Composition for promoting secretion of gastro-somatotropin

Abstract

The purpose of the present invention is to provide a novel composition for promoting the secretion of galactotropin. According to the present invention, provided is a composition for promoting secretion of gastro-somatotropin, which contains, as an active ingredient, one or more substances selected from the group consisting of oleic acid and acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids. The composition is preferably a composition for promoting appetite, improving inappetence, promoting secretion of growth hormone, improving low nutrition, promoting fat accumulation, increasing body weight, enhancing gastric acid secretion or enhancing gastric motility. The composition is preferably a food composition.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority of Japanese Patent Application No. 2022-197732 (filing date: December 12, 2022), the entire disclosure of which is incorporated herein by reference as part of this specification. TECHNICAL FIELD

[0003] The present invention relates to a composition for promoting ghrelin secretion. BACKGROUND ART

[0004] Ghrelin is a peptide hormone mainly secreted by the stomach, and the serine residue at the third amino acid is acylated with octanoic acid to express its activity. In addition to enhancing food intake, ghrelin has effects such as fat accumulation and weight gain, and is related to energy metabolism regulation. In addition, a wide range of physiological effects of ghrelin have been reported, such as the effect of promoting growth hormone secretion by acting on the growth hormone releasing factor receptor in the pituitary gland, gastric acid secretion in the digestive system, and enhancement of gastric motility.

[0005] For the normal development of the appetite regulation function required for infants and young children with significant physical and intellectual growth to intake the required energy, and for the development of functions based on the physiological effects of ghrelin and growth hormone, it is important to promote ghrelin secretion. On the other hand, it is also possible to expect effects of preventing and improving anorexia in the elderly, reducing energy intake, and reducing muscle mass and muscle strength caused by reduced growth hormone secretion. As a clinical application, clinical studies are underway expecting improvement effects on cachexia caused by gastrectomy, cancer, heart failure, chronic renal failure, autoimmune diseases, etc., chronic obstructive pulmonary disease, functional gastroenteritis, and anorexia nervosa.

[0006] Acylglycerol has a structure in which 1 to 3 fatty acids are ester-bonded to the 3 hydroxyl groups of the glycerol backbone. Triacylglycerol occupies most of the lipids in food, and is hydrolyzed by lipase in the stomach and small intestine to produce free fatty acids and diacylglycerol or monoacylglycerol. Fatty acids bonded to the β-position of the glycerol backbone are not easily affected by lipase and are absorbed by small intestinal epithelial cells as 2-monoacylglycerol. As described above, various fatty acids and acylglycerols exist in the digestive tract, and it is considered that each component has different effects on the expression of physiological activity and the control of gene expression. However, up to now, although there are reports that free fatty acids inhibit ghrelin secretion (Non-Patent Documents 1 and 2), the effects of acylglycerol are not clear.

[0007] PRIOR ART DOCUMENTS

[0008] NON-PATENT DOCUMENTS

[0009] Non - Patent Document 1: Z Gong et al., Am J Physiol Endocrinol Metab., 2014, 306(1): E28 - 35

[0010] Non - Patent Document 2: X Lu et al., Am J Physiol Gastrointest Liver Physiol., 2012, 303(3): G367 - 76 SUMMARY OF THE INVENTION

[0011] PROBLEMS TO BE SOLVED BY THE INVENTION

[0012] An object of the present invention is to provide a novel composition for promoting the secretion of ghrelin.

[0013] SOLUTION TO THE PROBLEM

[0014] The present inventors have verified the effect on the secretion of active ghrelin by adding free fatty acids and acylglycerols to the ghrelin - secreting cell line MGN3 - 1 derived from the mouse stomach. In particular, focusing on the differences in the bonding position of fatty acids to the glycerol backbone of acylglycerols and the types of fatty acids bonded, the effects of various acylglycerols on the secretion of active ghrelin have been verified. As a result, it has been found that acylglycerols having oleic acid and palmitic acid as constituent fatty acids significantly promote the secretion of active ghrelin. The present invention has been obtained based on these findings.

[0015] According to the present invention, the following technical solutions are provided.

[0016] [1]. A composition for promoting the secretion of ghrelin and a ghrelin secretion promoter, which contain one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid as an active ingredient.

[0017] [2]. The composition and agent according to the above [1], wherein, in the acylglycerol, palmitic acid and / or oleic acid are bonded to the sn - 1 position and / or sn - 2 position of glycerol.

[0018] [3]. The composition and agent according to the above [1], wherein the acylglycerol contains palmitic acid and oleic acid as constituent fatty acids.

[0019] [4]. The composition and agent according to the above [2], wherein, in the acylglycerol, any fatty acid is bonded to the sn - 3 position of glycerol.

[0020] [5]. The composition and agent according to the above [4], wherein the any fatty acid is palmitic acid or oleic acid.

[0021] [6]. The composition and agent according to [1] above, wherein the acylglycerol is one or more selected from the group consisting of 1-monopalmitin, 2-monopalmitin, 1-monoolein, 2-monoolein, 1-oleoyl-2-palmitoyl glycerol, 1-palmitoyl-2-oleoyl glycerol, 1,3-dioleoyl-2-palmitoyl triglyceride, and 1,3-dipalmitoyl-2-oleoyl triglyceride.

[0022] [7]. The composition and agent according to [1] above, wherein the content of the active ingredient relative to the composition is 1 to 95% by mass.

[0023] [8]. The composition and agent according to [1] above, which is used for promoting appetite, improving anorexia, promoting the secretion of growth hormone, improving malnutrition, promoting fat accumulation, increasing body weight, enhancing gastric acid secretion, or enhancing gastric motility.

