WO2005115427A1

WO2005115427A1 - Herbal medicine composition for suppression of obesity and preparation method thereof

Info

Publication number: WO2005115427A1
Application number: PCT/KR2005/001626
Authority: WO
Inventors: Hyun-Su Bae; Moon-Kyu Kang; Jung-Wan Oh; Chong-Woon Cho; Chang-Sook Kim; Hwa-Jin Lee; Moo-Chang Hong; Min-Kyu Shin; Hwan-Suck Chung; Hee-Kyoung Lee; Sang-Moon Lee; Hong-Yeoul Kim
Original assignee: Purimed Co Ltd
Current assignee: Purimed Co Ltd
Priority date: 2004-05-31
Filing date: 2005-05-31
Publication date: 2005-12-08
Anticipated expiration: 2006-11-30
Also published as: KR20050114040A; KR100641807B1

Abstract

The present invention relates to a herbal medicinal composition for inhibiting obesity and a preparation method thereof. The herbal composition comprises 12~17 parts by weight of Lycium chinensis Miller, 12~17 parts by weight of steamed rehmannia glutinosa, 10~38 parts by weight of Coicis semen, 9~14 parts by weight of Carthamus tinctorius, 5~7 parts by weight of Poria cocos, 9~14 parts by weight of Angelicae gigantis radix, 5~7 parts by weight of lotus fruit, 5~7 parts by weight of Dioscoreae rhizoma, and 5~7 parts by weight of Citrus aurantium. The composition allows the reduction of body fat or blood fat without causing fatal side effects, and thus, is effective in inhibiting or treating over body weight, obesity and various diseases induced by obesity.

Description

Description HERBAL MEDICINE COMPOSITION FOR SUPPRESSION OF OBESITY AND PREPARATION METHOD THEREOF Technical Field

[1] The present invention relates to a herbal medicinal composition for inhibiting obesity and a preparation method thereof, and more particularly, to a herbal medicinal composition for inhibiting obesity, which comprises Lycium chinensis Miller, steamed rehmannia glutinosa, Cocicis semen, Carthamus tinctorius, Poria cocos, Angelicae gigantis radix, lotus fruit, Dioscoreae rhizoma, and Citrus aurantium, as well as a preparation method thereof. Background Art

[2] Obesity refers to a condition where body fat was excessively accumulated in the body. It does not means a condition of excessive bodyweight but rather means a condition where fat was excessively accumulated in the body due to metabolic disorder. Namely, calorie intake exceeds energy required for the body activity and growth so that it is excessively accumulated in fat tissue in the form of neutral fat, thus causing obesity.

[3] Even by itself, obesity causes so-called "5D" indicating that obesity causes not only disfigurement, discomfort and disability, but also diseases, such as cardiovascular diseases, including hyperlipidemia, hypercholesterolemia, hypertension, ate- riosclerosis, and myocardial infarction, renal disease, type II insulin-independent diabetes, and pulmonary disease, and these diseases lead to death. In highly developed countries, 30% of total adults have obesity, and particularly, the mortality of men with obesity is about 12 times higher in a young age group (25-34 years old), and the main cause of the death was found to be cardiovascular diseases.

[4] In order to treat this obesity, studies are currently performed on diet therapy, exercise therapy, behavior modification therapy, surgical therapy, drug therapy and the like. Meanwhile, drugs for the treatment of obesity include fat accumulation inhibitors (appetite inhibitors and agents for inhibiting food absorption or fatty acid production) and fat utilization stimulants (thermogenic or lypolytic agents), and agents recently frequently used in the clinical field include fluoxetine, orlistat, sibutramine and the like. Fluoxetine (commercially available under the tradename "Prozac") is a selective serotonin reuptake inhibitor used as an antidepressant, and it has only a temporary effect on a reduction in bodyweight and involves side effects, such as enervation, perspiration and lethargy. Orlistat (commercially available under the tradename "Xenical") inhibits the activity of lipase in the small intestines to reduce fat absorption by about 30%, but causes fat feces and requires the supplement of fat-soluble vitamin upon long-term administration. Sibutramine (commercially available under the tradename "Reductil") shows the double action of inhibiting the reuptake of serotonin and norepinephrine, but an increase in serotonin activates the sympathetic system to increase exothermic reaction in brown fat tissue and involves side effects, such as blood pressure increase, mouth drying, constipation and insomnia.

