CROSSREFERENCE TO RELATED APPLICATIONS

This is a PCT filing claiming priority from US provisional application no. 62664395, filed on 30 April 2018.

BACKGROUND OF INVENTION

FILED OF INVENTION

The present invention relates to obesity management. Specifically the present invention relates to compositions containing extracts of Cyperus rotundus, Garcinia sp Coleus forskohtii in effective ratios for managing obesity and related conditions in mammals.

DESCRIPTION OF PRIOR ART

[Para 001] Obesity is a condition in which there is excess build up of fat in the body. The national institutes of health has defined obesity as Body mass index (BMI) of 30 and above, a ratio of weight to height which correlate with the total body fist content (William Shiel, Medical Definition of Obesity, MedicineNet, https://www.medicinenet.com/script/main/art.asp?articlekey= 11760 accessed 20 ^ft April 2019). Obesity is a multi-factorial disorder which is caused due to both lifestyle and genetics, leading to the development of many diseases and disorders which include diabetes, hypertension, heart diseases, stroke, neurodegenerative diseases, cancer, steep apnea, arthritis and many more.

[Para 002] Obesity also leads to the development of liver dysfiractian by being the most common cause for non-alcoholic fatty liver disease (NAFLD) and non-atchoholic steato hepatitis (NASH) (Sarwar et al., Obesity and nonalcoholic fatty liver disease: current perspectives, Diabetes Metab Syndr Obes. 2018; 11: 533-542). The levels of circulating lipids are elevated in people with obesity (Klop et al., Dyslipidemia in Obesity: Mechanisms and Potential Targets, Nutrients. 2013 Apr; 5(4): 1218-1240). Further, kidney functions are also disrupted (Kovesdy et. al., Obesity and Kidney Disease, Hidden Consequences of the Epidemic, Can J Kidney Health Dis. 2017; 4: 2054358117698669) in obese individuals thereby augmenting the overall disruption and deterioration in health and well being. [Para 003] There are many treatment methods being employed for the management of obesity which include diet restrictions and increase in physical activity. Drugs like orlistat are associated with side effects, induce limited weight reduction and are being withdrawn from the market due to low risk vs. benefit ratio. Natural molecules from different plant sources offer a safe and efficacious option for weight management and are now finding their way in managing obesity and related conditions.

[Para 004] The use of natural molecules for obesity management is well described in the scientific art.

[Para 005] Extracts of Garcinia cambogia, have been reported to have a weight loss potential. US 7063861, discloses a weight loss composition containing garcinol and hydnoxycitiric acid (HCA) and optionally with anthocyanins. US8329743 also discloses a weight loss formulation containing garcinol, pterostilbene and anthocyanin. US patent application no. 16007212 discloses the anti obesity potential of garcinol per se. Extracts of other plant materials like Cypeirus rotundas (US9387193, US9782450) and Coleus forskahlii (EP0977564) are also used for reducing body weight and managing obesity and related conditions.

[Para 006] Combination drug therapies are also used for treating obesity (Gadde and

Allision, Combination Pharmaceutical Therapies for Obesity, Expert Opin Pharmacother. 2009 Apr, 10(6): 921-925). Combinations of natural molecules can synergistically increase the efficacy of the treatment. The present invention discloses one such combination comprising extracts of Cyperus rotundas, standardized to contain 3-5% total stilbenes, extracts of Garcinia sp., standardized to contain 20% garcinol and extracts of Coleus forskohlii standardized to contain not less than 10% forskolin for the therapeutic management of obesity and related conditions.

[Para 007] The three natural extracts used in die combination reduce obesity by different mechanisms, Forskolin the cAMP activator, is known to activate hormone sensitive lipase and induce fat hydrolysis and increase mitochondrial uncoupling protein to tranactivate brown adipocytes. Garcinol is reported to modify the gut mictobiome in favor of Akkermamia species apart from activating the genes related to adipocyte browning, while 3-5% total stilbenes from cyperus prevent adipogenesis, _: increase adiponectin and reduce cholesterol and leptin leading to an overall loss in weight.

[Para 008] It is the principle object of the invention to disclose a composition comprising extracts of Cyperus ratundus, standardized to contain 3-5% total stilbenes, extracts of Garcinia sp ., standardized to contain 20% garcinol and extracts of Coleus forskohlii standardized to contain not less than 10% forskolin for the therapeutic management of obesity.

