JP2014201568A - Glp-1 secretion promoter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide pharmaceuticals, quasi drugs, food, feed and materials blendable thereto, having excellent GLP-1 secretion promoting effect and also high safety.SOLUTION: In this invention, Dioscorea nipponica Makino or its extract is used as an active ingredient.

Description

  The present invention relates to a GLP-1 (Glucagon-like peptide-1) secretion promoter.

  In recent years, lifestyle-related diseases such as diabetes, dyslipidemia, and hypertension have become major problems. In lifestyle-related diseases, lifestyle factors such as dietary habits are considered to contribute to the onset in addition to genetic factors. Although lifestyle improvement is considered effective in preventing and improving these lifestyle-related diseases, it is useful as a material useful for the development of lifestyle-related diseases by adjusting the physiological system, especially as a food and drink that can be taken on a daily basis. Expectations for possible materials are growing.

  GLP-1 is a hormone produced from a common gene and precursor with glucagon, which is an endocrine hormone. Glucagon is produced in the α cells of the islets, whereas GLP-1 is produced in the endocrine cells (L cells) of the lower gastrointestinal tract (ileum to colon) mucosal epithelium, and its precursor processes differently from glucagon. It is produced after. GLP-1 is a hormone with an incretin (Intestine Secretion Insulin) action that plays an important role in glucose metabolism. It is secreted into the blood by ingestion of nutrients and acts on the pancreatic β-cell to secrete insulin. Promotes and lowers blood sugar levels. GLP-1 also suppresses glucagon secretion from pancreatic alpha cells, thereby reducing glucose release from the liver and lowering blood glucose levels. Therefore, enhancing the effect of GLP-1 is useful for improving lifestyle diseases such as diabetes. In recent years, development of diabetes treatment methods using GLP-1 replacement therapy and GLP-1 receptor (GLP-1R) agonists has also been promoted.

  Furthermore, GLP-1 is considered useful for controlling blood glucose levels in diabetic patients. When GLP-1 suppresses pancreatic glucagon secretion, glucose release from the liver decreases and blood glucose decreases. It has been reported that this action does not antagonize glucagon secretion due to hypoglycemia and does not depend on insulin concentration. It has also been reported that administration of GLP-1 decreased the amount of insulin required to make blood glucose constant in both type 1 diabetic patients and type 2 diabetic patients. Furthermore, GLP-1 can exert an effect on blood glucose level control in the long term by acting on the central nervous system and suppressing appetite. Therefore, GLP-1 may improve the symptoms of patients with diabetes and insulin resistance through these actions. Exenatide and Liraglutide, which are actually GLP-1 analog preparations, have been used as antidiabetic drugs and reported to have an effect of improving insulin resistance (Non-patent Document 1).

  It has been reported that GLP-1 promotes glucose uptake in skeletal muscle to improve glucose tolerance (Non-patent Document 2), or promotes sugar uptake in cardiac muscle to improve cardiac function (Non-patent Document 3). ing. Thus, increasing GLP-1 secretion can increase sugar (glucose) uptake.

  GLP-1 is also known to have an effect on the central nervous system such as suppression of gastric excretion and gastric acid secretion, and suppression of appetite and food intake. It has been reported that an eating suppression effect is exhibited (Non-patent Document 4). Therefore, increasing GLP-1 secretion is useful for appetite suppression.

Furthermore, GLP-1 enhances myocardial contractile force by increasing cAMP in myocardial cells by signaling via GLP-1 receptors present in cardiomyocytes, endocardium, coronary vascular endothelial cells and smooth muscle. It has been reported that it promotes NO production and increases glucose uptake through GLUT1 to show an effect of improving cardiac function. GLP-1 has been reported to increase NO production from vascular endothelial cells and improve vasorelaxation by signaling via GLP-1R present on vascular endothelial cells (Non-patent Document 5). . Increased NO production has an effect of inhibiting platelet aggregation (Non-Patent Document 6) and an effect of suppressing PAI1, which is a factor that promotes thrombus formation (Non-Patent Document 7), and has been reported to improve arteriosclerosis. ing. It has also been reported that administration of GLP-1 and exenatide (GLP-1 receptor agonist) analogs to Dahl salt-sensitive rats (4 weeks, subcutaneous administration) significantly reduces systolic blood pressure ( Non-patent document 8).
Therefore, enhancing the effect of GLP-1 is useful for improving lifestyle-related diseases such as cardiac function improvement, arteriosclerosis improvement, and hypertension.

