WO2008140178A1

WO2008140178A1 - Composition comprising an extract of processed ginseng for preventing and treating obesity and the use thereof

Info

Publication number: WO2008140178A1
Application number: PCT/KR2008/001076
Authority: WO
Inventors: Gwi Seo Hwang; Sung Jae Jung; Han Shin Lee; Hyun Young Kim; Bok Deuk Kim; Jeong Hill Park; Hyang Jin Lee
Original assignee: Ginseng Science Inc
Current assignee: Ginseng Science Inc
Priority date: 2007-05-09
Filing date: 2008-02-25
Publication date: 2008-11-20
Anticipated expiration: 2009-11-09
Also published as: KR20080099362A; KR100877604B1

Abstract

The present invention relates to compositions comprising an inventive extract of processed Panax genus of the present invention and the inventive extract reduced body weight, the level of total cholesterol, LDL and triglyceride in blood, increased the level of blood HDL as well as inhibited the lipid accumulation of Caenorhabditis elegans (C. elegans). Therefore, it can be used as the therapeutics or health food for treating and preventing obesity without adverse action.

Description

COMPOSITION COMPRISING AN EXTRACT OF PROCESSED GINSENG FOR PREVENTING AND TREATING OBESITY AND

THE USE THEREOF

Technical Field

[1] The present invention relates to a pharmaceutical composition and functional health food comprising an extract of processed Panax genus plant as an active ingredient for preventing and treating obesity and the use thereof.

[2]

Background Art

[3] Obesity is one of the most disadvantageous nutritional problems in industrial society.

One third of the people, 20% of children are reported to be suffering from obesity and more than 70% patients suffering from type 2 diabetes mellitus are obese, which give rise to various adult diseases, i.e., the risk of high blood pressure, high cholesterol and certain kinds of cancer according to US statistics.

[4] Although it is well known that obese people frequently are accompanied by carbohydrate metabolism disorder and non-insulin dependent diabetes mellitus, there still remains a point of dispute on the relationship between obesity and diabetes mellitus. The person suffering with severe obesity does not always have diabetes, therefore obesity itself is not sufficient to give rise to non-insulin dependent diabetes mellitus, but genetic factors of diabetes or environment factors altogether are regarded as main factors of diabetes mellitus. Although non-insulin dependent diabetes mellitus are more frequent among obese people than normal people, the occurrence of non-insulin dependent diabetes mellitus are closely correlated with the obese carrier in the past and the duration of obese time, which suggests that obesity is a risk factor of non-insulin dependent diabetes mellitus.

[5] Recently, it has been reported that not only obesity but also the distribution of the adipocyte cell is closely correlated with the obesity-involved diseases, in particular, the abdominal obesity.

[6] Through previous reports, obesity precedes abnormal glucose tolerance and non- insulin dependant diabetes mellitus and obese people with abnormal glucose tolerance are in high risk group of non-insulin dependant diabetes mellitus (Carey VJ. et al., Body fat distribution and risk of non-insulin dependent diabetes mellitus in women, The nurses' health study, Am. J. Epidemiol, 145, pp.614-619, 1997).

[7] The mechanism of the progress from obesity to diabetes mellitus has not been confirmed yet up to date, however the increase of insulin resistance plays important role in the progress. From epidemiology observations, Felberue et al. classified obese people into four categories, i.e., normal glucose tolerance, impaired glucose tolerance, diabetes mellitus with hyperinsulinemia and diabetes with hypoinsulinemia, according to the response to glucose tolerance test and insulin, and suggested the process from obesity to diabetes mellitus is similar (Golay A. et al., Obesity and NIDDMP, the retrograde regulation concept, Diabetes Rev, 5, pp.69-82, 1997).

[8] In obesity, although the carbohydrate metabolism at glucose tolerance state shows normal, the secreting response of insulin is higher than normal, which shows typical aspect of insulin resistance and occurs at early stages of obesity, i.e., one of abnormal physiological conditions of obesity and obese non-insulin dependant diabetes mellitus. Various hypotheses regarding on certain mechanism of increased insulin response has been suggested, however it has not been fully identified yet. Namely, it has been regarded that the decreased function of various factors such as insulin receptor, glucose transporter, the enzymes involved in glycogen synthesis, glucose oxidation and etc. are just secondary phenomena of obesity although observed during obesity (Colay A. et al. , Obesity and NIDDMP, the retrograde regulation concept, Diabetes Rev, 5, pp.69-82, 1997).

[9] Considering circunstantial evidence, adipocyte cell is thought to be correlated with the occurrence of insulin resistance, in other words, the factors secreting from adipocyte cell or metabolic messenger are considered to inhibit the action of insulin within the liver and muscle.

