ABC transporter expression promoter, cholesterol excretion promoter, inflammatory cytokine production inhibitor, anti-inflammatory agent, and arteriosclerosis prophylactic agent

Abstract

The purpose of the present invention is to provide an ABC transporter expression promoter, a cholesterol excretion promoter, an inflammatory cytokine production inhibitor, an anti-inflammatory agent, and a prophylactic agent for arteriosclerosis. Provided are an ABC transporter expression promoter, a cholesterol excretion promoter, an inflammatory cytokine production inhibitor, an anti-inflammatory agent, and an arteriosclerosis prophylactic agent, each of which contains at least one substance selected from the group consisting of 10-hydroxypalmitic acid and 16-hydroxypalmitic acid.

Description

Technical Field

[0001] The present invention relates to an ABC transporter expression promoter, a cholesterol excretion promoter, an inflammatory cytokine production inhibitor, an anti-inflammatory agent, and an arteriosclerosis preventive agent. Background Art

[0002] With the increase in lifestyle-related diseases (such as metabolic syndrome), cardiovascular diseases including arteriosclerotic diseases occupy the second place in the causes of death of Japanese people, and the increase in cardiovascular diseases has gradually become a medical problem. Therefore, the prevention and treatment of arteriosclerotic diseases are urgent social issues.

[0003] For example, Patent Document 1 discloses that 10-hydroxyoctadecanoic acid has an effect of inhibiting the accumulation of visceral fat, an effect of inhibiting cholesterol absorption in the intestine, an effect of reducing the concentration of neutral fat in the blood, and an effect of increasing the concentration of small HDL cholesterol in the blood.

[0004] In addition, Patent Document 2 discloses that hydroxy fatty acids, dihydroxy fatty acids, and epoxy fatty acids having 18 carbon atoms have an effect of preventing or improving obesity, hyperlipidemia, arteriosclerosis, and coronary artery diseases.

[0005] In addition, Patent Document 3 discloses that unsaturated fatty acids having 18 or 20 carbon atoms having a hydroxyl group or a carbonyl group at the 13-position, and dihydroxy unsaturated fatty acids having a hydroxyl group also at the 10-position in addition to the 13-position have an effect of improving metabolism.

[0006] In addition, Patent Document 4 discloses that unsaturated fatty acids having 18 carbon atoms, unsaturated fatty acids having 18 carbon atoms having a hydroxyl group or a carbonyl group at the 10-position, 12-position, and 13-position, and dihydroxy unsaturated fatty acids having 18 carbon atoms having a hydroxyl group also at the 13-position in addition to the 10-position have an anti-inflammatory effect.

[0007] In addition, Patent Document 5 discloses that hydroxy unsaturated fatty acids having 18 carbon atoms having a hydroxyl group at the 10-position or 12-position have an effect of improving metabolism.

[0008] Prior Art Documents

[0009] Patent Documents

[0010] Patent Document 1: Japanese Unexamined Patent Application Publication No. 2020-050602

[0011] Patent Document 2: Japanese Unexamined Patent Application Publication No. 2009-051732

[0012] Patent Document 3: Pamphlet of International Publication No. 2015 / 111700

[0013] Patent Document 4: Pamphlet of International Publication No. WO2015 / 111701

[0014] Patent Document 5: Pamphlet of International Publication No. WO2014 / 069227 Summary of the Invention

[0015] Problems to be Solved by the Invention

[0016] ABC (ATP-Binding Cassette) transporters are membrane proteins that participate in the transport of substances across biological membranes using ATP as a driving force.

[0017] ABC transporters are present in various cells and tissues and are important for regulating the material environment inside and outside cells and maintaining the homeostasis of organisms. It is known that their functions or expression levels are reduced due to changes in lifestyle habits, gene mutations, etc. For example, it is known that ABC transporters participate in the cholesterol homeostasis of organisms via lipid transport, and disruption of cholesterol homeostasis can cause hyperlipidemia and then arteriosclerosis.

[0018] Cholesterol is an important component of organisms, is actively synthesized in the liver, and is transported through the bloodstream by lipoproteins as carriers. Lipoproteins are classified into LDL (Low density lipoprotein) and HDL (High density lipoprotein) according to their density. LDL is responsible for transporting cholesterol from the liver to peripheral cells. LDL becomes oxidized LDL by reactive oxygen species in the body. Macrophages phagocytose oxidized LDL, and then foam macrophages accumulate, causing arterial thickening and becoming atherosclerotic lesions. The cholesterol in the remaining atherosclerotic lesion macrophages is transported to the liver by HDL (cholesterol reverse transport). Cholesterol reverse transport consists of multiple steps starting from cholesterol scavenging based on HDL. Specifically, excess cholesterol in peripheral cells is transported out by ABC transporters (such as ABCA1 and ABCG1) and is scavenged by HDL. HDL matures while taking up cholesterol, transfers cholesterol to LDL through a transporter called CETP, and transports cholesterol to the liver via the LDL receptor. A part directly transfers cholesterol to the liver through the HDL receptor (SR-BI).

[0019] As described above, the accumulation of cholesterol in peripheral cells represented by macrophages is one of the causes of arteriosclerosis. On the other hand, cholesterol reverse transport from peripheral cells to the liver is one of the anti-atherosclerotic mechanisms present in organisms. ABC transporters (such as ABCA1 and ABCG1) play an important role in cholesterol reverse transport.

[0020] Arteriosclerosis is a state in which cholesterol, neutral fat, etc. accumulate in the arteries, causing the arteries to thicken and harden. The various morbid conditions caused thereby are called arteriosclerosis. It is known that arteriosclerosis is caused by risk factors such as dyslipidemia, diabetes, hypertension, and smoking, and ultimately restricts or blocks the blood flow in the arteries, thereby causing cardiovascular diseases, cerebrovascular diseases, etc.

[0021] The mechanism of arteriosclerosis is considered as follows. The inner cavity of the blood vessel is covered by a layer of endothelial cells, and smooth muscle cells in the tunica media surround the periphery thereof to adjust blood pressure and blood flow. If the vascular endothelial cells are damaged, inflammatory cells, etc. infiltrate into the blood vessel wall. That is, LDL in the blood enters the intima, is oxidized and changed into oxidized LDL. In order to process it, monocytes, which are a type of white blood cells, also enter the intima and change into macrophages. Macrophages take up oxidized LDL, become foam cells, release various cytokines, and cause a local chronic inflammatory reaction in the blood vessel. This becomes an inducement, causing the smooth muscle cells in the tunica media to transform, migrate into the intima and increase.

[0022] When cholesterol accumulates in peripheral cells represented by macrophages, inflammatory cytokines are produced, causing inflammation. In an inflammatory state, the excretion of cholesterol becomes sluggish, and further cholesterol accumulates, and the inflammation deteriorates. Such a vicious cycle is one of the causes of arteriosclerosis. Promotion of cholesterol excretion in peripheral cells represented by macrophages is related to suppressing inflammation and thus preventing arteriosclerosis.

[0023] Therefore, it is considered that by promoting cholesterol excretion via promoting the expression of ABC transporters or independently of promoting the expression of ABC transporters (i.e., independently of promoting the expression of ABC transporters), arteriosclerosis can be prevented. In addition, it is considered that by promoting the expression of ABC transporters or independently of promoting the expression of ABC transporters (i.e., independently of promoting the expression of ABC transporters) to promote cholesterol excretion, and by promoting cholesterol excretion to suppress inflammation, arteriosclerosis can be prevented. In addition, it is considered that by suppressing inflammation by suppressing the production of inflammatory cytokines, arteriosclerosis can be prevented.

[0024] Therefore, the object of the present invention is to provide an ABC transporter expression promoter, a cholesterol excretion promoter, an inflammatory cytokine production inhibitor, an anti-inflammatory agent, and an arteriosclerosis preventive agent.

