Note: Descriptions are shown in the official language in which they were submitted.
The present invention relates to medicine,
particularly to experimental and clinical therapy
and can be utilized for producing adaptogenic effect
on the organism of a person in extreme conditions or
5 who has suffered a grave illness, and for improving
his mental, physical capacity and endurance in
sports exercises.
There are universally known agents of a
vegetable origin exhibiting adaptogenic effect, such
10 as extracts of ginseng and eleuterococcus roots
which are capable of inducing the state of
nonspecifically high resistance of the organisms of
mammals.
Under experimental conditions said
15 adaptogens created adaptation of experimental
animals to unfavorable conditions.
Administration of the extract of
eleuterococcus roots in 2 ml daily doses during two
l-month courses in autumn and winter period to
20 workers of chemical enterprises has shown a
noticeable reduction of chills in many cases.
This preparation is recommended for
improving working capacity in the North. The ginseng
extract is also capable of stimulating the function
25 of cerebral cortex ~see Brekhman G.I. et al
"Eleuterococcus as a Means for Improving Nonspecific
Resistance of Organism" AN USSR, series, 5, 1965,
pp. 762-764 and "New Data on Eleuterococcus and
Other Adaptogens" Vladivostok, DVNTs AN USSR, 1981,
30 pp. 79-83, 88-112). However, adaptogenic agents of
vegetable origin have considerable inherent
disadvantages:
1. Seasonal limitation of curative effect,
i.e. most conspirous adaptogenic properties are
35 displayed only in autumn and winter.
-- 2
2. Scarcity of vegetable sources and
resultant high price, e.g. of ginseng extract, which
hampers their wide administration.
Among the easily available and more
accessible synthetic adaptogenic agents except
dibasol and, to a lesser degree, some of its
derivatives at present there are no agents with a
pronounced adaptogenic effect. Thus, there is a
known synthetic adaptogenic agent, dibasol, taken
for a prototype (see Rusin V. Ya. "On Adaptation to
Cold and Heat during Muscular Training and
Administration of Dibasol", J. "Pathological
Physiology and Experimental Therapy", 1962, No. 6,
pp. 63-65 and Rosin M.A. "State on Nonspecific High
Resistance under the Effect of Some Pharmacological
Agents", Ch. II in the book "Nonspecific Medicinal
Prophylaxis and Therapy of Cancer" AMN USSR, L.,
"Medicine", 1968, pp. 27-29).
The adaptogenic properties of dibasol have
been confirmed in experimental conditions by
administering it subcutaneously in a physiological
solution at the rate of 1 mg per 1 kg of animal body
weight daily during 30 days. This stimulated
adaptation of animals to cold, heat and raised their
working capacity (forced swimming).
Dibasol can be used to a limited extent
for prophylaxis of seasonal catarrhs of upper
respiratory tracts, tracts, and anginas.
A substantial disadvantage of both dibasol
and adaptogens of a vegetable origin lies in a
marked seasonal limitation of their effect in autumn
and winter only.
Another serious disadvantage of dibasol is
its vasodilative and hypertensive side effects so
that it is generally used to arrest hypertensive
crises in patients with exacerbated hypertension.
(See Machkovsky M.D. "Medicinal Agents", part 1 M.,
"Medicine", 1985, pp. 450-451).
In view of the above, we hereby disclose
the use of a synthetic aminoacid DL-valine in the
capacity of an adaptogenic agent.
Known in the prior art is the
administration of DL-valine in the capacity of an
aminoacid food component of aminoacid mixtures:
aminofusine, steramine, trophizane used for
parenteral feeding which satisfies the nitrogen
needs of the organism of surgical patients after
partial or complete ablation of the stomach. (See
Sudzhan A.K. et al "Parenteral Feeding in
Oncosurgery", M. "Medicine", 1973, pp. 70-71).
DL-valine is also used in experimental
oncology as an antitumoral agent in vitro (see Inv.
Cert. No. 750787 of 2 .03.1980 A 61 K 31/195
"Antitumoral Agent" by Kislyakov N.D. et al).
As distinct from the known adaptogens of
vegetable origin and from the known synthetic
adaptogen (dibasol). DL-valine exhibits its
adaptogenic properties not only in winter and autumn
but also in spring and summer inducing the state of
more pronounced nonspecifically-high-resistance of
the organism of mammals, and man in particular, with
prolonged aftereffect.
