HK1148465B - Sesamin/episesamin compositions - Google Patents

Abstract

Sesamin and episesamin are incorporated at specified weight ratios in oral compositions so that the oral absorption of episesamin and/or its transfer into blood circulation is increased. Sesamin and episesamin are also incorporated at specified weight ratios in oral compositions so that the physiological activities of sesamins are enhanced.

Description

Sesamin/episesamin composition

The application is a divisional application of Chinese patent application No. 200510135319.6, the application date of the patent application No. 200510135319.6 is 2005-12-28, and the invention name is 'sesamin/episesamin composition'.

Technical Field

The present invention relates to a composition containing sesamin and episesamin (sesamin/episesamin composition) which can improve the physiological activity of sesamins because it contains sesamin and episesamin which is an epimer (isomer) thereof at a predetermined ratio.

The present invention also relates to a food or drink, a liquid beverage, a pharmaceutical composition, an animal feed, or a pet food to which the sesamin/episesamin composition is added or contained.

Background

In the present invention, sesamin compounds are a generic term for sesamin and episesamin. In the present invention, a mixture of sesamin and episesamin is referred to as a sesamin/episesamin composition.

The isosesamin and sesamin are related by stereoisomers. That is sesamin (sesamin) is of the formula I:

[ Compound 1]

An optically active compound of the structure shown, and the isomer episesamin (episesamin) is of the formula II:

[ Compound 2]

An optically active compound of the structure shown. As shown in the chemical structural formula, sesamin has a plane-symmetric structure, and episesamin has an asymmetric structure.

Sesamin is one of main lignan compounds in sesame, and is contained in sesame seeds by 0.1-0.5%. On the other hand, episesamin is not present in the original sesame seeds, and is a secondary product produced by epimerization of sesamin during the refining process (decoloring, deodorizing) from sesame oil to salad oil (non-patent document 1), and it is known that sesamins refined from sesame oil contain sesamins and episesamin in a weight ratio of substantially 1: 1 (non-patent document 2).

The following physiological activities of sesame are disclosed in the prior art documents. For example, from experiments using refined sesamin, an effect of inhibiting intestinal cholesterol or bile acid metabolism (patent document 1), an effect of alleviating alcoholism or withdrawal symptoms (patent document 2), an effect of improving liver function (patent document 3), an effect of stabilizing polyunsaturated fatty acids in vivo (patent document 4), an effect of inhibiting Δ 5-desaturase (non-patent documents 3 to 4 and patent document 5), an effect of inhibiting migraine (patent document 6), an effect of inducing apoptosis in human leukemia cells (patent document 7), an effect of inhibiting oxidative decomposition of pheochromosin (patent document 8), and the like have been demonstrated. In addition, the Δ 5-desaturase inhibitory action in patent document 5 and the apoptosis inducing action in human leukemia cell in patent document 7 were confirmed not only from refined sesamin but also from episesamin.

Furthermore, from experiments using sesamin-containing sesame oil, there have been clarified an ameliorating action of inflammatory diseases (amyotrophic lateral sclerosis) (patent document 9), an anti-inflammatory and infection-protective action (patent document 10), and an action of preventing and ameliorating allergy by using oil and fat containing at least one of α -linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (patent document 11).

Furthermore, the sesamin/episesamin compositions are reported below. For example, from experiments using sesame oil extracts containing lignan compounds as the main component (sesamin 19.6%, episesamin 30.6%, sesaminol and episesamin phenol 10.2%, lignan compound content 60.4%), it was confirmed that the effects of reducing blood cholesterol and blood neutral fat (patent document 12) and improving liver function (patent document 3) were exhibited. Further, from experiments using a refined sesamin/episesamin composition, for example, experiments using sesamin/episesamin approximately equal to 6: 4, liver function improving effects (sesamin: 61.5%, episesamin: 38.0%) (patent document 3), active oxygen removing effects (sesamin: episesamin approximately equal to 6: 4) (patent document 13), anti-intoxication effects (sesamin: 55.2%, episesamin: 44.4%, purity 99.6%) (patent document 14), allergic symptom preventing and improving effects (sesamin: 55.2%, episesamin: 44.4%, purity 99.6%) (patent document 15) and the like, from experiments using sesamin/episesamin approximately equal to 1: 1, equilibrium regulating effects of ω 6 ω 3 series unsaturated fatty acids (sesamin: 51.3%, episesamin: 47.8%) (patent document 16) were also confirmed, Examples of the lipid-lowering agent include those inhibiting the formation of lipid peroxide (sesamin: 51.3% and episesamin: 47.8%) (patent document 17), those inhibiting the breast cancer (sesamin: 51.3% and episesamin: 47.8%) (patent document 18), those inhibiting the hypertension (sesamin: 51.5%, episesamin: 47.8%, and other dioxabicyclo (dioxabicyclo) (3, 3, 0] octane derivatives: 1.1%) (patent document 19), those reducing body fat (sesamin: episesamin: about 1: 1 and having a purity of 99.5%) (patent document 20), those inhibiting the prostatic hypertrophy using saw palm oil (sesamin: episesamin: about 1: 1) (patent document 21), and the like.

