JP2016094347A - Somatostatin concentration increasing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a somatostatin concentration increasing agent that is capable of increasing somatostatin concentrations and can be administered easily continuously.SOLUTION: A somatostatin concentration increasing agent comprises docosahexaenoic acid, or a salt or ester thereof as an active ingredient.SELECTED DRAWING: None

Description

  The present invention relates to a somatostatin concentration-increasing agent.

  Somatostatin (SST) is a peptide hormone discovered as a growth hormone secretion inhibitor. SST is produced in the hypothalamus of the brain, pancreatic Langerhans islet D cells, endocrine cells (D cells) of the gastrointestinal tract, etc. In addition to inhibiting growth hormone secretion, it inhibits insulin and glucagon secretion, secretin and gastric acid secretion, etc. It is also known as a neurotransmitter. After biosynthesis, SST is converted into SST-14 consisting of 14 peptides in the pancreas and hypothalamus by post-translational processing, and into SST-28 consisting of 28 peptides in the gastrointestinal tract, and released into the blood for paracrine and auto It exhibits a kulin regulating action.

  Acromegaly is a disease in which the tip of the body, such as the forehead, chin, and limbs, is enlarged due to excessive secretion of growth hormone from the pituitary gland. Furthermore, if excessive growth hormone secretion continues due to acromegaly, complications such as diabetes, hypertension, and hyperlipidemia develop, which further worsens angina, myocardial infarction, cerebrovascular disorder, etc. There is a risk of causing. Therefore, early detection and early treatment are important for acromegaly.

  For the treatment of acromegaly, surgical treatment to remove the pituitary tumor (transsphenoid sinus pituitary tumor excision; TSS) is the first option, and when surgery is difficult or surgery does not improve, Drug therapy is performed. As main therapeutic agents, somatostatin analogs (such as octreotide), GH receptor antagonists (such as pegvisomant), and dopamine receptor agonists (such as bromocriptine) are known. However, these therapeutic agents have a short half-life in vivo and must be administered every day, and also cause side effects such as injection site pain, diarrhea, nausea / vomiting, and gastrointestinal motility disorders. large. Thus, somatostatin analog sustained-release preparations have been proposed to overcome the shortcomings associated with the short half-life of conventional therapeutic agents for acromegaly (Patent Documents 1 to 3).

  On the other hand, ω3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) are known to have various physiological functions such as cardiovascular disorders, dyslipidemia, anti-inflammatory action, anticancer action, and central action. For example, Patent Document 4 describes the use of pharmaceutical preparations containing DHA for the treatment of cardiovascular disorders, nutritional disorders, central nervous system disorders, autoimmune disorders, inflammatory disorders, or chronic pain. ing. Patent Document 5 describes the use of DHA for the treatment of cats with inflammatory bowel disease. However, it has never been known that DHA is involved in the regulation of somatostatin concentration.

Special table 2011-526289 Special table 2010-529982 gazette Special table 2008-535882 Special table 2009-520824 Special table 2009-525949 gazette

  An object of the present invention is to provide an agent for increasing SST concentration that can increase the concentration of somatostatin (SST) and can be easily administered continuously.

  As a result of examining the effect of many naturally-occurring components on the concentration of SST, the present inventors have found that blood SST concentration is increased by oral administration or ingestion of docosahexaenoic acid (DHA).

Therefore, the present invention provides a somatostatin concentration-increasing agent containing docosahexaenoic acid, or a salt or ester thereof as an active ingredient.
The present invention also provides a somatostatin concentration-increasing agent comprising an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof as an active ingredient.
Furthermore, this invention provides the ameliorating agent of the acromegaly which uses docosahexaenoic acid or its salt or ester as an active ingredient.
Furthermore, this invention provides the ameliorating agent of the acromegaly which uses the fats and oils composition containing docosahexaenoic acid, its salt, or ester as an active ingredient.

  The SST concentration increasing agent of the present invention can increase blood SST concentration by oral administration or ingestion. The SST concentration increasing agent of the present invention is useful for improving diseases and conditions associated with excess growth hormone such as acromegaly.

Change in blood somatostatin concentration by DHA administration. A: Transition of concentration (*; p <0.05), B: iAUC (0-1h) relative value (*; p <0.05).

