KR20070038677A - The composition of ginsenoside mixture which suppresses blood-sugar level after meal - Google Patents

Abstract

The present invention relates to an antidiabetic composition containing ginsenoside, a glycoside of the pharmacologically active ingredient of ginseng, as an active ingredient. The composition according to the present invention extracts ginsenosides (or mixtures thereof) from ginseng and ginseng processed products, and isolates only triols to enhance Rg1, Re, R1, etc. It is excellent in inhibiting the rise in blood sugar.

Ginsenosides, triols, blood sugar

Description

The composition of ginsenoside mixture which suppresses blood-sugar level after meal}

1 is a graph showing changes in blood glucose over time by oral administration of the composition of the present invention (aka "T-2" sample) and R1, Rg1, Re, aka "PC-1" and acarbose in an oral maltose load test system. *** p <0.001, ** p <0.01

Figure 2 is a composition of the present invention (aka "T-2" sample) HPLC analysis.

Figure 3 is an HPLC analysis of the complex ginsenoside composition (aka "PC-1").

The present invention relates to an antidiabetic composition containing ginsenoside, a glycoside of the pharmacologically active ingredient of ginseng, as an active ingredient. The composition according to the present invention extracts ginsenosides (or mixtures thereof) from ginseng and ginseng processed products, and separates only triols to enhance Rg1, Re, R1, etc. It is excellent in inhibiting the rise in blood sugar.

Currently, various kinds of excellent hypoglycemic agents such as sulfonylureas, biguanides, alpha-glycosidase inhibitors, thiazolidinediones, and meglitinides are produced and marketed. However, these drugs range from mild symptoms such as vomiting, abdominal pain and abdominal bloating (International Hepatology Comminications, 5: 289-296 (1996)) to hypoglycemia and decreased liver function (Pract. Diabetes. 1993: 10 (6): S28-31, Diabetes Care 1995: 18 (6): 817-824) and severely deaths (International Hepatology Comminications, 5: 289-296 (1996)), and their use is limited to medicines, liver disease and gastrointestinal tract. Persons with disabilities, kidney disease, pregnancy, etc. are restricted to use as a medicine.

Therefore, extensive research has been conducted on natural products and modified forms of modified natural products, which have been used in oriental medicine and folk medicine for the development of new anti-diabetic drugs and functional foods with little toxicity and side effects and excellent pharmacological activity.

Among them, ginseng has been introduced as a prescription for treating diabetes, and 22 of the 48 Sogal (消渴: diabetes) prescriptions introduced in Dongbobom have 46% of the prescriptions containing ginseng (Ginseng and Tobacco Research Institute, the latest. Korean ginseng (Ingredient and Efficacy), p. 79), has been a potent ingredient in treating diabetes. Recently, the scope of research has been extended to American ginseng (Panax ginseng) and American ginseng (American ginsenog, Panax quiquefolius) and Chinese ginseng (Panax notoginseng) (Pharmacologic. Research. 49 (2004) 113, 113, Diabetes Care. 26 ( 2003) 1277) The scope of the experiment is not limited to roots, but has been expanded to various materials such as fruits and leaves (Diabetes, 51 (2002) 1851, J. Chinese Med. 30 (2-3), 187).

The inventors have noted that a variety of experiments have a high ginsenoside content, the sample containing a lot of triol-based components such as Re, Rg1 has good pharmacological activity (Pharmacologic. Research. 49 (2004), Diabetes, 51 ( 2002) 1851), a high purity ginsenoside triol formulation was developed as an antidiabetic substance through this experiment.

As shown in the results of the present experiment, ginsenoside (PC-1) without ginsenosides extracted from ginseng showed little hypoglycemic effect, but the composition of the present invention (details and drawings of the present invention) In combination with the abbreviation “T-2”) has a very good hypoglycemic effect.

Triol ginsenosides, in addition to hypoglycemic effects, have an immune enhancing effect (Okamura N et al. Biol . Pharm . Bull . 17 (2), 270 (1994)) and anti-fatigue (Saito H et al. Japan J. Pharmacology , 24, 119 (1974)), Vasodilation ( Life Science 56 (19), 1577 ( 1995),) and cardiovascular protection (Clin Exp Pharmacol Physiol 23 (8 ....): 728 (1996)) , etc. It has various pharmacological activity exhibit other beneficial effects other than glucose lowering Expect to be.

