JP4547892B2 - α-Glucosidase inhibitor - Google Patents

Description

  The present invention relates to an α-glucosidase inhibitor that is safe and effective even when taken for a long period of time.

  In recent years, lifestyle-related diseases, for which lifestyle habits such as eating habits, exercise habits, rest, smoking, and alcohol consumption are thought to affect the onset and progression of the disease, have attracted attention. In developed countries, obesity, non-insulin dependent diabetes mellitus (type II diabetes), hyperlipidemia, hypertension, etc., which have a strong relationship with dietary habits and exercise habits, have hindered people's health maintenance. Not only does it lead to a decline in quality of life (QOL), but it has also become a major social problem, causing a rapid increase in national medical expenses.

  α-Glucosidase is an enzyme that decomposes disaccharides such as maltose and sucrose in the intestine into monosaccharides, and can inhibit the absorption of carbohydrates by inhibiting its action. Therefore, an α-glucosidase inhibitor is effective in preventing or improving diabetes, obesity, and the like because it significantly suppresses postprandial hyperglycemia.

  Currently, α-glucosidase inhibitors such as acarbose and voglibose are used as antidiabetic agents for the treatment of diabetes. Although these drugs are not serious, such as an increase in intestinal gas, unpleasant symptoms have been reported for patients, and better drugs have been demanded.

  Conventionally, as an α-glucosidase inhibitor derived from natural products, an extract of α-glucosidase inhibitor (Patent Document 1), allspice, and clove extract obtained by extracting from water of Maou, polar solvent or a mixed solvent thereof is used. Α-Glucosidase inhibitor as an active ingredient (Patent Document 2), Carbolytic digestive enzyme inhibitor (Patent Document 2) containing ellagitannin as an active ingredient 3), α-glucosidase inhibitor (Patent Document 4) containing an extract of Rahma, Keihi, eucalyptus, and loquat (excluding fruit parts) is known.

  Herb medicine (soybean bean) is a dried product of the mature seed nodules of Alpinia katsumadai of the ginger family, and is known for its use as an aromatic stomachic medicine, an antipruritic drug and the like. In addition, Sakuhakuyo (acupuncture leaves) is obtained by drying branches with leaves of the cypress family Thuja orientalis, and its use as an astringent, analgesic and hemostatic agent is known (Non-patent Document 1).

  However, these natural products are not known to have an α-glucosidase inhibitory action and an action to improve obesity and diabetes based on this.

Japanese Patent Laid-Open No. 9-2963 JP 2001-181194 A Japanese Patent Laid-Open No. 9-176019 Japanese Patent Laid-Open No. 2001-163795 Written by Namba Tsuneo, “Wakan Yakuen Encyclopedia”, Yoikusha, [I] November 30, 1993, all revised new edition, [II] February 28, 1994, all revised new edition, p.89-90, p. 239-240

  An object of the present invention is to provide an α-glucosidase inhibitor that is safe and effective even when continuously taken for a long time.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that certain herbal medicines or extracts thereof have excellent α-glucosidase inhibitory activity and suppress the increase in blood sugar during glucose tolerance or diabetes. Furthermore, the present invention was completed by finding that it is useful as a pharmaceutical and a food because it suppresses the weight gain of dietary obesity.

  That is, the present invention is an α-glucosidase inhibitor, a preventive or ameliorating agent for diabetes, and a prophylactic or improving agent for obesity, characterized in that it contains one or two selected from the group consisting of Suzuku and Sakuhakuyo.

  The present invention is effective in preventing or improving obesity and diabetes because it is effective in inhibiting carbohydrate absorption based on α-glucosidase inhibitory action and improving postprandial hyperglycemia.

  The saw crab and sakuhakuyo of the present invention can be used as a crude drug powder, an extract extracted with water, a polar solvent, a mixed solvent thereof or the like, a dry extract, a flow extract and the like.

  The dose of the herbal medicine of the present invention can be appropriately increased or decreased in consideration of age, sex, etc., but can be generally used in the range of 100 mg to 50 g as a crude drug equivalent per day for an adult, preferably 500 mg to 30 g.

The present invention is a qualitative and quantitative range not to impair the effects of the invention, vitamins, xanthine derivatives, amino acids, excipients, pH adjustment agents, refreshing agents, suspending agents, antifoaming agents, thickener , Solubilizers, disintegrants, binders, lubricants, antioxidants, coating agents, coloring agents, flavoring agents, surfactants, plasticizers, fragrances, etc. Oral or parenteral preparations such as granules, powders, capsules, dry syrups, chewable tablets, and transmucosal agents.

  According to the present invention, it has become possible to provide a highly safe drug or food that can prevent or ameliorate an increase in blood sugar level due to excessive intake of carbohydrates, and can further prevent or ameliorate lifestyle-related diseases such as obesity and diabetes. .

  The present invention will be specifically described below with reference to examples and test examples.