[10] Among these factors, the most recognized one is free fatty acid released by the hydrolysis from triglyceride stored in fat tissue. Besides the fatty acid, TNF-α and leptin secreted from adipocyte cell are suggested as a factors of insulin resistance in obesity recently (Hotamisligil GS. et al., Tumor necrosis factor-α, a key component of the obesity-diabetes link, Diabetes, 43, pp.1271-1278, 1994; Cohen B., Novick D., Rubinstein M., Modulation of insulin activities by leptin, Science, 274. pp.1185-1188, 1996).

[11] In obesity, lipid is the major consumed component in the process of energy metabolism and both lipid synthesis and lipid degradation were increased. The increase of lipid degradation and utilization of free fatty acid thereby are characteristic phenomena of obesity, in particular, abdominal obesity and showed close correlation between lipid volune and lipid oxidation, which are regarded as the main cause of increased free fatty acid and lipid oxidation in the serum. The increase of lipid oxidation is observed in the early stage of obesity, even after fasting or glucose tolerance.

[12] Recently, the number of obese people has been increased due to westernized food life and elevated cultural level. Obesity is becoming the cause of the generation and deterioration of high blood pressure, arteriosclerosis, fatty liver, diabetes mellitus and other various diseases. Therefore, it is essential to prevent obesity or to reduce body fat and to alleviate the lipid metabolism to harmonize the body metabolism after obesity has occurred.

[13] In particular, the deficiency of estrogen caused by decreased function of ovary has been primary factor of the obesity of menopausal women and estrogen inhibits the activity of lipoprotein lipase (LPL) in the adipocyte cell and inhibits the lipid accumulation (Hamosh M. et al., J. Clin. Invest.,55., pp.1132- 1135, 1975). The deficiency of estrogen increases the activity of lipoprotein lipase enzyme, which causes to accumulate the lipid in the adipocyte cell resulting in increased body weight. However, lipid accumulation can be inhibited by administration of estradiol (E2) (Geary, N. et al. , J. Physiol. Regul. Intergr. Comp. Physiol.,2&l, pp.1293- 1294, 2001). The action of E2 induces the release of a hormone sensitive lipase (Palin S. L. et al, Metabolism, 52, pp.383-388, 2003) or increases the action of fatty acid β-oxidation of epinephrine, resulting in inhibiting lipid accumulation (Ackerman G.E. et al., Endocrinology.109. pp.2084-2088, 1981), to inhibit the adipocyte cell production from bone stromal cell (Heim M. et al., Endocrinology, 145, pp.848-859, 2004; Okazaki, R. et al., Endocrinology, 143, pp.2349-2356, 2002; Hαmma, H. et al., J. Biol. Chem..215. pp.5793-5796, 2000) and to increase hepatic lipid metabolism resulting in stimulating the absorption and degradation of cholesterol (Hewitt K.N., et al., Endocrinology, 145. pp.1842- 1848, 2004).

[14] Meanwhile, the number of patients suffering from abnormal lipid metabolism, arteriosclerosis and circulatory system disorder caused thereby has been increased in estrogen deficient patients (Mendelsohn, M.E. et al, Circ. Res., 87, pp.956-960, 2000; Mendelsohn, M.E. et al, N. Engl. J. Med., 340, pp.1801-1811, 1999). The result is consistent with the reports, for example, estrogen inhibits the overexpression of vascular cell adhesion molecule- 1 (VCAM-I), E-selectin and intercellular adhesion molecule- 1 (EAM-I) in the vascular endothelial cell (Caulin-Glaser, T. et al, J. Clin. Invest,9&., pp.36-42, 1996); inhibits the interaction between monocyte cell and vascular endothelial cell (Nathan, L. et al, Circ, 85, pp.377-385, 1999); decreases the level of total cholesterol and LDL (Hough, J.L. et al., Arteriosclerosis, 6, pp.57-63, 1986); reacts with HDL to form cholesterol esterification (Banka, CL. et al., Harwood Academic Publishers, Amsterdam, pp.91-106, 1998; Abplanalp, W. et al., J. Endocrinol., 142. pp.79-83, 2000); inhibits the reproduction of oxLDL in a macrophage cell (Sack, M.N. et al., Lancet., 343, pp.269-270, 1994); and simultaneously, inhibits the expression of vascular thickening factor of a macrophage resulting in preventing various disorders of circulatory system (Shanker, G., et al., Lymphokine Cytokine Res., 13, pp.1-7, 1994; Shanker, G. et al., Life Sci.,56, pp.499-507, 1995).

[15] As described above, obesity due to the deficiency of estrogen in menopausal women induces high cholesterol, arteriosclerosis and etc. caused by abnormal lipid metabolism, cardiovascular disease and various metabolic diseases.

[16] Accordingly, it is critical to inhibit the adipocyte cell function and to lose body weight for the prevention and treatment of the above^nentioned adult diseases.

[17] It has been known that there are many genus of Panax genus plants belonged to

Araliaceae, for example, Panax ginseng distributed or cultivated in far-eastern Asia region, Panax quinquefolia in America and Canada, Panax Notoginseng in China, Panax trifolia in eastern region of north America, Panax vietnamensis in Vietnam, Panax elegatior, Panax wangianus, Panax bipinratifidus and etc.