Furthermore, in recent years, it has been confirmed that sesamin is different from episesamin in physiological activity. For example, it has been reported that the migration rate of episesamin to internal organs is more than 2 times that of sesamin in the distribution in vivo of a mixture of sesamin and episesamin (about 1: 1) orally administered to rats (non-patent document 5). Meanwhile, it has been reported that in a test in which sesamin and episesamin are administered orally to rats, episesamin significantly increases gene expression and enzymatic activity of liver β -oxidase as compared with sesamin, and there is no difference between sesamin and episesamin in inhibiting the activity of fatty acid synthase (non-patent document 6).

[ patent document 1] Japanese patent No. 3183664

[ patent document 2] U.S. Pat. No. 4427694

[ patent document 3] Japanese patent No. 3075358

[ patent document 4] Japanese patent application laid-open No. 11-269456

[ patent document 5] Japanese patent No. 3070611

[ patent document 6] Japanese patent application laid-open No. 2003-183172

[ patent document 7] Japanese patent application laid-open No. 2001 + 151676

[ patent document 8] Japanese patent laid-open No. 2000-143546

[ patent document 9] Japanese Kokai publication No. 2005-533042

[ patent document 10] Japanese Kohyo publication Hei 10-500937

[ patent document 11] Japanese patent application laid-open No. 5-58902

[ patent document 12] Japanese patent No. 3001589

[ patent document 13] Japanese patent application laid-open No. 6-227977

[ patent document 14] Japanese patent No. 3124062

[ patent document 15] Japanese patent No. 3512196

[ patent document 16] Japanese patent No. 3512196

[ patent document 17] Japanese patent application laid-open No. 5-051388

[ patent document 18] Japanese patent application laid-open No. 5-43458

[ patent document 19] Japanese patent application laid-open No. 8-268887

[ patent document 20] Japanese patent No. 3205315

[ patent document 21] Japanese patent laid-open No. 2000-256204

[ non-patent document 1] science and functionality of sesame, Shuangmu et al, Wanshan PLANET corporation (1998)

[ non-patent document 2] Fukuda, Y., et al., J.am.oil.chem.Soc., 63, 1027-

[ non-patent document 3] S.Shimizu, et al, J.Am.oil chem.Soc., 66, 237-

[ non-patent document 4] S.Shimizu, et al., Lipid, 26, 512(1991)

[ non-patent document 5] Sawada R., et al., Lipids, 34, 633(1999)

[ non-patent document 6] Kushiro M., et al.J.Nutr.biochem., 13, 289-295(2002)

Disclosure of Invention

As described above, sesamins have various physiological activities, but are a valuable compound which is contained only in the range of 0.1% to 0.5% in natural sesame seeds. Accordingly, the present inventors have studied a method for enhancing the action of sesamins in order to more effectively exert the physiological activity of sesamins, and have found that α -vitamin E enhances the action of dioxabicyclo [3, 3, 0] octane derivatives such as sesamins (patent No. 3283274). However, a method for enhancing the physiological activity of sesamins itself is not known at all.

The present inventors have made intensive studies on a method for enhancing the physiological activity of sesamins themselves, based on the following consideration that the useful physiological activity of sesamins can be more efficiently and effectively exerted, for example, by enhancing the physiological activity of sesamins themselves.

First, from the fact that episesamin can significantly increase the gene expression and enzymatic activity of β -oxidase in the liver as compared with sesamin (non-patent document 6), it is assumed that episesamin should have an activity equal to or higher than that of sesamin at least in terms of improving the liver function, and a method for enhancing the physiological activity of sesamin compounds is studied by allowing episesamin to be more efficiently absorbed in the body. Specifically, the sesamin/episesamin compositions (oil-soluble reagents) prepared were prepared so that the sesamin and episesamin contained therein were in various weight ratios, and the oral absorption and blood migration properties of episesamin were examined when they were orally administered. According to the above non-patent documents 5 and 6, it is assumed that the blood migration performance should be highest when episesamin is administered alone, but surprisingly, contrary to this assumption, when a sesamin/episesamin composition in which a certain amount of sesamin coexists is used, the oral absorption performance and/or blood migration performance of episesamin are higher than those when episesamin is administered alone. In addition, when studies were made on the antihypertensive effect, which is a physiological activity of sesamins, and the gene expression of liver β oxidase, it was surprisingly found that a sesamin/episesamin composition in which sesamin and episesamin are blended at a predetermined ratio (50: 50 to 1: 99) has higher activity than administration of sesamin alone and administration of episesamin alone, and the present invention was completed.

