JP5666760B2 - Composition containing lignan compounds - Google Patents

Description

  The present invention relates to a lignan compound-containing composition. More specifically, the present invention relates to a composition containing sesamin and / or episesamin and a medium chain fatty acid glyceride having 8 to 12 carbon atoms.

Lignans compounds are known for use in various applications. For example, US Pat. No. 4,427,694 discloses that sesamin is effective in alleviating alcohol addiction and withdrawal symptoms of alcohol and smoking, and JP-A-2-138120 discloses that sesaminol and episesaminol are used to treat allergic diseases such as bronchial asthma. -It is disclosed that it is effective for prevention. The present applicants have also confirmed various physiological actions of lignan compounds, and so far, blood cholesterol lowering action (Patent No. 3001589), Δ ⁵ -desaturase inhibiting action (Patent No. 3070611), liver Function improving action (patent 3075358), cholesterol lowering action (patent 3075360), anti-intoxication action (patent 3124062), cholesterol and bile acid metabolism inhibition, cholesterol lowering action (patent 3283274), carcinogenesis inhibiting action (patent 3183664) No.), breast cancer inhibitory action (Japanese Patent Laid-Open No. 05-043458), lipid peroxide production inhibitory action (Japanese Patent Laid-Open No. 05-05388), active oxygen removal action (Japanese Patent Laid-Open No. 06-227977), etc. Yes.

By the way, in general, fat-soluble substances are poorly absorbed by humans or animals when ingested. Therefore, a method for enhancing absorption of a fat-soluble substance has been proposed. For example, Ubidecalenone, which is a fat-soluble substance, has been disclosed as a method for enhancing absorption by dissolving it in edible natural fats and oils and triglycerides of medium chain fatty acids (Japanese Patent Laid-Open No. 54-92616).
USP 4427694 JP-A-2-138120 Patent 3001589 Japanese Patent No. 3070611 Japanese Patent No. 3075358 Patent 3075360 Patent 3124062 Japanese Patent No. 3283274 Japanese Patent Laid-Open No. 04-159221 (Japanese Patent No. 3183664) JP 05-043458 A JP 05-05388 Japanese Patent Laid-Open No. 06-227977 JP 54-92616

  The present inventors conducted an absorption experiment in rats in the case of a suspension in which water and fat (wheat germ oil) were dissolved, with respect to sesamin and episesamin, which are fat-soluble substances. As a result, it was confirmed that the latter was remarkably excellent in absorption in the body. It can be said that sesamin and / or episesamin is a preferred form to be dissolved in fats and oils, but sesamin and / or episesamin is poorly soluble and has low solubility in fats and oils (wheat germ oil) and should be formulated at a high concentration. In addition to being difficult, even when blended at a low concentration, crystals sometimes precipitated during storage due to poor storage stability. Since this crystal precipitation may cause a decrease in absorbability, in consideration of storage stability, it has only been blended at a concentration considerably lower than the solubility in fats and oils (wheat germ oil). Because of this situation, if you try to increase the amount of sesamin and / or episesamin that are consumed at one time, the amount of fats and oils that are solvents must be increased, and there is a problem that excessive caloric intake is forced. It was. Moreover, the volume per unit dose of the prescribed sesamin and / or episesamin-containing composition may become too large, or the intake quantity may become too large, resulting in inconvenience. In particular, when formulated for oral administration, the formulation (capsule, etc.) becomes too large, or the number of ingested grains increases too much, which may impede intake.

  An object of this invention is to provide the composition which can mix | blend sesamin and / or episesamin which are fat-soluble substances with a high density | concentration.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors use a medium-chain fatty acid triglyceride having 8 to 12 carbon atoms as a solvent, compared with the case of wheat germ oil that is a long-chain fatty acid. As a result, it has been found that the solubility of sesamin and / or episesamin is improved by about 2.5 to 5.5 times. As a result of further study, the present inventors have found that there is a difference in solubility between sesamin and its isomer, episesamin, that episesamin is more sparingly soluble, and in medium-chain fatty acid triglycerides, the sesamin and episesamin As a result, the present inventors have found that the difference in solubility is large.

