Note: Descriptions are shown in the official language in which they were submitted.
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METHODS FOR TREATING POST-TRAUMATIC STRESS DISORDER
The present application is a divisional of Canadian Patent Application
No. 2885570, filed on September 19, 2013.
PRIORITY CLAIM
This application claims the benefit of the filing date of United States Patent
Application Serial Number 13/623,101, filed September 19, 2012, for "METHODS
FOR TREATING POST-TRAUMATIC STRESS DISORDER"; and United States
Patent Application Serial Number 13/623,097, filed September 19, 2012, for
"METHODS FOR IMPROVING SLEEP EFFICIENCY IN HEALTHY HUMAN
BEINGS."
TECHNICAL FIELD
Embodiments of the invention generally relate to methods and supplements for
treating post-traumatic stress disorder. Other embodiments of the invention
generally
relate to methods and supplements for improving sleep efficiency in healthy
humans.
BACKGROUND
Posttraumatic stress disorder (PTSD) is a severe anxiety disorder that can
develop after exposure to any event that results in psychological trauma. This
event
may involve the threat of death to oneself or to someone else, typically
overwhelming
the individual's ability to cope. As an effect of psychological trauma, PTSD
is less
frequent and more enduring than the more commonly seen acute stress response.
Diagnostic symptoms for PTSD include re-experiencing the original trauma(s)
through
flashbacks or nightmares, avoidance of stimuli associated with the trauma, and
increased arousal, such as difficulty falling or staying asleep, anger, and
hypervigilance.
Posttraumatic stress disorder is classified as an anxiety disorder,
characterized
by aversive anxiety-related experiences, behaviors, and physiological
responses that
develop after exposure to a psychologically traumatic event (sometimes months
after).
Its features persist for longer than 30 days, which distinguishes it from the
briefer acute
stress disorder. These persisting posttraumatic stress symptoms cause
significant
disruptions of one or more important areas of life function.
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Although most people (50-90%) encounter trauma over a lifetime, only about
8% develop full PTSD. Vulnerability to PTSD is believed to stem from an
interaction
of biological diathesis, early childhood developmental experiences, and trauma
severity.
A variety of medications has shown adjunctive benefit in reducing PTSD
symptoms, but there is no clear drug treatment for PTSD. Positive symptoms
(re-experiencing, hypervigilance, increased arousal) generally respond better
to
medication than negative symptoms (avoidance, withdrawal), and it is
recommended
that any drug trial last for at least 6-8 weeks.
Medication classes that have been used for symptom management include:
SSRls (selective serotonin reuptake inhibitors, such as citalopram,
escitalopram,
fluoxetine, fluvoxamine, paroxetine, and sertraline); anti-depressants (such
as,
bupropion, venlafaxine, sertraline, fluoxetine, nefazodone, heterocyclics, and
paroxetine); alpha-adrenergic antagonists (such as, prazosin and clonidine);
anti-convulsants, mood stabilizers, anti-aggression agents (such as
carbamazepine,
zolpidem, lamotrigine, valproic acid, and buspirone); antipsychotics; atypical
antidepressants (such as nefazodone and trazodone); beta blockers;
benzodiazepines;
glucocorticoids; heterocyclic / tricyclic anti-depressants (such as
amitriptyline and
imipramine); and monoamine-oxidase inhibitors (MA01s). Medication classes that
have been used for symptom prevention include: alpha-adrenergic antagonists;
beta
blockers; and glucocorticoids.
A direct correlation has been observed between low growth hormone curves at
onset of sleep and sleep problems in PTSD. (See, e.g., van Liempt, Decreased
nocturnal growth hormone secretion and sleep fragmentation in combat-related
posttraumatic stress disorder; potential predictors of impaired memory
consolidation,
Psychoneuroendocrinology (2011) 36,1361-1369).
A circadian rhythm is any biological process that displays an endogenous,
entrainable oscillation of about 24 hours. These rhythms are driven by a
circadian
clock, and rhythms have been widely observed in plants, animals, fungi and
cyanobacteria. The term circadian comes from the Latin circa, meaning "around"
(or
"approximately"), and diem or dies, meaning "day." The folinal study of
biological
temporal rhythms, such as daily, tidal, weekly, seasonal, and annual rhythms,
is called
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chronobiolo gy. Although
circadian rhythms are endogenous ("built-in,"
self-sustained), they are adjusted (entrained) to the local environment by
external cues
called zeitgebers, commonly the most important of which is daylight.
