JP2009084198A - Aldose reductase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an aldose reductase inhibitor that exhibits an excellent reductase inhibiting action and is highly safe. <P>SOLUTION: The aldose reductase inhibitor comprises as an effective ingredient a processed product of at least one selected from the group consisting of a testa of a peanut, Euphrasia officinalis, a leaf of a birch, a catuaba, a linden and a chamomile. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an aldose reductase inhibitor containing an extract of a natural product or a component thereof as an active ingredient.

  Normally, glucose is metabolized to glycolysis by hexokinase. However, during diabetes in which a hyperglycemic state persists, aldose reductase activity is increased and metabolism through the polyol pathway is promoted. D-sorbitol produced at this time is relatively stable, and once produced, it accumulates in the cell. The accumulation of sorbitol increases the intracellular osmotic pressure, causing cell edema and neuronal degeneration and causing tissue damage. As a result, diabetic complications such as retinopathy, peripheral neuropathy and nephropathy are considered to develop. Since these complications significantly reduce the quality of life (QOL) of diabetic patients, it is important to suppress these complications in the treatment of diabetes. From such a background, it is considered necessary to suppress aldose reductase for the prevention and treatment of diabetic complications (Non-patent Documents 1 and 2).

  So far, aldose reductase inhibitors have been developed and are also used clinically as new therapeutic agents for diabetic complications. For example, Kinedak (registered trademark, general name: Epalrestat, Ono Pharmaceutical Co., Ltd.) has been known as a pharmaceutical product for inhibiting aldose reductase. However, Kinedak has side effects such as thrombocytopenia and liver dysfunction, and it has a problem that it cannot be generally used because it requires prescription by a doctor. Therefore, there is a need for an aldose reductase inhibitor that reduces side effects and does not require a doctor's prescription.

So far, it has been reported that ginseng has an aldose reductase inhibitory effect, and it is known that ginseng is useful for preventing diabetic complications (Patent Document 1).
Japanese Patent No. 3803504 Forefront of AGEs Research Tsutomu Imaizumi Medical Review Inc. Published May 20, 2004 P69-71 Diabetes complications and pharmacotherapy Chihiro Yabe The Journal of Matsujinkai 2001 40 (2) P81

  The main object of the present invention is to provide an aldose reductase inhibitor containing a processed natural product as an active ingredient, and a pharmaceutical composition and a food and drink composition containing the aldose reductase inhibitor as an active ingredient.

  As a result of intensive studies to solve the above problems, the present inventors have found that a processed product of a specific plant has a high aldose reductase inhibitory action. The present invention has been completed as a result of further studies based on the above findings, and is described below.

The present invention provides the following aldose reductase inhibitors, pharmaceutical compositions and food / beverage product compositions.
Item 1. An aldose reductase inhibitor comprising, as an active ingredient, a processed product of at least one plant selected from the group consisting of peanuts, i-bright, oak, katsava, linden, and chamomile.
Item 2. Item 2. The aldose reductase inhibitor according to Item 1, comprising a processed product of peanut and a processed product of at least any one plant selected from the group consisting of Ibright, Inoki, Katsubaba, Linden, and Chamomile as active ingredients. .
Item 3. Item 2. The aldose reductase inhibitor according to Item 1, which contains, as an active ingredient, a processed product of at least two types of plants selected from the group consisting of at least Ibright, Inoki, Katsuba, Linden, and Chamomile.
Item 4. Item 4. A pharmaceutical composition comprising the aldose reductase inhibitor according to Item 1 as an active ingredient together with a pharmaceutically acceptable carrier and / or additive.
Item 5. Item 4. The pharmaceutical composition according to Item 3, which is used for prevention and / or improvement of diabetic complications.
Item 6. Item 5. A food or beverage composition comprising the aldose reductase inhibitor according to Item 1 as an active ingredient.
Item 7. Item 7. The food or beverage composition according to Item 6, which is used for prevention and / or improvement of diabetic complications.

  The aldose reductase inhibitor of the present invention has an aldose reductase inhibitory action so far, and is superior to aldose reductase inhibitors derived from ginseng, which has been known to be useful for the prevention of diabetic complications. Has an effect. The active ingredient of the aldose reductase inhibitor of the present invention is a processed plant product, and these plants are safe because they are already known to be edible.

