U.S. patent application number 11/985767 was filed with the patent office on 2008-03-20 for method for treating wounds to promote healing.
This patent application is currently assigned to Medical Nutrition USA, Inc.. Invention is credited to Arnold M. Gans.
Application Number | 20080070844 11/985767 |
Document ID | / |
Family ID | 32230328 |
Filed Date | 2008-03-20 |
United States Patent
Application |
20080070844 |
Kind Code |
A1 |
Gans; Arnold M. |
March 20, 2008 |
Method for treating wounds to promote healing
Abstract
A method of treating a mammal to promote wound healing in the
mammal in need thereof, comprising orally administering to the
mammal an effective amount of a palatable, concentrated protein
composition comprising an effective amount of hydrolysed gelatin
and tryptophan, and an ingestible carrier, the composition
comprising the essential amino acids required by the mammal.
Palatability is preferably achieved by the use of an effective
amount of a sweetener. The method is particularly useful for
treating wounds resulting from decubitus ulcers and bariatric
surgery.
Inventors: |
Gans; Arnold M.; (Englewood,
NJ) |
Correspondence
Address: |
LERNER, DAVID, LITTENBERG,;KRUMHOLZ & MENTLIK
600 SOUTH AVENUE WEST
WESTFIELD
NJ
07090
US
|
Assignee: |
Medical Nutrition USA, Inc.
Englewood
NJ
|
Family ID: |
32230328 |
Appl. No.: |
11/985767 |
Filed: |
November 16, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10689236 |
Oct 20, 2003 |
7318934 |
|
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11985767 |
Nov 16, 2007 |
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60422164 |
Oct 29, 2002 |
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Current U.S.
Class: |
514/5.5 ;
514/17.2; 514/9.4 |
Current CPC
Class: |
A61K 31/405 20130101;
A61K 9/0095 20130101; A61P 17/02 20180101; A61K 31/405 20130101;
A61K 38/014 20130101; A61K 2300/00 20130101; A61K 38/014 20130101;
A61K 2300/00 20130101 |
Class at
Publication: |
514/021 ;
514/002 |
International
Class: |
A61K 38/17 20060101
A61K038/17; A61P 17/02 20060101 A61P017/02 |
Claims
1. A method of inducing compliance by a person with a treatment
requiring ingestion of a high protein nutritional supplement,
comprising providing to the person for oral administration a
concentrated protein nutritional supplement without excess fluids,
the supplement comprising an effective amount of a concentrated
protein composition comprising about 5 to about 75 parts by weight
of enzymatically hydrolyzed gelatin, about 0.02 to about 2.0 parts
by weight of tryptophan, about 0.1 to about 2 parts by weight of a
sweetener, and about 5 to about 100 parts by weight of an
ingestible carrier, the composition comprising the essential amino
acids required by the person, and wherein the total fluid amount
administered is about 15 mL to about 60 mL, such that the treatment
does not unduly burden the person with excess fluids.
2. The method of claim 1 wherein the composition is in liquid form
and wherein the carrier is water in a proportion of about 15 to
about 80 parts by weight, said composition additionally comprising,
in parts by weight, about 0.3 to about 10 parts of a palatable
acid, about 7 to about 25 parts of sorbitol (70 wt. %), about 0.1
to about 3 parts of a preservative, and about 0 to about 0.4 parts
of a flavoring agent.
3. The method of claim 1 wherein said sweetener is a natural
sweetener, an artificial sweetener or mixtures thereof.
4. The method of claim 3 wherein said artificial sweetener is
selected from the group consisting of acesulfame potassium,
aspartame, neotame, saccharin, sucralose, alitame, cyclamate and
mixtures thereof, and said natural sweetener is selected from the
group consisting of tagatose, trehalose, a dihydrochalcone,
clycyrrhizin, stevioside, thaumatin, erythritol, hydrogenated
starch hydolysates, isomalt, lactitol, maltitol, mannitol,
sorbitol, xylitol and mixtures thereof.
5. The method of claim 1 wherein the composition includes about 10
to about 30 grams of all essential and non-essential amino acids.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a divisional application of U.S.
patent application Ser. No. 10/689,236 filed Oct. 20, 2003, which
claims the benefit of U.S. Provisional Application No. 60/422,164
filed Oct. 29, 2002, the entire disclosure of which is incorporated
herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention is directed to a method and a
composition for treating wounds in a mammal, preferably a person,
wherein the composition is taken orally, i.e., ingested, in order
to promote healing of such wounds. The composition provides a
concentrated and complete source of protein in a palatable form.
Consequently, the palatable nature of the composition encourages
compliance with a regimen of ingestion by a person in need of such
treatment.
[0003] In U.S. Pat. No. 4,025,650, and its divisional patents, U.S.
Pat. No. 4,042,687, U.S. Pat. No. 4,042,688, and U.S. Pat. No.