Drawings

FIG. 1 is a bar graph showing the oral absorption rate of episesamin when a mixture of sesamin and episesamin at a composition ratio of (4: 6, 5: 5, 3: 7, 2: 8, 1: 9, 0: 10) is administered orally.

FIG. 2 is a bar graph showing the oral absorption rate of episesamin when a mixture of various sesamin/episesamin compositions at a ratio of 1: 9, 0.5: 9.5, 0: 10 is administered orally.

FIG. 3 is a graph showing the 24-hour blood pressure changes in DOCA-salt hypertensive rats when a single dose of a mixture of a variety of sesamin to episesamin in a ratio of 10: 0, 5: 5, 0: 10 was administered.

FIG. 4 is a graph showing the change in blood pressure in DOCA-salt hypertensive rats at 8 hours after administration of a mixture of sesamin and episesamin at a ratio of 10: 0, 5: 5, 0: 10.

FIG. 5 is a graph showing the change in blood pressure in DOCA-salt hypertensive rats at 8 hours after administration of a mixture of sesamin and episesamin at a ratio of 5: 5, 3: 7, 1: 9.

FIG. 6 is a graph showing the effect of administration of a mixture of various sesamin/episesamin compositions (10: 0, 5: 5, 3: 7, 1: 9, 0: 10) on the expression of the beta-oxidation gene.

Detailed Description

The present invention relates to a sesamin/episesamin composition which can efficiently and effectively exhibit the physiological activity of sesamin compounds, and a method for enhancing the physiological activity of sesamin compounds by using the composition. In particular, the first and second (c) substrates,

1. a sesamin/episesamin composition is characterized by comprising sesamin and episesamin at a weight ratio of 50: 50 to 1: 99.

2. The sesamin/episesamin composition according to 1, which comprises sesamin and episesamin at a weight ratio of 39: 61 to 1: 99.

3. The sesamin/episesamin composition according to 1, which comprises sesamin and episesamin at a weight ratio of 30: 70 to 5: 95.

4. The sesamin/episesamin composition according to any one of 1 to 3, wherein the total amount of sesamin and episesamin is 51% by weight or more of the composition.

5. A food or beverage comprising the sesamin/episesamin composition described in 1 to 4 above.

6. A pharmaceutical composition comprising the sesamin/episesamin composition described in 1 to 4 above.

7. An animal feed or pet food comprising the sesamin/episesamin composition described in 1 to 4 above.

8. A method for enhancing the physiological activity of sesamin compounds by using the sesamin/episesamin compositions described in 1 to 4.

9. According to the method described in the above 8, the physiological activities of the sesamins include blood cholesterol lowering action, neutral fat lowering action, antihypertensive action, antioxidant action of unsaturated fatty acids, liver function improving action, active oxygen removing action, Δ 5 desaturase inhibitory action, and in vivo stabilization action of polyunsaturated fatty acids.

The sesamin/episesamin composition of the present invention is characterized by containing sesamin and episesamin at a predetermined ratio. The preferable ratio of sesamin to episesamin is 50: 50-1: 99 (weight ratio), more preferably 39: 61-1: 99, and most preferably 30: 70-5: 95. The sesamin/episesamin composition of the present invention containing sesamin and episesamin in the above-described predetermined ratio has a property of higher oral absorbability and/or blood migration of episesamin than when episesamin is administered alone. Furthermore, the sesamin/episesamin composition of the present invention containing sesamin and episesamin in the above-mentioned predetermined ratio has enhanced physiological properties of sesamins, i.e., antihypertensive effect, liver function improving effect, and lipid metabolism improving effect, as compared with administration of sesamin alone and administration of episesamin alone, and therefore can more efficiently and effectively exert the physiological activity of sesamins.

The method for producing the sesamin/episesamin composition of the present invention is not particularly limited, and for example, the composition of the present invention can be produced by blending refined products of sesamin and episesamin at a desired ratio. In this case, purified products of sesamin and episesamin can be produced, for example, by the method described in non-patent document 2, and the details thereof will be described in example 1 below. However, the purified product may be obtained by other suitable methods.

