that
simulate administration of normal meals.
[0065] Additional features and advantages are described herein, and
will be apparent from the following Detailed Description.
DETAILED DESCRIPTION
[0066] As used herein, "about" is understood to refer to numbers in
a range of numerals. Moreover, all numerical ranges herein should
be understood to include all integer, whole or fractions, within
the range.
[0067] As used herein the term "amino acid" is understood to
include one or more amino acids. The amino acid can be, for
example, alanine, arginine, asparagine, aspartate, citrulline,
cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline,
hydroxyserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine,
lysine, methionine, phenylalanine, proline, serine, taurine,
threonine, tryptophan, tyrosine, valine, or combinations
thereof.
[0068] As used herein, "animal" includes, but is not limited to,
mammals, which include but is not limited to, rodents, aquatic
mammals, domestic animals such as dogs and cats, farm animals such
as sheep, pigs, cows and horses, and humans. Wherein the terms
"animal" or "mammal" or their plurals are used, it is contemplated
that it also applies to any animals that are capable of the effect
exhibited or intended to be exhibited by the context of the
passage.
[0069] As used herein, the term "antioxidant" is understood to
include any one or more of various substances such as beta-carotene
(a vitamin A precursor), vitamin C, vitamin E, and selenium) that
inhibit oxidation or reactions promoted by Reactive Oxygen Species
("ROS") and other radical and non-radical species. Additionally,
antioxidants are molecules capable of slowing or preventing the
oxidation of other molecules. Non-limiting examples of antioxidants
include astaxanthin, carotenoids, coenzyme Q10 ("CoQ10"),
flavonoids, glutathione Goji (wolfberry), hesperidine,
lactowolfberry, lignan, lutein, lycopene, polyphenols, selenium,
vitamin A, vitamin C, vitamin E, zeaxanthin, or combinations
thereof.
[0070] As used herein, "complete nutrition" includes nutritional
products and compositions that contain sufficient types and levels
of macronutrients (protein, fats and carbohydrates) and
micronutrients to be sufficient to be a sole source of nutrition
for the animal to which it is being administered to. Patients can
receive 100% of their nutritional requirements from such complete
nutritional compositions.
[0071] As used herein, "effective amount" is an amount that
prevents a deficiency, treats a disease or medical condition in an
individual or, more generally, reduces symptoms, manages
progression of the diseases or provides a nutritional,
physiological, or medical benefit to the individual. A treatment
can be patient- or doctor-related.
[0072] While the terms "individual" and "patient" are often used
herein to refer to a human, the invention is not so limited.
Accordingly, the terms "individual" and "patient" refer to any
animal, mammal or human having or at risk for a medical condition
that can benefit from the treatment.
[0073] As used herein, non-limiting examples of sources of
.omega.-3 fatty acids such .alpha.-linolenic acid ("ALA"),
docosahexaenoic acid ("DHA") and eicosapentaenoic acid ("EPA")
include fish oil, poultry, eggs, or other plant or nut sources such
as flax seed, walnuts, almonds, algae, krill, modified plants,
etc.
[0074] As used herein, "food grade micro-organisms" means
micro-organisms that are used and generally regarded as safe for
use in food.
[0075] As used herein, "incomplete nutrition" includes nutritional
products or compositions that do not contain sufficient levels of
macronutrients (protein, fats and carbohydrates) or micronutrients
to be sufficient to be a sole source of nutrition for the animal to
which it is being administered to. Partial or incomplete
nutritional compositions can be used as a nutritional
supplement.
[0076] As used herein, "long term administrations" are preferably
continuous administrations for more than 6 weeks. Alternatively,
"short term administrations," as used herein, are continuous
administrations for less than 6 weeks.
[0077] As used herein, "mammal" includes, but is not limited to,
rodents, aquatic mammals, domestic animals such as dogs and cats,
farm animals such as sheep, pigs, cows and horses, and humans.
Wherein the term "mammal" is used, it is contemplated that it also
applies to other animals that are capable of the effect exhibited
or intended to be exhibited by the mammal.
[0078] The term "microorganism" is meant to include the bacterium,
yeast and/or fungi, a cell growth medium with the microorganism, or
a cell growth medium in which microorganism was cultivated.
[0079] As used herein, the term "minerals" is understood to include
boron, calcium, chromium, copper, iodine, iron, magnesium,
manganese, molybdenum, nickel, phosphorus, potassium, selenium,
silicon, tin, vanadium, zinc, or combinations thereof
[0080] As used herein, "normal bone growth" refers to the process
by which childhood and adolescent bones are sculpted by modeling,
which allows for the formation of new bone at one site and the
removal of old bone from another site within the same bone. This
process allows individual bones to grow in size and to shift in
space. During childhood bones grow because resorption (the process
of breaking down bone) occurs inside the bone while formation of
new bone occurs on its outer (periosteal) surface. At puberty the
bones get thicker because formation can occur on both the outer and
inner (endosteal) surfaces. The remodeling process occurs
throughout life and becomes the dominant process by the time that
bone reaches its peak mass (typically by the early 20s). In
remodeling, a small amount of bone on the surface of trabeculae or
in the interior of the cortex is removed and then replaced at the
same site. The remodeling process does not change the shape of the
bone, but it is nevertheless vital for bone health. Modeling and
remodeling continue throughout life so that most of the adult
skeleton is replaced about every 10 years. While remodeling
predominates by early adulthood, modeling can still occur
particularly in response to weakening of the bone.
[0081] As used herein, a "nucleotide" is understood to be a subunit
of deoxyribonucleic acid ("DNA") or ribonucleic acid ("RNA"). It is
an organic compound made up of a nitrogenous base, a phosphate
molecule, and a sugar molecule (deoxyribose in DNA and ribose in
RNA). Individual nucleotide monomers (single units) are linked
together to form polymers, or long chains. Exogenous nucleotides
are specifically provided by dietary supplementation. The exogenous
nucleotide can be in a monomeric form such as, for example,
5'-Adenosine Monophosphate ("5'-AMP"), 5'-Guanosine Monophosphate
("5'-GMP"), 5'-Cytosine Monophosphate ("5'-CMP"), 5'-Uracil
Monophosphate ("5'-UMP"), 5'-Inosine Monophosphate ("5'-IMP"),
5'-Thymine Monophosphate ("5'-TMP"), or combinations thereof. The
exogenous nucleotide can also be in a polymeric form such as, for
example, an intact RNA. There can be multiple sources of the
polymeric form such as, for example, yeast RNA.
[0082] "Nutritional products," or "nutritional compositions," as
used herein, are understood to include any number of optional
additional ingredients, including conventional food additives, for
example one or more, acidulants, additional thickeners, buffers or
agents for pH adjustment, chelating agents, colorants, emulsifies,
excipient, flavor agent, mineral, osmotic agents, a
pharmaceutically acceptable carrier, preservatives, stabilizers,
sugar, sweeteners, texturizers, and/or vitamins. The optional
ingredients can be added in any suitable amount.
[0083] As used herein the term "patient" is understood to include
an animal, especially a mammal, and more especially a human that is
receiving or intended to receive treatment, as it is herein
defined.
[0084] As used herein, "phytochemicals" or "phytonutrients" are
non-nutritive compounds that are found in many foods.
Phytochemicals are functional foods that have health benefits
beyond basic nutrition, and are health promoting compounds that
come from plant sources. Non-limiting examples of phytonutrients,
or phytochemicals, include those that are flavonoids and allied
phenolic and polyphenolic compounds, terpenoids such as
carotenoids, alkaloids and sulphur-containing compounds; including
curcumin, limonin, and quercetin or combinations thereof
[0085] As used in this disclosure and the appended claims, the
singular forms "a," "an" and "the" include plural referents unless
the context clearly dictates otherwise. Thus, for example,
reference to "a polypeptide" includes a mixture of two or more
polypeptides, and the like.
[0086] As used herein, a "prebiotic" is a food substance that
selectively promotes the growth of beneficial bacteria or inhibits
the growth or mucosal adhesion of pathogenic bacteria in the
intestines. They are not inactivated in the stomach and/or upper
intestine or absorbed in the GI tract of the person ingesting them,
but they are fermented by the gastrointestinal microflora and/or by
probiotics. Prebiotics are, for example, defined by Glenn R. Gibson
and Marcel B. Roberfroid, Dietary Modulation of the Human Colonic
Microbiota: Introducing the Concept of Prebiotics, J. Nutr. 1995
125: 1401-1412 (1995). Non-limiting examples of prebiotics include
acacia gum, alpha glucan, arabinogalactans, beta glucan, dextrans,
fructooligosaccharides, fucosyllactose, galactooligosaccharides,
galactomannans, gentiooligosaccharides, glucooligosaccharides, guar
gum, inulin, isomaltooligosaccharides, lactoneotetraose,
lactosucrose, lactulose, levan, maltodextrins, milk
oligosaccharides, partially hydrolyzed guar gum,
pecticoligosaccharides, resistant starches, retrograded starch,
sialooligosaccharides, sialyllactose, soyoligosaccharides, sugar
alcohols, xylooligosaccharides, or their hydrolysates, or
combinations thereof
[0087] As used herein, probiotic micro-organisms (hereinafter
"probiotics") are food-grade microorganisms (alive, including
semi-viable or weakened, and/or non-replicating), metabolites,
microbial cell preparations or components of microbial cells that
could confer health benefits on the host when administered in
adequate amounts, more specifically, that beneficially affect a
host by improving its intestinal microbial balance, leading to
effects on the health or well-being of the host. See, Salminen S,
Ouwehand A. Benno Y. et al., Probiotics: how should they be
defined?, Trends Food Sci. Technol. 1999:10, 107-10 (1999). In
general, it is believed that these micro-organisms inhibit or
influence the growth and/or metabolism of pathogenic bacteria in
the intestinal tract, and may also influence the microflora in the
mouth. The probiotics may also activate the immune function of the
host. For this reason, there have been many different approaches to
include probiotics into food products. Non-limiting examples of
probiotics include Aerococcus, Aspergillus, Bacteroides,
Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus,
Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc,
Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus,
Penicillium, Peptostrepococcus, Pichia, Propionibacterium,
Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus,
Streptococcus, Torulopsis, Weissella, or combinations thereof.
[0088] As used herein, a "processed whole food" is a whole food
that has been modified from its natural or prepared state and is in
a state so that it can be placed into a tube feed formulation.
[0089] The terms "protein," "peptide," "oligopeptides" or
"polypeptide," as used herein, are understood to refer to any
composition that includes, a single amino acid (monomers), two or
more amino acids joined together by a peptide bond (dipeptide,
tripeptide, or polypeptide), collagen, precursor, homolog, analog,
mimetic, salt, prodrug, metabolite, or fragment thereof or
combinations thereof For the sake of clarity, the use of any of the
above terms is interchangeable unless otherwise specified. It will
be appreciated that polypeptides (or peptides or proteins or
oligopeptides) often contain amino acids other than the 20 amino
acids commonly referred to as the 20 naturally occurring amino
acids, and that many amino acids, including the terminal amino
acids, may be modified in a given polypeptide, either by natural
processes such as glycosylation and other post-translational
modifications, or by chemical modification techniques which are
well known in the art. Among the known modifications which may be
present in polypeptides of the present invention include, but are
not limited to, acetylation, acylation, ADP-ribosylation,
amidation, covalent attachment of a flavanoid or a heme moiety,
covalent attachment of a polynucleotide or polynucleotide
derivative, covalent attachment of a lipid or lipid derivative,
covalent attachment of phosphatidylinositol, cross-linking,
cyclization, disulfide bond formation, demethylation, formation of
covalent cross-links, formation of cystine, formation of
pyroglutamate, formylation, gamma-carboxylation, glycation,
glycosylation, glycosylphosphatidyl inositol ("GPI") membrane
anchor formation, hydroxylation, iodination, methylation,
myristoylation, oxidation, proteolytic processing, phosphorylation,
prenylation, racemization, selenoylation, sulfation, transfer-RNA
mediated addition of amino acids to polypeptides such as
arginylation, and ubiquitination. The term "protein" also includes
"artificial proteins" which refers to linear or non-linear
polypeptides, consisting of alternating repeats of a peptide.