  However, the active body of GLP-1 is a polypeptide, and when GLP-1 is orally ingested, it is easily digested and degraded by digestive enzymes in the digestive tract and has a very short half-life in vivo. Therefore, even if GLP-1 is administered from outside the body, it is very difficult to keep the blood concentration constant. Therefore, in order to increase the in vivo GLP-1 concentration over a long period of time, it is desirable to promote the secretion of endogenous GLP-1 rather than the administration of GLP-1 from outside the body.

  Here, as a substance that promotes secretion of GLP-1 from research in a culture system, palmitic acid, oleic acid, meat hydrolyzate (MH), gastrin releasing peptide (GRP), carbachol, forskolin, ionomycin, myristic acetate Acid phorbol (PMA), essential amino acid (EAA), leucine, isoleucine, skim milk, casein, leptin, muscarinic receptor M1, M2, kiraya or its extract, lysophosphatidylinositol or its salt have been reported so far (Non-patent documents 9 to 13, Patent documents 1 and 2).

On the other hand, Uchiwadokoro is a plant of the mosquito family, and the Uchiwadokoro or an extract thereof has been reported to have an effect of promoting blood circulation and improving liver function and to have an anti-obesity effect (Non-Patent Document 14) by lipase inhibition. .
However, the relationship between prickly pear and GLP-1 secretion promotion is not known.

JP 2012-131742 A International Publication No. 2012/086406

History of Medicine, 2009, 231 (7): 755-758 FEBS letters, 1994, 349 (2), 313-316 J pharmacol Exp Ther, 2006, 317 (3), 1106-1113 Eur J Pharmacol, 2002, 440 (2-3): 269-279 History of Medicine, 2012, 241 (7): 507-516 Br J Pharmacol. 1987; 92: 181-187 Arterioscler Thromb Vasc Biol. 1998; 18: 1771-1779., Eur J Biochem. 2000; 267: 1001-1007 Cardiovascular Diabetology 2010, 9:32 Endocrinology, 2001, 142 (10): 4522-4528 Journal of Endocrinology, 2006, 191,159-170 Nutrition, 2009, 25 (3): 340-349 Endocrinology, 2003, 144 (7): 3244-3250 Diabetes, 2006, 52 (2): 252-259 Biosci. Biotechnol. Biochem., 2003 67 (7), 1451-1456,

  The present invention relates to providing pharmaceuticals, quasi-drugs, foods, feeds, and materials that can be blended in them, which have an excellent GLP-1 secretion promoting action and are highly safe.

  As a result of researches to solve the above-mentioned problems, the present inventors have found that the extract of Prickly Plow has GLP-1 secretion promoting action.

That is, the present invention relates to the following.
(1) A GLP-1 secretion promoter containing prickly pear or an extract thereof as an active ingredient.
(2) A glucagon secretion inhibitor containing prickly pear or an extract thereof as an active ingredient.
(3) A preventive and / or ameliorating agent for postprandial hyperglycemia comprising prickly throat or an extract thereof as an active ingredient.
(4) A prophylactic and / or ameliorating agent for insulin resistance comprising a prickly throat or extract thereof as an active ingredient.
(5) A preventive and / or ameliorating agent for diabetes comprising prickly throat or an extract thereof as an active ingredient.
(6) An appetite suppressant containing prickly pear or an extract thereof as an active ingredient.
(7) A preventive and / or ameliorating agent for deterioration of cardiac function comprising prickly throat or an extract thereof as an active ingredient.
(8) A preventive and / or ameliorating agent for arteriosclerosis comprising prickly pear or an extract thereof as an active ingredient.

  Since the GLP-1 secretion promoter of the present invention has an excellent GLP-1 secretion promoting action and is highly safe even when ingested for a long time, it suppresses glucagon secretion, prevents postprandial hyperglycemia, and / or It has the effect of improving, preventing and / or improving insulin resistance, preventing and / or improving diabetes, suppressing appetite, suppressing gastric excretion, preventing and / or improving deterioration of cardiac function, preventing and / or improving arteriosclerosis. It is useful as a pharmaceutical product, quasi-drug and food product to be obtained, or as a material or preparation for blending them.

