JP5280029B2 - Composition containing sesamin and γ-oryzanol - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for efficiently developing the physiological actions of sesamin compounds to reinforce the actions of the sesamin compounds, and to provide an effective compound used together to achieve the object. <P>SOLUTION: Provided is a composition which contains both the sesamin compounds (contained in sesame seeds in an amount of 0.1 to 0.5%, preferably sesamin and/or episesamin) and &gamma;-oryzanol, synergistically reinforces the physiological actions, such as anti-fatigue action, of the sesamin compounds, is safe for humans and animals, and can therefore continuously be taken. <P>COPYRIGHT: (C)2009,JPO&amp;INPIT

Description

TECHNICAL FIELD OF THE INVENTION

  The present invention relates to a composition containing sesamin and γ-oryzanol, and more particularly relates to a composition with enhanced physiological action of sesamin and food and drink containing the composition.

  Sesamin is one of the major lignan compounds of sesame and is contained in the sesame seeds in an amount of 0.1 to 0.5%. In contrast, episesamin does not originally exist in sesame seeds, but sesamin is epimerized and produced as a secondary product in the purification process (decolorization, deodorization) of sesame oil to salad oil. (Non-patent document 1), sesamin purified from this sesame oil is known to contain sesamin and episesamin at a ratio of approximately 1: 1 (weight ratio) (non-patent document 2).

  The following physiological effects are disclosed for sesamin containing these compounds. For example, cholesterol or bile acid metabolism inhibiting action in the intestine, alcohol poisoning and withdrawal symptoms alleviating action, liver function improving action, in vivo stabilization action of highly unsaturated fatty acids (Patent Document 1), Δ5-unsaturation Enzyme inhibitory action, migraine inhibitory action, apoptosis induction action on human leukemia cells, melatonin oxidative degradation inhibitory action, inflammatory disease (amyotrophic lateral sclerosis) improving action, anti-inflammatory and infection protective action, α- Allergy prevention or amelioration action by combined use with oils and fats containing at least one of linolenic acid, eicosapentaenoic acid, docosahexaenoic acid (Patent Document 2), active oxygen scavenging action, anti-drunk action, omega-6 / omega-3 unsaturated Fatty acid balance regulating action (Patent Document 3), lipid peroxide production inhibition, breast cancer inhibiting action, antihypertensive action, body fat reducing action, saw palmetto Prostatic hypertrophy suppression effect by combined use with oil has been clarified.

Regarding the combination of sesamin and γ-oryzanol, there is a document describing that rice germ oil is used as a solvent when recrystallizing sesamin. (Patent Document 4)
JP-A-11-269456 JP-A-5-58902 Japanese Patent No. 3512196 WO2007 / 037385 Geriant.med. 19, 1812-1840, 1981 Namiki et al., “Sesame Science and Functionality”, Maruzen Planet Co., Ltd. (1998) Fukuda, Y., et al., J. Am. Oil. Chem. Soc., 63, 1027-1031 (1986)

  As described above, various physiological actions have been reported for sesamin, but there are few reports on substances that can enhance the physiological action of sesamin when used in combination with sesamin.

  An object of the present invention is to provide a composition containing sesamin with enhanced physiological action. Another object of the present invention is to provide an agent having high physiological action, which contains sesamin as an active ingredient.

  As a result of intensive studies to solve the above problems, the present inventors have used γ-oryzanol together with sesamin, so that the physiological action of sesamin, for example, anti-fatigue action, From the action and the action of γ-oryzanol alone, it was found that it was significantly increased beyond the expected range, and the present invention was completed.

That is, this invention relates to the composition containing the following food and drink.
1. A composition containing sesamin and γ-oryzanol;
2. 2. The composition according to 1, wherein the ratio (weight ratio) of the total amount of γ-oryzanol is 0.4 or more to the total amount of sesamin 1;
3. The composition according to 1 or 2, wherein the content of sesamin is 1% by weight or more based on the total weight of the composition;
4). The composition according to any one of 1 to 3, wherein the sesamin is sesamin and / or episesamin;
5. Composition in any one of 1-4 in which (gamma)-oryzanol is mix | blended as rice germ oil;
6). The composition according to any one of 1 to 5, which is for oral use;
7). The composition according to any one of 1 to 6, which is a food and drink;
8). An anti-fatigue agent containing sesamin and γ-oryzanol as active ingredients.