The adaptogenic effect of DL-valine on the
human organism after a course of its administration
is expressed in the following:
1. Substantial increase of
immunoresistance of human organism to all chills
(acute respiratory illness, angina, pharyngitis,
post-flu complications, etc.) both in autumn-winter
and spring-summer periods which is characteristic of
neither analogs nor prototype of the disclosed
agent.
:
-- 4
2. Weakening and, after repeated
administration of DL-valine, even vanishing of many
a chronic inflammatory process, such as gastritis,
cholecystitis, chronic pharingitis, bronchitis, etc.
due to development of stable resistance of harmful
biological factors (bacterial organisms).
It is worthy of note that, already a few
days after the beginning of DL-valine administration
there appear pains at points of old and long-
forgotten chronic inflammations. However, in two or
three days these sensations vanish completely and do
not reappear. Antiflammatory effect of other
adaptogens is less expressed and little
investigated.
3. Gradual normalization of metabolic
processes of both general metabolism (normalization
of weight) and in individual organs, e.g.
cardiovascular system, liver, etc. Repeated courses
deepen and consolidate this normalization.
4. Regulating and normalizing influence on
the nervous activity of man, i.e. his psychic
condition. Thus, in persons with more or less
pronounced symptoms of astheno-depressive syndrome
with a prevailing feeling of depression, uneasiness
and, on the contrary, in persons susceptible to
sharp excitement spells with inadequate reaction to
weak irritant (weakness of inhibiting processes)
their psychic state becomes normalized already
within the first month of taking the DL-valine.
There appear a feeling of calm, well-being and
adequate reaction to various irritants. This
normalization is finally consolidated by repeating
the course of DL-valine after 6-7 months.
Of all the known adaptogens such
regulating effect on psychics of man by stimulating
his cerebral cortex can be caused by ginseng alone
, ," ," ~"~ ~ ", , , ;~
which~ however, is least available to people because
of its scarcity.
Besides, administration of ginseng in
treating various degrees of asthenodepressive
syndrome brings about only temporary improvement in
the psychic condition state but fails to normalize
it as is achieved by using the disclosed agent (see
Petkov B. "On Mechanism of Action of Ginseng as a
Regulator of Organism's Reactivity", in the book
"New Data on Eleuterococcus and Other Adaptogens",
Vladivostok, DVNTs AN USSR, 1981, pp. 106-112).
5. Activating effect of DL-valine on
short-term and long-term memory processes which is
particularly important in the gerontological aspect
and in raising the mental activity. This is probably
associated with the activating influence of DL-
valine on metabolic processes, particularly
metabolism of chlolesterine and proteins in the
nervous tissues of the central nervous system.
6. Substantial reduction of fatigue and
stable improvement of physical activity, development
of the need for physical exercises and sports
training.
Bearing in mind that this effect of DL~
valine on the organism of a sportsman is fully
devoid of seasonal limitations, it acquires a
particular value in comparison with other
adaptogens.
7. Thus, the disclosed agent has a novelty
feature since at the present development stage of
medicine its adaptogenic function is unknown.
The inventive level of the disclosed agent
evidently is not based on the known achievements of
modern medicine (analogs and prototypes).
The disclosed invention can be widely
introduced into the practice of prophylaxis,
physical and psychic improvement of people's health.
The essence of the invention lies in the combination
of essential features sufficient for the attainment
of the result sought for.
For providing and confirming the presence
of comprehensively pronounced adaptogenic properties
of the new disclosed agent, DL-valine, and for
revealing some mechanisms of forming these
properties we have conducted a series of experiments
on white nondescript rats subjected to the effect of
DL-valine in comparison with control groups of the
same animals (not treated with DL-valine) and with
groups of animals treated with the known agent, i.e.
dibasol (prototype).
The first step was to determine the
optimum dose of DL-valine on milk introduced
perorally (by probe into stomach) for white female
and male nondescript rats.
It has been established that the course
should not exceed 3-4 weeks (once daily, five days a
week). Otherwise, overdosage will reduce the
adaptogenic effect of DL-valine. The daily dose of
the agent depends only on the animal body weight.