4,053,589, A. M. Gans, et al. disclose a method and composition for
preventing nutritional deficiency and preventing or treating
various medical conditions, including body wastage during oncologic
treatment of cancer, obesity, providing rapid body build-up,
treatment of nutritional deficiency, particularly that associated
with surgery, cardiac cachexia, diabetes, hypoglycemia,
gastroenterology, skin conditions related to lipid, cell glycogen
and keratin deficiencies, and alcoholism. The disclosure of these
patents is incorporated herein by reference to the extent
permitted.
[0004] Various methods have been proposed for the treatment of
wounds; see for example, in U.S. Pat. No. 5,929,050, G. D. Petito,
U.S. Pat. No. 5,733,884, A. Barbul et al., and U.S. Pat. No.
5,985,339, A. Kamarei. The disclosures of these patents are
incorporated herein by reference to the extent permitted.
[0005] A review of the medical journal literature reporting on the
relationship between pressure sores or decubitus ulcers and
nutrition was undertaken by T. E. Finucane, J. Am. Geriatric Soc.,
43(4): 447-51 (1995). Overall, the author of the review concluded
that data about the relationship between malnutrition and pressure
sores are incomplete and contradictory. Several studies reporting
on possible factors that influence pressure wound formation and
healing have been reported in the literature including reviews that
have carefully considered these reports and tried to analyze their
sometimes conflicting conclusions. In general, there is reported a
general association between improved nutrition and reduced
incidence and improved healing of pressure ulcers. However, the
studies rely on the intake of dietary protein requiring digestion,
and digestion can be affected by the overall health, well-being and
the functionality of critical organs, including the liver and
kidneys. In contrast, the supplemental use of enzymatically
hydrolyzed collagen, fortified so as to provide all of the
essential amino acids, in the form of "pre-digested" protein, has
not been considered for its effect on wound healing.
[0006] Pressure ulcers are also known as bedsores or decubitus
ulcers. The ulcerated area of skin and tissue becomes injured or
broken down typically as a consequence of an extended period of
uninterrupted pressure or other continuing assault to the skin.
Typically, pressure sores develop when the skin and underlying
tissue is squeezed between a bone and an external surface, such as
a bed or chair. The most common places for pressure ulcers are over
bony prominences, such as the elbow, heels, hips, tailbone, ankles,
shoulders, back, and the back of the head. Generally, pressure
ulcers occur when a person is in a sitting or lying position for
too long without shifting his or her weight. Thus, while anyone
confined to a chair or bed is at risk, it is more commonly observed
in the elderly and infirm. Incontinence and decreased sensory
perception, e.g., due to a stroke, also increase the likelihood of
developing bedsores. The constant pressure against the skin
squeezes the blood vessels that supply nutrients and oxygen to the
skin and nearby tissue partially or completely closed, causing a
decreased blood supply to the area. The absence or severe reduction
of oxygen and nutrients, results in the death of the skin and,
potentially, underlying tissues. Left untreated, nearby tissue
begins to die, eventually resulting in an ulcer that can also
affect the bone. Severe ulceration, i.e., resulting in an opening
in the skin can provide an entry for secondary infections; in
particularly severe cases decubitus ulcers can result in death.
[0007] Several factors have been identified that increase the risk
for decubitus ulcers, including: age, elderly people are at higher
risk; inability to move certain parts of the body without
assistance, such as the result of spinal or brain injury, and
neuromuscular disease; malnutrition; being bedridden or in a
wheelchair; a chronic condition such as diabetes or an arterial
disease that inhibits prevents proper blood flow and nutrition;
incontinence resulting in moisture next to the skin for long
periods of time causing skin irritation and breakdown; reduced skin
strength; and mental disability due to a condition such as
Alzheimer's disease, that reduces the ability of an individual to
take proper care or seek appropriate treatment when an ulcer
forms.
[0008] The standard care taken for prevention or treatment include:
identifying individuals at high risk for pressure ulcers;
frequently changing the position of immobile patients, e.g., at
least every two hours to relieve pressure; using items that can
help reduce pressure caused by bedsheets and wheelchairs, e.g.,
pillows, sheepskin, and foam padding, to relieve pressure, and the
use of powdered lubricants, salves or skin creams; making sure
patients eat healthy, well-balanced meals; encouraging daily
exercise, including range-of-motion exercises for immobile
patients; following good skin care and personal hygiene.
[0009] The National Pressure Ulcer Advisory Panel (NPUAP), and
corresponding panels in other countries and regions, e.g., Europe,
Australia, etc. provides a rating system for evaluating decubitus
ulcers covering a range from Stage I, the earliest signs, to Stage
IV, most advanced, as follows:
[0010] Stage I: Non-blanchable erythema of intact skin, i.e., a
reddened area that does not turn white or lighten when pressed.
Discoloration of the skin, warmth, edema, induration or hardness
may also be used as indicators, particularly on individuals with
darker skin.
[0011] Stage II: Partial thickness skin loss involving epidermis,
dermis, or both. The ulcer is superficial and presents clinically
as an abrasion, blister or shallow crater.