[0025] Means for Solving the Problems

[0026] The present invention provides the following agents.

[0027] [A1] An ABC transporter expression promoter, which contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0028] [A2]The ABC transporter expression promoter according to [A1], wherein the ABC transporter expression promoter contains a Camembert cheese extract, and the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0029] [A3]A cholesterol efflux promoter containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0030] [A4]The cholesterol efflux promoter according to [A3], wherein the cholesterol efflux promoter contains a Camembert cheese extract, and the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0031] [A5]The cholesterol efflux promoter according to [A3] or [A4], wherein the cholesterol efflux promoter is administered to a subject in an inflammatory state.

[0032] [A6]An inflammatory cytokine production inhibitor containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0033] [A7]The inflammatory cytokine production inhibitor according to [A6], wherein the inflammatory cytokine production inhibitor contains a Camembert cheese extract, and the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0034] [A8]An anti-inflammatory agent containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0035] [A9]The anti-inflammatory agent according to [A8], wherein the anti-inflammatory agent contains a Camembert cheese extract, and the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0036] [A10]An arteriosclerosis preventive agent containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0037] [A11]The arteriosclerosis preventive agent according to [A10], wherein the arteriosclerosis preventive agent contains a Camembert cheese extract, and the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0038] In addition, the present invention also provides the following uses.

[0039] [B1]Use of at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid in the preparation of an ABC transporter expression promoter.

[0040] [B2]Use of a Camembert cheese extract in the preparation of an ABC transporter expression promoter, wherein the Camembert cheese extract contains at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid.

[0041] [B3]Use of at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid in the preparation of a cholesterol excretion promoter.

[0042] [B4]Use of a Camembert cheese extract in the preparation of a cholesterol excretion promoter, wherein the Camembert cheese extract contains at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid.

[0043] [B5]The use according to [B3] or [B4], wherein the cholesterol excretion promoter is administered to a subject in an inflammatory state.

[0044] [B6]Use of at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid in the preparation of an inflammatory cytokine production inhibitor.

[0045] [B7]Use of a Camembert cheese extract in the preparation of an inflammatory cytokine production inhibitor, wherein the Camembert cheese extract contains at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid.

[0046] [B8]Use of at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid in the preparation of an anti - inflammatory agent.

[0047] [B9]Use of a Camembert cheese extract in the preparation of an anti - inflammatory agent, wherein the Camembert cheese extract contains at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid.

[0048] [B10]Use of at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid in the preparation of an arteriosclerosis preventive agent.

[0049] [B11]Use of a Camembert cheese extract in the preparation of an arteriosclerosis preventive agent, wherein the Camembert cheese extract contains at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid.

[0050] In addition, the present invention provides the following methods.

[0051] [C1]A method for promoting the expression of ABC transporters, which comprises the step of administering to a subject in need of promoting the expression of ABC transporters at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0052] [C2]A method for promoting the expression of ABC transporters, which comprises the step of administering to a subject in need of promoting the expression of ABC transporters Camembert cheese extract, wherein the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0053] [C3]A method for promoting cholesterol excretion, which comprises the step of administering to a subject in need of promoting cholesterol excretion at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0054] [C4]A method for promoting cholesterol excretion, which comprises the step of administering to a subject in need of promoting cholesterol excretion Camembert cheese extract, wherein the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0055] [C5]The method according to [C3] or [C4], wherein at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid or the Camembert cheese extract is administered to a subject in an inflammatory state.

[0056] [C6]A method for inhibiting the production of inflammatory cytokines, which comprises the step of administering to a subject in need of inhibiting the production of inflammatory cytokines at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0057] [C7]A method for inhibiting the production of inflammatory cytokines, which comprises the step of administering to a subject in need of inhibiting the production of inflammatory cytokines Camembert cheese extract, wherein the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0058] [C8]A method for preventing or treating inflammation, which comprises the step of administering to a subject in need of preventing or treating inflammation at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0059] [C9]A method for preventing or treating inflammation, which comprises the step of administering to a subject in need of preventing or treating inflammation Camembert cheese extract, wherein the Camembert cheese extract contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0060] [C10]A method for preventing arteriosclerosis, which comprises the step of administering to a subject in need of preventing arteriosclerosis at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0061] [C11]A method for preventing arteriosclerosis, which comprises the step of administering to a subject in need of preventing arteriosclerosis a Camembert cheese extract, said Camembert cheese extract containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0062] In addition, the present invention provides the following uses.

[0063] [D1]Use of at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid as an active ingredient of an ABC transporter expression promoter.

[0064] [D2]Use of a Camembert cheese extract as an active ingredient of an ABC transporter expression promoter, said Camembert cheese extract containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0065] [D3]Use of at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid as an active ingredient of a cholesterol excretion promoter.

[0066] [D4]Use of a Camembert cheese extract as an active ingredient of a cholesterol excretion promoter, said Camembert cheese extract containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0067] [D5]The use according to [D3] or [D4], wherein the cholesterol excretion promoter is administered to a subject in an inflammatory state.

[0068] [D6]Use of at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid as an active ingredient of an inflammatory cytokine production inhibitor.

[0069] [D7]Use of a Camembert cheese extract as an active ingredient of an inflammatory cytokine production inhibitor, said Camembert cheese extract containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0070] [D8]Use of at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid as an active ingredient of an anti-inflammatory agent.

[0071] [D9]Use of a Camembert cheese extract as an active ingredient of an anti-inflammatory agent, said Camembert cheese extract containing at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

[0072] [D10] Use of at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid as an active ingredient of an arteriosclerosis preventive agent.

[0073] [D11] Use of a Camembert cheese extract as an active ingredient of an arteriosclerosis preventive agent, wherein the Camembert cheese extract contains at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid.

[0074] Effects of the invention

[0075] According to the present invention, it is possible to provide an ABC transporter expression promoter, a cholesterol excretion promoter, an inflammatory cytokine production inhibitor, an anti - inflammatory agent, and an arteriosclerosis preventive agent. BRIEF DESCRIPTION OF THE DRAWINGS

[0076] Figure 1 It is a diagram showing the fractionation result of the lower layer extract by thin - layer chromatography (TLC) in Example 2.

[0077] Figure 2 It is a diagram showing the result of Western blotting in Example 7. DETAILED DESCRIPTION OF THE INVENTION

[0078] Hereinafter, the present invention will be described.

[0079] The present invention provides an ABC transporter expression promoter (hereinafter referred to as "the first agent"), a cholesterol excretion promoter (hereinafter referred to as "the second agent"), an inflammatory cytokine production inhibitor (hereinafter referred to as "the third agent"), an anti - inflammatory agent (hereinafter referred to as "the fourth agent"), and an arteriosclerosis preventive agent (hereinafter referred to as "the fifth agent").

[0080] <Active ingredient>

[0081] Each of the first to fifth agents contains at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid. Hereinafter, at least one selected from 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid is referred to as "the active ingredient".

[0082] In one embodiment, each of the first to fifth agents contains one of 10 - hydroxypalmitic acid or 16 - hydroxypalmitic acid.

[0083] In another embodiment, each of the first to fifth agents contains both 10 - hydroxypalmitic acid and 16 - hydroxypalmitic acid.

