JP2007277099A - Hyperinsulinemia-improving agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hyperinsulinemia-improving agent administered safely and simply for a long period and excellent in an effect of improving the hyperinsulinemia. <P>SOLUTION: This hyperinsulinemia-improving agent contains Dunaliella obtained by using a dried material of Dunaliella frond [Donaliella salina (Donal) Teodoresco]. By orally administering the hyperinsulinemia-improving agent, the sensitivity of insulin is improved to suppress the secretion of the insulin, and various diseases such as diabetes, hypertension, lipid metabolism abnormality accompanying with insulin resistance and arteriosclelosis, etc., associated with these diseases can be improved or prevented. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an agent for improving hyperinsulinemia, and more particularly to an agent for improving hyperinsulinemia that improves hyperinsulinemia associated with insulin resistance.

  Obesity is an inevitable physical condition in modern society and can lead to diabetes, hyperlipidemia, gout, arteriosclerotic disease, hypertension and the like. In order to treat or prevent such obesity or obesity-related diseases, it is necessary to practice diet and exercise for a long time and / or administer a therapeutic drug for a long time.

  Insulin, an endocrine hormone associated with obesity, has the effect of lowering blood glucose levels. In obese subjects, glucose tolerance tests show a decrease in glucose tolerance despite a sufficient insulin secretion. Even when insulin is administered, the blood glucose lowering of obese is weaker than that of normal weight. Thus, in a state showing insulin resistance in which the ability of insulin to lower blood sugar is reduced, the B cells of the pancreas recognize that insulin secretion is insufficient, and further try to normalize the hyperglycemic state by increasing insulin secretion. To do. However, if such a state continues for a long time, the insulin secretion ability of B cells eventually decreases, and the hyperglycemic state becomes more serious. Therefore, treatment with drugs is essential.

  As an anti-obesity agent or anti-obesity food, for example, in Japanese Patent No. 3404235 (Patent Document 1), a yeast fermented strawberry fruit is used as an active ingredient, and the anti-obesity action is an α-amylase inhibitory action and / or lipase inhibitory action. An anti-obesity agent that is based on the above is described, and Japanese Patent No. 3487079 (Patent Document 2) includes soy protein in a dry solid content (a soy protein hydrolyzate having a hydrolysis rate of 30 to 80%). ) Is 30 to 60% by weight as crude protein, 2 to 10% by weight of glycerides and fats, 27 to 60% of carbohydrates and vitamins and minerals are described in Japanese Patent No. 3591166 (Patent Document 3) ) Describes an anti-obesity agent containing a water extract of gold wire lotus as an active ingredient, and Japanese Patent No. 3302346 (Patent Document 4) describes rye, barley, banaba, mulberry leaves and sarah. One or more selected from the group consisting of powders and extracts of a reticulata, and powders and extracts of Gymnema sylvestre, Gymnema indrum, cod and tomburi, indigestible dextrin, galactomannan and soluble sodium alginate An anti-diabetic, anti-obesity and / or postprandial blood glucose rise inhibitory food containing at least one selected from the group consisting of the following groups is described, and Japanese Patent No. 3029907 (Patent Document 5) describes 4-cholesten-3-one. An antiobesity agent characterized in that it contains is described.

  Regarding insulin resistance, for example, in Japanese Patent No. 2513360 (Patent Document 6), hyperlipidemia, hyperglycemia, obesity, impaired glucose tolerance, hypertension, which contains a condensed heterocyclic compound as an active ingredient. Insulin resistance such as diabetes, osteoporosis, cachexia, fatty liver, diabetic complications, arteriosclerosis, cataracts and other prophylactic and / or therapeutic agents, gestational diabetes other than the above diseases, polycystic ovary syndrome, etc. Patent No. 3357378 (Patent Document 7) describes a preventive agent and / or a therapeutic agent for a disease caused by the disease, and a novel aryl having an excellent effect on increasing the action of insulin in an insulin resistant symptom. Alkyl- or aryloxyalkyl-substituted oxirane carboxylic acids are described.