  By administering such a pharmaceutical composition containing the aldose reductase inhibitor of the present invention, it is possible to inhibit the reaction by aldose reductase in the body, thereby suppressing the promotion of metabolism in the polyol pathway, It can prevent and / or improve diabetic complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy and the like.

  In addition, since the food and beverage composition containing the aldose reductase inhibitor of the present invention can be easily ingested on a daily basis, it can continuously inhibit aldose reductase activity in the body. In addition, metabolic activity in the polyol pathway can be effectively suppressed, and the diabetic complication can be prevented and / or improved more easily and without causing discomfort to the patient.

  Thus, the aldose reductase inhibitor of the present invention, the pharmaceutical composition containing the aldose reductase inhibitor as an active ingredient, and the food and drink composition are all useful for the prevention and / or improvement of diabetic complications caused by aldose reductase. It is.

The aldose reductase inhibitor aldose reductase is an enzyme that can convert glucose into sorbitol using NADPH as a coenzyme in the polyol pathway. In the present invention, the aldose reductase inhibitor refers to an agent that inhibits the function of this aldose reductase.

  Hereinafter, each component of the aldose reductase inhibitor of the present invention will be described.

(1) Various processed materials Examples of the raw material of the processed plant material contained as an active ingredient in the aldose reductase inhibitor of the present invention include peanuts, i-bright, persimmon, cuttlefish, linden, and cutlet.

  If it is these plants, a site to be used is not particularly limited, but preferably a peanut seed coat, an above-ground part of Ibright, an oak leaf, a cuttle bark, a linden flower, and a cutlet flower.

  As an active ingredient of the aldose reductase inhibitor of the present invention, one of the above processed plant products may be used alone, or two or more may be used in combination. When two or more kinds of the processed plant products are used in combination, these combinations are not particularly limited, and the use site of each plant is not limited.

  For example, when two types are used in combination, it is preferable to combine any one plant selected from the group consisting of peanuts, i-bright, oak, bonito, linden, and chopped. More preferably, it is a combination of peanut seed coat and any one plant selected from the group consisting of the above-ground part of Ibright, oak leaves, cuttle bark, linden flowers and bonito flowers, more preferably Peanut seed coat and ivy above ground, peanut seed coat and linden flower, and peanut seed coat and chamomile flower.

  In addition, when these two or more types are used in combination, the weight ratio of the workpiece is not particularly limited. However, for example, when two types are used in combination, with respect to 1 part by weight of one workpiece, One is 0.05 to 100 parts by weight, preferably 0.3 to 50 parts by weight, and more preferably 0.5 to 10 parts by weight.

  Specifically, in the case of the above-ground part of peanut seed coat and eyebright, 0.5 to 10 parts by weight, preferably 0.5 to 3 parts by weight, more preferably 0.5 to 3 parts by weight of above-ground part of eyebright with respect to 1 part by weight of peanut seed coat. 0.5 to 1 part by weight. In the case of peanut seed coat and linden flower, the amount is, for example, 0.5 to 10 parts by weight, preferably 0.5 to 3 parts by weight, and more preferably 0.5 to 1 part by weight. In the case of peanut seed coat and chamomile flower, it is 0.5 to 10 parts by weight, preferably 3 to 10 parts by weight, more preferably 5 to 10 parts by weight.

  Thus, by appropriately combining and blending two or more kinds of processed products of plants, a superior aldose reductase inhibitory effect can be obtained than when these compounds are used alone.

  In the present invention, the processed plant product includes a pulverized product, a dried product, an extract thereof, and the like of each part of the plant. Usually, after drying, pulverization is performed according to the form and the target dosage form. It refers to one prepared as a processed product after being subjected to various processing treatments such as treatment, extraction treatment, purification treatment, concentration treatment, and drying treatment (including spray-drying treatment and freeze-drying treatment). The processed product targeted by the present invention may be referred to as “processed plant product”, “processed product derived from plant”, or “processed product”.

  Examples of the processed product in the present invention include, for example, a pulverized processed product (which may be either coarse powder or fine powder), a dried processed product, an extract extracted with various solvents, a dried product (dried extract), The powder dry extract etc. which made this the powder can be mentioned.