  As used herein, “an increase in somatostatin (SST) concentration” refers to an increase in blood SST concentration, and more specifically, a transient or continuous increase in blood SST concentration. Preferably, the transient increase refers to an increase in blood SST concentration within 30 minutes after administration of the SST concentration increasing agent, and the continuous increase refers to after 30 minutes after administration of the SST concentration increasing agent. Increase in blood SST concentration.

  As used herein, “improvement” refers to improvement of a disease, symptom or condition, prevention or delay of worsening of the disease, symptom or condition, or reversal, prevention or delay of progression of a disease or symptom.

  The SST concentration increasing agent of the present invention contains DHA or a salt or ester thereof as an active ingredient. The salt or ester of DHA is not particularly limited as long as it can be used in pharmaceuticals or foods. Examples of the salt include sodium salt and calcium salt. Examples of the ester include methyl ester and ethyl ester. .

  The DHA or salt or ester thereof contained as an active ingredient in the SST concentration increasing agent of the present invention may be in the form of acylglycerol. The acylglycerol may be monoacylglycerol, diacylglycerol or triacylglycerol containing DHA as a fatty acid (constituent fatty acid) bonded to the glycerol skeleton, or a salt or ester thereof, or a mixture thereof.

  When the acylglycerol is diacylglycerol or triacylglycerol, at least one of the constituent fatty acids of the di- or triacylglycerol is DHA, or a salt or ester thereof. The constituent fatty acid of the di- or triacylglycerol may contain other fatty acid other than the DHA, or a salt or ester thereof, and the other fatty acid may be either a saturated fatty acid or an unsaturated fatty acid. Good. Preferably, in the other fatty acids, preferably 70 to 100% by mass, more preferably 75 to 100% by mass, and still more preferably 80 to 98% by mass are unsaturated fatty acids, and the carbon number of the unsaturated fatty acids is Preferably it is 14-26, More preferably, it is 16-24. Preferably, the carbon number of the saturated fatty acid contained in the other fatty acid is preferably 14 to 24, more preferably 16 to 24. The content of medium chain fatty acids having 8 to 10 carbon atoms in the other fatty acids is preferably 5% by mass or less, more preferably 0 to 2% by mass, and still more preferably 0 to 1% by mass. Preferably, the content of trans-unsaturated fatty acid in the other fatty acid is preferably 0 to 4% by mass, more preferably 0.1 to 3.5% by mass, and still more preferably 0.2 to 3% by mass. It is.

  The SST concentration increasing agent of the present invention can also contain an oil or fat composition containing DHA or a salt or ester thereof as an active ingredient. Examples of the oil / fat composition include an oil / fat composition containing DHA or a salt or ester thereof in the form of a free fatty acid or the acylglycerol described above.

  The content of DHA, its salt or ester in the oil composition is preferably 0.01% by mass or more, more preferably in terms of the mass of DHA (free form) in the total fatty acid mass contained in the oil composition. Preferably it is 0.1-50 mass%, More preferably, it is 1-30 mass%.

  The oil and fat composition may further contain free fatty acid, monoacylglycerol, diacylglycerol, or triacylglycerol other than the above-mentioned DHA, salts or esters thereof, and acylglycerol containing them.

  Preferably, the total triacylglycerol content in the oil composition is preferably 85% by mass or more, more preferably 88-99.8% by mass, and still more preferably 90-90%, based on the total mass of the oil composition. It is 99.5 mass%, More preferably, it is 92-99% mass. Preferably, the total diacylglycerol content in the oil composition is preferably 0 to 5% by mass, more preferably 0 in the total mass of the oil composition in terms of industrial productivity and stability. It is -4 mass%, More preferably, it is 0.1-3 mass%. Preferably, the content of the total monoacylglycerol in the oil / fat composition is preferably 0 to 5% by mass, more preferably 0 in the total mass of the oil / fat composition from the viewpoint of flavor and industrial productivity. It is -2 mass%, More preferably, it is 0.1-2 mass%. Preferably, the content of the total free fatty acid or a salt or ester thereof contained in the oil / fat composition is, in terms of flavor and industrial productivity, in the total mass of the oil / fat composition, preferably 5% by mass or less, More preferably, it is 0-2 mass%, More preferably, it is 0-1 mass%.

DHA and salts or esters thereof can be purified by a conventional method from a mixture of fats and oils derived from natural products rich in DHA, such as fish oil, sea animal oil, microbial oil, algal oil and the like. Or a commercial item can be used for DHA, its salt, or ester.

