Anorexigenic composition

Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution...

Reexamination Certificate

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Details

C514S188000, C514S556000, C514S649000

Reexamination Certificate

active

06426096

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention relates to anorexigenic compositions, their use in carbohydrate craving control with consequent weight control of the human body, and to methods of treating carbohydrate craving in a human.
It is reasonably well accepted that obesity is associated with carbohydrate craving at least in the majority of obese persons. Obesity is also associated with metabolic disturbances related to insulin resistance, particularly hyperinsulinaemia and elevated triglyceride levels. Insulin resistance, in turn, is believed to be associated with depressed serotonin levels in the brain which are believed to cause carbohydrate craving to the end that more carbohydrate would cause the insulin levels to rise and counteract the insulin resistance. A vicious circle ensues and obesity in some degree generally follows.
Hypericin which is an extract from the herb St John's Wort, is presently available in the market as a remedy for depression, anxiety and hyperactivity. It is believed to act by inhibiting the enzyme monoamine oxidase (MAO), which is responsible for the breakdown of serotonin in the brain.
Sibutramine is also a compound that has been used for the treatment of depression. It is believed to act as a serotonin re-uptake inhibitor.
Metabolisable chromium compounds such as chromium picolinate, for example, are known as supplements which can have the effects of reducing body fat; retaining and building lean muscles; and lowering elevated blood sugar and cholesterol levels. They have also been shown to have significant effects on elevated circulating insulin levels and insulin resistance.
It has now surprisingly been found that combinations of these compounds exhibit a desirable synergistic effect when employed together in the treatment of obesity, for example.
SUMMARY OF THE INVENTION
In accordance with one aspect of this invention there is provided a method of treating carbohydrate craving in a human patient comprising administering to the patient an anorexigenic composition comprising a compound which elevates serotonin levels in the brain of the patient in a mixture with a physiologically acceptable metabolisable chromium compound.
The compound which elevates serotonin levels in the brain may be hypericin, preferably in the form of St John's Wort Extract, or sibutramine, or a salt thereof, in particular sibutramine hydrochloride monohydrate.
Further features of the invention provide for the chromium compound to be selected from chromium picolinate, chromium polynicotinate, chromium chelate, chromium proteinate, or any other bioavailable chromium compound; and for the mixture to optionally include laevorotary carnitine or a racemic mixture of carnitine.
Preferably the anorexigenic composition is produced in unit dosage form.
In one form of the invention a dosage unit will comprise:
10 mg-1000 mg St John's Wort Extract;
<1000 &mgr;g chromium compound; and
0 mg-500 mg L-carnitine.
The dosage unit may conveniently be a capsule or tablet typically containing from 20-150 mg St John's Wort Extract, 80-600 &mgr;g chromium compound, preferably as chromium picolinate; and 80-200 mg L-carnitine either alone or in a racemic mixture with D-carnitine.
The dosage unit containing hypericin from St John's Wort Extract is typically administered to the patient as a single capsule taken once to three times daily.
A preferred capsule or tablet comprises:
St. John's Wort Extract
 20 mg-150 mg
Chromium Picolinate or other
100 &mgr;g-300 &mgr;g
bioavailable chromium salt:
L-carnitane.
 80 mg-150 mg
In an alternative form of the invention a dosage unit will comprise:
 1 mg- 30 mg
sibutramine
100 &mgr;g- 800 &mgr;g
chromium compound; and
 0 mg- 800 mg
L-carnitine.
Once again the dosage unit can conveniently be a capsule or tablet typically containing 5-20 mg sibutramine, preferably as sibutramine hydrochloride monohydrate, 100-600 &mgr;g chromium compound, preferably as chromium picolinate/polynicotinate or other bioavailable salt, and 100-180 mg L-carnitine either alone or in a racemic mixture with D-carnitine.
The dosage unit form containing sibutramine is typically administered to the patient as a single capsule taken once a day. The dosage may be increased, where necessary, to a single capsule twice daily.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
It is generally accepted that obesity is associated with carbohydrate craving in 100% of obese woman and about 70% of obese men. For years scientists have suspected that there is a link between a condition called insulin resistance and carbohydrate craving.
In order to appreciate the manner in which it is believed that the composition of the invention functions, it is important to understand the concept of “Insulin Resistance”.
Under normal circumstances, when a patient eats carbohydrates, the following sequence occurs:
However, in patients who are insulin resistant, the following sequence would appear to take place:
When an excessive amount of insulin is released in insulin resistant patients, their serotonin levels drop. This starts carbohydrate craving which drives them to eat more carbohydrate and a vicious cycle begins. In a relatively short period of time very low serotonin levels are experienced. Symptoms of a low serotonin level include depression, insomnia, lack of libido, fatigue and increased craving for carbohydrate.
The composition of the invention is aimed not only at increasing the levels of serotonin in the brain but also the combating of insulin resistance too. In order to increase the brain's serotonin level the product contains a compound which elevates serotonin levels in the brain, for example hypericin or sibutramine.
It is believed that hypericin works by inhibiting an enzyme called Monoamine Oxidase (MAO). MAO is responsible for the breakdown of serotonin. By inhibiting the breakdown of serotonin it is believed that the brain's serotonin level increases. An increased brain serotonin level will alleviate craving for carbohydrate hence affording the patient greater self-control enabling him to stick to his eating plan.
Sibutramine, on the other hand, works by acting as a serotonin re-uptake inhibitor (as well as by noradrenaline and dopamine re-uptake inhibition). It is believed that sibutramine increases the brain's serotonin levels by inhibiting the re-uptake of serotonin and thus alleviates the craving for carbohydrate.
However, the benefits of simply increasing the brain's serotonin level are limited because in the insulin resistant patient, every time he eats carbohydrate (even as part of a balanced eating plan) excess insulin is released and his serotonin level drops.
In order to counteract this, it is preferable to stop the release of excessive insulin and hence stop the rebound drop in serotonin while at the same time further increasing the serotonin levels using hypericin or sibutramine. It is believed that this can be achieved, at least in part, by including a bioavailable chromium compound in the composition.
Chromium is a component of the dinicotinic acid-gluthathione-chromium complex, the glucose tolerance factor, which enhances insulin sensitivity in a person. However, dietary intake of chromium is generally suboptimal causing chromium deficiency.
Chromium deficiency in turn causes hyperinsulinemia and insulin resistance. Moreover, hyperinsulinemia causes increased urinary chromium loss leading to a vicious cycle.
Chromium supplementation has been shown to have a significant effect on elevated circulating insulin levels, insulin resistance, hypertrygliceridemia and decreased HDL cholesterol levels. Chromium supplementation has also been found to decrease LDL cholesterol levels and revert atherosclerotic lesions.
These properties when combined with those of a compound which elevate serotonin levels in the brain provide a two pronged attack on obesity. The chromium compound is complexed with certain ligands (e.g. picolinate or nicotinate) so as to be fully active. Since chromium supplementation increases insulin sensi

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