  In the case where the workpiece targeted by the present invention is a pulverized workpiece, the adjustment method may follow a conventionally known method. For example, each part of the plant can be directly subjected to a pulverizer known in the art such as a jet mill to prepare a pulverized product. In addition, for example, each part of the plant is dried by constant temperature drying (drying using a constant temperature device, etc.), hot air drying, freeze drying, etc., and then the obtained dried product is used in a pulverizer or the like to obtain a pulverized processed product. Can be prepared.

  Moreover, when the processed product of the present invention is a dried processed product, the dried processed product can be obtained by drying the plant as it is. Here, the dried processed product can be prepared according to a conventionally known method such as sun drying, far-infrared irradiation, dryer (hot air drying, cold air drying, vacuum freeze drying) and the like. The water content in the dried processed product is preferably 10% by weight or less, and more preferably 5% by weight or less. In the present invention, the form of the dried processed product is not limited, and any of a dried product of the plant itself and a pulverized product of the dried product may be used. In the case of the pulverized product of the dried product, the pulverized product can be obtained according to the same method as the pulverized product. Moreover, what was obtained by drying, after drying the plant body used as a raw material as a dried material after fermenting treatment or an enzyme treatment can also be used.

  In addition, when the processed product of the present invention is an extract, its production method (extraction method), extraction conditions, and the like are not particularly limited, and may be a conventionally known method. Each part of the plant (whole plant, flower, fruit, leaf, branch, bark, rhizome, seed, seed coat, etc.) can be obtained as it is or after cutting, pulverizing, etc., and then extracting by extraction or solvent extraction. As a method for solvent extraction, a method known in the art may be adopted, and for example, a conventionally known extraction method such as water extraction, hot water extraction, hot water extraction, alcohol extraction, supercritical extraction or the like may be used. it can.

  When performing solvent extraction, examples of the solvent include water; lower alcohols such as methanol, anhydrous ethanol, and ethanol; and alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (anhydrous or water-containing). Not); ketones such as acetone; esters such as diethyl ether, dioxane, acetonitrile, and ethyl acetate; xylene, benzene, chloroform, and the like. Preferred are water, ethanol, and the like. These solvents may be used alone or in combination of two or more.

  Although the obtained extract can be used as it is, it may be dried and used in a powder form. Moreover, you may refine | purify, a concentration process, etc. to the extract obtained as needed. As the purification treatment, treatment such as filtration or adsorption or decolorization using an ion exchange resin or activated carbon column can be performed. As the concentration treatment, a conventional method such as an evaporator can be used.

  Alternatively, the obtained extract (or purified product or concentrate) is subjected to lyophilization and pulverized. Additives such as dextrin, corn starch and gum arabic are added and pulverized by spray drying. It may be pulverized according to a conventionally known method such as a method to obtain a processed product used in the present invention. Moreover, you may use this processed material by melt | dissolving in a pure water, ethanol, etc. as needed.

  Preferably, the processed plant is obtained by drying and crushing a plant as a raw material, extracting and filtering using a suitable solvent, and drying the resulting extract.

  The amount of the processed product in the aldose reductase inhibitor of the present invention is not particularly limited as long as the desired effect of the present invention is exhibited. For example, it is about 0.001 to 100% by weight, preferably about 0.01 to 80% by weight, and more preferably about 0.1 to 50% by weight in terms of dry weight of the processed product. In addition, the said compounding quantity is shown with the value converted into the weight of a raw material dried material. In the present specification, “dried material” refers to a dried material plant used as a processed product.

(2) Other components In the aldose reductase inhibitor of the present invention, the above active ingredients can be used alone, but in addition to the above components, conventionally known excipients, fragrances, colorants, emulsifiers, stabilizers. , Thickener, enzyme, preservative, lubricant, surfactant, disintegrant, disintegration inhibitor, binder, absorption enhancer, adsorbent, moisturizer, solubilizer, preservative, flavoring agent, sweetener Etc. can be blended as necessary within a range not impairing the effects of the present invention.

Pharmaceutical Composition The present invention provides a pharmaceutical composition comprising the aldose reductase inhibitor together with a pharmaceutically acceptable carrier and / or additive.

  The pharmaceutical composition of the present invention can be prepared in various dosage forms regardless of whether it is oral or parenteral. For example, liquid preparations such as liquids (including syrups), powders, granules, tablets Oral preparations in the form of solid preparations such as pills, powders, granules, capsules (including soft capsules); liquid preparations such as liquids, drops, injections, eye drops, tablets, pills, capsules (soft capsules) And parenteral preparations in the form of solid preparations. The pharmaceutical composition of the present invention is preferably an oral preparation.