  After mincing the sawtooth, 10 times the amount of 50% ethanol was added, and the mixture was extracted by heating at about 80 ° C. After filtration, the ethanol was distilled off under reduced pressure, and further concentrated to obtain an extract.

  After crushing Sakuhakuyo, 10 times the amount of 50% ethanol was added, extracted by heating at about 80 ° C., filtered and evaporated under reduced pressure, and further concentrated to obtain an extract.

Test Example 1 (Measurement of α-glucosidase inhibitory action)
Each crude drug extract obtained in Examples 1 and 2 (dissolved in 2.5% DMSO) 25 μL, phosphate buffer (0.25 M, pH 6.5) 125 μL, substrate solution 50 μL (1.4 mM p-nitrophenyl-α-D-glucopyranoside) Then, 50 μL of an enzyme solution (Bacillus stearothermophilus-derived α-Glucosidase 1.0 U / mL) was added and reacted at 37 ° C. for 30 minutes, and then the absorbance at a wavelength of 405 nm was measured. Each crude drug extract was added at final concentrations of 6.25 , 12.5 , 25 , 50 and 100 μg / mL.

  The results are shown in Table 1 and FIG.

表および図から明らかなように、ソウズクおよびソクハクヨウはα−グルコシダーゼ阻害作用を示し、糖尿病、肥満に対して予防あるいは改善作用を有することが明らかになった。

As is apparent from the tables and figures, it was clarified that Suzuku and Sakuhakuyo have an α-glucosidase inhibitory action and have a preventive or ameliorating action on diabetes and obesity.

Test Example 2 (Measurement of blood glucose elevation inhibitory effect after sucrose administration)
The effect of each herbal extract obtained in Examples 1 and 2 on the increase in blood glucose after sucrose administration was examined.

  Each herbal extract was orally administered to SD male rats (6 weeks old, Nippon Charles River) at a dose of 300 mg / kg (converted to dry extract), and 5 minutes later, a sucrose solution was orally administered at a dose of 2 g / kg. Twenty minutes later, blood was collected from the posterior vena cava under ether anesthesia, and the serum was separated by centrifugation (3000 rpm, 20 ° C.). The glucose concentration in serum was quantified using Glucose CII Test Wako (Wako Pure Chemical Industries).

  The results are shown in Tables 2 and 3 and FIGS.

  As is apparent from the tables and figures, Souzuki significantly suppressed the increase in blood glucose level, and Sakuhakuyo tended to suppress the increase in blood glucose level. From this, it has been clarified that Sakuhakuyo and Suzukuku suppress sugar absorption and have a preventive or ameliorating action on diabetes and obesity.

Test Example 3 (Measurement of inhibitory effect on body weight gain of diet-induced obesity model rat)
The extract obtained in Example 1 and Example 2 was orally administered to SD male rats (8 weeks old, Charles River) at a dose of 300 mg / kg (converted to dry extract) once a day for 7 weeks. Body weight was measured. In addition, during the period from the start of the extract administration to the end of the experiment, the rats were fed a high preference food (high calorie food) . However, the normal group was fed a normal diet.

  The results are shown in Table 4 and FIG.

  As is clear from the table and the figure, Souzuki significantly suppressed the increase in body weight caused by the intake of a high-calorie diet, and Sakuhakuyo showed this tendency. That is, it was revealed that both extracts are effective in preventing or improving obesity.

  The present invention is effective in preventing or improving obesity and diabetes because it is effective in inhibiting carbohydrate absorption based on α-glucosidase inhibitory action and improving postprandial hyperglycemia.

  According to the present invention, it has become possible to provide a highly safe drug or food that can prevent or ameliorate an increase in blood sugar level due to excessive intake of carbohydrates, and can further prevent or ameliorate lifestyle-related diseases such as obesity and diabetes. .

It is the figure which showed the alpha-glucosidase activity inhibition rate about each crude drug extract of this invention, and showed the inhibition rate on each vertical axis | shaft, and the density | concentration on each horizontal axis. It is the figure which showed the alpha-glucosidase activity inhibition rate about a saw crab extract, the blood glucose level was shown on the vertical axis | shaft and the crude drug name was shown on the horizontal axis. It is the figure which showed the alpha-glucosidase activity inhibition rate about Sakuhakuyo extract, the blood glucose level was shown on the vertical axis | shaft and the crude drug name was shown on the horizontal axis. It is the figure which showed the effect | action with respect to the body weight increase by a high-calorie diet intake about the saw crab and Sakuhakuyo of this invention, and showed the administration period on the vertical axis | shaft and the horizontal axis | shaft.

Claims (3)

  An α-glucosidase inhibitor characterized by containing Sakuhakuyo.   A preventive or ameliorating agent for diabetes, comprising Sakuhakuyo.   A preventive or ameliorating agent for obesity characterized by containing Sakuhakuyo.

Images