[0090] Non-limiting examples of sources of proteins include dairy
based proteins, plant based proteins, animal based proteins and
artificial proteins. Dairy based proteins include, for example,
casein, casein hydrolysates, caseinates (e.g., all forms including
sodium, calcium, potassium caseinates), whey hydrolysates, whey
(e.g., all forms including concentrate, isolate, demineralized),
milk protein concentrate, and milk protein isolate. Plant based
proteins include, for example, soy protein (e.g., all forms
including concentrate and isolate), pea protein (e.g., all forms
including concentrate and isolate), canola protein (e.g., all forms
including concentrate and isolate), other plant proteins that
commercially are wheat and fractionated wheat proteins, corn and it
fractions including zein, rice, oat, potato, peanut, and any
proteins derived from beans, buckwheat, lentils, and pulses. Animal
based proteins may include, for example, beef, poultry, fish, lamb,
seafood, pork, egg, or combinations thereof.
[0091] All dosage ranges contained within this application are
intended to include all numbers, whole or fractions, contained
within said range.
[0092] As used herein, a "synbiotic" is a supplement that contains
both a prebiotic and a probiotic that work together to improve the
microflora of the intestine.
[0093] As used herein, the terms "treatment," "treat" and "to
alleviate" include both prophylactic or preventive treatment (that
prevent and/or slow the development of a targeted pathologic
condition or disorder) and curative, therapeutic or
disease-modifying treatment, including therapeutic measures that
cure, slow down, lessen symptoms of, and/or halt progression of a
diagnosed pathologic condition or disorder; and treatment of
patients at risk of contracting a disease or suspected to have
contracted a disease, as well as patients who are ill or have been
diagnosed as suffering from a disease or medical condition. The
term does not necessarily imply that a subject is treated until
total recovery. The terms "treatment" and "treat" also refer to the
maintenance and/or promotion of health in an individual not
suffering from a disease but who may be susceptible to the
development of an unhealthy condition, such as nitrogen imbalance
or muscle loss. The terms "treatment," "treat" and "to alleviate"
are also intended to include the potentiation or otherwise
enhancement of one or more primary prophylactic or therapeutic
measure. The terms "treatment," "treat" and "to alleviate" are
further intended to include the dietary management of a disease or
condition or the dietary management for prophylaxis or prevention a
disease or condition.
[0094] As used herein, a "tube feed" is a complete or incomplete
nutritional product or composition that is administered to an
animal's gastrointestinal system, other than through oral
administration, including but not limited to a nasogastric tube,
orogastric tube, gastric tube, jejunostomy tube ("J-tube"),
percutaneous endoscopic gastrostomy ("PEG"), port, such as a chest
wall port that provides access to the stomach, jejunum and other
suitable access ports.
[0095] As used herein the term "vitamin" is understood to include
any of various fat-soluble or water-soluble organic substances
non-limiting examples include choline, vitamin A, vitamin B1
(thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin or
niacinamide), vitamin B5 (pantothenic acid), vitamin B6
(pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine
hydrochloride), vitamin B7 (biotin), vitamin B9 (folic acid), and
vitamin B12 (various cobalamins; commonly cyanocobalamin in vitamin
supplements), vitamin C, vitamin D, vitamin E, vitamin K, folic
acid and biotin) essential in minute amounts for normal growth and
activity of the body and obtained naturally from plant and animal
foods or synthetically made, pro-vitamins, derivatives,
analogs.
[0096] In an embodiment, a source of vitamins or minerals can
include at least two sources or forms of a particular nutrient.
This represents a mixture of vitamin and mineral sources as found
in a mixed diet, and may include natural forms. Also, a mixture may
also be protective in case an individual has difficulty absorbing a
specific form, a mixture may increase uptake through use of
different transporters, or may offer a specific health benefit. As
an example, there are several forms of vitamin E, with the most
commonly consumed and researched being tocopherols (alpha, beta,
gamma, delta) and less commonly tocotrienols (alpha, beta, gamma,
delta), which all vary in biological activity. There is a
structural difference such that the tocotrienols can more freely
move around the cell membrane; several studies report various
health benefits related to cholesterol levels, immune health, and
reduced risk of cancer development. A mixture of tocopherols and
tocotrienols would cover the range of biological activity.
[0097] The source of selenium can be of inorganic (e.g., selenite,
selenate) or organic in origin (e.g., selenomethionine,
selenocysteine, seelnoyeast), all occurring in a habitual mixed
diet. Inorganic and organic have distinct, complementary uptake and
distribution mechanisms in the body, thus allowing to optimize
selenium provision to the body.
[0098] As used herein, "whole food," "whole food component," "real
food" or "real food component" is understood to mean a food
typically ingested by an individual in a normal daily diet when the
food is in its natural or prepared state as opposed to any reduced
components of the food. For example, a whole food may include any
known fruits, vegetables, grain, meats or sources of protein,
carbohydrate or fat. The "whole food," "whole food component,"
"real food" or "real food component" may be processed so they can
be used in a tube feed. In an embodiment, this processing is
minimal to keep it as close to the "unprocessed" food as possible,
and still be usable in the tube feed. The skilled artisan will
appreciate that the use of a "whole food," "whole food component,"
"real food" or "real food component" does not limit the use of
other nutrient sources. For example, powdered fruits and vegetables
may also be included in the compositions.
[0099] As used herein, "zoo-chemicals" refers to functional foods
that have health benefits beyond basic nutrition, and are health
promoting compounds that are found in animal sources.
[0100] Patients that are either inactive or fed one single formula
diet for a significant amount of time are susceptible to metabolic
disturbances that may result from a lack of variety or proper
nutrient values in their diets. For example, long-term tube-fed
patients may suffer from such disturbances. Although the basic
nutritional needs of the patient may be met through tube feeding,
current formulas for tube feeding are not optimized for maintenance
of patient health over long time periods.
[0101] Patients who receive long-term tube feeds often remain on a
single dietary source for weeks, months, or even years. Therefore,
the long-term tube feeding formula must deliver not only the
essential macro- and micronutrients, but other dietary constituents
that may become conditionally essential or important for
well-being. A short-term tube feeding patient would consume an oral
diet before and after the tube feeding episode, thus limiting any
negative effects caused by any missing conditionally essential
compounds. Long-term, tube fed patients (often sedentary or
bedridden), however, may suffer from any number of health
complications for example, increased bone or muscle loss, low-grade
inflammation, reduced gastrointestinal motility, increase insulin
resistance and depressed or altered immune systems. The nutritional
needs of such long-term, tube fed patients with these types of
chronic diseases will certainly differ from those requiring
short-term tube feedings. Accordingly, Applicant has found that
patients suffering from these processes associated with decreased
activity, should be administered tube feed formulations having
adequate calcium, vitamin D, and protein, complex carbohydrates,
fiber (including prebiotics), nucleotides, .omega.-3 fatty acids,
antioxidants, phytonutrients, and/or various herbs, spices and
flavorings, or combinations thereof Although the feeding needs of
long-term tube feed patients is different than short-term tube feed
patients, the skilled artisan will appreciate that the present
compositions may be used for either short or long-term tube feed
patients, as well as patients receiving supplemental
nutritional.
[0102] Many patients on long-term tube feed formulations are older
adults. Although the aging process is natural, there are a number
of physiological changes that should be limited or slowed if
possible. These physiological changes include, for example,
sarcopenia (loss of lean body mass), increase risk of osteoporosis
or fracture, depressed gut health, altered immune function,
increase oxidative stress, increased insulin resistance and loss of
appetite. Particularly in older adults, dysphagia, stroke head and
neck cancer, and neurological cases including, but not limited to,
Parkinson's Disease, Alzheimer's and other neurological changes
associated with aging are common conditions that require tube
feeding.
[0103] There are many similarities between elderly adult and
sedentary adult populations. The nutritional compositions that are
fed to these patients should address, among other conditions,
musculoskeletal health, gut health, immune function, low grade
inflammation, oxidative stress and insulin resistance. Applicant
has identified several key nutrients to address the needs of adult
patients who experience any or all of the physiological impacts
listed above.
[0104] For example, adult patients experiencing a change in glucose
metabolism, which includes, for example, insulin resistance and
impaired glucose uptake, may be fed nutritional compositions that
include ingredients such as, but not limited to, complex
carbohydrates, fiber, herbs, spices, phytochemicals and/or
flavorings such as ginseng or cinnamon. Likewise, adult patients
experiencing a change in gut function may be fed nutritional
compositions that include ingredients such as, but not limited to,
fiber (both soluble and insoluble), prunes, nucleotides, prebiotics
and probiotics.
[0105] Further, for adult patients experiencing
hypercholesterolemia or hypertriglyceridemia or for prevention of
related diseases, tube feed formulations or oral nutritional
supplements (liquid or solid) may include, for example, .omega.-3
polyunsaturated fatty acids, monounsaturated fatty acids,
phytochemicals, plant sterols/stanols, soluble fiber, and herbs,
spices and/or flavorings including, for example, garlic or
cinnamon. The saturated fatty acids, however, should be limited to
less than 7% of the total energy, the cholesterol should be limited
to less than 200 mg, and the trans fatty acids should also be
limited.
[0106] Nutritional compositions including, for example,
antioxidants, nucleotides, prebiotics and .omega.-3 polyunsaturated
fatty acids may be fed to adult patients experiencing a decrease in
immune function or an increase in oxidative stress.
[0107] Additionally, adult patients experiencing an impact on
musculoskeletal health including, for example, bone health and
muscle mass/strength, may be fed nutritional compositions having
calcium, high amounts of vitamin D and high quality protein. A
large bolus of protein may be administered at a given time to
optimize protein synthesis in elderly individuals. See, Arnal M A,
et al., Protein pulse feeding improves protein retention in elderly
women, Am. J. Clin. Nutr., 69:1202-8 (1999); see also, Symons et
al., Aging does not impair the anabolic response to a protein-rich
meal, Am. J. Clin. Nutr., 86:451-6 (2007). Indeed, a bolus of 20-30
g protein is thought to optimally stimulate protein synthesis.
Details of many of these conditions are discussed further below
with respect to the nutritional needs of pediatric patients. In
this way, the skilled artisan will appreciate that many nutrients
required by adult patients may also be required by pediatric
patients.
[0108] With respect to children, there are a few basic concepts
that apply to most, if not all, pediatric or young adult patients.
For example, these patients require adequate and appropriate
nutrition to ensure proper growth. These patients would also
benefit from measures to prevent chronic diseases. Indeed,
preventative nutrition to reduce the risk of developing coronary
vascular disease and cancer later in life may be particularly
relevant for this population.
[0109] More specifically, there are conditions common to pediatric
patients that may require long-term feedings (e.g., tube feedings).
Several conditions include, but are not limited to, cystic
fibrosis, quadriplegia, cerebral palsy and neuromuscular disorders.
Applicant has also identified several key nutrients to address the
needs of pediatric patients who experience any or all of the
physiological impacts listed above.