[0012] Stage III: Full thickness skin loss involving damage to or
necrosis of subcutaneous tissue that may extend down to, but not
through underlying fascia. The ulcer presents clinically as a deep
crater with or without undermining of adjacent tissue.
[0013] Stage IV: Extensive destruction, tissue necrosis, or damage
to muscle, bone, or supporting structures with or without full
thickness skin loss. Undermining and sinus tracts may also be
present.
[0014] Guidelines for patient assessment and treatment are also
provided, including ensuring adequate dietary intake to prevent
malnutrition to the extent that this is compatible with the
individual's wishes or condition. A protocol for wound treatment is
also summarized and includes the following elements (described in
further detail on the European website):
[0015] Debridement, which is defined as the removal of devitalized
tissue from a wound. Methods of debridement include surgical,
enzymatic, autolytic, larvae or a combination.
[0016] Cleanse wounds as necessary with tap water or with water
suitable for drinking or with saline.
[0017] Use a dressing that maintains a moist environment at the
wound/dressing interface. Reduce the risk of infection and enhance
wound healing by hand washing, wound cleansing and debridement.
[0018] Institute, where appropriate, systemic antibiotic therapy
for patients with bacteraemia, sepsis, advancing cellulitis or
osteomyelitis. Systemic antibiotics are not required for pressure
ulcers that exhibit only clinical signs of local infection.
[0019] As noted, evaluation of nutritional status is generally
considered, as well as a general recommendation such as eating a
balanced diet and, if that is not possible, the use of dietary
supplements. This is also referred to in an article by D. R. Revis,
published at eMedicine.com, wherein it is suggested that dietary
supplements, enteral or parenteral feedings may be useful to
restore a positive nitrogen balance and a serum protein level of 6
mg per 100 mL or higher to facilitate wound healing.
[0020] Bariatric surgery refers to surgical procedures undertaken
to relieve morbid obesity, typically defined as being more than 100
pounds above ideal body weight or having a body mass index of
greater than 40 kg/m.sup.2, in patients unresponsive to
non-surgical therapy for weight loss. Such procedures are divided
into restrictive and malabsorptive types of operations. The
operations most frequently performed include Roux-en-Y gastric
bypass, vertical banded gastroplasty, biliopancreatic diversion and
its variations, various gastric banding procedures and, in certain
circumstances Silastic.RTM. ring gastroplasty. These procedures are
also performed using minimally invasive and laparoscopic
techniques. Naturally, following these surgeries, as with all
others, external as well as internal wounds of varying degrees are
present. However, bariatric surgery patients are also subject to
severely restricted nutritional intake following the surgery. For
example, the total daily caloric intake ranges from about 150 to
about 300 calories based on three meals each having a volume of
less than 2 cooked ounces. Additionally, patients are typically
advised to avoid sugar and fat and to eat protein-dense foods.
Immediately after surgery only liquids are consumed; subsequently,
a combination of liquids and semi-solids is permitted and then,
about three weeks after surgery, solid foods are introduced.
Consequently, it can be seen that there is a particular need for
promoting wound healing in patients undergoing bariatric surgery.
The composition of the present invention, having a complete amino
acid profile in combination with a high protein concentration and
low calorie content, may be particularly suitable for the long-term
maintenance of a bariatric patient.
[0021] While various protein supplements are commercially available
including some with disclosed uses for providing nutritional
support to patients with wounds, the need remains for a method of
promoting wound healing based on an ingestible composition that
provides the proper balance of amino acids and calories in a
concentration that does not unduly burden the body with excess
fluids and fats.
SUMMARY OF THE INVENTION
[0022] A method of treating a mammal to promote wound healing in
said mammal in need thereof, comprising orally administering to
said mammal an effective amount of a palatable, concentrated
protein composition comprising an effective amount of hydrolyzed
gelatin and tryptophan, and an ingestible carrier, said composition
comprising the essential amino acids required by said mammal. A
preferred composition further includes a sweetener, or a flavoring
agent or mixtures thereof, in an amount effective to enhance the
palatability to the mammal of the composition. An embodiment
comprises a method of treating a mammal to promote wound healing in
the mammal, e.g., a person, in need thereof, comprising orally
administering to the person an effective amount of a composition
comprising hydrolyzed gelatin, e.g., about 5 to about 75 parts by
weight; tryptophan, e.g., about 0.02 to about 2.0 parts by weight;
a sweetener, e.g., about 0.1 to about 2 parts by weight; and an
ingestible carrier, e.g., about 5 to about 100 parts by weight. The
composition comprises the essential amino acids required by the
person. In a preferred embodiment, the composition is in a liquid
form, e.g., an aqueous composition, and is administered as a 1
ounce (30 mL) dosage in which there is present 15 grams of
enzymatically hydrolyzed protein, a sweetener and flavoring agent.