[18] The most important ingredient in the plant belonged to Panax genus is dammarane saponin having 1-4 numbers of saccharides, particularly Korean ginseng comprises high amount of ginsenosides, such as ginsenoside RbI, Rb2, Rc, Rd, RgI, Re and etc. These saponins show various potency and pharmacological activities according to their structure.

[19] Recently, there have been several attempts to strengthen pharmacological effects among ginseng by modifying the method of ginseng processing, for example, Park et al. developed new methods for preparing a processed ginseng under specific high temperature and high pressure as disclosed in Korean Patent Registration No. 192678 and US Patent No. 5776460, which changes main ginseng saponins such as ginsenosides RbI, Rb2, Rc and Rd, into new saponin metabolites such as ginsenosides Rg3, Rg5 and RkI showing new and more potent pharmacological effects, for examples, anti- oxidative activity, anti-cancer activity and alleviating activity of blood circulation etc (Kim WY et al, J. Nat. Prod., 63(12), pp.1702- 1704 ; Kwon SH et al, J. Chromatogr A., 921(2), pp.335-339, 2001). Especially, the pharmacological effect of ginsenosides Rg3, Rg5 and RkI has been known to be strongest among these and when produced through said new processing method, ginsenosides are formed by the process that a part of sugar moiety in dammarane glycoside, i.e., ginsenosides RbI, Rb2, Rc and Rd, was cleaved and continuously subjected to dehydration reaction at the position of C- 20. Accordingly, these new metabolites can be produced in the root, stem or leaf of any Panax genus plants such as Panax ginseng, Panax quinquefolia, Panax no- to ginseng, Panax japonica, Panax trifolia, Panax pseudoginseng, Panax vietnamensis, Panax elegatior, Panax wangianus and Panax bipinratifidus which contains dammarane glycoside through the processing method of Park et al. (Korean Patent Registration No. 192678 and US Patent No. 5776460).

[20]

[21] However, there has been not reported or disclosed about the preventing or treating activity of the processed Panax genus plant extract prepared by above-described methods disclosed in US Patent No. 5776460 against obesity in any of the above cited literatures, the disclosures of which are incorporated herein by reference.

[22] The inventors of the present invention have investigated an inhibiting effect of an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) over 1.0 against obesity through already well-known screening tests, i.e., the determination test on the change of body weight, the level of total cholesterol, LDL and triglyceride in blood using estrogen- deficient obesity rat model caused by ovariectomy and etc., and finally completed the present invention by confirming that the inventive extract reduces body weight, the level of total cholesterol, LDL and triglyceride within blood, increases the level of blood HDL as well as inhibits the lipid accunulation of Caenorhabditis elegans (C. elegans).

[23]

[24] These and other objects of the present invention will become apparent from the detailed disclosure of the present invention provided hereinafter.

[25]

Disclosure of Invention Technical Problem

[26] The present invention provides a pharmaceutical composition comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, as an active ingredient in an effective amount to treat and prevent obesity.

[27] The present invention also provides a use of an extract of processed ginseng so as to make a ratio of gnsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, for the manufacture of pharmaceutical composition to treat and prevent obesity.

[28] The present invention also provides a health functional food comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, for the prevention or alleviation of obesity.

[29]

Technical Solution

[30] Accordingly, it is an object of the present invention to provide a pharmaceutical composition comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, as an active ingredient in an effective amount to treat and prevent obesity.

[31]

[32] The present invention to provide a pharmaceutical composition comprising an extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, Ci-C₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, as an active ingredient and pharmaceutically acceptable carrier, diluents or adjuvants to treat and prevent obesity.

[33]

[34] The present invention provides a use of extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0 as an active ingredientfor the manufacture of therapeutic agent for the treatment and prevention of obesity.

[35] The present invention provides a use of extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C 1-C₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, as an active ingredientfor the manufacture of therapeutic agent for the treatment and prevention of obesity.

[36]

[37] It is an object of the present invention to provide a method of treating or preventing obesity in a mammal comprising administering an effective amount of an extractof processed ginseng so as to make a ratio of gmsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, together with a pharmaceutically acceptable carrier thereof to said mammal in need thereof.

[38] It is an object of the present invention to provide a method of treating or preventing obesity in a mammal comprising administering an effective amount of an extractof processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C₁-C₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, together with a pharmaceutically acceptable carrier thereof to said mammal in need thereof.

[39] The term "extract of processed ginseng" disclosed herein means "an extract of Panax genus plant", which specifically comprises the extract prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C _rC₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract of the present invention.

[40] The term Panax genus disclosed herein comprises the root, stem, leaf of Panax ginseng, Panax quinquefolia, Panax notoginseng, Panax japonica, Panax trifolia, Panax pseudoginseng, Panax vietnamensis, Panax elegatior, Panax wangianus or Panax bipinratifidus.

[41]

[42] Hereinafter, the present invention is described in detail.

