JP2007210988A - Composition for physiologically increasing male and female hormone by diterpene forskolin and its derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a composition for physiologically increasing the blood serum level of testosterone, estrogen or HGH. <P>SOLUTION: The composition for physiologically increasing male and female hormones such as testosterone, estrogen and HGH comprises an effective amount of forskolin and/or its derivative. The composition comprises forskolin and/or its derivative in an amount of about 1% to 100% in combination with at least one kind of pharmacologically acceptable carrier or excipient. The method for preparing forskolin or its derivative from a Coleus forskohlii plant is provided. The composition of forskolin and its derivative is prepared from the method. A forskolin and its derivative compositions are prepared by the method. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  Most weight-loss pharmaceutical compositions and nutritional supplements reduce an individual's appetite for food, reduce the amount of food absorption in the individual, slow the rate of fatty acid synthesis in vivo, or the rate of fatty acid catabolism Designed to reduce the amount of body fat in an individual by increasing. The following are some examples of weight loss products and their mechanisms. Dexfenfluramine increases brain levels of serotonin, neurotransmitters and neurohormones that suppress appetite. In addition, sibutramine increases not only serotonin but also noradrenaline levels and acts to suppress appetite. Neuropeptide Y inhibitors not only suppress appetite, but also stimulate the body to burn more sugar and less fat. Bromeleptin mimics the neurotransmitter dopamine and can reduce blood sugar and adipogenesis by the liver. Leptin, a hormone produced by adipocytes, affects the hypothalamus. Cholecystokinin, a hormone and neurotransmitter, acts to reduce appetite. Butabinzide blocks an enzyme that inactivates cholecystokinin. Orlistat interferes with pancreatic lipase, which results in insufficient absorption of dietary fat. Insulinotropin is a glucagon-like hormone that prevents obesity by delaying stomach emptying. Bta-243 stimulates adipocyte beta-adrenergic receptors leading to increased fatty acid burning. Troglitazone is a synthetic hormone that sends a signal to muscle cells and uses fat instead of sugar for energy. Cytokine regulators alter the activity of hormone-like cytokines and alter cell-cell communication, resulting in weight loss. Hydroxycitric acid acts as an inhibitor of the enzyme citrate triase, which subsequently slows the synthesis of fatty acids and increases the rate at which the fatty acids are burned.

The average amount of body fat in US men is 22-25%, and in US women, the average amount of fat is 33-35%. These values are far above the optimal values (these are 15-19% for 20-29 year old men and 19-23% for 20-29 year old women). The corresponding values for 40-49 years are 17-21% and 21-25%, respectively, and for 60 years, the corresponding values are 19-23% and 23-27%, respectively. In highly overweight individuals, adipose tissue can constitute up to 70% of body weight.
The remaining% of the biological composition corresponds to fat free body weight. Fat free body weight includes muscles, living organs, bones, connective and other non-adipose tissues in the body, and most of the body water. The metabolic rate of the living body is directly proportional to the amount of fat-free body weight. Therefore, considering fat free weight is important for weight loss strategies.
The weight control means does not consider the importance of maintaining or increasing fat free body weight in the process of weight loss. In fact, regimens to reduce body fat often contribute to fat-free weight catabolism. Increased fat-free body weight not only regulates body metabolism and helps to lose weight, but also maintains the weight loss achieved. On the other hand, reduced fat-free weight slows down the body metabolism and creates difficulties in maintaining a proper and healthy weight. Thus, the ideal weight management approach should be to reduce weight to an acceptable level by restoring the optimal proportion of fat to fat-free weight. A weight loss regimen could be used for the general purpose of improving an individual's overall health by maintaining or increasing lean body weight while simultaneously reducing body fat.
Maintaining or increasing lean body weight (eg, skeletal muscle) is an important consideration in weight loss strategies. Because fatless body weight determines the rate of metabolism and the body's fever response to food, food-induced heat generation and metabolic rate, in turn, control body weight by increasing catabolism of body fat. This is because heat generation is preferentially supported by body fat stores and fatty acids derived from food. In addition, fast heat generation contributes to the preferential accumulation of fat-free body weight, as more food is absorbed and not adipose tissue.