In other embodiments, each dosage has about 64 calories or about
101 calories; selection of the calorie level being made according
to the patient's condition and/or the nature or source of the wound
being treated.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 illustrates the results of a patient study relating
to decubitus ulcers using the method of the invention and expressed
in terms of number of patients treated and improved.
[0024] FIG. 2 illustrates the results of the patient study as in
FIG. 1 and expressed in terms of the reduction in the number of
decubitus ulcer sites.
[0025] FIG. 3 illustrates the results of a patient study relating
to pressure ulcers using the method of the invention and expressed
in terms of the total number of residents with pressure ulcers and
the total number of pressure ulcer sites as a function of time of
treatment.
DETAILED DESCRIPTION
[0026] In its liquid form, the present invention comprises an
aqueous composition preferably containing a gelatin hydrolysate,
sorbitol, a palatable acid, such as citric acid, fumaric acid or
adipic acid, for maintaining an appropriate acid pH, tryptophan, a
synthetic sweetener, and flavoring agents when desired. Preferably,
one or more preservatives are included for stabilization purposes.
Preferably, the flavoring agent is one which is highly palatable
and sweet, for example, cherry, orange, green apple, or the like,
while the preservative agent may be any of a number of
preservatives generally recognized as safe for human consumption,
such as potassium sorbate, sodium benzoate, and the methyl-,
propyl-, butyl-, and ethylesters of p-hyroxybenzoic acid, the
latter esters available under trade names methyl paraben, propyl
paraben, etc. The preservatives can be used either alone or in
admixture.
[0027] The gelatin hydrolysate used for preparing the concentrated
protein composition used in the present invention is made by
hydrolyzing animal collagen. For example, the animal collagen can
be derived from the skin of one or more animals selected from the
group consisting of the pig, bovine, ox, cow, calf, bull, sheep,
goat, antelope and buffalo. Preferred are the commercially
available collagen hydrolysate products derived, for example, from
the skin of pork bellies and cattle, e.g. cows, calves, etc., by
means of well-known hydrolysis processes to produce a gelatin
product. Commercial sources of gelatin can be obtained from various
manufacturers including, e.g., Atlantic Gelatin/Kraft Foods,
Cangel, Inc., Eastman Gelatine Corp., Gelita North America, P B
Leiner and Rousselot, Inc., as well as others worldwide. Although
gelatin is soluble in warm water, cooling such a solution results
in a gel. In contrast, an aqueous composition of enzymatically
hydrolyzed gelatin, used to produce the desired peptides for use in
the present invention, does not gel. It is particularly preferred
to carry out enzymatic hydrolysis rather than acid or base
hydrolysis because the use of an enzyme converts the gelatin to the
more palatable small peptides (i.e., mono-, di-, or tri-peptides)
rather than to the less palatable amino acids. In addition,
enzymatic hydrolysis produces fewer distasteful impurities. For
convenience however, compositions are described herein in terms of
the amino acids.
[0028] The structural breakdown of proteins, for example by
enzymatic hydrolysis, is referred to as proteolysis. Similarly, a
proteolytic enzyme that weakens or breaks the peptide linkages in
proteins is referred to as a protease. Many food grade proteases
are available for protein hydrolysis and they can be characterized
by their origin, e.g., animal, plant or microbial as well as their
mode of action. For example, endoproteases cleave amide bonds
within the protein chain and exoproteases remove terminal amino
acids from proteins or peptides. Examples of proteases useful for
hydrolysis of food proteins and potentially useful herein include
the serine proteases trypsin, chymotrypsin, and elastase; and the
bacterially sourced bacillus licheniformis (commercially available
as "Alcalase") and amyloliquefaciens (e.g., "Substilsin Novo").
Cysteine proteases from plants include papain, bromelain and ficin.
Aspartic proteases from animals include pepsin (from porcine and
bovine sources) and chymosin (from calves). Fungal aspartic
proteases are considered chymosin-like (from mucor pusillus and
miehei or endothia parasitica), aspergillo-peptidase A and newlase
(from rhizopus sp.). Animal metallo protease such as carboxy
peptidase A (from the pancreas) and bacterial metallo proteases
such as neutral protease (commercially available as "Neutrase" and
"Thermolysin") from bacillus amyloliquefaciens and
thermoproteolyticus, respectively. Commercial mixtures of proteases
are available such as crude papain, which is a mixture of papain,
chymopapain, and lysozyme; pancreatin, which is a mixture of
trypsin, chymotrypsin, elastase, and carboxypeptidase; "Veron P",
"Sumyzyme LP", and "Biozyme A," which are mixtures of serine-,
aspartic-, and metalloprotease; and "Pronase," which is a mixture
of endo- and exoproteases, active at neutral and alkaline pH. (The
compilation of useful food-grade proteases is published in the PhD
dissertation by C. van der Ven, entitled Biochemical and functional
characterisation of casein and whey protein hydrolysates." Jun. 4,
2002) The preferred enzymes for use in the hydrolysis for the
present invention are those generally recognized as safe for human
consumption. The enzymes particularly preferred for use in the
present invention are bromelain, papain, and ficin, especially
papain, although the other enzymes described may possibly be used.