It is the figure which measured GLP-1 secretion by ELISA by the extract of Prickly Pear.

  In the present invention, “GLP-1 secretion promotion” refers to promoting GLP-1 secretion from endocrine cells (L cells) of the digestive tract mucosal epithelium when ingested or meals, particularly carbohydrates or lipids. This refers to promoting in vivo GLP-1 secretion caused by ingesting a diet rich in. Alternatively, the increase in blood GLP-1 concentration associated with GLP-1 secretion in vivo mainly after meal is maintained, the increased GLP-1 concentration is maintained, or the decrease in the increased GLP-1 concentration is suppressed. To do.

Further, “suppression of glucagon secretion” refers to suppression of the action of increasing blood glucose via glucagon secretion suppression action. The suppression includes not only suppression of glucagon secretion by direct action of GLP-1 on pancreatic α cells, but also paracrine α cell suppression via insulin from β cells and somatostatin from δ cells.
“Appetite suppression” refers to a decrease in appetite or food intake and the accompanying suppression of weight gain. The suppression is mainly effected via the hypothalamic feeding center of the central nervous system of GLP-1.

In the present invention, “prevention” means prevention or delay of the onset of a disease or symptom in an individual, or reduction of the risk of onset of a disease or symptom in an individual. “Improvement” refers to improvement of a disease, symptom or condition, prevention or delay of worsening of the disease, symptom or condition, or reversal, prevention or delay of progression of the disease or symptom.
“Improving cardiac function” refers to enhancing the muscle contraction force of the heart, enhancing insulin sensitivity of the heart muscle and glucose uptake of the heart, and improving the accompanying cardiac function. This action includes not only the direct action of GLP-1 on the heart but also the action via nerve stimulation transmitted from the brain by the vagus nerve.
“Improving arteriosclerosis” refers to improving arteriosclerosis by improving endothelium-dependent vasodilator response through eNOS activation. The effect is not only due to the signal transduction of GLP-1 through vascular endothelial cells via GLP-1R, but also suppresses monocyte / macrophage accumulation and inflammatory reaction in the arterial wall, and regulates chylomicron secretion in the intestine Including the action via
“After meal” means the time until the carbohydrates in the ingested meal are generally absorbed. Immediately after taking the meal (0 minutes) to 6 hours later, preferably 5 hours later, more preferably 4 hours. Time until later, more preferably after 3 hours (Diabete Care, 2001, 24 (4): 775-778).

  In the present invention, Prickly Pear refers to Dioscorea nipponica Makino belonging to the genus Dioscorea.

Such prickly wings can use any arbitrary part, for example, whole grass, leaves, stems, buds, flowers, buds, roots, rhizomes, calluses, corms, tubers, seeds, etc., or combinations thereof. It is preferable to use a rhizome.
Such a prickly throat can be used as it is or as a squeezed juice obtained by squeezing it, a dried product or pulverized product thereof, or an extract extracted therefrom, but it is preferably used as an extract.

  As the above-mentioned extract, various solvent extracts obtained by known extraction methods such as extraction of prickly throat at room temperature or under heating, or extraction using an extraction device such as a Soxhlet extractor, or a diluted solution thereof , Its concentrated liquid, its dry powder, paste, or its activated carbon-treated one.

Known extraction methods include, for example, solid-liquid extraction, liquid-liquid extraction, immersion, decoction, leaching, reflux extraction, ultrasonic extraction, microwave extraction, stirring, and the like. In order to shorten the extraction time, solid-liquid extraction with stirring is desirable. Examples of suitable conditions for this solid-liquid extraction include stirring at 10 to 100 ° C. and 100 to 400 rpm / min for 1 to 30 minutes. As a suitable example of immersion, the immersion for 1 hour-14 days is mentioned at 10-50 degreeC. Moreover, when shortening extraction time, solid-liquid extraction with stirring is desirable.
In order to prevent oxidation of the extract, a means for extraction under a so-called non-oxidizing atmosphere while removing dissolved oxygen by bubbling degassing or inert gas such as nitrogen gas may be used in combination.