For example, it is 40 mg per 100 g of body weight
for animals weighing 100-150 g while for those
25 weighing about 200 g and over the dose shall be 60
mg per 100 g of animal's body weight. To prevent
development of aminoacidic unbalance, the DL-valine
is introduced mostly against the background of
protein food ration.
Initially, the adaptogenic properties of
DL-valine were checked by administering it once, 1 h
before the action of the unfavorable factor, using
all conventional tests (see Kovalyev G.V. et al "On
Comparative Adaptogenic and Antistress activity of
Compounds with Different Chemical Structure", in the
book "New Data on Eleuterococcus and Other
Adaptogens", Vladivostok DVNTs AN USSR, 1981, pp.
51-56) in spring and summer (April, May, June) in
order to corroborate the absence of seasonal
limitations in its activity.
Simultaneously, the adaptogenic activity
of dibasol was tested under the same conditions for
comparative assessment of adaptogenic properties of
the new synthe~ic agent and the known medicament -
dibasol (prototype).
Test I. Assessing the influence of DL-
valine on general physical activity (repeatedforced swimming). Test animals were white
nondescript male rats (weight 250-260 g): 10 test
animals and 10 control ones. Water temperature was
21C during both initial and repeated (three days
later) swimming. Both test and control animals were
swimming synchronously in pairs. Before repeated
swimming the test animals were given 60 mg of DL-
valine in 1 ml of milk per 100 g of body weight, 60
min. before plunging into water. The medicament was
administered through a probe into the stomach. The
control rats received 1 ml of milk per 100 g of body
weight.
The time of repeated swimming of test
animals was increased by 8.25il.47 min., while that
of the control animals, by 3.40il.36 min.,
respectively, so that p < 0.05 (statistical
processing by conventional parametric method using
"Student-Fisher criterion"). This point to the fact
that administration of DL-valine increases physical
activity of animals.
Adaptogenic effect of dibasol was checked
under the same conditions on 10 test and 10 control
nondescript male rats weighing 200-215 g. Dibasol
dissolved in Ringer solution was administered to
test animals subcutaneously in a dose of 0.1 mg per
100 g of body weight in 0.2 ml of Ringer solution
(or 1 mg/kg of body weight, a dose considered to be
most effective` 60 min. before repeated swimming.
The control rats were also given subcutaneously 0.2
ml of Ringer solution per 100 g of body weight.
The increased time of repeated swimming in
the test group was reliably lower (1.12~0.37) than
that in the control group (4.37~1.25) at p < 0.05
which indicates that physical activity is not
increased under the effect of dibasol but may even
diminish, probably due to the seasonal nature of its
action.
Test II. Checking protective
anticonvulsive effect of DL-valine under the
damaging action of strychnine ~factor of chemical
nature). Test animals were white nondescript male
rats (weight 200-250 g). The test group (7 animals)
was given DL-valine in the test dose (see above) 60
min. before intra-abdominal injection of toxic dose
of strychnine at the rate of 0.2 mg per 100 g, i.e.
0.2 ml of 0.1~-solution per 100 g of body weight
(conventional dose). The control group (7 animals)
received milk.
Within the first hour 2 rats perished in
the test group and seven animals in the control
group. Result: 5 from 7 animals survived in the test
group and none in the control group. According to
the table in "accurate Method for fisher (from the
book by V.S. genes "Tables of Reliable Differences
between Observed Groups by Qualitative Indices",
"Medicine", 1964, pp. 11-15) the differences in the
survival rate after administration of DL-valine as
compared with the control group are reliable (p <
0.025).
Repetition of this test under the same
conditions but with subcutaneous administration of
dibasol 60 min. before injection of toxic dose of
strychnine (same dose 0.2 ml of solution containing
0.1 mg per 100 g of body weight) has demonstrated
:
that 5 animals died out of 7 within the first hour
and 2 survived. Out of 6 control animals, 6 died and
none survived (according to Fisher method p > 0.025,
the difference is unreliable).
Thus, as distinct from dibasol,
adminlstration of DL-valine has exerted a pronounced
protective effect against the damaging factor of
chemical nature.