One of the important ingredients in maintaining fat-free weight maintenance and preventing loss of biological composition is having a sufficient supply of endogenous testosterone, estrogen and human growth hormone. Testosterone and estrogens are the end products of several hormonal reactions in the somatotroph axis. For example, the somatotrophic axis for testosterone begins with gonadotropin releasing hormone (GnRH) secreted by the hypothalamus and controls the pulsatile secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) by the anterior pituitary gland. Luteinizing hormone regulates testosterone production and secretion by testicular Leydig cells, and FSH stimulates spermatogenesis.
Aging is associated with events that were thought to result in decreased somatotrophic axis, decreased production of estrogen and testosterone, increased harmful forms of hormones, e.g., dihydrotestosterone (DHT)-many catabolic sequelae of normal aging. ing. For example, bone mass loss with age (osteoporosis) is an example of fat-free weight loss, leading to degradation of biological composition in elderly individuals. Decreased GH (IGF-1, exemplified by but not limited to growth hormone) secretion is a change in age, metabolism, bone, muscle, cardiovascular system, central nervous system, immune system and well-being Can be partially explained. Because of the clinical similarity between aging and growth hormone deficiency, the relative GH deficiency of elderly subjects was postulated as one important factor contributing to their fragility.
Another example of a detrimental change in biological composition is hypogonadism. Men with reduced sexual function and low levels of serum testosterone have negative changes in biological composition, such as decreased muscle mass, increased proportion of body fat, and changes in body fat distribution. Independent of decreased sexual function, reduced fatless body weight, increased body fat and total body weight contribute to hormonal imbalance and low levels of serum testosterone. In addition, testosterone and estrogen serum levels are negatively correlated with serum cortisol levels, especially in overweight and obese individuals.

  The present invention is a member of the mint family (Fam. Lamiaceae), Coleus forskohlii, Briq. (Syn. C. barbatus Benth., Plectranthus barbatus, Andr. Diterpene forskolin and its natural derivatives isoforskolin and 7-deacetylforskolin obtained from the roots of Forskoli and Willd., P. comosus Willemse.). Forskolin has been reported to have antihypertensive activity, positive inotropic action and suppress platelet aggregation (de Souza et al., 1983; Ammon and Muller, 1985). The mechanism of action of forskolin is related to its stimulatory action on adenylate cyclase, which increases intracellular levels of cyclic adenosine monophosphate (cAMP), which mediates several biological responses (De Souza et al., 1983; Ammon and Muller, 1985; Dohadwalla, 1985; Seamon, 1985). Numerous pharmacological studies on the various effects of forskolin have been conducted in laboratory animals and humans after treatment of local, intravenous (iv), intraarterial, intraperitoneal (ip), intratracheal (it), and inhalation. It was. Physiological effects of cAMP (these were also demonstrated by forskolin) include suppression of platelet aggregation, increased adipocyte lipolysis in vitro, positive inotropic effects on heart muscle, enhanced insulin secretion by the pancreas, Increased secretion of thyroid hormone, increased steroidogenesis by the adrenal gland, increased corticotropin (ACTH) release by the pituitary gland, and reduced intraocular pressure in topical applications (Dubey et al., 1981; Caprioli and Sears, 1983; Malaisse and Malaisse-Lagae, 1984; Ammon and Muller, 1985; Dohadwalla, 1985; Potter et al., 1985). The secretory capacity of aged rat Leydig cells was found to be lower than that of young rat Leydig cells with and without forskolin stimulation (Deng et al., 2005). Forskolin also induces bronchodilation in guinea pigs (1 mL dose / kg body weight and 30 μg it administered over 10 minutes) and asthmatic patients (inhaled 1-10 mg of forskolin as a dry powder) without causing significant side effects Have been reported (Lichey et al., 1984; Kreutner et al., 1985; Bauer et al., 1993). Both isoforskolin and forskolin have an inhibitory effect on ocular hypertension in rabbits (Li et al., 2000). 1-acetyl-7-deacetylforskolin forskolin activated adenylyl cyclase in cultured human endothelial cells, whereas 1-acetyl-7-deacetylforskolin was not activated (Sasaki et al., 1995). 7-deacetylforskolin was prepared to provide a water-soluble derivative of the diterpenoid forskolin with potent cardiac action (Khandelwal et al., 1988). Forskolin, rather than isoforskolin or 7-deacetylforskolin, has also been shown to increase fat-free weight in overweight and obese human subjects (Majeed, Badmaev, Rajendran US patent (1998)) ).