  By blending sesamin and γ-oryzanol, the physiological action of the composition, for example, anti-fatigue action, synergistically increases beyond the range expected from sesamin alone and γ-oryzanol alone, resulting in superior physiological action. A composition having is obtained.

  Further, the anti-fatigue agent of the present invention has excellent fatigue reduction and fatigue recovery promoting action, and sesamin derived from sesame and γ-oryzanol derived from rice have been used for many years. The composition of the present invention is widely applicable as a functional food or a pharmaceutical composition because it is a safe substance that is ingested as a food and drink, and is safe even if taken orally over the medium term and long term. .

BEST MODE FOR CARRYING OUT THE INVENTION

(Sesamin)
The sesamin of the present invention is a general term for a series of compounds including sesamin and its analogs. Examples of the sesamin analog include episesamin and dioxabicyclo [3.3.0] octane derivatives described in JP-A-4-9331. Specific examples of sesamin can include sesamin, sesaminol, episesaminol, sesamorin and the like, and these stereoisomers or racemates can be used alone or in combination, but in the present invention, , Sesamin and / or episesamin can be suitably used. In addition, metabolites of sesamin compounds (for example, described in JP-A-2001-139579) are sesamin analogs included in the sesamin compounds of the present invention as long as the effects of the present invention are exhibited, and are used in the present invention. Can do.

  The sesamin used for this invention is not restrict | limited at all by the form, manufacturing method, etc. For example, when sesamin is selected as the sesamin, sesamin (referred to as sesamin extract or concentrate) extracted from sesame oil by a known method (for example, a method described in JP-A-4-9331) is usually used. Although it can also be used, commercially available sesame oil (liquid state) can also be used as it is. However, when sesame oil is used, the sesamin content is low (usually less than 1%). Therefore, when trying to add sesamin necessary for obtaining the physiological action of sesamin, the composition of the γ-oryzanol-containing composition formulated Ingestion can be inconvenient because the volume per unit dose becomes too large. In particular, when formulated for oral administration, the dosage form (tablets, capsules, etc.) becomes too large, which causes problems in ingestion. Therefore, it is preferable to use a sesamin extract (or sesamin concentrate) from sesame oil from the viewpoint that the amount of intake may be small. In addition, since the flavor peculiar to sesame oil may be evaluated to be sensory unfavorable, the sesamin extract (or sesamin concentrate) may be made tasteless and odorless by a known means such as activated clay treatment.

  Thus, as sesamin, it is preferable to use a sesamin concentrate obtained by improving the concentration of sesamin by extraction and / or purification from a food-derived material such as sesame oil. The degree of concentration may be appropriately set depending on the type of sesamin used and the form of the composition to be blended. Usually, a sesamin concentrate concentrated so that the total amount of sesamin is 1% by weight or more is used. Is preferred. The total sesamin content in the sesamin concentrate is preferably 20% by weight or more, more preferably 50% by weight or more, still more preferably 70% by weight or more, and is concentrated (purified) to 90% by weight or more. Is optimal.

(Γ-oryzanol)
An effective component capable of enhancing the physiological action of sesamin is γ-oryzanol. In γ-oryzanol, blood neutral lipid lowering action (Geriant.med. 19, 1812-1840, 1981), endocrine / autonomic nerve regulating action (Japanese Pharmacology, 75 (4), 399-403, 1979), Various physiological effects such as gastric mucosal protective action (Nippon Pharmacological Journal, 84 (6), 537-542, 1984) are known, and purified products are used to treat hyperlipidemia and psychosomatic disorders (menopause, It is approved as a medicine for treating irritable bowel syndrome. In the present invention, γ-oryzanol is a generic name for ferulic acid obtained by ester-linking triterpene alcohol or sterol. Examples of the triterpene alcohol include cycloartenol, 24-methylenecycloartanol, cycloartanol, and cyclopranol. Examples of the sterol include campesterol, stigmasterol, β-sitosterol, and the like. It can be illustrated. In the present invention, these compounds can be used alone or as a mixture. As a method for quantifying γ-oryzanol, a known method such as a UV absorbance method or an HPLC method can be appropriately used. For example, dissolve the sample in heptane and measure the absorbance at the maximum wavelength of absorption at around 315 nm as described in the “Quasi-drug raw material standard” and “Food additive other than chemically synthesized products”. This can be quantified.

