JP2011121921A - Pancreatic lipase inhibitor, and food and drink composition and pharmaceutical composition comprising the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pancreatic lipase inhibitor that exhibits excellent effects for ameliorating/preventing and treating lifestyle-related diseases such as obesity, hyperlipemia, diabetes and the like induced by high-fat diet in a daily life and is safe, stable and inexpensive to be suitably incorporated with a food and drink composition or a pharmaceutical composition. <P>SOLUTION: The pancreatic lipase inhibitor comprises as an effective ingredient an extract from Quercus acutissima. Preferably, the extract solvent is a water-containing organic solvent. The food and drink composition and the pharmaceutical composition comprise the pancreatic lipase inhibitor. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a pancreatic lipase inhibitor, and in particular, to a food and beverage composition excellent in the effect of preventing and preventing lifestyle-related diseases such as obesity, hyperlipidemia and diabetes induced by a high-fat diet, and the therapeutic effect of these diseases The present invention relates to a pancreatic lipase inhibitor suitable for blending with an excellent pharmaceutical composition. Moreover, the invention regarding the food-drinks composition and pharmaceutical composition containing the pancreatic lipase inhibitor is also included.

In recent years, with the westernization of meals, the onset of lifestyle-related diseases such as obesity, hyperlipidemia and diabetes has increased remarkably, and the response is urgently needed. Pancreatic lipase inhibitors are being actively developed and applied for the prevention and improvement of dietary obesity, hyperlipidemia and diabetes.

In contrast, various lipase inhibitors extracted from plant fruits, their skin, seeds, leaves, rhizomes, etc. have been manufactured and tried to be incorporated into cosmetics, pharmaceuticals, foods, etc. In this case, the safety and procurement of the raw materials are problematic.

Lipase inhibitors derived from plant materials include lipase inhibitors (eg, patents) containing extract extracts such as yucca, ginseng, jasmine tea, yamazuko, yellow ginger tea, rooibos tea, soy germ, ginger and tochu tea. Pancreatic lipase inhibitor (for example, refer to Patent Document 2) containing an extract of Quillaja saponaria MOLINA bark as an active ingredient, or a lipase inhibitor containing chestnut skin extract (for example, Patent Document 3).

On the other hand, Quercus acutissima Carruthers is also known as a plant-derived material. Examples of the agent in which a component derived from kunugi effectively acts include, for example, an antioxidant (for example, see Patent Document 4), a testosterone 5α-reductase inhibitor (for example, see Patent Document 5), and an SCF binding inhibitor (for example, , Patent Document 6), antibacterial agents (for example, see Patent Document 7), cholesterol lowering agents (for example, see Patent Document 8), histamine release inhibitors (for example, see Patent Document 9), and the like.

However, it is not known that Kunugi extract has an action of inhibiting pancreatic lipase activity.

JP 2002-275077 A JP 2006-182722 A JP 2007-145802 A JP-A-7-126618 JP-A-10-109920 JP 2003-073290 A JP 2004-359664 A JP 2005-239684 A JP 2005-281220 A

The object of the present invention is to provide a safe, stable, and inexpensive food and drink that is excellent in preventing and treating lifestyle-related diseases such as obesity, hyperlipidemia and diabetes induced by a high fat diet in daily life. It is in providing a suitable pancreatic lipase inhibitor by mix | blending with a product composition and a pharmaceutical composition. Another object is to provide a food / beverage composition and a pharmaceutical composition containing the pancreatic lipase inhibitor.

As a result of intensive studies in view of the above circumstances, the present inventors have found that an extract obtained from Kunugi contains an active ingredient having an antihyperlipidemic action, and this extract is used as a food / beverage composition or pharmaceutical product. When blended in the composition, it has been found that it has a significant effect on the improvement of lifestyle-related diseases caused in daily life.

That is, the pancreatic lipase inhibitor of the present invention is characterized by containing a cucumber extract as an active ingredient. Alternatively, the pancreatic lipase inhibitor of the present invention is characterized by containing as an active ingredient an n-butanol fraction obtained by further fractionating a cucumber extract with water and n-butanol. A water-containing organic solvent is suitable as the extraction solvent. Furthermore, this invention is also the food-drinks composition and pharmaceutical composition containing the said pancreatic lipase inhibitor.