  That is, the present invention is a composition containing sesamin and / or episesamin and medium chain fatty acid triglyceride having 8 to 12 carbon atoms, and is a composition containing sesamin and / or episesamin dissolved in medium chain fatty acid triglyceride. .

  Moreover, this invention relates to the food / beverage products containing the said composition, The preferable form is a capsule.

  The composition of the present invention contains sesamin and / or episesamin at a much higher concentration than previously possible, and has excellent storage stability and high safety. Since the composition of the present invention contains sesamin and / or episesamin at a high concentration, when taken orally as a soft capsule or the like, the amount of capsules taken can be reduced, and the intake amount of oil as a solvent can be reduced. Can be suppressed.

  Further, according to the present invention, it is possible to provide a capsule containing 1.0% by weight or more of episesamin (or a composition containing episesamin at a high concentration) which has been difficult to achieve until now.

  Furthermore, according to the present invention, episesamin can be purified by utilizing the difference in solubility between sesamin and episesamin with respect to medium-chain fatty acid triglycerides.

Lignan compounds The sesamin and episesamin (sometimes referred to herein as “lignan compounds”) used in the present invention can be used alone or in combination.

The lignan compound added to the food of the present invention and a method for obtaining an extract containing the lignan compound as a main component can be performed by the following procedure. First, in order to obtain an extract based on lignan compounds from sesame oil, various organic solvents that are substantially immiscible with sesame oil and that can extract and dissolve lignan compounds are used. Obtained by extraction and concentration. Examples of such an organic solvent include acetone, methyl ethyl ketone, diethyl ketone, methanol, ethanol and the like. In order to obtain an extract containing a lignan compound as a main component, for example, sesame oil and any of the above-mentioned solvents are uniformly mixed, and then allowed to stand at a low temperature and subjected to phase separation according to a conventional method such as centrifugation, It is obtained by evaporating and removing the solvent from the components. More specifically, sesame oil is dissolved in 2 to 10 times, preferably 6 to 8 times the volume of acetone, and left overnight at -80 ° C. As a result, the oil component becomes a precipitate, and the organic solvent is distilled off from the filtrate obtained by filtration to obtain an extract containing a lignan compound as a main component. Alternatively, sesame oil is obtained by mixing sesame oil with hot methanol or hot ethanol, and then allowing to stand at room temperature, and evaporating and removing the solvent from the solvent fraction. More specifically, sesame oil is 2 to 10 times, preferably 5 to 5 times. Mix vigorously with 7 volumes of hot methanol (over 50 ° C) or hot ethanol (over 50 ° C). Phase separation is performed according to a conventional method such as standing at room temperature or centrifugation, and the solvent is distilled off from the solvent fraction to obtain an extract containing a lignan compound as a main component. Supercritical gas extraction can also be used. In order to obtain each lignan compound from this extract, the extract is treated according to conventional methods such as column chromatography, high performance liquid chromatography, recrystallization, distillation, liquid-liquid countercurrent chromatography and the like. The compound to be isolated may be isolated. More specifically, the extract was separated by high performance liquid chromatography using a reverse phase column and methanol / water (60:40) as an eluent, and the solvent was distilled off. By recrystallization from ethanol, lignan compounds such as sesamin, episesamin, sesaminol, episesaminol and the like are obtained. The sesame oil used may be a refined product, or any crude product before the decolorization step in the process of producing sesame oil, and may be sesame seeds or sesame seeds (defatted sesame seeds, residual oil content 8 to 10%). In this case, the sesame seeds or sesame seeds can be crushed as necessary, and then extracted by a conventional method using any solvent, for example, the solvent described above for extraction from sesame oil. After separating the extraction residue, the extract is obtained by evaporating the solvent from the extract by evaporation or the like. In addition to sesamin, episesamin, sesaminol, and episesaminol, sesamorin, 2- (3,4-methylenedioxy) can be obtained from the sesame seed extract, sesame seed extract, or crude sesame oil extract thus purified. Phenyl) -6- (3-methoxy-4-hydroxyphenyl) -3,7-dioxabicyclo [3,3,0] octane, 2,6-bis- (3-methoxy-4-hydroxyphenyl) -3 , 7-dioxabicyclo [3,3,0] octane, or 2- (3,4-methylenedioxyphenyl) -6- (3-methoxy-4-hydroxyphenoxy) -3,7-dioxabicyclo [ Each lignan compound of 3,3,0] octane is obtained in the same manner.