Circadian rhythmicity is present in the sleeping and feeding patterns of
animals,
including human beings. There are also clear patterns of core body
temperature, brain
wave activity, hormone production, cell regeneration and other biological
activities. In
addition, photoperiodism, the physiological reaction of organisms to the
length of day
or night, is vital to both plants and animals, and the circadian system plays
a role in the
measurement and interpretation of day length. The primary circadian "clock" in
mammals is located in the suprachiasmatic nucleus (or nuclei) (SCN), a pair of
distinct
groups of cells located in the hypothalamus. The SCN receives information
about
illumination through the eyes. The retina of the eye contains "classical"
photoreceptors
("rods" and "cones"), which are used for conventional vision. But the retina
also
contains specialized ganglion cells, which are directly photosensitive, and
project
directly to the SCN where they help in the entrainment of this master
circadian clock.
These cells contain the photopigment melanopsin and their signals follow a
pathway called the retinohypothalamic tract, leading to the SCN. If cells from
the SCN
are removed and cultured, they maintain their own rhythm in the absence of
external
cues.
The SCN takes the information on the lengths of the day and night from the
retina, interprets it, and passes it on to the pineal gland, a tiny structure
shaped like a
pine cone and located on the epithalamus. In response, the pineal secretes the
hormone
melatonin. Secretion of melatonin peaks at night and ebbs during the day and
its
presence provides information about night-length.
Several studies have indicated that pineal melatonin feeds back on SCN
rhythmicity to modulate circadian patterns of activity and other processes.
However,
the nature and system-level significance of this feedback arc unknown.
It would be desirable to provide a nutritional supplement for treating
post-traumatic stress disorder. It would also be desirable to provide a
nutritional
supplement for improving sleep efficiency in healthy humans.
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3a
SUMMARY
In some embodiments, there is provided a use of a nutritional supplement
orally to
treat post-traumatic stress disorder in a human being, the nutritional
supplement comprising:
0.1 to 6 mmol L-arginine; 0.1 to 8 mmol Oxo-proline; 0.1 to 12 mmol L-lysine;
0.001 to
6 mmol N-acetyl L-cysteine; and 0.001 to 6 mmol L-glutamine.
In some embodiments, there is provided a use of a nutritional supplement
orally to
treat post-traumatic stress disorder in a human being, the nutritional
supplement comprising:
L-arginine HC1; Oxo-proline; L-lysine HC1; and N-acetyl-L-cysteine, L-
glutamine, or both;
wherein each serving of the nutritional supplement contains 1 mmol L arginine,
1 mmol
Oxo proline, 2 mmol L lysine, 1.5 mol N acetyl L cysteine, and 2 mol L
glutamine.
In some embodiments, there is provided a nutritional supplement for use orally
to
treat post-traumatic stress disorder in a human being, the nutritional
supplement comprising:
0.1 to 6 mmol L-arginine; 0.1 to 8 mmol Oxo-proline; 0.1 to 12 mmol L-lysine;
0.001 to
6 mmol N-acetyl L-cysteine; and 0.001 to 6 mmol L-glutamine.
In some embodiments, there is provided a nutritional supplement for use orally
to
treat post-traumatic stress disorder in a human being, the nutritional
supplement comprising:
1 mmol L arginine in the form of L-arginine HC1; 1 mmol Oxo proline; 2 mmol L
lysine in
the form of L-lysine HCl; 1.5 mot N acetyl L cysteine; and 2 mot L
glutamine.
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DISCLOSURE
Described herein are nutritional supplement and method of using the same.
The nutritional supplement includes an amino acid secretagogue composition,
which,
taken orally, stimulates the pituitary gland to release hGH.
Some embodiments include an oral nutritional supplement that comprises
L-arginine, oxo-proline, and L-lysine.
A particular embodiment of the present disclosure relates to an oral
nutritional
supplement that includes the amino acids 1-lysine, 1-arginine, oxo-proline,
and one of
either cysteine or glutamine. The amino acids may be delivered as non-toxic
salts
thereof, effective complexes thereof, stable chelatcs thereof, active esters
thereof,
functional derivatives thereof, and mixtures thereof which are effective to
increase
hGH levels in the general population.
Another particular embodiment relates to an oral nutritional supplement that
consists essentially of 1-lysine HCl, 1-arginine HCl, oxo-proline, N-acetyl-l-
cysteine,
1-glutamine, and schizonepeta (aerial parts) powder.
Other embodiments are drawn to methods of treating post-traumatic stress
disorder in humans that include orally administering the disclosed nutritional
supplement to a human being suffering from post-traumatic stress disorder.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a linear regression analysis of time to fall asleep with
continued
use of the supplement over time; and
FIG. 2 shows time awake during sleep over time with continued use of the
supplement.
MODE(S) FOR CARRYING OUT THE INVENTION
The present invention relates to a nutritional supplement for use by a human
being. The present invention is drawn to a nutritional supplement and method
of using
the same. The nutritional supplement is an amino acid secretagogue
composition,
which, taken orally, treats one or more post-traumatic stress disorder (PTSD)
symptoms. The supplement of the present invention works as a dietary
supplement by
assisting the body's own ability to treat PTSD symptoms naturally in a manner,
which
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is safe and effective, as well as being affordable. The supplement of the
present
invention also works as a dietary supplement by assisting the body's own
ability to
improve sleep efficiency naturally in a manner which is safe and effective, as
well as
being affordable.