Processes for hydrolysis of the protein sources identified above
and useful in the present invention are well known to those skilled
in that art.
[0029] The enzymatically hydrolyzed gelatins based on animal
collagen do not contain the essential amino acid tryptophan.
Therefore, tryptophan is added to the compositions useful in the
present invention in an effective amount, for example from about
0.02 to about 2.0 parts by weight of the composition. Other
adjustments in the overall amino acid content as well as for
individual amino acid components may also be made as necessary or
for special purposes or applications. For example, the individual
and overall amount of amino acids used should be such that an
effective amount of each is provided even though the hydrolyzed
collagen source from which the amino acids is obtained varies,
e.g., in moisture content. Additionally, if desired, the
composition can include an additional amount of one or more amino
acid beyond that naturally present in the hydrolyzed animal
collagen. For example, an additional amount of hydrolyzed arginine
can be included. The content of each of the amino acids may vary
somewhat from batch-to-batch within acceptable values for such a
composition. Furthermore, the amino acid profile of a composition
suitable for use in the present invention can be varied by as much
as .+-.30% by weight; more typically .+-.25% by weight; for
example, .+-.20% by weight; provided that, if the amount of any
particular amino acid is less than the preferred amount, e.g., as
illustrated in Table 2 below, it is at least sufficient so that the
composition is suitable to achieve the desired wound healing
affect.
[0030] Although the gelatin hydrolysate of the present invention
has a significantly better taste and odor than other gelatin
hydrolyzates, particularly those not produced by enzymatic
hydrolysis, it does retain a certain amount of acridity. In the
case of other gelatin products, it usually is necessary to add
large amounts of sugar to at least partially mask the underlying
acrid taste. In such instances, artificial sweeteners, such as
sodium saccharin or the like, cannot readily be used because the
aftertaste of these artificial sweeteners, when combined with the
acrid taste of the gelatin product, would make the product
relatively unpalatable. In the present product, however, even
though a certain small amount of residual acridity might remain, it
is capable of being readily masked by artificial sweeteners, with
no serious aftertaste problem, except as may be present in the
sweeteners themselves. This, however, can be overcome by the
inclusion of sorbitol, which not only tastes sweet itself, but also
has a surface coating and lubricating effect thereby facilitating
ingestion of the composition. Additionally, the sorbitol coats the
taste buds, further masking any possible residual acrid taste. In
the present invention the sweetener can be a natural sweetener, an
artificial sweetener or mixtures thereof. For example, the
artificial sweetener is selected from the group consisting of
acesulfame potassium, aspartame, neotame, saccharin, sucralose,
alitame, cyclamate and mixtures thereof, and the natural sweetener
is selected from the group consisting of tagatose, trehalose, a
dihydrochalcone, clycyrrhizin, stevioside, thaumatin, erythritol,
hydrogenated starch hydolysates, isomalt, lactitol, maltitol,
mannitol, sorbitol, xylitol and mixtures thereof. Preferably, the
sweetener is the artificial sweetener sucralose. Finally, a flavor
enhancer or flavoring agent also can be included in the composition
to improve the palatability of the composition. Consequently, the
composition useful in the present invention is made palatable,
which is distinctly advantageous in order to encourage compliance
by the patient with an administration regimen suitable to promote
wound healing. In the above manner, a composition is produced that
is a sugarless, lipid-free, and free of carbohydrates that effect
rapid rise of blood glucose levels. In this respect, sorbitol,
unlike sugar, only slowly affects the blood glucose.
[0031] A typical electrolyte composition present in a 30 mL dose of
the preferred composition useful in the present invention includes,
in milliequivalents, about 2.85 Cl.sup.-, 3.18 Na.sup.+,
0.30K.sup.+, 0.21Mg.sup.++, and, in mg, 12.30 P and 4.20 Cu. If
desired, the electrolytes of the composition of the present
invention can be adjusted by a skilled practitioner to suit the
application.
[0032] As noted, the typical dose useful in the present invention
is about 15 to about 60 mL of the formulated composition;
preferably about 20 to about 40 mL; more preferably from about 25
to about 35 mL; for example, about 30 mL or about 1 ounce. While
the dose amount can be adjusted for individual needs, a 30 mL
portion has been found to be suitable for the average patient. Such
a dose is typically administered about three times daily, although
greater or fewer administrations are feasible, depending on
individual needs. For example, if the patient is in particular need
of protein supplementation prior to the presence of a wound, the
skilled physician or dietician can adjust the dosing amount and/or
frequency as required. In particular, an elderly or bedridden
patient who is not eating sufficient quantities of a well-balanced
diet and is particularly susceptible to developing, or has
developed decubitus ulcers or pressure sores, can be supplemented
with the present composition in order to facilitate healing.
