ESTRONE AND ESTRONE ESTERS AS GROWTH- AND FAT-DEPOSITION PROMOTING COMPOUNDS IN HUMANS

OESTRONE ET ESTERS D'OESTRONE COMME COMPOSES DE PROMOTION DE LA CROISSANCE ET DU DEPOT DES GRAISSES CHEZ LES HUMAINS

English Abstract

A compound with the general formula of estrone (3-hydroxy-estra-1, 3, 5(10)-
trien-17-
one) and its 3-acyl ester is effective for dietary and medical uses to promote
growth and
fat-deposition in humans.

Claims

CLAIMS
What is claimed is:
A compound with the general formula of estrone (3-hydroxy-estra-1, 3, 5(10)-
trien-17-one) and its acyl ester is used for the promotion of tissue growth
and fat-
deposition in humans.
2. A compound according to claim 1 in which the acid moiety of the said acyl
ester
is an organic acid.
3. A compound according to claim 2 in which the organic acid is a fatty acid
containing 1 carbon to 26 carbons
4. A compound according to claim 3 in which the degree of unsaturation of the
fatty
acid is between 1 and 10.
5. A compound according to claim 3 in which the fatty acid moiety is saturated
6. A compound according to claim 2 in which the fatty acid is oleic acid.
7. A compound according to claim 1 in which the said compound is used in a
food
preparation to facilitate its absorption in the human intestine.
8. A preparation according to claim 7 in which the said compound of claim 1 is
emulsified in a food substrate with the aid of a surfactant and/or dispersing
agent.
9. A compound according to claim 1 in which the dosing of the said compound is
set lower than that inducing eventual estrone overload and unwanted estrogenic
side effects.
10. A compound according to claim 1 in which the said chemical is used in a
medicinal preparation to facilitate its absorption in the human intestine.

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11. A preparation according to claim 9 is a pill, tablet, capsule or tonic.
12. A preparation according to claims 9 and 10 is a dietary supplement.
13. A compound according to claim 1 in which the said compound is used for the
treatment of malnutrition, insufficient growth or lack of fat reserve as
caused by
hyponutrition or chronic ailments.
14. A compound according to claim 1 in which the said compound is used to
treat
cachexia and malnutrition.
15. A method according to claim 14 in which cachexia is present in humans with
acquired immune deficiency syndrome.
16. A method according to claim 14 in which cachexia is present in humans with
eating disorders.

Description

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ESTRONE AND ESTRONE ESTERS AS GROWTH- AND FAT-DEPOSITION
PROMOTING COMPOUNDS IN HUMANS
BACKGROUND OF THE INVENTION
1. Field of Invention
The present invention relates to medicament for the treatment of humans
afflicted with
eating disorders due to malabsorption, cachexia and anorexia.
2. Prior Art
The body weight maintenance system relies in part on the equilibrium of free
and oleoyl-
ester of estrone. Adipose tissue takes up estrone and stores it as oleoyl
ester. Non-
adipose tissues break down oleoyl estrone to yield estrone (Sanchis, D. et
al., 1997.
Mol. Cell. Chem., 177:153-157). Equilibrium between circulating levels of
oleoyl estrone
and free estrone represents also an equilibrium between fat and lean body
mass. The
increase in either fat or lean body mass results in the brain ordering a
counteracting
metabolic adjustment to re-establish equilibrium. An excess in estrone is
interpreted as
predominance of lean body mass, i.e., insufficient fat, and fat storage is
stimulated
(Fernandez- Lopez, J.A. et al., 2000. Nutr, Obes., 3:26-35).
Thus, the intake of large amounts of estrone may destabilize the weight
control system
including fat accumulation. Conversely, the intake of large amount of intact
oleoyl
estrone would induce the loss of fat (Sanchis, D. et al., 1996. Int. J. Obes.,
20:588-594).
Estrone, mainly in the form of oleoyl estrone, is present in many common foods
at levels
ranging up to 12 micromols per kilogram (Remesar, X. et al., 1999. Eur. J.
Nutr.,
38:247-253). Its presence in dairy products is especially high, and it is
speculated that
this presence helps suckling to improve energy efficiency and prioritize
growth. Over
consumption of estrone ester-laden foods, may destabilize the body weight
control
system inducing the same effect of growth and fat deposition in suckling.
Although milk
is the preferred food for growth induction, much of its content such as
lactose and
saturated fats are functionally intolerable by many persons. Thus, the on-
purpose
addition of oleoyl estrone to foods would be particularly beneficial,
especially to those
persons with cachexic and undernourished conditions.