[43]

[44] R>r the present invention, for example, dried plant material of Panax genus was cut into small pieces and the piece was autoclaved at the temperature ranging from 70 to 15O⁰C, preferably 100 to 13O⁰C, for the period ranging from 2 to 6 hours, preferably 3 to 5 hours; and was mixed with 1 to 20-fold, preferably, 3 to 10-fold weight (kg) of water, C₁-C₄ lower alcohol, such as methanol, ethanol, butanol or the mixtures thereof, preferably ethanol; was heated for the period ranging from 3 to 10 hours, preferably 3 to 6 hours, by reflux extraction with water, cold water extraction, ultra-sonication or conventional extraction, preferably by reflux extraction with water; the residue was filtered and then the filtrate was dried at the temperature ranging from 40 to 8O⁰C, preferably from 50 to 7O⁰C, to obtain inventive extract of processed ginseng.

[45] To investigate the effect of inventive extract on the anti-obesity effect, the inventors of present invention have intensively carried out various experiments i.e., the determination test on the change of body weight, the level of total cholesterol, LDL and triglyceride in blood using by estrogen- deficient obesity rat model caused by ovariectomy etc, and finally completed present invention by confirming that an inventive extract reduces body weight, the level of total cholesterol, LDL and triglyceride in blood, increases the level of blood HDL as well as inhibits the lipid ac- cunulation of Caenorhabditis elegans (C. elegans).

[46] Inventive composition of the present invention has no toxicity and adverse effect therefore can be used with safe.

[47] The present invention provides a pharmaceutical composition comprising the processed ginseng extract prepared by the above-described method as an active ingredient to prevent and treat obesity.

[48] The inventive composition for treating and preventing obesity may comprise the above extract as from 0.01 to 50% by weight based on the total weight of the composition.

[49]

[50] The inventive composition may additionally comprise conventional carrier, adjuvants or diluents in accordance with a using method well known in the art. It is preferable that said carrier is used as appropriate substance according to the usage and application method, but not limited. Appropriate diluents are listed in the written text of Remington's Pharmaceutical Science (Mack Publishing co, Easton PA).

[51]

[52] Hereinafter, the following formulation methods and excipients are merely exemplary and in no way limit the invention.

[53]

[54] The composition according to the present invention can be provided as a pharmaceutical composition containing pharmaceutically acceptable carriers, adjuvants or diluents, e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calciun phosphate, calciun silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesiun stearate and mineral oil. The formulations may additionally include fillers, anti- agglutinating agents, lubricating agents, wetting agents, flavoring agents, emulsifiers, preservatives and the like. The compositions of the invention may be formulated so as to provide quick, sustained or delayed release of the active ingredient after their administration to a patient by employing any of the procedures well known in the art.

[55]

[56] R>r example, the compositions of the present invention can be dissolved in oils, propylene glycol or other solvents that are commonly used to produce an injection. Suitable examples of the carriers include physiological saline, polyethylene glycol, ethanol, vegetable oils, isopropyl myristate, etc., but are not limited to them. R>r topical administration, the extract of the present invention can be formulated in the form of ointments and creams.

[57]

[58] Pharmaceutical formulations containing present composition may be prepared in any form, such as oral dosage form (powder, tablet, capsule, soft capsule, aqueous medicine, syrup, elixirs pill, powder, sachet, granule), or topical preparation (cream, ointment, lotion, gel, balm, patch, paste, spray solution, aerosol and the like), or injectable preparation (solution, suspension, emulsion).

[59]

[60] The composition of the present invention in pharmaceutical dosage forms may be used in the form of their pharmaceutically acceptable salts, and also may be used alone or in appropriate association, as well as in combination with other pharmaceutically active compounds.

[61]

[62] The desirable dose of the inventive extract of the present composition varies depending on the condition and the weight of the subject, severity, drug form, route and period of administration, and may be chosen by those skilled in the art. However, in order to obtain desirable effects, it is generally recommended to administer at the amount ranging from 0.0001 to 100 mg/kg, preferably 0.001 to 10 mg/kg by weight/ day of the inventive extract or compounds of the present invention. The dose may be administered in single or divided into several times per day. In terms of composition, the amount of inventive extract or compound should be present between 0.01 to 50% by weight, preferably 0.5 to 40% by weight based on the total weight of the composition.

[63]

[64] The pharmaceutical composition of present invention can be administered to a subject animal such as mammals (rat, mouse, domestic animals or human) via various routes. All modes of administration are contemplated, for example, administration can be made orally, rectally or by intravenous, intramuscular, subcutaneous, intracutaneous, intrathecal, epidural or intracerebroventricular injection.

[65]

[66] Theinventive extractof the present invention also can be used as a main component or additive and aiding agent in the preparation of various functional health food and health care food.

[67]

[68] Accordingly, it is the other object of the present invention to provide a functional health food comprisingan extract of processed ginseng so as to make a ratio of gin- senoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, for preventing or improving obesity.