Similarly, a patient who is preparing to undergo bariatric surgery
can ingest the present composition in anticipation of such surgery
in order to facilitate healing of the surgical wounds. Importantly,
such a patient, having severe volume restrictions on the amount of
food that can be eaten at any one time, can ingest the liquid form
of the composition of the present invention and receive the
necessary daily requirements of protein in 3 to 4 doses of 30 mL's
each, particularly for a typical dose containing about 15 grams of
protein and including all of the essential and non-essential amino
acids. For patients being treated for decubitus ulcers, the
compositions and methods of the present invention are preferably
used in combination with the standard care previously used for such
condition in order to further improve the rate and/or extent of
wound healing.
[0033] The caloric value of the composition of the present
invention can be adjusted to suit the needs of the individual. For
purposes of the present invention, the term "calorie" means
kilogram calorie as is commonly the case in connection with foods
and beverages. Consequently, a reference herein to 100 calories
should be understood to mean 100 kilogram calories or 100 kcal. A
useful composition of the present invention can be prepared having
about 64 calories in a 30 mL dose. Alternatively, a high calorie
additive can be included to boost the caloric value of the
composition. Useful additives of this type include sucrose,
dextrose, fructose, corn syrup, high fructose corn syrup, etc.;
fructose is preferred. For example, fructose can be added to the
composition and the calorie level can be increased from 64 calories
to about 101 calories in the same 30 mL dose size. In this manner a
patient requiring high protein, but reduced calories can be
accommodated as well as a patient requiring a higher calorie
composition. Furthermore, the use of fructose rather than sucrose
can be beneficial to a patient with special dietary restrictions,
e.g., as a result of diabetes. If desired, teachings of the present
invention provide the guidance for adjusting the calorie level as
well as the protein level of the composition to suit the needs of
particular classes of patients, while still maintaining an
advantageous low dose volume.
[0034] The high protein concentration in the composition of the
present invention typically includes about 10 to about 30 grams of
all essential and non-essential amino acids: the non-essential
amino acids alanine, arginine (also considered an essential amino
acid for children), aspartic acid, cystine, glutamic acid, glycine,
hydroxylysine, hyroxyproline, proline, serine, and tyrosine; and
the essential amino acids histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, threonine, tryptophan and valine.
[0035] As an example, useful dosing regimens for promoting the
healing of decubitus ulcers and surgical wounds post surgery, based
on a 30 mL dose of the composition of the present invention having
about 15 grams of the complete amino acid profile described above
and about 64 calories, would be as follows: TABLE-US-00001
Condition Method Frequency Decubitus ulcers - Stages I/II PO or GT
BID Decubitus ulcers - Stages III/IV PO or GT TID Surgical Wounds
PO or GT BID or TID Abbreviations: PO = orally; GT = by
gastrointestinal tube; BID = twice/day; TID = three times/day
[0036] The composition of the present invention is particularly
rich in the amino acids arginine, glycine, proline and
hydoxyproline. These amino acids, particularly at the higher
concentrations found in the present invention, especially
facilitate wound healing. While various hypotheses can be put
forward in an attempt to explain the result, the interaction of the
combination of amino acids at various concentrations is complex.
The function of each additional ingredient or amino acid in a
system not only depends on the general conditions of the system
(e.g., temperature and pH), but also to a significant extent on the
presence or absence of other components. This can be understood
because each new amino acid functions as a new chemical entity that
can react with others in the system. These new reactions can
include degradation of vitamins, precipitation of minerals,
denaturation and crosslinking of proteins, changes in
hydrocolloidal behavior of carbohydrates, phase separations, and
changes in nutritional bioavailability. In a living system such as
a mammal or the human body, particularly one under stress due to a
wound or surgery, the effect of addition of an amino acid mixture
is understandably particularly complex. It is sufficient for the
patient that the benefit is obtained by practicing the method of
the present invention.
[0037] Furthermore, depending on the severity of the wound(s), the
treatment can be continued for as long as necessary in the opinion
of the skilled physician or medical professional. Where the wound
is associated with bariatric surgery, the composition of the
present invention can be continued beyond surgical wound healing in
order to facilitate protein supplementation by means of a low
volume composition. This is particularly important where the volume
permitted to be ingested by a person who has undergone bariatric
surgery is significantly limited, especially in the period
immediately following such surgery, e.g., about 2 ounces.
[0038] Compositions of the present invention are also useful, for
example, their use is indicated where an individual exhibits
hypoalbuminemia. In elderly individuals hypoalbuminemia is often
associated with malnutrition and such malnutrition is commonly
defined as an albumin level of less than 3.2 g/dL and associated
weight loss. For an institutionalized patient in particular, a low
albumin level is an indication for administration of compositions
of the present invention. For example, a dosing recommendation for
hypoalbuminemia as indicated by an albumin level of less than 2.8
g/dL is 30 cc by mouth (or gastrointestinal feeding tube) of the
composition of the present invention at a frequency of three times
per day.