According to the present invention, a safe, stable, and inexpensive pancreatic that is excellent in preventing and treating lifestyle-related diseases such as obesity, hyperlipidemia and diabetes induced by a high-fat diet in daily life. Lipase inhibitors can be provided. And this pancreatic lipase inhibitor is suitable for blending in food and beverage compositions and pharmaceutical compositions, and this food and beverage composition is obesity, hyperlipidemia and diabetes induced by a high fat diet in daily life. This pharmaceutical composition is excellent in the therapeutic effects on lifestyle-related diseases such as obesity, hyperlipidemia and diabetes induced by a high-fat diet in daily life.

Furthermore, in the pancreatic lipase inhibitor of the present invention, the cucumber bark that is preferably used is a cucumber bark that is discarded in large quantities at the time of harvest in the production area, and does not require new equipment to be obtained as a raw material. Available. Compared to pancreatic lipase inhibitors derived from conventional expensive raw materials, food and beverage compositions and pharmaceutical compositions containing the same, it is not only available in large quantities and at low cost, but also because it uses waste. It will also be considered.

Hereinafter, the present invention will be described in detail.

The cucumber used in the pancreatic lipase inhibitor of the present invention may be any place such as trunk, branch, leaf, root, bark, sap, bud, flower, fruit, seed of Quercus acutissima Carruthers. . Among these parts, bark is particularly preferred because it is discarded in large quantities in the production area and can be easily obtained without the need for new equipment. In the following description, it will be collectively referred to as “Knugi” unless the region is particularly limited.

The active ingredient contained in the pancreatic lipase inhibitor of the present invention is extracted from the above kunugi. Although it does not specifically limit as an extraction method for obtaining a kunugi extract, What extracted the solvent from said kunugi is preferable. When extracting with a solvent, kunugi may be used after drying or without drying. Further, kunugi may be used as it is regardless of drying, or may be used after being finely cut or pulverized. From the standpoint of extraction efficiency, it is preferable to extract the cucumber after drying and solvent extraction using the powdered one.

The solvent to be used is preferably water or a water-soluble organic solvent, or a mixed solvent thereof (hydrous organic solvent), but the hydrous organic solvent is particularly preferable because it has a pancreatic lipase inhibitory action. Examples of the water-soluble organic solvent include methanol, ethanol, propanol, water-saturated n-butanol, lower alcohols such as 1,3-butylene glycol, benzene, ethyl ether, chloroform, ethyl acetate, butyl acetate, and acetone. It is done. Among these, ethanol is preferable, and hydrous ethanol, which is a mixed solvent with water, is particularly preferable because of its strong pancreatic lipase inhibitory action.

The pancreatic lipase inhibitor of the present invention is formulated by blending the above-mentioned solvent extract, but the obtained solvent extract is blended with water and a component further fractionated with an organic solvent that does not mix with water arbitrarily. The pancreatic lipase inhibitor of the present invention may be used. In this case, n-butanol or the like is preferably used as an organic solvent which is not arbitrarily mixed with water. Both the water fraction and the n-butanol fraction can be added as an active ingredient to the pancreatic lipase inhibitor, but the n-butanol fraction is particularly preferable because of its strong pancreatic lipase inhibitory action.

The apparatus used at the time of solvent extraction is not specifically limited, A normal tank and a mixer may be used, and extractors, such as a Soxhlet extractor, may be used. The temperature at the time of extraction and the extraction time are not particularly limited. After solvent extraction, impurities may be removed by filtration, treatment with an adsorbent resin, activated carbon treatment, or the like.

As the dosage form of the pancreatic lipase inhibitor of the present invention, in addition to the liquid extract obtained by solvent extraction, the liquid extract is dried or concentrated by a normal drying method such as reduced pressure drying or freeze drying, a concentration method, or the like. It may be what you did. In addition, if necessary, it may be used after purification treatment such as deodorization and decoloration within a range that does not affect its efficacy, and it is formulated in a state that is easy to use, such as granulated with an appropriate excipient. What is necessary is just to use.

An example of the manufacturing method of the cucumber extract in this invention is demonstrated. Cut the barge bark finely. The cut bark is put into a mixer, and water or a water-containing organic solvent (preferably water-containing ethanol) is added and stirred for a predetermined time. Thereafter, it is filtered through a mesh. The obtained filtrate is a solvent extract of liquid Kunugi bark and can be used as it is as the pancreatic lipase inhibitor of the present invention. Furthermore, since the filtrate is freeze-dried under reduced pressure, and the resulting dried product is also a solvent extract of kunugi bark, it may be used as the pancreatic lipase inhibitor of the present invention in this state.