Thus, various anti-obesity agents, anti-obesity foods, therapeutic agents for insulin resistance, and the like have been proposed in the past. However, the demand for drugs and foods that can improve insulin resistance is expected to increase in the future.
Japanese Patent No. 3404235 Japanese Patent No. 3487079 Japanese Patent No. 3591166 Japanese Patent No. 3302346 Japanese Patent No. 3029907 Japanese Patent No. 2513360 Japanese Patent No. 3357378

  The present invention has been made in view of the above-described problems existing in the prior art, and the object of the present invention is to be able to administer safely and simply over a long period of time, and to improve hyperinsulinemia. The object is to provide an excellent agent for improving hyperinsulinemia.

  The hyperinsulinemia-improving agent of the present invention that achieves the above object is intended to improve hyperinsulinemia such as hyperinsulinemia associated with insulin resistance, and contains donariella. The hyperinsulinemia-improving agent of the present invention can be obtained by using a dried product of Donariella algae, various solvent extracts such as water and alcohol, and purified products thereof. The dried product of the Donariella alga body itself may be used, or the dried product of the Donaliella alga body may be subjected to a general treatment.

  The hyperinsulinemia-improving agent of the present invention can be safely and simply administered orally for a long period of time, and is used for various diseases such as diabetes associated with insulin resistance, hypertension, abnormal lipid metabolism, and arteriosclerosis associated with these diseases. Effective for improvement or prevention.

  The Dunaliella in the present invention belongs to the order of the green alga Ohihigenari, and examples thereof include Dunaliella parva, Dunaliella primolecta, Dunaliella salina (Dunal) Teodoresco, Dunaliella terti, Dunaliella tertiolecta, Dunaliella bardawil and the like. Most suitable for the present invention is Dunaliella salina (Dunal) Teodoresco.

  The hyperinsulinemia-improving agent of the present invention can be used, for example, by dispersing or dissolving a dried product such as a dried powder of Donariella alga in various reference solids, semi-fluids, or liquids.

  The dose of the hyperinsulinemia-improving agent of the present invention to an adult is suitably about 0.1 to 40 g per day when the dried product of Donariella alga is used as a reference.

  The form of oral administration in the hyperinsulinemia-improving agent of the present invention is not particularly limited, but preferably a nutritional food, a nutritional supplement, a powder, a granule, a tablet, a hard capsule, a soft capsule, or a beverage liquid It is a form.

  In forming various forms, various excipients, binders, disintegrants, lubricants, coating agents, coloring agents, flavoring agents, flavoring agents, plasticizers, and the like can be appropriately used.

  Examples of excipients include sugars (lactose, sucrose, glucose, mannitol), starch (potato, wheat, corn), minerals (calcium carbonate, calcium sulfate, sodium bicarbonate, sodium chloride), crystalline cellulose, plant powder ( Licorice powder, gentian powder) and the like.

  Examples of binders include starch paste, gum arabic, gelatin, sodium alginate, methyl / recellulose (MC), ethyl cellulose (EC), polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC). And carboxymethylcellulose (CMC).

  Examples of the disintegrant include starch, agar, gelatin powder, crystalline cellulose, CMC / Na, CMC / Ca, calcium carbonate, sodium hydrogen carbonate, sodium alginate and the like.

  Examples of lubricants include magnesium stearate, talc, hydrogenated vegetable oil, macrogol, silicone oil and the like.

  Examples of coating agents include sugar coating (sucrose, HPC, shellac), glue (gelatin, glycerin, sorbitol), film coating [hydroxypropylmethylcellulose (HPMC), EC, HPC, PVP], enteric coating [hydroxyprovir Methyl cellulose phthalate (HPMCP), cellulose acetate phthalate (CAP)] and the like.

  Examples of the colorant include water-soluble food dyes and lake dyes. Examples of the corrigent include lactose, sucrose, glucose, mannitol) and the like. Examples of flavoring agents include aromatic essential oils) and light blocking agents (titanium oxide). Examples of the plasticizer include phthalic acid esters, vegetable oils, and polyethylene glycol).

  Hyperinsulinemia improvement trial

  1. Test substance

  Using dry powder of Dunaliella salina (Dunal) Teodoresco

  2. Test animal

  Four weeks old Slc: ddY (SPF) male mice were fed with high fat (fed according to the composition of the control group in the following feed composition table) from 5 to 15 weeks of age and were raised as control groups. They were divided into Donariella administration groups.

