Composition for improving vascular endothelial function

Abstract

A composition for improving vascular endothelial function is provided. [Solution] A composition for improving vascular endothelial function is provided, which contains as an active ingredient a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters, and the ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition is 10% by weight or more. The present invention also provides a composition for improving sleep, which contains as an active ingredient a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters.

Description

[Technical field]

[0001] The present invention relates to a composition for improving vascular endothelial function.The present invention also relates to a composition for improving sleep. [Background technology]

[0002] It is known that fish are rich in n-3 polyunsaturated fatty acids, which are unsaturated fatty acids. Many studies have been reported to date that have shown that frequent consumption of fish reduces the risk of developing cardiovascular disease. In particular, an epidemiological study in Greenland is famous as a pioneering epidemiological study that drew attention to the n-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) in the prevention and treatment of cardiovascular disease. In this epidemiological study, it was revealed that the indigenous Inuit people of Greenland had a low incidence of acute myocardial infarction and a low mortality rate from ischemic heart disease. Furthermore, an investigation of their diet revealed that they consumed a lot of n-3 polyunsaturated fatty acids such as EPA and docosahexaenoic acid (DHA) due to their dietary habit of eating a lot of seals and fish, and conversely, they consumed little n-6 polyunsaturated fatty acids, which are abundant in terrestrial animals and plants. It has been reported that such differences in the fatty acid composition ingested in the diet are the reason for the low incidence of acute myocardial infarction and the low mortality rate from ischemic heart disease in the Inuit (Non-Patent Documents 1 to 3). In addition, human clinical trials have revealed the neutral fat lowering effect of EPA and DHA, but it is known that the cholesterol lowering effect is almost nonexistent or weak.

[0003] On the other hand, it has been reported that long-chain monounsaturated fatty acids (LC-MUFA) with carbon numbers of 20 and 22, which are known to be abundant in saury oil and Alaska pollock oil, have a cholesterol-lowering effect, unlike EPA and DHA (Patent Document 1). In addition, in diet-induced obesity model mice and type 2 diabetes model mice, the effects of consuming saury oil and Alaska pollock oil, such as lowering total cholesterol, LDL-cholesterol, triglyceride, and blood glucose levels in the blood and improving insulin resistance, have been found (Non-Patent Documents 4 to 6). A similar effect has also been confirmed in oils and fats selectively enriched with LC-MUFA (Non-Patent Document 5). In relation to this, a cohort study of 50,000 Japanese men and women has reported that men who consume more seafood have a lower risk of developing diabetes, and that the risk is particularly lower in groups that consume a large amount of small and medium-sized fish such as saury and mackerel, and fatty fish such as salmon (Non-Patent Document 7).

[0004] In addition, a study using an arteriosclerosis model mouse reported that ingestion of LC-MUFA inhibited the formation of atherosclerotic lesions in the aortic sinus, and that this was likely due to a protective effect that combined a reduction in blood inflammatory cytokine concentrations and promotion of cholesterol removal from macrophages by stimulating the PPAR signaling pathway (Non-Patent Document 8).However, Non-Patent Document 8 does not disclose at all the effects of ingestion of LC-MUFA on vascular endothelial function itself.

[0005] Vascular endothelial cells regulate the contraction and relaxation of the vascular wall by secreting vasoactive substances such as nitric oxide (NO) and endothelin. Vascular endothelial cells also play a role in maintaining blood pressure and regulating vascular permeability. A decrease in the function of vascular endothelial cells (i.e., vascular endothelial function) is thought to lead to various diseases, and is known to be involved in the onset and progression of arteriosclerosis, for example. In recent years, flow-mediated dilation (FMD) tests have attracted attention as a non-invasive vascular endothelial function test. Subjects with low FMD values ​​are thought to be more susceptible to cardiovascular events (Non-Patent Document 9). Furthermore, FMD tests are covered by health insurance in Japan and are used for early detection and early treatment of various diseases based on arteriosclerosis. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Retable No. 2012-121080 [Non-patent literature]

[0007] [Non-Patent Document 1] Dyerberg J, Bang HO, Hjorne N: Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr., 28(9):958-66, 1975. [Non-Patent Document 2] Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis. Lancet, 2(8081):117-9, 1978 [Non-Patent Document 3] Bang HO, Dyerberg J, Sinclair HM: The composition of the Eskimo food in northern western Greenland. Am J Clin Nutr., 33(12):2657-61.

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[0008] Diseases caused by decreased vascular endothelial function have become a problem in recent years, and there has been a demand for methods to improve vascular endothelial function that are highly safe and can be performed over the long term.

[0009] In addition, among LC-MUFA, positional isomers such as C20:1n-11 and C22:1n-11 are also found in fish oils derived from fish species other than saury, such as Alaska pollock, mackerel, and salmon, but are hardly found in vegetable oils. Since saury and Alaska pollock are popular fish among Japanese people and have high industrial value, there is a strong demand for the development of new applications for fish oils rich in LC-MUFA prepared from these fish species.

[0010] The present invention aims to provide new uses of fish oil components containing LC-MUFA, particularly new uses relating to health promotion. [Means for solving the problem]

[0011] As a result of intensive research conducted by the present inventors to achieve the above-mentioned object, they discovered that ingestion of saury oil rich in LC-MUFA improves flow-mediated vasodilation. Although there have been reports on the effects of EPA and DHA on vascular endothelial function, it was not known whether oil rich in LC-MUFA affects vascular endothelial function.

[0012] The inventors also found that consuming saury oil, which is rich in LC-MUFA, improves morning awakening. It was not previously known that oils rich in LC-MUFA affect sleep.

[0013] Based on these findings, the present inventors conducted further research and completed the present invention. That is, the present invention is as follows.

[0014] [1] A composition for improving vascular endothelial function, comprising: The present invention comprises, as an active ingredient, a component selected from monounsaturated fatty acids having 20 or more carbon atoms, salts thereof, and esters thereof, The ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition is 10% by weight or more; The composition.

[0015] [2] The composition according to [1], wherein the active ingredient is a component selected from a monounsaturated fatty acid having 20 carbon atoms, a salt thereof and an ester thereof, a component selected from a monounsaturated fatty acid having 22 carbon atoms, a salt thereof and an ester thereof, or a combination thereof.

[0016] [3] The composition according to [1] or [2], wherein the active ingredient is a glyceride containing a monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid.

[0017] [4] The composition described in [3], wherein the glyceride is a triglyceride.

[0018] [5] The composition according to any one of [1] to [4], further comprising an n-3 polyunsaturated fatty acid and an n-6 polyunsaturated fatty acid, wherein the area ratio of the n-3 polyunsaturated fatty acid to the n-6 polyunsaturated fatty acid is 4.0 or more.

[0019] [6] The composition described in any of [1] to [5], wherein the active ingredient is derived from fish oil.

[0020] [7] The composition described in [6], wherein the fish oil is saury oil.

[0021] [8] The composition according to any one of [1] to [7], characterized in that the composition is used so that 2 mg / kg body weight / day or more of the active ingredient, calculated as a monounsaturated fatty acid having 20 or more carbon atoms, is orally administered for 4 weeks or more.

[0022] [9] The composition described in any of [1] to [8], which is for improving flow-mediated vasodilation.

[0023]

[10] The composition according to any one of [1] to [9], which is for reducing the risk of contracting a disease caused by vascular endothelial dysfunction.

[0024]

[11] The composition according to any one of [1] to

[10] , which is a food composition.

[0025]

[12] The composition according to any one of [1] to

[10] , which is a pharmaceutical composition.

[0026]

[13] A composition for improving sleep, comprising as an active ingredient a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters.