A particular embodiment of the present disclosure relates to an oral
nutritional
supplement that includes 1-lysine, 1-arginine, oxo-proline, and one of either
cysteine or
glutamine. The supplement may additionally include both cysteine and glutamine
and/or schizonepeta powder. In particular embodiments, a functional dosage
includes
the l-arginine at a level between 0.1-6 mmol and the oxo-proline between 0.1-8
mmol,
and/or the 1-lysine in an amount between 0.1-12 mmol. The cysteine and/or
glutamine
may be contained at a level between 0.001-6 mmol. In another particular
embodiment,
a functional dosage includes the 1-arginine at a level between 2.5-4.5 mmol
and the
oxo-proline between 4-6 mmol, and/or the 1-lysine in an amount between 7-9
mmol.
The cysteine and/or glutamine may be contained at a level between 0.001-0.5
mmol.
The cysteine can be n-acetyl L-cysteine and the glutamine may be [-glutamine.
The
amino acids may be delivered as non-toxic salts thereof, effective complexes
thereof,
stable chelates thereof, active esters thereof, functional derivatives
thereof, and
mixtures thereof which are effective to increase hGH levels in the general
population.
The nutritional supplement may be present in an amount of 2.9 grams. The
nutritional
supplement may be in any acceptable and known oral formulation, such as
powder,
tablet, capsule, liquid, or wafer foini.
Another particular embodiment relates to an oral nutritional supplement that
consists essentially of 1-lysine HO, 1-arginine HC1, oxo-proline, N-acetyl-l-
cysteine,
1-glutamine, and schizonepeta (aerial parts) powder. In particular
embodiments, a
functional dosage includes the 1-arginine HC1 at a level between 0.1-6 mmol
and the
oxo-proline between 0.1-8 mmol, and/or the 1-lysine HC1 in an amount between
0.1-12 mmol. The n-acetyl L-cysteine and/or 1-glutamine may be contained at a
level
between 0.001-6 mmol. In another particular embodiment, a functional dosage
includes the 1-arginine HCI at a level between 2.5-4.5 mmol and the oxo-
proline
between 4-6 mmol, and/or the 1-lysine HC1 in an amount between 7-9 mmol. The
n-acetyl L-cysteine and/or 1-glutamine may be contained at a level between
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0.001-0.5 mmol. The nutritional supplement may be in any acceptable and known
oral
formulation, such as powder, tablet, capsule, liquid, or wafer form.
Other embodiments are drawn to methods of increasing human growth
hormone in humans that include orally administering the disclosed nutritional
supplement to a healthy human being. As used herein, "healthy human being"
means a
human being without any physiological deficiency in hGH independent of age.
Particular embodiments of the invention relate to oral administration of the
disclosed
nutritional supplement to a human that is at least 30 years old. The
nutritional
supplement may be administered from one to three times daily or,
alternatively, may be
administered every other day, or may be administered once a week. In
particular
embodiments, the nutritional supplement may be administered on an empty
stomach.
In accordance with the "consist essentially of" and "consisting essentially
of"
language, the nutritional supplement of the third embodiments is essentially
limited to
the aforementioned ingredients and does not include any additional active
ingredients
intended to add nutritional content (e.g., vitamins, minerals, etc.), but may
include
additional ingredients not intended to add nutritional content such as
ingredients
intended to fulfill a non-nutritional purpose (e.g., coloring, fillers,
flavoring, an
ingredient for maintaining the structural form, etc.).
Each ingredient of the nutritional supplement of the present invention may be
prepared in accordance with any method known to one of ordinary skill in the
art.
Alternatively, each ingredient may be obtained in a fully prepared from a
commercially
available source.
The nutritional supplement of the present invention may be in any suitable
oral
administration form, including but not limited to: a chewable form, a liquid
form, a
spray form, a capsule form, a suppository form, dissolvable wafer, and a
powder form.
Irrespective of the structural form of the nutritional supplement, the
ingredients
of the nutritional supplement may be distributed homogeneously or
non-homogeneously within the nutritional supplement.
The nutritional supplement of the present invention may be ingested on a
regular basis, such as a daily or weekly intake at a dosage tailored to an
individual's
needs; i.e., the nutritional supplement is to be taken regularly as multiples
(lx, 2x, etc.)
of the structural units (pills, tablets, capsules, liquid dose, etc.) in
accordance with the
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needs of the individual. For example, a senior citizen leading a sedentary
life may need
higher daily doses than does a young person engaged in regular strenuous
exercise
(e.g., a weight lifter). Alternatively, the nutritional supplement of the
present invention
may be ingested on an as-needed basis at a dosage tailored to the individual's
needs.
