JP6901274B2 - Composition for promoting absorption of ω3 fatty acids - Google Patents

Description

The present invention relates to a composition for promoting absorption of ω3 fatty acids.

ω (omega) 3 fatty acid (ω-3 fatty acid) is one of the classifications of unsaturated fatty acids, and generally refers to those having a carbon-carbon double bond at the ω3 position. In plants and microorganisms, linoleic acid can be produced by increasing one double bond of oleic acid by Δ12-fatty acid desaturase that forms a double bond at the ω6 position. Furthermore, in plants and microorganisms, α-linolenic acid can be produced by increasing the double bond of linoleic acid by one by Δ15-fatty acid desaturase that forms a double bond at the ω3 position. However, although animals including humans have Δ9-fatty acid desaturase that produces oleic acid from stearic acid, they do not have either Δ12-fatty acid desaturase or Δ15-fatty acid desaturase, so neither linoleic acid nor α- Neither linoleic acid can be synthesized by itself. Therefore, the ω3 fatty acid is an essential fatty acid together with the ω6 fatty acid. In recent years, the physiological function of ω3 fatty acids has been attracting attention. For example, it has become clear that deficiency of ω3 fatty acids causes deterioration of learning ability and visual acuity. Therefore, fish oil containing a large amount of ω3 fatty acid and a composition containing a large amount of ω3 fatty acid refined from fish oil are attracting attention as health foods.

As a naturally occurring ω3 fatty acid,
"Α-linolenic acid (ALA): 18: 3 (n-3): all-cis-9,12,15-octadecatrienoic acid",
"Stearidonic Acid (STD): 18: 4 (n-3): all-cis-6,9,12,15-octadecatetraenoic acid",
"Eicosatorieic Acid (ETE): 20: 3 (n-3): all-cis-11,14,17-Eicosatorieic Acid",
"Eicosatetraenoic acid (ETA): 20: 4 (n-3): all-cis-8,11,14,17-eicosatetraenoic acid",
"Eicosapentaenoic acid (EPA): 20: 5 (n-3): all-cis-5,8,11,14,17-eicosapentaenoic acid",
"Docosapentaenoic acid (DPA): 22: 5 (n-3): all-cis-7,10,13,16,19-docosapentaenoic acid",
"Docosahexaenoic acid (DHA): 22: 6 (n-3): all-cis-4,7,10,13,16,19-docosahexaenoic acid",
"Tetracosapentaenoic acid: 24: 5 (n-3): all-cis-9,12,15,18,21-tetracosapentaenoic acid",
"Tetracosahexaenoic acid: 24: 6 (n-3): all-cis-6,9,12,15,18,21-tetracosahexaenoic acid"
It has been known. The notation is "trivial name: numerical expression: chemical name".
As mentioned above, fish oil foods, especially cod liver oil, herring, mackerel, salmon, sardines, cod, and seafood such as sardines, are rich in ω3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). I'm out. It is known that most of the DHA contained in fish and other organisms is produced by marine microorganisms such as the genus Schizochytrium, which is a genus of labyrinthula, and is concentrated in the process of the food chain. Has been done.

When fats and oils containing ω3 fatty acids are ingested, they are decomposed into fatty acids and glycerin by lipase present in the small intestinal villi and absorbed, but the substances that affect the absorption rate are not well understood.

On the other hand, olive is a plant belonging to the genus Olive of the family Oleaceae, and is widely cultivated in the Mediterranean region and elsewhere. Its fruits are widely used in the production of olive oil and for food all over the world, and the eating experience is very rich. It is known that olive fruits and leaves contain polyphenol components such as oleuropein and hydroxytyrosol (Patent Document 1). Further, the polyphenol component contained in the olive extract and the fruit has a bone formation promoting action (Patent Document 1), an anti-inflammatory action (Patent Document 2), a fertility treatment effect (Patent Document 3), and a fatty liver preventive and improving action (Patent Document 1). It is also known to have various actions such as a whitening effect (Patent Document 5) and an antioxidant effect (Patent Document 6). It has been clarified that the center of these actions is oleuropein and its constituents, polyphenol compounds such as hydroxytyrosol.
However, it has not been known at all that olives, olive leaves, olive extracts or olive leaf extracts, and the polyphenol components contained therein are involved in the absorption of ω3 fatty acids.