[69] Accordingly, it is the other object of the present invention to provide a functional health food comprisingextract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C _rC₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, for preventing or improving obesity.

[70]

[71] The term "a functional health food" defined herein means "the functional food having enhanced functionality such as physical functionality or physiological functionality by adding the compound of the present invention to conventional food to prevent or improve obesity in human or mammal".

[72]

[73] It is the other object of the present invention to provide a health care food comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0,together with a sitologically acceptable additive for the prevention and alleviation of obesity.

[74] It is the other object of the present invention to provide a health care food comprising extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C₁-C₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, together with a sitologically acceptable additive for the prevention and alleviation of obesity.

[75]

[76] The term "a health care food" defined herein means "the food containing the compound of the present invention showing no specific intended effect but general intended effect in a small amount of quantity as a form of additive or in a whole amount of quantity as a form of capsule, pill, tablet or etc".

[77]

[78] The term "a sitologically acceptable additive" defined herein means "any substance the intended use which results or may reasonably be expected to result directly or indirectly in becoming a component or otherwise affecting the characteristics of any food" for example, thickening agent, maturing agent, bleaching agent, sequesterants, humectant, anti-caking agent, clarifying agents, curing agent, emulsifier, stabilizer, thickner, bases and acid, foaming agents, nutrients, coloring agent, flavoring agent, sweetner, preservative agent, antioxidant or etc., which shall be explained in detail as follows.

[79] If a substance is added to a food for a specific purpose, it is referred to as a direct additive and indirect food additives are those that become part of the food in trace amounts due to its packaging, storage or other handling.

[80]

[81] Above described health foods can be contained in food, health beverage, dietary therapy etc, and may be used as a form of powder, granule, tablet, chewing tablet, capsule, beverage etc for preventing or improvingobesity.

[82]

[83] Also, above described extract can be added to food or beverage for prevention and improvement of obesity. The amount of above described compound in food or beverage as a functional health food or health care food may generally range from about 0.01 to 100 w/w % of total weight of food for functional health food composition. In particular, although the preferable amount of the compound of the present invention in the functional health food, health care food or special nutrient food may be varied in accordance to the intended purpose of each food, it is preferably, in general, used as a additive in the amount of the extract of the present invention ranging from about 0.01 to 5% in food such as noodles and the like, from 40 to 100% in health care food on the ratio of 100% of the food composition.

[84] [85] Providing that the health beverage composition of present invention contains above described extract as an essential component in the indicated ratio, there is no particular limitation on the other liquid component, wherein the other component can be various deodorant or natural carbohydrate etc such as conventional beverage. Examples of aforementioned natural carbohydrate are monosaccharide such as glucose, fructose and etc.; disaccharide such as maltose, sucrose and etc.; conventional sugar such as dextrin, cyclodextrin; and sugar alcohol such as xylitol, erythritol and etc. As the other deodorant than aforementioned ones, natural deodorant such as taunatin, stevia extract such as levaudioside A, glycyrrhizin and etc., and synthetic deodorant such as saccharin, aspartam and etc., may be useful favorably. The amount of above described natural carbohydrate is generally ranges from about 1 to 20 g, preferably 5 to 12 g in the ratio of 100 m# of present beverage composition.

[86]

[87] The other components than aforementioned composition are various nutrients, vitamin, mineral or electrolyte, synthetic flavoring agent, coloring agent and improving agent in case of cheese, chocolate and etc., pectic acid and the salt thereof, alginic acid and the salt thereof, organic acid, protective colloidal adhesive, pH controlling agent, stabilizer, preservative, glycerin, alcohol, carbonizing agent used in carbonate beverage and etc. The other component than aforementioned ones may be fruit juice for preparing natural fruit juice, fruit juice beverage and vegetable beverage, wherein the component can be used independently or in combination. The ratio of the components is not so important but is generally range from about 0 to 20 w/w% per 100 w/w% present composition. Examples of addable food comprising aforementioned extract therein are various food, beverage, gun, vitamin complex, health improving food and the like.

[88]

[89] Inventive extract of the present invention have no toxicity and adverse effect therefore; they can be used with safe.

[90]

[91] It will be apparent to those skilled in the art that various modifications and variations can be made in the compositions, use and preparations of the present invention without departing from the spirit or scope of the invention.

