Compositions for weight loss

Abstract

The present invention discloses 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 forskohlii standardized to contain not less than 10% w/w forskolin for the therapeutic management of diet induced obesity and weight gain and related conditions like liver dysfunction, NASH, NAFLD, liver cirrhosis, hypercholesterolemia, hyperlipidemia, kidney dysfunction by bringing about a reduction in body weight, increasing lean body mass and by normalizing the levels of liver enzymes, kidney markers and circulating lipids.

Claims

1. A method for therapeutic management of kidney dysfunction in mammals in need thereof, said method comprising step of administering a composition consisting essentially of extracts of Cyperus rotundus, standardized to contain 3-5% w/w total stilbenes, extracts of Garcinia sp., standardized to contain 20% w/w garcinol, extracts of Coleus forskohlii standardized to contain not less than 10% w/w forskolin and 10% phospholipids in effective doses to said mammals to bring about a reduction in the elevated levels of markers of kidney damage.

2. The method as in claim 1, wherein the effective doses of the total stilbenes, forskolin and garcinol are 50 mg/day, 25 mg/day and 10 mg/day respectively.

3. The method as in claim 1, wherein the stilbenes of Cyperus rotundus extracts consists of picetannol, scirpusin A and scirpusin B.

4. The method as in claim 1, wherein the Garnicia sp. include Garcinia cambogia and Garcinia indica.

5. The method as in claim 1, wherein the kidney dysfunction is induced by high fat diet.

6. The method as in claim 1, wherein the markers of kidney dysfunction is selected from the group consisting of creatinine, uric acid, blood urea nitrogen, and total protein.

7. The method as in claim 1, wherein the mammal is human.

8. The method as in claim 1, wherein the composition is formulated with pharmaceutically/nutraceutically accepted excipients, preservatives, bioavailability enhancers, antioxidants, and adjuvants and administered orally in the form of tablets, capsules, syrups, gummies, chewing gum, powders, suspensions, emulsions, chewables, candies, lozenges or eatables.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is graphical representation showing the fat pad weight of C57BL/6J mice treated with different formulations.

(2) FIG. 2 shows the decrease in body weight of test animals using a composition comprising total stilbenes, garcinol and forskolin at the dosages of 50 mg/day, 10 mg/day and 25 mg/day respectively.

(3) FIG. 3 is graphical representation showing the levels of total cholesterol and triglycerides in C57BL/6J mice treated with different formulations.

(4) FIG. 4 is graphical representation showing the levels of liver enzymes in C57BL/6J mice treated with different formulations.

DESCRIPTION OF PREFERRED EMBODIMENTS

(5) 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 forskohlii standardized to contain not less than 10% w/w forskolin 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 scirpusin B. In another related aspect, the Garnicia 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 the levels of HDL. In 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 the group consisting of SGOT 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.

(6) 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.

(7) In another related embodiment, the invention discloses 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 forskohlii 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, the Garnicia 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 the levels of HDL. In 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 the group consisting of SGOT and SGPT. In another related aspect, the composition prevent 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.

(8) 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.

(9) The following illustrative examples further describe in detail the preferred embodiments of the invention:

EXAMPLES

Example 1: Treatment

(10) 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 the research control with high fat diet (HFD) along with formulation as in Table 1

(11) TABLE-US-00001 TABLE 1 Treatment group (Cyperus ext., Garcinol and Forskolin Phospolipids and piperine composition) dose ratio/measurement Cyperus ext. (5% 20% 20% Phos- stilbenes) Forskolin Garcinol Piperine pho- mg/day mg/day mg/day mg/day lipids HFD + Dose I 50 10 1 10% HFD + Dose-II 50 20 1 10% HFD + Dose-III 50 50 10 1 10% HFD + Dose-IV 50 25 10 1 10% HFD + Dose-V 50 10 1 HFD + Dose-VI 50 20 1 HFD + Dose-VII 50 50 10 1 HFD + Dose-VIII 50 25 10 1 HFD Control

(12) 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 fasted overnight and sacrificed by CO.sub.2 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 meanSE. Statistical analysis was done by Student's t test and compared with HFD group.

Example 2: Body Weight Measurement

(13) The animals were weighed after one month (Table 2) and the animals fed with HFD showed increased body weight. The composition at the dose of Cyp 50+ For 25+Gar 10, with and without phospholipids significantly reduced increase in body weight even when administered with high fat diet.

(14) TABLE-US-00002 TABLE 2 Formulation/composition (Cyperus ext. (total stilbenes), Garcinol and Forskolin Phospolipids and piperine composition) Formulation Body weight After 1 month With 10% Phospholipids Cyp 50 + Gar 10 26.03 0.82 Cyp 50 + Gar 20 28.60 0.59 Cyp 50 + For 50 + Gar 10 27.35 1.09 Cyp 50 + For 25 + Gar 10 24.20 1.08 Without Phospholipids Cyp 50 + Gar 10 28.92 0.98 Cyp 50 + Gar 20 27.99 1.05 Cyp 50 + For 50 + Gar 10 26.13 1.00 Cyp 50 + For 25 + Gar 10 24.79 1.25 HFD 29.08 0.65 Control 22.50 1.33

(15) The body weight of the animals were also measured after 90 days before sacrifice.

(16) Table 3 shows the body weight of the animals after the 90 day period.