JP-A-2009-227616 Japanese Unexamined Patent Publication No. 2009-46439 Japanese Unexamined Patent Publication No. 2009-191012 Japanese Unexamined Patent Publication No. 2009-263257 Japanese Patent No. 4587200 Japanese Unexamined Patent Publication No. 2016-79127

The present inventors have studied the interaction between fats and oils containing ω3 fatty acids and olive extracts or olive leaf extracts, and the polyphenol components contained in olives and olive leaves, especially hydroxytyrosol, are ω3 fatty acids. It was discovered that it promotes the absorption of olive leaves, and the present invention was made.

That is, the subject of the present invention is the composition for promoting the absorption of ω3 fatty acids containing the olive extract or the olive leaf extract, and the promotion of the absorption of the ω3 fatty acids contained in the olive extract or the olive leaf extract and the fat and oil. It is an object of the present invention to provide a composition for promoting absorption of ω3 fatty acid contained in any one or more substances such as a composition for use, olive polyphenols and hydroxytyrosol and fats and oils.

The main configuration of the present invention is as follows.
(1) A composition for promoting absorption of ω3 fatty acids containing an olive extract or an olive leaf extract.
(2) The composition according to (1), wherein the olive extract or the olive leaf extract contains olive polyphenols.
(3) The composition according to (2), wherein the polyphenols are hydroxytyrosol.
(4) A composition for promoting absorption of ω3 fatty acids containing hydroxytyrosol.
(5) A composition for promoting absorption of ω3 fatty acids containing hydroxytyrosol and fats and oils containing ω3 fatty acids.
(6) The composition according to (5), wherein the fat and oil containing the ω3 fatty acid is fish oil.
(7) The composition according to any one of (1) to (6), wherein the ω3 fatty acid is eicosapentaenoic acid or docosahexaenoic acid.

INDUSTRIAL APPLICABILITY The present invention provides a composition for promoting absorption of ω3 fatty acids. The composition of the present invention increases the absorption efficiency of ω3 fatty acids such as docosahexaenoic acid (hereinafter “DHA”) and eicosapentaenoic acid (hereinafter “EPA”), so that the dose is smaller than the conventionally required dose. The effects of these ω3 fatty acids can be exerted.

It is a graph which shows the result of the absorption promotion test of docosahexaenoic acid (DHA). It is a graph which shows the result of the absorption promotion test of eicosapentaenoic acid (EPA).

The present invention relates to a composition for promoting absorption of an ω3 fatty acid containing an olive extract or an olive leaf extract. The present invention also relates to a composition for promoting absorption of fats and oils containing ω3 fatty acids and ω3 fatty acids containing hydroxytyrosol.
Olives include olive polyphenol compounds such as hydroxytyrosol, oleuropein and their glycosides. Hydroxytyrosol is a hydrolyzate of oleuropein. In the present invention, hydroxytyrosol or oleuropein, which are olive polyphenols, are effective as substances that promote the absorption of ω3 fatty acids, and hydroxytyrosol is particularly preferable. Olive polyphenols are contained in olive extract or olive leaf extract.
The olive extract or olive leaf extract used in the present invention means an extract of fruits or leaves.
It is an extract separated from natural olives (Olea europaea), and examples of the separated portion include fruits (flesh, juice, seeds), leaves and the like. An extract obtained by water extraction from the residue of olive fruit after oil extraction is commercially available.
For example, in commercially available Olivex HT6 (manufactured by Sunbright Co., Ltd .: fruit juice extract, extraction method: ethanol extraction), olive juice obtained by pressing olive fruits is acid-treated and then filtered and purified with ethanol. It is a powdered composition containing 30% by mass or more of total polyphenol, 6% by mass or more of hydroxytyrosol, and 1% by mass or more of tyrosol.
Commercially available Oleaselect (manufactured by Indena Co., Ltd .: fruit meat extract, extraction method: extraction with a mixed solvent of water and ethanol) is extracted from olive fruits with a mixed solvent of water and ethanol and pulverized, and is used as a total polyphenol. It is a composition containing 30% by mass or more, 5% by mass or more of velvascoside, and 1.5% by mass or more of hydroxytyrosol.
Commercially available OPEXTAN (manufactured by Indena Co., Ltd .: fruit meat extract, extraction method: extraction with a mixed solvent of water and ethanol) is extracted from olive fruits with a mixed solvent of water and ethanol and pulverized, and has 10 total polyphenols. It is a composition containing 2.0 to 3.5% by mass of velvascoside, and 4.5% by mass or more of hydroxytyrosol and a derivative thereof. These commercially available compositions can be used.