  When the pharmaceutical composition of the present invention is a liquid preparation, it can be stored frozen, or it may be stored after removing moisture by lyophilization or the like. Freeze-dried preparations, dry syrups and the like are used by dissolving again by adding distilled water for injection, sterilized water or the like at the time of use.

  For example, when the pharmaceutical composition of the present invention is prepared as an injection, infusion, etc., as a diluent, for example, water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene Sorbitan fatty acid esters and the like can be used. In this case, the pharmaceutical composition of the present invention may contain a sufficient amount of sodium chloride, glucose or glycerin to adjust a solution that is isotonic with the body fluid. Moreover, you may add the solubilizing agent, buffering agent, soothing agent, etc. which are generally used in this field | area.

  When the pharmaceutical composition of the present invention is prepared as a solid agent, for example, in the case of a tablet, those conventionally known in this field can be widely used as a carrier. Examples of such carriers include lactose, sucrose, maltose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc .; water, ethanol, propanol, simple syrup, glucose solution , Starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, etc .; dry starch, sodium alginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid ester Disintegrating agents such as sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose; disintegration inhibitors such as sucrose, stearin, cocoa butter, hydrogenated oil; quaternary ammonium base, sodium lauryl sulfate, etc. Moisturizers such as glycerin and starch; adsorbents such as starch, lactose, kaolin, bentonite and colloidal silicic acid; use of lubricants such as purified talc, stearate, boric acid powder and polyethylene glycol it can. Further, the tablets can be made into tablets with ordinary coatings as necessary, for example, sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, and multilayer tablets.

  Moreover, when preparing in the form of a pill, a conventionally well-known thing can be widely used as a support | carrier in this field | area. Examples include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin and talc, binders such as gum arabic powder, tragacanth powder, gelatin, ethanol, and disintegrants such as laminaran and agar. Can be used.

  In addition to the above, for example, surfactants, absorption promoters, adsorbents, fillers, preservatives, stabilizers, emulsifiers, solubilizers, salts that regulate osmotic pressure, dosage units of the preparations obtained It can be appropriately selected and used according to the form. In addition, other active ingredients (for example, ascorbic acid, vitamin B6, vitamin B1, vitamin B2, nicotinamide and other vitamins; alkali metal salts such as sodium chloride and potassium chloride, citrate, acetate and phosphoric acid Inorganic salts such as salts) may be contained. Furthermore, you may use in combination with another medicinal component. Moreover, in the pharmaceutical composition of this invention, a coloring agent, a preservative, a fragrance | flavor, a flavoring agent, a sweetening agent, etc. can also be mix | blended and prepared as needed.

  The dosage of the pharmaceutical composition of the present invention is not particularly limited as long as the effects of the present invention are exhibited, and can be appropriately set depending on the age, body weight, degree of symptoms, etc. of the patient. It is about 500 to 4000 mg / day per adult (weight 60 kg).

  Since the pharmaceutical composition of the present invention can exert a high aldose reductase inhibitory action in vivo, diseases caused by promotion of aldose reductase activity and metabolism of the polyol pathway in vivo, such as sorbitol accumulation, NADPH It can be used for the purpose of prevention and improvement of diseases caused by reduced synthesis of nitric oxide and reduced glutathione reductase reaction due to excessive consumption of NADPH. Examples of the disease include diabetic complications such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy.

Food / Beverage Composition The aldose reductase inhibitor of the present invention can be prepared in the form of a food / beverage product containing carriers and additives acceptable as food.

  Although it does not specifically limit as a kind of food / beverage products of this invention, For example, a drink (a milk drink, a lactic acid bacteria drink, a soft drink containing fruit juice, a carbonated drink, a fruit juice drink, a vegetable drink, a vegetable and fruit drink, an alcoholic drink, a coffee drink, Sports drinks, powdered drinks, tea drinks, green tea drinks, blended tea drinks and other tea drinks), confectionery (chewing gum, bubble gum and other gums (including plate gum and sugar-coated granular gum)); strawberry chocolate, bulberry chocolate, etc. Chocolates with the flavors of: hard candy (including bonbon, butterball, marble, etc.), soft candy (including caramel, nougat, gummy candy, marshmallow, etc.), film candy (edible film); hard biscuits, Baked goods such as cookies, rice crackers, rice crackers); breads; soups (powder) Various food and drink), and the like, including the soup, and the like.