  As the solvent for extraction, either a polar solvent or a nonpolar solvent can be used. Specific examples of the solvent include water; alcohols such as methanol, ethanol, propanol and butanol; polyhydric alcohols such as propylene glycol and butylene glycol; ketones such as acetone and methyl ethyl ketone; methyl acetate and ethyl acetate Esters; linear and cyclic ethers such as tetrahydrofuran and diethyl ether; polyethers such as polyethylene glycol; hydrocarbons such as squalane, hexane, cyclohexane and petroleum ether; aromatic hydrocarbons such as toluene; dichloromethane and chloroform And halogenated hydrocarbons such as dichloroethane; and supercritical carbon dioxide; pyridines; organic solvents such as oils and fats, other oils such as wax; and mixtures thereof. Preferable examples include water, alcohols, alcohol-water mixtures and hydrocarbons, with alcohol-water mixtures and hydrocarbons being more preferred. As the alcohol, an alcohol having 1 to 5 carbon atoms is preferable, and ethanol is more preferable. As the hydrocarbon, hexane is more preferable.

  When an alcohol-water mixture is used as a solvent for extraction, the blending ratio (volume ratio) of alcohols and water is preferably 0.001 to 100: 99.999-0, preferably 5 to 95. : 95-5 is more preferable, and 20-80: 80-20 is still more preferable. In the case of an ethanol aqueous solution, the ethanol concentration is preferably 40% by volume or more, more preferably 45% by volume or more. Moreover, Preferably it is 40-100 volume%, More preferably, it is 70-95 volume%.

  The amount of the solvent used is preferably 1 mL or more, more preferably 5 mL or more, preferably 100 mL or less, more preferably 50 mL or less with respect to 1 g of prickly throat (in terms of dry mass). Moreover, Preferably it is 1-100 mL, More preferably, it is 8-50 mL. The extraction time is preferably 1 minute or longer, more preferably 10 minutes or longer, preferably 30 days or shorter, more preferably 10 days or shorter. Moreover, it is preferably 1 minute to 30 days, more preferably 10 minutes to 10 days. The extraction temperature at this time is preferably 0 ° C. or higher, more preferably 10 ° C. or higher, still more preferably 20 ° C. or higher, preferably the solvent boiling point or lower, more preferably 100 ° C. or lower, still more preferably 90 ° C. or lower. Moreover, Preferably it is 0 degreeC-solvent boiling point, More preferably, it is 10-100 degreeC, More preferably, it is 20-90 degreeC.

  The extract thus obtained may be used as it is as an extract or fraction, or may be used as a diluted solution diluted with an appropriate solvent, or may be a concentrated extract or a dry powder, or prepared as a paste. But you can. Also, freeze-dry and dilute with a solvent usually used for extraction, such as water, ethanol, propylene glycol, butylene glycol, water / ethanol mixture, water / propylene glycol mixture, water / butylene glycol mixture, etc. It can also be used. It can also be used by encapsulating in vesicles such as liposomes or microcapsules.

  The extract may be a crude product as long as it conforms to food and pharmaceutical acceptable standards and exhibits the effects of the present invention, and the obtained crude product is further purified by a known separation and purification method. These purity may be increased by appropriately combining them. Examples of the purification means include organic solvent precipitation, centrifugation, ultrafiltration membrane, high performance liquid chromatograph, column chromatograph and the like.

As shown in Examples described later, the extract of Prickly Pear has the effect of promoting GLP-1 secretion from cells of the lower gastrointestinal tract (ileum to colon). Therefore, the above-mentioned prickly thigh or its extract is useful for promoting GLP-1 secretion, and these can be expected to have effects of inhibiting glucagon secretion, preventing and / or improving postprandial hyperglycemia, and suppressing appetite (the above non-patent document). 1-4).
In addition, it has been reported that the rate of developing diabetes decreases by continuously suppressing postprandial blood glucose elevation (Foods Food Ingredients J. Jpn., 310 (12), 2005). Therefore, the above prickly thigh or extract thereof is useful for preventing and / or improving postprandial hyperglycemia, and further preventing and / or improving diseases such as diabetes and insulin resistance. Furthermore, the prevention and / or improvement of cardiac function deterioration and the prevention and / or improvement of arteriosclerosis can be expected due to the vascular protection enhancing effect (Non-Patent Documents 5 to 8 above).