The olive leaf extract used in the present invention is an extract separated from the leaves of olive (Olea europaea L.). The leaves may be separated from all or part of the leaves using an extraction solvent or by squeezing.

As the extraction solvent, for example, water, an organic solvent (for example, one solvent selected from alcohol, acetone, etc., or a mixed solvent of two or more kinds), and a mixed solution of water and an organic solvent can be used. Of these, water, a mixed solution of water and alcohol, and alcohol are preferable. As the alcohol, ethanol and methanol are preferable. The extraction time and temperature can be appropriately determined depending on the extraction site for obtaining the olive leaf extract, the type of solvent, and the like. The olive leaf extract may be a crude extract extracted from olive leaves, or may be a crude extract that has been subjected to processing such as concentration, drying, and crushing. Further, those obtained by removing impurities by a treatment by a partitioning method or a purification treatment (for example, an adsorption treatment using an ion exchange resin, a column or the like, an elution with a solvent, and then a further concentration treatment if necessary) can also be used.

The olive leaf extract is generally marketed as an olive leaf extract, and a commercially available product can be used. Examples of such commercially available products include "Opiece" (Eisai Food & Chemical Co., Ltd.) containing 35% or more of oleuropein, and "Oralis" (Eisai Food & Chemical Co., Ltd.) containing 20% or more of hydroxytyrosol. And so on.

The olive extract or olive leaf extract used in the present invention preferably contains hydroxytyrosol in an amount of 0.02% by mass or more, and more preferably 0.1% by mass or more. In the present invention, purified hydroxytyrosol extracted and purified from olives or olive leaves or chemically synthesized hydroxytyrosol can also be used as the composition for promoting absorption of ω3 fatty acids.
In the present invention, the active ingredient hydroxytyrosol is ingested at the same time as ingesting fats and oils containing ω3 fatty acids in order to promote absorption of ω3 fatty acids. Alternatively, a composition containing hydroxytyrosol and an oil or fat containing an ω3 fatty acid such as fish oil can be prepared. In the case of a composition for promoting absorption of ω3 fatty acid containing fish oil or the like and hydroxytyrosole, 0.001 to 100 parts by mass of hydroxytyrosol is added to 1 part by mass of fish oil or refined fish oil containing a high amount of ω3 fatty acid. It can be preferably blended in an amount of 0.01 to 10 parts by mass.

