JP2006160710A - Composition for preventing/treating diabetes and health food containing the active ingredient thereof - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for preventing/treating diabetes high in biological safety through combining natural materials exerting excellent efficacy/effect, and to provide a health food containing the composition. <P>SOLUTION: The composition for preventing/treating diabetes comprises a combination of Salacia plant extract with Sinocrassula as a plant belonging to Crassulacea or extract thereof. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention relates to a composition for preventing / treating diabetes and a health food containing an active ingredient thereof.
More specifically, the present invention relates to a composition for preventing / treating diabetes based on the blood glucose level inhibitory effect of a combination of an extract of Salacia and an extract of stone lotus as active ingredients, and a health food containing the active ingredients.

  We eat a lot of carbohydrates (such as starch and sucrose) as a staple or side meal in our daily diet. Ingested carbohydrates are metabolized by enzymes in the body (such as α-glucosidase), decomposed into monosaccharides, and then absorbed from the digestive tract.

  When the intake of carbohydrates increases, the amount of monosaccharides absorbed from the digestive tract and transferred into the blood also increases, resulting in hyperglycemia. The daily persistence of this hyperglycemia usually results in obesity and diabetes, and in some cases, worsening diabetes can lead to serious illnesses such as complications.

  The three major complications due to diabetes are usually retinopathy, neuropathy and nephropathy, and it is said that the majority of blindness in adults is based on retinopathy due to diabetes. In addition to the above three major complications, vascular diseases such as stroke and arteriosclerosis and hypertension are also known as complications.

  Diabetes mellitus is caused by recent westernization of eating habits, that is, intake and overeating of high-calorie diets and changes in lifestyle habits due to the development of transportation and transportation systems, that is, lack of exercise, etc. It tends to increase and has become a major problem as a modern disease.

  Currently, the drugs used for the treatment of diabetes mainly include sulfonylureas that have the effect of promoting pancreatic insulin secretion; biguanides that have the effect of inhibiting hepatic gluconeogenesis and enhancing insulin sensitivity in peripheral muscles and adipose tissue. Drug: α-glucosidase inhibitor (eg, Acarbose (manufactured by Bayer) that inhibits α-glucosidase (a disaccharide hydrolase) that produces glucose from starch and sucrose by inhibiting the increase in blood glucose level And trade name: Glucoby) and Voglibose (manufactured by Takeda Pharmaceutical Co., Ltd., trade name: Basin), etc., and are widely used as a therapeutic agent for diabetes for oral administration.

  However, the above-mentioned therapeutic agents for diabetes are generally synthetic products, and gastrointestinal disorders, lactic acidosis, or severe liver disorders have been reported in recent years, and strict guidance and management by doctors is necessary for their use. It is. On the other hand, aldose reductase inhibitors (for example, Epartat (Ono Pharmaceutical, trade name: Kinedak)) for reducing these side effects are also widely used.

  Therefore, recently, natural materials with few side effects have been attracting attention, and various foods have been put on the market as health foods. In fact, there are few things that have been proven effective.

  Traditionally, Salacia plants have been used as natural drugs in traditional medicine in Sri Lanka and India. The Sri Lankan drug book describes that the above-mentioned plants of the genus Salacia are effective for the treatment of rheumatism, gonorrhea and dermatosis, and also used for the treatment of diabetes (Non-patent Document 1). In India, it has been handed down that plants of the genus Salacia are used for the same purpose as described above.

  Furthermore, in recent years, several reports have been made on the antidiabetic activity of the above-mentioned Salacia plants. That is, for example, for α-glucosidase inhibitory activity, a substance containing Salacia prinoides has been reported (Patent Document 1), and for α-glucosidase and aldose reductase inhibitory activity, Salacia reticulata, Substances containing Salacia oblonga and Salacia chinensis have been reported (Non-patent Document 1).

On the other hand, the stone lotus flower is a plant belonging to the genus Shiren, which is widely grown in China, and has been conventionally used for food in the Guangxi sorcery region in China.
In recent years, the application of this stone lotus flower as a blood glucose level lowering agent and the blood glucose level effect action have also been reported (Patent Documents 2 and 3).
However, no research results have been reported on the combined effect of the extract of Salacia and the extract of Shiren.

Japanese Patent No. 3030008 Patent No. 3097997 JP 2002-233342 A Food Style 21, Vol. 6, No. 5, pp. 72-78 Pharmaceutical Journal Vol. 121, No. 5, 371-378, 2001

  As described above, since existing anti-diabetic drugs may cause side effects, a safe and inexpensive natural material for the prevention and treatment of diabetes that has an effect of suppressing an increase in blood glucose level and has no side effects. Development is desired. Furthermore, by using the composition in combination with other antidiabetic agents, development of a composition having an inhibitory effect on an increase in blood glucose level that can reduce the use amount of each individual blood glucose level increase inhibitor or agent is eagerly desired. It was.