The present invention first demonstrates that oral administration of forskolin to an overweight and obese young man increases serum testosterone levels.
The present invention relates to a composition for physiologically increasing serum levels of testosterone, estrogen or HGH comprising forskolin, isoforskolin or 7-deacetylforskolin. The present invention also relates to the physiological increase in serum levels of testosterone, estrogen and HGH by administering forskolin, isoforskolin or 7-deacetylforskolin extracted from Coleus forskohlii or related species to humans. It relates to a characteristic method.
In addition, the present invention provides a safe, physiological, and increased serum testosterone, estrogen and HGH in the prevention of biological composition degradation expected in the aging process, among those with hormonal deficiencies or those likely to be overweight and obese. Related to the method. A method for improving mental and physical stamina is disclosed. Also disclosed are compositions suitable for the present invention comprising from about 1% to less than about 95% forskolin and / or derivatives thereof in combination with at least one physiologically acceptable carrier or excipient.
Further disclosed are not only methods for preparing forskolin and derivatives thereof from Coleus forskori plants, but also compositions of forskolin and derivatives thereof prepared by the method.

Forskolin, isoforskolin or 7-deacetylforskolin extracted from Coleus forskohlii or related species is preferably used.
Preferably, the composition is in a form that is administered at a daily dose of about 10 mg to about 100 mg. Further, it is preferred that the composition comprises about 1% to about 100% forskolin. A preferred amount is about 5% to about 20%, more preferably about 8% to about 15%, most preferably about 10% forskolin.
The compositions of the present invention may be used to prevent a subject's biological composition from deteriorating and to improve mental and physical stamina.
Yet another subject of the present invention is
(a) Obtained forskolin, isoforskolin and 7-diacetforskolin extracts of Coleus forskori plant by supercritical extraction method,
(b) obtaining isoforskolin and 7-diacetforskolin extracted from Coleus forskori plant with water and organic solvent,
(c) a forskolin composition having a predetermined forskolin content by combining the amount of forskolin obtained in steps (a) and / or (b) with at least one physiologically acceptable carrier or excipient. It is a method for preparing a forskolin composition from a forskolin extract of a Coleus forskori plant, characterized in that the forskolin composition is prepared by producing
In addition, the present invention includes not only the composition prepared from the above method, but also a method of using the composition thus prepared.
Furthermore, the present invention finely pulverizes dried Coleus root, extracts with a solvent selected from a mixture of water and alcohol, C1-C4 alcohol, methylene dichloride, toluene, or hexane, concentrates the extract, heptane, pentane Discloses a commercial process for the production of isoforskolin comprising precipitation with a non-polar solvent selected from hexane, filtration, back-extraction with a mixture of water and alcohol and crystallization in alcohol.

Furthermore, the present invention comprises pulverizing dried Coleus roots, extracting the root powder with supercritical carbon dioxide and co-solvent ethanol at a temperature of 45 ° C. to 55 ° C. and a pressure of 300 bar, and crystallizing in ethanol. A method for the commercial production of isoforskolin is disclosed.
Furthermore, the present invention pulverizes dried Coleus roots, the root powder is extracted with supercritical carbon dioxide and cosolvent ethanol at a temperature of 45 ° C. to 55 ° C. and a pressure of 300 bar, hydrolyzed with lipase enzyme, A process for the commercial production of 7-deacetylforskolin, comprising crystallization with
In addition, the present invention discloses a commercial supercritical or subcritical extraction method of dried Coleus root to remove essential oils.
In addition, the present invention discloses a commercial process with supercritical carbon dioxide containing various amounts of ethanol present in the supercritical gas. The pressure ranged from 110 bar to 400 bar below the critical temperature. Ethanol was used as a solvent improver. A wide range of compositions in which the amount of ethanol was varied from 0.01 mol% to 10 mol% was used.

