KR101697260B1 - Composition Comprising Voglibose As a Prebiotic for Improving Intestinal Microflora or Preventing Obesity - Google Patents

Abstract

The present invention relates to a composition for improving seminal plasma or intestinal microflora comprising voglibose, derivatives thereof or pharmaceutically allowable salts thereof as effective components. According to the present invention, voglibose has effects of weight reduction and improvement in seminal plasma and intestinal microflora, thereby being useful for preparing foods for preventing or improving obesity and diabetes.

Description

TECHNICAL FIELD The present invention relates to a composition for improving obesity, dressing or intestinal flora containing voglibose as an effective ingredient.

The present invention relates to a health functional food containing voglibose as an active ingredient.

Type 2 diabetes, non-insulin dependent diabetes mellitus, is one of the most common metabolic diseases with a worldwide prevalence rate of about 5%. The total number of diabetic patients worldwide is expected to double approximately over the next decade. The pathophysiology of type 2 diabetes is characterized by impaired insulin secretion and insulin resistance. Insulin resistance can lead to insulin secretion from the pancreatic beta cells, which in turn leads to hyperinsulinemia. Exist and act as independent risk factors for several other diseases. In this process, the function of the beta cells is eventually decreased and insulin deficiency occurs. As a result, diabetes characterized by impaired glucose tolerance and fasting glucose is developed after the meal. If diabetes persists for a long time, it will eventually lead to several complications such as microvascular complications such as retinopathy, neuropathy, or nephropathy, and macrovascular complications such as cardiovascular, cerebrovascular, or peripheral arterial blood vessels. These chronic complications reduce the quality of life of diabetic patients and greatly increase the mortality rate. Thus, management of type 2 diabetes is intended to prevent chronic complications, in other words, to delay the onset and progression of such chronic complications.

People with diabetes who are likely to experience chronic complications from diabetes should participate in the rigorous treatment of diabetes and have satisfactory metabolic control to maintain normal or at least normal glycated hemoglobin (HbA1c). The results of the Diabetes Control and Complication Trial and the United Kingdom Prospective Diabetes Study (UKPDS) show that strict glycemic control can lower the risk of developing chronic complications from diabetes have.

Alpha glucosidase is precisely the function of the brush border enzymes (maltase, sucrase, glucoamylase) in the intestinal mucosa to break down disaccharides into sugars. Alpha glucosidase inhibitors, which are oral hypoglycemic agents, have been shown to inhibit these enzymes, which can lead to a gradual rise in blood glucose after meals. However, since the absorption into the blood is extremely limited, there is a disadvantage that gastrointestinal symptoms appear as side effects. Acarbose, voglibose and miglitol have been developed and their intestinal action mechanism is not clearly known and it is necessary to confirm this.

Irritable bowel syndrome is characterized by changes in abdominal pain and bowel habits (diarrhea, constipation, or repeated diarrhea and constipation). Typical symptoms are chronic, sometimes intermittent, persistent, and lasting at least 3 months to be. Although IBS (irritable bowel syndrome) is not a life-threatening condition, it is estimated that there are about 42.4 million people suffering from irritable bowel syndrome (IBS) in the United States with constipation or diarrhea or both symptoms. Only 30% of them receive prescription drugs. Among them, only 8.8% take prescription drugs.

In the case of IBS disease, the main demand is a lot of nervous or stressed people, weak stomachs, lack of exercise, and people who are timid and timid. For example, it is essential to develop therapeutic and preventive technologies for various diseases such as office workers, examinees, young housewives, occupational drivers, frail postpartum or post-operative smokers, irregular smokers, and drinkers.

Although the cause of irritable bowel syndrome varies, it is very closely related to the imbalance of intestinal microorganisms, that is, the situation in which the number of harmful microorganisms that adversely affect metabolism is inadequate due to lack of beneficial bacteria. Therefore, in the western countries, a lot of beneficial microorganisms such as probiotics have.

Currently, the market for formal dressings is increasingly in demand for lifestyle-related diseases of modern people. It is not a "dressing-up" that only eat when the stomach is sick or diarrhea, but it is urgently required to develop new products that can enhance the function of digestive- do.