[Para 009] It is another object of the invention to disclose a method for the therapeutic management of obesity related conditions using a composition comprising extracts of Cyperus ronmdus, standardized to contain 3-5% total stilbenes, extracts of Garcinia sp., standardized to contain 20% garcinol and extracts of Coleus forskohlii standardized to contain not less thanlO% forskolin.

[Para 0010] The present invention solves die above mentioned objectives and provides further related advantages.

SUMMARY OF THE INVENTION

[Para 0011] The present invention discloses a composition comprising extracts of Cyperus rotundas, standardized to contain 3-5% w/w total stilbenes, extracts of Garcinia sp., standardized to contain 20% w/w garcinol and extracts of Coleus forskohlii standardized to contain not less than 10% w/w forskolin for die therapeutic management of diet induced obesity and weight gain by bringing about a reduction in body weight and increasing lean body mass.

[Para 0012] The invention also discloses the use of the composition comprising extracts of Cyperus rotundus, standardized to contain 3-5% w/w total stilbenes, extracts of Garcinia sp., standardized to contain 20% w/w garcihol and extracts of Coleus forskohlii standardized to contain not less than 10% w/w forskolin, in managing obesity related conditions selected from the group comprising liver dysfunction, NASH, NAFUD, liver cirrhosis, hypercholesterolemia, hyperlipidemia, kidney dysfunction by normalizing die levels of liver enzymes, kidney markers and circulating lipids. [Para 0013] Other features and advantages of the present invention will become apparent from the following more detailed description, taken in conjunction with die accompanying images, which illustrate, by way of example, the principle of the invention.

BRIEF DESCRIPTION OF DRAWINGS

[Para 0014] Fi 1 is graphical representation showing die fat pad weight of C57BL/6J mice treated with different formulations.

[Para 0015] Fig. 2 shows the decrease in body weight of test animals using a composition comprising total stilbenes, garcinol and forskolin at die dosages of 50 mg/day, 10 mg/day and 25 mg/day respectively.

[Para 0016] Fig. 3 is graphical representation showing the levels of total cholesterol and triglycerides in C57BL/6J mice treated with different formulations.

[Para 0017] Fig. 4 is graphical representation showing the levels of liver enzymes in C57BL/6J mice treated with different formulations.

DESCRIPTION OF PREFERRED EMBODIMENTS

[Para 0018] In a most preferred embodiment, the present invention discloses a method for preventing diet induced weight gain and related conditions in mammals, said method comprising step of administering a composition comprising extracts of Cyperus rotundus, standardized to contain 3-5% w/w total stilbenes, extracts of Garcinia sp., standardized to contain 20% w/w garcinol and extracts of Coleus farskohlti standardized to contain not less titan 10% w/w fcrskolin in effective doses to said mammals to bring about a reduction in body weight and increasing lean body mass. In a related aspect, the effective doses of the total stilbenes, forskolin and garcinol are 50 mg/day, 25 mg/day and 10 mg/day respectively. In a related aspect, the composition further comprises of Piper nigrum extract standardized to contain not less than 10% w/w piperine in an effective dose of 1 mg/day. In another related aspect, the composition further comprises of 10% w/w phospholipids. In another related aspect, the stilbenes of Cyperus rotundus extracts consists of picetannol, scirpusin A and sciipusin B. In another related aspect, the Gamicia sp. Include Garcinia cambogia and Garcinia indica. In another related aspect, the related conditions of diet induced weight gain are selected from the group comprising, but not limited to, _: liver dysfunction, NASH, NAFLD, liver cirrhosis, hypercholesterolemia, hyperlipidemia, kidney dysfunction. In another related aspect, the composition prevents diet induced hypercholesterolemia and hyperlipidemia by decreasing the levels of total cholesterol, triglycerides, VLDL and LDL and increasing die levels of HDL. In yet another related aspect, die composition prevents diet induced liver dysfunction, NASH, NAFLD, cirrhosis and improves liver function by normalizing the elevated live: enzymes selected from the group consisting of SCOT and SGPT. In another related aspect, the composition prevents diet induced kidney damage and improves kidney function by normalizing elevated circulating levels of creatinine, uric acid, blood urea nitrogen, and total protein. In yet another related aspect the mammals is human.