Example 1. Hormone adaptations associated with forskolin consumption in men The randomized, double-blind clinical study of this invention is 12 weeks in 30 overweight and obese young men (forskolin, n = 15; placebo, n = 15) Ingestion of 250 mg of 10% forskolin bid (standardized extract of Cereus forskori root) was studied. Effects of forskolin on biocomposition, testosterone, metabolic rate, and blood pressure in men with overweight and obesity (BMI> 26 kg / m (2)). Forskolin has been shown to induce beneficial changes in biological composition by significantly reducing body fat% (BF%) and fat mass (FM) as measured by DXA compared with placebo (p <0.05) . Furthermore, forskolin administration resulted in a significant increase in bone mass for the 12 week study compared to placebo (p <0.05). There was a trend for a significant increase in fat free body weight in the forskolin group compared to placebo (p = 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared to the placebo group (p <0.05). See Table 1 and Table 2.
Biocomposition and forskolin consumption, Godard, Johnon, and Richmond

Actual changes and% changes from previous and subsequent measurements are also included. All values are expressed as mean-SD.
Significant differences between groups over time * and significant differences within groups † (p <0.05)
Biocomposition and forskolin consumption, Godard, Johnon, and Richmond

Actual changes and% changes from previous and subsequent measurements are also included. All values are expressed as mean-SD.
* Significant difference between groups (p <0.05)
Reference Example 1 Clinical effect of oral forskolin administration in overweight women In a double-blind and randomized manner, 23 women were given forskolin (10% Coleus forskori extract 250 mg twice a day for 12 weeks) N = 7) or placebo (n = 12) supplemented their diet. Biological composition (DEXA), body weight, and psychometric instruments were obtained at weeks 0, 4, 8, and 12 of supplementation. No significant difference was observed with caloric intake or macronutrient intake. Forskolin tended to reduce weight gain (-0.7 ± 1.8, 1.0 ± 2.5 kg, p = 0.10) and scanned mass gain (-0.2 ± 1.3, 1.7 ± 2.9 kg, p = 0.08) . Subjects in the Forskolin group tended to report less fatigue (p = 0.07), hunger (p = 0.02), and fullness (p = 0.04). These results suggest that forskolin can help reduce weight gain in overweight women without apparently significant clinical side effects.

Reference Example 2 Comparative effects of isoforskolin, 7-deacetylforskolin and forskolin extracts and their compositions on animal models of obesity for a total of 84 animals divided into groups of 12 animals, 25-30 This was done in Swiss albino mice (Huffkin Society, Mumbai, India) at the age of the week. Treated mice were fed a diet rich in carbohydrates and fat. The diet resulted in a reliable weight gain over the control. Drug treatment was initiated only when the difference in body weight between control and treated mice exceeded 10 g. Mice in each group received isoforskolin extract, 10% 7-deacetylforskolin extract and forskolin extract (1 mg / ml) by gastric intubation twice a day for a period of 6 weeks. A daily constant dose of was given. At the end of 6 weeks, 6 mice per group were asleep after weighing and flab measurements. Blood was drawn by cardiac puncture and immediately centrifuged to separate plasma and analyzed for cholesterol levels, triglyceride levels, glucose levels, thyroxine T3, T4 and TSH levels.
Abdominal fat and thyroid were fixed for histopathology. Separate samples of adipose tissue were collected and analyzed for total lipid content. The remaining mice from each group were continued on the same diet as given during the first 6 weeks of treatment. This group was managed in this manner for an additional 6 weeks, at which time non-invasive parameters such as body weight and flav were assessed once again.
Results: Both control and treated mice withstood gastric intubation during the 6 week treatment period. Extract 10% isoforskolin, 10% 7-deacetoforskolin and 10% forskolin were better tolerated by the population of mice. At the end of 6 weeks, randomly selected mice from each group were put to sleep, incised (a) excised adipose tissue and thyroid for histopathology, (b) examined general dissection, organs For example, some changes in the intestine, heart, lungs, liver, pancreas, kidneys, genitals, etc. were recorded. It was observed that none of the animals showed abnormal anatomical features.
Abdominal fat shows interesting features in different groups. For example, control group mice on placebo or drug treatment showed good amounts of abdominal fat distribution in the leaflets on both sides of the adipose tissue. Animals from the obese placebo group had a significant amount of abdominal fat and bilateral adipose tissue lobes extended more than 1/3 of the abdominal cavity. On the other hand, animals in the obese group treated with 10% isoforskolin, 10% 7-deacetylforskolin and 10% forskolin actually excreted abdominal fat, which is 10% forskolin and It was more prominent in the 10% isoforskolin group. In these groups of animals, there was a significant loss of fat attachment not only peritoneal fat but also closely related to the uterus. Adipose tissue close to the kidney and ovary was apparently appropriate, but less than the obese group on placebo treatment.