  Therefore, the above-mentioned prickly pear or extract thereof is a GLP-1 secretion promoter, a glucagon secretion inhibitor, a postprandial hyperglycemia prevention and / or improvement agent, an insulin resistance prevention and / or improvement agent, a diabetes prevention and / or It can be used as an improving agent, an appetite suppressant, an agent for preventing and / or improving cardiac function deterioration, an agent for preventing and / or improving arteriosclerosis (hereinafter referred to as “GLP-1 secretion promoter, etc.”), Furthermore, it can be used to produce these agents.

  The GLP-1 secretion promoter and the like itself, when ingested or administered to animals including humans, promote GLP-1 secretion, suppress glucagon secretion, prevent and / or improve postprandial hyperglycemia, prevent insulin resistance and Pharmaceuticals or pharmaceuticals for humans or animals that exhibit the effects of / or improvement, prevention and / or improvement of diabetes, suppression of appetite, prevention and / or improvement of cardiac function, prevention and / or improvement of arteriosclerosis It may be a quasi-drug, food, or feed, or may be a material or formulation used by blending with the drug, quasi-drug, food or feed.

The use of the GLP-1 secretion promoter or the like when administered to humans or animals may be therapeutic use or non-therapeutic use.
Here, “non-therapeutic” is a concept that does not include medical practice, that is, does not include a method for operating, treating, or diagnosing a human.

  In addition, the food includes GLP-1 secretion promotion, glucagon secretion suppression, appetite suppression, glucagon secretion suppression, prevention and / or improvement of postprandial hyperglycemia, prevention of appetite, deterioration of cardiac function, etc. And / or improvement, prevention and / or improvement of arteriosclerosis, and foods, functional foods, foods for the sick, and foods for specified health use that are indicated as such. Since these foods are foods whose function is permitted, they can be distinguished from general foods.

  The dosage forms of the above-mentioned pharmaceuticals (including quasi-drugs) containing the above-mentioned prickly pear or extract thereof are tablets, capsules, granules, powders, syrups, intravenous injections, intramuscular injections, suppositories, inhalation Any of agent, percutaneous absorption agent, eye drop, nasal drop, poultice, poultice, ointment, lotion, cream and the like may be used. The administration form may be either oral administration (internal use) or parenteral administration (external use, injection). Of these dosage forms, the preferred form is oral administration.

  In addition, in order to prepare pharmaceutical preparations of such various dosage forms, the above prickly crocodile or an extract thereof is used alone or in combination with other pharmaceutically acceptable excipients, binders, extenders, disintegrations. It can be prepared by appropriately combining agents, surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, medicinal ingredients other than the present invention. Oral liquid preparations can be prepared by conventional methods with the addition of flavoring agents, buffers, stabilizers and the like.

  In the preparation for oral administration, the content of the above prickly or extract thereof is generally preferably 0.01% by mass or more, more preferably 0.1% by mass or more, preferably 20% by mass as the solid content concentration. Hereinafter, it is more preferably 10% by mass or less. Moreover, Preferably it is 0.01-20 mass%, More preferably, it is 0.05-10 mass%.

  Examples of the form of the food containing the prickly pear or extract thereof include soft drinks, tea beverages, coffee beverages, fruit juice beverages, carbonated beverages, juices, jelly, wafers, biscuits, breads, noodles, sausages In addition to various foods such as foods and nutritional foods, further, nutritional supplement compositions in the same form (tablets, capsules, syrups, etc.) as the above-mentioned oral administration preparations can be mentioned.

  For various forms of food, the above prickly pear or extract thereof alone or other food ingredients, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, coloring agents, antioxidants, moisturizing agents It can be prepared by appropriately combining agents, thickeners, active ingredients other than the present invention and the like.

  In general, the content of the prickly pear or extract thereof in the food feed is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, preferably 10% by mass or less, more preferably 5%. It is below mass%. Moreover, Preferably it is 0.01-10 mass%, More preferably, it is 0.05-5 mass%.

  Examples of the feed include feed for small animals used for rabbits, rats, mice, etc., feed for pet foods used for dogs, cats, small birds, squirrels, etc., and can be prepared in the same form as the above foods.