  The γ-oryzanol used in the present invention is not limited at all by its origin, form, production method and the like. γ-Oryzanol is known to be contained in brown rice, corn, barley and the like, but in the present invention, it is particularly preferable to use rice bran oil or rice germ oil extracted from brown rice. Commercial rice bran oil, rice germ oil, etc. can be used as they are, but as described above, the active ingredient that enhances the physiological action of sesamin is γ-oryzanol, so that the one with high γ-oryzanol content should be used. Preferably, for example, a γ-oryzanol concentrate from rice bran oil or rice germ oil is used. When the concentrate of γ-oryzanol is used, the total amount of γ-oryzanol in the γ-oryzanol concentrate is preferably 1% by weight or more, and more preferably 30% by weight or more. Such a concentrate of γ-oryzanol is industrially obtained from rice bran oil or rice germ oil extracted with an organic solvent or purified after resin treatment. For example, rice germ oil gamma 30 (Tsukino) Food Industry Co., Ltd.), γ-oryzanol, oryzadorim V-50, rice bran oil, brown rice germ oil (Oryza Oil Co., Ltd.).

(Composition containing sesamin and γ-oryzanol)
The composition of the present invention can synergistically enhance the physiological action of sesamin by using the above-mentioned sesamin and γ-oryzanol in combination. The composition of the present invention can be used as a health food having a high anti-fatigue action.

  The ingestion form of the composition containing sesamin and γ-oryzanol in the present invention is not particularly limited, but in the present invention, ingestion for the purpose of promoting health is preferably ingested as an oral composition. . The oral composition in the present invention includes a pharmaceutical composition or a food or drink.

  The total blending ratio of sesamin in the composition containing the sesamin of the present invention and γ-oryzanol is 1% by weight or more, preferably 1-50% by weight, more preferably 1-10% by weight. The total blending ratio of γ-oryzanol in the composition is not particularly limited as long as the synergistic enhancing effect of the physiological action of the above-mentioned sesamin is exerted, such as the form of the composition and the target disease state, etc. Although it may be appropriately selected depending on the conditions, it is preferably blended at 0.1 to 50% by weight, preferably 0.5 to 30% by weight, more preferably 1 to 10% by weight, based on the total amount of the composition.

  Usually, it is preferable to take sesamin so as to be 1 to 200 mg per day for an adult, preferably 5 to 100 mg. In general, it is preferable to take γ-oryzanol at 1 to 200 mg per day for an adult, more preferably about 5 to 100 mg.

  Depending on the total weight of the composition, for example, sesamin can be added to the composition of the present invention in an amount of about 1 to 100 mg, preferably 1 to 50 mg, more preferably about 3 to 30 mg. Moreover, (gamma)-oryzanol can be mix | blended in the quantity of about 1-100 mg, Preferably it is 1-60 mg, More preferably, it is about 3-30 mg. Generally, adding more than 200 mg of γ-oryzanol is economically disadvantageous because a synergistic effect of enhancing anti-fatigue action cannot be expected.

  As will be described in detail below, in the experiment using the fatigue animal model by the present inventors, in addition to sesamin 50 mg / kg (the amount of sesamin per kg body weight of the animal model (mg)), rice germ oil 200 mg / kg (60 mg / kg as γ-oryzanol) significantly enhances anti-fatigue action compared to administration of sesamin 50 mg / kg alone and γ-oryzanol 60 mg / kg alone It was done. When rice germ oil 50 mg / kg (15 mg / kg as γ-oryzanol) was administered in addition to sesamin 50 mg / kg, the anti-fatigue action was not enhanced (see FIG. 1). That is, the specific ratio of γ-oryzanol to sesamins capable of exerting a synergistic enhancing effect on the physiological action of sesamins is 0.4 or more, preferably 1.2 or more of γ-oryzanol, with the total weight of sesamin being 1. .