[0024] [9]. The composition and agent according to [1] above, which is a food composition.

[0025]

[10] . The composition and agent according to [1] above, which is for ingestion by infants and / or the elderly.

[0026]

[11] . A method for promoting the secretion of ghrelin, a method for promoting or enhancing appetite, a method for improving or alleviating anorexia, a method for promoting or enhancing the secretion of growth hormone, a method for improving or alleviating malnutrition, a method for promoting or enhancing fat accumulation, a method for increasing body weight, a method for promoting or enhancing gastric acid secretion, or a method for promoting or enhancing gastric motility, which comprises: administering to a subject in need or causing a subject in need to ingest one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid, or a composition containing the same.

[0027]

[12] . Use of one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid, or a composition containing the same, for the manufacture of a ghrelin secretion promoter, an appetite promoter or enhancer, an anorexia improver or reliever, a growth hormone secretion promoter or enhancer, a malnutrition improver or reliever, a fat accumulation promoter or enhancer, a weight gain agent, a gastric acid secretion promoter or enhancer, or a gastric motility promoter or enhancer; or, the use is as a ghrelin secretion promoter, an appetite promoter or enhancer, an anorexia improver or reliever, a growth hormone secretion promoter or enhancer, a malnutrition improver or reliever, a fat accumulation promoter or enhancer, a weight gain agent, a gastric acid secretion promoter or enhancer, or a gastric motility promoter or enhancer; or, the use is for a method of promoting ghrelin secretion, a method of promoting or enhancing appetite, a method of improving or relieving anorexia, a method of promoting or enhancing growth hormone secretion, a method of improving or relieving malnutrition, a method of promoting or enhancing fat accumulation, a method of increasing weight, a method of promoting or enhancing gastric acid secretion, or a method of promoting or enhancing gastric motility.

[0028]

[13] . One or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid, or a composition containing the same, for promoting ghrelin secretion, promoting or enhancing appetite, improving or relieving anorexia, promoting or enhancing growth hormone secretion, improving or relieving malnutrition, promoting or enhancing fat accumulation, increasing weight, promoting or enhancing gastric acid secretion, or promoting or enhancing gastric motility.

[0029] In this specification, the composition of the above [1] is sometimes referred to as "the composition of the present invention". In addition, in this specification, the agent of the above [1] is sometimes referred to as "the agent of the present invention".

[0030] The active ingredients of the composition and agent of the present invention are oils and fats that have been used as food raw materials for many years. Therefore, while the composition and agent of the present invention exhibit the effect of promoting ghrelin secretion, there is no need to worry about side effects even if taken continuously for a long time, which is advantageous in terms of high safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Figure 1 It is a graph showing the ghrelin secretion activity based on 2-monopalmitin (30 μM) (n = 4) (Example 1). The measured values are expressed as mean ± standard error, and * indicates p < 0.05.

[0032] Figure 2 ​​​​Figure 2 It is a graph showing the ghrelin - secreting activity based on 2 - monopalmitin, 1 - monoolein, or 2 - monoolein (all at 30 μM) (Example 1). The measured values are expressed as mean ± standard error, and lowercase letters indicate significant differences between different symbols (p < 0.05). Detailed implementation mode

[0033] The composition and agent of the present invention contain one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid and oleic acid as active ingredients. In the present invention, the "one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid" as the active ingredient is sometimes referred to as "the acylglycerol and / or oleic acid of the present invention". In the present invention, the "acylglycerol containing palmitic acid and / or oleic acid as constituent fatty acids" refers to a substance in which palmitic acid and / or oleic acid is ester - bonded to glycerol, and in terms of chemical formula, it refers to all the same compounds. In the present invention, the "acylglycerol containing palmitic acid and / or oleic acid as constituent fatty acids" as the active ingredient is sometimes referred to as "the acylglycerol of the present invention". In the present invention, oleic acid as the active ingredient is sometimes referred to as "the oleic acid of the present invention".

[0034] The acylglycerol of the present invention includes acylglycerols with palmitic acid ester - bonded to the sn - 2 position of glycerol, acylglycerols with oleic acid ester - bonded to the sn - 2 position of glycerol, acylglycerols with palmitic acid ester - bonded to the sn - 1 position of glycerol, and acylglycerols with oleic acid ester - bonded to the sn - 1 position of glycerol. The acylglycerol of the present invention also includes monoacylglycerol, diacylglycerol, and triacylglycerol. That is, in the above - mentioned acylglycerols in which the fatty acid and its bonding position are specified, fatty acids may not exist at the two positions other than the position where the fatty acid exists, or any fatty acids (optionally the same or different) may exist, or any fatty acid may exist at one of the two positions other than the position where the specific fatty acid exists, and no fatty acid exists at the other position. For example, for acylglycerols with palmitic acid or oleic acid ester - bonded to the sn - 2 position of glycerol, fatty acids may not exist at the sn - 1 and sn - 3 positions, or any fatty acids (optionally the same or different) may exist, or any fatty acid may exist at one of the sn - 1 and sn - 3 positions, and no fatty acid exists at the other position.

[0035] As any fatty acid constituting the acylglycerol, saturated fatty acids and unsaturated fatty acids having 2 to 24 carbon atoms can be cited, such as oleic acid, palmitic acid, caprylic acid, and docosahexaenoic acid.

[0036] The acylglycerol of the present invention is preferably an acylglycerol containing either or both of palmitic acid and oleic acid as constituent fatty acids. Preferred examples of the acylglycerol of the present invention include the following (1) to (4).