In the pancreatic lipase inhibitor of the present invention, in addition to the above-mentioned Kunugi extract, which is an active ingredient, a component that is usually used in a food or beverage composition or a pharmaceutical composition depending on the purpose or a component that is allowed to be used, It can mix | blend suitably within the range which does not impair the effect of this invention.

In the food / beverage product composition or pharmaceutical composition containing the pancreatic lipase inhibitor of the present invention, the compounding amount of the Kunugi extract, which is an active ingredient, is converted to a dry solid content based on the total amount of the food / beverage product composition or pharmaceutical composition. From 0.005 wt% (abbreviation of mass%) to 10 wt% is preferable in view of the effect and cost. In particular, 0.005 wt% or more and 5 wt% or less is preferable when blended and applied to a product.

It does not specifically limit as a form of the food-drinks composition of this invention, For example, a gel, powder, a liquid, a granule, cream form, paste form, solid etc. can be mentioned. Also, the type is not particularly limited, and examples thereof include confectionery (chewing gum, candy, gummi, tablet, chocolate, jelly, etc.), ice confectionery (ice candy, ice cream, sorbet, etc.), frozen confectionery (jelly, pudding, mizuyokan, etc.) ), Starch-based foods such as noodles, powdered foods and drinks, beverages (soups, coffee, teas, juices, carbonated beverages, cocoa, alcoholic beverages, jelly drinks, etc.), bakery foods (cookies, biscuits, bread, pie , Cakes, etc.), fat and oil foods (margarine, shortening, fat spread, etc.), dairy products (milk, yogurt, whey drink, lactic acid bacteria drink, butter, cream, cheese, etc.).

Each of the above-mentioned food and beverage composition of the present invention can be produced by a conventional method, and if necessary, the following components are appropriately selected within a range that does not impair the object of the present invention, and pancreatic lipase inhibition containing a cucumber extract Can be blended with the agent. For example, sugar sweeteners (monosaccharides such as fructose, glucose, tagatose and arabinose, oligosaccharides such as lactose, oligosaccharides, maltose and trehalose, powdered starch syrup, dextrin, sugar alcohol etc.), high sweetness sweeteners (sucralose, Acesulfame K, stevia, etc.), polysaccharides such as starch, fats and oils, dairy products, stabilizers, emulsifiers, fragrances (vanillin, linalool, natural fragrances, etc.), pigments, colorants, acidulants, flavor ingredients (eggs, coffee, Tea, cocoa, fruit pulp, yogurt, alcoholic beverages, etc.), flavoring (raspberry flavor, apple flavor, coffee flavor, etc.), anti-wetting agent, electrolyte, antioxidant, preservative, wetting agent, protein, amino acid, peptide , Dietary fiber, organic acids (citric acid, malic acid, fumaric acid, malonic acid, succinic acid, tartaric acid, lactic acid, etc.), vitamins (L-Asco Binic acid, dl-α-tocopherol, vitamin B1, vitamin B2, niacin, pantothenic acid, vitamin B6, vitamin B12, folic acid, biotin, inositol, etc., mineral (zinc, iron, calcium, magnesium, chromium, selenium, potassium, Sodium, etc.), glucosamine, yeast, eggshell membrane, lycopene, astaxanthin, other carotenoids, silk, chondroitin, ceramide, placenta extract, shark fin extract, deep-sea cocoon extract, squalene, γ-aminobutyric acid, casein decapeptide, raw chestnut skin extract , Chestnut leaf extract, chestnut potato extract, chestnut pulp extract, chestnut bark extract, cabbage ferment extract, rose petal extract, grape leaf extract, grape seed extract, apple polyphenol, chamomile extract, Lychee seed extract, Gotsukola extract Moon peach leaf extract, lotus germ extract, star fruit leaf extract, mulberry leaf extract, guava tea extract, red wine, green tea, tea, oolong tea, coffee, cocoa, chocolate, black sesame, beans, soy milk, nuts, mushrooms, Green-yellow vegetables, egg-derived raw materials such as iodine egg, catechins, other polyphenols, raspberry ketone, low molecular weight alginic acid, psyllium seed coat, ginkgo biloba extract, pine bark extract, nattokinase, plant sterol, diacylglycerol, chitosan, Examples include hyaluronic acid, methylsulfonylmethane, kojic acid, ellagic acid, arbutin, lucinol, magnolignan, magnesium phosphate L-ascorbate, CoQ10, and α-lipoic acid.