[0039] Compositions of the present invention are also useful for
maintaining a positive nitrogen balance. Nitrogen balance indicates
that the rate of protein synthesis in the body equals that of
protein breakdown. It is important to maintain a positive nitrogen
balance in the body, in order to preserve muscle tissue--lean body
mass. If consumption of protein in one's diet is inadequate,
negative nitrogen balance will result. Subsequently, the body
breaks down the protein in its own muscle tissues in order to
reverse the imbalance. Protein is the body's main source of
nitrogen, and when it breaks down, nitrogen is excreted. Measuring
the amount of nitrogen excretion reflects how much protein is
breaking down. A negative nitrogen balance indicates the wasting
away of muscles. It is critical to prevent this, especially during
illness.
[0040] The Net Protein Utilization (NPU) measure reflects the
biological value and digestibility of dietary protein. In other
words, it indicates how much of the protein we consume is actually
available for use. Compositions useful in the present invention
exhibit a particularly high NPU. It is the high concentration of
four (4) amino acids, arginine, glycine, proline, and
hydroxyproline that is responsible for the high NPU in such
compositions. This quality will allow for a more vigorous uptake of
dietary protein and spare lean body mass from being degraded.
[0041] Compositions useful in the present invention generally can
be prepared as described in U.S. Pat. No. 4,025,650, incorporated
herein by reference to the extent permitted. Preferably, the
compositions are liquid, although pulverulent solid or powdered
compositions also can be prepared, the latter useful for further
preparing capsules, granules and tablets, as well as in gels,
lozenges, candy bars and the like, all as described therein. In
general, the compositions comprise the ingredients and range of
proportions shown in Table 1: TABLE-US-00002 TABLE 1 Parts by Wt.
Component (Liquid) Hydrolyzed gelatin 5-75 tryptophan 0.02-2.0
palatable acid (e.g., citric acid) 0.3-10 sorbitol (70 wt. %) 7-25
artificial sweetener (e.g. sucralose) 0.1-2 preservative(s) 0.4-1
flavor 0-0.4 water 15-80
[0042] As described above, unlike other food supplement
compositions that may be in use, the compositions useful in the
present invention advantageously include a high concentration of
amino acids in a relatively small volume of liquid. Selection of
the amounts of the above ingredients is generally made with the
objective of maintaining the substantial solubility of the
ingredients in the liquid carrier, e.g., water. This facilitates
administration of the composition and compliance by the
patient.
[0043] Two tablespoonfuls or one ounce, e.g., 30 mL, of a typical
gelatin hydrolysate according to the present invention includes the
following essential and non-essential amino acids. An example of a
suitable approximate composition, providing at least about 15 g of
soluble protein hydrolysate per 30 mL is shown in the following
table: TABLE-US-00003 TABLE 2 Amino Acid g/100 g Protein L-Alanine
8.60 L-Arginine 7.90 L-Aspartic Acid 5.90 L-Cystine 0.07 L-Glutamic
Acid 9.90 Glycine 23.10 L-Histidine 0.73 Hydroxylysine 1.00
L-Hydroxyproline 6.60 L-Isoleucine 1.30 L-Leucine 3.00 L-Lysine
4.30 L-Methionine 0.73 L-Phenylalanine 2.30 L-Proline 15.20
L-Serine 6.60 L-Threonine 2.00 L-Tryptophan 0.40 L-Tyrosine 0.70
L-Valine 2.40
EXAMPLE 1
[0044] The liquid composition prepared in the manner generally
disclosed above, and corresponding the amino acid profile in Table
2, was employed in an observational study at an extended care
facility for elderly patients. The study was carried out to assess
the therapeutic effect of the composition on the healing process of
decubitus ulcers in eighteen patients. The patients were followed
for a period of ten months and the data collected included the
following: diagnosis, decubitus ulcers progress, serum albumin
level and body weight. Decubitus ulcers progress information
included the following: ulcer site, stage and dimensions (length,
width, depth). Use of the composition of the invention was
initiated at the direction of a physician, registered dietitian
and/or registered nurse based on symptoms such as decubitus ulcers,
poor appetite, weight loss and low albumin level. Dosing and method
of administration are shown in Table 3 along with patient response.
TABLE-US-00004 TABLE 3 Patients with Decubitus Ulcers - Results and
Findings Original Decubitus Response Change Patient Ulcer (d/u) in
condition, I.D. Site Stage stage, or size of d/u Dose Comments H.A.
Buttocks I Healed BID Tube feeding H.A. Back II Healed BID Albumin
2.1 L.J. L lower leg III Healed OD L.J. Back II Healed OD W.I.
Sacrum IV Stage IV, in size BID Desirable wt. W.I. R lat buttocks
II Healed BID W.I. R med buttock II Healed BID W.I. L Buttocks II
Healed BID S.V. Sacrum IV Stage IV, in size TID C.W. R ear II Stage
II, in size BID M.C. R heel III Stage II, in size BID L.A. Sacrum
II Stage II, in size BID N.B. Sacrum I Healed OD M.L. R foot II
Healed BID M.L. L foot II Healed BID M.L. Sacrum I Healed BID L.A.