[0037] (1) An acylglycerol in which a palmitic acid or oleic acid ester is bonded to the sn-2 position of glycerol, and no fatty acid is present at the sn-1 and sn-3 positions.

[0038] (2) An acylglycerol in which a palmitic acid or oleic acid ester is bonded to the sn-2 position of glycerol, and palmitic acid or oleic acid is present at either or both of the sn-1 and sn-3 positions.

[0039] (3) An acylglycerol in which a palmitic acid or oleic acid ester is bonded to the sn-1 position of glycerol, and no fatty acid is present at the sn-2 and sn-3 positions.

[0040] (4) An acylglycerol in which a palmitic acid or oleic acid ester is bonded to the sn-1 position of glycerol, and palmitic acid or oleic acid is present at either or both of the sn-2 and sn-3 positions.

[0041] In the acylglycerols of (2) and (4) above, fatty acids may or may not be present at the positions where the presence of palmitic acid and oleic acid is not specified, and preferably, it is a state where no fatty acid is present.

[0042] Particularly preferred examples of the acylglycerol of the present invention include 1-monopalmitin, 2-monopalmitin, 1-monoolein, 2-monoolein, 1-oleoyl-2-palmitoyl glycerol (OP), 1-palmitoyl-2-oleoyl glycerol (PO), 1,3-dioleoyl-2-palmitoyl glycerol (OPO), and 1,3-dipalmitoyl-2-oleoyl glycerol (POP).

[0043] The acylglycerol of the present invention may be a pure product or a mixture with other substances. For example, the acylglycerol of the present invention can be measured using known measurement methods and directly used with the raw materials whose presence has been confirmed.

[0044] The oleic acid of the present invention may be a pure product or a mixture with other substances. For example, a raw material in which the oleic acid of the present invention is measured by a known measurement method and its presence is confirmed can be directly used. The oleic acid of the present invention may also be oleic acid liberated by hydrolysis of acylglycerol with a lipase. Examples of the lipase for hydrolyzing acylglycerol include triacylglycerol lipase (EC 3.1.1.3, sometimes referred to as gastric lipase in this specification). In addition, as the acylglycerol from which oleic acid is liberated by a lipase, an acylglycerol containing oleic acid as a constituent fatty acid can be used, and preferably an acylglycerol in which oleic acid is bonded to the sn-3 position of glycerol can be used. Examples thereof include 1,3-dioleoyl-2-palmitoylglycerol (OPO) and 1-linoleoyl-2-palmitoyl-3-oleoylglycerol.

[0045] According to one aspect of the composition and agent of the present invention, there is provided a composition and agent containing the acylglycerol and / or oleic acid of the present invention as an active ingredient. As a rich raw material (mixture) of the acylglycerol of the present invention, lard is representative. As a rich raw material (mixture) of the oleic acid of the present invention, olive oil, high-oleic sunflower oil, and high-oleic safflower oil are representative, and they can also be used in the composition and agent of the present invention. Alternatively, commercially available products of the acylglycerol of the present invention and commercially available products of the oleic acid of the present invention can be purchased and appropriately combined with other raw materials for use in the composition and agent of the present invention.

[0046] The composition and agent of the present invention may contain the acylglycerol and / or oleic acid of the present invention alone, or may also be mixed with other components. The lower limit of the content of the active ingredient (acylglycerol and / or oleic acid of the present invention) in the composition and agent of the present invention may be set to 1% by mass or 2% by mass, preferably 3% by mass, more preferably 5% by mass. In addition, the upper limit of the above content may be set to 95% by mass or 93% by mass, preferably 30% by mass or 25% by mass, more preferably 10% by mass or 5% by mass. These lower limits and upper limits can be arbitrarily combined respectively, and the range of the above content can be set, for example, to 1-95% by mass, 2-95% by mass, 2-30% by mass, 5-30% by mass or 2-5% by mass. The lower limit of the content of the acylglycerol in the composition and agent of the present invention may be set to 1% by mass or 2% by mass, preferably 3% by mass, more preferably 5% by mass. In addition, the upper limit of the above content may be set to 95% by mass or 93% by mass, preferably 30% by mass or 25% by mass, more preferably 10% by mass or 5% by mass. These lower limits and upper limits can be arbitrarily combined respectively, and the range of the above content can be set, for example, to 1-95% by mass, 2-95% by mass, 2-30% by mass, 5-30% by mass or 2-5% by mass. The lower limit of the content of the oleic acid in the composition and agent of the present invention may be set to 1% by mass or 2% by mass, preferably 3% by mass, more preferably 5% by mass. In addition, the upper limit of the above content may be set to 95% by mass or 93% by mass, preferably 30% by mass or 25% by mass, more preferably 10% by mass or 5% by mass. These lower limits and upper limits can be arbitrarily combined respectively, and the range of the above content can be set, for example, to 1-95% by mass, 2-95% by mass, 2-30% by mass, 5-30% by mass or 2-5% by mass. In the present invention, the agent of the present invention may contain the acylglycerol and / or oleic acid of the present invention, and the composition of the present invention may contain the acylglycerol and / or oleic acid of the present invention.

