Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
1(~4101~
The present invention relates to appetite curbing
compositions for mammals, methods for the preparation of
such compositions, and methods for curbing the appetite of
mammals by use of said compositions.
It is known to produce preparations based on
alignates for use as appetite curbing agents in slimming
diets. Since these preparations swell in the stomach and ~ `
intestinal tract, they produce a feeling of fullness and
satisfaction in human beings. However, the preparations
10 have a considerable disadvantage in that in the presence of
calcium ions they form calcium-containing deposits of low
solubility. As a result, it is possible for a calcium ion
deficiency to be produced, particularly in the intestinal
tract. The fear has therefore often been voiced that dis-
turbances of the metabolism could thereby be produced.
It is an object of the present invention to over-
come the above-described drawbacks of the prior art.
It is another object of the present invention to
proyide A preparation comprising alginic acid and a diphosphonic
20 acid ~or nontoxic pharmacologically acceptable water-soluble
salts thereof~ in which the diphosphonic- acid acts as inhibitor
of the precipitation of calcium salts; and thereby inhibits
precipitation of calcium ions; this preparation is useful for
curbing the appetite of a warm-blooded animal.
These and further objects of the present invention -~
will become apparent as the description thereof proceeds.
The present invention relates to alginic acid pre-
parations containing a diphosphonic acid (or nontoxic pharma-
cologically acceptable water-soluble salts thereof) as inhibitor
30 of the precipitation of calcium salts when the composition is
ingested. This preparation is useful as an appetite curbing
agent for warm-blooded animals.
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Accordingly, the present invention provides a pre-
paration for use in curbing the appetite of warm-blooded
animals which comprises an alginic compound and a diphosphonic
compound of the formula:
1 3 2
CH2 - CEI - I 1
COOH COOH P3H2
wherein Rl is hydrogen or methyl and the nontoxic pharma-
cologically acceptable water-soluble salts thereof, as
inhibitor of the precipitation of calcium salts when the
composition is administered to warm-blooded animals.
More particularly, the present invention is directed
to an appetite curbing preparation for warm-blooded animals
comprising
(A) an alginic compound selected from the groups
consisting of alginic acid and the nontoxic pharmacologically
acceptable water-soluble salts thereof, and
~ 3) a substoichiometric amount based on the calcium
ions required to gel said ~lginic compound of a diphosphonic
compound as precipitation inhibitor for calcium ions selected
; from the group consisting of a diphosphonic compound having
the formula
P03H2
CH2 ~ IH ~ I R
COOH COOH P3H2
wherein Rl is hydrogen or methyl and the nontoxic pharma-
cologically acceptable water-soluble salts thereof.
Also, the present invention provides an appetite
curbing composition for a warm-blooded animal consisting essen-
tially of 25% to 50% by weight of the above appetite curbingpreparation and 50~ to 75% by weight of a nontoxic pharma-
~ologically acceptable carrier.
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In addition, the present invention provides a method
for curbing the appetite of warm-blooded animals comprising ~ :
administering to said animals an anoretically effective amount
of the appetite curbing preparation mentioned above.
Also, the present invention provides an improvement
in a process for dieting, which consists essentially in con-
suming ~during or before a meal) an effective amount of the
appetite curbing preparation mentioned above as an anoretic
material.
It has become apparent that in principle it is
possible to preyent the formation of calcium alginate by add-
ing thereto a strong sequestering agent, for example, nitrilo-
triacetic acid or ethylenediaminetetraacetic acid. However,
the calcium ions are thereby sequestered to such an extent
that they may possibly no longer be available for physiological
processes in the warm-blooded animal. Moreover, the precipi-
tation of the calcium salts can be prevented for a consider-
able period of time by using compounds which have a strong -~
inhibiting effect (threshold effect). In this case, crystalline
growth is probably inhibited to a very great extent by the
incorporation of the inhibitor into seed crystals. Compounds
haying a threshold effect particularly include polyphosphates
haying a chain-like structure and include sequestering agent
phosphonic acids, such as methylphosphonosuccinic acid or 2-
phosphonobutane~l,2,4-tricarboxylic acid. However, condensed
phosphates are not suitable for this purpose since they are
split up by phosphatases in the body to give ineffective
monophosphate. Moreover, tests have shown that, under the
physiological conditions which prevail in the intestinal
tract, the majority of sequestering agent phosphonic acids
are either unsuitable or are not sufficiently effective.
It was therefore surprising that the above-
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mentioned dicarboxydiphosphonic acids and their nontoxicpharmacologically acceptable water-soluble salts constitute
suitable ingredients for the above preparation. The com-
pounds are diphosphonoalkanedicarboxylic acids selected from
the group consisting of l,l-diphosphonopropane-2,3-dlcarboxylic
acid and 2,2-diphosphonobutane-3,4-dicarboxylic acid, with the
former acid being preferred.
Instead of these acids, it is also possible to use
their nontoxic pharmacologically acceptable, water-soluble
salts, such as the alkali metal salts, for example, sodium
and potassium, and the magnesium salts, and the ammonium and
substituted ammonium salts such as the lower alkylol-ammonium
salts, for example, the mono-, di- or tri- ethylolammonium
salts. It is also possible to use the partial salts, in
which only a proportion of the acidic protons is replaced by
other cations. Partial salts, which produce a pH in the range
~om 6 to 8.5 in aqueous solution, are preferred. Mixtures
of the above-mentioned acids and their salts can also be used.
The proportion of the precipitation inhibitors in
the appetite curbing preparations containing an alginic com-
pound is variable. However, this proportion must be great
enough to inhibit the precipitation of calcium ions in the
intestinal tract. This precipitation is possibly caused by
the presence of calcium hardness (i.e., calcium ions) in the
wate~. Based upon a 10 gm amount of the alginic compound,
about 50 to 200 mg,preferably 100 to 200 mg, of the precipi-
tation inhibitor can be present in compositions of the invention.