(17) TABLE-US-00003 TABLE 3 Body weight Measurement (gm) Treatment group Day 90 Healthy control 26.27 1.53** HFD Diet control 32.76 0.60 Cyperus ext 50 + Garcinol 10 + 10% Phospholipids 27.46 0.99* Cyperus ext 50 + Garcinol 20 + 10% Phospholipids 27.36 0.59* Cyperus ext 50 + Garcinol 10 + Forskolin 50 + 10% 27.69 0.74* Phospholipids Cyperus ext 50 + Garcinol 10 + Forskolin 25 + 10% 23.90 1.26** Phospholipids Cyperus ext 50 + Garcinol 10 26.62 1.07* Cyperus ext 50 + Garcinol 20 26.27 1.44* Cyperus ext 50 + Garcinol 10 + Forskolin 50 26.67 1.44* Cyperus ext 50 + Garcinol 10 + Forskolin 25 22.14 1.20** **P < 0.01 and *P < 0.05

(18) High fat diet significantly increased the body weight of the animals compared to the normal control. The composition comprising Cyperus ext 50+ Garcinol 10+Forskolin 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)

(19) TABLE-US-00004 TABLE 4 Percentage Body weight Inhibition by the formulation Treatment group % Inhibition Healthy control HFD Diet control Cyperus ext. 50 + Garcinol 10 + 10% Phospholipids 16.17% Cyperus ext. 50 + Garcinol 20 + 10% Phospholipids 16.48% Cyperus ext. 50 + Garcinol 10 + Forskolin 50 + 10% 15.47% Phospholipids Cyperus ext. 50 + Garcinol 10 + Forskolin 25 + 10% 27.04% Phospholipids Cyperus ext. 50 + Garcinol 10 18.74 Cyperus ext. 50 + Garcinol 20 19.81% Cyperus ext. 50 + Garcinol 10 + Forskolin 50 18.58% Cyperus ext. 50 + Garcinol 10 + Forskolin 25 32.41%

(20) The fat pad weight was also less in the treatment group administered with Cyperus extract, garcinol and forskolin 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).

Example 3: Changes in Lipid Profile

(21) The circulating levels of lipids, viz total cholesterol, triglycerides, LDL, VLDL and HDL, was evaluated after the 90 day treatment using standard protocol.

(22) High fat diet significantly increased the cholesterol, triglycerides levels and 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 very effective in preventing increase in cholesterol and triglyceride levels (FIG. 3), compared to the other dosages. 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) also significantly decreased the circulating levels of LDL and VLDL and increased the levels of HDL (Table 5) compared to other dosages.

(23) The formulation thus plays an effective role in preventing hypercholesterolemia, and hyperlipidemia induced by high fat diet.

(24) TABLE-US-00005 TABLE 5 Levels of VLDL, LDL and HDL in treatment groups after 90 days VLDL LDL HDL Groups (mg/dl) (mg/dl) (mg/dl) Normal control 10.9 0.50** 7.52 0.32** 30.33 2.18** High fat Diet control 33.64 0.89 50.52 1.45 16.67 0.33 Cyperus ext. 50 + Garcinol 10 + 20.15 1.02** 12.83 0.42** 23.67 0.66** 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 20 + 22.85 1.45** 18.07 0.34** 22.33 0.76* 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 10 + 23.3 0.94** 12.44 0.23** 23.67 1.16** Forskolin 50 + 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 10 + 13.3 0.57** 13.40 0.34** 23.80 1.20** Forskolin 25 + 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 10 + 19.9 0.5** 27.02 0.23* 23.33 0.33** HFD Cyperus ext. 50 + Garcinol 20 + 13.05 1.26** 21.70 0.44* 24.00 1.15** HFD Cyperus ext. 50 + Garcinol 10 + 14.75 0.89** 20.02 0.54* 25.33 0.88** Forskolin 50 + HFD Cyperus ext. 50 + Garcinol 10 + 12.45 0.49** 12.42 0.33** 26.67 0.66** Forskolin 25 + HFD **P < 0.01 and *P < 0.05

Example 4: Improvement in Liver Function

(25) 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 SGOT and SGPT.

(26) The results indicated that high fat diet significantly increased the levels of liver markers SGOT and SGPT indicating increased liver damage and dysfunction. 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 liver damage and dysfunction which is evident by the decreased levels of the liver enzymes (FIG. 4).

Example 5: Effect of Different Formulation on Kidney Function

(27) 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 the kidney markers creatinine, uric acid, blood urea nitrogen (BUN) and total protein.

(28) 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).

(29) TABLE-US-00006 TABLE 6 Effect of different formulations on kidney function Creatinine Uric acid BUN Total Protein Groups (mg/dl) (mg/dl) (mg/dl) (g/dl) Normal control 0.50 0.03* 3.36 0.47* 161.33 4.31** 4.93 0.23* High fat Diet control 0.94 0.23 5.98 0.08 238.33 4.06 6.67 0.33 Cyperus ext. 50 + Garcinol 10 + 0.76 0.03 4.61 0.68 70.00 3.51** 5.53 0.12 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 20 + 0.78 0.06 5.10 0.47 67.33 2.33** 5.17 0.26* 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 10 + 0.73 0.03 4.16 0.37* 58.00 3.50** 4.47 0.61** Forskolin 50 + 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 10 + 0.80 0.05 3.82 0.58* 71.00 2.52** 4.80 0.25** Forskolin 25 + 10% Phospholipids + HFD Cyperus ext. 50 + Garcinol 10 + 0.87 0.03 4.14 0.21* 52.00 3.42** 5.73 0.26 HFD Cyperus ext. 50 + Garcinol 20 + 0.83 0.06 4.29 0.14 66.67 3.38** 4.97 0.39* HFD Cyperus ext. 50 + Garcinol 10 + 0.77 0.08 5.26 0.36 54.67 1.76** 5.53 0.33 Forskolin 50 + HFD Cyperus ext. 50 + Garcinol 10 + 0.72 0.10 4.18 0.30* 80.00 4.53** 4.33 0.22** Forskolin 25 + HFD **P < 0.01 and *P < 0.05

(30) 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.

(31) 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 the invention. The scope of the invention is to be interpreted only in conjunction with the appended claims.