[0047] The content of the active ingredient of the present invention in the composition and agent of the present invention can also be determined based on the mass of the solid components. That is, with respect to all the solid components of the composition and agent of the present invention, the lower limit value of the content of the active ingredient of the present invention (the acylglycerol and / or oleic acid of the present invention) can be set to 1% by mass or 2% by mass, preferably 3% by mass or 5% by mass, more preferably 10% by mass or 15% by mass. In addition, the upper limit value of the above content can be set to 95% by mass or 93% by mass, preferably 50% by mass or 40% by mass, more preferably 30% by mass or 25% by mass. These lower limit values and upper limit values can be arbitrarily combined respectively, and the range of the above content can be set, for example, to 1-95% by mass, 2-95% by mass, 2-30% by mass or 5-30% by mass. With respect to all the solid components of the composition and agent of the present invention, the lower limit value of the content of the acylglycerol of the present invention can be set to 1% by mass or 2% by mass, preferably 3% by mass or 5% by mass, more preferably 10% by mass or 15% by mass. In addition, the upper limit value of the above content can be set to 95% by mass or 93% by mass, preferably 50% by mass or 40% by mass, more preferably 30% by mass or 25% by mass. These lower limit values and upper limit values can be arbitrarily combined respectively, and the range of the above content can be set, for example, to 1-95% by mass, 2-95% by mass, 2-30% by mass or 5-30% by mass. With respect to all the solid components of the composition and agent of the present invention, the lower limit value of the content of the oleic acid of the present invention can be set to 1% by mass or 2% by mass, preferably 3% by mass or 5% by mass, more preferably 10% by mass or 15% by mass. In addition, the upper limit value of the above content can be set to 95% by mass or 93% by mass, preferably 50% by mass or 40% by mass, more preferably 30% by mass or 25% by mass. These lower limit values and upper limit values can be arbitrarily combined respectively, and the range of the above content can be set, for example, to 1-95% by mass, 2-95% by mass, 2-30% by mass or 5-30% by mass. It should be noted that in this specification, "solid components" refers to components other than moisture.

[0048] In addition to the acylglycerol and / or oleic acid of the present invention, the composition and agent of the present invention may further contain oils and fats containing medium-chain fatty acids (such as medium-chain fatty acid glycerides), general edible oils and fats (such as oils and fats mainly composed of long-chain fatty acids such as soybean oil), etc. The content of the oils and fats other than the acylglycerol and / or oleic acid of the present invention in the composition and agent of the present invention can be set, for example, to 0-99% by mass, and can be set preferably to 0-70% by mass. With respect to all the solid components of the composition and agent of the present invention, the content of the oils and fats other than the acylglycerol and / or oleic acid of the present invention can be set, for example, to 0-99% by mass, and can be set preferably to 0-70% by mass.

[0049] The composition and agent of the present invention can be used to promote ghrelin secretion. Here, "promote secretion" is used in the sense of not only including promoting the secretion of ghrelin, but also including inhibiting the decrease in ghrelin secretion and maintaining ghrelin secretion. In addition, in the present invention, promoting the secretion of ghrelin can be set as promoting the secretion of ghrelin in the stomach, preferably promoting the secretion of active ghrelin (acylated ghrelin) in the stomach of humans or non-human animals (such as mammals other than humans).

[0050] In the present invention, the promotion of ghrelin secretion can be evaluated using the secretion promotion rate as an index. Specifically, the ratio (%) of the amount of ghrelin secretion in the presence of the composition and agent of the present invention to the amount of ghrelin secretion in the absence of the composition and agent of the present invention can be used as the secretion promotion rate. The amount of secretion promotion can be indicated by the increase in the amount of ghrelin in the culture medium during culture, the increase in the amount of ghrelin in the blood of the organism, etc. In the present invention, when the secretion promotion rate (%) exceeds 110%, 120%, 130%, 150%, 170% or 200%, or when the amount of ghrelin secretion in the presence of the composition and agent of the present invention is significantly increased statistically compared to the amount of ghrelin secretion in the absence of the composition and agent of the present invention, it can be judged that there is an effect of promoting the secretion of ghrelin.

[0051] According to the following embodiments, the acylglycerol and oleic acid of the present invention can promote the secretion of ghrelin. Here, it is known that by promoting the secretion of ghrelin, the promotion of appetite, the improvement of anorexia, the promotion of growth hormone secretion, the improvement of malnutrition, the enhancement of fat accumulation, the increase in body weight, the enhancement of gastric acid secretion or the enhancement of gastric motility can be confirmed (Mercedes Gil-Campos, et al., Br J Nutr. 2006, 96(2):201-26, Masayasu Kojima, et al., Nature. 1999, 402(6762):656-60, Yutaka Masuda, et al., Biochem Biophys Res Commun., 2000, 276(3):905-8). That is, by ingesting or administering the acylglycerol and / or oleic acid of the present invention, these effects can be expected. Therefore, the composition and agent of the present invention can be ingested or administered to an object with low ghrelin secretion, an object who wants to enjoy the effects exerted by promoting ghrelin secretion, or an object who hopes to promote ghrelin secretion. As such an object, for example, infants and the elderly can be cited. The composition and agent of the present invention have an appetite-enhancing effect and a growth hormone secretion-promoting effect brought about by ghrelin secretion, and thus are suitable for promoting the normal growth and development of infants and improving the nutritional status of the elderly who have fallen into a state of malnutrition. The objects of ingestion or administration of the composition and agent of the present invention include healthy individuals.

[0052] In the present invention, the amount of ghrelin secretion of an object can be measured before the object ingests or the composition and agent of the present invention are administered to the object. The amount of ghrelin secretion of the object to be ingested or administered can be determined using the concentration of ghrelin in the blood (for example, in serum or plasma) as an index. For example, the composition and agent of the present invention can be ingested by an object with a ghrelin concentration in plasma of 10 pg / ml or less, 20 pg / ml or less, 30 pg / ml or less, or the composition and agent of the present invention can be administered to an object with a ghrelin concentration in plasma of 10 pg / ml or less, 20 pg / ml or less, 30 pg / ml or less. It should be noted that the concentration of ghrelin in plasma can be measured by an immunological assay method such as an enzyme-linked immunosorbent assay (ELISA method).