[0110] To ensure adequate growth, pediatric patients must maintain
adequate nutritional status (macro- and micronutrients), and be fed
nutritional compositions that provide adequate energy.
[0111] Pediatric patients suffering from poor bone health, which
includes, but is not limited to, osteopenia and osteoporosis, may
be fed nutritional compositions having adequate or high amounts of
calcium and vitamin D.
[0112] Gut health, including motility and microbiota composition
(impacted by a variety of factors, including antibiotic usage), in
pediatric patients may be improved by providing fiber (insoluble
and soluble), prebiotic fibers and probiotics, and nucleotides.
[0113] Nutritional compositions having increased amounts of fat
(e.g., 35-40% total energy), protein, and vitamins and minerals may
be fed to patients suffering from pancreatic insufficiency and/or
malabsorption of fat and fat soluble vitamins. Often times, a
low-fat diet is recommended in patients with pancreatic
insufficiency to reduce steatorrhea.
[0114] Patients suffering from inflammation may be fed nutritional
compositions including antioxidants, nucleotides, prebiotics and
.omega.-3 polyunsaturated fatty acids.
[0115] In a more specific example, cerebral palsy is a chronic,
non-progressive motor disability that results from an injury to the
developing brain early in life. Cerebral palsy is generally
characterized by dysfunctions in motor coordination and muscle
tone. Because long-term tube fed pediatric patients are often
wheel-chair bound or have severe difficulty with ambulation, their
energy needs are significantly lower than those of healthy
children, but their protein needs are often higher. Additionally,
as described below, maintenance of bone health, prevention of
pressure ulcers and maintenance of healthy immune function, gut
health are common concerns. These children often require exclusive
tube feeding.
[0116] Indeed, bone fractures are a significant problem in children
with spastic quadriplegia due to many factors. Many children with
cerebral palsy are taking anticonvulsant medications for seizure
control, and alterations in vitamin D and calcium metabolism are
associated with some anticonvulsant use. See, Hahn, T. J. et al.,
Effect of Chronic Anticonvulsant Therapy on Serum
25-Hydroxycalciferol Levels in Adults, The New England J. of Med.,
pp. 900-904 (1972). See also, Hunter, J. et al., Altered Calcium
Metabolism in Epileptic Children on Anticonvulsants, British
Medical Journal, pp. 202-204 (1971). See also, Hahn, T. J. et al.,
Phenobarbital-Induced Alterations in Vitamin D Metabolism, J. of
Clinical Investigation, Vol. 51, pp 741-748 (1972). Although the
influence of anticonvulsant medication on vitamin D status is not
completely clear, it is apparent that non-ambulatory children are
at increased risk for bone fractures.
[0117] Studies have shown that medications to control seizures,
such as phenobarbital and Dilantin, can alter the metabolism and
the circulating half-life of vitamin D. Research has also suggested
that patients on at least two anti-seizure medications who are
institutionalized and, therefore, not obtaining most of their
vitamin D requirement from exposure to sunlight, increase their
vitamin D intake to approximately 25 .mu.g (1,000 IU)/day to
maintain their serum 25(OH)D levels within the mid-normal range of
25 to 45 ng/ml (62.5 to 112.5 nmol/liter). It is thought that this
should prevent the osteomalacia and vitamin D deficiency associated
with anti-seizure medications. Applicant has found that pediatric
patients suffering from such bone health/anticonvulsant issues may
see improvement in these areas if administered nutritional
compositions having increased amounts of calcium and vitamin D.
[0118] In yet another example, patients, and especially children,
with cerebral palsy and neuromuscular disorders are also frequently
at risk of developing pressure ulcers or chronic wounds and, as
such, may require special diets. Individuals that are susceptible
to chronic wounds include, for example, those with prolonged
immobilization, bed and chair bound and/or experiencing
incontinence, those that are experiencing protein-energy
malnourishment, those with neurological, traumatic or terminal
illnesses, or those with circulatory or sensory deficits. See,
Agency for Health Care Policy and Research, 1992, 1994. Receiving
adequate nutrition plays a key role in prevention and treatment of
such chronic wounds.
[0119] For example, specific nutrients including protein, vitamin
A, vitamin C, vitamin E, zinc, arginine, citrulline and glutamine
can play a role in reducing the risk of developing pressure ulcers,
particularly if a deficiency is suspected. Adequate hydration also
plays a significant role in reducing the risk of developing
pressure ulcers. Indeed, it has been reported that incidence of
pressure ulcer development was lower in a group receiving
additional protein, arginine, vitamin C and zinc when compared to a
control group (13% versus 72%). See, Neander, et al., A specific
nutritional supplement reduces incidence of pressure ulcers in
elderly people, Numico Research, www.numico-research.com.
[0120] Once a chronic wound or pressure ulcer has developed,
various nutrients play an important role in healing, with specific
nutrients having an impact at different phases of the process. For
example, Table 1 below demonstrates the key nutrients that impact
different phases of wound healing. As is shown in Table 1, certain
vitamins, minerals and amino acids should be present at the
different phases of wound healing.
TABLE-US-00001 TABLE 1 Phase Process Key Nutrients Phase I:
Inflammation Wound exudation Vitamin C Fibrin clot formation
Vitamin E Selenium Arginine Cysteine Methionine Phase II:
Proliferation Angiogenesis Vitamin A Fibroblast proliferation
Vitamin C Collagen synthesis Thiamin Wound matrix formation
Pantothenic acid and epithetialization Zinc Manganese Phase III:
Collagen cross linkage Vitamin A Maturation and Remodeling Wound
contraction Vitamin C Tensile strength Zinc development Copper
Manganese
[0121] Applicant has surprisingly found that pediatric patients
suffering from pressure ulcers may see improvement in these areas
if administered nutritional compositions having increase amounts of
protein, vitamin A, vitamin C, vitamin E, zinc, arginine,
citrulline and glutamine.
[0122] There are also significant health economic implications with
prevention of pressure ulcer development or progression. For
example, the average healing times for pressure ulcers are longer
at later stages of the ulcers, with Stage III and Stage IV ulcers
requiring substantially longer treatment than Stage II. In a UK
cost of illness study, it is clear that there are increased
treatment costs with increased severity of pressure ulcers. See,
Bennett G, et al., The cost of pressure ulcers in the UK, Age and
Ageing, 33: 230-235 (2004). In another study, it was shown that
Stage III and Stage IV pressure ulcers cost substantially more to
treat than Stage II pressure ulcers. See, Xakellis G C, et al., The
cost of healing pressure ulcers across multiple health care
settings, Adv. Wound Care, 9:18-22 (1996). These significant costs
are shown below in Table 2.
TABLE-US-00002 TABLE 2 Total Treatment Treatment Cost Cost per
Pressure per Pressure Hospitalization Ulcer Including Ulcer
Excluding Cost per Hospital Stay Hospital Stay Pressure Stage Mean
(SD) Mean (SD) Ulcer Stage I $1,119 $443 $676 (n = 37) (4,234)
(581) Stage III and IV $10,185 $700 $9,485 (n = 8) (27,635) (831)
All ulcers $2,731 $489 $2,242 (n = 45) (12,184) (629)
[0123] In another example, central adiposity has been associated
with insulin resistance and low grade inflammation, thus is it
possible that provision of low energy, high protein diets to
growing children with low physical activity will prevent the
insulin resistance thus permitting more effective insulin activity
and thus anabolism. High protein diets have been shown to modulate
secretion of anabolic hormones such as growth hormone. See, Clarke,
et al., Effect of high-protein feed supplements on concentrations
of growth hormone ("GH`), insulin-like growth factor-I ("IGF-I")
and IGF-binding protein-3 in plasma and on the amounts of GH and
messenger RNA for GH in the pituitary glands of adult rams, J.
Endocrinol. 138 (3):421-427 (1993). See, also, J. R. Hunt, et al.,
Dietary protein and calcium interact to influence calcium
retention: a controlled feeding study, Am. J. Clin. Nutr. 89
(5):1357-1365 (2009). See, also, G. Blanchard, et al., Rapid weight
loss with a high-protein low-energy diet allows the recovery of
ideal body composition and insulin sensitivity in obese dogs, J.
Nutr. 134 (8 Suppl):21485-2150S (2004).
[0124] These benefits are particularly important during rapid
growth as the growth hormone axis has been shown to be associated
with chronic diseases later in life. Therefore modulation of the
growth hormone axis (including IGF-1) will benefit the clinical
outcome of the patient both in the short term and also in later
years. This can lead to significant improvement in quality of life
but also in positive health economic outcomes. See, J. M. Kerver,
et al., Dietary predictors of the insulin-like growth factor system
in adolescent females: results from the Dietary Intervention Study
in Children (DISC), Am. J. Clin. Nutr. 91 (3):643-650 (2010).
[0125] In another example, hospitalized, institutionalized, and
recovering patients may be at an increased risk of metabolic
disturbances caused by poor renal and/or pulmonary function. While
the body's blood pH is fairly well maintained over time, primarily
through regulation by the kidneys and lungs, dietary intake can
significantly influence the body's acid/base balance. As a result,
the acid-base potential of the diet becomes increasingly important
in maintenance of the patient's health, including musculoskeletal
and immune health.
[0126] Upon ingestion and after metabolism, foods can be
categorized as either more acidic or more alkaline producing.
Correlational human intake data suggests that diets higher in
fruits and vegetables support a net alkaline environment to help
maintain metabolic homeostasis. Conversely, acid producing diets
have been found to negatively impact musculoskeletal health.
Correction of low-grade metabolic acidosis through diet
modification may help to preserve skeletal muscle mass and improve
the health of patients with a variety of pathological conditions
including, for example, muscle loss.
[0127] Because long-term tube fed pediatric patients, for example,
lack variation in their food sources they may be particularly
susceptible to the effects of such acid-forming diets. Although the
kidneys are efficient at neutralizing acids, long term exposure to
high acid is believed to overwhelm the kidneys' capacity to
neutralize acid and potential damage may occur. As a result,
alkaline compounds that include, but are not limited to, calcium
are used to neutralize these dietary acids (in the case of muscle,
glutamine can act as a buffer). The most readily available source
of calcium in the body is bone. One theory is that high acid diets
may contribute to bone loss as the body mobilizes stored calcium to
buffer metabolic acid. The hypothesis is that low acid diets may
result in benefits that include attenuation of bone and muscle loss
as well as maintaining renal health. See, Wachman, A., et al., Diet
and Osteoporosis, Lancet, 1:958-959 (1968); see also, Frassetto L,
et al., Potassium Bicarbonate Reduces Urinary Nitrogen Excretion in
Postmenopausal Women, J. Clin. Endocrinol. Metab., 82:254-259
(1997).
[0128] In addition to bone specific effects, human correlational
data suggests that dietary intake of fruits and vegetables support
a net alkaline environment which can help regulate metabolic
homeostatis. This net alkaline state has been associated with an
enhanced preservation of lean body mass, at least in older
individuals. See, Dawson-Hughes B, et al., Alkaline diets favor
lean tissue mass in older adults, Am. J. Clin. Nutr., March;
87(3):662-5 (2008). Thus, the manipulation of Phosphorus (P),
Sodium (Na), Magnesium (Mg), Potassium (K) and Calcium (Ca) in
complete nutritional formulas can serve to enhance net alkaline
production to further minimize endogenous skeletal muscle
proteolysis as well as preserve lean body mass. The same is true of
the manipulation of a protein source.