Obesity is a biological phenomenon caused by the interaction of complex factors such as genetic, metabolic, environmental, and behavioral factors, and is generally recognized as excess weight, but medically speaking, the body mass index (BMI) Or more than 30% of body weight), a BMI of 27 or more, and other circulatory diseases such as diabetes, hypertension, and hyperlipidemia. In particular, obesity is an important cause of various adult diseases associated with insulin resistance, diabetes, hypertension, cancer, gallbladder disease, hyperlipidemia, arteriosclerosis and the like. In addition, in obese patients and animals, Which has recently become known as a cause of social concern. The cause of obesity known to date is known to be over 70% of the genetic predisposition. Other environmental factors are known to be high intake and lack of exercise. Recently, however, we are interested in the amount of energy consumed and the amount of energy consumed It is gathering. In other words, although genetic predisposition has not changed much over the last decades, the incidence has increased rapidly, and it is difficult to see it as a genetic cause. Therefore, genetic and environmental factors that destroy the energy balance are important in weight determination It is recognized as an argument. Therefore, accurate identification of the cause of obesity is urgently required. Currently known obesity treatments include Xenical (Roche Pharmaceuticals, Switzerland), Reductil (Evothe, USA), Acomplia (Sanofi-aventis, France), Exolise (Atopama, France) It is largely classified into fat absorption inhibitor, appetite suppressant, and energy consumption stimulant. Xenical is a lipase inhibitor that inhibits the absorption of fat in the small intestine and pancreas by inhibiting the absorption of fat. In the case of reductile, it inhibits appetite by inhibiting the re-uptake of noradrenaline and serotonin, the hormones controlling the appetite in the brain. In addition, accompia acts as an antagonist of the CB1 receptor that regulates appetite in the brain, suppressing the appetite. Exocrine exacerbates heat metabolism, increases gastrointestinal lipase, and lowers fat absorption. Current treatments are low-fat vitamin absorption, hypertension, depression, anxiety, suicidal impetus and other side effects, such as the persistence of the effect is low, the development of improved treatment of obesity is required, and products currently being developed without satisfactory treatment It is necessary to develop a new therapeutic agent for obesity.

delete

delete

delete

Accordingly, the present inventors have made intensive efforts to solve the above problems. As a result, the present inventors have found that when a composition containing valiolamine derivatives as an active ingredient is administered, a weight loss effect occurs, an effect in the body is promoted, And the present invention has been completed.

delete

KR 10-2006-0104224 B KR 10-2010-0112814 B KR 10-2012-0053095 A KR 10-2013-0024157 B KR 10-2013-0129111 B

Another object of the present invention is to provide a food or food additive for improving a dressing or intestinal flora containing a valiolamine derivative as an active ingredient.

delete

In order to achieve the above object, the present invention provides a food or food additive for improving dressing or intestinal flora containing the valiolamine derivative of the formula (1) or a salt thereof as an active ingredient.

[Chemical Formula 1]

여기서, A는 C_1-10 비사이클릭 탄화수소기; C_5-6 사이클릭 탄화수소기; C_1-10 직쇄 또는 분지 지방족 탄화수소기 및 당 잔기로 구성된 군에서 선택되는 화합물이다.

Wherein A is a C _1-10 cyclic hydrocarbon group; A C _5-6 cyclic hydrocarbon group; C _1-10 linear or branched aliphatic hydrocarbon groups and sugar residues.

delete

The composition for improving a dressing or intestinal flora containing an effective ingredient comprising a derivative of valiamine or a salt thereof according to the present invention is useful for improving a dressing effect and intestinal flora by promoting growth of an enteric bacterium in the intestines.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing the results of (A) body weight, (B) weight gain, (C) total white fat mass, (D) , (F) glucose concentration, and (D) triglyceride concentration.
FIG. 2 is a graph showing the total composition of the intestinal microflora in the phylum unit when the composition containing the active ingredient of voglibose is administered to rats, (B) the phylum unit of intestinal microbes in each individual And (C) the change in the mean Firmicutes / Bacteroidetes ratio of each experimental group and the control group.
FIG. 3 is a graph showing changes in constitutional changes of intestinal microorganisms in genus units and species when mice were administered with a composition containing voglibose as an active ingredient.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

In the present invention, a composition containing a valiolamine derivative or a pharmaceutically acceptable salt thereof as an active ingredient was examined for the effect of improving weight, dressing effect and improving intestinal flora.

In the present invention, a valiolamine derivative, such as voglibose (1S, 2S, 3R, 4S, 5S) -5- (1,3-dihydroxypropan-2-ylamino) -1- (hydroxymethyl) cyclohexane -1,2,3,4-tetraol) as an active ingredient was administered to rats. As a result, it was confirmed that the composition had the effects of improving body weight, improving lipid metabolism, improving dressing effect and improving intestinal flora.