[0053] The acylglycerol and oleic acid of the present invention can be used respectively to promote or enhance appetite, improve or relieve anorexia, promote or enhance the secretion of growth hormone, improve or relieve malnutrition, promote or enhance fat accumulation, increase body weight, promote or enhance gastric acid secretion, or promote or enhance gastric motility. That is, according to the present invention, there is provided a promoter or enhancer of appetite, an improver or reliever of anorexia, a promoter or enhancer of growth hormone secretion, an improver or reliever of malnutrition, a promoter or enhancer of fat accumulation, a body weight increaser, a promoter or enhancer of gastric acid secretion, or a promoter or enhancer of gastric motility, which contains acylglycerol and / or oleic acid as an active ingredient.

[0054] The composition and agent of the present invention can be provided in the forms of pharmaceuticals and quasi-pharmaceuticals (such as pharmaceutical compositions), foods (such as food compositions), feeds (such as feed compositions), etc., and can be implemented as described below.

[0055] The acylglycerol and oleic acid of the present invention can be orally administered to humans and non-human animals. As oral preparations, granule, powder, tablet (including sugar-coated tablet), pill, capsule, syrup, emulsion, and suspension can be mentioned. These preparations can be formulated using pharmaceutically acceptable carriers by the methods commonly used in the art. As pharmaceutically acceptable carriers, excipients, binders, diluents, additives, flavors, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc. can be mentioned.

[0056] Depending on the form of the composition and agent of the present invention, the acylglycerol and oleic acid of the present invention can also be administered into the body of humans and non-human animals by means other than oral administration, such as intragastric administration and nasogastric intubation. For example, by preparing the composition and agent of the present invention into a viscous liquid composition containing the acylglycerol and oleic acid of the present invention, or a semi-solid composition containing the acylglycerol and oleic acid of the present invention, humans and non-human animals with reduced chewing and swallowing functions, who are unable to ingest or be orally administered, can be made to ingest or be administered. By ingesting or administering the composition and agent of the present invention by means other than oral ingestion, even if the chewing and swallowing functions of the ingestion or administration object are not developed due to young age, or are reduced due to aging, etc., a promoting effect on the secretion of ghrelin in the object can be expected.

[0057] The acylglycerol and oleic acid of the present invention can be orally ingested by humans and non-human animals. When orally ingesting the acylglycerol and oleic acid of the present invention, it can be in a separated, refined or crudely refined form, or in the form of a food or a food raw material containing the acylglycerol and oleic acid of the present invention.

[0058] When the acylglycerol and oleic acid of the present invention are provided as foods, the foods can contain them, and such foods are foods containing an effective amount of the acylglycerol and oleic acid of the present invention. When the acylglycerol and oleic acid of the present invention are provided as foods in the present invention, foods or raw materials already containing them can also be provided as the foods of the present invention, and such foods are foods containing an effective amount of the acylglycerol and oleic acid of the present invention. Here, the "containing an effective amount" of the acylglycerol and oleic acid of the present invention means that when the amount usually consumed in each food is ingested, the content of the acylglycerol and oleic acid of the present invention is ingested within the range described below. In addition, "foods" are used in the sense of including health foods, functional foods, health functional foods (such as foods for specified health uses, foods with nutrient functions, functionally labeled foods), foods for special purposes (such as foods for those with swallowing difficulties, infant formula milk, milk powder for pregnant and lactating women, foods for patients), nutritional supplements (supplements), and foods for infants and young children.

[0059] The form of the "foods" is not particularly limited. For example, it can be in a liquid form such as a beverage or a liquid food, or in a paste, semi-liquid, or gel form, or in a solid, bar, or powder form. When the use form of the composition and agent of the present invention is in powder form, it can be manufactured by means such as spray drying and freeze drying.

[0060] When the composition and agent of the present invention are provided as foods containing the acylglycerol and / or oleic acid of the present invention, in addition to blending the acylglycerol and / or oleic acid of the present invention, they can be manufactured according to the usual food manufacturing methods. That is, regardless of the form of liquid, solid, powder, etc., of the foods of the present invention, the acylglycerol and / or oleic acid of the present invention can be added to various foods (such as milk, soft drinks, fermented milk, yogurt, chocolate, gummy candies, cheese, bread, biscuits, cookies, soda crackers, pizza crusts, jellies, ice cream, high-energy nutritional supplements, high-energy pastes, formula milk powder, liquid foods, foods for special purposes, foods for patients, comprehensive nutritional foods, nutritional supplements, frozen foods, processed foods, other commercially available foods) or their raw materials for preparation. In addition, the subject itself can also ingest the acylglycerol and oleic acid of the present invention in various forms (liquid, solid, powder, paste, etc.) by adding them to water, food and drink, and food. In particular, in the present invention, by blending an effective amount of the acylglycerol and oleic acid of the present invention in a liquid food, a food with the function of promoting ghrelin secretion can be prepared, and such a food can be ingested by infants and young children with undeveloped chewing and swallowing functions or patients and the elderly with reduced chewing and swallowing functions, or given to infants and young children with undeveloped chewing and swallowing functions or patients and the elderly with reduced chewing and swallowing functions, so it is advantageous.

[0061] When the composition and agent of the present invention are provided in the form of foods and raw materials (especially processed raw materials) already containing the acylglycerol and / or oleic acid of the present invention, examples of such foods and raw materials include edible oils such as lard and vegetable oils (olive oil, high-oleic sunflower oil, and high-oleic safflower oil).