[0129] In an embodiment, the nutritional compositions of the
present disclosure may be administered as a bolus or a continuous
tube feeding. In an embodiment, the tube feedings are administered
as a bolus since it maximizes the physiological response to the
feeding occasion. This method provides complete nutrition to
patients in that a concentrated dose of protein is delivered at
each feeding. This concentrated provision of protein is essential
to increasing plasma amino acids (e.g., leucine), stimulating
protein synthesis, and attaining a net positive protein balance.
This anabolic state post-feeding is required to optimize growth
though the accrual of lean body mass and linear bone growth
(accrual of bone mineral density). The mechanism is related to the
above mentioned increase in serum leucine as well as anabolic
endocrine response including the stimulation of the
insulin-IGF-1-GH axis leading to increased uptake and
bio-utilization of substrates for musculoskeletal development
(thus, leading to reduced accumulation of visceral adiposity).
[0130] The present disclosure is directed to nutritional products
and compositions that provide patients requiring tube feedings
and/or oral nutritional supplements with sufficient levels of
certain micronutrients and macronutrients and that mimic a healthy,
whole food diet and provide physiological benefits and emotional
appeal. In order to mimic a "whole food" diet, the formulas of the
present disclosure may, for example, increase the number and
variety of fruits and vegetables, increase the variety of
macronutrient sources and include other components found in whole
foods including, for example, nucleotides, phytonutrients, herbs,
spices or flavorings, plant sterols, etc.
[0131] One manner in which tube feeding formulas can mimic healthy,
whole food diets is to increase the servings of fruits and
vegetables administered per day. Indeed, any incremental increase
in fruit and vegetable content as compared to current market tube
feed formulations would be beneficial to a tube fed patient or
patient requiring oral nutritional supplements. From a review of
200 epidemiological studies, increase intakes of fruits and
vegetables reduced the risk of several types of cancers. See, Block
et al., Fruit, vegetables and cancer prevention: A review of the
epidemiological evidence, Nutrition and Cancer, 18: 1-29 (1992).
Further, for every one serving per day increase in fruits or
vegetables, there was a 4% reduction in coronary heart disease
risk. See, Joshipura et al., The effect of fruit and vegetable
intake on risk for coronary heart disease, Ann. Intern. Med.
134:1106-1114 (2001). In addition, other studies have shown
benefits of flavonoid consumption and reduced risk of death from
coronary heart disease. The major sources of flavonoids included
teas, apples, and onions. See, Hertog et al., Dietary antioxidant
flavonoids and risk of coronary heart disease: the Zutphen Elderly
Study, The Lancet, vol. 342, Issue 8878:1007-1011 (1993).
[0132] Applicant has found that providing at least 5 servings or at
least 400 g of fruits and vegetables per complete feeding provides
the tube fed patient with amounts of fruits and vegetables
typically recommended to individuals consuming an oral, whole food
diet. In an embodiment, at least 6 or 7 servings of fruits and
vegetables are provided in the present nutritional compositions. In
yet another embodiment, at least 8 servings of fruits and
vegetables are provided in the present nutritional compositions. In
an embodiment, the fruits and vegetable reduce the risk of several
chronic diseases.
[0133] As such, in an embodiment, nutritional compositions of the
present disclosure include a whole food, or a real food, component.
Whole foods contain beneficial food constituents in addition to the
well-recognized macronutrients, vitamins and minerals. Several of
these food constituents include phytochemicals and nucleotides,
which provide several benefits to a patient on a long-term tube
feeding diet, or requiring oral nutritional supplements, as will be
further discussed below.
[0134] For example, phytonutrients can act as antioxidants within
the body. See, Carlson et al., The total antioxidant content of
more than 3100 foods, beverages, spices, herbs and supplements used
worldwide, Nutr. J., 9:3 (2010). Thus, it is beneficial to provide
phytonutrients in certain amounts. For example, in a 2008 report,
it was estimated that if an individual consumed 5 servings of
fruits and/or vegetables daily, polyphenol intake would be greater
than 500 mg, and probably closer to 500-1,000 mg if cocoa, tea or
coffee is consumed. See, Williamson, et al., Dietary reference
intake (DRI) value for dietary polyphenols: are we headed in the
right direction?, British Journal of Nutrition, 99, Suppl. 3,
S55-59 (2008).
[0135] In a study including Finnish adults (n=2007), mean total
intake of polyphenols (phenolic acids, anthocyanidins, and other
flavonoids, proanthocyanidins, and ellagitannins) was 863.+-.415
mg/d; intakes of specific classes included 641 mg/d phenolic acids,
128 mg/d total proanthocyanidins, 47 mg/d anthocyanidins, 33 mg/d
total flavonoids, 12 mg/d ellagitannins, 309 mg/d isoflavones, 0.9
mg/d lignans, 5.9 mg/d carotenoids, and 368 mg/d sterols. The
largest contributors to phenolic acid intake was coffee followed by
breads and tea; berries and berry products to anthocyanins; fruits
and tea to flavonols, flavonones and flavones; apples, berries, tea
and chocolate to proanthocyanidins; vegetables to carotenoids; soy
products to isoflavonoids; and seeds, soy products, rye and cereal
products to lignans. See, Ovaskaincn et al., Dietary Intake and
Major Food Sources of Polyphenols in Finnish Adults, American
Society for Nutrition J. Nutr. 138:562-566 (March 2008). This
information is, however, an example and is not necessarily
representative of worldwide intake as it may vary depending on food
patterns and preferences. In a another study near Indianapolis
involving 280 people, average intakes of lutein and zeaxanthin, and
B-carotene, were 1101.+-.838 and 2935.+-.2698 .mu.g/d,
respectively. See, Curran-Celentano et al., Relation between
dietary intake, serum concentrations, and retinal concentrations of
lutein and zeaxanthin in adults in a Midwest population, American
Journal of Clinical Nutrition, Vol. 74, No. 6, 796-802 (December
2001).
[0136] It is possible to estimate phytonutrient content to foods by
using the USDA Standard Reference database (Release 23). This
database contains, for example, data on carotenoid content in
foods. Examples of such carotenoid contents include: (i) 1 cup
chopped, raw carrots (NDB No: 11124), beta carotene 10605 mcg,
alpha carotene 4451 mcg, lycopene 1 mcg, lutein+zeaxanthin 328 mcg;
(ii) 1 cup spinach (NDB No: 11457): beta carotene 1688 mcg,
lutein+zeaxanthin 3659 mcg; (iii) 1 cup tomatoes, red, ripe, cooked
(NDB No: 11530): beta carotene 703 mcg, lycopene 7298 mcg,
lutein+zeaxanthin 226 mcg; (iv) 1 cup chopped broccoli, raw (NDB
No: 11090): beta carotene 329 mcg, alpha carotene 23 mcg, beta
cryptoxanthin 1 mcg, lutein+zeaxanthin 1277 mcg; (v) 1 cup
broccoli, frozen, chopped, cooked, boiled, drained, without salt
(NDB No: 11093): beta carotene 1098 mcg, alpha carotene 35 mcg,
beta cryptoxanthin 2 mcg, lutein+zeaxanthin 2015 mcg; (vi) 1 cup
blueberries, raw (NDB No: 09050): beta carotene 47 mcg,
lutein+zeaxanthin 118 mcg; (vii) 1 cup halves, strawberries, raw
(NDB No: 09316): beta carotene 11 mcg, lutein+zeaxanthin 40 mcg;
and (viii) 1 cup slices apple, raw with skin (NDB No: 09003) beta
carotene 29 mcg, beta cryptoxanthin 12 mcg lutein+zeaxanthin 32
mcg.
[0137] The phytonutrient content of foods, however, may vary
depending on processing, growing conditions, cultivar, etc. See,
Kim H J et al., Changes in Phytonutrient Stability and Food
Functionality during Cooking and Processing, Korean J Food Cookery
Sci., Vol 22 No 3: 402-417 (2006). Since processing and handling
can influence the phytonutrient content of the final product, the
present disclosure relates to a tube feed that contains fruit and
vegetable ingredients with known/standardized levels of select
phytonutrients, and are processed in such a manner to maintain a
desired level of phytonutrients in the end product.
[0138] There are many factors that may impact the phytonutrient
content of various fruits and vegetables. For example, physical
factors may include, but are not limited to, temperature, pressure,
oxidation/reduction potential, pH, enzymes, metals, leaching,
light, water activity, etc. Biological factors affecting food
constituents may include, but are not limited to, maturity,
cultivar, state of the tissue, composition, etc. See, Kalk, Effects
of Production and Processing Factors on Major Fruit and Vegetable
Antioxidants, Journal of Food Science, Vol 70, Nr 1 (2005); see,
also, Kim H J, et al., Changes in Phytonutrient Stability and Food
Functionality during Cooking and Processing, Korean J Food Cookery
Sci., Vol 22 No 3: 402-417 (2006). Depending on the
phytonutrient/fruit or vegetable, processing may destroy or enhance
presence and/or bioavailability. Additionally, Kalk reports that
carotenoids are relatively stable through processing, while
phenolic antioxidants are more prone to losses. See, Kalk, Table
3.
[0139] Furthermore, the impact of processing on tomatoes
phytonutrient levels has been well studied, such that thermal
processing increases the bioavailable content of lycopene. See,
Dewanto et al., Thermal Processing Enhances the Nutritional Value
of Tomatoes by Increasing Total Antioxidant Activity, J. Agric.
Food Chem., 50 (10), pp 3010 3014 (2002). On the other hand,
thermal processing of other fruits and vegetables may degrade these
components. Severe heat treatment of red cabbage (e.g., canning)
resulted in 73% degradation of glucosinolates. See, Oerlemans et
al., Thermal degradation of glucosinolates in red cabbage, Food
Chemistry, 95; 19-29 (2006). Similar results were found during
cooking of broccoli (74% loss after microwaving). See, Vallejo, F.
et al., Glucosinolates and vitamin C content in edible parts of
Broccoli florets after domestic cooking, European Food Research and
Technology, 215, 310-316 (2002).
[0140] Another manner in which nutritional compositions can mimic
healthy, whole food diets is to increase the variety of food
consumed per day. For example, with respect to macronutrients, it
is important that nutritional compositions include a variety
protein, fat and carbohydrate sources. Indeed, formulations having
a variety of protein, fat and carbohydrate sources more closely
resemble a whole food diet. With respect to micronutrients, the
source of vitamins and minerals includes at least two sources or
forms of a particular nutrient.
[0141] The present nutritional compositions may include at least 4
different sources of macronutrients, which include, for example,
protein, fat, and carbohydrates. In another embodiment there may be
at least 5, 6, 7, or 8 different sources of macronutrients. In an
embodiment, there exists at least one source each of protein, fat
and carbohydrates in the nutritional compositions. However, the
skilled artisan will appreciate that there may be any combination
of the at least 8 different sources of macronutrients. For example,
there may be 3 or more protein sources in the present nutritional
compositions. In an embodiment, there may be 3 or more carbohydrate
sources in the nutritional compositions. In another embodiment,
there may be at least 3 or more fat sources in the nutritional
compositions. Alternatively there may be 4 or more of the protein,
carbohydrate, fat or fiber sources in the composition. The sources
may be the same source, or a different source. In another
embodiment, there may be at least 3 or more fiber sources in the
nutritional compositions.
[0142] In an embodiment, vegetable proteins may be included to
further enhance the net alkaline profile of the formula while
delivering high quality protein blends that provide the essential
nutritional requirements for supporting growth and development.
