KR20040008830A - γ-oryzanol with reducing effect on blood glucose level - Google Patents

Abstract

PURPOSE: Provided is γ-oryzanol which is extracted from rice bran and has reducing effect on blood glucose level. Therefore, it is useful for the reduction of blood glucose level of a diabetic. CONSTITUTION: A pharmaceutical composition for the reduction of blood glucose level is characterized by containing, as an active ingredient, γ-oryzanol in the amount of 1-50 wt.%, based on the total weight of the composition. The composition is used for the treatment of diabetes.

Description

Γ-oryzanol with reducing effect on blood glucose level

The present invention finds that gamma oryzanole has a hypoglycemic effect, and relates to a pharmaceutical formulation containing the gamma oryzanol as an active ingredient for lowering blood sugar.

The increase in diabetes prevalence and mortality rate is well known in Korea. Diabetes is one of the three major diseases in addition to cancer and circulatory disease. In addition, patients with poor blood sugar control have complications such as arteriosclerosis. The problem is that the impact on the socio-economic level as well as the individual is serious.

The purpose of diabetes management is to maintain normal blood sugar and prevent complications. Various drugs such as hypoglycemic agents and insulins are used, but various side effects and rejection have been reported for diabetics. Recently, surgery for transplanting the pancreas has been developed. However, it is expected to take considerable time to generalize.

Diabetic formulations are currently produced mainly in the form of injections, so there is a problem in that patients cannot directly administer to the hospital. Recently, the individual can be injected at home, but blood sugar can be drastically lowered after the injection, time, and dosage should be checked, and the cumbersome points such as changing the injection location are becoming stressful.

In general, gamma-orizanol is high in rice bran and its high antioxidant power has been used to enhance food stability. In addition, gamma-orizanol has been used mainly for the treatment of menopause, elevated cholesterol levels, and various gastrointestinal diseases, but it has not been known about the hypoglycemic effect, and it has not been used for the treatment of diabetes.

Accordingly, the inventors of the present invention, while studying the components that reduce the blood sugar without side effects and without objection to the patient, found that gamma oryzanole extracted from discarded rice bran has a hypoglycemic effect, and gamma oryzanol is effective in reducing blood glucose. By using it as a component, this invention was completed.

Therefore, the present invention is to provide a diabetic therapeutic agent and dietary supplement containing gamma oryzanol as an active ingredient for reducing blood sugar.

The present invention was devised to supplement the problems that may occur in various drugs or surgery that are used for the treatment and management of diabetes mellitus, and searched for substances suspected of having a hypoglycemic effect among natural substances whose safety has already been examined. In the diabetes model, it is intended to provide functional foods having hypoglycemic effects after confirming that blood glucose-related factors such as fasting and non-fasting blood sugars, glycated hemoglobin as long-term glycemic state indicators, and insulin levels may be affected.

In particular, the present invention is to provide a therapeutic agent for diabetes that can be administered orally and can be added to foods.

The present invention provides a pharmaceutical and food composition for treating diabetes containing gamma-orizanol as an active ingredient. In the present invention, the gamma oryzanol can be extracted and used in the discarded rice bran, in which case, it is possible to improve the added value of the by-products.

The present invention is characterized by containing 1 to 50% by weight of gamma-orizanol relative to the total weight of the pharmaceutical formulation composition.

The gamma oryzanol used in the present invention used γ-orizanol manufactured by Wako pure chemical industries in Japan.

In addition, the formulation of the pharmaceutical preparations according to the present invention is not particularly limited, oral or injectable pharmaceuticals may be used for oral administration, and may also be used as food additives.

The composition of the present invention may be in the form of a solution, suspension or emulsion in oil or an aqueous medium, or in the form of a dry powder which is dissolved in sterile, pyrogen-free water before use, oral formulation, subcutaneous injection, intravenous injection, It may be formulated into parenteral formulations such as intramuscular injection.

In the case of oral formulations, the compositions of the present invention may be prepared by known methods using pharmaceutically acceptable carriers and excipients, for example tablets, troches, sugar-containing tablets, aqueous or oily suspensions, dispersible flours or particles. It is formulated in the form of emulsions, soft or hard capsules, syrups, elixirs, which can be prepared in unit dosage forms and in multi-dose containers.

In oral formulations, tablets may be inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, sodium phosphate; Granulating agents such as corn, starch and alginic acid; Disintegrants; Binders such as starch, gelatin and acacia; It may be prepared in admixture with excipients usable for the manufacture of tablets, such as lubricants such as magnesium stearate, stearic acid, talc and the like. Tablets can be used uncoated or coated to inhibit absorption and degradation of the tablets in the gastrointestinal tract. For example, you may apply time inhibiting substances, such as glyceryl monostearate and glyceryl distearate. Hard capsule is a compound of the present invention is mixed with an inert solid diluent such as calcium carbonate, calcium phosphate, kaolin, etc., soft capsule is a solvent such as polypropylene glycol, PEGs (polyethylene glycol), ethanol, etc. that can be mixed with water And the active ingredients in oil solvents such as peanut oil, liquid paraffin and olive oil.