[0084] The amount of the active ingredient contained in each of the first to fifth agents can be appropriately adjusted in consideration of the form of each agent, the number of administrations per day of each agent, the amount of administration per day of each agent, and the like. Each of the first to fifth agents may consist only of the active ingredient. The amount of the active ingredient contained in each of the first to fifth agents is based on the mass of each of the first to fifth agents, and can be adjusted, for example, to 0.00000001% by mass or more and 10% by mass or less, preferably adjusted to 0.0000001% by mass or more and 1% by mass or less, and more preferably adjusted to 0.000001% by mass or more and 0.1% by mass or less. It should be noted that when each of the first to fifth agents contains one of 10-hydroxy palmitic acid or 16-hydroxy palmitic acid, the amount of the active ingredient refers to the amount of that one, and when each of the first to fifth agents contains both 10-hydroxy palmitic acid and 16-hydroxy palmitic acid, the amount of the active ingredient refers to the total amount of the two.

[0085] 10-Hydroxy palmitic acid may be contained in each of the first to fifth agents in a free form, or may be contained in each of the first to fifth agents in a form combined with glycerol (that is, in the form of a glycerol monoster, glycerol diester, or glycerol triester containing 10-hydroxy palmitic acid). 16-Hydroxy palmitic acid may be contained in each of the first to fifth agents in a free form, or may be contained in each of the first to fifth agents in a form combined with glycerol (that is, in the form of a glycerol monoster, glycerol diester, or glycerol triester containing 16-hydroxy palmitic acid). For "each of the first to fifth agents contains 10-hydroxy palmitic acid", in addition to the case where each of the first to fifth agents contains 10-hydroxy palmitic acid in a free form, it also includes the case where each of the first to fifth agents contains 10-hydroxy palmitic acid in a form in which 10-hydroxy palmitic acid is bound to glycerol (that is, in the form of a glycerol monoster, glycerol diester, or glycerol triester containing 10-hydroxy palmitic acid). For "each of the first to fifth agents contains 16-hydroxy palmitic acid", in addition to the case where each of the first to fifth agents contains 16-hydroxy palmitic acid in a free form, it also includes the case where each of the first to fifth agents contains 16-hydroxy palmitic acid in a form in which 16-hydroxy palmitic acid is bound to glycerol (that is, in the form of a glycerol monoster, glycerol diester, or glycerol triester containing 16-hydroxy palmitic acid).

[0086] 10-Hydroxypalmitic acid can be included in each of the first to fifth agents in the form of a pharmaceutically acceptable salt or solvate. 16-Hydroxypalmitic acid can be included in each of the first to fifth agents in the form of a pharmaceutically acceptable salt or solvate. "Each of the first to fifth agents contains 10-hydroxypalmitic acid" also includes the case where each of the first to fifth agents contains 10-hydroxypalmitic acid in the form of a pharmaceutically acceptable salt and / or solvate. "Each of the first to fifth agents contains 16-hydroxypalmitic acid" also includes the case where each of the first to fifth agents contains 16-hydroxypalmitic acid in the form of a pharmaceutically acceptable salt and / or solvate. Examples of pharmaceutically acceptable salts include acid addition salts, metal salts, ammonium salts, organic amine addition salts, etc. Examples of pharmaceutically acceptable acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, nitrate, sulfate, phosphate, etc., and organic acid salts such as acetate, oxalate, maleate, fumarate, citrate, benzoate, methanesulfonate, etc. Examples of pharmaceutically acceptable metal salts include alkali metal salts such as sodium salt, potassium salt, etc., alkaline earth metal salts such as magnesium salt, calcium salt, etc., aluminum salt, zinc salt, etc. Examples of pharmaceutically acceptable ammonium salts include salts such as ammonium, tetramethylammonium, etc. Examples of pharmaceutically acceptable organic amine addition salts include addition salts such as morpholine, piperidine, etc.

[0087] 10-Hydroxypalmitic acid and 16-hydroxypalmitic acid can be included in Camembert cheese. Therefore, each of the first to fifth agents can contain a Camembert cheese extract, and the Camembert cheese extract can contain at least one selected from 10-hydroxypalmitic acid and 16-hydroxypalmitic acid. The safety of 10-hydroxypalmitic acid and 16-hydroxypalmitic acid is supported by the rich eating experience of humans represented by Camembert cheese.

[0088] The Camembert cheese extract can be obtained by subjecting the Camembert cheese as the extraction raw material to an extraction treatment using an extraction solvent. Before the extraction treatment, the extraction raw material can be subjected to a drying treatment and / or a pulverization treatment as needed. In addition, before the extraction treatment, the extraction raw material can be subjected to a defatting treatment using a nonpolar solvent (such as hexane) as needed.

[0089] The extraction treatment is a treatment for extracting the target components (10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid) from the extraction raw material with an extraction solvent, and can be carried out according to a conventional method. The extraction treatment can be carried out, for example, by bringing the extraction raw material into contact with the extraction solvent. The amount of the extraction solvent used is, for example, 0.1 to 10 L, preferably 0.25 to 5 L, more preferably 0.5 to 2.5 L, relative to 100 g of the extraction raw material. The temperature when bringing the extraction raw material into contact with the extraction solvent is, for example, 0°C to 40°C, preferably 15°C to 40°C, more preferably 25°C to 40°C. The time for bringing the extraction raw material into contact with the extraction solvent is, for example, 0.01 to 96 hours, preferably 0.1 to 48 hours, more preferably 0.5 to 24 hours. The contact between the extraction raw material and the extraction solvent can be carried out, for example, by immersing the extraction raw material in the extraction solvent. After the extraction treatment, the mixture of the extraction raw material and the extraction solvent is subjected to a solid-liquid separation treatment to remove the extraction residue, whereby an extract can be obtained. The solid-liquid separation treatment can be selected, for example, from filtration, centrifugation, decantation, etc. By diluting or concentrating the extract, a diluted solution or a concentrated solution can be obtained. By drying the extract, the diluted solution, the concentrated solution, or the dried product, a dried substance can be obtained. By purifying the extract, the diluted solution, the concentrated solution, or the dried substance, a crude purified product or a purified product can be obtained. Dilution, concentration, drying, and purification can be carried out respectively according to conventional methods. The extract also includes any form of the extract, the diluted solution, the concentrated solution, the dried substance, the crude purified product, and the purified product.

[0090] The extraction solvent is not particularly limited as long as it can extract the target components (10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid). One solvent can be used as the extraction solvent, or a mixed solvent of two or more solvents can be used as the extraction solvent. The extraction solvent is preferably used at room temperature or a temperature below the boiling point.

[0091] The extraction solvent can be a polar solvent or a non-polar solvent as long as it can extract the target components (10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid). When the target components (10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid) exist in the form of free fatty acids, polar solvents such as low-polarity solvents can be used as the extraction solvent. When the target components (10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid) exist in the form combined with glycerol (i.e., in the form of monoglycerides, diglycerides or triglycerides containing 10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid), non-polar solvents can be used as the extraction solvent. The extraction solvent can be selected from, for example, acetone, ethanol, methyl ethyl ketone, glycerol, ethyl acetate, methyl acetate, diethyl ether, cyclohexane, dichloromethane, edible oils, 1,1,2-tetrafluoroethane, 1,1,2-trichloroethylene, carbon dioxide, 1-butanol, 2-butanol, butane, 1-propanol, 2-propanol, propane, propylene glycol, hexane, water, methanol, acetonitrile, etc. From the viewpoint of efficiently extracting the target components (10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid), the extraction solvent preferably contains acetonitrile.

[0092] In one embodiment, hexane and acetonitrile can be used as the extraction solvent. The mixed solvent of hexane and acetonitrile can be added to the extraction raw material, or acetonitrile and hexane can be sequentially added to the extraction raw material and then mixed. The volume ratio of hexane to acetonitrile (volume of hexane: volume of acetonitrile) is, for example, 1:10 to 10:1, preferably 1:5 to 5:1, more preferably 1:2 to 2:1. When hexane and acetonitrile are used as the extraction solvent, the acetonitrile layer (lower layer) can be obtained in the form of an extract containing at least one selected from 10-hydroxypalmitic acid and 16-hydroxypalmitic acid. The obtained extract can be subjected to treatments such as dilution, concentration, drying, purification, etc. according to conventional methods to obtain a diluent, a concentrate, a dried product, a crude purified product, a purified product, etc.