[92]

Advantageous Effects

[93] Inventive extract of present invention showed potent anti-obesity activity through various experiments. The inventive extract reduced body weight, the level of total cholesterol, LDL and triglyceride in blood, increased the level of blood HDL as well as inhibited the lipid accunulation of Caenorhabditis elegans (C. elegans). Therefore, it can be used as the therapeutics or health food for treating and preventing obesity without adverse action

[94]

Brief Description of the Drawings

[95] The above and other objects, features and other advantages of the present invention will more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which;

[96]

[97] Eg. 1 shows the change of rat body weight of each group according to the 6 weeks- treatment of SG;

[98]

[99] Eg. 2 shows the level of seran total cholesterol of each group according to the 6 weeks-treatment of SG;

[100]

[101] Bg. 3 represents the level of serum triglyceride of each group according to the 6 weeks-treatment of SG;

[102]

[103] Eg. 4 represents the level of serum blood high density lipoprotein (HDL) of each group according to the 6 weeks -treatment of SG;

[104]

[105] Eg. 5 represents the level of serum low density lipoprotein (LDL) of each group according to the 6 weeks -treatment of SG;

[106]

[107] Eg. 6 presents the inhibitory effect on the lipid droplet production in Caenorhabditis elegans (C. elegans) according to the 6 weeks-treatment of SG.

[108]

Best Mode for Carrying Out the Invention

[109] It will be apparent to those skilled in the art that various modifications and variations can be made in the compositions, use and preparations of the present invention without departing from the spirit or scope of the invention.

[HO] Mode for the Invention

[111] The present invention is more specifically explained by the following examples. However, it should be understood that the present invention is not limited to these examples in any manner.

[112]

[113] Reference example 1. Preparation of experimental animals

[114] 5 weeks old female Sprague-Dawley (SD) rats (Daehanbiolink, Korea) ranging from 190 to 210 g were used for experiment. The rats were acclimated to environment for 1 week before use. The breeding room was controlled by automatic light system from 7:00 A.M. to 7:00 P.M, for 12 hours with adjusting the temperature to 22⁰C and the humidity to 60%. The animal feed (Samyangsa, Korea) consisting of 21% crude protein, 3.5% crude lipid, 5.0% cellulose, and 8.0% mineral was provided and tap water were freely accessible.

[115]

[116] Example 1. Preparation of the extract of processed ginseng

[117] The processed ginseng extract (Jinseng Co., Korea) was prepared by the procedure disclosed in US Patent No. 5776460 and hereinafter, the process is described in detail.

[118] 1 kg of dried root of Panax ginseng was cut into small pieces and the sliced pieces were heated at 12O⁰C for 4 hours in autoclave. The processed ginseng was mixed with 2 I of ethanol and heated for 4 hours by reflux extraction with water. The residue was filtered and then the filtrate was evaporated to obtain 300 g inventive extract of processed ginseng, which is designated as "SG" hereinafter.

[119]

[120] Example 2. Analysis of the gensenoside amount of processed ginseng product

[121] The ginseng saponin component in white ginseng and red ginseng was compared with each other.

[122] The processed ginseng prepared by the above-described Example 1 was pulverized, and then with 1 g of each sample was extracted with 70% ethanol 20 ml for 3 times, each for 3 hours in a 50 mL flask. Each extract were concentrated by vacuum evaporation and the residue were dissolved in 20 ml methanol, used as sample.

[123] The white ginseng and red ginseng purchased commercial market, were extracted according to similar method to the above mentioned processing method disclosed in Example 1 and the extract of each sample was used as a sample.

[124] The HPLC analysis of each saponin compound was performed by the method disclosed in the literature (Kwun et al., Journal of Chromatography A, ^"VbI. 921, pp.335-339) through comparing with the data of standard of ginsenoside RbI and Rg3; the results are shown in Table 1.

[125] In the case of processed ginseng, it was confirmed that the sum of (Rg3+Rg5+Rkl) is higher than the sun of (Rbl+Rb2+Rc+Rd) through the analysis of each relative peak area of ginsenosides in SG, differently from the results of white ginseng and red ginseng ( See Table 1)

[126] [127] Table 1 [Table 1] [Table ]

[128] [129] Experimental Example 1. Estrogen-Deficient Obesity Rat Model and Pharmaceutical Administration Experiment

[130] Experimental rat was anesthetized by intramuscular injection of ketamine (Yuhan, Korea) in the amount of 1 m^/kg, and then the abdominal fur was removed. The surgery region was sterilized with 70% ethanol and the skin, abdominal muscle and peritoneum were cut in about 1 cm. After exposing the ovary, ovariectomy was operated and the incised part was sutured. Sham operation, i.e., the peritoneum of the rat was cut and ovariectomy was not operated, in normal control group.

[131] The experiment rats were classified into four groups, i.e., (1) normal group (NC group) consisting of 10 rats: the group which the sham operation was performed after incising peritoneun, (2) control group (OC group) consisting of 10 rats: the group not treated with drug after ovariectomy, (3) high-dose test group (SGH group) consisting of 8 rats: the group orally treated with SG in an amount of 200 mg/kg after ovariectomy, and (4) low-dose test group (SGL group) consisting of 8 rats: the group orally treated with SG in an amount of 100 mg/kg after ovariectomy.

[132] The lyophilized SG extract was dissolved in physiological saline solution and administrated into the rats once a day for 6 weeks. [133] 24 hours after the administration of SG extract, the blood was collected, centrifuged at 3,000 rpm for 10 minutes, and 20 jΛ of the collected upper layer was tested for determining the level of total cholesterol (TC), high density lipoprotein (HDL) and triglyceride (TG) level using by commercial kit (Youngdong Pharmaceutical Company, Korea).