  The method for producing these foods and drinks is not particularly limited as long as the effects of the present invention are not impaired, and may follow the methods used by those skilled in the art for each application.

  In addition, health foods (nutrient functional foods, foods for specified health use, etc.), supplements, patients with the purpose of inhibiting aldose reductase activity in the body and preventing or ameliorating diseases caused by promoting metabolism of the polyol pathway The food / beverage composition of the present invention can also be prepared as a food for food.

  For example, when preparing the food / beverage product composition of the present invention as such a food / beverage product, for example, granules, capsules, tablets (including chewable agents, etc.), beverages (drinks) so as to facilitate continuous ingestion. It is desirable to prepare it in the form of a tablet etc., and the form of a tablet is especially preferable. The food / beverage product composition of the present invention in the form of a tablet can be appropriately prepared according to a conventional method using the aforementioned pharmaceutically acceptable carrier. Moreover, even if it is a case where it prepares in another form, what is necessary is just to follow a conventionally well-known method.

  Specific health foods (including conditional special health foods) and sick foods are, for example, diabetic complications (for example, diabetic kidneys) caused by promotion of aldose reductase activity in the living body or promotion of metabolism of the polyol pathway. , A diabetic retinopathy, a diabetic neuropathy, etc.) is a food that can display a description of the function and effect of the food for a disease on its packaging container. In this case, the dose of the present invention is not particularly limited as long as the effects of the present invention are exhibited, and can be appropriately set depending on the age, body weight, degree of symptoms, etc. of the patient. It is about 500 to 4000 mg / day per adult (weight 60 kg).

  Although it does not specifically limit as long as the effect of this invention is show | played as the compounding quantity of the aldose reductase inhibitor of this invention to the food-drinks composition of this invention, For example, 0.001-100 in conversion of the dry weight of a processed material About 0.1% by weight, preferably about 0.01 to 80% by weight, more preferably about 0.1 to 30% by weight.

  By daily intake of the food / beverage product composition of the present invention, the effect of preventing and / or improving the above-mentioned diseases caused by the promotion of aldose reductase activity in vivo can be expected.

  EXAMPLES Hereinafter, although an Example is shown and this invention is demonstrated in detail, this invention is not limited to these.

Test Example 1: Inhibitory activity against aldose reductase
In this example, the raw material of the processed plant contained in the aldose reductase inhibitor as an active ingredient is peanut seed coat, ibrite aerial part, oak leaf, cutlet bark, linden flower And chamomile flowers were used. As a comparative example, the roots of Western ginseng were used as plants. These plants were treated according to the following procedures to obtain processed products (extracts) of each plant.
(Preparation Example 1)
50 g of dried peanut seed coat (moisture content of 5% or less) was crushed and added to 500 mL of 50% ethanol, followed by stirring and extraction at room temperature for 3 hours, and then filtered to recover 451 mL of the extract. The obtained extract was dried with a rotary evaporator to obtain 14.5 g of a processed product of peanut seed coat. The obtained workpiece is referred to as Example 1.
(Preparation Example 2)
50 g of the above-ground portion of dried Ibright (moisture content of 5% or less) was crushed, added to 500 mL of water, stirred and extracted at room temperature for 3 hours, and then filtered to recover 467 mL of the extract. The obtained extract was dried with a rotary evaporator to obtain 12.3 g of a processed product of the above-ground part of iBright. The obtained workpiece is referred to as Example 2.
(Preparation Example 3)
50 g of dried Kashiwagi leaves (moisture content of 5% or less) were crushed, added to 500 mL of water, stirred and extracted at room temperature for 3 hours, and then filtered to recover 435 mL of the extract. The obtained extract was dried with a rotary evaporator to obtain 8.1 g of processed leaves of persimmon leaves. The obtained workpiece is referred to as Example 3.
(Preparation Example 4)
50 g of dried cuttle bark (water content 5% or less) was crushed, added to 500 mL of water and stirred and extracted at room temperature for 3 hours, and then filtered to recover 460 mL of extract. The obtained extract was dried with a rotary evaporator to obtain 9.9 g of processed cuttlefish bark. The obtained workpiece is referred to as Example 4.
(Preparation Example 5)
50 g of dried linden flowers (moisture content of 5% or less) were crushed, added to 500 mL of 70% ethanol and stirred for 3 hours at room temperature, and then filtered to recover 442 mL of extract. The obtained extract was dried with a rotary evaporator to obtain 11.0 g of a processed linden flower. The obtained workpiece is referred to as Example 5.
(Preparation Example 6)
50 g of dried chamomile flowers (water content 5% or less) were crushed, added to 500 mL of 50% ethanol and stirred for 3 hours at room temperature, and then filtered to recover 448 mL of extract. The obtained extract was dried with a rotary evaporator to obtain 12.9 g of a chamomile flower processed product. The obtained workpiece is referred to as Example 6.
(Preparation Example 7)
50 g of dried ginseng root (water content 5% or less) was crushed, added to 500 mL of water, stirred and extracted at room temperature for 3 hours, and then filtered to recover 452 mL of extract. The obtained extract was dried with a rotary evaporator to obtain 15.2 g of a processed product of roots of Western ginseng. The obtained workpiece is referred to as Comparative Example 1.