Test III. Checking resistance to the
damaging factor of biological nature, i.e. intra-
abdominal injection of ascitic cancer cells (0
STRAIN + cancer of rats ovaries). Test animals were
white nondescript female rats (weight 260-300 g)
which were given the above-stated dose of DL-valine
in the test group (8 animals) while the control
group (7 animals) received milk. 60 minutes later
the animals in both groups were reinoculated intra-
abdominally with ascitic cells of rats'cancer of
ovaries (0~) in the amount of 11.5 x 106 cells per
100 g of body weight. Survival rate in days in the
test group was 15 (11-20 days) while in the control
group it was 12.1 (7-15 days) p = 0.05 (reliability
of difference at p = 0.05), reliability of
difference at p ~ 0.05; nonparametric method of
statistical processing by criterion " " of
Wilkokson-Mann-Vitney (see E.K. Gubler et al in the
book "Using Nonparametric Statistics Criteria for
Assessing Difference between Two Observation Groups
in Medico-Biological Studies", M, 1969, p. 9).
Administration of DL-valine has increased
resistance of the animal organism to tumoral
intoxication.
Subcutaneous introduction of dibasol under
the same conditions gave survival rate of 13.4 (8-17
35 days) in the test group (7 animals) and 12.0 (7-17
days) in the control group, p > 0.05, i.e. with
~ -- 10 --
unreliable difference. Dibasol falled to improve
resistance of animals to tumoral intoxication.
Test IV. Checking the antistress effect.
According to the stressing method, the test was made
on female rats of Vistar line (weight 80-lO0 g). 60
min. before suspension the rats of stress-test group
(7 animals) were given a test dose of DL-valine
through a probe into the stomach while the stress-
control group (7 animals) received milk. The gr~up
of intact rats (11 animals) received nothing before
killing. These animals, like the first two groups
(stress-test and stress-control ones) were starving
for 18 h in advance. When assessing the weight
changes of adrenal glands, thymus gland, spleen and
the number of ulcerations of the mucous membranes in
the control group (in comparison with intact
animals) the result was 9 points while in the test
group it was 4 points. The difference was 5 points
which demonstrates a high antistress activity of DL-
valine.
The result of this dibasol activity testunder the same conditions (7 test animals and 7
control ones) was 7 points in the control group and
6 points in the test group. The difference was l
point which indicates that in this case there is no
antistress effect according to the assessment
adapted in the method.
The obtained data are an evidence of a
pronounced adaptogenic effect of DL-valine
administered in a single dose regardless of the
season.
The next step was to compare the prolonged
effect of DL-valine (4 weeks) and of the prototype
(dibasol) under the same conditions in spring and
autumn, obtained from the same four tests which were
described for a single administration. The produced
results were identical.
,-";~ "~ ,,",,~i",",, "- " ,,~
The prolonged effect of DL-valine (4
weeks) was additionally checked in spring by two
more tes~s ln comparison with a control group of
animals for whom DL-valine was replaced by its
solvent, i.e. milk.
Test V. Checking resistance to damaging
factor of physical nature, i.e. cold.
The nondescript male rats (weight 100-130
g) were put to a cold test in spring after daily
administration (24 days running) of 40 mg of DL-
valine per 100 g of body weight (test group) and
milk (control group). The rats were placed for 5
min. into a freezer at a temperature of minus 10C
and the result was assessed by changes in the rectal
temperature of each of the test and control animals.
The temperature was measured before and immediately
after the cold test.
The average temperature, C, in the control
group (20 animals) before the cold test was
Man av =38.9C while after the test it was
Man av.=38.5C(i m = 0.115; p < 0.05) thus showing a
reliable reduction of rectal temperature.
In the test group (20 animals) the
respectively parameters were Man~aV~=39oc before and
25 Man av =38.9C after the test (i m = 0.154; p 0.1).
It means that there is no reduction of rectal
temperature which proves a higher resistance of the
organism of a mammal to considerable cooling after
long-term medication with DL-valine.
Test VI. Checking radioprotecting effect
of DL-valine in spring.
The first of the two tests was made on ten
control nondescript female rats (100-200 g) which
received milk in the course of four weeks, and on
nine test animals treated daily within the same time
period with 40 mg of DL-valine dissolved in milk per
100 g of body weight.
; ~ .