In another embodiment of the present invention, the weight ratio of the two components in the raw material mixture containing sesamin and episesamin can be determined, and a refined product of sesamin or episesamin (or a mixture containing more sesamin or episesamin than the other) is added to the mixture so as to obtain the sesamin-episesamin composition ratio defined in the present invention.

In still another embodiment of the present invention, sesamin may be removed from a mixture (e.g., a composition ratio of 1: 1) of sesamin and episesamin. Removal of sesamin can be carried out by recrystallization, chromatography, distillation, etc., alone or in appropriate combination.

In particular, in another embodiment, the present invention can adjust the sesamin-episesamin composition ratio by subjecting sesamin, a sesamin-episesamin mixture, or episesamin to an isomerization reaction.

Further, the following methods developed by the present inventors in recent years for increasing the concentration of episesamin in a sesamin-episesamin mixture can be used. That is to say that the first and second electrodes,

dissolving the sesamin-episesamin mixture in alcohol or an aqueous alcohol solution, and then selectively crystallizing and precipitating episesamin by recrystallization to obtain a sesamin/episesamin mixture with an increased episesamin concentration.

Alternatively, the sesamin/episesamin mixture having an increased episesamin concentration can be obtained by dissolving a sesamin-episesamin mixture in a specific fat or oil under heating, and then selectively crystallizing and precipitating episesamin by recrystallization.

In particular, a method of dissolving a sesamin-episesamin mixture in water, a water-soluble solvent or a mixture thereof, adding an alkali as necessary, and precipitating sesamins to obtain a sesamin/episesamin mixture having an increased episesamin concentration can also be used.

In the practice of the present invention, the composition of sesamin-episesamin in the raw material mixture and the composition of the present invention can be obtained by a known analytical method such as High Performance Liquid Chromatography (HPLC).

The raw material mixture containing sesamin and episesamin may, for example, be a sesame lignan composition purified from sesame seeds, sesame meal and sesame oil. Sesame lignan compositions are commercially available products (e.g., those made from bamboo oil and fat), and can also be obtained from sesame oil by a method such as the method described in non-patent document 2, or a method in which sesame oil is distilled with steam to obtain a distillate and sesamin is precipitated and separated from the distillate in the presence of an alkali (see Japanese patent application laid-open No. 10-7676). The raw material mixture containing sesamin and episesamin is not limited to the sesame lignan composition purified from the above-mentioned sesame seeds, sesame meal and sesame oil, and any mixture containing substantially the components thereof, such as cortex acanthopanacis, tung wood, ginkgo bark, etc., can be used.

The sesamin/episesamin composition of the present invention has a high oral absorbability of episesamin and/or high migration in blood. The oral absorbability and blood migration property of episesamin can be confirmed by the method described in example 2 (quantitative determination by LC-MS/MS), for example, but other suitable methods may be used.

Since the sesamin/episesamin composition of the present invention has a property of higher oral absorbability and/or higher migration ability of episesamin, various actions of episesamin can be more effectively and effectively exerted. The action of episesamin may be, for example, an action of improving the migration of sesamins into internal organs and an action of improving liver function.

In addition, the sesamin/episesamin composition of the present invention has a higher physiological activity than sesamin alone and episesamin alone, although the detailed mechanism thereof is not clear, and therefore, it can more efficiently and effectively exhibit various physiological activities of sesamin because sesamin has a property of higher physiological activity. Examples of the physiological activity of sesamins include an action of lowering blood cholesterol and neutral fat, an antihypertensive action, an antioxidant action of unsaturated fatty acids, an action of improving liver function, an active oxygen-removing action, a Δ 5 desaturase inhibitory action, and a stabilization action of polyunsaturated fatty acids in vivo.

The sesamin/episesamin composition of the present invention can also be suitably used in the form of a food, drink or pharmaceutical composition. The ratio of the sesamin/episesamin composition of the present invention to be added to a food, drink or pharmaceutical composition is not particularly limited as long as it has the function, and may be selected from the range of usually 0.01 to 100% (by weight). The content of episesamin contained in the food, drink or pharmaceutical composition is preferably 0.5 to 100mg, more preferably 1 to 60mg, and still more preferably 3 to 60mg per oral administration.

The production of a food or beverage or pharmaceutical composition containing the sesamin/episesamin composition of the present invention can be carried out by adding the sesamin/episesamin composition of the present invention to the food or beverage, or by adding sesamin, episesamin and/or a sesamin-episesamin mixture simultaneously or separately so that sesamin and episesamin are contained at the weight ratio of the present invention. The weight ratio of the two compounds can be adjusted by the methods described in connection with the production of the sesamin/episesamin composition.