Table 3. Effect of treatment on weekly recordings of body weight of experimental mice

** Significant reduction in weight by one-way analysis of variance (ANOVA) Extract 1: Extract containing 10% forskolin 2: Extract containing 10% 7-deacetoforskolin 3: 10% isofors Containing Choline As seen in the table above, there is a significant reduction in total body weight in all treatment groups, with the% change being the largest in the Forskolin group.

Table 4. Effect of treatment on weekly recordings of abdominal flabs in experimental mice

** indicates statistical significance in one-way analysis of variance (ANOVA) Extract 1: Extract containing 10% forskolin 2: Extract containing 10% 7-deacetoforskolin 3: 10% Containing isoforskolin As seen in the table above, there is a significant reduction in abdominal flav in all treatment groups, with the percent change being the largest in the forskolin group.

Table 5 Effect of treatment on adipose tissue and fat content of experimental mice after 6 weeks of treatment

Extract 1: Extract containing 10% forskolin 2: Extract containing 10% 7-deacetoforskolin 3: Reference example containing 10% isoforskolin In vitro preclinical and clinical toxicological studies of forskolin of the present invention (standardized 10% extract of Coleus forskori root) Acute toxicity study In acute toxicity studies, male and female Wistar rats were 2,000 / kg body weight A single oral dose of mg forskolin was given (Graver, 2000). There was no death. However, diarrhea, dirt on the anogenital area, and wetness of the mouth and anogenital area have been reported. Histopathological lesions were not observed after autopsy. LD ₅₀ was reported to be> 2,000 mg / kg body weight. Previous studies by de Sousa et al. (1983) showed that forskolin acute LD ₅₀ was 3,100 mg and 2,550 mg / kg by oral administration in mice and rats, respectively, and 105 mg / kg and 92 mg when administered intraperitoneally. / kg.
Subchronic Toxicity Studies in Rats Five SD rats / sex groups were dosed with 0, 100, 300, or 1,000 mg C. forskori 10% extract per kg body weight per day by gavage over a period of 28 days (Bhide, 2004). Possible when two additional groups of rats (5 / sex / group) receive the extract at a dose of 0 or 1,000 mg / kg body weight per day for 28 days, followed by observation over a 14-day recovery period The reversibility of the effect was evaluated. Daily observations of clinical signs and mortality and weekly measurements of body weight and food consumption were performed. An eye examination was performed at the beginning and end of the dosing period and at the end of the recovery period. Hematological, biochemical and urine parameters were evaluated at the end of the dosing and recovery periods. All animals were necropsied and organ histopathological examination was performed. No toxicological effects were observed on any of the measured parameters at any dose. The non-observed level of action (NOEL) of the 10% extract of C. forskori was considered to be the highest dose tested, 1,000 mg / kg body weight per day. This NOEL represents an appropriately high dose (120 times) of the intended human dose (approximately 8.3 mg / kg body weight per day).