An object of the present invention is to provide a natural high-purity ginsenoside composition having excellent hypoglycemic effect, almost no toxicity and side effects, and is applicable to both functional foods and pharmaceuticals, and has a constant component ratio.

In order to prepare a complex ginsenoside composition having a strong hypoglycemic action, the present inventors reproducibly separate triols such as Rg1, Re, and R1 with a total component of ginsenoside content of 80% or more and a single component, and thus, the complex ginsenoside The effect of the hypoglycemic effect of the pharmacological activity compared to the various single ginsenosides have been found to invent a better hypoglycemic composition.

The present invention relates to a hypoglycemic agent containing ginsenoside R1 as an active ingredient.

In addition, the present invention comprises 50% by weight or more of ginsenosides, characterized in that the triol component containing two or more of Rg1, Re, R1 is included as an active ingredient of 50% by weight or more of the total ginsenosides It relates to a hypoglycemic composition.

In addition, the present invention relates to a hypoglycemic composition, wherein the ginsenoside triol component is 60-83 wt% of Rg1, 7-20 wt% of Re, and 10-20 wt% of R1.

In addition, the present invention relates to a blood glucose lowering agent composition, wherein at least one of ginsenosides Rb1 and Rd is additionally included in an amount of less than 15% by weight relative to the triol component.

In the present invention, the ginsenoside is characterized in that it is obtained from ginseng and extracts including Korean ginseng (Panax ginseng), Panax notoginseng, American ginseng (Panax quiquefolius).

The present invention provides a diabetes prevention and treatment composition comprising a ginsenoside composition comprising ginsenoside triols Rg1, Re, and R1 as an active ingredient.

In addition, the present invention provides a health supplement food composition for preventing and alleviating diabetes comprising ginsenoside composition containing ginsenoside triol Rg1, Re, R1 as an active ingredient.

Hereinafter, the present invention will be described in more detail.

Ginseng ginsenoside triol Rg1, Re, R1 (20 (S) -protopanaxatriol 6- [O-β-D-xylopyranosyl- (1 → 2)-containing as an active ingredient in the diabetes prevention and treatment composition according to the present invention β-D-glucopyranosyl] -20-O-β-D-glucopyranoside) is a substance having the structures of the following Chemical Formulas 1, 2, and 3, respectively.

The ginsenoside triols Rg1, Re, R1 are commercially available but expensive. The inventors obtained the ginsenoside triol composition from dried ginseng in the same manner as described in Example 1 below.

The ginsenoside triol composition of this invention can be used as it is.

The diabetic prophylactic and therapeutic composition of the present invention may be formulated into various pharmaceutical formulations including ginsenoside triols Rg1, Re, R1 as active ingredients, such as oral or parenteral formulations such as granules, tablets, capsules, injections, and the like. . When formulating the diabetic prophylactic and therapeutic composition of the present invention, various carriers used in medicine, for example, excipients or other additives, such as stabilizers, emollients, emulsifiers, etc., may be used, as long as they do not adversely affect the effect of the active ingredient. have. In pharmaceutical formulations, the unit content of the ginsenoside triol composition can vary widely depending on the formulation and can be used in accordance with conventional methods.

In addition, the diabetic prevention and treatment composition of the present invention can be administered in various ways, such as the condition of the patient, for example, the dosage of the ginsenoside triol composition may be 30-3000mg per day for adults.

Hereinafter, the specific configuration of the present invention in detail in the Examples. However, the scope of the present invention is not limited only to the description of these examples.

Example 1 Preparation of Complex Ginsenosides and Ginsenoside Triols

1 kg of dried ginseng was extracted with 90% ethanol at 60 ° C. for 3 hours, filtered through a filter paper, and concentrated in a vacuum concentrator (20L, Heidolph). After the extraction, the remaining dried product was again extracted with 90% ethanol at 60 ° C. for 3 hours twice to obtain 200 g of the finally obtained extract. After dissolving it in water, it was adsorbed by passing through a column filled with methacrylate type resin (HP2MG, Mitsubishi Chemical), and then desorbed with 95% ethanol after washing with water and low concentration of ethanol to give a purity of 80% or more. 50g of side (aka "PC-1") was obtained. The extract was concentrated under reduced pressure, powdered, dissolved in water, adsorbed onto methacrylate resin (Methacrylate type resin, HP2MG, Mitsubishi Chemical), and 15% EtOH and 20% EtOH were sequentially used as a desorbent, purity 80% 20 g of the complex ginsenoside triol composition (hereinafter, abbreviated as "T-2") as the composition of the present invention was obtained.

