FIELD OF THE INVENTION:

The present invention relates to a pharmaceutical composition for the treatment of obesity. More particularly the present invention relates to a pharmaceutical composition comprising of lipase inhibitor, orlistat.

BACK GROUND OF THE INVENTION AND PRIOR ART:

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems. Body mass index (BMI), a measurement which compares weight and height, defines people as overweight (pre-obese) if their BMI is between 25 and 30 kg/m2, and obese when it is greater than 30 kg/m2 [World Health Organisation].

Obesity increases the likelihood of various diseases, particularly heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Obesity is most commonly caused by a combination of excessive food energy intake, lack of physical activity, and genetic susceptibility, although a few cases are caused primarily by genes, endocrine disorders, medications or psychiatric illness.

Dieting and physical exercise are the mainstays of treatment for obesity. Moreover, it is important to improve diet quality by reducing the consumption of energy-dense foods such as those high in fat and sugars, and by increasing the intake of dietary fiber. To supplement this, or in case of failure, anti-obesity drugs may be taken to reduce appetite or inhibit fat absorption.

Anti-obesity medication or weight loss drugs are all pharmacological agents that reduce or control weight. These drugs alter one of the fundamental processes of the human body, weight regulation, by altering appetite, metabolism, or absorption of calories. Anti-obesity drugs operate either through suppression of the appetite or increase of the body's metabolism or interference with the body's ability to absorb specific nutrients in food.

One of the anti-obesity drugs used is orlistat (Xenical). It reduces intestinal fat absorption by inhibiting pancreatic lipase. Adverse effects which observed in patients treated with lipase inhibitors are anal leakage of oil (oily spotting) and fecal incontinence. Oily spotting results from physical separation of some of the ingested but unabsorbed dietary fat from the bulk of the fecal mass in the colon.

U.S. Pat. No. 5,447,953 disclose a method of treating adiposity comprising administering to a subject a biomass comprising a lipase inhibitor, in an effective amount for treating adiposity. It has been shown that by combining a lipase inhibitor with substantial amounts of water insoluble crude fibers, the inhibiting effect on fat absorption can be increased.

US 6,030,953 discloses an orally administrable pharmaceutical compositions containing an inhibitor of gastrointestinal lipase, and at least one compound selected from the group consisting of chitosan, its derivatives and salts thereof.

US 6,251,421 discloses an orally administrable pharmaceutical compositions containing an inhibitor of gastrointestinal lipase, and at least one compound selected from the group consisting of psyllium husk, its seeds and leaves thereof.

US 6,703,369 discloses a pharmaceutical composition containing at least one inhibitor of lipases and at least one fatty acid ester of polyol. In the composition, the fatty acid ester has a melting point above the body temperature and the polyols are chosen from the group consisting of sugars, sugar derivatives, and mixtures thereof.

US 7,816,342 discloses an anti-obesity compositions comprising a lipase inhibitor such as orlistat, and glucomannan such as konjac as well as methods for utilizing such compositions and kits for carrying out this method.

US 8,012,494 disclose a pharmaceutical composition comprises at least one inhibitor of lipases, preferably an inhibitor of gastrointestinal and pancreatic lipases, such as orlistat, at least one surfactant, and at least one dispersant.

The prior art discussed above discloses various pharmaceutical compositions for the treatment of obesity. Lipase inhibitors are used as anti-obesity drug as it reduces intestinal fat absorption by inhibiting pancreatic lipase. But anal leakage of oil (oily spotting) is an adverse effect which is observed in patients treated with lipase inhibitors. It results from physical separation of some liquid unabsorbed dietary fat from the bulk of the fecal mass in the lower large intestine. Various studies have been made to control oily leakage and to inhibit the fat adsorption by combining the lipase inhibitor with components such s sugar derivatives or surfactants or fiber supplements.

OBJECT OF THE INVENTION:

The main object of the present invention is to formulate a synergistic pharmaceutical composition for the treatment of obesity.

Another object of the present invention is to formulate a synergistic composition comprising of lipase inhibitor.

Yet another object of the present invention is to formulate a synergistic composition comprising of fiber supplements along with lipase inhibitor for the purpose of inhibiting digestion and lowering caloric absorption in the treatment of obesity.

Yet another object of the present invention is to use galactomannan obtained from fenugreek seed as fiber supplements which galactomannan consisting of a mannose backbone with galactose side groups in the ratio 1:1of galactose and mannose.