Based on the nutritional profile of specific vegetable proteins
(e.g., pea protein isolate) there are limitations in the amount of
vegetable protein sources that can be included in a formula. For
example, the amino acid profile of pea protein includes all of the
indispensable amino acids. Pea protein is relatively rich in
arginine, but limiting in the sulphur-containing amino acids,
methionine, and cysteine. However, it is possible, for example, to
blend pea protein isolates with a complete protein source (such as
milk protein or complete vegetable proteins) having sufficient
sulphur-containing amino acids to offset such deficiency. Canola
protein (i.e., isolates, hydrosylates and concentrates) is one such
vegetable protein which can provide appreciable amounts of
sulfur-containing amino acids to further augment the amino acid
profile to deliver the necessary protein quality to the patient.
Additionally, animal derived proteins are typically more abundant
in sulphur-containing amino acids than vegetable proteins.
Furthermore, given the potential for viscosity limitations
associated with, for example, tube feeding and the need to maintain
the necessary nutritional value of protein, the formula may include
about 10-50% protein coming from a vegetable source.
[0143] The present compositions may also use a mixture of
macronutrient sources that have associated health benefits and/or
emotional appeal. For example, the protein may be derived from
vegetable sources while maintaining high Protein Digestibility
Corrected Amino Acid Scores ("PDCAAS"). The fat sources may include
olive and canola oil, and may be less refined to maintain higher
polyphenol content.
[0144] The skilled artisan will appreciate that the protein content
of the present nutritional compositions may be higher than typical
long-term tube feed formulations in embodiments having high amounts
of protein. For example, the Recommended Dietary Allowance ("RDA")
of protein for both men and women is 0.80 g of good quality
protein/kg body weight/day and is based on careful analysis of
available nitrogen balance studies. See, National Academy of
Sciences, Institute of Medicine, Food and Nutrition Board, Dietary
Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty
Acids, Cholesterol, Protein, and Amino Acids (Macronutrients),
Chapter 10 (2005). In an embodiment, the present compositions
provide protein to a patient in an amount of from about 1.0 to 2.5
g/kg body weight/day. In another embodiment, the present
compositions provide protein to a patient in an amount of about 1.5
to 2.0 g/kg body weight/day. Accordingly, the present compositions
may provide protein to a patient in an amount that is nearly twice
the RDA of protein for men and women.
[0145] In another embodiment, the protein is provided in an amount
to provide about 5 to about 40% energy from protein per day. In
another embodiment, the protein is provided in an amount to provide
from about 10% to about 35% energy from protein per day. In another
embodiment, the protein is provided in an amount to provide from
about 25% to about 30% energy from protein per day.
[0146] Sources of complex carbohydrates or whole grains such as,
for example, bran, oatmeal, barley, beans, rice, and peas, may be
used in the present compositions, as recommended in the Dietary
Guidelines of the Dietary Guidelines Advisory Committee. Any
suitable carbohydrate may be used in the present nutritional
compositions including, but not limited to, sucrose, lactose,
glucose, fructose, corn syrup solids, maltodextrin, modified
starch, amylose starch, tapioca starch, corn starch or combinations
thereof. Carbohydrates may be provided in an amount sufficient to
provide from about 40% to about 70% total energy. In an embodiment,
the carbohydrates are provided in an amount sufficient to provide
from about 45% to about 65% total energy of the nutritional
compositions.
[0147] A source of fat may also be included in the present
nutritional compositions. The source of fat may include any
suitable fat or fat mixture. For example, the fat source may
include, but is not limited to, vegetable fat (such as olive oil,
corn oil, sunflower oil, rapeseed oil, hazelnut oil, soy oil, palm
oil, coconut oil, canola oil, lecithins, and the like), animal fats
(such as milk fat, tallow, lard, poultry fat, fish oil, etc.), or
combinations thereof. Additionally, fats such as olive oil and
canola oil may be used in the present compositions and are commonly
purported to have heart health benefits. Fats may be provided in an
amount sufficient to provide from about 20% to about 40% total
energy. In an embodiment, the fats are provided in an amount
sufficient to provide from about 25% to about 35% total energy of
the nutritional compositions.
[0148] With respect to fruits and vegetables, the present
compositions may increase the variety of foods consumed per day by
combining and using several different types of fruits and
vegetables. The nutritional compositions of the present disclosure
may provide fruits and vegetables in an amount recommended by
individuals consuming a whole food diet. In one embodiment, the
effective amount is at least about 3 servings of fruits and
vegetables. In an embodiment, the nutritional compositions include
from about 4 to about 10 servings of fruits and vegetables. In an
embodiment, the nutritional compositions include at least about 6
or 7 servings of fruits and vegetables. In an embodiment, any
incremental amount of fruits and vegetables is beneficial.
[0149] Fruits included in the present nutritional compositions may
include any known fruit such as, but not limited to, apples,
bananas, coconut, pear, apricot, peach, nectarines, plum, cherry,
blackberry, raspberry, mulberry, strawberry, cranberry, blueberry,
grapes, prunes, grapefruit, kiwi, rhubarb, papaya, melon,
watermelon, pomegranate, lemon, lime, mandarin, orange, tangerine,
guava, mango, pineapple, etc. Similarly, vegetables may include any
known vegetable such as, but not limited to, amaranth, arugula,
brussels sprouts, cabbage, celery lettuce, radicchio, water cress,
spinach, pumpkin, squash, mushrooms, peas, beans, beets, carrots,
potatoes, radish, rutabaga, turnips, etc.
[0150] It is also possible to include fruits and vegetables from
the five different colors categories, which represent a variety in
the types of phytochemicals provided in the formulation. See, Heber
D, et al., Applying Science to Changing Dietary Patterns, J. Nutr,
131:3078S-3081S (2001). Phytochemicals are non-nutritive compounds
that are found in many fruits and vegetables, among other foods.
There are thousands of phytochemicals that can be categorized as
flavonoids and allied phenolic and polyphenolic compounds,
terpenoids, e.g., carotenoids and plant sterols, or alkaloids and
sulfur containing compounds.
[0151] With respect to the color groups of fruits and vegetables,
the present compositions may include at least one fruit/vegetable
from each of the colors green, blue/purple, red, orange and white.
Green fruits/vegetables include, for example, spinach, broccoli,
peas, beans and kiwi. Blue/purple fruits/vegetables include, for
example, grapes, blueberries and eggplant. Red fruits/vegetables
include, for example, raspberries, cranberries and tomatoes. Orange
fruits/vegetables include, for example, carrots, mangoes, pumpkin,
oranges and squash. White fruits/vegetables include, for example,
cauliflower, onion and banana. Accordingly, it is possible to
diversify the nutrient and phytonutrient content by including
fruits and vegetables from all color groups. The skilled artisan
will appreciate that this list is not exhausted and that other
colored fruits/vegetables may be used in addition to those listed
above. The skilled artisan will appreciate that any known fruits
and vegetables may be used in the present nutritional compositions.
Further, the skilled artisan will also appreciate that the fruits
and/or vegetables may be provided in any amounts effective to
achieve the advantages described above.
[0152] Phytochemicals are active in the body and, in general, act
similarly to antioxidants. They also appear to play beneficial
roles in inflammatory processes, clot formation, asthma, and
diabetes. Researchers have theorized that to receive the most
benefit from consumption of phytochemicals, they should be consumed
as part of whole foods, because of the complex, natural combination
and potentially synergistic effects. See, Liu R H., Health benefits
of fruit and vegetables are from additive and synergistic
combinations of phytochemicals, Am. J. Clin. Nutr., 78:517S-520S
(2003). This may partially explain the health benefits associated
with consumption of whole fruits and vegetables. Increased intake
of fruits and vegetables is associated with reduced risk of many
chronic diseases. In order to enhance the phytochemical profile of
the present nutritional compositions, in an embodiment, the
compositions include various fruits and vegetables containing these
compounds.
[0153] Another manner in which tube feeding formulas can mimic
healthy, whole food diets is to include food components that are
typically present in a healthy, whole food diet. To this end, the
present compositions may have added spices, herbs or flavorings
with purposed health benefits such as, for example, antioxidant
activity, or that provide emotional appeal for certain populations.
For example, the present compositions may include garlic and/or
cinnamon to reduce cholesterol and lower blood pressure, ginseng
and cinnamon for glycemic control, tumeric, curcumin, basil,
rosemary, mint and lemon grass for anti-carcinogenic properties,
ginger for arthritic pain, Ginkgo biloba and ginseng for cognitive
function, curcumin and ginger for anti-inflammatory properties,
ginger for an anti-nausea, and herbs for improving general health
conditions.
[0154] Variety in food and tastes may maintain the various taste
receptors in the gut. Increased variety of foods and/or food
components and flavors may be delivered to stimulate specific taste
receptors in the gut, thus eliciting different physiological
responses. For example, umami receptors have been identified in the
gastrointestinal tract, which sense the presence of savory flavors
(mushrooms, seafood, fermented soy flavorings, or common flavor
enhancers such as monosodium glutamate ("MSG") and/or
inosine-5'-monophosphate ("IMP")). Animal data has shown that the
addition of MSG and/or IMP to diets improves the secretion of mucus
and protection of the small bowel. In an embodiment, mushrooms and
fermented soy flavorings may be added to the present compositions
because mushrooms and fermented soy flavorings such as, for
example, soy sauce, contain the highest naturally occurring levels
of these compounds and could be useful as ingredients in tube feed
formulations for support of the gastrointestinal tract. In this
manner, umami receptor activation may have dual benefits in glucose
metabolism (increase GLP-1 release) and in duodenal mucosal
protection and regeneration due to GLP-2 release from L cells. See,
Nakamura E, et al., Physiological roles of dietary free glutamate
in gastrointestinal functions, Biol. Pharm. Bull., 31, 10:1841-1843
(2008); Kojo A, et al., Effects of glutamate, the "umami"
substance, on development and healing of NSAID-induced small
intestinal lesions in rats, Abstract presented at Digestive Disease
Week 2010 (W1345); Wang J, et al., Umami receptor activation
increases duodenal bicarbonate secretion via GLP-2 release in rats,
Abstract presented at Digestive Disease Week 2010 (W1719).
[0155] Also, stimulation of other taste receptors has been shown to
have effects in animal or cell culture studies. For example,
stimulation of bitter taste receptor in the gut increases CCK
release and delays gastric emptying. See, Chen M C, et al., Bitter
stimuli induce Ca2 signaling and CCK release in enteroendocrine
STC-1 cells: role of L-type voltage-sensitive Ca2 channels, Am. J.
Physiol. Cell Physiol. 291, C726-C739 (2006); Jang H J, et al., Gut
expressed gustacin and taste receptors regulate secretion of
glucagon-like peptide 1., Proc. Natl. Acad. USA 104:15069-74
(2007); Margolskee R F, et al., T1R3 and gustducin in gut sense
sugars to regulate expression of Na-glucose cotransporter 1., Proc.
Natl. Acad. USA 104:15075-80 (2007); Mace O J, et al., Sweet taste
receptors in rat small intestine stimulate glucose, J. Physiol.
582.1, pp 379-392 (2007).
[0156] In an embodiment, the present compositions include plant
sterols for heart health to reduce absorption of cholesterol in the
gut. Phytosterols (also called plant sterols) are a group of
steroid alcohols that naturally occur in plants. Phytosterols occur
naturally in small quantities in vegetable oils, especially sea
buckthorn oil, corn oil, and soybean oil. One example of a
phytosterol complex, isolated from vegetable oil, is cholestatin,
composed of campesterol, stigmasterol, and brassicasterol. The
skilled artisan will appreciate that any known phytosterols may be
used herein. In an embodiment, up to about 5 g of plant sterols may
be added to the present compositions per complete feed. In an
embodiment, about 1 to about 4 g of plant sterols may be added to
the present compositions. In another embodiment, about 2 g of plant
sterols are added to the present compositions per complete feed. In
this manner, plant sterols may be beneficial in compositions
containing cholesterol, or an oral nutritional supplement in which
the consumer is consuming other food items containing cholesterol.