The form of the food, drink or pharmaceutical composition containing the sesamin/episesamin composition of the present invention is not particularly limited, and may be any form such as a solid form such as powder, granule or tablet, a solution form such as liquid or emulsion, a capsule filled with the solution composition, or a semi-solid form such as paste.

In this case, the sesamin/episesamin composition of the present invention may be formulated into any formulation by further adding a diluent, a carrier, an additive or the like. The diluent or carrier is not particularly limited as long as the physiological activity of sesamins is not affected, and examples thereof include sugars such as sucrose, glucose, fructose, maltose, trehalose, lactose, oligosaccharides, dextrin, dextran, cyclodextrin, starch, syrup, and isomerized liquid sugar, alcohols such as ethanol, propylene glycol, and glycerol, sugar alcohols such as sorbitol, mannitol, erythritol, lactitol, xylitol, maltitol, reduced palatinose, reduced amylolysis products, solvents such as triacetin, polysaccharides such as gum arabic, carrageenan, xanthan gum, guar gum, gellan gum, and pectin, and water. The additive may, for example, be an auxiliary such as a chelating agent, a perfume, a spice extract, or a preservative.

When the above-mentioned diluent, carrier or additive is used to prepare the above-mentioned preparation for convenience of use, etc., the sesamin/episesamin composition is preferably contained in a proportion of 0.01 to 100% by weight, preferably 0.1 to 50% by weight, based on 100% by weight of the preparation. In this case, when a sesamin/episesamin composition as a raw material, for example, a composition in which the total amount of sesamin and episesamin is less than 51% is used, the volume of the obtained preparation containing the sesamin/episesamin composition becomes too large if the required amount of sesamin is added because the content of sesamin is low, and inconvenience is caused in taking the preparation. In particular, when the sesamin/episesamin composition of the present invention is dissolved in an oil or fat to produce a preparation such as a soft capsule for oral administration, or the preparation needs to be increased in size, or the preparation needs to be taken in a large number of grains at a time, there arises a problem that not only is the taking of the preparation hindered, but also a large amount of the oil or fat as a solvent is taken in an amount exceeding the required amount. Therefore, from the viewpoint of better dosage, it is preferable to use a sesamin/episesamin composition so that the total amount of sesamin and episesamin after preparation is 51% or more of the composition, and it is particularly preferable to use a sesamin/episesamin composition having a purity of 90% or more.

Examples of foods and drinks containing a sesamin/episesamin composition include foods and drinks containing the sesamin/episesamin composition of the present invention as an active ingredient as it is, and functional foods (including specific health foods and conditioned specific health foods) containing the sesamin/episesamin composition of the present invention as one of its ingredients and having a physiological activity of sesamin group in general foods and drinks. These foods and drinks also include those characterized in that the physiological effects of the foods and drinks, which are mainly to reduce cholesterol and/or neutral fat in blood, are shown in a container or a specification, and that sesamin and episesamin are contained or added in the weight ratio specified in the present invention. Other physiological actions of foods and beverages include antihypertensive action, antioxidant action of unsaturated fatty acids, liver function improving action, active oxygen removing action, Δ 5 desaturase inhibitory action, and in vivo stabilization action of polyunsaturated fatty acids.

The target food or drink is not limited, and examples thereof include beverages such as fruit juice beverages, refreshing beverages, sports beverages, alcoholic beverages, and tea, agricultural products such as bread, noodles, rice, snacks (biscuits, cakes, candies, chocolates, japanese snacks), bean curd and processed products thereof, fermented foods such as sake, medicinal liquor, sweet cooking wine, vinegar, soy sauce, and sauces, fat and oil foods such as sauce, salad dressing, butter, margarine, shortening, and edible fat and oil, food products for storage such as yogurt, ham, salted pork, and sausage, aquatic products such as fish cakes, fried fish cakes, fish meat and sweet potato cakes, and animal feeds or pet foods.

Examples

The present invention will be more specifically described by the following examples, but the present invention is not limited thereto.

Example 1 purification of sesamin and episesamin

A mixture of sesamin and episesamin (raw material mixture containing sesamin and episesamin), a mixture of commercially available bamboo oil and fat [ purity of sesamin group: 99.5 percent, and the ratio of sesamin to episesamin is 51.8 percent to 48.0 percent (weight percentage).

Highly purified products of sesamin and episesamin were prepared by the reverse phase HPLC method using the following conditions. That is, 100mg of the above mixture dissolved in DMSO was injected into a column of Develosil ODS-UG-5 (20. PHI. times.250 mm, manufactured by Nomura chemical Co., Ltd.), eluted by a linear gradient of 20% → 80% acetonitrile (elution time: 100 minutes, flow rate: 5 ml/minute), and separated by detection of absorbance at 280nm to obtain 38.9mg of sesamin (retention time: 89 minutes) and 35.0mg of episesamin (retention time: 94 minutes). Each purified sample (all purities were 99% or more) obtained by repeating this operation 10 times was used in the test of example 2.