That is, in one embodiment of the present invention, C57BL / 6 mice raised in a SPF (Specific Pathogen Free) environment are administered a normal diet, a high fat diet or a high fat diet + boglibose to their body weight, As a result of analysis of composition of fat mass, cholesterol, glucose, triglyceride concentration and intestinal microorganism, it was confirmed that the high fat diet was effective in weight gain, lipid metabolism improvement, dressing effect and intestinal microflora in the + Voglibose intake group (Figs. 1, 2 and 3).

Accordingly, in one aspect, the present invention relates to a food or food additive for improving a dressing or intestinal flora containing as an active ingredient a valiolamine derivative of the formula (1) or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

In the present invention, A in the above formula (1) may be substituted with the following compounds, but is not limited thereto. Specifically, A is a C1-10 bicyclic hydrocarbon group which may be substituted with hydroxyl, phenoxy, thienyl, furyl, pyridyl, cyclohexyl, alkyl alcohol, alkyldiol or optionally substituted phenyl; A C5-6 cyclic hydrocarbon group which may be substituted with hydroxyl, hydroxymethyl, methyl or amino; Or sugar residue.

delete

In the present invention, A in the above formula (1) also includes C1-10 linear or branched aliphatic hydrocarbon groups which may be saturated or unsaturated, and which may be substituted by hydroxy, phenoxy, thienyl, furyl, pyridyl, cyclohexyl, Lt; / RTI > Tooth

(E.g., C1-6), lower alkoxy (e.g., C1-6), lower dialkoxy (e.g., C1-6), halogen (e.g., fluorine, chlorine, Bromine, iodine), phenyl, and the like.

 In the present invention, A represents a C5-6 cyclic hydrocarbon group or a sugar residue. These groups may be substituted with hydroxy, hydroxymethyl, methyl or amino.

As used herein, the term " sugar residue " refers to the group upon removal of one hydrogen atom from a polysaccharide molecule, and thus may refer to a residue derived, for example, from a monosaccharide or oligosaccharide.

In the present invention, the derivative can be used in the form of a salt with an inorganic acid (for example, hydrochloric acid) or an organic acid (for example, citric acid).

 The term " pharmaceutically acceptable "of the present invention means the approval of the government or equivalent regulatory body that can be used for animals, and more specifically for humans, by avoiding significant toxic effects when used in conventional medicinal dosages Or approved, or listed in pharmacopoeia or other general pharmacopoeia.

The term "salt" of the present invention means a salt according to one aspect of the present invention having the desired pharmacological activity of the parent compound. The salt may be (1) formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; (3-hydroxybenzoyl) benzoic acid, or an acetic acid, propionic acid, hexanoic acid, cyclopentenepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4- chlorobenzenesulfonic acid, 2- 4-methylbicyclo [2,2,2] -oct-2-en-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert Acid addition salts formed with organic acids such as butylacetic acid, laurylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; Or (2) salts formed when the acidic proton present in the parent compound is substituted.

The term "active ingredient" of the present invention means an ingredient that alone exhibits the desired activity or can exhibit activity with a carrier that is not self-active.

In the present invention, the valioamine derivative may be selected from the group consisting of voglibose (1S, 2S, 3R, 4S, 5S) -5- (1,3- dihydroxypropan- 2- ylamino) -1- (hydroxymethyl) cyclohexane-1,2,3,4-tetraol), a derivative thereof, or a salt thereof, and the chemical structure of voglibose is represented by Chemical Formula 2 below.

(2)

The term " derivative of voglibose "of the present invention means any compound which is changed to another substituent at a substitutable position of voglibose, and there is no limitation on the kind of such substituent. In one embodiment, the voglibose derivative may be represented by Formula (3), but is not limited thereto. Specifically, in the general formula (2), n or m may independently be an integer of 2 to 10.

(3)

In the present invention, the intestinal intestinal microflora is selected from the group consisting of TM7, fusobacteria, tenericutes, deferribacteres, verrucomicrobia, proteobacteria, actinobacteria, , One or more fungus (s) selected from the group consisting of bacteroidetes and posterior wall fungi (fungicetes).

In the present invention, the intestinal flora is a group consisting of Bacteroides vulgatus, Bacteroides acidifaciens, Helicobacter muridarum and Lactobacillus johnsonii And at least one strain selected from the group consisting of:

In the present invention, the food is preferably a health functional food, a health functional drink or a food additive, but is not limited thereto.

delete

delete

delete

delete

The food according to the present invention may further comprise a pharmaceutically acceptable additive, excipient or flavoring agent. The food may be in the form of tablets, capsules, granules, powders, tea bags, pouches, pills, , Soups, sauces, oils, liquid preparations, drinks, gums, ice cream, chocolate, tea, drinks, alcoholic beverages, dairy products, milk, cheese, meat products, liquid foods, porridge, breads, cakes, candy, snacks, , Noodles, or a combination of vitamins.