- 12 -
In the second test nine control and nine
test male rats of Vistar species (180-200 g) were
given 60 mg DL-valine per lO0 g of body weight.
Upon completion of 4-week administration
of DL-valine, the control and test animals were
irradiated al over once on a static gamma-
therapeutic apparatus AGAT-S (power rating P-245
rad/min., irradiation time 2.86 min., D = 7.0 Gr
(equal to 730 r Co). Inasmuch as LD1oo for rats is
750 g for a single total irradiation with ~-rays
Co60 at an irradiation rate of 366-417 rad/min., -the
kind of irradiation used in the test was sublethal.
The radioprotecting effect of the disclosed agent
(DL-valine) was estimated by the duration of
survival (in days) of the test animals in comparison
with the control ones.
Experiment I.
Ten control animals lived on an average
ll.l days (8-20) and all perished.
Nine test animals lived 20.2 days 9-30)
and four of them survived (for statistical
processing the life span was arbitrarily indicated
as 30 days) p < 0.01 difference in survival days is
reliable).
Experiment II.
Nine control animals lived M - 12.4 (8-30)
days and one survived; nine test animals lived 16.3
(9-30) days and four of them survived; p ~ 0.05
(difference reliable).
Hence, long-term administration of DL-
valine to animals causes radioprotective effect
which is another proof of high adaptogenic effect of
DL-valine on the organism of mammals.
The mechanisms of forming adaptogenic
effect on the organism of mammals by long-term
administration of DL-valine was revealed by a series
of experimental studies.
The obtained data have confirmed that
long-term daily administration of DL-valine for four
weeks produced the following effects.
l. Favorable stimulating influence on
hematogenic function of the organism of mammals.
Thus, the level of hemoglobin was increased (within
the upper normal limits) from Man.av. = 86-7 (80 98)
in control animals to Man av = 96.8 (86-102) in
test animals (p < 0.05), the number of erythrocytes
increased from M = 4420000 (3360000-4920000) in
control animals to M = 4775000 (4560000-5050000) in
test animals (p < 0.05), the number of reticulocytes
(in per cent) increased to 2.8 (0.6-4.5) as compared
with control animals - 1.6 (1.3-2.1) p < 0.05. This
condition of red blood is indicative of stimulated
medullary hematogenesis which, however, is devoid by
any toxic effect because the number of thrombocytes
stays unchanged. The condition of white blood is
also changed: the number of segmental nuclear
neutrophilic leucocytes diminishes and that of
lymphocytes increases within normal limits. The
increased number of lymphocytes points to
intensification of non-specific immune reactions in
the organism of animals mainly due to an increase in
the number of macrolymphocytes, because this
increase is accompanied by an increase in the number
of ~-globulins produced by them in the blood serum
of these animals.
2. Favorable influence on protein
metabolism in the organism of mammals, i.e. a
considerable anabolic effect which is evidenced by
an increased amount of general protein in the blood
serum (to the upper normal limits) from Man av
7.5% (7-8.4) in control animals to Man.av. = 8-5 (8-
94) at p < 0.01 in test animals.
Increased absolute number of -globulins
and, particularly, of -globulins: from Man~aV~ = 0.8
:
- 14 -
(0.56-108) to Man av = 1.6 (0.26-2.9) at p < 0.01
and from Man.av. = 0-7 (0.44-0.85) to Man av = 1.9
(0.77-3.48) at p < 0.01, respectively, which is
associated with activation of reticuloendothelium
intensifying the nonspecific immune reactions of the
organism, i.e. its resistance to various
unfavourable effects. The anabolic effect may also
contribute to normalizatlon of enzymic processes in
such vital organs as the liver, kidneys, the cardiac
muscle, etc. which are most responsible for protein
metabolism in the organism of mammals.
3. Favorable influence directly on the
immune system of mammals: while determining the
blast-transformation reaction of peripheric blood in
test and control animals we have observed
spontaneous (without mitogenic stimulants)
stimulation in vivo of development of lymphoblasts
from lymphocytes in peripheric blood of test
animals. Thus, after the monthly administration of
milk, the summary percentage of lymphoblast cells in
the control group of animals amounted only to 0.30 i
0.14 while in the test group after administration of
DL-valine it was 4.61 i 1.13 at p = 0.002
(difference reliable).