  Acylglycerol containing DHA or a salt or ester thereof as a constituent fatty acid can be synthesized by a condensation reaction of glycerol and a fatty acid according to a known method. Or it can obtain by performing transesterification etc. so that it may become a fatty-acid composition which desires edible fats and oils according to a conventional method, and refine | purifies as needed. The edible fat may be any of vegetable oil and animal fat, such as rapeseed oil (canola oil), sunflower oil, corn oil, soybean oil, linseed oil, sesame oil, rice oil, safflower oil, cottonseed oil, Palm oil, palm oil, olive oil, grape oil, avocado oil, sesame oil, peanut oil, macadamia nut oil, hazelnut oil, walnut oil; lard, beef tallow, chicken oil, butter oil, coconut oil, coconut oil, coconut oil, squid Oil, fish oil such as mackerel oil, sea animal oil such as whale oil, microbial oil, algal oil, and a mixture or mixture thereof. Especially, it is preferable to use fish oil, sea animal oil, microbial oil, algal oil, or a mixture thereof from the point which contains DHA abundantly as a constituent fatty acid. Commercial products may be used for these edible oils and fats.

  Examples of the raw material of the fat composition containing the DHA, its salt or ester, or acylglycerol include the above-mentioned edible fat and oil, its hydrogenated product, and fats and oils whose fatty acid composition is adjusted by subjecting them to a transesterification reaction or the like. . From the viewpoint of reducing the content of trans-unsaturated fatty acids in the oil / fat composition, it is preferable to use non-hydrogenated oil / fat as a raw material.

  The oil and fat composition preferably contains an antioxidant from the viewpoint of oxidative stability during storage and cooking. Examples of the antioxidant include one or more selected from natural antioxidants, tocopherol, ascorbyl palmitate, ascorbyl stearate, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), and the like. The content of the antioxidant in the oil / fat composition is preferably 0.01 to 2% by mass, more preferably 0.01 to 1% by mass, and still more preferably 0.01 to 0.5% by mass.

  As shown in Examples below, ingestion of DHA, its salt or ester results in an increase in blood SST concentration. Therefore, DHA or a salt or ester thereof, acylglycerol containing the same, or an oil or fat composition containing them can be used for increasing the SST concentration.

  In addition, since SST is a growth hormone secretion inhibitor, increasing its concentration suppresses growth hormone secretion and is useful for improving diseases and conditions associated with excessive growth hormone such as acromegaly. is there. Therefore, DHA or a salt or ester thereof, acylglycerol containing the same, or an oil / fat composition containing them is useful for improving acromegaly.

  Therefore, in one aspect, the present invention provides an SST concentration increasing agent containing DHA, or a salt or ester thereof as an active ingredient. Moreover, this invention provides the SST density | concentration raiser which uses the fats and oils composition containing DHA or its salt or ester as an active ingredient. Furthermore, this invention provides the acromegaly improving agent which uses DHA or its salt or ester as an active ingredient. Furthermore, this invention provides the acromegaly improving agent which uses the oil-and-fat composition containing DHA or its salt or ester as an active ingredient.

  In another aspect, the present invention provides DHA, or a salt or ester thereof, for use in improving acromegaly. Moreover, this invention provides the fats and oils composition containing DHA for using it for acromegaly improvement, or its salt or ester.

  In yet another aspect, the present invention provides the use of DHA, or a salt or ester thereof, for the manufacture of an agent for increasing SST concentration, or an agent for improving acromegaly. Moreover, this invention provides use of the fat and oil composition containing DHA, its salt, or ester for manufacture of a SST concentration increasing agent or an acromegaly improvement agent.

  In yet another aspect, the present invention provides the use of DHA, or a salt or ester thereof, for increasing SST concentration. Moreover, this invention provides use of the fats and oils composition containing DHA, its salt, or ester for a raise of SST density | concentration.

  The use can be in humans or non-human animals, or specimens derived therefrom. Examples of the non-human animal include, but are not limited to, non-human mammals such as dogs, cats, hamsters, mice, rats, rabbits, horses, cows, pigs, sheep, goats, monkeys, and the like. Examples of the specimen include a neuroendocrine cell in the hypothalamus of a brain derived from a mammal, a pancreatic Langerhans islet D cell, an endocrine cell (D cell) in the digestive tract, a tissue containing them, or a culture of these cells or tissues, etc. However, it is not limited to these.