Although it does not specifically limit as a dosage form of the pharmaceutical composition of this invention, Oral administration formulation is desirable. Specifically, solutions, extracts, elixirs, capsules (hard capsules, soft capsules, microcapsules), granules, pills, suspensions, emulsions, powders, spirits, tablets (plain tablets, coated tablets, special Tablets), syrups, soaking agents and decoction. These preparations can be produced by a conventional method in the pharmaceutical technical field, for example, by the method described in the Japanese Pharmacopoeia. These preparations can be safely administered to mammals including humans.

Since the pancreatic lipase inhibitor containing the cucumber extract of the present invention is a compound having low toxicity to living organisms, it can be used as it is or in combination with a pharmacologically acceptable non-toxic and inert carrier. Can be applied as a pharmaceutical composition (including animal drugs) to mammals (eg, mice, rats, rabbits, dogs, cats, cows, horses, pigs, monkeys, etc.), fish, and the like.

The pharmacologically acceptable carrier is not particularly limited, and various carrier substances known as pharmaceutical materials can be used. The carrier substance is not particularly limited, and examples of solid carrier include excipients, lubricants, binders, and disintegrants. In addition to the above carrier substances, formulation additives such as preservatives, colorants, natural pigments, sweeteners and the like can be used as necessary. These substances include lactose, hydroxypropylmethylcellulose, hydroxypropylcellulose, low substituted hydroxypropylcellulose, ethylcellulose, corn starch, crystalline cellulose, carmellose calcium, silicic anhydride,
Specific examples include synthetic aluminum silicate, magnesium stearate, and talc, but are not limited thereto.

The carrier substance in the liquid preparation is not particularly limited, and examples thereof include those formulated as a solvent, a solubilizing agent, a suspending agent, an isotonic agent, a buffering agent, and the like. Furthermore, formulation additives such as preservatives, colorants, water-insoluble lake pigments, sweeteners and the like can be used as necessary. These substances include isotonic agents such as mannitol, sodium chloride, glucose, sorbitol, glycerol, xylitol, fructose, maltose, mannose, stabilizers such as sodium sulfite, preservatives such as benzyl alcohol and methyl parahydroxybenzoate. In addition to the above, a solubilizer, a soothing agent, a pH adjuster and the like can be specifically exemplified, but are not limited thereto.

Hereinafter, the present invention will be specifically described by illustrating examples and comparative examples. In addition, this invention is not limited at all by these Examples.

-Kunugi extracts 1 to 3 (hereinafter, extracts 1 to 3)
After putting 200 g of dried Kunugi bark into a beaker, 2000 ml of a predetermined solvent (using one of three kinds of pure water, ethanol and 50% ethanol aqueous solution) was added and stirred for 48 hours to obtain each solvent extract. It was. Each extract was lyophilized to dryness after ethanol was distilled off under reduced pressure as necessary. The dried product (13 g) obtained from the water extract of Kunugi bark was designated as extract 1 and the dried product (15.5 g) obtained from the ethanol extract was designated as extract 2 and obtained from the 50% ethanol aqueous solution extract. The dried product (18 g) was subjected to the following test as Extract 3.

-Kunugi extract 4-5 (hereinafter referred to as extract 4-5)
5 g of the same dried product as the above extract 3 (dried product obtained from a 50% ethanol aqueous solution of Kunugi bark) was prepared, dissolved in 100 ml of pure water, and then 1000 ml of n-butanol saturated with pure water. Partition extracted. The respective solvents were distilled off from the aqueous phase and n-butanol phase under reduced pressure to obtain a water fraction (0.14 g) and an n-butanol fraction (4.86 g). The obtained water fraction was used as an extract 4 and the n-butanol fraction was used as an extract 5 for the following tests.

Evaluation test Measurement of pancreatic lipase inhibitory activity Pancreatic lipase activity was calculated by measuring the amount of oleic acid released from triolein. Triolein (SIGMA Chemical Co. (US)) 80 mg, lecithin 10 mg (Wako Pure Chemical Industries, Ltd.), bile acid (SIGMA Chemical Co. (US)) 5 mg, 9 ml of 0.1 mol (M) TES buffer A uniform suspension was obtained by sonication in a liquid (pH 7.0) for 10 minutes, and this was used as a substrate liquid. 0.05 ml of pancreatic lipase solution (SIGMA Chemical Co. (made in USA)) (final concentration 1 μg / ml) and 0.1 ml of the test substance were added to 0.1 ml of the substrate solution, reacted at 37 ° C. for 30 minutes, and free fatty acid Was quantitatively measured by the copper reagent method. As the pancreatic lipase activity value, the pancreatic lipase activity value and standard deviation of each test substance were calculated with the value of no test substance added (control) being 100%. The lower the activity value, the stronger the pancreatic lipase inhibitory action.