[0062] The composition and agent of the present invention are suitable for ingestion by infants, the elderly, or the aged who require the action of promoting ghrelin secretion.

[0063] In the present invention, for example, the acylglycerol and oleic acid of the present invention can be combined with other raw materials and the like to provide a composition, supplement, etc. for the purpose of promoting ghrelin secretion.

[0064] The daily intake or dosage of the composition and agent of the present invention as a medicine or food varies depending on the condition, age, symptoms, weight, use, etc. of the subject, and thus is not particularly limited. When ingested and administered for the purpose of promoting ghrelin secretion, the daily intake or dosage (in terms of solid components) of the acylglycerol and oleic acid of the present invention for adults is not particularly limited. The lower limit is, for example, 0.01 g, preferably 0.1 g. In addition, the upper limit is, for example, 65 g or 60 g, preferably 5 g or 1 g. These lower limit values and upper limit values can be arbitrarily combined. In addition, the frequency and frequency of ingestion or administration can be appropriately determined according to the degree of the action of promoting ghrelin secretion required. The intake and dosage, as well as the intake interval and administration interval, can be determined by the attending physician, pharmacist, dietitian, nutritionist, care welfare worker, care administrator, assistant, staff of the care facility, caregiver such as the family member of the subject, or the subject himself / herself.

[0065] There is no limitation on the combined use of the composition and agent of the present invention with other orally ingestible compositions and agents. For example, by combining with raw materials and compositions such as fermented milk and lactic acid bacteria that can be expected to have the effect of promoting ghrelin secretion, the effect of promoting ghrelin secretion can be further improved.

[0066] The composition and agent of the present invention can be provided in the form of a composition and agent with an intake amount effective for promoting ghrelin secretion in a daily dose. In this case, the composition and agent of the present invention can be packaged in such a way that the effective intake amount of the acylglycerol and oleic acid of the present invention can be ingested. As long as the effective intake amount of the daily dose can be ingested, the packaging form can be a single package or multiple packages. When provided in a packaged form, it is preferably recorded in the package in a manner related to the intake amount so that the effective intake amount of the daily dose can be ingested, or a text with such a record is provided together. In addition, when multiple packages of the effective intake amount of the daily dose are provided, for the convenience of intake, multiple packages of the effective intake amount of the daily dose can also be provided as a set.

[0067] The packaging form for providing the composition and agent of the present invention is not particularly limited as long as it is a form that defines a certain amount. For example, it can be exemplified by containers that can accommodate such as wrapping paper, bags, flexible bags, paper containers, cans, bottles, capsules, etc.

[0068] In order to better exert the effects of the composition and agent of the present invention, it is desirable to continuously administer or ingest for at least 1 week. The administration and ingestion period is preferably more than 2 weeks (for example, 2 to 14 weeks), and more preferably more than 3 weeks (for example, 3 to 21 weeks). Here, "continuously" means administering or ingesting at least continuously once a week (for example, 1 to 7 times). When the composition and agent of the present invention are provided in a packaged form, for continuous ingestion, the effective intake amount for a certain period (for example, 1 week) can be provided as a set.

[0069] The food of the present invention can also carry a label with the meaning of having the following effects: the effect of promoting ghrelin secretion, the effect of promoting or enhancing appetite, the effect of improving or alleviating anorexia, the effect of promoting or enhancing the secretion of growth hormone, the effect of improving or alleviating malnutrition, the effect of promoting or enhancing fat accumulation, the effect of increasing body weight, the effect of promoting or enhancing gastric acid secretion, or the effect of promoting or enhancing gastric motility. In this case, in order to make the label easy for consumers to understand, the following part or all of the labels can also be attached to the food of the present invention.

[0070] · Helps to improve the appetite that decreases with age.

[0071] · Helps to improve anorexia caused by stress and fatigue.

[0072] · Ghrelin has the effect of promoting the secretion of growth hormone that decreases with age. It is known that growth hormone has effects such as promoting protein synthesis, tissue repair and regeneration, and fatigue recovery.

[0073] · Helps to improve the malnourished state that is prone to occur with age.

[0074] · It helps to improve the low-nutrition state based on stress and fatigue.

[0075] · It has the effect of promoting lipid accumulation, and the lipid helps to supplement the energy that is prone to deficiency with age.

[0076] · It has the effect of promoting lipid accumulation, and the lipid helps to supplement the energy that is prone to deficiency due to stress and fatigue.

[0077] · It helps to maintain and increase the body weight that decreases with age.

[0078] · It helps to maintain and increase the body weight that decreases due to stress and fatigue.

[0079] · It improves the gastric acid secretion ability that decreases with age and helps to promote digestion.

[0080] · It improves the gastric motility that decreases with age and helps to promote digestion.

[0081] According to another aspect of the present invention, there is provided a method for promoting ghrelin secretion, a method for promoting or enhancing appetite, a method for improving or alleviating anorexia, a method for promoting or enhancing growth hormone secretion, a method for improving or alleviating malnutrition, a method for promoting or enhancing fat accumulation, a method for increasing body weight, a method for promoting or enhancing gastric acid secretion, or a method for promoting or enhancing gastric motility, which comprises administering or giving an effective amount of the acylglycerol and oleic acid of the present invention, or a composition containing the same, to a subject in need. The method of the present invention can be carried out according to the description of the composition and agent of the present invention.