[Para 0019] la a related embodiment the composition is formulation with phafmaceutically/nutraceuticaUy accepted excipients, preservatives, antioxidants, and adjuvants and administered orally in the form of pharmaceutically/nutraceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, chewing gum, powders, suspensions, emulsions, chewables, candies, lozenges or eatables.

[Para 0020] In another related embodiment, die invention discloses a composition comprising extracts of Cyperus rotundus, standardized to contain 3-5% w/w total stilbenes, extracts of Gareitiia sp., standardized to contain 20% w/w garcinol and extracts of Coleus forskoklii standardized to contain not less than 10% w/w forskolin for use in preventing diet induced and related conditions. In a related aspect, the composition is administered in effective doses of 50 mg/day total stilbenes, 25 mg/day forskolin and 10 mg/day garcinol. In a related aspect, the composition further comprises of Piper nigrum extract standardized to contain not less than 10% w/w piperine in an effective dose of 1 mg/day. In another related aspect, the composition further comprises of 10% w/w phospholipids. In another related aspect, the stilbenes of Cyperus rotundus extracts consists of picetannol, scirpusin A and scirpusin B. In another related aspect, tile Gamicia sp. include Gareinia cambogia and Garcinia indica. hi another related aspect, the related conditions of diet induced weight gain are selected from the group comprising, but not limited to, liver dysfunction, NASH, NAFLD, liver cirrhosis, hypercholesterolemia, hyperlipidemia, kidney dysfunction. In another related aspect, the composition prevents diet induced hypercholesterolemia and hyperlipidemia by decreasing the levels of total cholesterol, triglycerides, VLDL and LDL and increasing the levels of HDL. hi yet another related aspect, the composition prevents diet induced liver dysfunction, NASH, NAFLD, cirrhosis and improves liver function by normalizing the elevated liver enzymes selected from die group consisting of SCOT and SGPT. hi another related aspect, the composition prevent diet induced kidney damage and improves kidney function by normalizing devated circulating Ievds of creatinine, uric acid, blood urea nitrogen, and total protein hi yet another related aspect the mammals is human.

[Para 0021] In a related embodiment the composition is formulation with pharmaceutically/nutraceutically accepted excipients, preservatives, antioxidants, and adjuvants and administered orally in the form of pharmaceutically/nutraceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, chewing gum, powders, suspensions, emulsions, chewables, candies, lozenges or eatables.

[Para 0022] The following illustrative examples further describe in detail the preferred embodiments of the invention:

[Para 0023] EXAMPLES

[Para 0024] Example 1: Treatment

[Para 0025] Male C57BL/6J mice at 5 weeks of age were used in the invention. After 1 week of acclimation, animals were randomly distributed into four groups of 8 animals each as described in the following Table 1: The control group animals were fed with normal diet and die research control with Mgh fat diet (HFD) along with formulation as in Table 1

[Para 0026] Table 1. Treatment group (Cyperns ext, Gardnol and Forskolin

Phospolipids and pipeline composition) dose ratio/measurement

(Para 0027) The diet intake of animals was monitored every day and the body weight was recorded. All animal experimental protocol used in this study was approved by Institutional Animal Care and Use Committee of the National Kaohsiung Marine University (IACUC, NKMU). At the end of the study, all animals were fitsted overnight and sacrificed by CO2 asphyxiation. Blood samples were collected from the heart for biochemical analysis. Liver, spleen, kidney and fat pads (perigonadal, retroperitoneal and mesenteric fat) were immediately removed. Body weight was monitored and the average body weight of each group was expressed as the mean ± SB. Statistical analysis was done by Student’s t test and compared with HFD group.

[Para 0028] Example 2 : Body weight measurement

(Para 6025] The animals were weighed after one month (Table 2) and the animals fed with HFD showed increased body weight. The composition at fire dose of Cyp 5<H- For 25+Gar 10, with and without phospholipids significantly reduced increase in body weight even when administered with hi# frit diet [Para 0030] Table 2. Formulation/composition (Cyperus ext (total stflbenes), Garcinol and Forskolih Phospo!ipids and piperine composition)

[Para 0031] The body weight of the animals were also measured after 90 days before sacrifice. Table 3 shows the body weight of the animals after the 90 day period.