Accordingly, the food of the present invention includes all forms of functional foods, nutritional supplements, health foods, and food additives. These types of health functional foods can be prepared in various forms according to conventional methods known in the art. For example, the health food may be prepared by preparing the voglibose of the present invention in the form of tea, juice and drink, drinking it, granulating it, encapsulating it and pulverizing it. Functional foods also include beverages (including alcoholic beverages), fruits and their processed foods (such as canned fruits, bottled, jam, marmalade, etc.), fish, meat and processed foods such as ham, sausage, (Such as butter, cheese, etc.), edible vegetable oil, margarine, vegetable protein, retort food, fruit juice, fruit juice, Frozen foods, various kinds of seasonings (e.g., soybean paste, soy sauce, sauces, etc.) by adding the present voglibose.

The health functional food also includes various forms such as a functional food, a nutritional supplement, a health food, a food additive and the like as a food composition. The health functional food may be manufactured in various forms according to a conventional method known in the art, for example, It can be prepared in the form of tea, juice or drink, granulated, encapsulated, powdered or added to various foods such as beverages, fruits and processed foods, fish, meat and processed foods, breads, noodles and seasonings ≪ / RTI >

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like.

In addition to the above, the voglibose of the present invention may be used in various forms such as various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, , A carbonating agent used in carbonated drinks, and the like. In addition, the ruterion of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination.

In the present invention, it is preferable that the content of the valiolamine derivative of the formula (1) or the salt thereof is 0.0001 to 10% by weight, but not limited thereto.

[Example]

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments.

Example 1 Effect of Boglibose Composition on Weight Loss and Blood Glucose

Five-week-old C57BL / 6 mice raised in SPF (Specific Pathogen-free) environment were raised for about 12 weeks. Four cows were categorized randomly in the cage, and after a week of adaptation period with general feed and water for laboratory animals of PURINA, they were kept in a stainless steel cage maintained at a temperature of 18 to 24 ° C and a humidity of 50 to 60% . At the end of the adaptation period, the body weights were measured to make the average weight among the groups equalized, and the animals were randomly divided into two groups: normal diet (HF) and high fat diet (HF) The CTL group rats fed a normal diet, the HF group rats fed a high fat diet, and the VO rats fed a high fat diet and a boglivoz. Dietary intake was measured daily and body weight was measured twice a week. Special diets were freshly fed daily at -20 ° C while kept frozen.

After 12 weeks of feeding, weight gain and total white fat mass of each experimental group and control group were measured. Dietary efficiency was calculated by dividing weight gain by dietary intake. Changes in serum cholesterol, glucose and triglyceride levels were measured using the Olympus AU400 (Tokyo Japan).

1, weight, weight gain, total white fat mass, dietary efficiency, cholesterol concentration, glucose concentration, and triglyceride concentration of mice administered with a composition containing voglibose as an active ingredient were only administered in a high fat diet Which is significantly lower than that of one experimental group.

Example 2: Effect of improving the dressing and intestinal flora of the voglibose composition

In Example 1, microbiota analysis was performed using the feces of a mouse. Genomic DNA was extracted from each fecal sample and polymerase chain reaction was performed. Sequences with low quality were excluded and identified based on the EzTaxon-e database and analyzed using the CLcommunity ^TM program (ChunLab). The differences between the groups were confirmed by the one-way ANOVA method and analyzed by post-test, and the significance between the groups was expressed as a, b, c.

As shown in FIG. 2 and FIG. 3, it was confirmed that the composition of the intestinal flora in a mouse to which a composition containing voglibose as an active ingredient was administered showed a similar improvement to a mouse administered with a normal diet And the average Firmicutes / Bacteroidetes ratio, which is a representative value of the dressing effect, also drastically decreased.

[Manufacturing Example]

Hereinafter, the present invention is exemplified by the formulations of foods containing voglibose, and the contents of the present invention are not limited by the following production examples.

Preparation Example 1: Preparation of powder

300 mg of voglibose, 100 mg of lactose, 10 mg of talc

The above components are mixed and filled in airtight bags to prepare powders.