The water-soluble suspending agent is a mixture of excipients and active ingredients suitable for the preparation of water-soluble suspending agents. Excipients include, for example, sodium carboxymethyl cellulose, methyl cellulose, hydroxy-propyl methyl cellulose, sodium alginate, polyvinyl-pi Suspending agents such as ralidone, gum tragacanth, gum acacia and the like; Compounds condensing fatty acids such as polyoxyethylene stearate and alkylene oxides; Compounds in which alkylene oxides are condensed with long fatty acids such as heptadecaethyleneoxycetanol; Compounds which condensate partial esters derived from hexitol anhydride and fatty acids with ethylene oxide, such as polyoxyethylene sorbitol monooleate; Wetting agents; Or dispersing agents. Water-soluble suspensions contain preservatives, colorants, spices, sweeteners and the like.

The oily suspension is a suspension of an active ingredient in a vegetable oil such as olive oil, sesami oil, or a mineral oil such as liquid paraffin. For example, a thickening agent such as beeswax, hardened paraffin, cetyl alcohol, etc. may be used. It contains. It also contains preservatives, colorants, spices, sweeteners and the like, which can be preserved by adding antioxidants such as vitamin C.

Dispersible powders and particles have an active ingredient in a state in which a dispersing agent, a wetting agent, a suspending agent, a preservative and the like are mixed together. Suitable dispersing, wetting or suspending agents can be mentioned by way of example already mentioned above. Additional excipients are, for example, sweeteners, spices, colorants and the like.

Water-in-oil emulsions are derived from vegetable oils such as olive oil or mineral oils such as liquid paraffin, and are derived from natural phospholipids such as soy bean lecithin, and esters of anhydrous hecitol or fatty acids such as sorbitan monooleate. And compounds obtained by condensation of ethylene oxide with partial esters derived from anhydrous hexitol anhydride and fatty acids, such as lyoxyethylene sorbitol monooleate, as emulsifiers.

Syrups and elixirs can be prepared by mixing the active ingredient with sweeteners such as glycerol, propylene glycol, sorbitol, sucrose and the like.

Parenteral formulations may be injected by injection into a sterile injectable solution or a suspension in which the active ingredient is suspended in a non-toxic usable diluent or solvent such as 1,3-butanediol. Among the excipients or solvents available are water, Ringer's solution and isotonic saline solution. Cosolvents such as ethanol, polyethylene glycol, and polypropylene glycol can also be used. In addition, sterile, nonvolatile oils can be customarily used as solvents or suspending solvents. Mixed, non-stimulating, bland fixed oils for this purpose include synthetic mono- and diglycerides. In addition, fatty acids such as oleic acid can be used for the preparation of injectables. The suppository form is formulated by mixing the drug with a suitable non-irritating excipient, e.g. cocoa butter, polyethylene glycol, which is solid at room temperature but liquid at the rectal temperature and will melt in the rectum to release the drug. May be administered.

Food additives include beverages, baking, drinks, oils, ice cream, sweets, rice cakes, snacks, baby foods, alcoholic beverages, seasonings, retorts, canned foods.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples.

Production Example 1 Production of Bread

A dough was prepared with 23.7 wt% water by adding 5.0 wt% gamma oryzanol, 65.0 wt% flour, 4.2 wt% sugar, 0.6 wt% salt and 1.5 wt% yeast. The dough was fermented at 37 ° C. for 4 hours and then heated at 180 ° C. for 40 minutes to prepare bread.

Preparation Example 2 Preparation of Ice Cream

Gamma Orizanol 0.5 wt%, fresh cream (35%) 18 wt%, mixed skim milk powder 11 wt%, ice sugar 6 wt%, emulsifying stabilizer (guar gum 22.5 wt%, locust bean gum 19.5 wt%, carrageenan 4.5 wt%, tamarind 3.5% by weight of gum, 50% by weight of glycerin fatty acid ester) 0.2% by weight, 10% by weight per pure water, 54.3% by weight of purified water was prepared according to the conventional ice cream manufacturing process ice cream containing gamma oryzanol.

Production Example 3 Production of Cereal Milk

2.5% by weight of gamma oryzanol, 0.12% by weight of wild yam, 0.2% by weight of brown rice and 0.12% by weight of yulmu were mixed with 92.56% by weight of milk, 2.4% by weight of fructose, 2.0% by weight of sugar and 0.1% by weight of bamboo salt Mix with stirring. After mixing was completed, the mixture was passed through a homogenizer, homogenized, sterilized at 130 ° C. for 3 seconds, and cooled to prepare a milk containing gamma-orizanol.