[5] As described above, obesity is the main factor of mortally threatening life, but there is still no therapeutic agent of effectively treating such obesity without involving the above-described side effects. Accordingly, there is an urgent need for the development of a safe and effective antiobesity agent. Disclosure of Invention Technical Problem

[6] It is an object of the present invention to provide a herbal medicinal composition which is excellent in inhibitory and therapeutic effects against obesity and symptoms involved in obesity and has no side effects, as well as a preparation method thereof. Technical Solution

[7] To achieve the above object, in one aspect, the present invention provides a herbal medicinal composition comprising 12-17 parts by weight of Lycium chinensis Miller, 12-17 parts by weight of steamed rehmannia glutinosa, 10-38 parts by weight of Cocicis semen, 9-14 parts by weight of Carthamus tinctorius, 5-7 parts by weight of Poria cocos, 9-14 parts by weight of Angelicae gigantis radix, 5-7 parts by weight of lotus fruit, 5-7 parts by weight of Dioscoreae rhizoma, and 5-7 parts by weight of Citrus aurantium.

[8] In another aspect, the present invention provides a method for preparing a herbal medicinal composition for inhibiting obesity, the method comprising the steps of: crushing a herbal mixture comprising Lycium chinensis Miller, steamed rehmannia glutinosa, Cocicis semen, Carthamus tinctorius, Poria cocos, Angelicae gigantis radix, lotus fruit, Dioscoreae rhizoma, and Citrus aurantium extracting the crushed powder with a solvent; filtering the extract to obtain a filtrate; concentrating the filtrate; and freeze-drying the concentrate.

[9] In the inventive method, the extraction step is preferably performed by a hot- water extraction process at 80-100 °C for 1-3 hours. Advantageous Effects

[10] As described above, according to the present invention, the composition for inhibiting or treating obesity can be provided which reduces blood fat levels without fatal side effects, and thus, is effective in inhibiting or treating over bodyweight, obesity, and various diseases induced by obesity. Brief Description of the Drawings

[11] FIG. 1 is a graphic diagram showing the comparison of the cholesterol level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [12] FIG. 2 is a graphic diagram showing the comparison of the LDL-cholesterol level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [13] FIG. 3 is a graphic diagram showing the comparison of the total lipid level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [14] FIG. 4 is a graphic diagram showing the comparison of the triglyceride level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [15] FIG. 5 is a graphic diagram showing the comparison of the free fatty acid level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [16] FIG. 6 is a graphic diagram showing the comparison of the phospholipid level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [17] FIG. 7 is a graphic diagram showing the comparison of the SGOT level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [18] FIG. 8 is a graphic diagram showing the comparison of the SGPT level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [19] FIG. 9 is a graphic diagram showing the comparison of the creatinine level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-causing high-fat feed. [20] FIG. 10 is a graphic diagram showing the comparison of the BUN level of rats ingested with obesity-inhibiting feed with those of rats ingested with normal feed and rats ingested with obesity-inducing high-fat feed. [21] Values shown in each of the drawings are expressed as mean+SEM.

[22] * p<0.05, ** p<0.01, *** p<0.005, **** p<0.001: showed a statistically significant difference when compared with the high-fat feed group (C)and the normal feed group (N). Best Mode for Carrying Out the Invention [23] Hereinafter, the present invention will be described in detail. [24] Cocicis semenis low in calorie and has various functions, such as the promotion of urination. Thus, it is used regularly used as diet food for diabetes and has the pharmacological action to reduce appetite.

[25] Carthamus tinctorius has the effects of mitigating and treating ischemic heart diseases and brain diseases and inhibiting platelet aggregation reaction, thus inhibiting blood thrombosis.

[26] Poria cocos has pharmacological actions, such as urination, lowering of blood glucose, hemolysis inhibition, increase of heart contraction, and immune enhancement.

[27] Angelicae gigantis radix has the actions of blood nourishing, removal of ex- travasated blood, and sedation, and has the pharmacological action to activate blood circulation by reducing blood clots in blood.

[28] The lotus fruit contains a large amount of useful proteins and is used for nutrition strengthening, body weakness, recovery of the body from diarrhea, and the like. In addition, it has the pharmacological actions to reduce the blood fat of obesity rats induced by high-fat diets, and to inhibit platelet aggregation reaction, thus inhibiting blood thrombosis.