In another embodiment, however, some long-term tube-fed patients
receive very little amounts of exogenous cholesterol. In this case,
the present compositions may not include sterols that may hamper
cholesterol.
[0157] As discussed above, nucleotides are food constituents found
in several types of food including red meats, organ meats, poultry,
fish, shellfish, lentils, beans, asparagus and fermented beverages,
among others. Although endogenous synthesis constitutes a major
source of nucleotides, nucleotides can also be obtained in the form
of nucleoproteins naturally present in all foods of animal and
vegetable origin including, for example, animal protein, peas,
yeast, beans and milk. Further, concentrations of RNA and DNA in
foods are dependent on cell density. Thus, meat, fish and seeds
have higher nucleotide content than milk, eggs and fruits.
Consequently, organ meats, fresh seafood, and dried legumes are
rich food sources. Endogenous synthesis of nucleotides, although a
high energy requiring process, appears to be sufficient in healthy
individuals. However, the need for exogenous (dietary source)
nucleotides occurs during situations of growth or stress, e.g., gut
injury, sepsis, and immune challenge. See, Kulkarni et al., The
Role of Dietary Sources of Nucleotides in Immune Function: A
Review, J. Nutr., vol. 124 pp. 1442S-1446S (1994). Therefore,
several segments of the population on long-term tube feeds
(elderly, pediatric populations, sedentary, bedridden and those
with wounds), or patients requiring oral nutritional supplements,
may particularly benefit from exogenous nucleotides.
[0158] The skilled artisan will appreciate that although endogenous
synthesis constitutes a major source of nucleotides, nucleotides
can also be obtained in the form of nucleoproteins naturally
present in all foods of animal and vegetable origin including, for
example, animal proteins, peas, yeast, beans, milk, etc.
[0159] The cell energy charge has been proposed as an important
control for the cell to favor either anabolic or catabolic
processes. Cell energy charge is defined Energy charge=(ATP+1/2
ADP)/(ATP+ADP+AMP), where ATP, ADP, and AMP signify adenosine
5'-triphosphate, -diphosphate, and -monophosphate, respectively.
Metabolic stress, nutritional stress, or both may result in a loss
of nucleotides from the adenylate pool and become conditionally
essential under these conditions. The maintenance of the cell
energy charge can attenuate the upregulation of catabolic processes
resulting from metabolic stress, nutritional stress, or both, which
includes protein breakdown.
[0160] AMP Protein Kinase ("AMPK") is a protein that serves as a
cell energy charge sensor that responds to ATP/AMP as well
phosphocreatine/creatine ("PCr"/"Cr") changing ratios for the
prioritization of cellular processes based on available energy.
Specifically, AMPK can target the translational control of skeletal
muscle protein synthesis as well as upregulate the ubiquitin
proteosome pathway.
[0161] Additionally, nucleotides can be beneficial in the
nutritional management of pressure ulcer by improving the
resistance to infection at the wound site. Chronic nucleotide
supplementation may counteract the hormonal response associated
with physiological stress, resulting in an enhanced immune
response.
[0162] Extensive experimentation on the influence of dietary
nucleotides on lymphocyte function and cellular immunity in rodent
models has also been conducted. Evidence exists to assert that the
absence of dietary nucleotides does significantly decrease specific
and non-specific immune responses. Findings include decreased
maturation and proliferation of lymphoid cells in response to
mitogens, decreased resistance to bacterial and fungal infection,
and increased allograft survival.
[0163] Lymphocyte differentiation and proliferation can be
stimulated by specific nucleosides and, in turn, nucleotide
metabolism may be influenced by stages of lymphocyte activation and
function. Furthermore, de novo synthesis and salvage of purines and
pyrimidines is increased in stimulated lymphocytes. In support, an
established marker for undifferentiated T-cells, terminal
deoxynucleotidyl transferase ("TdT"), has been identified in
undifferentiated bone marrow and thymocytes of rodents fed diets
devoid of nucleotides.
[0164] In vitro and in vivo studies of rodents on nucleotide free
diets have demonstrated suppressed cell-mediated immune responses.
Splenic lymphocytes from nucleotide free hosts evidenced
significant decreases in proliferate response to mitogens,
decreased interleukin-2 ("IL-2") production and lower levels of
IL-2 receptor and Lyt-1 surface markers. IL-2 is a growth factor
for lymphocytes, while Lyt-1 is a marker of helper-inducer T-cell
immunity. Delayed cutaneous hypersensitivity was also lower.
[0165] These responses were largely reversed with additions of RNA
or uracil, suggesting a formidable role for pyrimidines and/or
limited capacity for their salvage. Furthermore, dietary
nucleotides were shown to reverse lost immune response secondary to
protein-calorie malnutrition more so than calories and protein
alone. However, this reversal was limited to pyrimidines.
[0166] Investigations of the role of nucleotides in bacterial and
fungal infection have also revealed increased resistance. Rodents
on nucleotide containing diets demonstrated significant resistance
to intravenous challenge of Staphylococcus aureus compared to those
on nucleotide free diets. A decreased ability to phygocytose S.
aureus was observed. Moreover, decreased survival times were
observed in rodents on a nucleotide free diet after similar
challenge with Candida albicans. Additions of RNA or uracil, but
not adenine were shown to increase survival time.
[0167] The immunosuppressive effects of nucleotide free diets have
also produced prolonged cardiac allograft survival in rodents as
well as synergistic immunosuppression with cyclosporine A. These
findings evidence influence on T-helper cell numbers and function.
Various mechanisms of action have been proposed to explain these
findings. Restriction of exogenous nucleotides is believed to
influence the initial phase of antigen processing and lymphocyte
proliferation via action on the T-helper-inducer as evidenced by
increased levels of TdT in primary lymphoid organs. This is also
suggestive of suppression of uncommitted T-lymphocyte response.
Also, nucleotide restriction may cause arrest of T lymphocytes in
the G phase of the cell cycle, thus inhibiting transition of
lymphocytes to the S phase to illicit necessary immunological
signals. Nucleotide restriction may also lower the cytolytic
activity of natural killer ("NK") cells and lower macrophage
activity.
[0168] Dietary nucleotides may also modulate T-helper cell mediated
antibody production. A review of studies investigating nucleotide
actions on humoral immune response identified effects in in vitro
and in vivo animal models as well as in vitro actions in human
systems. In vitro findings in splenic rodent cells primed with
T-cell-dependent antigens displayed significant increases in the
number of antibody producing cells in yeast RNA containing
cultures. RNA additions to normal strains demonstrated similar
results and were nullified by T-cell depletion. Thus, the antibody
did not increase in response to T-cell independent antigens or
polyclonal B cell activation. The specific antibody response of
yeast RNA was attributed to nucleotides.
[0169] Immunoglobulin production has also been shown to increase in
in vitro adult human peripheral blood mononuclear cell in response
to T-cell dependent antigen and stimuli. Specifically, this
involved increased immunoglobulin M ("IgM") and G ("IgG")
production. IgM production increased in the functionally immature
umbilical cord mononuclear cells in response to T-cell dependent
stimuli as well.
[0170] Accordingly, in a state of nucleotide deficiency,
incorporated dietary nucleotides could potentially exert similar
immune effects in vivo. Antibody response to T-cell dependent
antigen was suppressed in rodents maintained on nucleotide free
diets for prolonged periods, and immune function was rapidly
restored with nucleotide supplementation. However, the mixture used
for supplementation showed no effect on in vitro antibody
production to antigen-dependent antigens suggestive of nucleotide
effects on local, specific immune response. In addition,
significant increases in the numbers of antigen-specific
immunoglobulin-secreting cells were observed in rodent splenic
cells in the presence of nucleotides. Additions of AMP, GMP or UMP
have also resulted in increased IgG response in rodents. GMP was
also shown to increase IgM response. Studies in preterm infants on
nucleotide supplemented formulas have revealed increased
circulating levels of IgM and IgA in the first three months of life
as well as higher concentrations of specific IgG against
.alpha.-casein and .beta.-lactoglobulin in the first month of life.
Specific IgG levels to low response antigens may also increase in
normal infants receiving dietary nucleotide containing
formulas.
[0171] Mechanistically, in vitro and in vivo observations are
thought to involve nucleotide effects on T-helper-cells at antigen
presentation, modulations via interactions with cell surface
molecules of T-cells, suppressed nonspecific activation of T-cells
in response to antigen stimulus, and increased specific antibody
response mediated through resting T-cells. Therefore, dietary
nucleotides may favor the balance of T-cell differentiation to
T-helper-2 cells which are primarily involved in B cell response.
Thus, it is clear that nucleotides, as well as phytochemicals, can
present several physiological benefits to patients having any of
the above-mentioned conditions.
[0172] The skilled artisan will appreciate that any known fruits
and vegetables may be used in the present nutritional compositions.
Further, the skilled artisan will also appreciate that the fruits
and/or vegetables may be provided in any amounts effective to
provide nutrients to achieve the advantages described above. The
skilled artisan will also appreciate that the major sources of
nucleotides include red meats, organ meats, poultry, fish,
shellfish, lentils, beans, asparagus, etc. In an embodiment, the
nutritional compositions of the present disclosure may provide
nucleotides in an amount of at least about 10 mg/100 kcal. In an
embodiment, the nutritional compositions include from about 13
mg/100 kcal to about 19 mg/100 kcal nucleotides. In an embodiment,
the nutritional compositions provide about 16 mg/100 kcal
nucleotides.
[0173] In another embodiment, the nutritional compositions may
include polymeric forms of nucleotides. The nucleotides may be
present in amounts from about 0.9 to about 1.5 g/1000 kcal. In an
embodiment, the nucleotides may be present in amounts up to about
1.2 g/1000 kcal. As discussed above, the skilled artisan will
appreciate that although fruits and vegetables may provide an
amount of nucleotides, exogenous synthesis may also constitute a
major source of nucleotides.
[0174] In an embodiment, the nutritional compositions of the
present disclosure may be hypocaloric (e.g., characterized by a low
number of dietary calories) in order to provide a patient with
proper nutrients but to manage weight gain without compromising
musculoskeletal health. Typically, hypocaloric diets usually
provide between 1,000 and 1,200 kcal/day. The present nutritional
compositions may have caloric densities that range from about 0.3
to about 1.0 kcal/ml. In an embodiment, the nutritional
compositions have a caloric density from about 0.5 to about 0.8
kcal/ml. The tube feed formula may also be of average to high
energy density, from about 1.0 kcal/mL to 2.0 kcal/mL.
[0175] Osmolality is a measure of the osmoles of solute per
kilogram of solvent (osmol/kg tube feeding or Osm/kg tube feeding).
In an embodiment, the present nutritional compositions may have an
osmolality that is less than or equal to 800 mOsm/kg water. In
another embodiment, the present nutritional compositions have an
osmolality that is less than or equal to 400 mOsm/kg water. In
another embodiment, the present nutritional compositions have an
osmolality that is less than or equal to 380 mOsm/kg water.
[0176] In an embodiment, the nutritional compositions further
include one or more prebiotics. Non-limiting examples of prebiotics
include acacia gum, alpha glucan, arabinogalactans, beta glucan,
dextrans, fructooligosaccharides, fucosyllactose,
galactooligosaccharides, galactomannans, gentiooligosaccharides,
glucooligosaccharides, guar gum, inulin, isomaltooligosaccharides,
lactoneotetraose, lactosucrose, lactulose, levan, maltodextrins,
milk oligosaccharides, partially hydrolyzed guar gum,
pecticoligosaccharides, resistant starches, retrograded starch,
sialooligosaccharides, sialyllactose, soyoligosaccharides, sugar
alcohols, xylooligosaccharides, their hydrolysates, or combinations
thereof.
