Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-04-22
2001-04-24
O'Sullivan, Peter (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S184000, C514S185000, C514S186000, C514S458000, C514S474000, C514S574000, C562S580000, C562S582000
Reexamination Certificate
active
06221901
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a new (−)hydroxycitrate compound, its preparation process and the compositions containing it.
BACKGROUND OF THE INVENTION
(−)hydroxycitrate ((−)hydroxycitric acid or also Garcinia acid) is the active ingredient obtained from the extract of
Garcinia indica
or
Garcinia cambogia
, trees found in south-east Asia and in particular in southern India.
These two species of plant directly contain a (−)stereoisomer of hydroxycitrate. The extract of the fruit of these two plants is widely used in traditional Indian medicine for treating various diseases.
A mixture of (−)hydroxycitrate and chromium is commercialized in the United States as a dietary product for combatting excess weight and obesity, under the name of Citrin®.
Known pharmacological activities and processes for preparing (−)hydroxycitrate from fruit are already described in the literature.
This product is further commercialized by different manufacturers such as the FLUKA company.
Majeed M. et al. in “CITRIN®: a revolutionary herbal approach to weight management”, New Editions Publishing, 1675 Rollins Road, Burlingame, Calif. 94010, Pages 1-69, 1994, describes a certain number of studies which show that (−)hydroxycitrate reduces body weight by reducing the synthesis of fatty material.
Many people throughout the world, for example approximately 4 million people in France, suffer from hypercholesterolemia. When the levels of circulating cholesterol exceed normal levels, due to the peroxidation of lipids, the cholesterol and cholesterol esters are capable of accumulating in the cells of arterial smooth muscles, provoking their proliferation, the accumulation of lipids on the artery wall (atheroma), which may lead to the formation of thrombus, followed by the blocking of coronary or cerebral arteries.
Existing treatments (fibrates, HMG coenzyme-A reductase inhibitors, etc.) aim to reduce levels of circulating cholesterol but play no protective role in the pathological effects of cholesterol on the artery wall, either by reducing proliferation or by inhibiting the accumulation of cholesterol in the cells of arterial smooth muscles.
Furthermore, owing to their side effects, such as hepatic or renal insufficiency, these medicaments are used only when the levels of circulating cholesterol greatly exceed physiological limits.
It would therefore be desirable to find a product endowed with the following properties:
capable of reducing the synthesis of cholesterol,
capable of inhibiting the accumulation of lipids in the cells of vascular smooth muscles,
capable of aiding the elimination of lipids which have accumulated in the cells of vascular smooth muscles,
capable of reducing cell proliferation due to the reduction in intracellular lipids,
endowed with a sufficient therapeutic margin, and
devoid of side effects or toxic effects at high doses.
SUMMARY OF THE INVENTION
For this reason, a subject of the present invention is a new compound of (−)hydroxycitrate, namely magnesium (−)hydroxycitrate, in particular crystallized magnesium (−)hydroxycitrate, quite particularly substantially pure.
A subject of the present invention is also a process for the preparation of magnesium (−)hydroxycitrate, characterized in that an extract of
Garcinia cambogia
is reacted with an aliphatic alcohol in order to obtain a precipitate which is subjected to the action of a tannin fixing agent, the solids are eliminated and the supernatant is recovered and subjected to batch chromatography on an anion exchanger resin, then left in contact under agitation, the supernatant is eliminated followed by elution of the magnesium (−)hydroxycitrate, the eluate is dried in order to obtain the expected magnesium (−)hydroxycitrate.
Under preferential conditions for the implementation of the process described above,
the aliphatic alcohol is a C
1
-C
6
alcohol, preferably propanol, isopropanol or ethanol,
the tannin fixing agent is a Polypyrrolidone derivative, preferably Polyvinyl Polypyrrolidone,
elimination of the solids is carried out by centrifugation,
the anion exchanger resin is preferably a DEAE SEPHADEX A50 resin,
drying of the eluate is carried out by lyophilization.
Magnesium (−)hydroxycitrate has very useful pharmacological properties. It is in particular endowed with remarkable hypolipemia, anticholesterol, antiatheromatous and antioxidant properties in particular with espect to free radicals. It is in particular capable of reducing cholesterol synthesis, inhibiting the accumulation of lipids in the cells of vascular smooth muscles, aiding the elimination of lipids accumulated in the cells of the vascular smooth muscles, reducing cell proliferation due to the reduction in intracellular lipids, and as a result, reducing the deposit of fats on the vascular endothelium. It is further endowed with antistress, antifatigue and cell regeneration properties. It has also been found to be endowed with antihypertensive properties.
These properties are illustrated below in the experimental part. They justify the use of magnesium (−)hydroxycitrate as a medicament.
The medicaments according to the present invention are used for example in both the curative and preventative treatment of pathologies caused by the local accumulation of lipids or by an increase in the circulating cholesterol level, which causes diseases such as vascular stenosis, lipidic striae, the formation of atheroma, thrombosis and vascular diseases affecting both macro- and microcirculation as well as hypercholesterolemia.
They are also used in ageing disorders linked to the effects of oxidants such as free radicals.
They are also used in both the curative and the preventative treatment of arterial hypertension.
The usual dose, which may vary according to the patient treated and the affliction in question, can be, for example from 100 to 1000 mg of magnesium (−)hydroxycitrate per day by oral route in human, for at least 20 days.
A subject of the invention is also pharmaceutical compositions containing at least magnesium (−)hydroxycitrate as active ingredient.
In these compositions, the active ingredient is advantageously present at effective physiological doses; the aforementioned compositions contain in particular an effective antihypercholesterolemia or antihypertensive dose of at least one active ingredient above.
As medicaments, magnesium (−)hydroxycitrate can be incorporated in pharmaceutical compositions intended for administration by the digestive or parenteral route.
These pharmaceutical compositions can be, for example, solid or liquid and be presented in the pharmaceutical forms commonly used in human medicine, such as for example plain or sugar-coated tablets, capsules, granules, caramels, suppositories, injectable preparations, creams, lotions or gels; they are prepared according to the usual methods. They may incorporate the active ingredient(s) with excipients usually used in these pharmaceutical compositions such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, fatty matter of animal or vegetable origin, paraffin derivatives, glycols, various wetting, dispersing or emulsifying agents, preservatives.
The Applicant has further discovered that magnesium (−)hydroxycitrate was capable of potentiating the effects of minerals, in particular of metals involved in physiological enzymatic reactions, quite particularly zinc, copper, manganese, selenium and silicon, and was also capable of potentializing the effects of vitamins, particularly vitamins A, C and E.
But while the aforementioned mineral and vitamin products showed slight protective effects with respect to hypercholesterolemia, these effects are not at a sufficient level to envisage therapeutic use. However, potentiated by magnesium (−)hydroxycitrate, they have quite surprising effects.
For this reason, a further subject of the present invention is a synergistic combination, characterized in that it comprises
Lambropoulos Patrick
Shrivastava Ravi
Browdy and Neimark
O'Sullivan Peter
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