  The said DHA, its salt or ester, or the oil-and-fat composition containing them can be used for manufacture of a pharmaceutical, a quasi-drug, food / beverage products, feed, etc. as an active ingredient for a SST density | concentration raise. The medicine, quasi drug, food and drink, feed and the like can be produced for human or non-human animals. The kind of the non-human animal is as described above.

  The said pharmaceutical and quasi-drug contain the said DHA, its salt or ester, or the oil-fat composition containing them as an active ingredient for a SST density | concentration raise. The medicine and quasi-drug may contain other active ingredients, pharmacological ingredients and the like as long as the SST concentration increasing action of the present invention is not lost. Preferably, the medicament is an acromegaly drug.

  The medicine and quasi-drug are obtained from the DHA, a salt or ester thereof, or an oil or fat composition containing them, or if necessary, a pharmaceutically acceptable carrier, the other active ingredients or pharmacological ingredients. In combination, it can be produced by a conventional method. The drug and quasi drug can be prepared in any dosage form, but are preferably prepared in an oral dosage form.

  The said food-drinks and feed contain the said DHA, its salt or ester, or the oil-fat composition containing them as an active ingredient for a SST density | concentration raise. The food and drink and feed are intended to obtain a function of increasing SST concentration, and the food and drink, functional food and drink, health food, food and drink for the sick, food and drink for specified health, which are displayed as necessary. , Feed, pet food and the like. In addition, food / beverage products, functional food / beverage products, health foods, food / beverage foods for the sick, and food / beverage products for specified health use that are designated as necessary, It is distinguished from food and drink.

  The food and drink includes all forms and types of foods and beverages. For example, the form of food includes any form such as solid, semi-solid, and liquid. The feed is the above-described feed or pet food for non-human animals and includes all forms and types. These foods and drinks and feeds can be produced by a conventional method by appropriately combining the above DHA, a salt or ester thereof, or an oil and fat composition containing them with additives that can be used for foods, foods and feeds.

  The content of the DHA, its salt or ester, or the oil or fat composition containing them in the pharmaceutical and quasi-drug is 0.01 to 100% by mass in the total mass in terms of the mass of DHA (free form). However, it is preferably 0.1 to 100% by mass, more preferably 1 to 100% by mass, and further preferably 5 to 100% by mass.

  Content of the said DHA, its salt or ester, or the oil-fat composition containing them in the said food-drinks and feed may differ with the usage forms. For example, in the case of a liquid form such as a beverage or liquid feed, it may be 0.01 to 50% by mass, preferably 0.01 to 20% by mass, more preferably, in terms of the mass of DHA (free body). It is 0.01-10 mass%, More preferably, it is 1-50 mass%, More preferably, it is 5-50 mass%. Further, for example, in the case of solid forms such as tablets, solid foods, solid feeds, etc., it may be 0.001 to 100% by mass, preferably 0.01 to 80% by mass, in terms of the mass of DHA (free body). More preferably, it is 0.01-50 mass%, More preferably, it is 1-80 mass%, More preferably, it is 5-50 mass%.

  In yet another aspect, the present invention provides a method for increasing a subject's SST concentration. The present invention also provides a method for improving acromegaly in a subject. The method of the present invention includes orally administering or ingesting the subject with the DHA, a salt or ester thereof, or an oil or fat composition containing them in an effective amount.

  Examples of the “subject” in the method of the present invention include animals that require an increase in blood SST concentration and animals that require improvement of acromegaly. Examples of the target animal include humans and the above-described non-human animals, preferably humans.

  The “effective amount” of oral administration or ingestion of the DHA, salt or ester thereof, or oil / fat composition containing them in the method of the present invention is according to the species, condition, weight, sex, age or other factors of the subject. Although it may fluctuate, 0.1-20 g / day is preferable in terms of the amount of DHA (free body) for adults (60 kg). The DHA, a salt or ester thereof, or an oil or fat composition containing them can be applied to a subject according to any administration schedule, but is preferably administered or taken orally once to several times a day.

  Alternatively, the method for increasing the SST concentration of the present invention may be an in vitro or ex vivo method for a mammal-derived tissue, organ, cell, culture thereof, or fraction thereof. The tissues, organs, cells, cultures thereof, or fractions thereof include brain-derived hypothalamic neuroendocrine cells derived from mammals, pancreatic islets of Langerhans D cells, endocrine cells of the digestive tract (D cells), Examples include tissues containing them, or cultures of those cells or tissues, and fractions thereof.