[0093] <Use of the first agent>

[0094] 10-Hydroxypalmitic acid and 16-hydroxypalmitic acid respectively have the effect of promoting the expression of ABC transporters. Therefore, the first agent can be administered to a subject in order to promote the expression of ABC transporters. The subject is preferably a mammal such as a human, a mouse, a rat, a hamster, a rabbit, a dog, a cat, a pig, a cow, a horse, a monkey, etc., more preferably a human. Promoting the expression of ABC transporters includes promoting the expression of ABC transporter genes and promoting the expression of ABC transporters (proteins). The promotion of the expression of ABC transporter genes is preferably to promote the expression of mRNA, more preferably to promote the transcription into mRNA. The promotion of the expression of ABC transporters (proteins) is preferably achieved by promoting the expression of genes.

[0095] In one embodiment, the first agent may be administered to a subject to promote the expression of an ABC transporter gene (preferably to promote the expression of mRNA, more preferably to promote transcription into mRNA). The promotion of the expression of the ABC transporter gene can be confirmed by an increase in the amount of mRNA after administration of the first agent compared to the amount of mRNA before administration. The amount of mRNA after administration of the first agent is preferably 1.5-fold or more, more preferably 2-fold or more, and further preferably 2.5-fold or more, compared to the amount of mRNA before administration. The amount of mRNA can be measured by a conventional method such as RT-PCR. In addition, the promotion of the expression of the ABC transporter gene can be confirmed by an increase in the protein expression level of the ABC transporter after administration of the first agent compared to the protein expression level of the ABC transporter before administration. The protein expression level of the ABC transporter after administration of the first agent is preferably 1.25-fold or more, more preferably 1.5-fold or more, and further preferably 2.0-fold or more, compared to the protein expression level of the ABC transporter before administration. The protein expression level can be measured by a conventional method such as Western blotting.

[0096] In another embodiment, the first agent may be administered to a subject to promote the expression of an ABC transporter. The promotion of the expression of the ABC transporter can be confirmed by an increase in the protein expression level of the ABC transporter after administration of the first agent compared to the protein expression level of the ABC transporter before administration. The protein expression level of the ABC transporter after administration of the first agent is preferably 1.25-fold or more, more preferably 1.5-fold or more, and further preferably 2.0-fold or more, compared to the protein expression level of the ABC transporter before administration. The protein expression level can be measured by a conventional method such as Western blotting.

[0097] Examples of the ABC transporter include the ABCA subfamily (e.g., ABCA1 and ABCA3), the ABCB subfamily (e.g., ABCB1, ABCB4, and ABCB11), the ABCC subfamily (e.g., ABCC1, ABCC2, ABCC7, ABCC8, and ABCC9), the ABCD subfamily (e.g., ABCD1), the ABCG subfamily (e.g., ABCG1, ABCG2, ABCG4, and ABCG5 / 8), etc. Among them, ABCA1 and ABCG1 are preferred. That is, in order to promote the expression of at least one selected from ABCA1 and ABCG1, it is preferred to administer the first agent to a subject.

[0098] The cells expressing the ABC transporter are not particularly limited, and as suitable specific examples, macrophages, astrocytes, nerve cells, pancreatic β cells, adipocytes, fibroblasts, etc. can be mentioned. That is, in order to promote the expression of the ABC transporter in cells selected from macrophages, astrocytes, nerve cells, pancreatic β cells, adipocytes, and fibroblasts, it is preferred to administer the first agent to a subject. The cells are preferably cells derived from mammals such as humans, mice, rats, hamsters, rabbits, dogs, cats, pigs, cows, horses, monkeys, etc., and more preferably cells derived from humans. The cells can be cells in a living body or isolated cells. The isolated cells can be maintained and cultured according to conventional methods.

[0099] <Use of the second agent>

[0100] 10-Hydroxypalmitic acid and 16-hydroxypalmitic acid each have an effect of promoting cholesterol efflux. Therefore, the second agent can be administered to a subject to promote cholesterol efflux. It should be noted that the cholesterol efflux promoting effect can be exerted through the ABC transporter expression promoting effect (especially the expression promoting effect of at least one selected from ABCA1 and ABCG1), but is not limited thereto. The cholesterol efflux promoting effects of 10-hydroxypalmitic acid and 16-hydroxypalmitic acid can be exerted independently of the ABC transporter expression promoting effect (that is, independently of the ABC transporter expression promoting effect). For example, even in a state where the expression of the ABC transporter has been induced (that is, a state where cholesterol efflux has been promoted by the ABC transporter expression promoting effect), 10-hydroxypalmitic acid and 16-hydroxypalmitic acid can each further promote cholesterol efflux. The subject is preferably a mammal such as a human, mouse, rat, hamster, rabbit, dog, cat, pig, cow, horse, monkey, etc., and more preferably a human. Promoting cholesterol efflux includes promoting the efflux of cholesterol from inside the cell to the outside of the cell and promoting the efflux of cholesterol in the body to the outside of the body. For example, it is considered that ABCG5 / 8 is involved in the efflux of cholesterol from the liver to bile. In addition, ABCA1 and ABCG1 can indirectly contribute to the efflux of cholesterol in the body to the outside of the body by activating the reverse cholesterol transport system from peripheral cells to the liver. Promoting the efflux of cholesterol in the body to the outside of the body is preferably achieved by promoting the efflux of cholesterol from inside the cell to the outside of the cell. Cholesterol includes free cholesterol and cholesterol esters (substances formed by the esterification of cholesterol and fatty acids). In addition, cholesterol includes (3β)-cholest-5-en-3-ol, cholest-5-en-3β-ol, and their derivatives and analogs described in International Publication No. 2013 / 061969.

[0101] In one embodiment, the second agent can be administered to a subject to promote the efflux of cholesterol from inside the cell to outside the cell. The cells that accumulate cholesterol inside the cell are not particularly limited, and examples include macrophages, adipocytes, vascular endothelial cells, etc. Among them, macrophages, adipocytes, etc. are preferred. That is, in order to promote the efflux of cholesterol from inside the cells selected from macrophages and adipocytes to outside the cell, it is preferred to administer the second agent to the subject. The cells are preferably cells derived from mammals such as humans, mice, rats, hamsters, rabbits, dogs, cats, pigs, cows, horses, monkeys, etc., and more preferably cells derived from humans. The cells can be cells in a living body or isolated cells. The isolated cells can be maintained and cultured according to conventional methods.

[0102] In another embodiment, the second agent can be administered to a subject to promote the efflux of cholesterol from inside the tissue to outside the tissue. The tissues that accumulate cholesterol inside the tissue are not particularly limited, and examples include central tissues, peripheral tissues, etc. That is, the second agent can be administered to a subject to promote the efflux of cholesterol from inside the tissues selected from central tissues and peripheral tissues to outside the tissue. The tissues are preferably tissues derived from mammals such as humans, mice, rats, hamsters, rabbits, dogs, cats, pigs, cows, horses, monkeys, etc., and more preferably tissues derived from humans. The tissues can be tissues in a living body or isolated tissues. The isolated tissues can be maintained and cultured according to conventional methods.