[Test Example 1]

In this experiment, 100-year-old male KK mice were fed high-fat diet containing 20% soybean oil for 2 weeks to express diabetes. 40 diabetic mice with non-fasting blood glucose of 200 mg / dl or more were fed with blood sugar and body weight. In consideration of this, 20 animals were completely randomized and used in two groups. Dietary and water intakes were examined two to three times per week for eight weeks with one diet containing no gamma oryzanol-free diet and the other group with a 0.2% gamma oryzanol diet. Measured once a week at a fixed time, glucose tolerance was examined at the 8th week of gamma-orizanol supplementation. Blood glucose was measured in the vein, and the glucose tolerance test was performed for 30 hours and 120 minutes before and after administration at the level of 500 μl or less so that glucose (30g / 100mL) was 0.3g / 100g level in the abdominal cavity of the animals fasted for 14 hours. Blood glucose was measured by the blood glucose sensor (Medisense, USA) in the vein and the glucose area was calculated by the area under the curve from the blood glucose response curve measured during the glucose tolerance test. As a general safety item, liver, heart and kidney weights of diabetic mice were examined, and some blood was stored in EDTA-treated test tubes and refrigerated at 4 ° C for analysis of glycated hemoglobin within one week, and the rest was used for 20 minutes at 3000 rpm. After centrifugation it was used for serum insulin concentration analysis. The glycated hemoglobin concentration was analyzed by Micromat ^TM Ⅱ hemoglobin A _1C Test Catridge as an indicator of long-term blood glucose levels. Measured. The analytical data were analyzed using SAS program and presented as mean and standard error. The results are shown in Table 1.

Experimental group Dietary Intake (g / day) Water intake (ml / day) Weight gain (g / day) Dietary efficiency Control 7.22 ± 1.12 5.49 ± 0.86 0.17 ± 0.01 0.024 ± 0.001 Gamma-Orizanol group 7.06 ± 1.02 6.10 ± 0.49 0.15 ± 0.02 0.021 ± 0.002

* Dietary efficiency = weight gain / dietary intake

As shown in Table 1, when gamma oryzanol extracted from rice bran was fed to diabetic mice, the dietary efficiency calculated from the dietary and water intake and weight gain, and the dietary intake and weight gain did not show a significant difference from the control group. As shown in Table 2, the weights of liver, heart and kidney were also not significantly different in the gamma-orizanol-added group, so gamma-orizanol did not appear to affect the general growth and safety items of animals, including dietary intake or tissue weight.

Experimental group Liver (g / 100g body weight) Heart (g / 100g body weight) Height (g / 100g weight) Control 4.68 ± 0.21 0.53 ± 0.01 1.32 ± 0.03 Gamma-Orizanol group 4.73 ± 0.24 0.57 ± 0.02 1.37 ± 0.05

Table 3 shows the hypoglycemic effects of gamma-orizanol. When diabetic mice were fed gamma-orizanol for 8 weeks at the 0.2% level of the experimental diet, fasting blood sugar levels were 31%, non-fasting blood sugar levels were 15%, and long-term blood glucose concentration indexes. The glycated hemoglobin level was reduced by 7%, glucose tolerance improved by 26%, and serum insulin level was increased by 86%.

Experimental group Fasting blood sugar (mg / dl) Non-fasting blood sugar (mg / dl) Blood Sugar Area (mg / dl * hr) Glycation hemoglobin (%) Insulin (ng / ml) Control 106.7 ± 9.6 190.6 ± 8.9 569.9 ± 23.3 4.95 ± 0.16 0.63 ± 0.08 Gamma-Orizanol group 74.0 ± 4.1 162.9 ± 16.1 422.7 ± 37.4 4.58 ± 0.27 1.17 ± 0.21

Recently, as the preference for natural health supplements and functional foods has increased, studies on the separation and identification of functional ingredients contained in natural plant raw materials have been actively conducted.However, blood sugar-related factors from rice bran produced during the milling process There was little effort to find. However, as a result of the test, gamma-orizanol has a hypoglycemic effect, which may be used in various health supplements and functional foods to contribute to glycemic control of diabetics and to improve the added value of by-products.

Claims (10)

A blood glucose lowering pharmaceutical composition containing gamma-orizanol as an active ingredient. The pharmaceutical composition for lowering blood glucose according to claim 1, wherein the gamma oryzanol is contained in an amount of 1 to 50% by weight based on the total weight of the composition. The pharmaceutical composition for lowering blood glucose according to claim 1, wherein the formulation of the medicament is for oral use. 4. The hypoglycemic pharmaceutical composition according to any one of claims 1 to 3, wherein the gamma oryzanol is extracted from rice bran. A medicament for the treatment of diabetes containing the pharmaceutical composition according to any one of claims 1 to 3. A pharmaceutical for treating diabetes containing the pharmaceutical composition according to claim 4. A blood sugar lowering food composition containing gamma oryzanol as an active ingredient. 8. The food composition of claim 7, wherein the gamma-orizanol content is 1 to 30% by weight based on the total weight of the composition. The food composition of claim 7, wherein the food includes various cooked foods such as beverages, drinks, bread, drinks, fats, ice cream, sweets, rice cakes, snacks, baby foods, alcoholic beverages, seasonings, retorts, and canned foods. . The food composition according to any one of claims 7 to 9, wherein the gamma oryzanol is extracted from rice bran.