[0027]

[14] The composition described in

[13] , wherein the active ingredient is a component selected from a monounsaturated fatty acid having 20 carbon atoms, a salt thereof and an ester thereof, a component selected from a monounsaturated fatty acid having 22 carbon atoms, a salt thereof and an ester thereof, or a combination thereof.

[0028]

[15] The composition according to

[13] or

[14] , wherein the active ingredient is a glyceride containing a monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid.

[0029]

[16] The composition described in

[15] , wherein the glyceride is a triglyceride.

[0030]

[17] The composition according to any one of

[13] to

[16] , wherein the proportion of monounsaturated fatty acids having 20 or more carbon atoms relative to the total fatty acids in the composition is 10% by weight or more.

[0031]

[18] The composition according to any one of

[13] to

[17] , further comprising an n-3 polyunsaturated fatty acid and an n-6 polyunsaturated fatty acid, wherein the area ratio of the n-3 polyunsaturated fatty acid to the n-6 polyunsaturated fatty acid is 4.0 or more.

[0032]

[19] The composition described in any of

[13] to

[18] , wherein the active ingredient is derived from fish oil.

[0033]

[20] The composition described in

[19] , wherein the fish oil is saury oil.

[0034]

[21] The composition according to any one of

[13] to

[20] , wherein the composition is used so that 2 mg / kg body weight / day or more of the active ingredient calculated as a monounsaturated fatty acid having 20 or more carbon atoms is orally administered for 4 weeks or more.

[0035]

[22] The composition described in any of

[13] to

[21] , which is for improving awakening.

[0036]

[23] The composition according to any one of

[13] to

[22] , which is a food composition.

[0037]

[24] The composition according to any one of

[13] to

[22] , which is a pharmaceutical composition.

[0038]

[25] A method for improving vascular endothelial function, comprising: The method includes administering to a subject a composition containing an effective amount of a component selected from a monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, and an ester thereof as an active ingredient, The ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition is 10% by weight or more; The method.

[0039]

[26] The method according to

[25] , wherein the active ingredient is a component selected from a monounsaturated fatty acid having 20 carbon atoms, a salt thereof and an ester thereof, a component selected from a monounsaturated fatty acid having 22 carbon atoms, a salt thereof and an ester thereof, or a combination thereof.

[0040]

[27] The method according to

[25] or

[26] , wherein the active ingredient is a glyceride containing a monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid.

[0041]

[28] The method according to

[27] , wherein the glyceride is a triglyceride.

[0042]

[29] The method according to any of

[25] to

[28] , wherein the composition further contains an n-3 polyunsaturated fatty acid and an n-6 polyunsaturated fatty acid, and the area ratio of the n-3 polyunsaturated fatty acid to the n-6 polyunsaturated fatty acid in the composition is 4.0 or more.

[0043]

[30] The method according to any of

[25] to

[29] , wherein the active ingredient is derived from fish oil.

[0044]

[31] The method according to

[30] , wherein the fish oil is saury oil.

[0045]

[32] The method according to any of

[25] to

[31] , comprising orally administering to the patient at least 2 mg / kg body weight / day of an active ingredient calculated as a monounsaturated fatty acid having 20 or more carbon atoms for at least 4 weeks.

[0046]

[33] The method according to any of

[25] to

[32] , which is for improving flow-mediated vasodilation.

[0047]

[34] The method according to any of

[25] to

[33] , for reducing the risk of contracting a disease caused by vascular endothelial dysfunction.

[0048]

[35] The method according to any of

[25] to

[34] , wherein the composition is a food composition.

[0049]

[36] The method according to any of

[25] to

[34] , wherein the composition is a pharmaceutical composition.

[0050]

[37] Use of a monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof for the manufacture of a composition for improving vascular endothelial function, comprising: The ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition is 10% by weight or more. The above uses.

[0051]

[38] The use according to

[38] , wherein the monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is a component selected from a monounsaturated fatty acid having 20 carbon atoms, a salt thereof, and an ester thereof, a component selected from a monounsaturated fatty acid having 22 carbon atoms, a salt thereof, and an ester thereof, or a combination thereof.

[0052]

[39] The use according to

[37] or

[38] , wherein the monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is a glyceride containing a monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid.

[0053]

[40] The use according to

[39] , wherein the glyceride is a triglyceride.

[0054]

[41] The use according to any one of

[37] to

[40] , wherein the composition further contains an n-3 polyunsaturated fatty acid and an n-6 polyunsaturated fatty acid, and the area ratio of the n-3 polyunsaturated fatty acid to the n-6 polyunsaturated fatty acid in the composition is 4.0 or more.

[0055]

[42] The use according to any one of

[37] to

[41] , wherein the monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is derived from fish oil.

[0056]

[43] The use described in

[42] , wherein the fish oil is saury oil.

[0057]

[44] The use according to any one of

[37] to

[43] , wherein the composition is used so that a monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is orally administered at a concentration of 2 mg / kg body weight / day or more, calculated as a monounsaturated fatty acid having 20 or more carbon atoms, for four weeks or more.

[0058]

[45] The use described in any of

[37] to

[44] , wherein the composition is for improving flow-mediated vasodilation.

[0059]

[46] The use described in any of

[37] to

[45] , wherein the composition is for reducing the risk of contracting a disease caused by vascular endothelial dysfunction.

[0060]

[47] The use described in any of

[37] to

[46] , wherein the composition is a food composition.

[0061]

[48] ​​The use described in any of

[37] to

[46] , wherein the composition is a pharmaceutical composition.

[0062]

[49] A method for improving sleep, comprising: The method includes administering to a subject a composition containing an effective amount of a component selected from a monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, and an ester thereof as an active ingredient. The method.

[0063]

[50] The method according to

[49] , wherein the active ingredient is a component selected from a monounsaturated fatty acid having 20 carbon atoms, a salt thereof and an ester thereof, a component selected from a monounsaturated fatty acid having 22 carbon atoms, a salt thereof and an ester thereof, or a combination thereof.

[0064]

[51] The method according to

[49] or

[50] , wherein the active ingredient is a glyceride containing a monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid.

[0065]

[52] The method according to

[51] , wherein the glyceride is a triglyceride.

[0066]

[53] The method according to any one of

[49] to

[52] , wherein the proportion of monounsaturated fatty acids having 20 or more carbon atoms relative to the total fatty acids in the composition is 10% by weight or more.

[0067]

[54] The method according to any of

[49] to

[53] , wherein the composition further contains an n-3 polyunsaturated fatty acid and an n-6 polyunsaturated fatty acid, and the area ratio of the n-3 polyunsaturated fatty acid to the n-6 polyunsaturated fatty acid in the composition is 4.0 or more.

[0068]

[55] The method according to any of

[49] to

[54] , wherein the active ingredient is derived from fish oil.

[0069]

[56] The method according to

[55] , wherein the fish oil is saury oil.

[0070]

[57] The method according to any of

[49] to

[56] , comprising orally administering to the patient at least 2 mg / kg body weight / day of an active ingredient calculated as a monounsaturated fatty acid having 20 or more carbon atoms for at least 4 weeks.

[0071]

[58] The method according to any one of

[49] to

[57] , for improving wakefulness.

[0072]

[59] The method according to any of

[49] to

[58] , wherein the composition is a food composition.

[0073]

[60] The method according to any of

[49] to

[58] , wherein the composition is a pharmaceutical composition.

[0074]

[61] Use of a monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof for the manufacture of a composition for improving sleep.

[0075]

[62] The use according to

[61] , wherein the monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is a component selected from a monounsaturated fatty acid having 20 carbon atoms, a salt thereof, and an ester thereof, a component selected from a monounsaturated fatty acid having 22 carbon atoms, a salt thereof, and an ester thereof, or a combination thereof.