[0103] The second agent can be administered to a subject in an inflammatory state (i.e., a subject with inflammation) or to a subject without an inflammatory state (i.e., a subject without inflammation). Whether the subject is in an inflammatory state or not, the second agent can promote the efflux of cholesterol. The inflammation can be inflammation caused by the accumulation of cholesterol in peripheral cells represented by macrophages, or inflammation caused by other reasons. Inflammation includes various reaction mechanisms caused by various stimuli, injuries, infections, etc. Known inflammatory markers can be used to determine whether inflammation is caused. As inflammatory markers, for example, interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), tumor necrosis factor (TNF-α), C-reactive protein (CRP), etc. can be cited. For example, when the gene expression level (e.g., mRNA level) of the inflammatory marker increases, it can be judged that inflammation has occurred. It should be noted that the description of inflammation in <the use of the fourth agent> also applies to the second agent.

[0104] In one embodiment, the second agent may be administered to a subject to promote the efflux of cholesterol from cells in an inflammatory state to the extracellular space. Examples of cells that can be in an inflammatory state include macrophages, cells of the leukocyte lineage (lymphocytes, plasma cells, etc.), mast cells, vascular endothelial cells, etc. Among them, macrophages, adipocytes, etc. are preferred. That is, in order to promote the efflux of cholesterol from cells in an inflammatory state selected from macrophages and adipocytes to the extracellular space, it is preferred to administer the second agent to the subject. The cells are preferably cells derived from mammals such as humans, mice, rats, hamsters, rabbits, dogs, cats, pigs, cows, horses, monkeys, etc., and more preferably human-derived cells. The cells can be cells in a living body or isolated cells. The isolated cells can be maintained and cultured by conventional methods.

[0105] In another embodiment, the second agent may be administered to a subject to promote the efflux of cholesterol from tissues in an inflammatory state to the extracellular space. The tissues that can be in an inflammatory state are not particularly limited, and examples include central tissues, peripheral tissues, etc. That is, the second agent may be administered to a subject to promote the efflux of cholesterol from tissues in an inflammatory state selected from central tissues and peripheral tissues to the extracellular space. The tissues are preferably tissues derived from mammals such as humans, mice, rats, hamsters, rabbits, dogs, cats, pigs, cows, horses, monkeys, etc., and more preferably human-derived tissues. The tissues can be tissues in a living body or isolated tissues. The isolated tissues can be maintained and cultured by conventional methods.

[0106] <Use of the third agent>

[0107] 10-Hydroxypalmitic acid and 16-hydroxypalmitic acid each have an inhibitory effect on the production of inflammatory cytokines. Therefore, the third agent may be administered to a subject to inhibit the production of inflammatory cytokines. The subject is preferably a mammal such as a human, mouse, rat, hamster, rabbit, dog, cat, pig, cow, horse, monkey, etc., and more preferably a human. Inhibiting the production of inflammatory cytokines includes inhibiting the expression of inflammatory cytokine genes (preferably inhibiting the expression of mRNA). The inhibitory effect on the production of inflammatory cytokines includes not only the complete inhibition of the production of inflammatory cytokines but also the partial inhibition of the production of inflammatory cytokines such as the inhibition of the overproduction of inflammatory cytokines.

[0108] In one embodiment, the third agent may be administered to a subject to inhibit the production of inflammatory cytokines by inhibiting the expression of inflammatory cytokine genes (preferably inhibiting the expression of mRNA). Inhibition of the expression of inflammatory cytokine genes can be confirmed by a decrease in the amount of mRNA after administration of the third agent compared to the amount of mRNA before administration. The amount of mRNA after administration of the third agent is preferably 0.5-fold or less, more preferably 0.1-fold or less, and further preferably 0.05-fold or less compared to the amount of mRNA before administration. The amount of mRNA can be measured by conventional methods such as RT-PCR.

[0109] Inflammatory cytokines are substances involved in inflammation associated with tissue damage, bacterial infection, viral infection, tumors, etc., and are produced by lymphocytes, macrophages, monocytes, etc. Examples of inflammatory cytokines include G-CSF, IL-1, IL-6, IL-8, IL-11, IL-17, IL-18, IFN-α, IFN-β, IFN-γ, TNF-α, TNF-β, chemokines, etc. Among them, IL-1 and IL-6 are preferred. That is, in order to inhibit the production of at least one selected from IL-1 and IL-6, it is preferred to administer the third agent to a subject. It should be noted that IL-1 includes IL-1α and IL-1β.

[0110] <Use of the fourth agent>

[0111] 10-Hydroxypalmitic acid and 16-hydroxypalmitic acid each have an anti-inflammatory effect. Therefore, the fourth agent may be administered to a subject for anti-inflammation (i.e., prevention or treatment of inflammation). It should be noted that the anti-inflammatory effect can be exerted by promoting cholesterol excretion and / or by inhibiting the production of inflammatory cytokines, but is not limited thereto. The subject is preferably a mammal such as a human, mouse, rat, hamster, rabbit, dog, cat, pig, cow, horse, monkey, etc., and more preferably a human. Prevention of inflammation includes preventing, inhibiting, and delaying the onset of inflammation. Treating inflammation includes delaying the development of inflammation and relieving, reducing, improving, and curing symptoms.

[0112] Inflammation can be inflammation caused by the accumulation of cholesterol in peripheral cells represented by macrophages, or inflammation caused by other reasons. Inflammation includes various reaction mechanisms caused by various stimuli, injuries, infections, etc. Known inflammatory markers can be used to determine whether inflammation has occurred. Examples of inflammatory markers include prostaglandins, IL-1, IL-6, IL-8, IL-12, TNF-α, IFN-γ, bradykinin, complement components, blood coagulation factors, C-reactive protein, etc. For example, when the gene expression level (e.g., mRNA level) of an inflammatory marker increases, it can be judged that inflammation has occurred. In addition, it is possible to determine whether inflammation has occurred based on the erythrocyte sedimentation rate (ESR), white blood cell count, morphological changes in blood and other cells, etc.

[0113] The inflammation can be any inflammation that can occur in the subject. As the site where inflammation can occur, for example, intravascular, intestinal (such as in the small intestine, large intestine, etc.), nasal cavity, bronchus, skin, oral cavity, etc. can be cited.

[0114] As the inflammation, for example, the inflammation in inflammatory diseases can be cited. Inflammatory diseases are diseases accompanied by an inflammatory response. For example, gout, arteriosclerosis, gastric ulcer, nephritis (glomerulonephritis, IgA nephropathy, diabetic nephropathy, etc.), periodontal disease (gingivitis, periodontitis, etc.), hepatitis (alcoholic hepatitis, non-alcoholic hepatitis, etc.), liver cirrhosis, asthma, bronchitis, cerebral infarction, aneurysm, delayed hypersensitivity, endometriosis, acute respiratory distress syndrome, injury caused by kidney transplantation, acute myocardial infarction, diabetes, systemic lupus erythematosus, Crohn's disease, pneumonia, arthritis (rheumatoid arthritis, etc.), endotoxin shock, sepsis caused by infectious diseases, chronic ulcerative colitis, chronic bronchitis, cystitis, chronic osteomyelitis, reflux esophagitis, cholangitis, chronic cholecystitis, gastritis, chronic cervicitis, neuroinflammatory diseases, inflammatory skin diseases, etc. can be cited. As neuroinflammatory diseases, for example, diabetic neuropathy, dementia (Alzheimer's type, etc.), multiple sclerosis, etc. can be cited. As inflammatory skin diseases, for example, atopic dermatitis, seborrheic dermatitis, diaper dermatitis, allergic contact dermatitis, irritant contact dermatitis (including dermatitis caused by contact with pharmaceuticals, etc.), contact dermatitis of unknown details, exfoliative dermatitis, dermatitis caused by ingested substances, chronic simple lichen, prurigo, pruritus, etc. can be cited. Inflammatory diseases are preferably inflammatory diseases in which macrophages are involved. As inflammatory diseases in which macrophages are involved, for example, hepatitis, asthma, systemic lupus erythematosus, Crohn's disease, atopic dermatitis, arthritis, diabetic neuropathy, dementia, etc. can be cited.