Such stimulation ensures a high functional
activity of cellular immunity. The same is proved by
histological data. As compared with the control
animals, the lymph`nodes and the spleen of test rats
have undergone some changes which testify to a
pronounced immune reaction of cellular type effected
mainly by T-lymphocytes and to activation of immune
reaction of humoral type.
4. Activation of the pituitary body-
adrenal gland - thyroid gland system which ensures
nonspecifically high resistance of the organism of
mammals.
--
- 15 -
5. Activating effect on cholesterol
metabolism which is quite important for prevention
of sclerotic changes in the cardiovascular system.
6. As has been established by biological
tests of healthy animals the disclosed perorally
administered agent - DL-valine - is completely
devoid of toxic properties because its lethal dose
cannot be determined even after administration on of
its maximum possible quantity.
Bearing in mind the impossibility of
determining the lethal dose of DL-valine
administered perorally to experimental animals and
the fact of using it as a component of aminoacid
mixtures for parenteral feeding of oncosurgical
patients in the amount of 5 to 11 g daily per 50 kg
of body weight which undoubtedly proves its full
harmlessness and nutrient value (see Sudzhan A.K. in
the book "Parenteral Feeding in Oncosurgery", M.
"Medicine", 1973, pp. 70-71) we deemed it possible
to check its adaptogenic effect on man, i.e. on
volunteers, practically healthy persons but
suffering from frequent chills, severe physical and
mental fatiguability and showing symptoms of
neurotic disorders.
Synthetic aminoacid - DL-valine
featuring a strong adaptogenic effect on the
organism of mammals, as has been established and
described above, was used for man in an empirically
chosen daily dose of 0.250 to 1.500 g depending on
age bracket, weight, weakening or sensitivity of the
organism to medicaments and inclination to
hypertension.
The disclosed invention has been used on
volunteers as follows. An optimum daily dose for
children after nine years of age and for old people
(after 70 years~ is, approximately not over 200-250
mg (0.2-0.25 g) of DL-valine.
v ~ A ~ ~>
- 16 -
The daily dose for adult women is from
0.500 g to 1.000 g and 1.000 to 1.500 g for adult
men. In persons sufferings from hypertension a
certain overdose causes a temporary rise of arterial
pressure. If so, the dose shall immediately be cut
in half.
The course of treatment with the disclosed
agent is 2 months of which 1.5 months (6 weeks) a
full daily dose is given daily, on the 7th week -
half a dose daily and the last (8th week), half adose every other day, thus gradually reducing the
daily dose.
It is good practice for prophylactic
purposes to repeat the course of treatment with DL-
valine during especially active restructuring of themetabolic processes in the human organism caused by
adaptation to cold and heat, also after a severe
illness.
It is recommended that the disclosed agent
be administered perorally, first dissolving the
entire daily dose in half a glass of warm milk, once
daily in the morning on an empty stomach (30-60 min.
before breakfast) or in the evening (before
bedtime). In Case of frequent insomnia spells it is
preferable to take the medicament in the morning.
During the treatment course the everyday ration
should include protein food of animal origin such as
meat, poultry, fish, dairy products, eggs, etc. once
or twice a day.
The disclosed invention is illustrated by
the following examples of using the new agent by
volunteers.
I. A woman (F.N.S.) of 55 in a
postmenopausal state periodically suffering from
attacks of hypertension, stenocardia, nervous
depressions, post-flu complications (rhinitis), with
- 17 -
surplus weight, quickly getting tired or mental and
physical work.
The course of DL-valine was connoted in
February-March 1992, daily dose 0.500 g in half a
glass of warm milk taken before bedtime. Summary
course dose 30 g i.e. 0.5 g daily within 2 months
(without gradual diminishing).
RESULTS
1. A fortnight after the beginning of the
course the arterial pressure became fully
normalized, remaining so for the current period
(June 1992).
2. Symptoms of stenocardia in the form of
sporadic pains in the cardiac region vanished
completely after the first month of treatment with
the new agent and do not reappear.
3. Psychic state has normalized gradually.
A feeling of calm developed along with adequate
reserved reaction to all the psychic irritants and
stresses.
4. Post-flu complication - rhinitis
develops from time to time in a very weak form.