Example 2 composition ratio of Sesamin-Isosesamin and oral absorbability/migration in blood-1

Male rats (6 weeks old) of sd (igs) line were purchased from japan CHARLES RIVER, and after acclimatization for one week in a test environment, animals that had developed successfully were subjected to the test. After dividing 5 rats after one night fasting into 6 groups, high purity sesamin and episesamin obtained in example 1 were mixed at various composition ratios, and the obtained sesamin/episesamin mixture [ sesamin: episesamin (weight ratio) ═ 6: 4, 5: 5, 4: 6, 3: 7, 1: 9, 0: 10] was dissolved in olive oil at a dose of 10mg/kg, and administered orally with an oral syringe (sonde). Blood was collected from the caudal vein by a heparin blood collection tube before administration and 1, 2, 4, 6, 8, and 24 hours after administration, and plasma samples were obtained after centrifugation (8,000rpm, 10 min). Adding internal standard, extracting with Oasis HLB solid phase, concentrating the extractive solution under reduced pressure, suspending with methanol, filtering with filter, and quantifying sesamin and episesamin with LC-MS/MS. The amount of sesamin or episesamin is determined by the ratio of the peak area of each of sesamin and episesamin to the peak area of eucalyptol (FUNAKOSHI) used as an internal standard. The analysis conditions of LC-MS/MS are shown below.

(HPLC)

A chromatographic column: develosil C30-UG-5(5 μm, 2.0. phi. times.50 mm, product of Nomura chemical Co., Ltd.)

Mobile phase: a: distilled water, B: methanol, D: 100mM ammonium acetate in water

Flow rate: 0.25mL/min

Gradient: 55% for solution B, 10% for solution D, and 2 minutes, and then, 3 minutes, a linear gradient of 55% to 60% for solution B, 10% for solution D, and 2 minutes, 60% to 85% for solution B, and 10% for solution D

(MS/MS)

Measurement mode: selective reaction monitoring

And (3) detection: episesamin (retention time: about 5.6 minutes); parent ion M/z 372([ M + NH4] +), daughter ion M/z 233

: eucalyptol (retention time: about 2.8 minutes); parent ion M/z 404([ M + NH4] +), and daughter ion M/z 249

An ionization method: ESI method

The blood episesamin concentration rose to a maximum value by about 6 hours after administration and then gradually decreased, and episesamin was not substantially detected in the blood after 24 hours. The Area under the curve (AUC) of the concentration curve in the blood at 0 to 24 hours was used as an index of the absorption amount. Since the amount of episesamin added to each drug administration group is different, the absorption rate should be calculated by dividing each AUC by the amount ratio of episesamin administration and correcting the result, and comparing the calculated absorption rate with the calculated absorption rate. The results are shown in FIG. 1. The absorbance was 72.5 for administration of episesamin alone and a higher absorbance of 76.7 was obtained with a 50: 50 ratio of sesamin to episesamin. In particular, the absorption rate increased with the increase in the weight ratio of episesamin, and the absorption rate reached the highest value at a ratio of 30: 70, and also showed a high value at a ratio of 10: 90. In other words, it was also shown that when sesamin and episesamin were combined at a composition ratio of 50: 50 to 10: 90, the absorption rate of episesamin was higher than that when episesamin was administered alone (0: 100 weight ratio).

Therefore, the results of this example show that by blending sesamin and episesamin at a certain weight ratio, the absorption rate of episesamin can be improved.

Example 3 composition ratio of Sesamin-Isosesamin and oral absorbability/migration in blood-2

For the purpose of specifying an effective sesamin ratio, the effect of further reducing the sesamin ratio was evaluated according to the method of example 2. In other words, the high-purity sesamin and episesamin obtained in example 1 were mixed at various composition ratios, and the obtained sesamin/episesamin mixture [ sesamin/episesamin (weight ratio): 1: 9, 0.5: 9.5, 0: 10] was dissolved in olive oil in an amount of 10mg/kg, and orally administered by an oral syringe (sonde), and the absorption rate was calculated. The results are shown in FIG. 2. The absorbance for administration of episesamin alone was 59.7, giving a higher absorbance of 64.7 for administration at a 5: 95 ratio of sesamin to episesamin and 72.4 for administration at a 10: 90 ratio. It can also be said that even when sesamin and episesamin are blended at a composition ratio of 5: 95, the absorption rate of episesamin is higher than that when episesamin alone (0: 100 weight ratio) is administered.