[0115] <Use of the fifth dose>

[0116] 10-Hydroxypalmitic acid and 16-hydroxypalmitic acid promote cholesterol efflux by promoting the expression of ABC transporters (especially promoting the expression of at least one selected from ABCA1 and ABCG1) or independently of promoting the expression of ABC transporters (i.e., independently of promoting the expression of ABC transporters), thereby preventing arteriosclerosis. In addition, 10-hydroxypalmitic acid and 16-hydroxypalmitic acid promote cholesterol efflux by promoting the expression of ABC transporters (especially promoting the expression of at least one selected from ABCA1 and ABCG1) or independently of promoting the expression of ABC transporters (i.e., independently of promoting the expression of ABC transporters), and inhibit inflammation by promoting cholesterol efflux, thereby preventing arteriosclerosis. In addition, 10-hydroxypalmitic acid and 16-hydroxypalmitic acid inhibit inflammation by inhibiting the production of inflammatory cytokines, thereby preventing arteriosclerosis. Therefore, the fifth agent can be administered to a subject for the prevention of arteriosclerosis. The subject is preferably a mammal such as a human, mouse, rat, hamster, rabbit, dog, cat, pig, cow, horse, monkey, etc., and more preferably a human. As arteriosclerosis, for example, atherosclerotic arteriosclerosis (atherosclerosis), medial sclerosis (Monckeberg arteriosclerosis), arteriolosclerosis, etc. can be mentioned. Atherosclerotic arteriosclerosis (atherosclerosis) is the most common form of arteriosclerosis and is the cause of cardiovascular diseases including arteriosclerotic diseases. Therefore, the fifth agent can also be used for the prevention of cardiovascular diseases. Cardiovascular diseases are diseases related to the heart and blood vessels. As cardiovascular diseases, for example, coronary heart diseases such as angina pectoris and myocardial infarction; cerebrovascular diseases such as stroke, cerebral infarction, cerebral hemorrhage, and cerebral thrombosis; peripheral arterial diseases; rheumatic heart diseases; deep vein thrombosis; pulmonary embolism, etc. can be mentioned.

[0117] <Dosage and Administration>

[0118] The daily dosage of each of the first to fifth agents can be appropriately adjusted considering the gender, age, weight, symptoms, etc. of the subject. The daily dosage of the active ingredient for an adult is, for example, 0.0000001 to 0.1 g, preferably 0.000001 to 0.01 g, and more preferably 0.00001 to 0.001 g.

[0119] The administration period, administration interval, and number of daily administrations of each of the first to fifth agents can be appropriately adjusted considering the gender, age, weight, symptoms, etc. of the subject. Each of the first to fifth agents is, for example, administered daily, every other day, or every two days for a period of one week or more, preferably for a period of two weeks or more, and more preferably for a period of four weeks or more, daily, every other day, or every two days. The number of daily administrations is not particularly limited and is usually 1, 2, or 3 times.

[0120] The administration route of each of the first to fifth agents is not particularly limited as long as the target use can be achieved. In one embodiment, the administration route is oral administration. In another embodiment, the administration route is parenteral administration. Examples of parenteral administration include administration routes such as intranasal, eye drops, ear drops, percutaneous, intratracheal, intrarectal, intraurinary, subcutaneous, intramuscular, and intravenous.

[0121] <Form of the agent>

[0122] Each of the first to fifth agents is preferably a composition, more preferably a food or drink composition or a pharmaceutical composition.

[0123] Examples of food or drink compositions include health foods, nutritional supplements, functional foods, health functional foods (such as foods for specified health uses, nutritional functional foods, functionally labeled foods), special-purpose foods (such as milk powder for pregnant and lactating women), etc.

[0124] Examples of the form of food or drink compositions include solid, powder, paste, semi-liquid, colloidal, liquid, etc.

[0125] As long as it is a food or drink that can contain 10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid, the food or drink composition is not particularly limited. Examples include instant foods such as instant noodles, steamed foods, canned foods, microwave foods, instant soups and miso soups, freeze-dried foods; beverages such as soft drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee drinks, tea drinks, powder drinks, concentrated drinks, alcoholic beverages; wheat flour products such as bread, pasta, noodles, baking powder, and bread flour; confectioneries such as sugar, caramel, chewing gum, chocolate, cookies, biscuits, bars, cakes, pies, snacks, soda crackers, Japanese confectioneries, mousses, and desserts; seasonings such as sauces, tomato processed seasonings, flavor seasonings, cooking mixes, sauce-like seasonings, sauce-like seasonings, soup stocks, and vegetarian curries and stews; oils and fats such as processed oils, butter, margarine, and mayonnaise; dairy products such as milk drinks, milk-based drinks, fermented milk, cheeses, yogurts, lactic acid bacteria drinks, milk-based drinks, cheeses, ice creams, creams, formula milk powder, liquid milk, and solid milk; agricultural processed products such as canned agricultural products, jams and marmalades, and cereal flakes; frozen foods, liquid foods, supplements, etc. The food or drink composition can be manufactured according to the usual manufacturing methods in addition to containing 10-hydroxypalmitic acid and / or 16-hydroxypalmitic acid.

[0126] The components other than 10-hydroxy palmitic acid and / or 16-hydroxy palmitic acid contained in the food and drink composition are not particularly limited. As components other than 10-hydroxy palmitic acid and / or 16-hydroxy palmitic acid, for example, water, proteins, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juices, flavoring agents, etc. can be cited. As proteins, for example, whole milk powder, skim milk powder, partially skimmed milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, α-casein, β-casein, κ-casein, β-lactoglobulin, α-lactalbumin, lactoferrin, soy protein, egg protein, meat protein and other animal and plant proteins, their hydrolysates, butter, whey minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipids, lactose and other various milk-derived components, etc. As carbohydrates, general sugars, processed starches (such as dextrin, soluble starch, British starch, oxidized starch, starch esters, starch ethers, etc.), dietary fiber, etc. can be cited. As lipids, for example, lard, fish oil, etc., their fractionated oils, hydrogenated oils, interesterified oils and other animal fats; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, their fractionated oils, hydrogenated oils, interesterified oils and other vegetable oils, etc. As vitamins, for example, vitamin A, carotenoids, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, nicotinic acid, niacin, pantothenic acid, biotin, inositol, choline, folic acid, etc. can be cited. As minerals, for example, calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium, whey minerals, etc. can be cited. As organic acids, for example, malic acid, citric acid, lactic acid, tartaric acid, etc. can be cited. These components can be used alone or in combination of two or more.

[0127] As the pharmaceutical composition, for example, granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, suspensions, etc. can be cited. These preparations can be manufactured using pharmaceutically acceptable carriers according to conventional methods. As pharmaceutically acceptable carriers, for example, excipients, binders, diluents, additives, flavoring agents, buffers, thickeners, coloring agents, stabilizers, emulsifying agents, dispersing agents, suspending agents and preservatives, etc. can be cited. Pharmaceutically acceptable carriers can be used alone or in combination of two or more. The pharmaceutical composition thus manufactured contains at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid and one or two or more pharmaceutically acceptable carriers. In one embodiment, the pharmaceutical composition is an orally administered pharmaceutical composition (oral preparation).

[0128] As the carrier, examples include water, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, pharmaceutically acceptable surfactants and other substances, as well as artificial cell structures such as liposomes.

[0129] The third or fourth agent may be a skin cosmetic. The third or fourth agent is useful as a skin cosmetic for preventing or treating inflammatory skin diseases.

[0130] Examples of skin cosmetics include: lotion, emulsion, cream, milk, sunscreen, cleanser, shaving agent, facial wash, facial mask, cosmetic oil, body rinse, foundation, hair styling agent, hair conditioner, scalp agent, hair coloring agent, shampoo, hair rinse, treatment, etc.