[0082] According to another aspect of the present invention, there is provided a use of acylglycerol and oleic acid of the present invention, or a composition containing the same, which is used for manufacturing a ghrelin secretion promoter, an appetite promoter or enhancer, an anorexia improver or reliever, a growth hormone secretion promoter or enhancer, a malnutrition improver or reliever, a fat accumulation promoter or enhancer, a weight gain agent, a gastric acid secretion promoter or enhancer, or a gastric motility promoter or enhancer; or, the use is as a ghrelin secretion promoter, an appetite promoter or enhancer, an anorexia improver or reliever, a growth hormone secretion promoter or enhancer, a malnutrition improver or reliever, a fat accumulation promoter or enhancer, a weight gain agent, a gastric acid secretion promoter or enhancer, or a gastric motility promoter or enhancer; or, the use is for a method of promoting ghrelin secretion, a method of promoting or enhancing appetite, a method of improving or relieving anorexia, a method of promoting or enhancing growth hormone secretion, a method of improving or relieving malnutrition, a method of promoting or enhancing fat accumulation, a method of increasing weight, a method of promoting or enhancing gastric acid secretion, or a method of promoting or enhancing gastric motility. The use of the present invention can be implemented according to the descriptions of the composition and agent of the present invention and the method of the present invention.

[0083] According to still another aspect of the present invention, there is provided acylglycerol and oleic acid of the present invention, or a composition containing the same, which is used for promoting ghrelin secretion, promoting or enhancing appetite, improving or relieving anorexia, promoting or enhancing the secretion of growth hormone, improving or relieving malnutrition, promoting or enhancing fat accumulation, increasing weight, promoting or enhancing gastric acid secretion, or promoting or enhancing gastric motility. These inventions can be implemented according to the descriptions of the composition and agent of the present invention and the method of the present invention.

[0084] The method and use of the present invention can be used in mammals including humans, considering both therapeutic and non-therapeutic uses. In this specification, "non-therapeutic" means not including the acts of performing surgery, treatment or diagnosis on humans (i.e., medical acts on humans), specifically, it means not including the methods of performing surgery, treatment or diagnosis on humans by doctors or those under the instructions of doctors.

[0085] Examples

[0086] The present invention will be more specifically described based on the following examples, but the present invention is not limited to these examples.

[0087] Example 1: Effects of acylglycerol and fatty acid on the secretion of active ghrelin

[0088] (1) Test method

[0089] In a 96-well plate at 1×10 5Inoculate ghrelin-secreting cell line MGN3-1 derived from mouse stomach at a density of Figure 2 cells / well, and culture in medium for 24 hours. After culturing, wash the cells with 200 μL of Dulbecco’s PBS, and add 100 μL of a solution containing the test substance shown in Table 1 (buffer: 50 μM sodium caprylate / DMEM) (test group). The concentration of the test substance is set to 10 μM or 30 μM. Additionally, add 100 μL of buffer without the test substance to the control group. Each group is performed with a test number of n = 4. After culturing each group for 2 hours, collect the culture medium, and obtain 80 μL of supernatant through centrifugation (800 g, 5 minutes, 4 °C). Add 8 μL of 1 N HCl to the supernatant and store at -80 °C. Then, measure the active ghrelin (acylated ghrelin) in the sample by ELISA method (Ghrelin(Acylated)EIAKit A05117, Bertin Pharma). Calculate the average value of the measured values of ghrelin secretion concentration when the test substances shown in Table 2 or Table 3 are added, and express it as a value (%) with the control set to 100 (Tables 2 and 3). Repeat the experiment using the same test method as above, and measure the secretion concentration of active ghrelin (acylated ghrelin) in the sample (

[0090] [Table 1]

[0091] Table 1: Test substance names and CAS registry numbers

[0092]

[0093] (2) Statistical analysis

[0094] Perform t-test or one-way ANOVA (one-way analysis of variance), and use Tukey-Kramer test for multiple comparison tests.

[0095] (3) Results

[0096] The results are shown in Tables 2 and 3 and Figure 1 and 2 as shown.

[0097] [Table 2]

[0098] Table 2: Concentration dependence of acylglycerol and fatty acid on the secretion of active ghrelin

[0099]

[0100] [Table 3]

[0101] Table 3: Secretion concentrations of active ghrelin based on acylglycerol and fatty acid (30 μL each)

[0102]

[0103] As shown in Table 2, oleic acid, 2-monopalmitin, 1-monoolein, and 2-monoolein increased the concentration of active ghrelin to about 1.5 to 2 times compared with the control. In addition, for palmitic acid and 1-monopalmitin (10 μM), although no difference from the control was confirmed, for 1-monopalmitin (30 μM), an increase in the concentration of active ghrelin was observed compared with the control.

[0104] As shown in Table 3, oleic acid, 2-monopalmitin, 1-monoolein, 2-monoolein, 1-oleoyl-2-palmitoyl glycerol (OP), and 1-palmitoyl-2-oleoyl glycerol (PO) increased the concentration of active ghrelin to about 2 to 4 times compared with the control. In addition, in 1,3-dioleoyl-2-palmitoyl glycerol (OPO) and 1,3-dipalmitoyl-2-oleoyl glycerol (POP), an increase in the concentration of active ghrelin was observed compared with the control.

[0105] As Figure 1 shown, 2-monopalmitin significantly increased the concentration of active ghrelin to about 1.2 times compared with the control.

[0106] As Figure 2 shown, 2-monopalmitin, 1-monoolein, and 2-monoolein significantly increased the concentration of active ghrelin to about 1.5 to 3 times compared with the control.