Example 4 for Deoxycorticosterone acetate (Deoxycorticosterone) Effect of lowering blood pressure in rats having acetate-salt (DOCA-salt) hypertension model

SD male rats (6 weeks old) (SLC of Japan) were subjected to a right kidney extirpation operation under sodium pentobarbital anesthesia. After 1 week of recovery, DOCA-salt was administered subcutaneously 2 times per week at a dose of 15mg/kg, and 1% saline was fed as drinking water. Systolic Blood Pressure (SBP) was measured by the tail cuff method using a noninvasive automatic blood pressure measuring apparatus (BP-98A, Softron, Tokyo). Blood pressure was measured 5 weeks after the start of the DOCA-salt treatment, and an experiment was performed using animals whose blood pressure was confirmed to have sufficiently increased. In rats fasted for 8 hours, olive oil was orally administered once by using an oral syringe (sonde) as a control group, sesamin/isosesamin mixtures (sesamin: isosesamin (weight ratio): 10: 0, 5: 5, 0: 10) obtained in high purity in example 1 were mixed at various composition ratios as test groups, suspended in olive oil at a dose of 100mg/kg, and orally administered once by using an oral syringe (sonde). SBP was measured before dosing, 2, 4, 6, 8, 10, 12, 24 hours after dosing. Feeding was started after blood pressure was measured from hour 12. The test was conducted at 1 week intervals, and the measurement was conducted 3 times at the maximum for the same individual.

The blood pressure changes (n is 5 to 7) 24 hours after single administration are shown in fig. 3. In the sesamin-alone, episesamin-alone and olive oil-administered drug groups, no major change in blood pressure was observed, whereas in the sesamin/episesamin mixture (5: 5) administered drug group, a significant blood pressure lowering effect with a peak after 8 hours of administration was shown. Comparing the change in blood pressure after 8 hours of administration among the groups, the blood pressure value after 8 hours of administration of the sesamin/episesamin mixture (5: 5) was-32 mmHg, which was significantly reduced as compared with the sesamin alone group (-13mmHg) and the episesamin alone group (-6mmHg) (FIG. 4).

Example 5 blood pressure lowering Effect on DOCA-salt hypertension model rats-Mixed ratio Influence of

Hereinafter, the difference in effect depending on the compounding ratio was compared by the method of example 3 based on the most effective sesamin/episesamin mixture (5: 5). And the effect was too strong when the amount was 100mg/kg, so that the difference was more easily seen, the amount was reduced to 1/2.

Sesamin-episesamin mixtures containing sesamin-episesamin at various composition ratios [ sesamin/episesamin (weight ratio) 5: 5, 3: 7, 1: 9] were dissolved in olive oil at a dose of 50mg/kg, and administered orally at a single time using an oral syringe (sonde), and the blood pressure values were measured.

The blood pressure change (n: 3 to 4) after 8 hours of administration is shown in fig. 5. No effect of reducing the bleeding pressure was shown in the 50mg/kg dosage of the sesamin/episesamin mixture (5: 5). On the other hand, the effect of reducing the blood pressure was exhibited in the sesamin/episesamin mixtures (3: 7) and (1: 9), and the effect was most remarkable particularly at 3: 7.

The above results show that by mixing sesamin and episesamin at a certain ratio, synergistic blood pressure lowering effects can be obtained. Moreover, the effect is most obvious when the ratio is 3: 7.

Example 6 Effect on beta-Oxidation Gene expression

Male rats of Wistar line (6 weeks old) were purchased from clearer in japan, and after acclimation for one week in a test environment, well-developed animals were subjected to the test. The animals were divided into 6 groups of 5 animals, and the solvent olive oil was orally administered 3 times at intervals of 24 hours in the control group, and the high purity sesamin and episesamin obtained in example 1 were mixed at various composition ratios in the test group, and the obtained sesamin/episesamin mixture [ sesamin/episesamin (weight ratio) 10: 0, 5: 5, 3: 7, 1: 9, 0: 10] was suspended in the olive oil at 200mg/kg, and orally administered 3 times at intervals of 24 hours. After the final 4 hours of administration, the liver was anesthetized with sodium pentobarbital and RNA was extracted, and the effect on the expression of the beta-oxidation gene (10 species) was investigated by using TaqMan Chemistry quantitative RT-PCR (Heid CA, Stevens J, Livak KJ, Williams PM. real time quantitative PCR. genome Res.19966 (10): 986-94.).