  3. Bait composition table

単位：g

Unit: g

  4). Test method

  A high-fat diet (control group) prepared based on the above-mentioned diet composition table, a high-fat diet (Donariera administration group) formulated with the test substance, and water freely orally over 8 weeks Ingested.

  1) Blood biochemical examination

  From the last day of administration of a high fat diet (control group) and a high fat diet containing a test substance (Donariella administration group) for 8 weeks, the mice were fasted for 18 hours or more while drinking water, and pathological anatomical examination (hereinafter, “ Prior to autopsy, blood was collected from a posterior vena cava under ether anesthesia using a syringe containing 0.05 mL of heparin sodium (trade name: Novoheparin injection 1000, 10000 U / 10 mL Aventis Pharma). Plasma was fractionated by subjecting the collected blood to centrifugation at 3000 rpm for 10 minutes at 4 ° C. About the obtained plasma, the following item (Glu: glucose) was measured.

  2) Endocrine test

  The plasma was immediately stored frozen at -80 ° C or lower. The following items were measured for this frozen specimen.

  Insulin measurement method is as follows.

  The frozen specimen was transferred to a refrigerator set at 4 ° C., thawed and kept at that temperature.

  In addition, the concentrated washing solution is diluted 10 times with distilled water, the biotin-conjugated anti-insulin antibody is diluted 4000 times with the sample dilution buffer, and the insulin standard solution is increased from 2 times to 128 times with the sample dilution buffer. Diluted.

  Next, the plate was washed four times with the diluted washing solution, and biotin-conjugated anti-insulin antibody was dispensed into each well at a rate of 45 μL / well and then stirred. Thereafter, a sample or serially diluted insulin standard solution (for calibration curve preparation) was dispensed to each well at a rate of 5 μL / well, stirred, and incubated at room temperature for 2 hours.

  About 15 minutes before the end of the incubation, the peroxidase avidin conjugate was diluted 500 times with the sample dilution buffer.

  After completion of the incubation, the plate was washed four times with the washing solution, and the peroxidase avidin conjugate was dispensed into each well at a rate of 50 μL / well, stirred, and then incubated at room temperature for 30 minutes.

  After completion of the incubation, the plate was washed four times with a washing solution, and a coloring solution (TMB) was dispensed at a rate of 50 μL / well to each well, followed by stirring, and then incubated at room temperature for 30 minutes.

  After the incubation was completed, the reaction stop solution was dispensed at a rate of 50 μL / well into each well without washing, and then stirred, and each absorbance was immediately measured with a microplate reader. The measurement wavelength in the absorbance measurement was set to a main wavelength λ1 = 450 nm and a subwavelength λ2 = 620 nm.

  4). Test results

  1) Blood biochemical examination

  The plasma glucose concentration was 127.8 ± 8.1 mg / dL in the control group and 123.9 ± 7.6 mg / dL in the Donariella administration group.

  2) Endocrine test

  The plasma insulin concentration was 3.29 ± 0.65 ng / mL in the control group and 1.26 ± 0.23 ng / mL in the Donariella administration group. The plasma insulin concentration in the Donariella administration group was significantly reduced by 61.63% compared to the control group.

  3) When 23-week-old Slc: ddY male mice were bred on a standard chow diet (non-high fat diet), plasma glucose concentration and plasma insulin concentration were 110.5 ± 6.5 mg / dL and 0.28, respectively. ± 0.19 ng / mL.

  That is, it can be seen that the control group loaded with high fat in this test had a high plasma glucose concentration and a very high plasma insulin concentration despite blood sampling under fasting for 18 hours.

  Therefore, the animals in the control group are in a state where the plasma glucose concentration cannot be sufficiently reduced despite the large amount of insulin being secreted, which is a condition of hyperinsulinemia due to so-called insulin resistance. The condition was recognized.

  On the other hand, the plasma insulin concentration in the Donariella administration group was significantly lower than that in the control group. The insulin sensitivity was improved by administration of Donariella, and the secretion of insulin was suppressed in a smaller amount than that in the control group. The hyperinsulinemia associated with was improved.

Claims (3)

  A hyperinsulinemia-improving agent comprising Donariella.   2. The hyperinsulinemia-improving agent according to claim 1, which improves hyperinsulinemia associated with insulin resistance.   The hyperinsulinemia-improving agent according to claim 1 or 2, wherein a dried product of Donariella alga is used.