Preparation for weight loss management

FIELD OF INVENTION

This invention relates to weight loss management and compositions therefor.

BACKGROUND OF INVENTION

A relatively high percentage of U.S. population is overweight, that is, exhibiting a basic metabolic index or body mass index (BMI) greater than 25, and one quarter of the U.S. population is obese, exhibiting a BMI greater than 30. Annually, a large number of deaths can be attributed to obesity. Therefore, a healthy weight maintenance requires a balance between energy intake and energy output for an individual.

Adipose derived hormones such as adiponectin and leptin are secreted by adipose tissue and control various physiological systems in a mammalian body. Low leptin levels, for example, stimulate food intake, reduce energy expenditure, and modulate neuroendocrine and immune functions to conserve energy stores. While normally leptin is a signal that reduces appetite, it is known that obese persons have an unusually high circulating concentration of leptin and may be resistant to the usual effects of leptin in a manner similar to patients suffering from Type 2 diabetes that are resistant to the effects of insulin. High sustained concentrations of leptin may result in undesirable leptin desensitization or leptin resistance.

Adiponectin is produced by adipocytes in adipose tissue and is secreted into the bloodstream. Levels of adiponectin in the bloodstream are inversely correlated with body fat percentage in adults. It is believed that adiponectin plays a role in the suppression of metabolic events that may result in Type 2 diabetes and obesity.

SUMMARY OF THE INVENTION

The present invention is directed to compositions that reduce the leptin-to-adiponectin ratio in overweight patients and promote weight loss.

The compositions comprise a solid, ethanolic extract derived from Gymnema sylvestre leaves which contains no more than about 55 weight percent of a gymnemic acid and one or more of (1) a solid, ethanolic extract from Boswellia serrata gum containing at lest 70 weight percent boswellic acids, (2) a solid, ethanolic extract from the stems of Tinospora cordifolia, and (3) a solid, ethanolic extract from Commiphora mukul gum.

The daily dosage for a patient desiring weight management preferably is about 500 milligrams to about 1,000 milligrams of the composition or the components thereof administered substantially concurrently.

DESCRIPTION OF PREFERRED EMBODIMENTS

The present compositions include an ethanolic extract from Gymnema sylvestre leaves in powder form. This ethanolic extract is constituted by about 25 to about 55 weight percent of gymnemic acids, but may also contain gymnemasaponins. There are 18 known gymnemic acids, i.e., gymnemic acids I-XVIII, and the term "gymnemic acid" as used herein includes one or more of the aforementioned gymnemic acids which may or may not be acylated. Particularly desirable for the present compositions are gymnemic acids III, IV, V and VII.

A preferred solid, ethanolic extract from Gymnema sylvestre is prepared as set forth below. (1) Gymnema sylvestre leaves are sourced and checked for their botanical purity. The leaves are then disintegrated (powdering the leaves into smaller size using a pulveriser) to a size passing through a 20 Mesh sieve, U.S. Standard Sieve Series. (2) Obtained powder is then extracted with 50% v/v ethanol and demineralized water (solvent). 40 grams of powdered leaves are held in 1 liter of solvent at room temperature overnight-up to 12 hours in a shaker, distributed in four Erlenmeyer flasks. The contents are then pooled and filtered. (3) The obtained micelle is concentrated under reduced pressure (650-700 mm) to 30% solids at pH of less than or equal to 2. (4) The concentrate from above is dissolved in 1 liter of demineralized water at room temperature, in a shaker for 4 hours while adjusting the final pH to about 4.5 to about 5, and filtered to remove any precipitate and sludge. (5) The obtained filtrate is adjusted to a pH of about 2 and filtered to remove any precipitate and sludge. (6) The new filtrate is concentrated under reduced pressure (650-700 mm) to 30% solids, and sterilized (Heat Sterilization) at about 80.degree. C. for 2 hours. (7) The product is adjusted for at least 25 but no more than 55% by weight gymnemic acid, preferably about 35 to about 45 weight percent gymnemic acid. (8) The product is then dried in spray dryer at inlet temp of 160.degree. C. and outlet temp of 85.degree. C. (9) The dried product is checked for gymnemic acid content. (10) The powder is homogenized and sifted to 80-100 Mesh, U.S. Standard Sieve Series.

The solid, ethanolic extract from Boswellia serrata gum is rich in boswellic acids, particularly the alpha, beta, and gamma boswellic acids. These acids comprise a pentacyclic triterpene, a carboxyl group, and at least one other functional group which can be a hydroxyl group, an acetyl group or a keto group.