  As long as the effect is not impaired, the composition of this invention may mix | blend arbitrary desired components other than sesamin and (gamma) -oryzanol. For example, vitamins such as vitamin E and vitamin C, minerals, hormones, nutritional ingredients, physiologically active ingredients such as fragrances, emulsifiers, tonicity agents (isotonic agents), buffers, Solubilizing agents, preservatives, stabilizers, antioxidants and the like can be appropriately blended.

  The composition of the present invention can be suitably used as a health food because a synergistically enhanced anti-fatigue action can be obtained by blending sesamin and γ-oryzanol. Examples of health foods in this specification include preparations and foods containing the composition itself containing the sesamin of the present invention and γ-oryzanol as active ingredients, such as capsules and tablets, and general foods. Functional foods (including special health foods and conditional special health foods) that are formulated by adding the invention composition as a single component and adding various functions such as anti-fatigue action to living bodies. Can be mentioned. Furthermore, foods and the like having an anti-fatigue action with an indication to reduce fatigue of the living body or an indication to promote fatigue recovery are also included in the composition of the present invention.

  The form of the health food containing sesamin and γ-oryzanol is not particularly limited, for example, a solid form such as powder, granule, or tablet; a liquid such as solution, emulsion, or dispersion; or paste It is prepared in an arbitrary form such as a semi-solid state.

The composition of the present invention can also be used as a pharmaceutical composition. In that case, for example, the composition of the present invention may be prepared into a dosage form such as a liquid, tablet, granule, powder, capsule, dry syrup, or pill and administered orally, or an injection. May be prepared and administered. The administration form can be appropriately selected depending on the disease state, its progress, and other conditions.
(Anti-fatigue action and anti-fatigue agent)
The composition of the present invention is also useful as an anti-fatigue agent for human and non-human animals. Here, a non-human animal refers to an animal that is subject to anti-fatigue, and among them, the anti-fatigue agent of the present invention is used for humans, industrial animals, pets, and experimental animals that perceive fatigue, and particularly against humans. Are preferably used. Here, industrial animals represent domestic animals such as cattle, horses, pigs, goats, sheep, and competing horses, hounds, etc. Pets represent dogs, cats, marmosets, hamsters, etc., and laboratory animals represent mice, rats , Guinea pigs, beagle dogs, miniature pigs, rhesus monkeys, cynomolgus monkeys, and other animals used for research in the fields of medicine, biology, agriculture, pharmacy and the like. The anti-fatigue agent of the present invention is used for humans, industrial animals, pets and laboratory animals that perceive fatigue, and is particularly preferably used for humans.

Fatigue is a temporary decline in physical and mental performance that occurs when physical or mental loads are continuously applied. Or it means the quantitative fall. Further, the "fatigue" of the present invention also include chronic fatigue syndrome and death by overwork.

  The anti-fatigue agent of the present invention refers to the above-mentioned action to reduce fatigue and the action to recover fatigue, specifically, to improve the duration of exercise and the action of the affected part (including the brain), and Suppress the increase of fatigue substances with the same amount of exercise and action (improve endurance and physical strength), and the brain and nerves are in a fatigue-sensing state even though the part where exercise or action is not fatigued This refers to the effect of promoting the recovery of the fatigue state of the part where the exercise or the action has been performed to the normal state.

  The chronic fatigue syndrome targeted by the anti-fatigue agent of the present invention is long-term general fatigue, fatigue, slight fever, lymphadenopathy, muscle pain, joint pain, mental Means basic symptoms such as neurological symptoms. The anti-fatigue agent of the present invention can treat this chronic fatigue syndrome, that is, alleviate each symptom of chronic fatigue syndrome, and shift it to a normal state. Furthermore, overwork death intended by the anti-fatigue agent of the present invention is a severe overwork state, and despite being unable to maintain physical vitality, fatigue cannot be fully felt, and as a result, It means a condition where cerebrovascular disease or heart disease has developed, resulting in permanent inability to work or death. The anti-fatigue agent of the present invention can treat chronic fatigue syndrome, thereby preventing overwork death.