[0107] Regarding the results in Table 3, as described above, it was shown that 1-oleoyl-2-palmitoyl glycerol (OP), 1-palmitoyl-2-oleoyl glycerol (PO), 1,3-dioleoyl-2-palmitoyl glycerol (OPO), and 1,3-dipalmitoyl-2-oleoyl glycerol (POP) had an effect of promoting ghrelin secretion. On the other hand, there was no gastric lipase in this experimental system. Here, it is known that triacylglycerol is specifically hydrolyzed at the sn-3 position by gastric lipase in the stomach (ghrelin-secreting cells are present in the gastric mucosa) to produce free fatty acids and diacylglycerol (Rogalska et al., JBC, 1990, 265, 33: 20271-20276). Therefore, it was suggested that acylglycerols (e.g., triacylglycerols such as OPO and POP) that produce 1-oleoyl-2-palmitoyl glycerol (OP) or 1-palmitoyl-2-oleoyl glycerol (PO) by physiological hydrolysis using gastric lipase also promote ghrelin secretion.

[0108] Example 2: Blending examples in food compositions for infants and young children

[0109] Regarding the food composition for infants and young children of the present invention, typical components (per 100 kcal) are shown in Table 4.

[0110] [Table 4]

[0111] Table 4: Blending components of food compositions for infants and young children

[0112]

[0113] Example 3: Blending examples in food compositions for the elderly

[0114] Regarding the food composition for the elderly of the present invention, typical components (per 100 ml) are shown in Table 5.

[0115] [Table 5]

[0116] Table 5: Blending components of food compositions for the elderly

[0117]

[0118] ※ μgRAE in the table represents the retinol activity equivalent, and mgNE represents the equivalent of niacin.

[0119] Industrial applicability

[0120] By providing a method for manufacturing a food containing acylglycerol and / or free fatty acids with high safety, it is possible to enable the normal development of the appetite regulation function required for the intake target including infants and young children to intake the necessary energy, and to develop the function through the physiological action of growth hormone, prevent or improve the loss of appetite or reduced energy intake in the elderly, and the reduction of muscle mass or muscle strength caused by reduced growth hormone secretion, which contributes to the improvement of national health.

Claims

1. A composition for promoting ghrelin secretion, which contains one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid as an active ingredient.

2. The composition according to claim 1, wherein, In the acylglycerol, palmitic acid and / or oleic acid are bonded to the sn-1 position and / or sn-2 position of glycerol.

3. The composition according to claim 1, wherein, The acylglycerol contains palmitic acid and oleic acid as constituent fatty acids.

4. The composition according to claim 2, wherein In the acylglycerol, any fatty acid is bonded to the sn-3 position of glycerol.

5. The composition according to claim 4, wherein Any fatty acid is palmitic acid or oleic acid.

6. The composition according to claim 1, wherein, The acylglycerol is one or more selected from the group consisting of 1-mono-palmitin, 2-mono-palmitin, 1-mono-olein, 2-mono-olein, 1-oleoyl-2-palmitoyl glycerol, 1-palmitoyl-2-oleoyl glycerol, 1,3-dioleoyl-2-palmitoyl glycerol, and 1,3-dipalmitoyl-2-oleoyl glycerol.

7. The composition according to claim 1, wherein, The content of the active ingredient relative to the composition is 1 to 95% by mass.

8. The composition according to claim 1, which is used for promoting appetite, improving anorexia, promoting the secretion of growth hormone, improving malnutrition, promoting fat accumulation, increasing body weight, enhancing gastric acid secretion, or enhancing gastric motility.

9. The composition according to claim 1, which is a food composition.

10. The composition according to claim 1, which is for ingestion by infants and / or the elderly.

11. A method for promoting ghrelin secretion, a method for promoting or enhancing appetite, a method for improving or alleviating anorexia, a method for promoting or enhancing growth hormone secretion, a method for improving or alleviating malnutrition, a method for promoting or enhancing fat accumulation, a method for increasing body weight, a method for promoting or enhancing gastric acid secretion, or a method for promoting or enhancing gastric motility, comprising: Administering or giving to a subject in need one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid, or a composition containing the same.

12. Use of one or more selected from the group consisting of acylglycerols containing palmitic acid and / or oleic acid as constituent fatty acids and oleic acid, or a composition containing the same, for the manufacture of a ghrelin secretion promoter, an appetite promoter or enhancer, an anorexia improver or reliever, a growth hormone secretion promoter or enhancer, a malnutrition improver or reliever, a fat accumulation promoter or enhancer, a weight gain agent, a gastric acid secretion promoter or enhancer, or a gastric motility promoter or enhancer; or, the use as a ghrelin secretion promoter, an appetite promoter or enhancer, an anorexia improver or reliever, a growth hormone secretion promoter or enhancer, a malnutrition improver or reliever, a fat accumulation promoter or enhancer, a weight gain agent, a gastric acid secretion promoter or enhancer, or a gastric motility promoter or enhancer; or, the use in a method for promoting ghrelin secretion, a method for promoting or enhancing appetite, a method for improving or relieving anorexia, a method for promoting or enhancing growth hormone secretion, a method for improving or relieving malnutrition, a method for promoting or enhancing fat accumulation, a method for increasing body weight, a method for promoting or enhancing gastric acid secretion, or a method for promoting or enhancing gastric motility.

13. An acylglycerol selected from the group consisting of those containing palmitic acid and / or oleic acid as constituent fatty acids, oleic acid, or one or more of these, or a composition containing the same, which is used for promoting ghrelin secretion, promoting or enhancing appetite, improving or alleviating anorexia, promoting or enhancing growth hormone secretion, improving or alleviating malnutrition, promoting or enhancing fat accumulation, increasing body weight, promoting or enhancing gastric acid secretion, or promoting or enhancing gastric motility.

Images