  In addition, sesamin obtained from fine spice has the same effect as sesamin obtained from sesame seeds and sesame oil, and these optically active substances are also included in the lignan compounds. Furthermore, lignan compounds can also be obtained from byproducts of the sesame oil production process. In addition, the purification method of a lignan compound and the method of obtaining an extract are not restricted to this. Furthermore, the above lignan compounds and extracts based on lignan compounds are not limited to those obtained from sesame oil, sesame seeds, and sesame seeds, and natural products containing lignan compounds themselves can also be used. it can. Examples of such natural products include pentagonal bark, paulownia tree, white fruit bark, hihatsu, and spicy.

  Examples of methods for obtaining lignan compounds by synthesis include the following. For example, sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)), and pinoresinol can be synthesized by the method of Freundenberg et al. (Chem. Ber., 86, 1157 ( 1953)), syringaresinol can be synthesized by the method of Freundenberg et al. (Chem. Ber., 88, 16 (1955)).

  Furthermore, the lignan compounds can be used in the form of glycosides, and these can be used alone or in appropriate combination as a component of the composition.

Solvent (medium chain fatty acid glycerides)
In this invention, a lignan compound is melt | dissolved in fats and oils (what consists of 1 or more types of mono, di, or triglyceride) containing C8-C12 medium chain fatty acid glyceride.

  In the present specification, the term “medium chain fatty acid glyceride having 8 to 12 carbon atoms” refers to mono-, di- or triglycerides in which a fatty acid is ester-linked with glycerol (sometimes referred to as mono-, di-, or triacylglycerols), unless otherwise specified. ) Wherein at least one of the constituent fatty acid moieties is derived from a medium chain fatty acid having 8 to 12 carbon atoms. The carbon chain of the fatty acid may be linear or branched.

  In the present specification, a portion derived from a medium chain fatty acid constituting a part of glyceride may be simply referred to as “medium chain fatty acid”.

  The medium chain fatty acid glyceride serving as a solvent for the lignan compound in the composition of the present invention may be any of monoglyceride, diglyceride, or triglyceride, or a mixture thereof. A triglyceride that is a fatty acid (in this specification, sometimes referred to as “MCT”, for example, tricaprylin) can be preferably used.

  In the present invention, the medium chain fatty acid may be either a saturated fatty acid or an unsaturated fatty acid, but a saturated fatty acid is preferred from the viewpoint of improving the stability of the fatty acid glyceride against oxidation and the like.

  Preferred medium chain fatty acids in the present invention include, for example, caprylic acid, pelargonic acid, capric acid, undecyl acid, and lauric acid. In the case of constituting diglyceride or triglyceride, these fatty acids can be constituted singly or in combination of two or more.

  A particularly preferred medium chain fatty acid glyceride is a triglyceride in which all the fatty acids are medium chain fatty acids, and the medium chain fatty acid is at least one selected from the group consisting of caprylic acid, capric acid and lauric acid. Is mentioned.

  As the medium-chain fatty acid triglyceride, those existing as components in vegetable oils such as coconut oil, coconut oil, and babassu oil can be used, and artificially synthesized ones can also be used.