This corresp~nds to the weight ratio of l50 to 200):1 for the
alginic compound to the precipitation inhibitor, equivalent
to 1/2% to 2% of the inhibitor on the weight of the alginic
compound. However, for the ressons as stated above, precipi-
tation inhibitor is preferably present in substoichiometric
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amount based on the calcium required to gel said alginic
compound.
Commercial alginic acid, or its nontoxic pharma-
cologically acceptable water-soluble salts such as the alkali-
metal salts, are suitable as the alginic ingredient. Potassium
alginate or, preferably, sodium alginate can be used as alkali
metal salts. Ammonium alginate can also be used. The pre-
parations can be produced for administration in the form of
tablets, pills or powder and may contain known ingredients
such as sodium bicarbonate or Na2HPO4 as well as binding
agents for the production of tablets. Further additives
which may be present in the appetite curbing compositions
are flavorings, vitamins and sugar/fruit concentrates.
Generally speaking, the appetite curbing composi-
tions according to the invention contain from 25% to 50% by
weight of the alginate-diphosphonic acid preparation, with
the balance up to 100% by weight being the other known ingred-
ients and/or additives mentioned aboye which constitute an
inert nontoxic pharmacologically acceptable carrier.
The appetite curbing compositions are administered
orally to warm-bloQded animals in units which contain an
anoretically effective amount, or about 15 to 70 mg/kg of body
weight ~preferably 25 to 50 mg/kg of body weight~, of the
alginic-diphosphonic acid combination. These dosage units
can be in the form of tablets, pills or powders and are con-
veniently administered by dissolving the tablets, pills or
powders of the combination in a suitable liquid medium such
as water, milk, fruit juice or a carbonated beverage. The
liquid medium contains from 0.5% to 5% by weight of the appetite
' 30 curbing composition, and can be consumed by drinking.
The appetite curbing preparations of the present
invention have the advantage of preventing precipitation
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or excessive sequestering of calcium ions. The ease of digest-
ibility of the anoretic agent is greatly increased, even for
sensitive persons.
The following examples illustrate the present
invention without limiting it in any manner.
EXAMPLE
In order to test the activity of the compositions
containing compounds which might be effective as precipitation
inhibitors, the following experiments were carried out. 600 mg
of sodium alginate was slowly stirred into 50 ml of a solution
of sodium bicarbonate ~Na2HPO4) containing the inhibitor stated
in Table I. After filling up to the final volume, the follow-
ing concentrations were obtained per liter of alginate solution:
6 gm of sodium alginate
0.075 gm of precipitation inhibitor
; 2 gm of HC03 ions
0.1 gm of HPO4 ions
The above concentrations of bicarbonate and hydrogen
phosphate ions were approximately equivalent to the inorganic
components of intestinal juice. The solution had a pH of 8.
As soon as the sodium alginate had homogeneously dissolved,
- 50 ml of 40 dH ~German hardness) hard water was added, so
that the sQlution had a calcium hardness of 20 dH. The
: precipitatlon of calcium alginate became apparent through
~elling or clotting, whlch could readily be observed by
means of deposlts on the walls of the container when the
sample was shaken.
A control sample of the alginic compound was also
mixed with the bicarbonate-hydrogen phosphate solution. The
; 30 results of the control test together with the results of the
test with a composition of the inyention are reported in
Table I. The results of the same tests with comparative
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precipitation inhibitors are reported in Table II. The com-
parative tests clearly indicate that the desired results are
not achieved with other prior art compounds, even though
these do in part have a yery similar sequestering effect.
Table I
ecipitation Inhibitor Results
None ~control) Strong to very strong gelation
l,l-Diphosphonopropane-
2,3-dicarboxylic acid Weak gelation
Table II
Precipitation Inhibitors
tComparative) Results
Methylenediphosphonic
acid Strong to medium strong gelation
Ethane-l,l-diphosphonic
acid Strong to very strong gelation
Propane-1,2,3-tri-
phosphonic acid Strong gelation
Methylphosphonosuccinic
20 acid yery strong gelation
: 2-Phosphonobutane-
1,2,4-tricarboxylic
acid Medium strong gelation
Amino-tris-(methylene- Strong to extremely strong
phosphonic acid) gelation
Dimethylaminomethane-
diphosphonic acid Medium strong to strong gelation
Aminoacetic acid-
N,N-dimethylene-
30 phosphonic acid Very strong gelation
Chlorobenzyl-
diphosphonic acid Strong to very strong gelation
- Ethylenediamine-
tetrakis-~methylene~
phosphonic acid) Strong to yery strong gelation
Hexamethylenediamine-
tetrakis-(methylene-
phosphonic acid) Strong to very strong gelation
Cyclohexanehexa-
carboxylic acid Medium strong to strong gelation
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EXAMPLE 2
A preparation which was suitable as an appetite
curbing agent was prepared from the following composition
by weight:
64.5% sugar/fruit concentrate
35% sodium alginate
0.5~ of the diphosphonic acid
of Example 1
in the form of the sodium salt.
10 Approximately 6 gm of the anoretic preparation
was placed in a dry glass and filled up with 200 gm of cold
water while being stirred. The drink was imbibed approximately
15 minutes before the reduced meals.
Although the present inventlon has been disclosed
in connection with a few preferred embodiments thereof,
variations and modifications may be resorted to by those
skilled in the art without departing from the principles of
the new invention. All of these variations and modifications
are considered to be within the true spirit and scope of the
present invention as disclosed in the foregoing description
and defined by the appen~ed claims.
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