  The intake of the GLP-1 secretion promoter of the present invention may vary according to the subject's species, weight, sex, age, condition or other factors. The dose, route, interval, and amount and interval of intake can be determined as appropriate by those skilled in the art, but generally preferred as the above-mentioned prickly thigh or extract thereof (in terms of dry matter) per day for adults. Is 20 μg / 60 kg body weight or more, more preferably 200 μg / 60 kg body weight or more, more preferably 2 mg / 60 kg body weight or more, preferably 1000 mg / 60 kg body weight or less, more preferably 500 mg / 60 kg body weight or less, more preferably 200 mg / 60 kg body weight or less. It is. Moreover, it is preferably 20 μg to 2000 mg / 60 kg body weight, more preferably 200 μg to 1000 mg / 60 kg body weight, still more preferably 2 to 5000 mg / 60 kg body weight.

  The subject of administration or ingestion is not particularly limited as long as it is a person who needs or desires it regardless of whether it is a sick person or a healthy person, but is preferably an exercise deficient person or a middle-aged person. The GLP-1 secretion promoter of the present invention is not limited to patients with diabetes or insulin resistance, but also subjects who do not suffer from diabetes or insulin resistance, such as high postprandial hyperglycemia but abnormal fasting blood glucose. The present invention can be applied to a subject who does not need to lower fasting blood glucose but does not need to lower postprandial hyperglycemia. Alternatively, the cardiac function is lowered or the vascular endothelial function is lowered, and it can be applied not only to patients with arteriosclerosis and hypertension, but also to the reserve group.

With respect to the above-described embodiment, the following aspects are disclosed in the present invention.
<1> A GLP-1 secretion promoter containing prickly pear or an extract thereof as an active ingredient.
<2> A glucagon secretion inhibitor comprising a prickly throat or an extract thereof as an active ingredient.
<3> A preventive and / or ameliorating agent for postprandial hyperglycemia comprising a prickly throat or an extract thereof as an active ingredient.
<4> A preventive and / or ameliorating agent for insulin resistance comprising a prickly pear or an extract thereof as an active ingredient.
<5> A preventive and / or ameliorating agent for diabetes comprising prickly pear or an extract thereof as an active ingredient.
<6> An appetite suppressant comprising prickly pear or an extract thereof as an active ingredient.
<7> Preventive and / or ameliorating agent for deterioration of cardiac function comprising prickly throat or extract thereof as active ingredient <8> Preventive and / or ameliorating agent for arteriosclerosis comprising prickly wing or extract thereof as active ingredient.
<9> Use of prickly throat or an extract thereof for producing a GLP-1 secretion promoter.
<10> Use of a prickly pear or an extract thereof for producing a glucagon secretion inhibitor.
<11> Use of prickly throat or an extract thereof for producing an agent for preventing and / or improving postprandial hyperglycemia.
<12> Use of prickly throat or an extract thereof for producing an agent for preventing and / or improving insulin resistance.
<13> Use of Uchiwadokoro or an extract thereof for producing an agent for preventing and / or improving diabetes.
<14> Use of prickly pear or an extract thereof for producing an appetite suppressant.
<15> Use of prickly throat or an extract thereof for producing an agent for preventing and / or improving cardiac function deterioration.
<16> Use of prickly throat or an extract thereof for producing an agent for preventing and / or improving arteriosclerosis.
<17> Uchiwadokoro or an extract thereof for use in promoting GLP-1 secretion.
<18> Uchiwadokoro or an extract thereof for use in suppressing glucagon secretion.
<19> Uchiwadokoro or an extract thereof for use in prevention and / or improvement of postprandial hyperglycemia.
<20> Uchiwadokoro or an extract thereof for use in preventing and / or improving insulin resistance.
<21> Uchiwadokoro or an extract thereof for use in the prevention and / or improvement of diabetes.
<22> Uchiwadokoro or an extract thereof for use in appetite suppression.
<23> Prickly throat or extract thereof for use in preventing and / or improving deterioration of cardiac function.
<24> Uchiwadokoro or an extract thereof for use in preventing and / or improving arteriosclerosis.
<25> The plant according to <17> to <24> or an extract thereof for non-therapeutic use.
<26> A method for promoting GLP-1 secretion, comprising administering or ingesting a prickly pear or an extract thereof to a human or an animal.
<27> A method for inhibiting glucagon secretion, comprising administering or ingesting a human or animal with a prickly pear or an extract thereof.
<28> A method for preventing and / or improving postprandial hyperglycemia, in which a prickly pear or extract thereof is administered or ingested to a human or an animal.
<29> A method for preventing and / or improving insulin resistance, wherein a prickly throat or extract thereof is administered or ingested to a human or an animal.
<30> A method for preventing and / or ameliorating diabetes by administering or ingesting a prickly pear or an extract thereof to a human or an animal.
<31> An appetite suppression method of administering or ingesting a human or animal with a prickly pear or extract thereof.
<32> A method for preventing and / or improving deterioration of cardiac function by administering or ingesting a prickly pear or extract thereof to a human or an animal.
<33> A method for preventing and / or ameliorating arteriosclerosis, wherein a prickly throat or extract thereof is administered or ingested to a human or an animal.
<34> The method according to <26> to <33>, which is a non-therapeutic method.
<35> A weight loss agent comprising prickly throat or an extract thereof as an active ingredient.
<36> A glucose uptake increasing agent comprising prickly pear or an extract thereof as an active ingredient.
<37> A gastric excretion inhibitor comprising a prickly throat or an extract thereof as an active ingredient.
<38> A vascular protection enhancer comprising prickly pear or an extract thereof as an active ingredient.
<39> In any one of <1> to <38>, the extract is preferably a water extract or an ethanol aqueous solution extract.