Method for Measuring Inhibitory Activity against Aldose Reductase The processed plant product obtained was measured for aldose reductase inhibitory action by the following method.

The activity of aldose reductase was measured with some modifications based on the method of Hayman and kinoshita (the journal of Biological Chemistry, 240, 877, 1965). 200 mM phosphate buffer (pH 6.2), 1.5 mM NADPH (nicotinamide adenine dinucleotide phosphate reduced type), 0.03 Unit / mL aldose reductase (manufactured by Wako Pure Chemical Industries), and 0.005 to 2.5 mg / mL test solution was added, and finally 100 mM DL-glyceraldehyde was added and reacted at 25 ° C. Absorbance at 340 nm was measured with a spectrophotometer immediately after substrate addition and 30 minutes later. The aldose reductase inhibition rate was calculated by applying the following aldose reductase inhibition activity calculation formula. The test solution is a soluble part obtained by suspending the processed products of Examples 1 to 6 and Comparative Example 1 with 200 mM phosphate buffer (pH 6.2). Moreover, what added the same amount of phosphate buffer solution (pH 6.2) instead of the test solution was used as a control. It shows that the aldose reductase inhibitory activity is weaker, so that the decreasing width of the light absorbency in a test liquid is close to a control. The results are shown in Table 1.
Composition of reaction solution:
60 μL of phosphate buffer (200 mM pH 6.2);
NADPH (1.5 mM) 10 μL;
Test solution (phosphate buffer in the control) 10 μL;
DL-glyceraldehyde (100 mM) 10 μL;
Aldose reductase (0.03Unit / mL) 10 μL;
(Total amount, 100 μL)
Aldose reductase inhibitory activity calculation formula Aldose reductase inhibitory activity%
= {1- (Absorption value of sample before reaction−Absorption value of sample after reaction) / (Absorption value of control before reaction−Absorption value of control after reaction)} × 100
The results are shown in Table 1 below and FIG.

  When compared with the IC50 (50% inhibitory concentration of enzyme activity) of Western ginseng (Comparative Example 1, Patent Document 1), which has been reported to inhibit aldose reductase inhibitory activity, peanut seed coat (Example 1), above ground of iBright IC50 of parts (Example 2), oak leaves (Example 3), bonito bark (Example 4), linden flowers (Example 5), chamomile flowers (Example 6), respectively, of Comparative Example 1 It was 2.6 times, 1.42 times, 1,31 times, 1.38 times, 1.36 times, and 1.25 times, and in all of Examples 1 to 6, high aldose reductase inhibitory activity was observed.

Test Example 2: aldose reductase peanut than combined action Test Example 1 of a plant in inhibiting activity of, Eyebright, birch trees, Catuaba, Linden, observed high aldose reductase inhibitory activity in chamomile, found in particular peanuts having a high activity It was. Therefore, the interaction between peanuts and other plants was examined. The test was performed in the same manner as in Test Example 1, changing the composition of the reaction solution. The test solution was prepared by mixing a processed product of peanut seed coat and a processed product of another plant in a weight ratio of 1: 0.5 to 1:10, and suspending in 20 mM phosphate buffer (pH 6.2). Soluble ingredients were added. Moreover, what added the same amount of phosphate buffer solution (pH 6.2) instead of the test solution was used as a control. The results are shown in Table 2.
Composition of reaction solution:
Phosphate buffer (200 mM pH 6.2) 50 μL;
NADPH (1.5 mM) 10 μL;
20 μL of test solution (phosphate buffer in the control);
DL-glyceraldehyde (100 mM) 10 μL;
Aldose reductase (0.03Unit / mL) 10 μL;
(Total amount, 100 μL)