[29] Lycium chinensis Miller has the effects of removing the deposition of cholesterol, decomposing fat accumulated in the liver, and lowering blood glucose level. Steamed rehmannia glutinosa has the effects of reducing appetite and inducing lipolysis.

[30] Dioscoreae rhizoma has the effects of lowering blood glucose level and acting on the digestive system to recover the renal tube from damage and to protect blood vessels from inflammation and the lever from damage. In addition, Citrus aurantium has the effect of lowering blood pressure.

[31] Meanwhile, if the content of Lycium chinensis Miller in the inventive composition is less than 12 parts by weight, it cannot effectively remove blood fat, and if the content of Lycium chinensis Miller is more than 17 parts by weight, it can result in a rapid reduction in blood fat levels, particularly blood cholesterol levels, thus causing side effects, such as myasthenia.

[32] If steamed rehmannia glutinosa inducing lipolysis in fat cells is used in an amount of 12 parts by weight in the inventive composition, it will be effective in lipolysis, but it is used in an amount of 17 parts by weight, it can result in excessive lipolysis, thus causing an increase in blood fat level, an opposite phenomenon to antiobesity.

[33] The content of Cocicis semen in the inventive herbal composition should be 10-38 parts by weight, in which case it can provide effective urination while preventing gout and the like, the general side effects of a diuretic. The reason why Poria cocos is added in an amount of 5-7 parts by weight is similar to the case of Cocicis semen.

[34] If the content of Carthamus tinctorius in the inventive herbal composition is less than 9 parts by weight, it will not be effective in treating cardiovascular diseases induced by obesity, and if it is more than 14 parts by weight, it can show a side effect of bleeding. For this reason, Carthamus tinctorius is preferably used in an amount of 9-14 parts by weight.

[35] Angelicae gigantis radixis preferably used in an amount of 9-14 parts by weight in the inventive herbal composition, in order to effectively blood circulation disorder and to prevent myasthenia, bleeding and the like, which occur in the existing drugs for inhibiting blood fatness and thrombosis.

[36] If the content of the lotus fruit in the inventive herbal composition is less than 5 parts by weight, it will not be effective in mitigating thrombosis, ateriosclerosis and the like, and if it is used in an amount of more than 7 parts by weight, it can cause myasthenia, bleeding and the like.

[37] Dioscoreae rhizoma, when used in an amount of 5-7 parts by weight in the inventive herbal composition, is effective in recovering the renal tube to remove the inflammation of blood vessels and to inhibit liver damage and prevents immune deterioration.

[38] Citrus aurantium, when used in an amount of 5-7 parts by weight in the inventive herbal composition, is effective in maintaining blood pressure at a suitable level. Mode for the Invention

[39] Hereinafter, the present invention will be described in detail by examples. It is to be understood, however, that these examples are for illustrative purpose only and not construed to limit the scope of the present invention.

[40] Example

[41] Each of the herbal materials of the inventive herbal medicinal composition was crushed to powder. Then, the crushed powders were mixed with each other at a weight ratio given in Table 1 below, and the mixed powder was placed in a flask containing distilled water and extracted with hot water at 100 °C for 1 hour. Then, the extract was filtered through gauze, and the filtrate was concentrate in reduced pressure and freeze- dried.

[42] Meanwhile, for use in animal tests to examine whether the inventive herbal composition has the effect of inhibiting obesity, feed was prepared in such a manner that the inventive composition was contained in an amount of 2.2 g per 100 g of the feed.

[43] Table 1

[44] [45] Test Example 1 : Preparation of high-fat feed and obesity-inducing test using the same

[46] 85~95-day-old male Sprague-Dawley rats weighing 19~250g were accommodated in a breeding chamber with constantly maintained temperature and humidity and no pathogenic bacteria for 2 weeks while permitting free access to water and feed. Then, the rats were divided into the following three groups each consisting of 8 animals:

[47] (1) Normal feed group: general rat feed (Samtako Co.; 5% fat content; indicated by "N"). [48] (2) Obesity-inducing high-fat feed group: feed with a total fat content of 20% (Purina Korea Inc.; 20% tallow fat; indicated by "C"). [49] (3) Obesity-inhibiting feed group: obesity-inducing high-fat feed group + the inventive composition (indicated by "C + P"). [50] The components and contents thereof in the inventive composition, and the contents of the components in the prepared feed, are shown in Table 1 above. The two feeds except for normal feed group were prepared in the following manner. Purina feed containing 20% of fat was crushed with a grinder, introduced with either a small amount of water or the inventive composition and a small amount of water, and then kneaded into the general shape of feed. Next, the kneaded material was dried in a hood at room temperature for 24 hours.