The present inventor has demonstrated effectiveness and safety from many years of use experience because of the long-term use of the therapeutic agent due to the nature of diabetes and the fact that conventional synthetic drugs can cause side effects. We paid attention to natural drugs and medicinal plants used in Oriental medicine such as Chinese traditional medicine and Indian traditional medicine Ayurveda.
And with the aim of reducing the side effects caused by antidiabetics such as those mentioned above, it is possible to reduce the amount of each substance used to suppress the increase in blood glucose levels by using it together with other antidiabetic drugs and / or blood glucose rise inhibitors. The development of a combination of compositions having the effect of suppressing the increase in blood glucose level was started.

As a result of earnest research, the inventor has surprisingly found that the combined use of the extract of Salacia and the extract of stone lotus has a synergistic effect in suppressing the increase in blood glucose, and has completed the present invention.
That is, according to the present invention, there is provided a composition for preventing / treating diabetes, characterized in that the extract of Salacia and the extract of stone lotus are contained as active ingredients in a ratio that exhibits a synergistic effect.

More specifically, the composition for preventing / treating diabetes, comprising an extract of Salacia and an extract of stone lotus as active ingredients in a dry weight ratio of 1: 0.05 to 1: 7. Is provided.
Moreover, according to this invention, the health food containing said composition is provided.

Salacia and lotus flowers used in the extract according to the present invention have been used in oriental medicine for many years, and since they have been used as health food materials in recent years, they have side effects even when used over a long period of time. It can be used with peace of mind.
Furthermore, due to the synergistic effect of the extract of Salacia and the extract of stone lotus according to the present invention, it is possible to reduce the respective amounts used for the purpose of suppressing an increase in blood glucose level.

  The term `` Salacia '' used in the present invention is a general term for Salacia genus plants belonging to the Hippocrataceae (formerly Celastrineae), and a health developed using the same genus plants as raw materials. It is used as a general name for food materials. The plants of the genus Salacia are perennial vines widely distributed in tropical regions such as Brazil, Southeast Asia such as India, Sri Lanka, Thailand and Indonesia, and Brazil. Currently, about 120 species are known as the genus plants.

  Examples of Salacia used in the present invention include Salacia reticulata, Salacia oblonga, Salacia chinensis, Salacia prinoides, Salacia latifolia, Salacia brononia ), Salacia grandiflora, Salacia macrosperma or Salacia roxburghii, and their roots and stems can be used.

  Of these, Salacia reticulata, Salacia oblonga and Salacia chinensis, which are readily available, are preferred. In addition, health food materials made from Salacia plants available on the market can be used.

  In addition, the term "stone lotus flower" used in the present invention is a Chinese medicine name, and is a general term for the plant of the genus Sinocrassula belonging to Crassulacea, and was further developed from the same genus plant as a raw material. It is used as a general name for health food ingredients. Stone genus plants are biennial or perennial plants that are widely distributed from Pakistan and northern India to various parts of China and grow naturally on rocks and stones.

  In addition, the genus plant has many synonyms depending on the region. For example, in tropical America such as Mexico, it is also known as Echevaria glauca or Cotyledon glauca. The stone lotus flower in the present invention is not limited to any of them.

  For example, Sinocrassula indica, Sinocrasula unnanensis, Sinocrassula yunnanensis, Sinocrasula ambigua, Sinocrasula densirosula sinosula densirosulata), Sinocrassula techinesis, Sinocrassula lanaistyla, and may also include Echevaria glauca or Cochiredon glauca, with leaves and stems Can be used. Moreover, the health food raw material which makes the raw material of the genus genus genus commercially available can also be used.

  As the Salacia or stone lotus flower according to the present invention, any of the above-mentioned materials or a predetermined part of the plant or the whole plant can be collected immediately or dried, and used as it is or after being shredded and pulverized. . Of these, chopped and pulverized products are preferred in terms of extraction efficiency.

For the preparation of the extract according to the present invention, water, lower alcohol or a mixture thereof can be used.
As the lower alcohol, methanol, ethanol, propanol or butanol or a solvent as an isomer of propanol or butanol can be used, and methanol or ethanol is preferably used.

Preferably, water or water-containing methanol can be used for extraction of Salacia, and methanol can be used for extraction of stone lotus flowers.
These extraction solvents are used in an amount of about 1 to 50 times (volume), preferably about 2 to 10 times the extraction material.