Mutagenicity studies The present invention relates to Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and Escherichia coli strains at doses up to 5,000 μg / plate, both in the presence and absence of metabolic activation. It was reported not to be mutagenic in a bacterial backmutation assay with an independent repeat assay using WP2 uvrA (Wagner and Klug, 2001).
Clinical studies Several clinical studies examining the efficacy of the present invention with respect to weight loss were conducted and are summarized in Table 1. It is important to note that safety parameters were also monitored, but efficacy was the main purpose of these studies. Clinically significant interactions are seen in weekly reports of metabolic markers, blood lipids, muscle and liver enzymes, electrolytes, red blood cells, white blood cells, hormones (insulin, TSH, T3, and T4), heart rate, blood pressure, or side effects I couldn't.

^a Thyroid-stimulating hormone
^b Triiodothyronine
^c thyroxine
^d high density lipoprotein
^e serum glutamic - oxaloacetic transaminase
^f Serum glutamate-pyruvate transaminase
^g Low Density Lipoprotein Preparation Example 1: Method for Commercial Production of Isoforskolin The present invention also includes a method for preparing an isoforskolin composition from a forskolin extract of Coleus forskolin plants. The method involves extracting the finely ground roots of the plant with water, a chlorinated solvent such as C1-C4 alcohol, MDC, a solvent selected from toluene or hexane, or the solvent is a mixture of water and alcohol. Of these, the preferred extraction medium is toluene. The concentrated toluene extract is precipitated with a more apolar solvent of type heptane, pentane, hexane, filtered, and the filtrate is back extracted with a mixture of aqueous alcohols in a ratio of 10:90 to 90:10 to give the desired molecule Isoforskolin is obtained and further crystallized with alcohol to obtain the desired purity.

Preparative Example 2: Commercial Method for Making 7-Deacetylforskolin The whole extract from the above examples is dissolved in a solvent medium (including but not limited to alcohol, toluene or hexane) and stirred for 12 hours Under treatment at 37 ° C. with fixed enzyme lipase at a concentration of 0.1-10%, preferably 1-5%. Once the reaction is complete, the material is back extracted with a mixture of aqueous alcohols in a ratio of 10:90 to 90:10 to give the desired molecule 7-deacetylforskolin, which is further crystallized with alcohol to give the desired Get purity.
Preparative Example 3: Commercial Method for Production of Isoforskolin and 7-Deacetylforskolin by Carbon Dioxide Extraction Supercritical fluid using carbon dioxide with or without an entrainer such as ethanol, acetone or ethyl acetate The extraction is described to extract isoforskolin and 7-deacetylforskolin from the roots of Coleus plants. The extract is obtained at a temperature in the range from 25 ° C. to 120 ° C., preferably 45 ° C.-55 ° C., using a co-solvent, preferably 5% -80% ethanol, more preferably 30-100% ethanol, Or, without use, the extraction fluid pressure was maintained at 100-300 bar, preferably 300 bar, at a carbon dioxide flow rate of 1-4 kg / hour, preferably 2 kg / hour, for 1-5 hours, preferably 3 hours. The resulting extract is hydrolyzed with a lipase enzyme in a liquid medium and crystallized from ethanol to obtain 7-deacetylforskolin of the desired purity.

Preparation Example 4: Commercial production method of forskolin, isoforskolin, 7-deacetylforskolin, 1-deoxyforskolin, 9-deoxyforskolin and 1,9-dideoxyforskolin by carbon dioxide extraction Coleus forskolin Roots and stems are a rich source of forskolin, isoforskolin and 7-deacetylforskolin. In addition, minor components such as 1-deoxyforskolin, 9-deoxyforskolin and 1,9-dideoxyforskolin are also present with the oil.
The supercritical method is based on differential extraction of these components depending on polarity. The polarity of carbon dioxide can be changed by changing some important parameters in the extraction process. Carbon dioxide has a critical pressure of 73.8 bar and a critical temperature of 31.06 ° C. This allows for the wide variation possible in the selection of experimental parameters. The first parameter is pressure. Changes in the pressure of the extraction gas change the properties of the extraction solvent. The second parameter is the temperature range. A third important variable in changing the polarity of supercritical carbon dioxide is the addition of a co-solvent. Several co-solvents are possible and were used in this work. Solvent improver comprises about 0.01 mol% to 10.0 mol%, MeOH, EtOH, PrOH, iso-PrOH, BuOH, benzyl alcohol, acetone, acetophenone, N-methyl-2-pyrrolidone, methyl ethyl ketone, DMSO, DMF, Solvents such as ethylene glycol and acetonitrile were included. The use of ethanol is particularly preferred and preferred in this work. In addition to the gas flow rate, the particle size of the plant material affects the extraction efficiency. The co-solvent has the greatest effect on the ability to extract supercritical carbon dioxide.
Plant roots or stem parts were thoroughly cleaned with water and then well dried without moisture by drying in sunlight or a closed oven.