[0076]

[63] The use according to

[61] or

[62] , wherein the monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is a glyceride containing a monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid.

[0077]

[64] The use according to

[63] , wherein the glyceride is a triglyceride.

[0078]

[65] The use according to any one of

[61] to

[64] , wherein the ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition is 10% by weight or more.

[0079]

[66] The use according to any one of

[61] to

[65] , wherein the composition further contains an n-3 polyunsaturated fatty acid and an n-6 polyunsaturated fatty acid, and the area ratio of the n-3 polyunsaturated fatty acid to the n-6 polyunsaturated fatty acid in the composition is 4.0 or more.

[0080]

[67] The use according to any one of

[61] to

[66] , wherein the monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is derived from fish oil.

[0081]

[68] The use described in

[67] , wherein the fish oil is saury oil.

[0082]

[69] The use according to any one of

[61] to

[68] , wherein the composition is used so that a monounsaturated fatty acid having 20 or more carbon atoms, a salt thereof, or an ester thereof is orally administered at 2 mg / kg body weight / day or more, calculated as a monounsaturated fatty acid having 20 or more carbon atoms, for four weeks or more.

[0083]

[70] The use described in any of

[61] to

[69] , wherein the composition is for improving wakefulness.

[0084]

[71] The use described in any of

[61] to

[70] , wherein the composition is a food composition.

[0085]

[72] The use described in any of

[61] to

[70] , wherein the composition is a pharmaceutical composition. Effect of the Invention

[0086] The present invention provides a composition for improving vascular endothelial function that contains a fish oil component rich in LC-MUFA, such as saury oil, thereby reducing the risk of contracting diseases caused by vascular endothelial dysfunction.

[0087] The present invention also provides a sleep-improving composition that contains a fish oil component rich in LC-MUFA, such as saury oil, which provides good sleep and promotes health, particularly in healthy individuals. [Brief description of the drawings]

[0088] [Figure 1-1]This is a graph showing the change in FMD value before and after taking the saury oil capsule of Example 1. It shows that the FMD value increased by about 44% after taking the capsule. ★★ indicates a significant difference (p=0.0003).

[0089] [Figure 1-2] 1 is a graph showing the change in FMD value before and after ingestion of the canned pacific saury of Example 1 in subjects, showing that the FMD value increased by about 12% after ingestion.

[0090] [Figure 1-3] This figure shows the change in FMD value before and after intake, and after a washout period of one month after the end of intake, for six subjects who took the saury oil capsules of Example 1 and whose FMD value increased after intake. It shows that the FMD value increased by about 82% after intake, and then decreased by 20% after the washout period. ★ indicates a significant difference (p=0.0402).

[0091] [Figure 1-4] This is a graph showing the changes in FMD values ​​before and after ingestion, and after a one-month washout period after the end of ingestion, for three subjects who had an increase in FMD value after ingestion of the canned pacific saury of Example 1. It shows that the FMD value increased by about 66% after ingestion, and then decreased by 18% after the washout period.

[0092] [Figure 1-5] This is a graph showing the change in FMD value before and after ingestion for four subjects who were suspected of having vascular endothelial disorder because their FMD value before ingestion was outside the normal range (less than 6%) among the subjects who took the saury oil capsule of Example 1. It shows that the FMD value increased by about 253% after ingestion.

[0093] [Figure 1-6]This figure shows the change in FMD value before and after ingestion for four subjects who were suspected of having vascular endothelial disorder because their FMD value before ingestion was outside the normal range (less than 6%) among the subjects who ingested the canned pacific saury of Example 1. It shows that the FMD value increased by about 45% after ingestion.

[0094] [Diagram 2] This is a diagram showing the change in the ease of waking up before and after taking the saury oil capsules of Example 1 in subjects. The mood upon waking up is quantified as a relative evaluation, with 100 being when you can wake up comfortably in the morning and 0 being when you cannot wake up comfortably at all. The higher the value, the better the awakening. This shows that morning awakening improved by 14% after taking the capsules compared to before taking the capsules.

[0095] [Diagram 3] This is a diagram showing the change in body fat mass before and after taking the Pacific saury oil capsule of Example 1. It shows that the body fat mass decreased by about 0.7% after taking the capsule. ★★ indicates a significant difference (p=0.0057).

[0096] [Figure 4] This is a graph showing the change in FMD value before and after ingestion of subjects who took the saury oil capsule or blended oil capsule of Example 2. *** indicates a significant difference (p=0.0008). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0097] The present invention will now be described in more detail.

[0098] In the present specification, the following abbreviations may be used. MUFA: Monounsaturated fatty acids LC-MUFA: A general term for long-chain monounsaturated fatty acids, especially the C20:1 and C22:1 isomers PUFA: Polyunsaturated fatty acids

[0099] <Composition for improving vascular endothelial function> The present invention provides a composition for improving vascular endothelial function, which contains as an active ingredient a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters, and the ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition is 10% by weight or more (hereinafter, sometimes referred to as the composition for improving vascular endothelial function of the present invention).

[0100] The monounsaturated fatty acid having 20 or more carbon atoms, its salt, or its ester used in the present invention is not particularly limited, and may be any one that is acceptable for pharmaceutical or food use. Glycerides containing monounsaturated fatty acids having 20 or more carbon atoms as constituent fatty acids can be produced by known methods, and can also be produced as oils and fats derived from natural products, for example, by the boiling method described in WO1996 / 26647. Examples of oils and fats derived from natural products include marine oils (for example, fish oils such as saury oil, and oils and fats from mammals such as seals and whales), microbial oils, etc. As described later, fish oils have a high content of monounsaturated fatty acids having 20 or more carbon atoms. Therefore, it is preferable that the active ingredient in the composition for improving vascular endothelial function of the present invention is derived from fish oil (for example, saury oil). In addition, free monounsaturated fatty acids having 20 or more carbon atoms, their salts, and esters other than glycerides can be prepared by known methods, for example, using the above-mentioned glycerides as raw materials.

[0101] For example, saury crude oil is usually extracted in the same way as other fish oils: Whole saury or processing residues from seafood processing such as fish heads, skin, backbone, and innards are crushed and steamed, then pressed to separate the broth (stick water, SW) and pressed meal. The oil obtained with the broth is separated from the broth by centrifugation.

[0102] The 2015 edition (7th revision) of the Standard Tables of Food Composition in Japan states that the fatty acids in saury (skinned, raw) contain 26.0% docosenoic acid (C22:1) by weight, 17.6% eicosenoic acid (C20:1) by weight, and 54.2% total monounsaturated fatty acids. Among fish oils, saury oil is characterized by its high content of monounsaturated fatty acids.

[0103] Crude fish oil is refined into refined fish oil through refining processes such as degumming, deacidification, bleaching, deodorization, etc. This refined fish oil can also be used as a supply source of a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters.

[0104] In one embodiment, an oil having an increased concentration of monounsaturated fatty acids may be used as a supply source of a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters. In this case, a triglyceride enriched in MUFA can be obtained by a method of concentrating the monounsaturated fatty acid ethyl esters after ethyl esterification, and then transesterifying the monounsaturated fatty acid with glycerin to reconstitute the triglyceride.

[0105] Examples of monounsaturated fatty acids having 20 or more carbon atoms include monounsaturated fatty acids having 20 carbon atoms (C20:1) (e.g., C20:1 n-11, C20:1 n-9, C20:1 n-7), monounsaturated fatty acids having 22 carbon atoms (C22:1) (e.g., C22:1 n-11, C22:1 n-9, C22:1 n-7, C22:1 n-13), and monounsaturated fatty acids having 24 carbon atoms (C24:1) (e.g., C24:1 n-9). In a preferred embodiment, the active ingredient of the composition for improving vascular endothelial function of the present invention is a component selected from C20:1, a salt thereof, and an ester thereof, a component selected from C22:1, a salt thereof, and an ester thereof, or a combination thereof.