[0131] Skin cosmetics can be manufactured using 10-hydroxy palmitic acid and / or 16-hydroxy palmitic acid and the raw materials of ordinary skin cosmetics. As the basic components of skin cosmetics, examples include ethanol, polyhydric alcohols, water, hydrocarbons, higher fatty acids, higher alcohols, oils and fats, waxes, ethers, esters, silicones, etc. In addition, components such as surfactants, moisturizing components, barrier function improving components, antioxidant components, whitening components, antibacterial components, stabilizers, fragrances, colorants, preservatives, etc. can also be used. Skin cosmetics can be manufactured by the usual manufacturing methods of skin cosmetics. The manufacturing method of skin cosmetics can include processes such as mixing, heating, dissolving, drying, filling, etc. of the raw materials.

[0132] Each of the first to fifth agents can be packaged in a manner that facilitates the administration of a single dose. The single dose can be one package or multiple packages. In the case of providing in a packaged form, in order to facilitate continuous intake, it is preferably provided in a set form for the intake amount for a certain period (for example, the intake amount for several days). The packaging form is not particularly limited as long as it defines a certain amount, and examples include wrapping paper, bag, soft bag, paper container, can, bottle, capsule, etc.

[0133] The uses, dosages, administration methods, etc. of the first to fifth doses may also be indicated on the packaging, container, or attachments (such as instructions, brochures, promotional materials, brand websites, etc.). Herein, "indication" includes all indications for notifying the above uses to those in need. Such indication only needs to be an indication that can remind or analogize the above uses, dosages, administration methods, etc., and may include all indications irrelevant to the purpose of the indication, the content of the indication, the object of the indication, the medium, etc.

[0134] Examples

[0135] [Example 1]

[0136] After adding 20 mL of acetonitrile to 2.0 g of Camembert cheese (Meiji Co., Ltd.'s "Meiji Hokkaido Tokachi Camembert Cheese"), 13 mL of hexane was added and mixed, followed by extraction treatment. The solvents in the upper layer (hexane layer) and the lower layer (acetonitrile layer) after liquid separation were removed by distillation to obtain an upper layer extract and a lower layer extract. The cholesterol excretion-promoting activity of these extracts was evaluated.

[0137] Human macrophage-like THP-1 cells were seeded in a 96-well plate at a density of 2.0×10 5 cells / well and differentiated for 72 hours. Subsequently, the medium was changed to RPMI1640 medium containing 0.02% (w / w) BSA (Bovine serum albumin), 5 μM T0901317 (Merck & Co., Inc.) and 5 μM 9-cis-retinoic acid (Cayman Chemical Company), and cultured for 24 hours to induce the expression of ABC transporters (endogenous ABCA1 and ABCG1). Then, the medium was changed to DMEM medium (Dulbecco's Modified Eagle Medium) containing 0.02% (w / w) BSA and 6 mM sodium taurocholate, and the lower layer extract was added at a concentration (final concentration in the well) of 0.04 - 40 mg / mL (0.04 - 40 mg cheese / mL) calculated based on the weight of the Camembert cheese used as the extraction raw material, and cultured for 4 hours. Then, the medium was recovered, and the amount of cholesterol excreted from the cells (the amount of cholesterol in the recovered medium) was measured by a fluorescence assay using Amplex Red (Invitrogen Corporation) to evaluate the cholesterol excretion-promoting activity of the lower layer extract (n = 4 - 5).

[0138] The results are shown in Table 1. It should be noted that in Table 1, the "cholesterol excretion amount" is the relative value when the value without adding the lower layer extract (when only adding dimethyl sulfoxide (DMSO) used as the dilution solvent for each extract) is set to 1. In addition, in Table 1, "*", "**", and "***" indicate that the cholesterol excretion amount is significantly higher statistically compared to when the lower layer extract is not added (*: P < 0.05, **: P < 0.01, ***: P < 0.001, all by Dunnett's test).

[0139] As shown in Table 1, it was confirmed that the lower layer extract has concentration-dependent cholesterol excretion-promoting activity.

[0140] [Table 1]

[0141]

[0142] [Example 2]

[0143] In order to further lock in the active ingredient, the lower layer extract was fractionated by thin layer chromatography (TLC). Specifically, the lower layer extract was applied to a silica gel plate (Silica gel 60, manufactured by Sperco), developed with hexane:ethyl acetate = 70:30, and the lower layer extract was fractionated.

[0144] The results are shown in Figure 1 . As Figure 1 shown, fractions (a) to (h) were obtained.

[0145] In the same manner as in Example 1, the cholesterol excretion-promoting activity of each fraction was evaluated (n = 1). Each fraction was added at a concentration of 20 mg / mL (20 mg cheese / mL) (final concentration in the wells) in terms of the weight of Camembert cheese used as the extraction raw material.

[0146] The results are shown in Table 2A. In addition, in Table 2A, the "cholesterol excretion amount" is the relative value when the value without adding the fraction (when only adding DMSO used as the dilution solvent for each fraction) is set to 1.

[0147] As shown in Table 2A, it was confirmed that fraction (c) has cholesterol excretion-promoting activity.

[0148] [Table 2A]

[0149]

[0150] The concentration-dependence of the cholesterol efflux-promoting activity of fraction (c) was evaluated in the same manner as in Example 1 (n = 3 - 4). Fraction (c) was added at a concentration of 5 - 40 mg / mL (5 - 40 mg of cheese / mL) in terms of the weight of Camembert cheese used as the extraction raw material (final concentration in the wells).

[0151] The results are shown in Table 2B. In addition, in Table 2B, the "cholesterol efflux amount" is the relative value when the value without adding fraction (c) (when only DMSO used as the dilution solvent for fraction (c) was added) was set to 1. In addition, in Table 2B, "**" and "***" indicate that the cholesterol efflux amount was significantly higher statistically compared to when fraction (c) was not added (**: P < 0.01, ***: P < 0.001, both by Dunnett's test).

[0152] As shown in Table 2B, it was confirmed that fraction (c) had a concentration-dependent cholesterol efflux-promoting activity.

[0153] [Table 2B]

[0154]

[0155] 〔Example 3〕

[0156] The cholesterol efflux-promoting activity of fraction (c) was also confirmed by a colorimetric method. Specifically, human macrophage-like THP-1 cells were inoculated at a density of 4.0 × 10 6 cells / well in a 6-well plate and differentiated for 72 hours. Then, the medium was replaced with RPMI1640 medium containing 0.02% by mass BSA (Bovine serum albumin), 5 μM T0901317 (Merck & Co., Inc.), and 5 μM 9-cis-retinoic acid (Cayman Chemical Company), and cultured for 24 hours to induce the expression of ABC transporters (endogenous ABCA1 and ABCG1). Then, the medium was replaced with DMEM medium (Dulbecco's Modified Eagle Medium) containing 0.02% by mass BSA and 6 mM sodium taurocholate, and fraction (c) was added at a concentration of 20 mg / mL (20 mg of cheese / mL) in terms of the weight of Camembert cheese used as the extraction raw material (final concentration in the wells), and cultured for 4 hours. Then, the medium was recovered, lipids were extracted using methanol and chloroform, and a free cholesterol assay kit (FUJIFILM Wako Pure Chemical Corporation) was used to measure the amount of cholesterol excreted from the cells (the amount of cholesterol in the recovered medium), and the cholesterol efflux-promoting activity of fraction (c) was evaluated (n = 3).

[0157] The results are shown in Table 3. It should be noted that in Table 3, the "cholesterol excretion amount" is the relative value when the value without adding fraction (c) (when only DMSO, the dilution solvent used as fraction (c), is added) is set to 1. In addition, in Table 3, "*" indicates that the cholesterol excretion amount is significantly higher statistically compared to when fraction (c) is not added (*: P < 0.05, Student's t-test).