[Para 0032] Table 3: Body weight Measurement (gm)

[Para 0033] High fiat diet significantly increased the body weight of the animals compared to the normal control. The composition comprising Cyperus ext 50+ Garcinol 10 + Forskoiin 25 (Dose 8) significantly inhibited the increase in body weight compared to all the other dosages by 32.41%. The same dosage actives along with phospholipids (Dose 4) was also effective in inhibiting the body weight by 27% (Table 4)

[Para 0034] Table 4: Percentage Body weight Inhibition by the formulation

[Para 0035] The fat pad weight was also less in the treatment group administered with Cyperus extract, garcinol and fofskolin at the dosages of 50 mg/day, 10 mg/day and 25 mg/day respectively (dose 8), (Fig. 1) indicating that the formulation prevents diet induced weight gain and promotes lean body mass by preventing fat accumulation. The animals also visually showed decreased weight gain after the 90 day treatment period even when administered with high fat diet (Fig. 2).

[Para 0036] Example 3: Changes in Lipid profile

[Para 0037] The circulating levels of lipids, viz total cholesterol, triglycerides, LDL, VLDL and HDL, was evaluated after the 90 day treatment using standard protocol.

[Para 0038] High fat diet significantly increased the cholesterol, triglycerides levels and tire formulation comprising Cyperus extract, garcinol and fbrskolin at the dosages of 50 mg/day, 10 mg/day and 25 mg/day respectively (dose 8), was very effective in preventing increase in cholesterol and triglyceride levels (Fig. 3) _» compared to the other dosages. The formulation comprising Cyperus extract, garcinol and fbrskolin at the dosages of 50 mg/day, 10 mg/day and 25 mg/day respectively (dose 8) also significantly decreased die circulating levels of LDL and VLDL and increased the levels of HDL (Table S) compared to other dosages.

[Para 0039] The formulation thus plays an effective tole in preventing hypercholesterolemia, and hyperlipidemia induced by high fat diet.

[Para 0040] Table 5: Levels of VLDL, LDL and HDL in treatment groups after 90 days

(Para 0041] Example 4: Improvement in liver function

[Para 0042] It is well known in the scientific literature that high fat diet causes liver dysfunction leading to the development of many conditions like NAFLD, NASH, cirrhosis etc. The effect of different formulations on liver function was assessed by measuring the liver markers SCOT mid SGPT.

[Para 0043J The results indicated that high fat diet significantly increased the levels of liver markers SCOT and SGPT indicating increased liver damage and dysfunction. The formulation comprising Cyperus extract, garcinol and forskolin at die dosages of 50 rng/day, 10 mg/day and 25 mg/day respectively (dose 8), w ^r as effective in preventing high fat diet induced liver damage and dysfunction which is evident by the decreased levels of the liver enzymes (Fig.4). [Para 0044] Example 5: Effect of different formulation on kidney function

[Para 0045] High fat diet, increased weight gain and obesity has a serious effect on kidney function. The effect of different formulations on kidney function was assessed by measuring die kidney markers creatinine, uric acid, blood urea nitrogen (BUN) and total protein.

[Para 0046] The results indicated that high fat diet significantly damaged the kidneys as evident with the increase in levels of kidney markers. The formulation comprising Cyperus extract, garcinol and forskolin at the dosages of 50 mg/day, 10 mg/day and 25 mg/day respectively (dose 8), was effective in preventing high fat diet induced kidney damage and dysfunction by normalizing the levels of the kidney markers (Table 6).

(Para 0047] Table 6: Effect of different formulations on kidney function

[Para 0048] Thus, the formulation comprising Cyperus extract garcinol and forskolin at the dosages of 50 mg/day, 10 mg/day and 25 mg/day respectively synergistically reduce diet induced weight gain and can be use as an effective supplement for the management of obesity and related conditions. The formulation in along with 10% phospholipids was also effective in reducing weight induced by high fat diet.

[Para 0049] Other modifications and variations to the invention will be apparent to those skilled in the art from the foregoing disclosure and teachings. Thus, while only certain embodiments of the invention have been specifically described herein, it will be apparent that numerous modifications may be made thereto without departing from the spirit and scope of die invention. The scope of the invention is to be interpreted only in conjunction with the appended claims.