[0106] The content of C22:1 and C20:1 varies depending on the fish species, but examples of fish species with high content of these include fish belonging to the family Sauryidae such as Pacific cod, Alaska pollock, Atlantic cod, and sablefish, fish belonging to the family Gadidae such as Chum salmon, Coho salmon, Sockeye salmon, Pink salmon, Pacific salmon, and Rainbow trout, fish belonging to the family Osmeridae such as Capelin and Shishamo, and fish belonging to the family Clupeidae such as Herring. In addition, fish such as sand lance, tuna, mackerel, and alfonsino are relatively rich in these. They are also rich in the liver oil of sharks such as the spiny dogfish, basking shark, and chimaera. In the present invention, fish oils prepared from these fish can be used as they are, purified, or concentrated.

[0107] The ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition for improving vascular endothelial function of the present invention is 10% by weight or more, for example, 11% by weight or more, 12% by weight or more, 13% by weight or more, 14% by weight or more, 15% by weight or more, 16% by weight or more, 17% by weight or more, 18% by weight or more, 19% by weight or more, 20% by weight or more, 21% by weight or more, 22% by weight or more, 23% by weight or more, 24% by weight or more, 25% by weight or more, 26% by weight or more, 27% by weight or more, 28% by weight or more, 29% by weight or more, 30% by weight or more, 40% by weight or more, 50% by weight or more, 60% by weight or more, 70% by weight or more, 80% by weight or more, or 90% by weight or more.

[0108] In this specification, unless otherwise specified, the ratio (wt%) of fatty acid to the total fatty acid in the composition is calculated based on the value measured by gas chromatography after esterification of the components in the composition according to AOCS official method Ce1b-89. The content of fatty acid also means the ratio (wt%) of the fatty acid to the total fatty acid. The analysis conditions for gas chromatography are as follows. Equipment: Agilent 6890N GC system (Agilent) Column: DB-WAX (Agilent Technologies, 30m x 0.25mm ID, 0.25im film thickness) Carrier gas: Helium (1.0 mL / min, constant flow) Inlet temperature: 250℃ Injection volume: 1μL Injection method: Split Split ratio: 20:1 Column oven: 180℃ - 3℃ / min - 230℃ Detector: FID Detector temperature: 250℃

[0109] In the present invention, examples of the salts of monounsaturated fatty acids having 20 or more carbon atoms include potassium salts and sodium salts. Examples of esters of monounsaturated fatty acids having 20 or more carbon atoms include esters of lower alcohols having 5 or less carbon atoms (e.g., methyl esters, ethyl esters, n-propyl esters, i-propyl esters, n-butyl esters, s-butyl esters, t-butyl esters, n-pentyl esters, etc.), esters with glycerin such as monoglycerides, diglycerides, and triglycerides (i.e., glycerides), and phospholipids. In a preferred embodiment, the active ingredient of the composition for improving vascular endothelial function of the present invention is a glyceride containing a monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid, and more preferably a triglyceride.

[0110] As the monounsaturated fatty acid having 20 or more carbon atoms in the present invention, fats and oils derived from natural products containing free monounsaturated fatty acids having 20 or more carbon atoms may be used as they are, or after purification or concentration. As the ester of monounsaturated fatty acids having 20 or more carbon atoms, fats and oils derived from natural products containing glycerides having monounsaturated fatty acids having 20 or more carbon atoms as constituent fatty acids may be used as they are, or after purification or concentration.

[0111] Also, as the ester of monounsaturated fatty acids having 20 or more carbon atoms, fractionated oils obtained by esterifying fats and oils derived from natural products and then fractionating them by high performance liquid chromatography, etc., can be used. Examples of fractionated oils include fractionated oils enriched in C20:1, fractionated oils enriched in C22:1, and fractionated oils enriched in C24:1.

[0112] The composition for improving vascular endothelial function of the present invention may further comprise n-3 polyunsaturated fatty acid and n-6 ​​polyunsaturated fatty acid.In this case, the area ratio of n-3 polyunsaturated fatty acid to n-6 polyunsaturated fatty acid is 4.0 or more, for example, 5.0 or more, 6.0 or more, 7.0 or more, 8.0 or more, 9.0 or more, or 10.0 or more. In this specification, n-3 polyunsaturated fatty acid refers to an unsaturated fatty acid having 18 or more carbon atoms and two or more carbon-carbon double bonds, in which the first double bond is between the third and fourth carbon atoms counting from the carbon of the methyl group at the end of the fatty acid chain. Examples of such fatty acids include α-linolenic acid (C18:3 n-3), octadecatetraenoic acid (C18:4 n-3), eicosatetraenoic acid (C20:4 n-3), eicosapentaenoic acid (C20:5 n-3), docosapentaenoic acid (C22:5 n-3), and docosahexaenoic acid (C22:6 n-3). The n-6 polyunsaturated fatty acid refers to an unsaturated fatty acid having 18 or more carbon atoms and two or more carbon-carbon double bonds, in which the first double bond is between the 6th and 7th carbon atoms counting from the carbon of the methyl group at the end of the fatty acid chain, such as linoleic acid (C18:2n-6) and arachidonic acid (C20:4n-6). In this specification, the area ratio of fatty acids refers to the ratio of peak areas detected by gas chromatography after esterifying the fatty acids in the composition according to AOCS official method Ce1b-89. The analysis conditions for gas chromatography are as described above.

[0113] In the present invention, improvement of vascular endothelial function refers to improvement of the function of vascular endothelial cells, for example, the function of regulating the contraction and relaxation of the vascular wall by secreting vasoactive substances such as nitric oxide (NO) and endothelin. Methods for evaluating such vascular endothelial cell functions (vascular endothelial function) include, for example, strain gauge plethysmography, flow-mediated dilatation (FMD), reactive hyperemia peripheral arterial tonometry (RH-PAT), etc. ("Guidelines for Non-invasive Evaluation of Vascular Function," Guidelines for Diagnosis and Treatment of Cardiovascular Disease 2013, p. 3-112, Japan Circulation Society). In a preferred embodiment of the present invention, FMD is used to evaluate vascular endothelial function. The FMD value (%) is the ratio of the maximum dilation width to the resting vascular diameter, and is calculated by the following formula. FMD value (%) = maximum dilation width (mm) / resting vessel diameter (mm) x 100

[0114] The composition for improving vascular endothelial function of the present invention can improve FMD values, and therefore can be used as a composition for improving flow-mediated vasodilation.

[0115] The test in the examples described below was conducted on healthy subjects, and the improvement of the FMD value does not mean the treatment of diseases such as arteriosclerosis, but the risk of suffering from diseases caused by vascular endothelial disorder can be reduced by further enhancing normal vascular endothelial function or improving the state of vascular endothelial disorder. Therefore, in one embodiment, the composition for improving vascular endothelial function of the present invention is a composition for reducing the risk of suffering from diseases caused by vascular endothelial disorder. Here, vascular endothelial disorder refers to a state in which vascular endothelial function is reduced without reaching arteriosclerosis. For example, even if no arteriosclerotic plaque is found in the blood vessel, if the FMD value is less than 5%, it is suspected that the blood vessel is in a state of vascular endothelial disorder. Examples of diseases caused by vascular endothelial disorder include cardiovascular diseases such as arteriosclerosis, hypertension, periodontal disease, type 2 diabetes, and hyperlipidemia.

[0116] The subject of administration of the composition for improving vascular endothelial function of the present invention is a mammal, preferably a human. The age of the subject is not particularly limited as long as the effect of the present invention can be obtained. In one embodiment, the age of the subject is 20 years or older, for example, 25 years or older, 30 years or older, 35 years or older, 40 years or older, 45 years or older, 50 years or older, 55 years or older, or 60 years or older.