  The fat or oil that is a solvent for dissolving the lignan compound may be composed only of medium-chain fatty acid glycerides, and the medium-chain in an amount or blending ratio effective for stably dissolving the lignan compound. As long as the fatty acid glyceride is contained, the composition which consists of medium chain fatty acid glyceride and another fatty acid glyceride may be sufficient. The blending ratio of medium-chain fatty acid glycerides in fats and oils is, for example, 5 to 100%, 10 to 100%, 25 to 100%, 50 to 100%, and 75 to 100% by weight with respect to the total amount of fats and oils. Can do.

  Medium-chain fatty acid glycerides have the advantage that they are difficult to accumulate in the body and are difficult to oxidize. In addition, medium chain fatty acid triglycerides are originally contained in fats of dairy products, palm oil and the like, and are rich in food experience.

Lignan compound-containing composition and food and drink To produce the composition of the present invention, a powdered lignan compound is added to a solubilizer (solvent) and mixed, preferably by stirring under heating. Dissolve thoroughly. If medium chain fatty acid triglyceride is used as a solvent, the lignan compound is sufficiently dissolved if the blending (weight) ratio is about lignan compound: solvent = 1: 15-100.

In the present specification, the food and drink includes seasonings, nutritional supplements, health foods, diet foods, general health foods, supplements and beverages, and orally administered medicines. The food and drink of the present invention are solid (for example, crystals, capsules, tablets, powders), semi-solid (for example, gels and pastes), and liquid (for example, mineral water, soft drinks, fruit drinks, sports drinks, alcoholic beverages). Although Ru can be, this time, lignan-class compound since it is preferably contained remains easy solution state is systemic absorption, food or beverage of the present invention, capsules (in particular soft capsule), beverages such as Form is preferred.

  The food / beverage products of this invention can be manufactured by containing the composition of this invention using the method well-known to those skilled in the art. The food / beverage products of this invention can anticipate the desired effect of a lignan compound stably and efficiently.

  The blending amount of the lignan compound in the food and drink of the present invention is not particularly limited, but referring to the preferred daily intake of the lignan compound, those skilled in the art will blend according to the intake form of the food and drink The amount can be set as appropriate. Usually, it adds so that lignan compounds may contain 0.0001 weight% or more with respect to the food / beverage products of this invention, especially 0.001 weight% or more.

  The composition of this invention can contain arbitrary additives other than a lignan compound and a C8-C12 medium chain fatty acid glyceride as needed. Moreover, the food / beverage products of this invention can contain the arbitrary components used for normal food / beverage products other than the composition of this invention. Examples of these additives and / or ingredients include vitamins such as vitamin E and vitamin C, sugars, excipients, disintegrants, binders, lubricants, emulsifiers, tonicity agents (isotonic agents), Buffering agents, solubilizers, preservatives, stabilizers, antioxidants, coloring agents, flavoring agents, fragrances, coagulants, pH adjusters, thickeners, extract powders, crude drugs, inorganic salts and the like can be mentioned.

  In addition, in the composition for food and drink or the food and drink of the present invention, its specific use (for example, for nutritional support and health maintenance) and / or its specific use (for example, intake) , Number of ingestion, ingestion method, etc.) can be displayed.

  Recently, episesamin significantly increased the gene expression and enzyme activity of β-oxidase in the liver compared to sesamin (Kushiro M., et al. J. Nutr. Biochem., 13, 289-295 ( 2002))) and the like, the excellent effect of episesamin is beginning to be reported. Therefore, development of a composition containing episesamin as an active ingredient is expected. However, studies by the present inventors have revealed that sesamin and episesamin have different solubility, and that episesamin has low solubility (see Example 1). Therefore, when an attempt is made to produce a composition or supplement (capsule) containing episesamin as an active ingredient using wheat germ oil or the like that exists in the past, there is a problem that episesamin precipitates during storage.