  The extraction can be performed while hot or at room temperature, and the extraction temperature can be arbitrarily set between room temperature and the boiling point of the solvent. In the case of hot extraction, it is appropriate to immerse the extraction material in the extraction solvent at a temperature between 50 ° C. and the boiling point of the extraction solvent, with or without shaking or under reflux. . When the extraction material is immersed under shaking, it is appropriate to perform for about 30 minutes to 5 hours, and when it is immersed under non-shaking, it is appropriate for about 1 hour to 20 days. Moreover, when extracting under reflux of an extraction solvent, it is preferable to heat to reflux for 30 minutes to several hours.

  In addition, although it is possible to extract by immersing at a temperature lower than 50 ° C., it is preferable to immerse for a longer time than the above time. The extraction operation may be performed only once for the same material, but is preferably repeated a plurality of times, for example, about 2 to 5 times.

After the extraction, the extract obtained by filtering the solid may be concentrated by a conventional method to obtain an extract. Concentration is preferably performed at a low temperature under reduced pressure. Concentration may be performed until the extract is dry.
The extract may be used as it is to prepare the composition of the present invention, but may also be used as a powder or lyophilized product. A method known in the art can be adopted as the method for forming these solids.

Therefore, the extract in the present invention includes any of extract, extract, and solid obtained by solidifying them.
In addition, the extract in this invention means all of a concentrate, an extract, a concentrated dried product, or a freeze-dried product.

  The extract may be subjected to a purification treatment before and after concentration. As the purification treatment, a chromatographic method, an ion exchange chromatographic method, a partition extraction with a solvent, or the like can be used alone or in combination. For example, as a chromatographic method, a column chromatography, a thin layer chromatography, a high performance liquid chromatography, a centrifugal liquid chromatography or the like using a normal phase or reverse phase carrier or an ion exchange resin, or a combination thereof is performed. Is mentioned. In this case, purification conditions such as a carrier and an elution solvent can be appropriately selected according to various chromatographies.

  However, the extract according to the present invention can be used as it is without purification and constitutes part of the present invention.

  That is, according to the present invention, the extract of the present invention as an active ingredient, that is, the extract of Salacia and the extract of stone lotus is in a dry weight ratio of 1: 0.05 to 1: 7, preferably 1: 0.1 to 1: 6. It was found that a synergistic effect was exerted in the effect of suppressing the increase in blood glucose level.

  More specifically, as shown in Table 2 below and animal group 2 in FIG. 1, the dry weight ratio of the extract of Salacia and the extract of stone lotus is about 1: 0.8 (the extract of Salacia and stone lotus When the extract was used at a rate of 75 mg / kg and 62.5 mg / kg), the blood glucose level inhibitory effect was approximately 1.4 hours after administration, compared with 75 mg / kg of Salacia extract alone. Double, 1 hour after administration, an increase in blood glucose level inhibition rate of about 1.8 times was observed.

  Therefore, according to the present invention, by using the extract of Salacia and the extract of stone lotus as active ingredients at a dry weight ratio in the above range, the amount of each extract used can be reduced, and diabetes can be prevented / treated. The composition can be used for the manufacture of a preventive / therapeutic agent for diabetes and also for health foods.

  The extract of the present invention can be used in various pharmaceutical forms such as powders, granules, tablets, capsules or liquids as they are, or diluted with an appropriate medium, or by a method known in the field of pharmaceutical production. Can be used.

  In these pharmaceutical forms, an appropriate medium may be added. Such vehicles include pharmaceutically acceptable excipients such as binders (e.g. syrup, gum arabic, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone), fillers (e.g. lactose, sugar, corn starch, calcium phosphate, Sorbitol or glycine), lubricants (eg magnesium stearate, talc or polyethylene glycol), disintegrants (eg potato starch) or wetting agents (eg sodium lauryl sulfate).

  Tablets may be coated by conventional methods. Liquid formulations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, and may be provided as a dry product that is regenerated with water or other suitable excipients prior to use. Good.

  Such liquid preparations are made up of conventional additives such as suspending agents (e.g. sorbitol, syrup, methylcellulose, glucose syrup, gelatin edible fats), emulsifiers (e.g. lecithin, sorbitan monooleate or gum arabic), (edible fats). Non-aqueous excipients (e.g. almond oil, fractionated coconut oil or oily esters such as glycerin, propylene glycol or ethyl alcohol), preservatives (e.g. methyl or propyl p-hydroxybenzoate, or Sorbic acid) and, if desired, colorants or fragrances.