  The anti-fatigue action of the present invention, that is, the effect as an “anti-fatigue agent” can be confirmed, for example, by a test such as measurement of swimming time in a water immersion sleep sleep test. Use a mouse raised in an environment where it is not possible to take sufficient sleeping or resting posture, such as underwater breeding, and where it is impossible to rest physically and mentally. Measure the swimming time (for example, if the nose is submerged for 10 seconds or more, the time until the submergence, or finally, if the tip of the nose is submerged (until it no longer rises again), the time until the submergence) This confirms the degree of fatigue. Since this animal model is a physical and mental fatigue model, if the swimming time was extended by administering the test substance, physical and mental fatigue and associated pain such as muscle pain could be prevented or improved. In addition, it is confirmed that there is resistance to fatigue, such as that the time until physical strength is increased and fatigue distress is extended, and that physical vitality is maintained under a fatigue state.

  The anti-fatigue agent of the present invention is less fatigued when ingested, and is effective in recovering from fatigue. In other words, when you feel physical fatigue during muscle exercise such as sports or when you feel mental fatigue during continuous work such as calculation work, you can try to recover from fatigue, and after taking it in advance, work, sports Etc. can also prevent fatigue. In addition, endurance can be expected by taking it before or during sports. Furthermore, mental fatigue and associated diseases can be prevented by daily intake.

  The dosage form of the anti-fatigue agent of the present invention may be administered orally in the form of a liquid, tablet, granule, powder, capsule, dry syrup, pill, etc., or in the form of an injection. Often, it can be appropriately selected depending on the disease state, its progress, and other conditions.

  In addition, if preparations containing sesamin and γ-oryzanol are individually prepared and taken at the same time, or after taking one of the preparations, while taking the other preparation, The anti-fatigue action enhancing action of sesamins intended by the invention can be obtained. Therefore, kits of sesamin-containing preparations and γ-oryzanol-containing preparations are also included in the scope of the anti-fatigue agent of the present invention.

EXAMPLES Hereinafter, although a test example and an Example demonstrate this invention more concretely, this invention is not limited to these.
Example 1. Sesamin and γ -oryzanol as test substances for anti-fatigue action by sesamin and γ-oryzanol include sesamin / episesamin mixture (sesamin: episesamin (weight ratio) = 5: 5) and rice germ oil (rice germ oil gamma 30 : 30% γ-oryzanol content, Tsukino Food Industry Co., Ltd.).

  The effect on fatigue was evaluated by a water immersion sleep sleep test. Evaluation was carried out by a method obtained by partially modifying Tanaka et al.'S method (Neuroscience, Let. 352, 159-162, 2003). Balb / c male mice (8 weeks old) were purchased from Japan SLC Co., Ltd. and acclimated in the test environment for 1 week, and animals that showed normal growth were subjected to the test. The mice were divided into 5 groups as shown in Table 1 with 10 animals per group so that the average body weight was uniform. Of these, 4 groups were water-soaked sleep stress groups, and instead of using floor covering (paper chips), tap water with a water temperature of 23 ° C was kept in a breeding cage at a water depth of 7 mm, and mice were soaked. Made me sleep. On the other hand, the mice in the control group were bred by placing a bedding (paper chip) in a breeding cage. Both rice germ oil gamma 30 and sesamin were dissolved in olive oil and used as test samples. Each test sample was orally administered by gavage once a day for 2 days during water immersion sleep for 2 days. In Table 1, the doses of “rice germ oil gamma 30” of 50 mg / kg and 200 mg / kg correspond to 15 mg / kg and 60 mg / kg as γ-oryzanol, respectively.