[51] The rats divided into the three groups were fasted for 24 hours before administration with the feed. Then, the rats were administered with the normal feed, the obesity-inducing high-fat feed and the obesity-inhibiting feed for 6 weeks. The body weight of the rats was measured at one- week intervals. The results are shown in Table 2. As could be seen in Table 2, the high-fat feed group showed a statistically significant increase in body weight for 1-6 weeks as compared to the normal feed group. On the contrary, the rats administered with the obesity inhibiting feed showed a significant inhibition in the increase of body weight induced by the high-fat diet.

[52] Also, the weight of renal fat, another index of obesity, was measured on each of the groups, and the results are shown in Table 2. As can be seen in Table 2, the high-fat feed group showed an increase of 26% in fat level as compared to the normal feed, but the obesity inhibiting feed group showed a reduction of 28% in the increased fat level. These results suggest that the high-fat diet induced increases in body weight and fat level (i.e., obesity), and the inventive composition has the effect of inhibiting obesity induced by the high-fat diet.

[53] Table 2

[54] [55] The values in Table 2 are expressed as mean+SEM. [56] ^ap<0.05, p<0.01, °p<0.005, p<0.001: showed a statistically significant difference when compared to the high-fat feed group.

[57] Test Example 2: Obesity inhibiting test using inventive composition in obesity- induced animal models

[58] Rats were divided into three groups as described in Test Example 1 and administered with different feeds for 6 weeks. Then, blood was collected from the heart of each of the rats. Serum was separated from the collected blood and measured for cholesterol, LDL-cholesterol, triglyceride, free fatty acid, phospholipid and total lipid levels, which are indicative of obesity. As a result, as can be seen in FIGS. 1 to 3, the high-fat feed group showed a statistically significant increase in cholesterol as compared to the normal feed group, LDL-cholesterol and total lipid levels, indicating that obesity was induced. On the contrary, the obesity-inhibiting feed group administered with the inventive composition showed a significant reduction in these increased levels.

[59] Also, as can be seen in FIGS. 4 to 6, the obesity-inhibiting feed group showed reductions of 22%, 27% and 10% in the increased triglyceride, free fatty acid and phospholipid levels, respectively, as compared to the high-fat feed group. This indicates that obesity was induced by the high-fat feed, thus increasing cholesterol, LDL-cholesterol, triglyceride, free fatty acid, phospholipid and total lipid levels, and the inventive composition reduced such levels.

[60] As can be seen in Test Examples above, the inventive composition can be used as agents for inhibiting obesity and treating obesity-related diseases, such as hyper- lipidemia, ateriosclerosisand the like.

[61] Moreover, the inventive composition reduced free fatty acid, phospholipid and neutral fat to a significant extent. Such reductions in total cholesterol and LDL- cholesterol levels are supposed to occur because the inventive composition either inhibits the HMG-CoA reductase, the most important regulatory enzymefor the biosynthesis of cholesterol, or promotes the effective distribution and migration of LDL-cholesterol into various tissues. Furthermore, the reductions in free fatty acid, phopholipid, neutral fat and total lipid levels by the inventive composition are because the inventive composition inhibits the absorption of fats ingested as food in the intestinal tracts, like a lipase inhibitor decomposing fats in the stomach and intestinal tracts into simple forms so as to make fat absorption easy.

[62] Test Example 3: Tests of inventive composition on liver toxicity and kidney toxicity

[63] L-alanine aminotransferase (ALT or SGPT) and L-aspartate aminotransferase (AST or SGOT)are known to be indicative of liver toxicity, and their significant increase means the deterioration of liver function and toxicity and can be frequently seen in obesity persons who mostly have fatty liver. Therefore, the inhibition of activity of such enzymes can be considered to be indicative of obesity inhibition and is important in determining the absence of toxicity. As shown in FIG. 8, the significance of SGPT was not found in the normal feed group, the high-fat feed group and the obesity-inhibiting feed group. This suggests that the high-fat diet containing the inventive composition does not cause an increase in the activities of these enzymes, and the inventive composition does not show liver toxicity harmful to the human body. On the other hand, as could be seen in FIG. 7, the feed containing the inventive composition significantly reduced the activity of SGOT. This indicates that the inventive composition has not only no liver toxicity but also the effect of protecting the liver.