Production Example 1: Prickly Pear Extract Dioscorea nipponica Makino Rhizome (from Liaoning Province, Shinwa Product) 40 g of shredded material added with 50 vol% ethanol water, at room temperature, standing condition , Extracted for 28 days. Then, it isolate | separated from the non-extraction part by filtration, and obtained 307 mL of Puchiwokoro 50 vol% ethanol extracts. The evaporation residue of this extract was measured and found to be 1.59% (w / v).

The extract obtained in the above production example was diluted with 50% ethanol water to an extract concentration of 1% (w / v) to obtain a test sample. As a control, 50 vol% ethanol water was used.
NCI-H716 cells (human colon-derived cells; purchased from ATCC, developed by Dr. Herbert K. Oie et al. And supplied by the Agencies of the United States Public Health Service) were cultured at 37 ° C. in the presence of 5% CO ₂ . As the culture solution, RPMI1640 (containing 10% fetal bovine serum, high glucose; Invitrogen) was used. The cells were seeded at a matrigel (100 μL / well (N = 4)) and cultured in a DMEM (containing 10% fetal bovine serum, high glucose; Invitrogen) medium 3 days later, the medium was added to the test sample / PMA. (Phorbol 12-myristate 13-acetate) (positive control) was replaced with KRB (Krebs-Ringer bicarbonate, Sigma) buffer 0.2% BSA and cultured for 2 hours, and then the medium was collected. (DPP4 inhibitor, Sigma) and PMSF (Phenylmethylsulfonyl fluoride, serine protease inhibitor, Sigma) were collected in a microcentrifuge tube, suspended cells were removed, and then GLP-1 quantification was performed at −80 ° C. GLP-1 in the medium was quantified by ELISA using GLUCAGON-LIKE PEPTIDE-1 (ACTIVE) ELISA KIT (LINCO Research), and the results are shown in FIG.

  From Table 1 and FIG. 1, the Prickly Pear extract significantly promoted GLP-1 secretion of cells at a concentration of 0.01%.

Claims (8)

  A GLP-1 secretion promoter containing prickly pear or an extract thereof as an active ingredient.   A glucagon secretion inhibitor comprising prickly pear or an extract thereof as an active ingredient.   A preventive and / or ameliorating agent for postprandial hyperglycemia comprising prickly pear or an extract thereof as an active ingredient.   A prophylactic and / or ameliorating agent for insulin resistance comprising prickly pear or an extract thereof as an active ingredient.   A prophylactic and / or ameliorating agent for diabetes comprising prickly pear or an extract thereof as an active ingredient.   An appetite suppressant containing prickly pear or an extract thereof as an active ingredient.   A preventive and / or ameliorating agent for deterioration of cardiac function comprising prickly pear or an extract thereof as an active ingredient.   A prophylactic and / or ameliorating agent for arteriosclerosis comprising prickly pear or an extract thereof as an active ingredient.

Images