[0177] The nutritional compositions may further include one or more
probiotics. Non-limiting examples of probiotics include Aerococcus,
Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium,
Debaromyces, Enterococcus, Fusobacterium, Lactobacillus,
Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Mucor,
Oenococcus, Pediococcus, Penicillium, Peptostrepococcus, Pichia,
Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces,
Staphylococcus, Streptococcus, Torulopsis, Weissella, or
combinations thereof.
[0178] One or more amino acids may also be present in the
nutritional compositions. Non-limiting examples of amino acids
include alanine, arginine, asparagine, aspartate, citrulline,
cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline,
hydroxyserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine,
lysine, methionine, phenylalanine, proline, serine, taurine,
threonine, tryptophan, tyrosine, valine, or combinations
thereof.
[0179] The nutritional compositions may further include one or more
synbiotics. Examples may include, for example, bifidobacteria and
fructo-oligosaccharides ("FOS"); Lactobacillus rhamnosus GG and
inulins; bifidobacteria or lactobacilli with FOS; or inulins or
galactooligosaccharides ("GOS").
[0180] One or more antioxidants may also be present in the
nutritional compositions. Non-limiting examples of ingredients with
antioxidant activities selected from the group consisting of herbs,
spices, and flavorings, carotenoids, flavonoids, polyphenols,
lignan, lutein, lycopene, quercetin, limonin, coenzyme Q10
("CoQ10"), glutathione, Goji (wolfberry), lactowolfberry,
hesperidine, selenium, vitamin A, vitamin C, vitamin E, or
combinations thereof. In an embodiment, the herbs, spices, and
flavorings may be selected from the group consisting of garlic,
cinnamon, ginseng, turmeric, curcumin, rosemary, mint, lemongrass,
ginkgo, ginger, or combinations thereof.
[0181] The nutritional compositions also include fiber or a blend
of different types of fiber. The fiber blend may contain a mixture
of soluble and insoluble fibers. Soluble fibers may include, for
example, fructooligosaccharides, acacia gum, inulin, etc. Insoluble
fibers may include, for example, pea outer fiber.
[0182] As discussed above, the present compositions may also
include a variety of herbs, spices and/or flavorings. Herbs that
are included may be selected from angelica, bay laurel, chives,
dill, catnip, fennel, lavender, lemon balm, majoram, mint, oregano,
parsley, rosemary, rue, sage, tarragon, thyme, verbena, or
combinations thereof. Spices may be selected from the group
consisting of black pepper, cumin, cardamom, cayenne, celery seeds,
chili pepper, cinnamon, clove, cumin, garlic, ginger, mustard,
nutmeg, onion, paprika, peppercorns, tabasco, tumeric or
combinations thereof. Flavorings may be any natural or artificial
flavors or flavor enhancers such as, for example, MSG, vanilla
extract, etc. The skilled artisan will appreciate that many herbs,
spices and flavorings may overlap in uses such that, for example, a
typical herb may be used as a spice.
[0183] The present compositions may further include a source of
.omega.-3 polyunsaturated fatty acids including, but not limited
to, .alpha.-linolenic acid ("ALA"), eicosatetraenoic acid ("ETA"),
eicosapentaenoic acid ("EPA"), docosapentaenoic acid ("DPA"),
docosahexaenoic acid ("DHA"), tetracosapentaenoic acid,
tetracosahexaenoic acid (nisinic acid), or combinations thereof.
Sources of .omega.-3 fatty acids include fish oil, poultry, eggs,
or other plant or nut sources such as flax seed, walnuts, almonds,
algae, krill, modified plants, or combinations thereof. The present
compositions may also include conjugated linoleic acid ("CLA"). CLA
is a naturally occurring lipid that supports lean body mass and
immune function. Grass-fed beef is a good source of CLA.
[0184] The present compositions may also include monounsaturated
fatty acids including, for example, palmitoleic acid, cis-vaccenic
acid, and oleic acid. Common sources of monounsaturated fatty acids
include, but are not limited to, natural foods such as nuts and
avocados, and monounsaturated fatty acids are the main component of
tea seed oil and olive oil (oleic acid). Canola oil is 57%-60%
monounsaturated fat, olive oil is about 75% monounsaturated fat
while tea seed oil is commonly over 80% monounsaturated fat. Other
sources of monounsaturated fatty acids include macadamia nut oil,
grapeseed oil, groundnut oil (peanut oil), sesame oil, corn oil,
whole grain wheat, oatmeal, safflower oil, sunflower oil, tea-oil,
and avocado oil.
[0185] As discussed above, the present disclosure also provides
compositions and method that provide an emotional appeal for tube
fed patients and/or their caretakers, as well as possible
physiological benefits to the patient. In order to provide such an
emotional appeal, the formulas of the present disclosure may, for
example, 1) incorporate organic, natural and sustainable
ingredients, 2) provide formulations that are specific to a certain
ethnicity, use natural ingredients to provide coloring, 3) provide
pediatric-friendly food blends and/or packaging that a parent would
consider "normal" for children consuming an oral diet, 4) provide a
component that allows for oral stimulation and a natural response
to eating, and/or 5) provide methods of tube feeding that mimic
typical meal times or a cycling menu.
[0186] One manner in which a nutritional composition (e.g., a tube
feed formulation) may evoke an emotional appeal (and/or potential
physiological benefit) is to provide organic, natural and
sustainable ingredients. For example, compositions of the present
disclosure may include 100% organic fruits and/or vegetables and
organic meat products such as chicken or beef. To be certified
organic, ingredients must be grown and manufactured according to
country-specific standards. The United States Department of
Agriculture ("USDA") Organic Certified Fruits and vegetables or
Meat provides that fruits and vegetables must be grown without
synthetic or non-organic pesticides, insecticides or
herbicides.
[0187] For organic meat, the USDA provides that meat must be grown
without the use of antibiotics and growth hormones. Organic
products are typically free of artificial food additives, and are
processed with fewer artificial methods such as chemical ripening,
food irradiation, genetically modified organisms, etc. In an
embodiment, the compositions of the present disclosure may include
meat that is obtained from free range chicken and/or grass-fed beef
and milk. Standards such as these, although not necessary, are more
aligned with the current marketing message of "the way nature
intended." Indeed, it is known that a cow's rumen is not intended
to process grains, and these standards assure that the meat is
raised without the use of antibiotics and growth hormones. See,
Steve Windley, Grass-fed Beef, purehealthMD.com (2008).
[0188] Similarly, all natural ingredients may be used in the
coloring of present compositions to avoid the chemicals in
artificial coloring. For example, to achieve a composition with red
color, amaranth, beets, or hibiscus may be added to the
compositions. Alternatively, to achieve a composition with
yellow/orange color, tumeric may be added to the compositions. The
skilled artisan will appreciate that these are merely examples of
color-providing fruits/vegetables and that any known fruits or
vegetables capable of providing color to the compositions may be
used.
[0189] Another manner in which a nutritional composition may evoke
an emotional appeal (and/or potential physiological benefit) is to
create ethnicity specific tube feed formulas. In an embodiment, the
present compositions are formulated with fruits, vegetables,
macronutrient sources and spices typically consumed in specific
regions of the world. For example, a tube feed formulation may
include curcumin or tumeric and be marketed as an Indian cuisine
formulation. Curcumin is a component of the spice tumeric (curcuma
Tonga) and is responsible for the yellow color of curry. Curcumin
has specifically been shown to possess anti-inflammatory,
antioxidant and anti-proteolytic properties. With regards to
long-term, tube fed pediatric patients who experience profound
decrements in lean body mass, for example, curcumin may provide
some attenuation of skeletal muscle proteolysis. Importantly,
curcumin has been shown to antagonize the upregulation of nuclear
factor-.kappa..beta. (NF-.kappa..beta.) and this gene is
inextricably tied to initiating an intracellular signaling cascade
responsible for inducing skeletal muscle atrophy during unloading
conditions. See, Farid, et al., Effects of dietary curcumin or
N-acetylcysteine on NE-.kappa..beta. activity and contractile
performance in ambulatory and unloaded murine soleus, J. Clin.
Invest., 114(10):1504-11 (2005).
[0190] Similarly, cumin, oregano and chili powder may be included
in compositions that are marketed as a Mexican cuisine formulation.
Other cuisine options include, but are not limited to, Thai,
Italian, Mediterranean, or American.
[0191] Another manner in which a nutritional composition may evoke
an emotional appeal is to include pediatric-friendly food blends,
or foods that parents would consider "normal" for kids consuming an
oral diet. Popular branded foods include, for example,
Cheerios.RTM., Juicy Juice.RTM., Campbell's Alphabet Soup.TM.,
chicken nuggets, strawberry shortcake, bananas, apple sauce,
etc.
[0192] Yet another manner in which a nutritional composition may
evoke an emotional appeal (and/or potential physiological benefit)
is to provide an extra, add-on component that has at least one
characteristic selected from the group consisting of visually
appealing/appetizing, an appealing aroma, an appealing flavor or
smell to stimulate the natural response to eating, or combinations
thereof. These components (smell, taste, thought, etc.) may also
have physiological benefits such that they elicit the cephalic
phase or the first part of digestion, which would allow the patient
begin the digestive processes in a more similar way to an oral
diet. Therefore, digestive processes begin with the sight, smell or
thought of food and physiological processes occur to prime the body
for digestion (e.g., salivation, gastric acid secretion, pancreatic
endocrine and exocrine).
[0193] The add-on component may be a tablet, lozenge, dissolvable
strip, or chewing gum. It may or may not be nutritive or contain
calories. If intended for a strictly Nothing Per Orem ("NPO")
patient, the add-on component could be tailored to ensure
compliance (e.g., provide dissolvable strip form).
[0194] The aroma may be any aroma known in the art. For example,
the aroma may be a dessert aroma such as, but not limited to
vanilla, chocolate, strawberry, lemon, custard, etc. The aroma may
also be related to an ethnic food such as, for example, curry,
chili powder, roasted red pepper, basil, etc. In another
embodiment, the aroma may be an aroma that is associated with
common American foods such as, but not limited to, meatloaf,
chicken, roast, mashed potatoes, etc. By providing a wide range of
aromas, the patients may be able to select an aroma that sounds
satisfying to the patient at the time of tube feeding. The aroma
may be released upon opening the packaging, or the smell may be
enhanced by a "scratch-and-sniff" device.
[0195] The packaging of the tube feeding formula, for example, and
add-on device can be designed to mimic a meal. For example, the
tube feed formula could simulate the appearance of a plate in that
it may be a circular, flat package with pictures of meal contents.
The patient could sit down for dinner with a "plate of food." The
add-on package may be any shape or size known in the art and may be
sized and shaped to simulate the appearance of a food item or an
eating utensil. In this way, the tube feeding package would mimic a
meal and include an extra, add-on component (e.g., lozenge,
dissolvable strip, chewing gum) that, upon opening/consuming, would
release a food scent. The patient would put the lozenge,
dissolvable strip, chewing gum in his/her mouth for flavor. This
would allow for a more "natural" eating routine and stimulate the
natural response to eating (e.g., the cephalic phase, smell, taste,
thought, etc.). The skilled artisan will appreciate that the add-on
package need not have a particular shape, may have any size and
shape known in the art, or may be sold separately from the tube
feeding formula.