  As exemplary embodiments of the present invention, the following compositions, production methods, uses or methods are further disclosed herein. However, the present invention is not limited to these embodiments.

<1> A somatostatin concentration-increasing agent containing docosahexaenoic acid, or a salt or ester thereof as an active ingredient.

<2> A remedy for acromegaly comprising docosahexaenoic acid, or a salt or ester thereof as an active ingredient.

<3> A somatostatin concentration-increasing agent comprising a fat or oil composition containing docosahexaenoic acid, or a salt or ester thereof as an active ingredient.

<4> An agent for improving acromegaly, comprising an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof as an active ingredient.

<5> The agent according to any one of <1> to <4>, wherein the docosahexaenoic acid or a salt or ester thereof is preferably in the form of acylglycerol.

<6> Preferably, the acylglycerol is monoacylglycerol, diacylglycerol or triacylglycerol containing docosahexaenoic acid or a salt or ester thereof as a constituent fatty acid, or a mixture thereof. Agent.

<7> The agent according to <6>, wherein the diacylglycerol and the triacylglycerol preferably contain a fatty acid other than docosahexaenoic acid, or a salt or ester thereof as a constituent fatty acid.

<8> Preferably, the oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof is an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof in the form of a free fatty acid or acylglycerol, <3 The agent according to any one of> to <7>.

<9> The fat composition contains docosahexaenoic acid in terms of free form, preferably 0.01% by mass or more, more preferably 0.1 to 50% by mass, and even more preferably 1 to 30% by mass, <8 > Agents described.

<10> Preferably, the oil and fat composition further comprises docosahexaenoic acid, a salt or ester thereof, and a free fatty acid other than acylglycerol containing the same, monoacylglycerol, diacylglycerol, or triacylglycerol, <8> or < 9> The agent described.

<11> Use of docosahexaenoic acid or a salt or ester thereof for the production of a somatostatin concentration-increasing agent.

<12> Use of docosahexaenoic acid, or a salt or ester thereof for the production of an agent for improving acromegaly.

<13> Use of an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof for the production of a somatostatin concentration-increasing agent.

<14> Use of an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof for the production of an agent for improving acromegaly.

<15> The use according to any one of <11> to <14>, wherein the docosahexaenoic acid or a salt or ester thereof is preferably in the form of acylglycerol.

<16> Preferably, the acylglycerol is monoacylglycerol, diacylglycerol or triacylglycerol containing docosahexaenoic acid or a salt or ester thereof as a constituent fatty acid, or a mixture thereof. use.

<17> The use according to <16>, wherein the diacylglycerol and the triacylglycerol preferably contain a fatty acid other than docosahexaenoic acid, or a salt or ester thereof as a constituent fatty acid.

<18> Preferably, the oil or fat composition containing docosahexaenoic acid or a salt or ester thereof is an oil or fat composition containing docosahexaenoic acid or a salt or ester thereof in the form of a free fatty acid or acylglycerol. Use of any one of>-<17>.

<19> The oil or fat composition contains docosahexaenoic acid in terms of a free form, preferably 0.01% by mass or more, more preferably 0.1 to 50% by mass, and even more preferably 1 to 30% by mass, <18 > Use as described.

<20> Preferably, the oil and fat composition further comprises docosahexaenoic acid, a salt or ester thereof, and a free fatty acid other than acylglycerol containing the same, monoacylglycerol, diacylglycerol, or triacylglycerol, <18> or < 19> Use as described.

<21> Docosahexaenoic acid or a salt or ester thereof for use in improving acromegaly.

<22> An oil and fat composition containing docosahexaenoic acid, or a salt or ester thereof, for use in improving acromegaly.

<23> The docosahexaenoic acid, a salt or ester thereof, or an oil or fat composition according to <21> or <22>, wherein the docosahexaenoic acid, or a salt or ester thereof is preferably in the form of acylglycerol.

<24> Preferably, the acylglycerol is monoacylglycerol, diacylglycerol or triacylglycerol containing docosahexaenoic acid or a salt or ester thereof as a constituent fatty acid, or a mixture thereof. Docosahexaenoic acid, a salt or ester thereof, or an oil or fat composition.

<25> Preferably, the above-mentioned diacylglycerol and triacylglycerol contain fatty acids other than docosahexaenoic acid, or a salt or ester thereof as constituent fatty acids, or docosahexaenoic acid, a salt or ester thereof, or an oil or fat composition according to <24> .