[0117] When a monounsaturated fatty acid having 20 or more carbon atoms, its salt, or its ester is administered to a subject with an FMD value of less than 6%, the effect of improving the FMD value may be more pronounced. Therefore, in one embodiment, the subject to which the composition for improving vascular endothelial function of the present invention is administered has an FMD value of less than 6%. For example, the subject to which the composition is administered may be 20 years old or older, such as 25 years old or older, 30 years old or older, 35 years old or older, 40 years old or older, 45 years old or older, 50 years old or older, 55 years old or older, or 60 years old or older, and the FMD value may be less than 6%.

[0118] The composition for improving vascular endothelial function of the present invention may be prepared in a form suitable for pharmaceutical compositions, food compositions (e.g., functional foods, health foods, supplements, etc.), for example, in the form of various solid preparations such as granules (including dry syrups), capsules (soft capsules, hard capsules), tablets (including chewable tablets, etc.), powders (powdered agents), pills, etc., or liquid preparations such as oral liquids (including liquids, suspensions, syrups, etc.). For example, the composition for improving vascular endothelial function of the present invention can be formulated as a soft capsule in which purified fish oil is filled in a gelatin membrane.

[0119] Examples of additives for formulation include excipients, lubricants, binders, disintegrants, fluidizers, dispersants, wetting agents, preservatives, thickeners, pH adjusters, colorants, flavorings, surfactants, and dissolution aids. When the formulation is in the form of a liquid, a thickener such as pectin, xanthan gum, or guar gum can be added. In addition, the formulation can be made into a coated tablet using a coating agent, or into a paste-like glue. Furthermore, when preparing other forms, conventional methods can be followed.

[0120] The composition for improving vascular endothelial function of the present invention can take the form of a food composition. In the present invention, the food composition means food in general, including beverages, and includes general foods, including health foods such as supplements, as well as specific health foods and nutritional functional foods as specified by the Health Functional Food System of the Consumer Affairs Agency. For example, functional foods labeled with the effect of improving vascular endothelial function are provided. For example, foods containing fish oil can be provided as they are. In addition, the food composition of the present invention also includes food materials that can be added to, mixed with, or applied to other foods to impart an effect of improving vascular endothelial function. In addition to foods, the food composition can also be provided as animal feed, etc.

[0121] When the composition for improving vascular endothelial function of the present invention is in the form of a food, the food is not particularly limited and may be beverages, confectioneries, breads, soups, etc., and includes, for example, general retort foods, frozen foods, instant foods (such as noodles), canned foods, sausages, cookies, biscuits, cereal bars, crackers, snacks (such as potato chips), pastries, cakes, pies, candies, chewing gum (including pellets and sticks), jellies, soups, ice cream, dressings, yogurt, etc., supplements in the form of tablets, capsules, emulsions, etc., soft drinks, etc. The manufacturing method of these foods is not particularly limited as long as it does not impair the effects of the present invention, and may follow the method used by those skilled in the art for each food.

[0122] It is within the scope of the present invention to sell the product of the present invention by displaying the effects of the composition for improving vascular endothelial function of the present invention on the packaging container, product instructions, pamphlets, etc. It is also within the scope of the present invention to advertise and sell the product of the present invention by displaying the effects of the present invention on television, Internet websites, pamphlets, newspapers, magazines, etc.

[0123] In the present invention, the amount of the component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters ingested by a subject is not particularly limited, and may be ingested in an amount equal to or greater than the effective amount for obtaining the desired effect. Here, the effective amount for obtaining the desired effect refers to the amount necessary for improving vascular endothelial function. For example, in the case of adults, depending on the age, weight, health condition, and other conditions of the subject, the daily intake may be 2 mg / kg body weight / day or more, e.g., 3 mg / kg body weight / day or more, 4 mg / kg body weight / day or more, 5 mg / kg body weight / day or more, 6 mg / kg body weight / day or more, 7 mg / kg body weight / day or more, 8 mg / kg body weight / day or more, 9 mg / kg body weight / day or more, 10 mg / kg body weight / day or more, 11 mg / kg body weight / day or more, 12 mg / kg body weight / day or more, 13 mg / kg body weight / day or more, 14 mg / kg body weight / day or more, 15 mg / kg body weight / day or more, 16 mg / kg body weight / day or more, 17 mg / kg body weight / day or more, 18 mg / kg body weight / day or more, 19 mg / kg body weight / day or more, 20 mg / kg body weight / day or more, 21 mg / kg body weight / day or more, 22 mg / kg body weight / day or more, 23 mg / kg body weight / day or more, 24 mg / kg body weight / day or more, calculated as monounsaturated fatty acids having 20 or more carbons. The active ingredient may be administered at a dose of 4 weeks or more, for example, 5 weeks or more, 6 weeks or more, 7 weeks or more, 8 weeks or more, 9 weeks or more, 10 weeks or more, 11 weeks or more, or 12 weeks or more. In addition, the ingredient selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters does not have any strong side effects, so there is no limit to the daily intake amount.

[0124] <Sleep improvement composition> The present invention provides a sleep-improving composition (hereinafter sometimes referred to as the sleep-improving composition of the present invention) containing, as an active ingredient, an ingredient selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters.

[0125] The monounsaturated fatty acid having 20 or more carbon atoms, its salt, or its ester used in the present invention is not particularly limited, and may be any one that is acceptable for pharmaceutical or food use. Glycerides containing monounsaturated fatty acids having 20 or more carbon atoms as constituent fatty acids can be produced by known methods, and can also be produced as oils and fats derived from natural products, for example, by the boiling method described in WO1996 / 26647. Examples of oils and fats derived from natural products include marine oils (for example, fish oils such as saury oil, and mammalian oils and fats such as seals and whales), microbial oils, etc. As described later, fish oils have a high content of monounsaturated fatty acids having 20 or more carbon atoms. Therefore, it is preferable that the active ingredient in the sleep-improving composition of the present invention is derived from fish oil (for example, saury oil). In addition, free monounsaturated fatty acids having 20 or more carbon atoms, their salts, and esters other than glycerides can be prepared by known methods, for example, using the above-mentioned glycerides as raw materials.

[0126] For example, saury crude oil is usually extracted in the same way as other fish oils: Whole saury or processing residues from seafood processing such as fish heads, skin, backbone, and innards are crushed and steamed, then pressed to separate the broth (stick water, SW) and pressed meal. The oil obtained with the broth is separated from the broth by centrifugation.

[0127] The 2015 edition (7th revision) of the Standard Tables of Food Composition in Japan states that the fatty acids in saury (skinned, raw) contain 26.0% docosenoic acid (C22:1) by weight, 17.6% eicosenoic acid (C20:1) by weight, and 54.2% total monounsaturated fatty acids. Among fish oils, saury oil is characterized by its high content of monounsaturated fatty acids.

[0128] Crude fish oil is refined into refined fish oil through refining processes such as degumming, deacidification, bleaching, deodorization, etc. This refined fish oil can also be used as a supply source of a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters.

[0129] In one embodiment, an oil having an increased concentration of monounsaturated fatty acids may be used as a supply source of a component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters. In this case, a triglyceride enriched in MUFA can be obtained by a method of concentrating the monounsaturated fatty acid ethyl esters after ethyl esterification, and then transesterifying the monounsaturated fatty acid with glycerin to reconstitute the triglyceride.