Moreover, what added the composition by this invention to food as an active ingredient can be utilized as health food.
Health food means food with a more positive meaning than normal food for the purpose of health, health maintenance and promotion, for example, solid, semi-solid or liquid products, specifically powders, granules In addition to pills, tablets, capsules or liquids, confectionery such as cookies, rice crackers, jelly, yokan, yogurt and manju, soft drinks, teas, nutritional drinks, soups and the like can be mentioned.
In the production process of these foods or to the final product, the above-mentioned extract can be added to make a health food.

  The amount of the extract of Salacia and the extract of Ishiren flower varies depending on the age, symptoms, etc., but when used for prevention and treatment, the extract of Salacia extract and Ishiren flower extract are used for each adult. About 0.1 to 10 g, preferably about 0.3 to 2 g, of a dry weight ratio mixture can be used, and it is desirable to take it three times a day about 30 minutes before a meal. Moreover, when using as a health food, said mixture can be used in the range which is about 0.1-5 g with respect to the quantity which does not have a bad influence on the taste and external appearance of a foodstuff, for example, 1 kg of target foodstuffs.

The following examples are provided to illustrate the present invention and are not intended to limit the present invention in any way.
Experimental materials:
Wistar male rats: Kiwa Laboratory Animal Research Institute.
Glucose, maltose, sucrose, gum arabic: Wako Pure Chemical Industries, Ltd.

Extract of stone lotus flower: 10 kg of pulverized dry product of stone lotus flower is extracted with 10 L of water-containing ethanol three times with heat, filtered, combined with ethanol extract, evaporated under reduced pressure, and freeze-dried. , 800 mg of stone lotus flower extract was obtained.
Extract of Salacia: 10 kg of pulverized Salacia dried product is extracted with 10 L of water three times with heat, filtered, combined with the filtrate, evaporated under reduced pressure, lyophilized and extracted with Salacia 1000 g of product was obtained.
As an alternative to the above extract, a commercially available Salacia extract (Takama Co., Ltd., lot No. 040203) can also be used.

Measuring method of blood glucose level rise suppression effect:
A group of 5 Wistar male rats (body weight 130-140 g) fasted for 20-24 hours. The test substance was suspended in a 5% aqueous solution of gum arabic powder as a test sample, and this test sample was orally administered to 3 groups of rats at a rate of 5 ml / kg. 30 minutes after administration of the test sample, 20% sucrose, 20% maltose or 10% glucose aqueous solution was orally administered to each group of rats at a rate of 5 ml / kg. At 30, 60 and 120 minutes after administration of the sugar solution, blood was collected approximately 0.4 ml from the orbital vein of the rat under ether anesthesia, and blood was separated by centrifugation (5000 rpm, 10 minutes), followed by glucose oxidase method (glucose Serum glucose concentration was measured by CII Test Wako, Wako Pure Chemicals).

The normal group was administered with 5% aqueous solution of gum arabic powder and water alone, and the control group was administered with 5% aqueous solution of gum arabic powder and the above sugar solution.
As a result of carrying out the above method using an extract of stone lotus as the test substance, the test sample showed an inhibitory effect on the increase in blood glucose level in the 20% sucrose administration group. Therefore, the following experiment was conducted on sucrose-loaded rats (the 20% sucrose administration group described above).

Test example 1
Inhibition of blood glucose level in sucrose-loaded rats by stone lotus flower methanol extract According to the above experimental method, stone lotus extract was orally administered to rats at a rate of 125, 250 and 500 mg / kg, and blood glucose levels of each test sample were The effect of suppressing the increase in value was compared. The results are shown in Table 1 below.

Table 1: Inhibitory effect of Ishiren flower extract on serum glucose level in sucrose-loaded rats

  From Table 1 above, it has been found that the extract of stone lotus shows a significant blood glucose level inhibitory effect on sucrose-loaded rats at doses of 250 mg / kg or more in sucrose-loaded rats.

Test example 2
Synergistic effect of combined use of stone lotus flower extract and Salacia plant extract Next, we investigated the combined effect of stone lotus flower extract and Salacia extract. As test substances, Salacia extract was used for 5 groups of rats in combination of 5 different ratios in the range of 100 to 0 mg / kg, and stone lotus flower extract in the range of 0 to 250 mg / kg. . That is, Salacia extract 100 mg / kg (Group 1), Salacia extract 75 mg / kg and Shiro Lotus extract 62.5 mg / kg (Group 2), Salacia extract 50 mg / kg and stone Lotus flower extract 125 mg / kg (group 3), Salacia extract 25 mg / kg and stone lotus flower extract 187.5 mg / kg (group 4), and stone lotus flower extract 250 mg / kg (group 3) A total of five test samples of each dose (group 5) were prepared according to the method described above.