Examples 1 to 7 and Comparative Example 1
The test substances added in Examples 1 to 5 were used by dissolving each extract in pure water so that the addition concentrations shown in Table 1 were obtained. Comparative Example 1 was pure water only. The measurement results are also shown in Table 1. Similarly, the test substances added in Examples 6 to 7 were used by dissolving each extract in pure water so that the addition concentrations shown in Table 2 were obtained. The measurement results are also shown in Table 2.

As is clear from the results shown in Table 1, all of the water extract, ethanol extract and 50% aqueous ethanol extract inhibited pancreatic lipase activity. In particular, a 50% ethanol aqueous extract of cucumber bark showed a stronger pancreatic lipase inhibitory effect, but it was also found that it had a dose dependency.

As is apparent from the results shown in Table 2, the extract obtained by fractionating the 50% ethanol aqueous extract of the cucumber bark with water and n-butanol is a pancreatic lipase in both the water fraction and the n-butanol fraction. It has an effect of inhibiting the activity, and particularly has an excellent inhibitory effect on the n-butanol fraction.

From this result, it is expected that the cucumber extract has an excellent pancreatic lipase inhibitory effect and delays intestinal absorption of lipids. Thus, it is considered that the composition containing the cucumber extract suppresses fat accumulation and has preventive, ameliorating and therapeutic effects for various diseases.

Below, the Example of the food-drinks composition and pharmaceutical composition containing the pancreatic lipase inhibitor of this invention are shown. The composition is expressed in Wt%.

Example 8 Chewing gum (food / beverage composition)
A chewing gum having the following composition was prepared by a conventional method.
Extract of 50% ethanol aqueous solution of Kunugi bark (Extract 3) 2.0
Gum base 20.0
Reduced water candy 4.0
Apple flavoring 0.5
Maltitol TO 100

When a monitor suffering from weight gain took the above chewing gum, which was 1500 mg per tablet, once a day, three times a day, for three months, the increase in body weight was suppressed compared to before.

Example 9 Tablet confectionery (food and beverage composition)
Tablet confectionery having the following composition was prepared by a conventional method.
Extract of 50% ethanol aqueous solution of extract of Kunugi bark (Extract 3) 5.0
Sucrose fatty acid ester 4.0
Raspberry flavor 0.1
Sorbitol TO 100

When a monitor suffering from an increase in body weight took 1 tablet of 2000 mg of the above tablet confection once a day, 3 times a day for 3 months, the increase in body weight was suppressed compared to before.

Example 10 Tablet (Pharmaceutical Composition)
Extract of 50% ethanol aqueous solution of Kunugi bark (Extract 3) 10.0
Vitamin C 20.0
Vitamin B1 0.5
Vitamin B2 0.5
Lactose 40.0
Dextrin 23.0
Synthetic aluminum silicate 5.0
Magnesium stearate 1.0

(operation)
Each of the above components was mixed, and the mixture was compressed into 500 mg per tablet using a tableting machine to obtain a tablet containing 50 mg of a solvent extract of kunugi bark in one tablet.

When a patient with hyperlipidemia took the above tablet once a day, 3 times a day for 3 months, the blood fat level decreased.

The pancreatic lipase inhibitor of the present invention acts as a lipolysis inhibitor, thereby suppressing digestion and absorption of fat in the body and preventing, treating, and improving fat accumulation in the body. Thus, the food and beverage composition and the pharmaceutical composition containing the pancreatic lipase inhibitor of the present invention can be used for the prevention, treatment and improvement of obesity, hyperlipidemia and fatty liver.

Claims (5)

A lipase inhibitor comprising kungi extract as an active ingredient. A pancreatic lipase inhibitor comprising, as an active ingredient, an n-butanol fraction obtained by further fractionating kungi extract with water and n-butanol. The pancreatic lipase inhibitor according to claim 1 or 2, wherein the extraction solvent is a hydrous organic solvent. The food-drinks composition containing the pancreatic lipase inhibitor as described in any one of Claims 1-3. Pharmaceutical composition containing the pancreatic lipase inhibitor according to any one of claims 1 to 3.