Medical or nutritional counseling may be beneficial for arriving at a
desirable or
optimal dosage tailored to the individual's needs.
The combination of types of amino acids, mass ranges, and specific
formulations have been selected to be synergistically balanced and of adequate
quantity
to achieve the desired physiological effect, namely, treatment of PTSD
symptoms.
Improper combinations of the amino acids may be ineffective. The component
amino
acids are synergistic in the sense that several of them when combined
together,
synergistically treat one or more symptoms of PTSD. The combination was also
chosen to reduce or inhibit chemical combination or reaction between the amino
acids.
EXAMPLES
Example 1
A double-blind clinical study involved 15 healthy subjects [10 males,
5 females; mean age = 33 7 years]. Each subject completed a baseline Epworth
Sleepiness Scale self-report questionnaire and a standardized assay of usual
sleep
habits. All subjects were deemed to have average sleep parameters within a
normal
range.
The subjects were then provided a three week supply of a novel supplement
SEROVITAL (2.9g/dose blend of 1-lysine HC1, 1-arginine HC1, oxo-proline,
N-acetyl-l-cysteine, 1-glutamine, and schizonepeta (aerial parts) powder). The
novel
SEROVITAIA blend has been shown previously to increase serum human growth
hormone hGH levels by 8 times (equivalent to 682%) 120 minutes after a single
dose
in healthy male and female volunteers. Because night-time onset of hGH has
been
directly correlated to sleep efficiency, we investigated sleep patterns with
continued
use of the supplement when taken on an empty stomach, two hours after dinner
prior to
bedtime, every night for three weeks. On each trial day, subjects reported 1)
time went
to bed; 2) time of final wakening; 3) estimated time to fall asleep; 4) time
of awakening
during sleep/length of time awake. Data was compiled by day for estimated time
to fall
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asleep and length of time awake during sleep in order to assess sleep
efficiency. Daily
values for each measure were plotted as an average (+S.D.) among the subjects
over
the time course of the study, and a linear regression was tabulated to assess
overall
trends over time. All available data was included in the analysis.
Linear regression analysis showed that both estimated time to fall asleep
(FIG. 1) and time awake during sleep (FIG. 2) tended to decrease over time
with
continued use of the supplement over the time course of the study. Time to
fall asleep
decreased with an average slope of -0.24min/day, and time awake during sleep
decreased by an average slope of -0.26min/day. Overall, these results so a
trend
towards greater sleep efficiency by measurements of both time to fall asleep
and time
awake during sleep, both with a quantified average decrease of about
0.25min/day over
three weeks with regular nighttime use of the novel SERoVrrAL supplement
(when
taken as directed, on an empty stomach, two hours after dinner prior to
bedtime).
Example 2
Veterans with PTSD are recruited through outpatient clinics and Veteran
Affairs Medical Centers. Trauma controls (TC; veterans without PTSD) and
healthy
controls (HC; service members never deployed or civilians) are recruited
through
advertisements. Controls arc matched with the PTSD group for age, year of
deployment (TC), and region of deployment (TC). All participants are screened
for
psychiatric illness. The diagnosis of PTSD is confirmed by the Clinician
Administered
PTSD Scale (CAPS) and patients are included when a score of over 50 is
obtained and
there is an absence of psychiatric disorders other than mood and anxiety
disorder. TCs
are included when they meet the criteria for PTSD (experienced, witness, or
was
confronted with an event involving actual or threatened death or serious
injury to self
or others), but has a CAPS score below 18. All participants are medically
healthy
individuals and arc free from psychotropic medication and alcohol or drug
dependence
in the past six months. All control subjects are without a history of
psychiatric
disorders and without sleep complaints.
Sleep registrations during two consecutive nights are conducted in a sleep
laboratory. Sleep recordings are acquired, including bipolar derivations of
EMG, EOG
for vertical and horizontal eye movements, EEG, and ECG.
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To assess declarative memory consolidation, a 15 word task is administered
three hours before sleep on the second evening. Fifteen neutral one syllable
words are
visually presented on a computer screen, and repeated three times. Every
presentation
is followed by a free immediate recall and is assessed the next morning
between 30-45
minutes after awakening.
Sleep data are analyzed in 30 second epochs by an experienced sleep technician
who is blind to PTSD diagnosis. The number of spontaneous awakenings fro Stage
2
sleep, slow wave sleep, or rapid eye movement sleep are determined for the
first half of
the night. Total sleep time is also determined.
While embodiments of the present invention have been described herein for
purposes of illustration, many modifications and changes will become apparent
to
those skilled in the art. Accordingly, the appended claims are intended to
encompass
all such modifications and changes as fall within the true spirit and scope of
this
invention.
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