Yet another object of the present invention is to formulate a synergistic composition comprising of synergistically effective combination of galactomannan and orlistat.

Yet another object of the present invention is to formulate a synergistic pharmaceutical composition comprising therapeutically acceptable amount of combination of galactomannan and orlistat.

Yet another object of the present invention is to formulate a synergistic pharmaceutical composition comprising of combination of galactomannan and orlistat along with pharmaceutically acceptable additives.

Yet another object of the present invention is to administer the formulated synergistic composition to the subjects (animals including humans) suffering from obesity.

Yet another object of the present invention is to formulate a synergistic composition that when administer into the subjects (animals including humans) suffering from obesity, will reduce the absorption of fatty acid from the diet thereby results in reduction of body weight in the obese subjects.

Yet another object of the present invention is to administer the synergistic combination in capsules, tablets, powders or any other form known to a person skilled in the art.

Further object of the present invention is to formulate a synergistic pharmaceutical composition which is devoid of the problem of anal leakage.

SUMMARY OF THE INVENTION:

The prior art discloses the usage of various compositions for the treatment of obesity which includes lipase inhibitor, orlistat in combination with sugar derivatives or surfactants or fiber supplements. The present invention relates to a new synergistic combination comprising of lipase inhibitor orlistat with galactomannan to reduce the absorption of fatty acid from the diet of obese patients which has not been envisaged in any of the prior art.

Thus the present invention relates to a synergistic pharmaceutical composition for the treatment of obesity. The composition comprises of synergistically effective combination of galactomannan and orlistat. The weight ratio of galactomannan to orlistat is between about 0.01g-100g galactomannan and about 10mg-500mg of orlistat, more preferably between about 1g-10g galactomannan and about 40mg-400mg of orlistat. The composition further includes pharmaceutical^ acceptable additives.

DESCRIPTION OF THE INVENTION:

The present invention relates to a synergistic pharmaceutical composition for the treatment of obesity. The composition of the present invention comprises of combination of lipase inhibitor with fiber supplement.

The fiber supplement used in the composition of the present invention is galactomannan. Galactomannans are polysaccharides consisting of a mannose backbone with galactose side groups (more specifically, a (1-4)-linked beta-D-mannopyranose backbone with branch points from their 6-positions linked to alpha-D-galactose, i.e. 1-6-linked alpha-D-galactopyranose).

The galactomannan used in the present study is obtained from fenugreek seed through a proprietary milling method without any chemical modification. Fenugreek is the only source of galactomannan where units of the backbone, mannose, exist in a 1:1 ratio with the side groups of galactose. This ratio is highly unique compared to other galactomannans. It is Non gelling hydrocolloid soluble in cold water. It hydrates and thickens faster. It is a Stabilized oil in water emulsion. It Bind moisture, reduce staling, provide texture and increase fiber content.

Galactomannan provides texture, gelling, thickening, emulsifying, stabilizing and encapsulating properties. It acts as a dietary fiber, in nutrition and cereal bars, yogurts, dairy products and nutritional beverages. Plain powders of soluble fiber or total dietary fiber can be mixed with fruit juices, other spice mixes and seasonings.

The lipase inhibitor used in the synergistic composition of the present invention is orlistat.

Orlistat is an anti-obesity drug used for lowering absorption of fat from human diet there by reducing calorie intake. Orlistat works by inhibiting gastric and pancreatic lipases, the enzymes that break down triglycerides in the intestine. When lipase activity is blocked, triglycerides from the diet are not hydrolyzed into absorbable free fatty acids, and are excreted undigested instead. Only trace amounts of Orlistat are absorbed systemically; the primary effect is local lipase inhibition within the Gl tract after an oral dose.

The combination of galactomannan and orlistat exhibits a notable synergistic effect in the reduction of the absorption of fatty acid from the diet, when the synergistic composition is administered to the subjects suffering from obesity thereby results in reduction of body weight in the obese subjects. This synergistic effect is likely attributable to acceleration of gastrointestinal transit of food by the fiber component. The consequent shortening of the time period available for fat digestion combined with the reducing effect on lipase activity intensifies the inhibitory effect on fat absorption. Furthermore the chance of getting diabetes mellitus is reduced in the subjects suffering from obesity.

In one of the preferred embodiment the present invention shall disclose a synergistic composition comprising a synergistically effective combination of galactomannan and orlistat.

According to the invention the galactomannan of the synergistic composition is a fenugreek gum consisting of a mannose backbone with galactose side groups in which the ratio of galactose and mannose is 1:1.