[134] The level of low density lipoprotein (LDL) was calculated according to following Math Hgure 1 introduced by Friedewald.

[135]

[136] MathEgure 1 [Math.l]

LDL - Total cholesterol - HDL- 1 / 5 Triglyceride

[137]

[138] 1-1. Change in body weight

[139] The body weight of the rats after treating with extract for 6 weeks was observed as approximately 224.4 g in normal group (NC group), 276.8 g in control group (OC group), 263.1 g in high-dose test group (SGH group) and 259.3 g in low-dose test group (SGL group), respectively.

[140] The control group (OC group) showed significant increased body weight comparing with normal group (NC group) while the test groups, i.e., high-dose test group (SGH group) and low-dose test group (SGL group) showed decreased body- weight comparing with the control group (OC group). ( See Table 2 and Hg. 1)

[141]

[142] Table 2

[Table 2] [Table ]

[143] [144] 1-2. Total cholesterol level [145] The level of serum total cholesterol in normal group (52.7+14.5 mg/dl in NC group), and control group (79.4+11.4 mg/dl in OC group) was significantly increased comparing with that in normal group (NC group). On the contrary, the level of serum total cholesterol in test groups, i.e., high-dose test group (66.1+8.1 mg/dl in SGH group) and low-dose test group (71.6+6.4 mg/dl in SGL group) was significantly decreased comparing with that in normal group (NC group). ( See Table 3 and Eg. 2)

[146] [147] Table 3 [Table 3] [Table ]

[148] [149] 1-3. Triglyceride level [150] The level of serum triglyceride in control group (111.2+34.2 rrg/dl in OC group) was significantly increased comparing with that in normal group (69.2+7.5 mg/dl in NC group). The level of serum triglyceride in high-dose test group (SGH group) was significantly decreased to 97.6+16.3 rrg/dl ( See Table 4 and Eg. 3).

[151] [152] Table 4 [Table 4] [Table ]

[153] [154] 1-4. HDL-cholesterol level [155] The level of HDL-cholesterol in normal group (46.58+8.22 rrg/dl in NC group) and control group (37.75+5.44 rrg/dl in OC group) was decreased comparing with normal group (NC group).

[156] The level of HDL-cholesterol in high-dose test group (46.15+6.06 rrg/dl in SGH group) was increased comparing with control group (OC group) while the level of HDL-cholesterol in low-dose test group (35.80+5.67 rrg/dl in SGL group) was decreased comparing with control group (OC group). ( See Table 5 and Hg. 4)

[157] [158] Table 5 [Table 5] [Table ]

[159] [160] 1-5. LDL-cholesterol level [161] The level of serum LDL-cholesterol in control group (OC group) showed 17.8+7.02 rrg/dl and that in normal group (NC group) showed 17.8+7.02 mg/dl.

[162] The level of serum LDL-cholesterol in test groups, i.e., high-dose test group (16.5+10.74 rrg/dl in SGH group) and low-dose test group (19.1+16.50 mg/dl in SGL group) was significantly decreased comparing with control group (OC group) ( See Table 6 and Eg. 5).

[163] [164] Table 6 [Table 6] [Table ]

[165] [166] Experimental Example 2. Inhibition test from the lipid accumulation of Caen- orhabditis elegans ( C. elegans ). [167] To investigate the effect of SG prepared in Example 1 on the formation of lipid droplet in Caenorhabditis elegans (C. elegans), following experiment was performed by the modified method disclosed in the literature (Greenspan P. et al., J. Cell Biol, 100(3). pp965-973, 1985) and stained with Nile Red, a dye used to confirm the accumulation of lipid droplet together with Oil Red.

[168] Caenorhabditis elegans (C. elegans) grown to L4 stage was placed to plate, one per plate and the groups were divided into control group and test sample group treated with 10 βg/md, of SG. On the next day, after eliminating the eel worm reached to PO generation among the test group, the plate was treated with Nile red solution and incubated for 3 days. After fixing the eelwormon each plate with sodium azide (NaN₃), the eelworm was photographed with fluorescence microscope (the length of WP: 628 nm, magnification at x400).

[169] As a result, the test sample group (C and D) showed decreased in the lipid droplet comparing with control group (A and B). ( See Eg. 6)

[170]

[171] Hereinafter, the formulating methods and kinds of excipients of pharmaceutical compositions or health functional food will be described, but the present invention is not limited to them.

[172]

[173] Preparation of powder

[174] SG 20 mg

[175] Lactose 100 mg

[176] Talc 10 mg

[177] Powder preparation was prepared by mixing above components and filling sealed package.

[178]

[179] Preparation of table

[180] SG lO mg

[181] Corn Starch 100 mg

[182] Lactose 100 mg

[183] Magnesium Stearate 2 mg

[184] Tablet preparation was prepared by mixing above components and entabletting.