  The obtained IC50 value was converted by the weight ratio of the workpiece, and the single amount of each material was calculated. Furthermore, when the inhibitory activity of the single material was obtained and the inhibitory activities of the two materials alone were summed (this was defined as “theoretical value”), none of the inhibitory activities reached 50%. From these results, it was confirmed that the inhibitory activity was increased when peanuts were used in combination with iBright, Inoki, Katsubaba, Linden, or Chamomile. Among them, peanuts and eyebright, peanuts and linden, peanuts and chamomiles showed a high increase in activity, and among them, peanuts and ibrite showed the highest increase in activity.

  In addition, the rate of increase in activity when peanuts and eyebright were used in combination increased effectively when 10 parts by weight of the above-ground part of eyebright was mixed with 1 part by weight of peanut seed coat, but 1 part by weight of peanut seed coat On the other hand, the case where 1 part by weight of the above-mentioned part of the eyebright was mixed further increased more effectively when 0.5 part by weight of the above-mentioned part of the eyebright was mixed with 1 part by weight of the peanut seed coat. From this, for example, when 3 parts by weight of the above-mentioned part of the eyebright is mixed with 1 part by weight of peanut seed coat, it is determined that the rate of increase in the activity is higher than when 10 parts by weight of the above-mentioned part of the eyebright is mixed. it can.

  The activity increase rate when peanut and linden were used in combination increased effectively when 10 parts by weight of linden flower was mixed with 1 part by weight of peanut seed coat, but with respect to 1 part by weight of peanut seed coat. When 1 part by weight of linden flower was mixed, the case of further mixing 0.5 part by weight of linden flower with 1 part by weight of peanut seed coat increased more effectively. From this, for example, when 3 parts by weight of linden flowers are mixed with 1 part by weight of peanut seed coat, it can be determined that the rate of increase in activity is higher than when 10 parts by weight of linden flowers are mixed.

  In addition, the rate of increase in activity when peanuts and chamomiles were used was effectively increased when 0.5 parts by weight of chamomile flowers were mixed with 1 part by weight of peanut seed coats, but with respect to 1 part by weight of peanut seed coats. When 1 part by weight of chamomile flower was mixed, the case where 10 parts by weight of chamomile flower was further mixed with 1 part by weight of peanut seed coat increased more effectively. From this, for example, when 3 parts by weight of chamomile flowers are mixed with 1 part by weight of peanut seed coat, it can be determined that the rate of increase in activity is higher than when 0.5 parts by weight of chamomile flowers are mixed.

  In addition, when the above-ground part of Ibright is used in combination with oak leaves, bonito bark, linden flowers or chamomile flowers, it is used in combination with oak leaves and bonito bark, linden flowers or chamomile flowers, An increase in inhibitory activity was also observed when the bark of bonito was used in combination with a linden flower or chamomile flower, and when the linden flower and chamomile flower were used in combination.

In accordance with the formulation examples shown below, powders and tablets were produced according to conventional methods. The obtained powder and tablets also showed similar aldose reductase inhibitory effect.
[Prescription example of pharmaceutical composition]
Formulation Examples 1-24. Powder (unit: mg)

[Prescription example of food and beverage composition]
Formulation Examples 25-48. Tablet (unit: mg)

Claims (5)

An aldose reductase inhibitor comprising, as an active ingredient, a processed product of at least one plant selected from the group consisting of peanuts, i-bright, oak, katsava, linden, and chamomile. 2. The aldose reductase inhibitor according to claim 1, comprising as an active ingredient a processed product of peanut and a processed product of at least any one plant selected from the group consisting of Ibright, Inoki, Katsubaba, Linden and Chamomile. Agent. A pharmaceutical composition comprising the aldose reductase inhibitor according to claim 1 or 2 as an active ingredient together with a pharmaceutically acceptable carrier and / or additive. The pharmaceutical composition according to claim 3, which is used for prevention and / or improvement of diabetic complications. A food composition comprising the aldose reductase inhibitor according to claim 1 or 2 as an active ingredient.