[0130] Examples of monounsaturated fatty acids having 20 or more carbon atoms include monounsaturated fatty acids having 20 carbon atoms (C20:1) (e.g., C20:1 n-11, C20:1 n-9, C20:1 n-7), monounsaturated fatty acids having 22 carbon atoms (C22:1) (e.g., C22:1 n-11, C22:1 n-9, C22:1 n-7, C22:1 n-13), and monounsaturated fatty acids having 24 carbon atoms (C24:1) (e.g., C24:1 n-9). In a preferred embodiment, the active ingredient of the sleep-improving composition of the present invention is a component selected from C20:1, its salts and its esters, a component selected from C22:1, its salts and its esters, or a combination thereof.

[0131] The content of C22:1 and C20:1 varies depending on the fish species, but examples of fish species with high content of these include fish belonging to the family Sauryidae such as Pacific cod, Alaska pollock, Atlantic cod, and sablefish, fish belonging to the family Gadidae such as Chum salmon, Coho salmon, Sockeye salmon, Pink salmon, Pacific salmon, and Rainbow trout, fish belonging to the family Osmeridae such as Capelin and Shishamo, and fish belonging to the family Clupeidae such as Herring. In addition, fish such as sand lance, tuna, mackerel, and alfonsino are relatively rich in these. They are also rich in the liver oil of sharks such as the spiny dogfish, basking shark, and chimaera. In the present invention, fish oils prepared from these fish can be used as they are, purified, or concentrated.

[0132] The ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the sleep improving composition of the present invention is 10% by weight or more, for example, 11% by weight or more, 12% by weight or more, 13% by weight or more, 14% by weight or more, 15% by weight or more, 16% by weight or more, 17% by weight or more, 18% by weight or more, 19% by weight or more, 20% by weight or more, 21% by weight or more, 22% by weight or more, 23% by weight or more, 24% by weight or more, 25% by weight or more, 26% by weight or more, 27% by weight or more, 28% by weight or more, 29% by weight or more, 30% by weight or more, 40% by weight or more, 50% by weight or more, 60% by weight or more, 70% by weight or more, 80% by weight or more, or 90% by weight or more.

[0133] In this specification, unless otherwise specified, the ratio (wt%) of fatty acids to the total fatty acids in a composition is calculated based on the value measured by gas chromatography after esterifying the components in the composition in accordance with the "Fifth Revised and Enlarged Manual for the Analysis of the Standard Tables of Food Composition in Japan" (Documents of the Food Ingredients Committee, Resource Survey Subcommittee, Council for Science and Technology, Ministry of Education, Culture, Sports, Science and Technology (2004)). The content of fatty acids also means the ratio (wt%) of the fatty acid to the total fatty acids mentioned above. The analysis conditions for gas chromatography are as follows: Equipment: Agilent 6890N GC system (Agilent) Column: DB-WAX (Agilent Technologies, 30m x 0.25mm ID, 0.25im film thickness) Carrier gas: Helium (1.0 mL / min, constant flow) Inlet temperature: 250℃ Injection volume: 1μL Injection method: Split Split ratio: 20:1 Column oven: 180℃ - 3℃ / min - 230℃ Detector: FID Detector temperature: 250℃

[0134] In the present invention, examples of the salt of monounsaturated fatty acid having 20 or more carbon atoms include potassium salt and sodium salt. Examples of ester of monounsaturated fatty acid having 20 or more carbon atoms include ester of lower alcohol having 5 or less carbon atoms (e.g., methyl ester, ethyl ester, n-propyl ester, i-propyl ester, n-butyl ester, s-butyl ester, t-butyl ester, n-pentyl ester, etc.), ester with glycerin such as monoglyceride, diglyceride and triglyceride (i.e., glyceride), and phospholipid. In a preferred embodiment, the active ingredient of the sleep improving composition of the present invention is a glyceride containing monounsaturated fatty acid having 20 or more carbon atoms as a constituent fatty acid, more preferably a triglyceride.

[0135] As the monounsaturated fatty acid having 20 or more carbon atoms in the present invention, fats and oils derived from natural products containing free monounsaturated fatty acids having 20 or more carbon atoms may be used as they are, or after purification or concentration. As the ester of monounsaturated fatty acids having 20 or more carbon atoms, fats and oils derived from natural products containing glycerides having monounsaturated fatty acids having 20 or more carbon atoms as constituent fatty acids may be used as they are, or after purification or concentration.

[0136] Also, as the ester of monounsaturated fatty acids having 20 or more carbon atoms, fractionated oils obtained by esterifying fats and oils derived from natural products and then fractionating them by high performance liquid chromatography, etc., can be used. Examples of fractionated oils include fractionated oils enriched in C20:1, fractionated oils enriched in C22:1, and fractionated oils enriched in C24:1.

[0137] The sleep-improving composition of the present invention may further comprise n-3 polyunsaturated fatty acid and n-6 ​​polyunsaturated fatty acid, in which the area ratio of n-3 polyunsaturated fatty acid to n-6 polyunsaturated fatty acid is 4.0 or more, for example 5.0 or more, 6.0 or more, 7.0 or more, 8.0 or more, 9.0 or more, or 10.0 or more. In this specification, n-3 polyunsaturated fatty acid refers to an unsaturated fatty acid having 18 or more carbon atoms and two or more carbon-carbon double bonds, in which the first double bond is between the third and fourth carbon atoms counting from the carbon of the methyl group at the end of the fatty acid chain. Examples of such fatty acids include α-linolenic acid (C18:3 n-3), octadecatetraenoic acid (C18:4 n-3), eicosatetraenoic acid (C20:4 n-3), eicosapentaenoic acid (C20:5 n-3), docosapentaenoic acid (C22:5 n-3), and docosahexaenoic acid (C22:6 n-3). The n-6 polyunsaturated fatty acid refers to an unsaturated fatty acid having 18 or more carbon atoms and two or more carbon-carbon double bonds, in which the first double bond is between the 6th and 7th carbon atoms counting from the carbon of the methyl group at the end of the fatty acid chain, such as linoleic acid (C18:2n-6) and arachidonic acid (C20:4n-6). In this specification, the area ratio of fatty acids refers to the ratio of peak areas detected by gas chromatography after esterifying the fatty acids in the composition according to AOCS official method Ce1b-89. The analysis conditions for gas chromatography are as described above.

[0138] In the present invention, improving sleep means improving sleep quality, and does not include treatment of sleep disorders including insomnia and hypersomnia. Improvement of sleep quality includes improvement of subjective symptoms, such as mood when waking up in the morning, ease of falling asleep, and depth of sleep. In one embodiment, the sleep improving composition of the present invention is for improving awakening.

[0139] The subject to which the sleep-improving composition of the present invention is administered is a mammal, preferably a human.

[0140] The sleep-improving composition of the present invention may be prepared in a form suitable for pharmaceutical compositions, food compositions (e.g., functional foods, health foods, supplements, etc.), for example, in the form of various solid preparations such as granules (including dry syrups), capsules (soft capsules, hard capsules), tablets (including chewable tablets, etc.), powders (powdered agents), pills, or liquid preparations such as oral liquids (including liquids, suspensions, syrups, etc.). For example, the sleep-improving composition of the present invention can be formulated as a soft capsule in which purified fish oil is filled in a gelatin membrane.

[0141] Examples of additives for formulation include excipients, lubricants, binders, disintegrants, fluidizers, dispersants, wetting agents, preservatives, thickeners, pH adjusters, colorants, flavorings, surfactants, and dissolution aids. When the formulation is in the form of a liquid, a thickener such as pectin, xanthan gum, or guar gum can be added. In addition, the formulation can be made into a coated tablet using a coating agent, or into a paste-like glue. Furthermore, when preparing other forms, conventional methods can be followed.