<26> Preferably, the oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof is an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof in the form of a free fatty acid or acylglycerol. The oil-and-fat composition of any one of>-<25>.

<27> The oil or fat composition contains docosahexaenoic acid in terms of free form, preferably 0.01% by mass or more, more preferably 0.1 to 50% by mass, and even more preferably 1 to 30% by mass, <26 > The oil-and-fat composition described.

<28> Preferably, the oil and fat composition further comprises docosahexaenoic acid, a salt or ester thereof, and a free fatty acid other than acylglycerol containing the same, monoacylglycerol, diacylglycerol, or triacylglycerol, <26> or <26 27> The fat and oil composition described.

<29> A method for increasing somatostatin concentration, comprising orally administering or ingesting docosahexaenoic acid or a salt or ester thereof in an effective amount to a subject.

<30> A method for improving acromegaly, comprising orally administering or ingesting docosahexaenoic acid, or a salt or ester thereof, in an effective amount to a subject.

<31> A method for increasing somatostatin concentration, comprising orally administering or ingesting an effective amount of an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof.

<32> A method for improving acromegaly, which comprises orally administering or ingesting an effective amount of an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof.

<33> The method according to any one of <29> to <32>, wherein the docosahexaenoic acid or a salt or ester thereof is preferably in the form of acylglycerol.

<34> Preferably, the acylglycerol is monoacylglycerol, diacylglycerol or triacylglycerol containing docosahexaenoic acid or a salt or ester thereof as a constituent fatty acid, or a mixture thereof. Method.

<35> The method according to <34>, wherein the diacylglycerol and the triacylglycerol preferably contain a fatty acid other than docosahexaenoic acid, or a salt or ester thereof as a constituent fatty acid.

<36> Preferably, the oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof is an oil or fat composition containing docosahexaenoic acid, or a salt or ester thereof in the form of a free fatty acid or acylglycerol, <31 The method according to any one of> to <35>.

<37> The oil and fat composition contains docosahexaenoic acid in terms of free form, preferably 0.01% by mass or more, more preferably 0.1 to 50% by mass, and even more preferably 1 to 30% by mass, <36 > The method described.

<38> Preferably, the oil and fat composition further comprises docosahexaenoic acid, a salt or ester thereof, and a free fatty acid other than acylglycerol containing the same, monoacylglycerol, diacylglycerol, or triacylglycerol, <36> or < 37>.

  Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1 DHA single dose test (DHA single dose)
Mice fasted for 18 hours (C57BL / 6J, male, 8 weeks old, n = 6; CLEA JAPAN) under anesthesia with a control emulsion (an emulsion containing 2 mg / g body weight of triolein) or an emulsion containing DHA ( An emulsion containing 2 mg / g body weight triolein and 0.4 mg / g body weight DHA) was administered intragastrically. Blood was collected from the orbital venous plexus of each mouse before emulsion administration and at 10, 30 and 60 minutes after administration.

(Measurement of blood components)
The collected blood was centrifuged at 11,000 rpm, 4 ° C. for 6 minutes to prepare plasma. From the prepared plasma samples, the blood somatostatin concentration was measured using a Somatostatin EIA kit (PHOENIX PHARMACEUTICALS, INC.).

(result)
FIG. 1 shows the transition of somatostatin concentration in mouse blood after single administration of the emulsion and the relative value of iAUC (0-1h) (change amount after 0 to 1 hour after administration). The blood somatostatin concentration 10 minutes after administration of the emulsion was significantly higher in the DHA-added emulsion administration group (DHA) than in the control emulsion administration group (Cont) (FIG. 1A, p <0.05). The relative value of somatostatin iAUC was significantly higher in the DHA-added emulsion administration group (DHA) than in the control emulsion administration group (Cont) (FIG. 1B, p <0.05).

Claims (4)

  A somatostatin concentration increasing agent comprising docosahexaenoic acid, or a salt or ester thereof as an active ingredient.   An agent for improving acromegaly comprising docosahexaenoic acid, or a salt or ester thereof as an active ingredient.   A somatostatin concentration-increasing agent comprising a fat or oil composition containing docosahexaenoic acid or a salt or ester thereof as an active ingredient.   A remedy for acromegaly comprising an oil or fat composition containing docosahexaenoic acid or a salt or ester thereof as an active ingredient.

Images