  Two days after breeding, the mouse tail was allowed to swim with a weight equivalent to 8% of the body weight, and the limit swimming time (when the nose was submerged for 10 seconds or more, the time until submergence) was measured. Mice in the water-immersed group (water-immersive sleep stress group) have shorter swimming times than mice in the normal-reared group, but fatigue can be reduced depending on how much the mice in the test sample administration group can reduce the swimming time. The effect on was determined.

The results are shown in FIG. As is clear from FIG. 1, the swimming time of the water-immersed control group was shorter than that of the normal control group. As a test sample, the effect of shortening swimming time was observed in the group administered with sesamin at 50 mg / kg. On the other hand, in the group administered with only 200 mg / kg of rice germ oil (60 mg / kg as γ-oryzanol), the effect of reducing the swimming time was not observed. However, in the group to which sesamin 50 mg / kg and rice germ oil 200 mg / kg were administered, the shortening suppression effect by sesamin alone was remarkably enhanced. From the above, it was confirmed that the composition of the present invention has a synergistic anti-fatigue action.

Example 2 Formulation Example (Formulation Example 1) Granule Sesamin 10g
10g rice bran extract containing γ-oryzanol (containing 50%)
Tocopherol acetate 50g
Silica anhydride 20g
110g corn starch
After uniformly mixing the above powder, 100 ml of 10% hydroxypropylcellulose / ethanol solution was added, kneaded as usual, extruded and dried to obtain granules.

(Formulation Example 2) Capsule gelatin 60.0%
Glycerin 30.0%
Methyl paraoxybenzoate 0.15%
Propyl paraoxybenzoate 0.51%
Water Appropriate amount The following composition was filled in a soft capsule skin composed of the above-mentioned components by a conventional method to obtain 360 mg soft capsules.
Sesamin 3.5mg
Glycerin fatty acid ester 15.0mg
Beeswax 15.0mg
γ-Oryzanol-rich oil (containing 30%) 11.5mg
Wheat germ oil 245mg
(Formulation example 3) Tablet sesamin 10g
γ-Oryzanol 100g
172 g starch
Sucrose fatty acid ester 9.0g
9.0g of silicon oxide
These were mixed and tableted with a single-punch tableting machine to produce tablets with a diameter of 9 mm and a weight of 300 mg.

(Formulation example 4) Drink agent flavor: DL-sodium tartrate 0.1 g
0.009 g of succinic acid
Sweetener: Liquid sugar 800g
Acidulant: Citric acid 12g
Vitamin C 10g
Sesamin 1g
γ-Oryzanol 2g
Vitamin E 10g
Cyclodextrin 5g
Emulsifier 10g
Fragrance 15ml
1g potassium chloride
Magnesium sulfate 0.5g
The above ingredients were blended and water was added to make 10 liters. About 100ml of this drink is drunk.

FIG. 1 is a graph showing the influence of sesamin and / or γ-oryzanol on swimming time under water-induced sleep stress.

Claims (7)

A composition containing sesamin and γ-oryzanol , wherein the sesamin is at least one compound selected from the group consisting of sesamin, episesamin, sesaminol, episesaminol, and sesamorin, The ratio (weight ratio) of the total amount of γ-oryzanol is 0.4 or more with respect to the total amount 1 of the class, and the total blending ratio of γ-oryzanol is 1 to 50% by weight based on the total amount of the composition . Content of the sesamin-class compound is 1 wt% or more relative to the total weight of the composition, The composition of claim 1. The composition according to claim 1 or 2 , wherein the sesamin is sesamin and / or episesamin. The composition according to any one of claims 1 to 3 , wherein γ-oryzanol is formulated as rice germ oil. It is for oral use, The composition in any one of Claims 1-4 . The composition according to any one of claims 1 to 5 , which is a food or drink. An anti-fatigue agent containing sesamin and γ-oryzanol as active ingredients , wherein the sesamin is at least one compound selected from the group consisting of sesamin, episesamin, sesaminol, episesaminol, and sesamorin Yes, the anti-fatigue agent whose ratio (weight ratio) of the total amount of (gamma)-oryzanol is 0.4 or more with respect to the total amount 1 of sesamins .