A preferred solid, ethanolic extract from Boswellia serrata gum is prepared as set forth below. (1) The boswellia gum exudate is cleaned by removing bark and foreign organic matter adhering to the exudate. (2) The exudate is then extracted with ethanol. (3) The ethanol is then partially distilled from the obtained micella which is adjusted to a slightly alkaline pH. (4) The obtained gum product is then extracted with petroleum ether and ethanol in a liquid-liquid extractor at ambient temperature. (5) The obtained liquid phases are separated and processed separately. (6) The petroleum ether fraction affords an aromatic fraction mainly composed of essential oil and resinous matter. The recovery is done by distillation. This matter is removed. (7) The ethanolic fraction is further processed by heating under vacuum to remove residual petroleum ether. (8) The processed ethanolic fraction is concentrated to 30-35% solids and poured under vigorous stirring into demineralized water to produce a boswellic acid precipitate which is recovered. (9) The precipitate is washed with 80/20 v/v ethanol and ethyl acetate mixture to remove any unwanted fractions of boswellic acid until 70% boswellic acid by weight is achieved with only an alpha, beta, and gamma boswellic acid present. (10) The aqueous phase is decanted off. Precipitate is washed further with demineralized water, and dried under vacuum at a temperature of about 60.degree. C. (11) The dried flakes obtained are pulverized, and contain at least 70% by weight of boswellic acids.

The solid, ethanolic extract from the stems of Tinospora cordifolia contains diterpenes such as tinosporaside, cordiofolide, cordifol, heptacosanol, clerodane furano diterpene, diterpenoid furanolactone tinosporidine, columbin and beta-sitosterol.

A preferred solid, ethanolic extract can be prepared as shown below. (1) Well matured Tinospora cordifolia stems, 3/8'' to 1/2'' diameter and 3'' to 5'' in length, with the outside bark color of dark brown having irregular thin red lines, are washed with water and dried in cool shade, and then crushed in a disintegrator into coarse chunks, from which the bark pieces are removed. (2) The coarse chunks of the stems are pulverized and the remainder of the bark is separated therefrom. The inner body of the stems, having light beige to light brown color, constitute the starting powder material ("core") which is then treated further. (3) 200 Grams of the "core" powder material are then extracted with two liters of 50% v/v ethanol followed by demineralized water. (4) The extracted solutions received from the foregoing hydro-alcoholic and aqueous extractions are concentrated separately, and then mixed in a homogenizer to make a homogenous solution before final concentration. (5) The concentration is done under controlled temperature at pH of less than about 4 for about two hours. (6) When a concentration of 30-35% solids is achieved, the material can be spray dried, or it can be further concentrated to a thick paste of 65-70% solids. (7) The concentrate or the thick paste are then dried in vacuum tray dryer or rotary vacuum dryer at a temperature not to exceed about 65.degree. C. (8) The obtained dried flakes are pulverized to 80-100 Mesh, U.S. Sieve Series, and packed under hygienic conditions. (9) Before packing the powder can be sterilized, if desired, by passing through a hot duct maintained at a temperature of 120.degree. C.

The solid, ethanolic extract from Commiphora mukul gum contains guggalsterone, also known as guggal lipid.

A preferred extract can be prepared as shown below. (1) The Commiphora mukul gum is first checked for purity by TLC, and subjected to a four step grading process. (2) 200 Grams of selected, crushed gum is then loaded into an extractor and ethanol, about five times the weight of gum with water (50/50) is charged through the extractor. (3) In the extractor the temperature is kept between 65-70.degree. C. and the ethanol-water is circulated under turbulence conditions for through mixing and efficient extraction. (4) Extracted mucilage is then taken to a falling film evaporator for solvent recovery. (5) The obtained guggal paste is then enriched in guggalsterones by solvent fractionation. (6) The enriched paste obtained in this manner is then kept under vacuum for solvent removal. (7) The product is then dried in a fluid bed dryer. (8) The dried product is sieved and again tested for guggalsterone content.

The present invention is illustrated by the following examples.

Example 1

Weight Reduction Using Enhanced G. sylvestre Extract

Obese volunteers (n=10; 6 male, 4 female), marginally diabetic and about 20 percent overweight patients, were treated with a solid, ethanolic extract of G. sylvestre or a solid, ethanolic extract of G. sylvestre enhanced by the addition of an amount of a solid, steranolic extract of B. serrata in an amount sufficient to provide a boswellic acid content of about 3.5 percent by weight of the total composition.

The patients exhibited a fasting blood sugar level (FBS) of 130-140 milligrams per deciliter (mg/dl). The average age of the patient group was 35-45 years.

The composition was administered orally in a capsule form. Each capsule contained 250 milligrams of the composition. One or more capsules were administered to obtain the desired dosage.

Physical parameters and blood chemistry were monitored. Serum leptin and adiponectin were determined using an ELISA kit (R&D System, Inc., Minneapolis, Minn., U.S.A.).