  Using the above test sample, the blood glucose level increase inhibitory effect of each test sample on sucrose-loaded rats was measured according to the method for measuring the blood glucose level increase inhibitory effect (Table 2).

Table 2: Inhibitory effect of serum lotus flower extract, Salacia extract and mixtures thereof on serum glucose levels in sucrose-loaded rats

  As is apparent from Table 2 above, in the second and third groups, the combined use of the extract of Salacia and the extract of stone lotus showed a significantly strong synergistic effect on the suppression of the increase in blood glucose level.

Therefore, in Table 2 above, for the first to fifth groups administered with the mixture of the above ratio of each extract, the blood glucose level increase inhibition rate 0.5 and 1 hour after administration of sucrose was calculated by the following equation: The result is shown in FIG.
Inhibition rate (%) = (control−test sample) / (control−standard) (100

  That is, administration of a mixture of Salacia extract 75 mg / kg and Ishiren flower extract 62.5 mg / kg (dry weight ratio of extract = 1: 0.8) in the second group is effective in suppressing blood glucose level. Compared to single use of 75 mg / kg of the product, the increase in blood glucose level inhibition rate was about 1.4 times 0.5 hours after administration and about 1.8 times 1 hour after administration.

  In addition, administration of a mixture of Salacia extract 50 mg / kg and Ishiren flower extract 125 mg / kg (dry weight ratio of extract = 1: 2.5) in Group 3 is effective in suppressing blood glucose levels. Compared to the use of 50 mg / kg of the product alone, the increase in the inhibition rate of blood glucose level was about 1.3 times after 0.5 hours and about 1.7 times after 1 hour of administration.

Example 1
50 parts by weight of rice flour, 5 parts by weight of sugar, 10 parts by weight of whole egg, and 0.5 parts by weight of a mixture having a dry weight ratio of 1: 0.8 of Salacia extract and Ishiren flower extract were weighed.
After mixing sugar with whole eggs, rice flour previously passed through a sieve was added and lightly mixed to make a dough, which was shaped into an appropriate shape and baked in an oven to make a rice cracker.

Examples 2-16
In Example 1, the dry weight ratio of about 1: 0.05, 1: 0.1, 1: 0.5, 1: 0.83, 1 instead of the mixture of the dry weight ratio of the extract of Salacia and the extract of stone lotus is about 1: 0.8. : 1, 1: 2, 1: 2.5, 1: 3, 1: 4, 1: 5, 1: 6, 1: 6.5, 1: 7, 1: 7.4 and 1: 7.45 In the same way, I made rice crackers.

Example 17
According to a method known in the art, 10 parts by weight of a dry weight ratio 1: 0.8 mixture of Salacia extract and Ishiren flower extract is mixed with 25 parts by weight of lactose, filled into gelatin capsules, and into one capsule. A gelatin capsule containing 500 mg of the mixture was obtained.

Examples 18-32
In Example 18, instead of the mixture of the extract of Salacia and the extract of stone lotus at a dry weight ratio of about 1: 0.8, the dry weight ratio of about 1: 0.05, 1: 0.1, 1: 0.5, 1: 0.83, 1 : 1, 1: 2, 1: 2.5, 1: 3, 1: 4, 1: 5, 1: 6, 1: 6.5, 1: 7, 1: 7.4 and 1: 7.45 In the same manner, a gelatin capsule was obtained.

Synergistic effect of extracts of Salacia and Ishiren flowers on the inhibitory effect of elevated blood glucose levels in sucrose-loaded rats

Claims (5)

A composition for preventing / treating diabetes, characterized in that an extract of Salacia and an extract of stone lotus are contained as active ingredients in a ratio that exhibits a synergistic effect. The composition according to claim 1, wherein the extract of Salacia and the extract of Shiren flowers are contained as an active ingredient in a ratio of 1: 0.05 to 1: 7 by dry weight ratio. The composition according to claim 1 or 2, wherein the Salacia is Salacia reticulata, Salacia oblonga, or Salacia chinensis, a plant of the genus Salacia. The composition according to claim 1 or 2, wherein the stone lotus flower is a Schiracula indica, Sino clathra unnanensis, Sino clathra ambigua, Sino clathra densirata, Sino clathra technesis, Sino clathra ronitis chiller, Echevaria glauca or Cochiredon glauca. A health food comprising the active ingredient according to any one of claims 1 to 4 added thereto.

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