  The present invention can be advantageously used to prepare capsules containing such episesamin as an active ingredient. Specifically, a capsule was prepared by adding episesamin, which could not be realized until now, in a state of being dissolved in the content composition (content portion excluding the outside of the capsule) to be 1.0% by weight or more. can do.

  Further, the difference in solubility between sesamin and episesamin tends to be large in MCT (see Example 1). Therefore, MCT can be used when obtaining a composition containing episesamin at a high concentration from the mixture of sesamin and episesamin for the purpose of preparing a composition containing episesamin as an active ingredient. Specifically, by dissolving a sesamin and episesamin mixture in MCT and performing recrystallization, episesamin can be purified, and a composition containing episesamin at a high concentration can be obtained.

  Hereinafter, although it further demonstrates along an Example, this invention is not limited to an Example.

<Example 1: Solubility test>
1. In addition to a mixture of sesamin and episesamin (sesamin: episesamin = 51.1: 48.2), three types of sesamin and episesamin purified from this mixture were used as experimental material samples. Wheat germ oil is manufactured by Riken Vitamin, olive oil is manufactured by Nacalai Tesque, and medium chain fatty acid (MCT) is Actor M-1 (C8: C10: C12 = 56: 42: 2 medium chain fatty acid triglyceride) manufactured by Riken Vitamin. And Actor M-2 (C8 medium chain fatty acid triglyceride). As diacylglycerol (DG), a commercially available oil (Econa cooking oil, Kao, edible oil containing about 80% diacylglycerol) was used.

2. Experimental Method 2 g of various oils and samples were weighed in test tubes so that the concentration was in increments of 0.25% within a range of 0.5 to 10% (weight). Next, these test tubes were heated to 120 ° C. to completely dissolve sesamin in fats and oils. Thereafter, the test tube was allowed to stand overnight at room temperature, and the presence or absence of crystals was observed.

3. Results As shown in Table 1, surprisingly, the solubility of sesamin and / or episesamin is very high with triglycerides (LCT) of long chain fatty acids such as wheat germ oil and olive oil, or with diacylglycerol (DG). It was found to be low and selectively highly soluble only in medium chain fatty acid triglycerides (MCT). From this result, when manufacturing a supplement containing sesamin and / or episesamin as an active ingredient, for example, as a soft capsule, a lignan compound (for example, sesamin) is dissolved in MCT to be added per grain. It has been found that the amount of compound can be increased.

Further, from the results in Table 1, it was found that there is a difference in solubility between sesamin and episesamin, and the solubility of episesamin tends to be low. From this result, it was proved that the above-described technique for dissolving a supplement containing episesamin as an active ingredient, for example, as a soft capsule in the MCT is useful.
In addition, sesamin, episesamin, and a mixture thereof dissolved in MCT were stable without precipitation at room temperature for at least 9 months.

<Example 2: Production of episesamin-containing composition>
MCT (Riken Vitamin Co., Actor M-1) or wheat germ oil was used as the fat. After weighing 20 g of fats and oils in a 50 ml eggplant flask and adding 4.0 g of a mixture of sesamin and episesamin (sesamin: episesamin = 55: 45) to the flask, heat to 120 ° C. in an oil bath and stir well. Dissolved. Then, it is slowly cooled by standing in an environment of 20 ° C., and when the liquid temperature reaches 60 ° C., 4.0 mg of episesamin 100% seed crystal is added and crystallized in an environment of 20 ° C. for 30 minutes. It was. The liquid in which the crystals were precipitated was subjected to solid-liquid separation by suction filtration, and then the solvent remaining in the crystal mixture was washed away with 99.5% ethyl alcohol. The crystal mixture thus obtained was subjected to HPLC under the following conditions to analyze the composition of sesamin and episesamin.