TABLE-US-00001 TABLE I Physical Parameters (Average Values) % decrease - after 60 days Body wt. Chest Waist Hip W/H Dosage Sex (Kg) (cm) (cm) (cm) Ratio BMI 500 mg Male (-) 3.00 No Change (-) 1.18 (-) 0.35 (-) 3.37 (-) 2.09 60 days Female (-) 2.10 (-) 0.125 (-) 1.02 (-) 0.26 (-) 3.92 (-) 1.44 1000 mg Male (-) 2.70 (-) 0.80 (-) 2.12 (-) 1.25 (-) 1.94 (-) 2.51 60 days Female (-) 4.24 (-) 0.63 (-) 1.25 (-) 0.50 (-) 2.35 (-) 2.35 W/O Male (-) 3.10 No Change (-) 1.19 (-) 0.36 (-) 3.30 (-) 2.08 W/H--waist-to-hip ratio BMI--basic metabolic index (body mass index) W/O--G. sylvestre extract without added enhancer

TABLE-US-00002 TABLE II Blood Chemistry Improvements (Average Values) % decrease - after 60 days Dosage Sex FBS TGL CHOL HDL LDL 500 mg Male (-) 11.50 (-) 6.00 (-) 6.00 (+) 6.50 (-) 2.80 60 days Female (-) 17.50 (-) 14.50 (-) 6.00 (+) 4.50 (-) 3.50 1000 mg Male (-) 14.61 (-) 14.61 (-) 6.50 (+) 18.00 (-) 11.16 60 days Female (-) 19.50 (-) 6.25 (-) 14.00 (+) 8.00 (-) 14.50 W/O Male (-) 11.62 (-) 6.10 (-) 6.15 (+) 6.60 (-) 2.78 FBS--fasting blood sugar, mg/dl TGL--triglycerides CHOL--Cholesterol HDL--high density lipoprotein LDL--low density lipoprotein W/O--G. sylvestre extract without added enhancer

TABLE-US-00003 TABLE III Leptin and Adiponectin Concentration After 60 Days at 500 mg/day Leptin (picogram/ml) Adiponectin (nanogram/ml) Code % decrease % increase L/A L/A Sex Name BT AT (-) BT AT (+) (BT) (AT) MALE DS 4987 4388 -13% 879 975 +11% 5.67 4.50 TH 4498 3868 -8% 2129 2320 +9% 2.11 1.67 NB 5237 4294 -18% 3267 3659 +12% 1.60 1.17 PB 3847 3269 -15% 6981 7609 +9% 0.55 0.42 SH 4428 3810 -14% 5390 5929 +13% 0.82 0.64 SM 4611 4252 -8% 1400 1568 +12% 3.29 2.71 FEMALE GP 3911 3324 -15% 5742 6316 +10% 0.68 0.53 DH 3787 3181 -17% 1059 1165 +10% 3.57 2.73 UC 4498 3643 -18% 1456 1630 +12% 3.08 2.23 TS 3618 3003 -17% 4488 5929 +13 0.81 0.50 BT--before treatment AT--after treatment L/A (BT)--leptin-to-adiponectin ratio before treatment L/A (AT)--leptin-to-adiponectin ratio after treatment

TABLE-US-00004 TABLE IV Leptin and Adiponectin Concentration After 60 Days at 1000 mg/day Leptin (picogram/ml) Adiponectin (nanogram/ml) Code % decrease % increase L/A L/A Sex Name BT AT (-) BT AT (+) (BT) (AT) Male AG2 4498 3643 -19% 911 1056 +16% 4.94 3.45 UM 5237 4032 -23% 7313 8409 +15% 0.72 0.48 GR 4264 3112 -27% 2543 2975 +17% 1.68 1.05 AG 4264 3411 -20% 5265 5844 +11% 0.81 0.58 AS 5012 3362 -33% 2666 3441 +29% 1.88 0.98 DC 4672 3504 -25% 1994 2392 +20% 2.34 1.20 Female GK 3632 2978 -18% 8923 10439 +17% 0.41 0.29 SM 3798 2772 -27% 1145 1385 +21% 3.32 2.00 UH 3911 2463 -37% 1783 2175 +22% 2.19 1.13 AM 4108 3286 -20% 3612 4478 +24% 1.14 0.73 BT--before treatment AT--after treatment

The foregoing results indicate the achievement of reduced fasting blood sugar level as well as an improved lipid profile and a decrease in the leptin-to-adiponectin ratio for each patient.

Example 2

Effect of Enhancers on G. sylvestre Efficacy

Capsules containing solid, ethanolic extract of G. sylvestre were prepared as well as capsules containing solid, ethanolic extracts of Tinospora cordifolia and Commiphora mukul. Predetermined dosages of the G. sylvestre extract alone or together with the extract of T. codifolia or C. mukul were administered to volunteer male patients which were marginally diabetic, exhibiting a fasting blood sugar level of 125-135 mg/dl, and about 20 percent overweight. The average age of the patient group was 30-45 years.