[0142] The sleep-improving composition of the present invention can take the form of a food composition. In the present invention, the food composition means food in general, including beverages, and includes general foods, including health foods such as supplements, as well as specific health foods and nutritional functional foods as specified by the Consumer Affairs Agency's Health Functional Food System. For example, functional foods labeled with a sleep-improving effect are provided. For example, foods containing fish oil can be provided as they are. The food composition of the present invention also includes food materials that can be added to, mixed with, or applied to other foods to impart a sleep-improving effect. In addition to foods, the food composition can also be provided as animal feed.

[0143] When the sleep-improving composition of the present invention is in the form of food, the food is not particularly limited and may be beverages, confectioneries, breads, soups, etc., such as general retort foods, frozen foods, instant foods (such as noodles), canned foods, sausages, cookies, biscuits, cereal bars, crackers, snacks (such as potato chips), pastries, cakes, pies, candies, chewing gum (including pellets and sticks), jellies, soups, ice cream, dressings, yogurt, etc., supplements in the form of tablets, capsules, emulsions, etc., soft drinks, etc. The manufacturing method of these foods is not particularly limited as long as it does not impair the effects of the present invention, and may follow the method used by those skilled in the art for each food.

[0144] It is within the scope of the present invention to sell the product of the present invention by displaying the effects of the composition for improving sleep of the present invention on the packaging container, product instructions, pamphlets, etc. It is also within the scope of the present invention to advertise and sell the product of the present invention by displaying the effects of the present invention on television, Internet websites, pamphlets, newspapers, magazines, etc.

[0145] In the present invention, the amount of the component selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters ingested by a subject is not particularly limited, and may be ingested in an amount equal to or greater than the effective amount for obtaining the desired effect. Here, the effective amount for obtaining the desired effect refers to the amount necessary for improving sleep. For example, in the case of adults, depending on the age, weight, health condition, and other conditions of the subject, the daily intake may be 2 mg / kg body weight / day or more, e.g., 3 mg / kg body weight / day or more, 4 mg / kg body weight / day or more, 5 mg / kg body weight / day or more, 6 mg / kg body weight / day or more, 7 mg / kg body weight / day or more, 8 mg / kg body weight / day or more, 9 mg / kg body weight / day or more, 10 mg / kg body weight / day or more, 11 mg / kg body weight / day or more, 12 mg / kg body weight / day or more, 13 mg / kg body weight / day or more, 14 mg / kg body weight / day or more, 15 mg / kg body weight / day or more, 16 mg / kg body weight / day or more, 17 mg / kg body weight / day or more, 18 mg / kg body weight / day or more, 19 mg / kg body weight / day or more, 20 mg / kg body weight / day or more, 21 mg / kg body weight / day or more, 22 mg / kg body weight / day or more, 23 mg / kg body weight / day or more, 24 mg / kg body weight / day or more, calculated as monounsaturated fatty acids having 20 or more carbons. The active ingredient may be administered at a dose of 4 weeks or more, for example, 5 weeks or more, 6 weeks or more, 7 weeks or more, 8 weeks or more, 9 weeks or more, 10 weeks or more, 11 weeks or more, or 12 weeks or more. In addition, the ingredient selected from monounsaturated fatty acids having 20 or more carbon atoms, their salts, and their esters does not have any strong side effects, so there is no limit to the daily intake amount. EXAMPLES

[0146] The present invention will now be described in further detail with reference to examples, but the present invention is not limited to these examples. In the examples, all percentages are by weight unless otherwise specified.

[0147] Example 1: Intervention Study 1 (1) Test method a) Test foods: Capsules containing 0.35 g of pacific saury-derived fish oil (containing approximately 29% LC-MUFA of total fatty acids (27% by weight of total fish oil)) and canned salted grilled pacific saury (commercially available from Nippon Suisan Kaisha, Ltd.).

[0148] The fatty acid composition of the refined saury oil in the capsules and the canned salted grilled saury is shown in Table 1. The fatty acid composition of the refined saury oil was calculated based on the values ​​measured by gas chromatography after esterification of the components in the composition according to AOCS official method Ce1b-89. The fatty acid composition of the canned salted grilled saury is the result of analysis by the Japan Food Research Laboratories. The analytical conditions for gas chromatography according to AOCS official method Ce1b-89 are as follows: Equipment: Agilent 6890N GC system (Agilent) Column: DB-WAX (Agilent Technologies, 30m x 0.25mm ID, 0.25im film thickness) Carrier gas: Helium (1.0 mL / min, constant flow) Inlet temperature: 250℃ Injection volume: 1μL Injection method: Split Split ratio: 20:1 Column oven: 180℃ - 3℃ / min - 230℃ Detector: FID Detector temperature: 250℃

[0149] [Table 1]

[0150] The general ingredient list and fatty acid content of the saury oil capsules are shown in Table 2, and the general ingredient list and fatty acid content of the canned salted grilled saury are shown in Table 3. The analytical results of the refined saury oil in the capsules (acid value, peroxide value, p-anisidine value, and lipid composition) are shown in Table 4.

[0151] [Table 2]

[0152] [Table 3]

[0153] [Table 4]

[0154] b) Subjects: 49 healthy adults, including students from Tokushima University, aged 20 or over, were divided into two groups (capsule intake group and canned food intake group). The capsule intake group consisted of 24 participants with an average age of 22 years (average body weight: 53.2 kg (before intake) and 52.9 kg (after intake)), while the canned food intake group consisted of 25 participants with an average age of 21 years (average body weight: 53.3 kg (before intake) and 53.0 kg (after intake)) (Tables 7-1 and 7-2). During the study, one participant in the capsule intake group discontinued the study due to high triglyceride levels, and one participant in the canned food intake group was excluded from the study due to violation of the intake criteria.

[0155] c) Study details: The capsule intake group took 12 capsules per day for four weeks. The canned food intake group took four cans per week for a total of four weeks. Each of the 12 capsules contained 4.2 g of saury oil, meaning that subjects consumed approximately 1.1 g of LC-MUFA per day. Additionally, canned salted grilled saury contained approximately 15 g of oil per can (75 g), meaning that subjects consumed approximately 4.9 g of LC-MUFA per day.

[0156] Blood and biochemical tests, a QOL questionnaire, and vascular endothelial function measurements were conducted before the start of the study and after four weeks of intake.

[0157] Blood and biochemistry tests were performed at SRL Co., Ltd.

[0158] The QOL questionnaire survey was conducted using a visual analogue scale (VAS) for six questions (hunger, fullness, fatigue, waking up, taste, and enjoyment). The subjects answered each question on a scale from 0 to 100 to indicate their current state. For example, for waking up, a score of 100 was assigned for being able to wake up feeling good in the morning, and a score of 0 for waking up feeling completely bad. The higher the score, the better the awakening experience.

[0159] Vascular endothelial function was evaluated by measuring the flow-mediated dilation (FMD) value using the UNESQ EF (UNESQ Co., Ltd.). The FMD value (%) was calculated as the maximum dilation width (mm) / resting vascular diameter (mm) x 100.

[0160] Statistical processing was performed using the statistical software Graphpad Prism (MDF, Ltd.). One-way analysis of variance was used for multigroup testing, and Tukey's multiple comparisons test was used for multiple comparison testing. For intergroup comparisons, an unpaired t-test was used, which compares two unpaired groups, and for intragroup comparisons, a paired t-test was used, which compares two paired groups.

[0161] d) Implementation period: April 5th to June 30th, 2016

[0162] (2) Test results (2-1) FMD testing As shown in Table 5 and Figures 1-1 and 1-2, 4 weeks after starting to take the capsules or the canned food, a significant improvement in FMD values ​​was observed in both groups compared to before intake. In the capsule intake group, an improvement of approximately 44% in FMD values ​​was observed. In the canned food intake group, an improvement of approximately 12% in FMD values ​​was observed.