The genes after evaluation are shown in table 1 below, and the gene expression levels are shown in fig. 6 (fig. 6A, B). In the sesamin single-dose drug combinations under these conditions, the expression of the β -oxidation gene was not substantially increased, but many genes were increased in the episesamin single-dose drug combinations. In addition, in any group of the sesamin/episesamin mixture-administered drug group, the gene expression was significantly increased as compared with that in the episesamin-alone group. Although there are some differences in gene expression caused by different ratios, there is no great difference between groups.

TABLE 1 evaluation Gene List

The above results show that the expression of the β -oxidation gene is synergistically enhanced by mixing episesamin and sesamin.

[ preparation examples ]

Formulation examples are noted below. The term "mixture" as used herein means a sesamin/episesamin composition having a sesamin/episesamin composition ratio within the range of the present invention (sesamin/episesamin: 30: 70, purity: 99.5%).

Preparation example 1 butter

"mixture" 1.2g

Butter fat 100g

Vitamin E acetate 1.2g

To 100g of butter fat from which buttermilk was removed by a stirring operation (whipped cream) in the butter manufacturing process was added 1.2g of "mixture", and then 1.2g of vitamin E acetate was added to conduct a kneading operation (working) to obtain a butter containing the composition of the present invention with a uniform texture.

(preparation example 2) granules

"mixture" 0.25g

Vitamin E acetate 0.25g

Silica 20.5g

Corn starch 79g

The above powders were mixed uniformly, and then 100ml of a 10% hydroxypropylcellulose ethanol solution was added, and kneaded, extruded, and dried by a usual method to prepare granules.

(preparation example 3) tablet

"mixture" 3.5g

Vitamin E acetate 0.5g

Silica 20g

Microcrystalline cellulose 10g

Magnesium stearate 3g

Lactose 60g

The above substances were mixed and tabletted with a single punch tablet to produce tablets having a diameter of 7mm and a weight of 100 mg.

(preparation example 4) capsules

Gelatin 70.0%

Glycerol 22.9%

0.15 percent of methyl p-hydroxybenzoate

Propyl p-hydroxybenzoate 0.51%

Proper amount of water

Calculated by 100 percent

The capsule shell of the soft capsule containing the above ingredients was filled with the following composition by a usual method to prepare 1 soft capsule of 200 mg.

"mixture" 10.8mg

Wheat beeswax 30mg

Alpha-vitamin E20 mg

Palm oil 10mg

The wheat germ oil is suitable

Calculated by 100 percent

Preparation example 5 healthy drink

Flavor development: DL-sodium tartrate 0.1g

Succinic acid 0.009g

Sweet taste: liquid sugar 800g

Sour taste: citric acid 12g

Vitamins: vitamin C10 g

"mixture" 1g

Vitamin E30 g

Cyclodextrin 5g

Spice 15ml

Potassium chloride 1g

Magnesium sulfate 0.5g

Mixing the above components, and adding water to make 10L. The health beverage has a volume of about 100ml for 1 time.

By administering the sesamin/episesamin composition of the present invention, various physiological activities of sesamins can be more effectively exerted. In particular, the sesamin/episesamin composition of the present invention has good oral absorbability and blood migration of episesamin, and therefore can more effectively exhibit various physiological activities of episesamin. Furthermore, by blending sesamin in a predetermined ratio to episesamin, the hypotensive effect of sesamins and the expression of the β -oxidation gene can be synergistically enhanced. In addition, since sesamin and episesamin are derived from plants, they have mild effects and are highly safe. Therefore, the composition of the present invention is very effective, and the application range thereof is not limited to health foods, but is also applicable to pharmaceuticals.

Claims (8)

1. Use of sesamin for the manufacture of a composition for improving the oral absorption and/or blood migration of episesamin, wherein the composition comprises sesamin and episesamin in a weight ratio of 50: 50 to 10: 90.

2. Use according to claim 1, wherein the composition comprises sesamin and episesamin in a weight ratio of 39: 61 to 10: 90.

3. Use according to claim 1, wherein the composition comprises sesamin and episesamin in a weight ratio of 30: 70 to 10: 90.

4. Use of sesamin and episesamin for the manufacture of a composition for enhancing the physiological activity of sesamins, wherein the composition comprises sesamin and episesamin in a weight ratio of 50: 50 to 10: 90.

5. Use according to claim 4, wherein the composition comprises sesamin and episesamin in a weight ratio of 39: 61 to 10: 90.

6. Use according to claim 4, wherein the composition comprises sesamin and episesamin in a weight ratio of 30: 70 to 10: 90.

7. The use according to any one of claims 1 to 6, wherein the composition is a food or drink.

8. The use according to any one of claims 1 to 6, wherein the composition is a pharmaceutical composition.