  In addition, a mixture of sesamin and episesamin was heated and dissolved at 120 ° C. in the same manner as described above, and then treated with activated clay, followed by recrystallization in the same manner as above to obtain a crystal mixture, and its composition analysis was performed. It was. Activated clay treatment is the addition of 0.57 g of activated clay (Mizusawa Chemical Co., Ltd., Galeon Earth V2R) to the heat-dissolved solution of sesamin and episesamin in an oil bath, treated at 120 ° C. for 30 minutes, and then filtered. This is a process that removes waste white clay.

(HPLC conditions)
Column: Inertsil ODS-3 (GL-SCIENCE) 4.6 × 150mm
Column temperature: 40 ° C
Moving layer: methyl alcohol / water = 7: 3
Flow rate: 1 ml / min
Detector: UV290nm.

  The episesamin content (purity) in the obtained crystal was 67.4% without active clay treatment and 94.0% with active clay treatment. Since the episesamin content before recrystallization was 45%, it was found that episesamin can be purified by recrystallizing a mixture of sesamin and episesamin in MCT.

<Example 3: Capsule-1>
Sesamin (sesamin: episesamin≈1: 1) having the following composition was dissolved in MCT under heating, and then cooled to prepare a sesamin-containing composition. This composition was filled into a soft capsule skin by a usual rotary method to obtain soft capsules of 250 mg (content liquid amount: 210 mg) per capsule.

(Content liquid)
Sesamin 10mg
MCT 200mg
(Skin)
Gelatin 60.0%
Glycerin 30.0%
Methyl paraoxybenzoate 0.15%
Propyl paraoxybenzoate 0.51%
Water proper amount.

<Example 4: Capsule-2>
As the lignan compound, two types of compositions containing high concentrations of episesamin prepared (purified) in Example 2 (sesamin: episesamin = 32.6: 67.4, 6.0: 94.0) were used. A lignan compound having the following composition was dissolved in an oil of MCT: wheat germ oil = 25: 75 under heating, and then cooled to prepare a lignan compound-containing composition. This composition was filled into a soft capsule skin by a normal rotary method to obtain 250 mg of soft capsules (content amount: 200 mg). In all cases, no crystal precipitation was observed during storage.

(Content liquid)
Lignans compounds 3mg
Vitamin E 20mg
Fat and oil 177mg
(Skin)
Gelatin 60.0%
Glycerin 30.0%
Methyl paraoxybenzoate 0.15%
Propyl paraoxybenzoate 0.51%
Appropriate amount of water

Claims (8)

A composition containing sesamin and / or episesamin dissolved in an oil or fat containing triglyceride (MCT) , wherein all the fatty acids constituting it are medium chain fatty acids having 8 to 12 carbon atoms ,
The composition whose compounding ratio of MCT in fats and oils is 25 to 100% by weight ratio. The composition of claim 1, wherein the weight ratio of sesamin and episesamin to MCT is from 1:15 to 1: 100 . The composition according to claim 1 or 2 , wherein the MCT contains one or more glycerides selected from caprylic acid, capric acid or lauric acid. Food-drinks containing the composition of any one of Claims 1-3 . The food-drinks of Claim 4 which are the form of a capsule. A capsule containing 1.0% by weight or more of episesamin dissolved in the content composition ,
The content composition is fats and oils containing episesamin and triglycerides (MCT) whose constituent fatty acids are all medium chain fatty acids having 8 to 12 carbon atoms,
The capsules, wherein the compounding ratio of MCT in the fat is 25 to 100% by weight. The capsule according to claim 6 , wherein the weight ratio of episesamin to MCT is 1:40 to 1: 100 . Resolving a mixture of sesamin and episesamin in an oil and fat containing triglycerides (MCT) in which all of the fatty acids constituting them are medium chain fatty acids having 8 to 12 carbon atoms ;
The method of refine | purifying episesamin whose compounding ratio of MCT in fats and oils is 25 to 100% by weight ratio.