[0163] [Table 5]

[0164] Furthermore, for the nine subjects who showed an increase in FMD, the FMD values ​​were measured again after a four-week washout period after the end of intake. As a result, as shown in Figures 1-3 and 1-4, a tendency for FMD values ​​to decrease after the washout period was observed. This confirmed the high possibility that FMD values ​​increased due to the intake of fish oil.

[0165] In addition, when data was analyzed for subjects suspected of having vascular endothelial dysfunction, whose FMD values ​​before ingestion were less than 6%, FMD values ​​tended to increase in both groups after ingestion. This suggests that saury oil intake not only enhances vascular endothelial function in subjects whose FMD values ​​are within the normal range, but may also improve vascular endothelial dysfunction in subjects whose FMD values ​​are outside the normal range. In addition, saury oil is rich in LC-MUFA, which suggests the possibility that LC-MUFA may affect the vascular endothelium and improve vascular endothelial function.

[0166] (2-2) QOL Questionnaire Survey As shown in Tables 6-1 and 6-2 and FIG. 2, wakefulness was improved in the capsule group.

[0167] [Table 6-1]

[0168] [Table 6-2]

[0169] (2-3) Body composition measurement Body composition evaluation (body weight, body fat, lean mass, muscle mass, body water, BMI) was measured using a dual frequency body composition monitor (DC-320, Tanita Corporation). As shown in Tables 7-1 and 7-2 and Figure 3, the body fat percentage was significantly reduced in the capsule group.

[0170] [Table 7-1]

[0171] [Table 7-2]

[0172] (2-4) Blood tests and blood biochemistry tests No abnormalities were found in the blood tests for either group (Table 8). Blood biochemistry tests showed that triglyceride (TG) levels were reduced in the capsule group after ingestion (Table 9).

[0173] [Table 8]

[0174] [Table 9]

[0175] (Example 2) Intervention Study 2 (1) Test method a) Test food: Sanma oil capsules contain 0.35g of fish oil derived from saury, which contains LC-MUFA at a ratio of approximately 29% to total fatty acids. Blended oil capsules contain 0.35g of tuna oil and refined olive oil mixed at a weight ratio of 1:1 (containing LC-MUFA at a ratio of approximately 1.8% to total fatty acids). The total of EPA+DPA+DHA in the fatty acid composition of the saury oil capsules and blended oil capsules was 19.4% and 19.7%, respectively, which was almost the same.

[0176] The fatty acid composition in the saury oil capsules and blended oil capsules is shown in Table 10. The fatty acid composition was calculated based on the value measured by gas chromatography after esterification of the components in the composition according to AOCS official method Ce1b-89.

[0177] [Table 10]

[0178] b) Subjects: 52 healthy adults, including students from Tokushima University, aged 20 or over, were divided into two groups (a group that took saury oil capsules and a group that took blended oil capsules). The saury oil capsule group consisted of 26 people with an average age of 21 (average body weight: 54.2 kg (before ingestion) and 54.8 kg (after ingestion)), while the blended oil capsule group consisted of 26 people with an average age of 21 (average body weight: 52.8 kg (before ingestion) and 53.0 kg (after ingestion)) (Table 11).

[0179] c) Study content: Subjects took 12 capsules per day for 4 weeks. Each of the 12 saury oil capsules contained 4.2g of saury oil, meaning that subjects took in approximately 1.1g of LC-MUFA and approximately 0.7g of n-3 polyunsaturated fatty acids (EPA+DPA+DHA) per day. Each of the 12 blended oil capsules contained 2.1g of tuna oil and 2.1g of refined olive oil, meaning that subjects took in approximately 0.07g of LC-MUFA and approximately 0.7g of n-3 polyunsaturated fatty acids (EPA+DPA+DHA) per day. Therefore, although the intake of LC-MUFA differed in each capsule group, the intake of n-3 polyunsaturated fatty acids (EPA+DPA+DHA) was approximately the same.

[0180] Vascular endothelial function was measured before the start of the study and after 4 weeks of intake. Vascular endothelial function was evaluated by measuring the flow-mediated dilation (FMD) value using a UNESQ EF (manufactured by UNESQ Co., Ltd.). The FMD value (%) was calculated as the maximum dilation width (mm) / resting vascular diameter (mm) x 100.

[0181] Statistical processing was performed using the statistical software Graphpad Prism (MDF, Ltd.). One-way analysis of variance was used for multigroup testing, and Tukey's multiple comparisons test was used for multiple comparison testing. For intergroup comparisons, an unpaired t-test was used, which compares two unpaired groups, and for intragroup comparisons, a paired t-test was used, which compares two paired groups.

[0182] d) Implementation period: October 17th to December 7th, 2017

[0183] (2) Test results (2-1) FMD testing As shown in Table 11 and Figure 4, in all groups, an improvement in FMD values ​​was observed 4 weeks after starting to take the capsules, compared to before intake. A significant improvement of approximately 44% in FMD values ​​was observed in the saury oil capsule intake group. An improvement of approximately 21% in FMD values ​​was observed in the blended oil capsule intake group. As each capsule contained the same amount of n-3 polyunsaturated fatty acids, the effect of LC-MUFA was shown to have the potential to enhance vascular endothelial function.

[0184] [Table 11] [Industrial Applicability]

[0185] The present invention provides a food composition and a pharmaceutical composition that reduce the risk of contracting a disease caused by vascular endothelial dysfunction, and also provides a food composition and a pharmaceutical composition for improving the feeling of awakening and the quality of life.

Claims

1. A food composition for reducing the risk of developing hypertension by improving flow-mediated vasodilation, The present invention comprises, as an active ingredient, a component selected from monounsaturated fatty acids having 20 or more carbon atoms, salts thereof, and esters thereof, The ratio of monounsaturated fatty acids having 20 or more carbon atoms to the total fatty acids in the composition is 10% by weight or more, The active ingredient is derived from fish oil. The active ingredient is a combination of a component selected from a monounsaturated fatty acid having 20 carbon atoms, a salt thereof, and an ester thereof and a component selected from a monounsaturated fatty acid having 22 carbon atoms, a salt thereof, and an ester thereof. The food composition.

2. 2. The food composition according to claim 1, wherein the active ingredient is a combination of a glyceride containing a monounsaturated fatty acid having 20 carbon atoms as a constituent fatty acid and a glyceride containing a monounsaturated fatty acid having 22 carbon atoms as a constituent fatty acid.

3. 3. The food composition of claim 2, wherein the glyceride is a triglyceride.

4. The food composition according to any one of claims 1 to 3, further comprising n-3 polyunsaturated fatty acids and n-6 ​​polyunsaturated fatty acids, and the area ratio of n-3 polyunsaturated fatty acids to n-6 polyunsaturated fatty acids is 4.0 or more.

5. The food composition according to any one of claims 1 to 4, wherein the improvement in flow-mediated vasodilation response is an increase in flow-mediated vasodilation response value (FMD value).

6. The food composition according to claim 5 , wherein the increase in FMD value is an increase in FMD value in a subject having an FMD value of 6% or more.

7. The food composition according to claim 5 , wherein the increase in FMD value is an increase in FMD value in a subject whose FMD value is less than 6%.

8. A food composition according to any one of claims 1 to 5 and 7, characterized in that it is ingested by a subject with an FMD value of 2.1% or more.

9. The food composition according to any one of claims 1 to 8, characterized in that it is ingested by subjects aged 20 years or older.

10. The food composition according to any one of claims 1 to 9, wherein the fish oil is saury oil.

11. The food composition according to any one of claims 1 to 10, characterized in that the food composition is used so that an active ingredient calculated as a monounsaturated fatty acid having 20 or more carbon atoms is orally administered at a dose of 2 mg / kg body weight / day or more for 4 weeks or more.

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