As per the invention the weight ratio of galactomannan to orlistat is between about 0.01g-100g galactomannan and about 10mg-500mg of Orlistat and more preferably preferably between about 1g-10g galactomannan and about 40mg-400mg of orlistat.

As per the invention the synergistic composition further includes pharmaceutical^ acceptable additives carriers, excipients and/or diluents.

In another preferred embodiment the present invention shall disclose a synergistic pharmaceutical formulation comprising a therapeutically effective amount of composition comprising of combination of galactomannan and orlistat along with pharmaceutically acceptable excipient.

In another preferred embodiment the present invention shall disclose a method of treating a subject suffering from obesity. The method comprises of administering to the subject a synergistically effective amount of a synergistic composition comprising of combination of galactomannan and orlistat. As per the invention the subject comprise of animal including humans.

The synergistic composition of the present invention may be administered orally.

According to the invention the dosage of the synergistic composition for the treatment of obesity is as follows Orlistat-100mg-200mg and galactomannan 1g-5g.

Example 1 :

In one preferred embodiment the present invention shall disclose a synergistic pharmaceutical composition comprising of synergistically effective combination of galactomannan and orlistat. The exemplary composition of this example is orally administered to animals including humans for the treatment of diabetes mellitus.

Example 2:

In another preferred embodiment, the present invention shall discloses a synergistic composition comprises of combination of galactomannan and Orlistat in a ratio ranging from 0.01g-100g galactomannan: 10mg-500mg Orlistat and more preferably from 1g-10g galactomannan: 40mg-400mg Orlistat. The exemplary composition of this example is orally administered to animals including humans for the treatment of obesity and diabetes.

Example 3:

In further preferred embodiment the present invention discloses the following synergistic formulation


Administration of the formulation of this example to animals including humans suffering from obesity results in significant reduction of fat absorption in the intestine.

Example 4:

In further preferred embodiment the present invention discloses the following synergistic formulation

Administration of the formulation of this example to animals including humans suffering from obesity results in significant reduction of fat absorption in the intestine.

Example 5:

In further preferred embodiment the present invention discloses the following synergistic formulation

Administration of the formulation of this example to animals including humans suffering from obesity results in significant reduction of fat absorption in the intestine.

Example 6:

In further preferred embodiment the present invention discloses the following synergistic formulation

Administration of the formulation of this example to animals including humans suffering from obesity results in significant reduction of fat absorption in the intestine.

Example 7:

In further preferred embodiment the present invention discloses the following synergistic formulation

Administration of the formulation of this example to animals including humans suffering from obesity results in significant reduction of fat absorption in the intestine.

Example 8:

In further preferred embodiment the present invention discloses the following synergistic formulation



Administration of the formulation of this example to animals including humans suffering from obesity results in significant reduction of fat absorption in the intestine.

Example 9:

In further preferred embodiment the present invention discloses the following synergistic formulation

Administration of the formulation of this example to animals including humans suffering from obesity results in significant reduction of fat absorption in the intestine.

Although the invention has been described above with reference to the disclosed embodiments, those skilled in the art will readily appreciate that the specific experiments detailed are only illustrative of the invention. It should be understood that various modifications can be made without departing from the spirit of the invention. Accordingly, the invention is limited only by the following claims.

WE CLAIM:

1.A synergistic composition comprising of a synergistically effective combination of galactomannan and orlistat wherein the wherein the said galactomannan is fenugreek gum consisting of a mannose backbone with galactose side groups in which the ratio of galactose and mannose is 1:1.

2.The synergistic composition as claimed in claim 1 wherein the weight ratio of galactomannan to orlistat is between about 0.01g-100g galactomannan and about 10mg-500mg of Orlistat.

3. The synergistic composition as claimed in claim 1 wherein the weight ratio of galactomannan to orlistat is more preferably between about 1g-10g galactomannan and about 40mg-400mg of orlistat.

4. A synergistic pharmaceutical formulation comprising a therapeutically effective amount of composition of claim 1 in combination with pharmaceutically acceptable excipient.

5. A composition as claimed in claim 1 for use in effective treatment of obesity in a subject, comprises of using synergistically effective amount of the composition where in the said subject is animal including humans.

6.A method of treating a subject suffering from obesity comprises of administering to the subject a synergistically effective amount of the formulation of claim 4.

7.The method as claimed in claim 6 where in the said subject is animal including humans.