5. The influenza after the course of
treatment lasted one day only and had no
complications.
6. Physical and mental activity has
increased markedly.
7. Body weight started normalizing
gradually without resorting to any special diet or
periodical fasting.
II. A child of nine (T.S.) suffering from
chronic pharingitis, a certain unbalanced psychic
state (weak inhibitory processes), frequent chills
(rhinitis, laryngitis), absence of appetite,
asthenic constitution, easily developing feeling of
fatigue after school day.
- 18 -
A 2-month course of treatment with the
disclosed agent was conducted in March-April of 1991
with an initial daily dose (45 days) of 0.250 mg on
warm milk given before bedtime. The summary course
dose was 12.5 g.
RESULTS. `
1. Chills vanished to the rest of the
year.
2. Normalization of inhibitory processes
was developed and consolidated. The child is active
emotionally steady up to the present day (June
1992).
3. Steady appetite developed. Weight
increased by 2-3 kg already in the course of
medication with neither gain nor loss of weight.
4. Strong after-school fatigue vanished.
School year was completed and new year started
successfully. A year later (spring 1992) some
weakness recurred which called for repeating a
course of treatment.
The new course was started in the middle
of May 1992, administered in the same dosage. A
month later the appetite improved considerably, the
child put on some weight, mental and physical
activities improved.
III. A man of 64 (K.S.V.) suffering from
mental disorders of climacteric origin (weakened
inhibitory processes, inadequate reaction to weak
psychic irritants), poor resistance to chills
(active form of tuberculosis in his youth), easy
fatiguability under physical load, symptoms of age~
induced predisposition to surplus weight, low blood
pressure.
A course of treatment was conducted in
September-October 1991 with an initial daily dose
(45 days) of 1.500 g on warm milk given before
bedtime a summary course dose of 75 g.
-.
. ' ~'': ' ' ' ,'" ", ~, ' '` . ' ' . " . "' . , .' ' '. i ' `', ''. . . ., , ' .,' ' ' . ' ' '
-- 19 --
RESULTS
1. Mental state started normalizing
already after 2 weeks of medication with the new
agent lasted for 1.5 months but after a sharp
cancellation of the prescribed medicament (during
administration of initial dose) the disorders
sometimes recurred. Medication was resumed for two
more weeks (entire course was 2 months) with gradual
reduction of the dose. The emotional state stays
normal to the present day.
2. There was not a single chill within the
entire autumn-winter-spring period after the course
of treatment.
3. On completion of the treatment course
with the new medicament the patient showed
considerable physical activity, absence of rapid
mental and physical fatiguability.
4. The weight was normalized, inclination
to obesity disappeared and is not observed at
present t7 months since).
5. Symptoms of low blood pressure
disappeared. The effect of the disclosed agent - DL
valine - which possesses pronounced adaptogenic
properties without seasonal limitations and
complications was checked on 12 volunteers: four
men, seven women (two of them beyond 70 years of
age) and one child of 9.
In all cases first of all we observed
prolonged normalization of mental state (up to a
year), considerable improvement of the immune
protection of the organism, pronounced steady
improvement of physical and mental activity and
vanishing of symptoms of some chronic inflammatory
processes, such as anacid and hyperacid gastritis,
cholecystitis, inflammations of otorhino-
laryngological organs. Other results included
functional normalizing of cardiovascular system,
- 20 -
liver, general metabolism (weight), disappearance of
psoriasis symptoms (1 case).
The technical result of administering the
disclosed new agent noted for raising
nonspecifically the resistance and activity of the
organism and normalizing its psychic activity lies
in that the disclosed medicament - synthetic
aminoacid - DL-valine -, being an easily synthesized
and available substance functioning as a nutrient
component of the food ration of man without any
harmful side effects is capable, unlike other known
adaptogens, of exerting a strongly expressed
adaptogenic effect on the organism of man, without
any seasonal limitations.
This new disclosed agent can be widely
utilized for prophylaxis, for physical and mental
health improvement of population, for overcoming
stresses and hardships caused by restructuring of
our society.
A complete harmlessness of the disclosed
agent has been proved by biological studies on
healthy animals and using it in the capacity of a
component of aminoacid mixtures for parenteral
feeding of surgical patients as has been described ;
above.
,
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