Sacrum IV Stage IV, no change BID Albumin 1.6 L.A. L inner heel II
Stage II, in size BID Tube feeding B.S. Trach III Healed BID
Albumin 1.9 G.M. Sacrum III Stage III, in size BID Tube feeding
M.M. Sacrum II Healed OD S.I. Sacrum IV Stage IV, in size BID Tube
feeding S.I. L big toe II Healed BID S.I. L hip IV Stage IV, BID
much reduced L.K. R heel II Healed OD G.B. L great toe II Healed
BID Tube feeding F.E. Sacrum II Stage I OD Redness F.E. L scapula
II Stage II, in size OD W.M. L heel I Healed TID Tube feeding W.M.
Sacrum IV Stage IV, in size TID Column headed "Dose" refers to
frequency of administration; abbreviation "OD" = every day; others
defined above.
[0045] The results of study are also shown in FIGS. 1 and 2 in the
form of bar charts. FIG. 1 shows that, following treatment with the
composition of the present invention, there was an overall 50%
reduction in the total number of patients with decubitus ulcers. In
addition, FIG. 2 shows that 17 of the original total number of
decubitus ulcer sites were completely healed following use of the
composition of the present invention.
EXAMPLE 2
[0046] The liquid composition described above was employed in a
study at an extended care facility for elderly patients. The study
was carried out to assess the therapeutic effect of the composition
on the healing process of decubitus ulcers in residents. The
patients were followed for a period of more than four months and
the data collected included the following: total number of
residents with pressure ulcers and total number of pressure ulcer
sites. Patient dosing was at least twice per day and three to four
times per day for those patients exhibiting Stage III or Stage IV
decubitus ulcers. The results of the study are shown in FIG. 3. The
arrow at Jul. 15, 2002 indicates the date on which administration
of the composition to residents started; it was continued
throughout the time period shown. Overall, there was a 60%
reduction in the total number of pressure ulcer sites and a 50%
reduction in the number of residents exhibiting pressure ulcers as
a result of the administration of the composition of the
invention.
[0047] The present invention is not only clearly valuable in the
treatment of patients exhibiting wounds resulting from decubitus
ulcers, but it is similarly valuable for patients undergoing
surgery in order to promote wound healing, e.g., particularly in
connection with bariatric surgery. In this respect, it may also be
used to provide proper nutrition to such patients since the volume
of food is severely limited and it is difficult for the patient to
consume sufficient nutrition in order to provide adequate protein
and/or amino acids. Administration of the composition of the
present invention provides such protein, particularly as a
consequence of its highly concentrated composition, e.g., 15 g of
protein comprising all of the essential and non-essential amino
acids in a 1 ounce (30 mL) dose size and in a hydrolyzed form that
is especially suitable for such patients. In a limited study, it
was observed that, for those patients following the required
dietary regimen following bariatric surgery based on the above
composition, there was a significant ease of administering the
necessary protein requirements even under circumstances where food
and fluid intake was severely volumetrically restricted.
Furthermore, the rate of wound healing was generally faster and,
especially compared to the use of powdered protein supplements,
there were fewer side effects and hair loss was minimal for such
patients.
[0048] Method of treating wounds to promote healing by
administering by ingestion to a mammal in need of such treatment a
composition comprising hydrolyzed gelatin, tryptophan, a sweetener,
and an ingestible carrier, the composition comprising the essential
amino acids required by the mammal. The treatment method is
particularly suitable for treating decubitus ulcers and wounds
resulting from bariatric surgery.
[0049] Any range of numbers recited in the specification, or
paragraphs hereinafter, describing various aspects of the
invention, such as that representing a particular set of
properties, units of measure, conditions, physical states or
percentages, is intended literally to incorporate expressly herein
by reference or otherwise, any number falling within such range,
including any subset of numbers or ranges subsumed within any range
so recited. Additionally, the term "about" when used as a modifier
for, or in conjunction with, a variable, is intended to convey that
the values and ranges disclosed herein are flexible and that
practice of the present invention by those skilled in the art
using, e.g., temperatures, concentrations, amounts, contents,
carbon numbers, properties such as viscosity, particle size,
surface area, solubility, etc., that are outside of the stated
range or different from a single value, will achieve the desired
result, namely, promoting wound healing by the ingestion of a
defined composition.
[0050] The principles, preferred embodiments, and modes of
operation of the present invention have been described in the
foregoing specification. The invention which is intended to be
protected herein, however, is not to be construed as limited to the
particular forms disclosed, since these are to be regarded as
illustrative rather than restrictive. Variations and changes may be
made by those skilled in the art, without departing from the spirit
of the invention.
* * * * *