[64] Meanwhile, increases in creatinine and BUN have been indicative of kidney damage and toxicity. As can be seen in FIG. 9, the significance of creatinine was not found in all the normal feed group, the high-fat feed group and the obesity-inhibiting feed group. This suggests that the high-fat feed containing the inventive composition does not cause an increase in creatinine level, and does not show kidney toxicity. Meanwhile, as shown in FIG. 10, BUN was significantly lower in the obesity- inhibiting feed group than the normal feed group. This suggests that the high-fat diet containing the inventive composition does not cause an increase in BUN level, and shows no kidney toxicity.

[65] Test Example 4: Toxicity test of inventive composition on reduction of body weight

[66] In order to examine whether the inventive composition shows toxicity causing a reduction in body weight even when a normal diet is made, feed having the inventive composition added to the normal feed was prepared in the same manner as in Example and administered to rats for 6 weeks. The body weight of the groups administered with the prepared feed was compared with the body weight of the normal feed group, and the results are shown in Table 3 below. As can be seen in Table 3, although the group administered with the inventive composition-containing feed showed a reduction in body weight after one week (this is perhaps thought to be caused by adaptation to drugs), it showed no change in body weight after that. This suggests that the inventive composition does not show the side effect or toxicity of body weight reduction in normal persons and is effective only in persons with obesity caused by high-fat diets.

[67] Table 3

[68]

[69] The values in Table 3 are expressed as mean+SEM. [70] ^ap<0.05: showed a statistically significant difference when compared to the normal feed group.

[71] Test Example 5: Examination of difference in feed intake between high-fat feed group and obesity-inhibiting feed group

[72] In order to examine whether a reduction in the body weight of an obesity-inhibiting feed group is caused by the substantial effect of the inventive composition on the reduction of body weight or caused by a reduction in feed intake due to the odor or taste of the inventive composition, rats were divided into a high-fat feed group and an obesity-inhibiting feed group and examined for feed intake during 5 days before the end of the test. As a result, as can be seen in Table 4, there was no difference in feed intake between the two groups, indicating that the obesity-inhibiting effect of the inventive composition is a result of the medicinal effect of the inventive composition.

[73] Table 4

[74] [75] The values in Table 4 are expressed as mean+SEM. [76] In the above Test Examples of the present invention, the inventive composition was measured for the following side effects: body weight reduction, which is the general toxicity of prior obesity-treating agents; BUN and creatinine levels indicative of kidney toxicity; and blood SGOT and SGPT levels indicative of liver toxicity. The measurement results showed that the inventive composition had no toxicity. In addition, it was found by the feed intake measurement that the obesity-inhibiting effect of the inventive composition is not a result of a nonpharmacological factor caused by taste or odor, i.e., food rejection.

Claims

[1] A herbal medicinal composition for inhibiting obesity, comprising 12-17 parts by weight of Lycium chinensis Miller, 12-17 parts by weight of steamed rehmannia glutinosa, 10-38 parts by weight of Cocicis semen, 9-14 parts by weight of Carthamus tinctorius, 5-7 parts by weight of Poria cocos, 9-14 parts by weight of Angelicae gigantis radix, 5-7 parts by weight of lotus fruit, 5-7 parts by weight of Dioscoreae rhizoma, and 5-7 parts by weight of Citrus aurantium.

[2] A method for preparing an herbal medicinal composition for inhibiting obesity, the method comprising the steps of: crushing a herbal mixture comprising Lycium chinensis Miller, steamed rehmannia glutinosa, Cocicis semen, Carthamus tinctorius, Poria cocos, Angelicae gigantis radix, lotus fruit, Dioscoreae rhizoma, and Citrus aurantium; extracting the crushed powder with a solvent; filtering the extract to obtain a filtrate; concentrating the filtrate; and freeze-drying the concentrate.

[3] The method of Claim 2, wherein the extraction step is performed by a hot-water extraction process at 80-100 °C for 1-3 hours.