Example 2: Component Analysis of T-2 and PC-1

The components of the complex ginsenoside composition “T-2” obtained in Example 1 were qualitatively and quantitatively analyzed by HPLC equipped with a C18 column (see FIG. 2).

Total ginsenoside content: 80% or more

Composition of major ginsenosides (triol fraction):

Rg1 (60-70%), Re (7-15%), R1 (10-20%), Rb1 (3-5%), Rd (4-8%)

Example 3: Hypoglycemic Effect of T-2 in Oral Maltose Tolerance Test

Normal ICR mice were used after fasting for 16 hours. T-2, PC-1 samples and acarbose were administered orally at concentrations of 40 and 50 mg / kg, respectively, as a positive control and 2 g after 90 minutes. Maltose of / kg was administered orally in a liquid amount of 10ml / kg. Blood glucose was measured before (0hr) and 15, 60, and 120 minutes post-maltose administration.

When the maltose was administered to normal mice, the blood glucose level rose to the highest level at 15 minutes, and then decreased to a normal level at 120 minutes. As a result of 15 minutes when the blood sugar level was raised to the highest level, the solvent administration group increased 230.8 mg / dl compared with the blood glucose before the maltose administration, and the composition of the present invention, “T-2” sample, 40 mg / kg administration group was 142.9 mg / dl. Statistically significant inhibition of blood glucose elevation was found in 38.1% (p <0.001) compared to solvent control. However, almost identical amounts of ginsenoside diol and triol were mixed in PC-1. In the case of positive control acarbose, blood glucose increase was 85.0 mg / dl, which was 63.2% (p <0.001). These results indicate that the composition of the present invention has a hypoglycemic effect by oral administration.

process Dose (mg / kg) Changes in blood glucose before and after malt sugar (mg / dl) Blood glucose increase (15 min-0hr) % Inhibition ^a 0hr 15min Solvent Control Group (Sterile Distilled Water) - 157.5 ± 13.2 388.3 ± 38.2 230.8 - Re 40 130.7 ± 16.6 372.9 ± 61.6 242.2 - R1 40 140.0 ± 16.8 288.7 ± 47.5 ** 148.7 37.9 Rg1 40 128.4 ± 18.5 277.8 ± 48.6 *** 149.4 37.6 PC-1 40 135.3 ± 14.8 335.0 ± 50.3 199.7 13.2 T-2 40 138.6 ± 18.0 286.8 ± 54.4 ** 148.2 38.1 Akabos 50 121.9 ± 28.2 206.9 ± 24.6 *** 85.0 63.2

*** p <0.001, ** p <0.01

^a % inhibition = [(sample blood glucose increase / solvent control blood glucose increase) x 100]-100

The present invention is a composition of a high purity ginsenoside mixture of more than 80% of a constant component having an excellent hypoglycemic effect in patients with type 2 diabetes. These ingredients provide pharmaceutical or food preparations in the form of single or multiple preparations.

As a ginsenoside mixture extracted from ginseng which is a natural substance for diabetic treatment according to the present invention, it can be used as a functional food as well as pharmaceuticals. In addition, it is expected to be an excellent antidiabetic agent because of its excellent hypoglycemic activity and excellent safety as a natural product derived from the oral antihyperglycemic agent, which is already on the market, with little side effects.

Claims (5)

Ginsenoside R1 (20 (S) -protopanaxatriol 6- [O-β-D-xylopyranosyl- (1 → 2) -β-D-glucopyranosyl] -20-O-β-D-glucopyranoside) as an active ingredient Hypoglycemic agents. The method according to claim 1, wherein the ginsenoside containing 50% by weight or more, and the triol component including two or more of Rg1, Re, R1 is contained as an active ingredient of 50% by weight or more of the total ginsenosides Hypoglycemic composition. The hypoglycemic composition according to claim 2, wherein the ginsenoside triol component is 60-83 wt% of Rg1, 7-20 wt% of Re, and 10-20 wt% of R1. The hypoglycemic composition according to claim 1 or 2, wherein at least one of ginsenosides Rb1 and Rd is further included in an amount of less than 15 parts by weight based on 100 parts by weight of the triol component. According to claim 1, wherein the ginsenoside ginseng (Panax ginseng), Ginseng (Panax notoginseng), American ginseng (Panax quiquefolius), including the ginseng and the extract, characterized in that obtained from the extract

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