The patient's physical parameters, levels of changes in fasting blood sugar, blood cholesterol, high density lipoprotein, low density lipoprotein, as well as triglyceride were determined. Leptin and adiponectin concentrations were measured. The results are reported below.

TABLE-US-00005 TABLE V Effects on Obesity Achieved by G. sylvestre Extract with Enhancers % decrease - after 60 days Body wt. Chest Waist Hip W/H Extract Dosage (Kg) (Cm) (Cm) (Cm) ratio BMI 500 mg G. sylvestre (-) 3.10 No (-) 1.19 (-) 0.36 (-) 3.30 (-) 2.08 change 250 mg G. sylvestre (-) 2.90 No (-) 1.28 (-) 0.36 (-) 3.55 (-) 2.10 250 mg. T. cordifolia change 250 mg G. sylvestre (-) 3.10 No (-) 2.00 (-) 0.48 (-) 4.16 (-) 2.21 250 mg G. mukul change W/H ratio--waist-to-hip ratio BMI--basic metabolic index (body mass index)

TABLE-US-00006 TABLE VI Effects on Blood Chemistry Achieved by G. sylvestre Extract with Enhancers % decrease - after 60 days Extract Dosage FBS TGL CHOL HDL LDL 500 mg G. sylvestre (-) 11.62 (-) 6.10 (-) 6.15 (+) 6.60 (-) 2.78 250 mg G. sylvestre (-) 12.20 (-) 8.00 (-) 4.50 (+) 2.80 (-) 3.00 250 mg T. cordifolia 250 mg G. sylvestre (-) 13.00 (-) 7.06 (-) 5.50 (+) 4.80 (-) 2.60 250 mg C. mukul FBS--fasting blood sugar, mg/dl TGL--triglycerides CHOL--cholesterol HDL--high density lipoprotein LDL--low density lipoprotein

The data shown in Tables V and VI show a beneficial decrease in the serum levels of fasting blood sugar, triglycerides, cholesterol and low density lipoproteins but a beneficial increase in high density lipoprotein level.

TABLE-US-00007 TABLE VII Decrease in Leptin-to-Adiponectin Ratio in Male Patients Leptin (picogram/ml) Adiponectin (nanogram/ml) % decrease % increase L/A L/A Dosage Code BT AT (-) BT AT (+) (BT) (AT) 500 mg SG 3925 3780 -3.69% 1020 1110 +8.82% 3.89 3.41 G. sylvestre TL 4045 3850 -4.82% 2215 2420 +9.25% 1.83 1.59 SK 4126 3910 -5.23% 2890 3120 +7.95% 1.43 1.25 AB 3950 3170 -19.74% 4950 5200 5.05% 0.80 0.61 SD 4880 4218 -13.56% 4612 4950 +7.32% 1.06 0.85 BP 4666 4155 -10.95% 1680 1920 +14.28% 2.78 2.16 250 mg MP 3980 3660 -8.04% 2566 3100 +20.80% 1.55 1.18 G. sylvestre BG 4610 4120 -10.62% 1880 2106 +12.02% 2.45 1.96 250 mg PG 4235 3980 -6.02% 1200 1300 +8.33% 3.53 3.06 T. cordifolia TS 5432 4880 -10.16% 2681 2920 +8.91% 2.03 1.67 MM 3656 3200 -12.47% 4880 5200 +6.55% 0.73 0.61 KC 3980 3650 -8.29% 5415 5820 +7.47% 0.73 0.63 250 mg KM 4220 3660 -13.27% 1120 1310 +16.96% 3.77 2.79 G. sylvestra BS 3568 2900 -8.72% 6520 6800 +4.27% 0.55 0.43 250 mg ST 4164 3020 -27.47% 2646 3100 +17.15% 1.57 0.97 C. mukul SP 5015 3960 -21.03% 5210 5920 +13.62% 0.96 0.67 NS 4522 3880 -14.19% 2800 3460 +23.57% 1.61 1.12 PB 3156 2220 -29.65% 2222 2480 +11.61% 1.42 0.90 BT--before treatment AT--after treatment L/A (BT)--leptin-to-adiponectin ratio before treatment L/A (AT)--leptin-to-adiponectin ratio after treatment

Data in Table VII show a consistent decrease in the leptin-to-adiponectin ratio for all patients.

The foregoing discussion and the Examples are intended to be illustrative but are not to be taken as limiting. Still other variants within the spirit and scope of the present invention are possible and will readily present themselves to those skilled in the art.