In practice, the dried part of the plant is first extracted with supercritical or subcritical carbon dioxide to remove the oil present therein. The plant part obtained had a very powdery appearance. The amount of ethanol present in the supercritical gas is changed and extracted again with supercritical carbon dioxide. The pressure ranged from 110 bar to 400 bar below the critical temperature. Ethanol was used as a solvent improver. A wide range of compositions was used in which the amount of ethanol was varied from 0.01 mol% to 10 mol%.
Forskolin, isoforskolin, 7-deacetylforskolin, 1-deoxyforskolin, 9-deoxyforskolin and 1,9-dideoxyforskolin compositions prepared by the above method are stable. The stability of the composition was measured by exposing the composition to accelerated storage conditions as well as normal ambient storage conditions. During this study, its quality was tested for stability indicator parameters. For that study, the extract is stable for a period of more than 5 years when it is stored under normal ambient storage conditions.
The present invention includes the product (ie, composition) produced by this method. The product will usually contain from about 1% to about 40% forskolin, but up to 100% pure forskolin is possible. A preferred amount is from about 5% to about 20%, more preferably from about 8% to about 15%, most preferably about 10% forskolin.
Reasonable modifications of the invention disclosed herein are well within the scope of those skilled in the art and are intended to be within the scope of the present invention. It is intended that the scope of the invention be limited not by the specific examples presented herein, but rather should be construed according to the claims that follow.

Claims (10)

  A composition for physiologically increasing the serum level of testosterone, estrogen or HGH, characterized in that it comprises forskolin, isoforskolin or 7-deacetylforskolin.   The composition of claim 1 used to physiologically increase target tissue levels of testosterone, estrogen or HGH.   The composition according to claim 1 or 2, comprising 1-deoxyforskolin, 9-deoxyforskolin and 1,9-dideoxyforskolin.   Finely pulverize the dried Coleus root and extract with a solvent selected from a mixture of water and alcohol, C1-C4 alcohol, methylene dichloride, toluene, or hexane, concentrate the extract, and select from heptane, pentane, hexane. A commercial process for the production of isoforskolin comprising precipitation with a non-polar solvent, filtration, back extraction with a mixture of water and alcohol and crystallization in alcohol.   Isoforskolin commercial consisting of milling dried Coleus roots, extracting the root powder with supercritical carbon dioxide and co-solvent ethanol at a temperature of 45 ° C to 55 ° C and pressure of 300 bar and crystallizing in ethanol Manufacturing method.   Grinding dried Coleus roots, extracting the root powder with supercritical carbon dioxide and co-solvent ethanol at a temperature of 45-55 ° C and a pressure of 300 bar, hydrolyzing with lipase enzyme and crystallizing in ethanol A process for the commercial production of 7-deacetylforskolin, comprising:   A commercial supercritical or subcritical extraction method of dried Coleus roots to remove essential oils.   Commercial process with supercritical carbon dioxide containing various amounts of ethanol present in supercritical gas under pressures below the critical temperature ranging from 110 bar to 400 bar.   4. The composition according to any one of claims 1 to 3, wherein the composition is in a form that is administered in a daily dose of about 10 mg to about 100 mg.   4. A composition according to any one of claims 1 to 3, comprising from about 1% to about 100% forskolin.