The composition for promoting absorption of the ω3 fatty acid of the present invention is formulated as it is or by adding various excipients. Examples of the pharmaceutical product include granules, tablets, and capsules.
Further, the composition can be used as it is or a formulated product can be added to foods and drinks.
In formulation, various excipients and additives can be used in the composition for promoting absorption of ω3 fatty acids as long as the purpose of the composition of the present invention is not impaired. Specifically, dietary fibers and thickeners such as cyclodextrin, hemicellulose, lignin, guar gum, konjak mannan, isagol, alginic acid, agar, carrageenan, chitin, carboxymethyl cellulose, polydextrose, cooking oil, calcium, iron, Minerals such as sodium, zinc, copper, potassium, phosphorus, magnesium, iodine, manganese, selenium; fat-soluble or water-soluble such as vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, niacin, fumaric acid, pantocitric acid Emulsifiers and dispersants such as vitamins, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, phospholipids, Arabic gum, xanthan gum, tragacanto gum, locust bean gum, and beeswax, bulking agents, excipients, Preservatives / antioxidants, flavor modifiers and fragrances, flavoring agents such as sodium chloride, sodium glutamate, glycerin, succinic acid, sodium lactate, citric acid, sodium citrate, acetic acid, adipic acid, fumaric acid, malic acid, etc. Acidic acid, low-calorie sweeteners such as martitol and aspartame, and colorants.
Acidulants, fragrances and the like can be added to the composition of the present invention, if necessary.

Hereinafter, the present invention will be described with reference to Examples, Comparative Examples, and Test Examples Using the Composition of the Present Invention.
1. 1. Preparation of test samples Table 1 below shows the compositions of the compositions of the present invention (Examples) and the compositions of Comparative Examples.

After weighing, each component was mixed by a conventional method using a homomixer to prepare the compositions of Examples and Comparative Examples.

2. Absorption test by animal test 1) Test animals and administration method After bringing in 7-week-old SD rats, the animals were cultivated for 7 days to make 6 animals per group, and the body weight was measured on the 7th day by the weight stratification method. Grouped. After fasting for 16 hours from the day before administration of the test substance, the test sample was orally administered intragastrically using a sonde from the next morning.
After administration, the patient was made wakeful by inhalation anesthesia with isoflurane, and blood was collected from the lateral tail vein. Blood sampling was performed at 9 points before administration and 1, 2, 3, 4, 6, 8, 10, and 24 hours after administration.
As for the dose to animals, the fatty acid composition of the samples of Examples and Comparative Examples was analyzed in advance by gas chromatography analysis, and based on the measurement results, the dose of one animal was adjusted to the amount shown in Table 2 below. did.

2) Measurement of blood DHA and EPA levels Plasma was separated from the collected blood and used as a sample for HPLC / MS measurement by the following procedure.
1 Add 100 μL of ethanol to 50 μL of plasma.
2 Add 200 μL of a solution of ethanol: 10N sodium hydroxide = 9: 1 and incubate at 90 ° C. for 60 minutes to saponify.
3 Add 400 μL of hexane, soak for 5 minutes and allow to stand to remove the separated hexane layer.
4 Add 200 μL of 6N hydrochloric acid aqueous solution to the aqueous layer and mix, then add 600 μL of hexane and allow to permeate for 5 minutes, then let stand to recover the hexane layer and dry it.
5 Add and mix 50 μL of acetonitrile, and use this as a sample for HPLC / MS measurement.
The conditions for HPLC and mass spectrum measurement and detection were as follows.

HPLC conditions BEH C18, 2.1 mm × 50 mm with 1.7 μm 40 ° C
A: 0.1% formic acid aqueous solution B: acetonitrile A: B = 20: 80
Flow velocity: 0.35 mL / min

MS condition

3) Measurement results Tmax, Cmax, and AUC, which are blood dynamic indicators, were obtained from changes in blood DHA concentration and EPA concentration, and are shown in Table 4 and FIG. 1 (DHA), Table 5 and FIG. 2 (EPA) below. It was. The blood kinetics index was tested by the Tukey-Kramer method. The significance level is p <0.05.

As shown in Tables 4 and 5 and FIGS. 1 and 2, the composition of the present invention containing hydroxytyrosol in both DHA and EPA markedly increased AUC. Therefore, it was clarified that the composition of the present invention promotes the absorption of ω3 fatty acids.

3. 3. Formulation Examples Table 6 below shows a formulation example for filling soft capsules of a composition containing hydroxytyrosol and an ω3 fatty acid based on the above test results.

Claims (1)

A composition for promoting absorption of ω3 fatty acids (excluding those containing stearidonic acid) containing an olive leaf extract containing 20% by mass or more of hydroxytyrosol.

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