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In US Patent 5,314,182, Pantic et al. teach the use of a mixture of estradiol
ester and
progesterone ester to treat meat-producing animals to improve yield and to
increase the
proportion of lean to fat meat. In US Patent 5,861,391, Yen et al., teach the
use of
dehydroepiandrosterone to treat humans with andrenal insufficiency due to
acquired
immune deficiency syndrome.
Estrone (3-hydroxy-estra-1, 3, 5(10)-17-one) is an approved prescription drug
for use in
the treatment of vasomotor syndrome associated with menopause and palliative
therapy
of advanced prostatic carcinoma. Its use has not hereunto found to be
surprising useful
for the promotion of tissue growth and fat-deposition in mammalian subjects.
SUMMARY OF THE INVENTION
The presence of estrone and acyl estrone in limited amounts in food, either
concentrated naturally or added specifically, has been discovered to induce
growth of
live matter in mammals when such foods are ingested. This invention is
particularly
useful to induce tissue growth and fat deposition in undernourished children
and
persons suffering from severe eating disorders. Moreover, this invention is
useful for
counteracting severe cachexia-inducing pathologies in persons afflicted with
such
ailments as cancer and acquired immune deficiency syndrome.
DETAILED DESCRIPTION OF THE INVENTION
The practice of the present invention is illustrated by the following
examples, without
limiting the general applicability of the present invention:
Example 1
Wistar female rats (Fa/?) weighing initially 245 to 255 grams were used in
groups of five
animals. A preparation of free estrone in a 20% isotonic lipid suspension
(Intralipid,
manufactured by Pharmacia & Upjohn, Sant Cugat, Barcelona, Spain) was used to
fill
up osmotic pumps (Model 2ML2, Alza Corp., Los Angeles, CA). The pumps were
inserted in the back of the rats under anesthesia, and were connected via
short capillary
tube to the left jugular vein. The mini-pump released 0.12 milliliters per
day, at a
constant rate, of the suspension into the rat blood stream. The daily dose of
free
estrone was set at 3.5 nanomols per gram of initial body weight, for a period
of 14 days.
Free estrone was found to increase the body weight of the test rats
substantially.

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of initial weieht, after 14 days
Control (no estrone) 6.3+0.8
Test (with estrone) 12.3+1.9
Example 2
Zucker lean rats (Fa/?) weighing initially 200 to 215 grams were used in
groups of five
animals. The test rats were fed a hyperlipidic powdered diet (18.6 MJ/kg), in
which lipids
accounted for 38% of the energy content, protein accounted for 17%, and
balance being
sugars and starches. This diet was intended to simulate a typical human diet.
The
content of total estrone of the control diet was 0.9+0.3 nanomols per gram.
The test diet
with oleoyl estrone (3-oleoyl-estra- 1, 3, 5(10)-men-17-one) added had a
content of total
estrone of 1.4~0.3 nanomols per gram. The test results after 16 days of
feeding showed
that the test group weight was substantially greater than the control group.
Avg foodconsumed, Total Estrone % of initial weight
g/day over the 16 ingested, nmol/kg
days over the 16 days
Control 13.1 +1.1 53 106+4
Test 14.5+1.1 90 114+3
Example 3
Female mice weighing initially 19 to 21 grams were used in groups of five
animals. The
mice were injected daily, subcutaneously in the back, with 0.2 milliliters of
a preparation
of oleoyl estrone {3-oleoyl-estra-1, 3, 5(10)-trien-17-one) dissolved in a 20%
isotonic
liquid suspension (Intralipid, manufactured by Pharmacia & Upjohn, Sant Cugat,
Barcelona, Spain). Four groups were studied for dose response. The tests were
continued for 14 days. The results showed that test mice achieved substantial
gain in
body weight. The results also indicated that higher dosing does not
necessarily result in
greater gain in body weight, cf. Group B versus Group C at Day 5.

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of initial weight
Daily Dosage of Day 5 Day 14
Total Estrone,
nmol/g
Control 0.0 102.6+1.5 105.7
+1.8
Group A 1.5 112.8_+0.6 _
not tested
Group B 3.5 116.8_+0.6 125.5
+0.9
Group C 7.0 110.6+1.4 _
not tested