[0196] Benefits of the add-on component relate to simulation of the
cephalic phase, and promotion of oral health. Methods of current
formula delivery include delivery directly into the GI tract which
bypasses this first phase of digestion, the cephalic phase. The
cephalic phase of digestion results in gastric acid secretion,
release of pancreatic enzymes including insulin and therefore, may
improve digestion and tolerance to the formula. With bypassing of
this first phase of digestion, it could be theorized that there are
several physiological consequences. First, with bypassing of
peristalsis in the esophagus, it could be theorized that "pacing"
is affected throughout the GI tract. Second, without use, there
could be atrophy of the oral/GI muscles which would result in
delayed recovery or may be problematic upon resumption of an oral
diet. Third, with the discovery of taste receptors in the gut,
there may be missing communication between the mouth and gut taste
receptors. Lastly, particularly in diabetic patients and related to
early release of insulin during the cephalic phase, there may
dysregulation in glycemic control
[0197] Moreover, the use of the add-on component may also enhance
oral health (components including saliva production and oral
microbiota) which is important for several areas of health, and has
been found to be a predictor of mortality. See, Awano S, et al.,
Oral health and mortality risk from pneumonia in the elderly, J.
Dent. Res., 87(4):334 339 (2008); Ide R, et al., Oral symptoms
predict mortality: a prospective study in Japan, J. Dent. Res.
87(5):485-489 (2008). Patients on tube feedings, for example, are
at higher risk for poor oral health and have a higher prevalence
reported of gram negative bacteria. See, Leibovitz A, et al.,
Saliva secretion and oral flora in prolonged nasogastric tube fed
elderly patients, IMAJ, 5:329-332 (2003). Reduced salivary flow or
poor oral health are associated with several conditions, which may
be common to individuals on long term tube feedings, including
history of radiation to head and neck, diseases of salivary gland,
cystic fibrosis, alcoholic cirrhosis, as well as medication usage
including anticholinergics, antidepressants, antipsychotics,
diuretics, antihypertensives, antihistamines, and nonsteroidal
anti-inflammatory medications.
[0198] The flavor and scent of the add-on component may or may not
be similar to the foods present in the tube feeding. In this
manner, the add-on component comes with a variety of flavors for
emotional appeal, which allows the patient to choose what they are
hungry for. For example, if the tube feed formulation contains
chicken, the add-on component may smell like chicken. The add-on
component may have a strong flavor to stimulate saliva production.
The strong flavor may be, for example, tart, ginger, etc.
[0199] Since the add-on component may be placed directly into the
mouth of the patient, the add-on component may include functional
ingredients as well. For example, the functional ingredients may
include probiotics to maintain healthy oral microflora, or
capsaisin to trigger the swallow reflex.
[0200] In an embodiment, the dissolvable strip would be used when
oral intake is contraindicated (e.g., dysphagia, neurological
impairment).
[0201] These types of extra, add-on components may be used when
oral intake is contraindicated and may allow for tube feed
formulations that are specifically designed to mimic the eating
process, which primes the body to absorb and use nutrients. In an
embodiment, the add-on component may be a flavor tab that is
packaged in a wrapper and releases a scent when opened. The flavor
tab may also create a range of flavors for the patient including,
for example, chicken seasoned with parsley, mashed potatoes, etc.
Based on the perceived scents and flavors, the patient can select
what types of flavors they are "hungry" for. In an embodiment, the
add-on component (e.g., flavor tab) is used just prior to and
during tube feeding administration. The flavor tab can be calorie
free and may only contain ingredients allowed on a Nothing Per Orem
("NPO") diet.
[0202] Physiological feeding includes introduction of routine and
variety into the diet. The idea includes bolus feeding which
resembles the breakfast, lunch, dinner, snack pattern in which an
enteral formulation is designed to include a variety of food
components representative of a varied, mixed, cycle menu diet. A
variety of bolus feeding may change depending on meal or week. The
variety of food in the menu cycle may be further specialized and
diversified by including ethnic food and various spices. This
regimen incorporates benefits of whole food beyond basic nutrients
and provides a source of phyto- and zoo-chemicals with health
benefits. The benefits include, but are not limited to oxidative
stress modulation with benefits related to musculoskeletal health,
blood pressure, cholesterol levels, glycemic control, cancer,
cognitive function, inflammation.
[0203] Along these lines, another manner in which to evoke an
emotional appeal is to provide methods of administering nutritional
compositions (e.g., tube feedings) that mimic regular meal times,
or create a cycling menu with unique foods, as mentioned above. For
example, in an embodiment, the tube feed formulations may be
administered three times daily at normal meal times of breakfast,
lunch and dinner, and/or with several snacks. Similarly, the
present compositions may be packaged with an appealing or
appetizing label or product name.
[0204] In another embodiment, the tube feedings may be administered
such that the administration creates a cycling menu with unique
foods having, for example, different protein sources, and different
fruits and vegetables. The skilled artisan will appreciate that
many different combinations of whole foods may be used in the
present compositions. Different examples of such combinations
include, as with Clinutren Mix products, but are not limited to,
turkey with mixed vegetables, veal with broccoli, spring vegetables
stew, cod with leek, Hungarian beef, salmon and spinach, chicken
and vegetables, and beef and carrots.
[0205] In another example, the tube feedings may be administered at
normal meal times. For example, a first feeding may be administered
at a typical breakfast time in the morning. A second feeding may be
administered at a typical lunch time around noon, and a third
feeding may be administered at a typical dinner time in the
evening. The tube feeding formula may also be administered at
several additional times, mimicking snack times.
[0206] The formulation of nutritional compositions of the present
disclosure may be varied from feeding to feeding, day to day, week
to week, or month to month to provide a patient with a variety of
food, which provide a variety of different nutrients. For example,
daily feedings may be varied as follows: a first daily feeding
(e.g., at breakfast time) may be the same as or different from a
second daily feeding (e.g., at lunch time), which may be the same
as or different from a third daily feeding (e.g., at dinner time).
Daily feedings may also vary by providing a first feeding (e.g., at
breakfast time) on day one that is the same as or different from a
first feeding (e.g., at breakfast time) on day two. The same goes
for second and third daily feedings.
[0207] In another embodiment, feedings may vary from week to week
or month to month. In this regard, a patient may be administered a
specific tube feed formulation for a week or a month before the
formulation changes to a second formulation. Similarly, the patient
may be administered a daily feeding menu of first, second and third
feedings, wherein each first feeding is the same for a week or a
month, each second feeding is the same for a week or a month, and
each third feeding is the same for a week or a month before the
feedings are changed to a second formulation.
[0208] The changing of a first formulation to a second formulation,
regardless of how frequently the formulations are changed, may
include changing of a specific component of the formulation. For
example, a tube feed formulation may be administered to a patient
on day one that has a certain amounts of protein, carbohydrates and
fats. On day two, a similar tube feed formulation may be
administered to the patient that has the same amount of protein and
carbohydrates, but an increased or decreased amount of fats. In
this manner, the amounts of macro and micronutrients in the
nutritional compositions of the present claims may vary from
formula to formula. In an embodiment, at least one source of
protein of a nutritional composition is different than a new, or
second, nutritional composition. In an embodiment, at least one
source of carbohydrates of a nutritional composition is different
than a new, or second, nutritional composition. In an embodiment,
at least one source of fats of a nutritional composition is
different than a new, or second, nutritional composition.
[0209] The nutritional compositions can be administered to an
individual having a preexisting medical condition, or at risk of
developing a medical condition, or having characteristics common to
patients on long term tube feeding formulas. The underlying medical
condition may be, for example, cerebral palsy, failure-to-thrive,
neuromuscular disorders, brain injury, developmental delay, immune
deficiency or dysregulation, compromised musculoskeletal and gut
health, low bone density, pressure ulcers, chronic wounds, insulin
resistance, or combinations thereof. The nutritional composition
can be a formulation designed for any mammal such as a human or an
animal. In an embodiment, the nutritional composition is a
tube-feed formulation.
[0210] Methods of improving the overall health of a patient having
an underlying medical condition are also provided. The methods
include administering to a patient having an underlying medical
condition a tube feed formulation having at least five different
whole food components, a source of protein, a source of fat, a
source of carbohydrate, a source of fiber and a source of vitamins
or minerals. The formulation includes at least five, six, seven, or
eight different whole food components and the whole food components
may be selected from the group consisting of a processed fruit, a
processed vegetable, a processed meat, a processed grain, or
combinations thereof.
[0211] Methods of improving the overall health of a patient having
an underlying medical condition are also provided. The methods
include administering to a patient having an underlying medical
condition a tube feed formulation having a processed whole food, at
least seven different sources of macronutrients selected from the
group consisting of protein, carbohydrates, fats, fibers, or
combinations thereof, and a source of vitamins or minerals. The at
least seven different sources of macronutrients includes at least
one protein, at least one carbohydrate and at least one fat. The at
least seven different sources of macronutrients may also include at
least three different proteins and/or at least three different
carbohydrates and/or at least three different fats.
[0212] Methods of administering tube feeding formulations are also
provided. The methods include administering a first tube feed
formulation having a whole food to a patient at a first time of a
day corresponding to a typical breakfast time, administering a
second tube feed formulation having a whole food to the patient at
a second time of the day corresponding to a typical lunch time, and
administering a third tube feed formulation having a whole food to
the patient at a third time of the day corresponding to a typical
dinner time. The first, second and third tube feed formulations
include at least one protein, and at least one of a fruit and a
vegetable. The protein of each of the first, second and third tube
feed formulations may be different. The at least one of a fruit and
a vegetable of each of the first, second and third tube feed
formulations may also be different. The tube feeding formula may
also be administered at several additional times with different
fruits and vegetables and macronutrient sources, mimicking snack
times. In this manner, the methods may include administering
fourth, fifth, sixth, etc. formulations correlating with typical
daily snack times.
[0213] The nutritional compositions of the present claims may be
administered at a temperature that is either warm or cold. It can
be theorized that differences in food temperature of a meal
containing protein, fat, carbohydrate and whole food components may
impact digestion and physiological response. Indeed, prior research
has shown that temperature (hot, warm, cold) of a simple food
beverage, sweetened instant coffee, administered via nasogastric
tube did not impact gastric acid secretion, serum gastrin
concentrations, or gastric emptying. See, K. McArthur, et al.,
Gastric acid secretion, gastrin release, and gastric emptying in
humans as affected by liquid meal temperature, Am. J. Clin. Nutr.,
49:51-54 (1989).
[0214] The present disclosure also provides tube feed packages. The
packages include a first component contained in the package that is
a tube feed formulation. The package may resemble the shape of a
plate or food item or combinations thereof. The package further
includes a second component contained with or attached to the first
component, or purchased separately. The second component is
comprised of a substance that is consumed by mouth and has a
flavor/taste and an aroma and being packaged separately from the
first component. The second component may be a tablet or lozenge,
dissolvable strip or chewing gum and would be tailored to be
NPO-compliant when necessary and may be contained in a package of a
particular size or shape.
[0215] By using the improved compositions and methods of
administering same, Applicant is able to provide improved
nutritional compositions to adult and pediatric patients that have
an increased number and variety of fruits and vegetables, an
increased variety of macronutrient sources, and the addition of
other components found in whole foods. The improved formulations
help to mimic a "whole food" tube feeding that best meets the
nutritional needs of the target population and also provides
physiological benefits and emotional appeal.
[0216] 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 subject matter and without diminishing its
intended advantages. It is therefore intended that such changes and
modifications be covered by the appended claims.
* * * * *
References