[185]

[186] Preparation of capsule

[187] SG lO mg [188] Crystallized cellulose 3 rrg

[189] Lactose 14.8 rrg

[190] Magnesiun Stearate 0.2 rrg

[191] Capsule preparation was prepared by mixing above components and filling gelatin capsule by conventional gelatin preparation method. [192]

[193] Preparation of injection

[194] SG 10 rrg

[195] Mannitol 180 rrg

[196] Distilled water for injection 2974 rrg

[197] Na₂HPO₄2H₂O 26 rrg

[198] Injection preparation was prepared by dissolving active component and then filling all the components in 2 ml ample and sterilizing by conventional injection preparation method. [199]

[200] Preparation of liquid

[201] SG 20 rrg

[202] Isomerized sugar 1O g

[203] Mannitol 5 g

[204] Distilled water optimum amount

[205] Liquid medicine was prepared by dissolving the components to distilled water with a proper dose of lemon scent, mixing, adjusting to 100 ml with distilled water in brown bottle and sterilizing by conventional liquid medicine preparation method. [206]

[207] Preparation of functional health food

[208] SG 1000 mg

[209] Vitamin mixture optimun amount

[210] Vitamin A acetate 70 μg

[211] Mtamin E l.O mg

[212] Mtamin B j 0.13 mg

[213] Mtamin B ₂0.15 mg

[214] Mtamin B ₆0.5 mg

[215] Mtamin B ₁₂ 0.2 /*g

[216] Vitamin C 10 mg

[217] Biotin 10 μg [218] Amide nicotinic acid 1.7 mg

[219] Iblic acid 50 μg

[220] Calcium pantothenic acid 0.5 mg

[221] Mineral mixture optimum amount

[222] Ferrous sulfate 1.75 mg

[223] Znc oxide 0.82 mg

[224] Magnesium carbonate 25.3 mg

[225] Monopotassium phosphate 15 mg

[226] Dicalcium phosphate 55 mg

[227] Potassium citrate 100 mg

[228] Magnesium chloride 24.8 mg

[229] The above mentioned vitamin and mineral mixture may be varied in many ways.

Such variations are not to be regarded as a departure from the spirit and scope of the present invention. [230]

[231] Preparation of health beverage [232] SG 1000 mg [233] Citric acid 1000 mg [234] Oligosaccharide 100 g [235] Apricot concentration 2 g [236] Taurine 1 g [237] Distilled water 900 mH [238] Health beverage preparation was prepared by dissolving active component, mixing, stirring at 85⁰C for 1 hour, filtering and then filling all the components in 2 I container and sterilizing by conventional health beverage preparation method. [239] [240] The invention being thus described, may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims. [241]

Industrial Applicability [242] As described in the present invention, the inventive extract of processed Panax genus of the present invention reduced body weight, the level of serum total cholesterol, low density lipoprotein (LDL) and triglyceride, increased the level of serum high density lipoprotein (HDL) as well as inhibited the lipid accumulation of Caenorhabditis elegans (C. elegans). Therefore, it can be used as the therapeutics or health food for treating and preventing obesity without adverse action.

Claims

[1] A use of extract of processed ginseng so as to make a ratio of ginsenoside

(Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0 as an active ingredientfor the manufacture of therapeutic agent for the treatment and prevention of obesity.

[2] A use of extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C i -C₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, as an active ingredientfor the manufacture of therapeutic agent for the treatment and prevention of obesity.

[3] The use according to claim 1 or claim 2, wherein said ginseng comprises the root, stem, leaf of Panax ginseng, Panax quinquefolia, Panax notoginseng, Panax japonica, Panax trifolia, Panax pseudoginseng, Panax vietnamensis, Panax elegatior, Panax wangianus, or Panax bipinratifidus.

[4] The use according to claim 1 or claim 2, wherein said extract is extracted with the solvent selected from the group consisting of water, C _rC₄ lower alcohols and the mixtures thereof.

[5] A pharmaceutical composition comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0, as an active ingredient in an effective amount to treat and prevent obesity.

[6] A pharmaceutical composition comprising an extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, Ci-C₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, as an active ingredient and pharmaceutically acceptable carrier, diluents or adjuvant to treat and prevent obesity.

[7] A functional health food comprising an extract of processed ginseng so as to make a ratio of ginsenoside (Rg3+Rg5+Rkl) to (Rbl+Rb2+Rc+Rd) of over 1.0.

[8] A health care food comprising an extract of processed ginseng prepared by the procedure comprising the step; heating the plant material belonged to Panax genus at the temperature ranging from 70 to 15O⁰C, for the period ranging from 2 to 6 hours to obtain processed plant; mixing the processed plant with 1 to 20-fold weight of water, C₁-C₄ lower alcohol and heating the solution with extraction; concentrating the filtrate with filtering the residue to obtain inventive extract, together with a sitologically acceptable additive for the prevention and alleviation of obesity.