Formulation Example 2. Preparation of tablets

300 mg of voglibose, 100 mg of corn starch, 100 mg of lactose, 2 mg of magnesium stearate

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation Example 3. Preparation of capsules

300 mg of voglibose, 3 mg of crystalline cellulose, 14.8 mg of lactose, 0.2 mg of magnesium stearate

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation Example 4. Preparation of liquid preparation

300 mg of voglibose, 10 g of isomerized sugar, 5 g of mannitol,

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation Example 5. Preparation of Healthy Foods

Voglibose 300 mg,

Vitamin A acetate 70 ㎍, Vitamin E 1.0 mg, Vitamin B1 0.13 mg, Vitamin B2 0.15 mg, Vitamin B6 0.5 mg, Vitamin B12 0.2 ㎍, Vitamin C 10 mg, Biotin 10 ㎍, Nicotinamide 1.7 mg, Folic acid 50 ㎍, calcium pantothenate 0.5 mg,

A suitable amount of an inorganic mixture, 1.75 mg of ferrous sulfate, 0.82 mg of zinc oxide, 25.3 mg of magnesium carbonate, 15 mg of potassium monophosphate, 55 mg of calcium phosphate, 90 mg of potassium citrate, 100 mg of calcium carbonate,

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health foods according to conventional methods.

Formulation Example 6. Preparation of Health Drink

300 g of Voglibose, 15 g of vitamin C, 100 g of vitamin E (powder), 19.75 g of iron lactate, 3.5 g of zinc oxide, 3.5 g of nicotinic acid amide, 0.2 g of vitamin A, 0.25 g of vitamin B1, dose

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 L container, Of healthy beverages.

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Formulation Example 7. Preparation of chewing gum

Boglibose 0.24-0.64%, gum base 20%, sugar 76.36-76.76%, fruit flavor 1%, water 2%

Chewing gum was prepared using the above-mentioned composition and content by a conventional method.

Formulation Example 8. Production of Candy

Boglibose 0.24-0.64%, sugar 50-60%, starch syrup 32.26-49.66%, orange flavor 0.1%

The composition and the content of the candy were prepared using a conventional method.

Formulation Example 9. Production of Dairy Products

5 to 10 parts by weight of voglibose according to the present invention was added to 100 parts by weight of milk and various dairy products such as butter and ice cream were prepared using the milk.

Preparation Example 10. Preparation of Flour

0.5 to 5 parts by weight of voglibose according to the present invention was added to 100 parts by weight of milk, and the bread was used to prepare bread, cake, cookies, crackers and noodles.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereto will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (10)

(1S, 2S, 3R, 4S, 5S) -5- (1,3-dihydroxypropan-2-ylamino) -1- (hydroxymethyl) cyclohexane-1,2,3,4-tetraol) A food for improving a dressing or intestinal flora containing an acceptable salt thereof as an active ingredient.
delete 2. The method of claim 1, wherein the intestinal flora is selected from the group consisting of TM7, fusobacteria, tenericutes, deferribacteres, verrucomicrobia, proteobacteria, actinobacteria, , Bacteroidetes, and back wall fungi (fungicides). The food for improving a dressing or intestinal flora.
The intestinal flora according to claim 1, wherein the intestinal flora is selected from the group consisting of Bacteroides vulgatus, Bacteroides acidifaciens, Helicobacter muridarum and Lactobacillus johnsonii Wherein the at least one strain is selected from the group consisting of: < RTI ID = 0.0 >
The method of claim 1 wherein the suit is the rear wall fungi (Firmicutes) / bacteroidetes suit, characterized in that appear to decrease the rate of (Bacteroidetes) or food for improving intestinal flora.
delete The food for improving a dressing or intestinal flora according to claim 1, wherein the food is a health functional food or a health functional drink.
The food according to claim 1, further comprising a pharmaceutically acceptable additive, excipient or flavoring agent.
The method of claim 1, wherein the food is selected from the group consisting of tablets, capsules, granules, powders, tea bags, pouches, pills, seasonings, cereal products, soups, sauces, oils, liquid formulations, beverages, gums, ice creams, Wherein the food is in the form of an alcoholic beverage, a dairy product, a milk, a cheese, a meat product, a liquid, a porridge, a bread, a cake, a candy, a snack, a confectionery, a nutrient bar, a noodle or a vitamin complex.
The method of claim 1, wherein the voglibose (1S, 2S, 3R, 4S, 5S) -5- (1,3- dihydroxypropan- 2- ylamino) -1- (hydroxymethyl) cyclohexane- , 4-tetraol) or a salt thereof is 0.0001 to 10% by weight.

Images