[0158] As shown in Table 3, the cholesterol excretion-promoting activity of fraction (c) was also confirmed by a colorimetric method.

[0159] [Table 3]

[0160]

[0161] [Example 4]

[0162] Analysis of the components contained in fraction (c) was performed. Specifically, 0.5 mL of methanol was added to fraction (c) to dissolve the content, and the solution was passed through a 0.2-μm PTFE filter that had been washed once with methanol in advance. The solution after passing was used as the measurement sample. The measurement sample was subjected to non-targeted analysis based on liquid chromatography-mass spectrometry (LC-MS). The analysis conditions for LC-MS are as follows.

[0163] <lc>

[0164] Equipment: Thermo Fisher Scientific Vanquish F UHPLC

[0165] Column: Accucore RT-MS 2.1×100 mm 2.6 μm (SN: 10737078)

[0166] Column temperature: 60 °C

[0167] Mobile phase A: 10 mM ammonium acetate, 0.1% acetic acid - aqueous solution / acetonitrile (= 90 / 10)

[0168] Mobile phase B: 2 mM ammonium acetate, 0.02% acetic acid - water / isopropanol (IPA) / acetonitrile (= 2 / 88 / 10)

[0169] Flow rate: 0.25 mL / min

[0170] Injection volume: 3 μL

[0171] Gradient conditions:

[0172] [Table 4]

[0173] Time (min) Mobile phase A (%) Mobile phase B (%) 0 75 25 25 0 100 33 0 100 33.1 75 25 43 75 25

[0174]

[0175] Device: Thermo Fisher Scientific TM -Q Exactive TM

[0176] Ionization conditions: ESIPositive((Spray voltage: 3 kV), ESI Negative (Spray voltage: 2 kV)

[0177] Heater temperature: 400 °C

[0178] Capillary temperature: 250 °C

[0179] Sheath gas: 50

[0180] Auxiliary Gas: 20

[0181] S-lens-level: 50

[0182] Scan conditions: Full MS / dd-MS2 (Top3)

[0183] Resolution: 70000 (Full MS), 17500 (dd-MS2)

[0184] Scan range: 100 - 1500 (Full MS), 100 - 1500 (dd-MS2)

[0185] For the data obtained by LC-MS analysis, the mass information obtained by parsing using Compound Discoverer 3.1 (manufactured by Thermo Fisher Scientific). As a result, information on the active candidate components contained in the active fraction was obtained. Among them, it was found that 10-hydroxy palmitic acid represented by the compositional formula C 16 H 32 O3 was an active candidate component.

[0186] 〔Example 5A〕

[0187] In a 96-well plate at 2.0×10 5 Human macrophage-like THP-1 cells were inoculated at a density of cells / well and differentiated for 72 hours. Subsequently, the medium was replaced with RPMI1640 medium containing 0.02% (w / w) BSA (Bovine serum albumin), and 10-hydroxy palmitic acid (manufactured by Angene) at a concentration of 10 - 40 μg / mL (final concentration in the well) was added, followed by culturing for 24 hours. Then, the medium was replaced with DMEM medium (Dulbecco's Modified Eagle Medium) containing 0.02% (w / w) BSA and 6 mM sodium taurocholate, and the medium was collected 4 hours later. The amount of cholesterol excreted from the cells (the amount of cholesterol in the collected medium) was measured in the same manner as in Example 1, and the cholesterol excretion-promoting activity of 10-hydroxy palmitic acid was evaluated (n = 3).

[0188] The results are shown in Table 5A. In Table 5A, the "cholesterol excretion amount" is the relative value when the value without the addition of 10-hydroxy palmitic acid (when only DMSO used as the dilution solvent for 10-hydroxy palmitic acid was added) was set to 1. In addition, in Table 5A, "*" and "***" indicate that the cholesterol excretion amount was significantly higher statistically compared to the case without the addition of 10-hydroxy palmitic acid (*: P < 0.05, ***: P < 0.001, both by Dunnett's test).

[0189] As shown in Table 5A, it was confirmed that 10-hydroxy palmitic acid has a concentration-dependent cholesterol excretion-promoting activity.

[0190] [Table 5A]

[0191]

[0192] [Example 5B]

[0193] The cholesterol excretion-promoting activity of 10-hydroxy palmitic acid was also confirmed by a colorimetric method. Specifically, human macrophage-like THP-1 cells were inoculated at a density of 4.0×10 6 cells / well in a 6-well plate and differentiated for 72 hours. Subsequently, the medium was replaced with RPMI1640 medium containing 0.02% (w / w) BSA (Bovine serum albumin), and 20 μg / mL (final concentration in the well) of 10-hydroxy palmitic acid (manufactured by Angene) was added. After culturing for 24 hours, the cells were collected. Then, lipids were extracted using methanol and chloroform, and the amount of cholesterol excreted from the cells (the amount of cholesterol in the collected medium) was measured using a free cholesterol assay kit (manufactured by Fujifilm Wako Pure Chemical Corporation), and the cholesterol excretion-promoting activity of 10-hydroxy palmitic acid was evaluated (n = 3).

[0194] The results are shown in Table 5B. It should be noted that in Table 5B, the "cholesterol excretion amount" is the relative value when the value without adding 10-hydroxypalmitic acid (when only adding DMSO used as the dilution solvent of 10-hydroxypalmitic acid) is set to 1. In addition, in Table 5B, "*" indicates that the cholesterol excretion amount is significantly higher statistically compared to when 10-hydroxypalmitic acid is not added (*: P < 0.05, Student's t-test).

[0195] As shown in Table 5B, the cholesterol excretion-promoting activity of 10-hydroxypalmitic acid was also confirmed by a colorimetric method.

[0196] [Table 5B]

[0197]

[0198] [Example 6]

[0199] Since the cholesterol excretion-promoting activity of 10-hydroxypalmitic acid was confirmed, the effect of 10-hydroxypalmitic acid on ABC transporters was evaluated. Specifically, human macrophage-like THP-1 cells were seeded in a 24-well plate at a density of 1.0 × 10 6 cells / well and differentiated for 72 hours. Then, the medium was changed to RPMI1640 medium containing 0.02% by mass of BSA (Bovine serum albumin), 20 μg / mL (final concentration in the well) of 10-hydroxypalmitic acid was added, and after culturing for 24 hours, mRNA was extracted using RNeasy Minikit (Qiagen), reverse transcription was performed using ReverTra Ace (registered trademark) qPCR RT Master Mix with gDNA Remover (Toyobo), and the mRNA expression levels of ABCA1 and ABCG1 were measured by real-time PCR using Thermal Cycler Dice TP800 (Takara). 18S ribosomal RNA was used as a control gene. The mRNA expression levels of ABCA1 and ABCG1 were corrected with the mRNA expression level of the control gene, and the ABC transporter expression-promoting activity of 10-hydroxypalmitic acid was evaluated (n = 3).

[0200] The results are shown in Tables 6A and 6B. It should be noted that in Tables 6A and 6B, the "mRNA expression level" is the relative value when the value without adding 10-hydroxypalmitic acid (when only adding ethanol (EtOH) used as the dilution solvent of 10-hydroxypalmitic acid) is set to 1. In addition, in Tables 6A and 6B, "***" indicates that the mRNA expression levels of ABCA1 and ABCG1 are significantly higher statistically compared to when 10-hydroxypalmitic acid is not added (P < 0.001, Student's t-test).

[0201] As shown in Tables 6A and 6B, it was confirmed that 10-hydroxypalmitic acid has the activity of promoting the expression of ABC transporters (particularly the activity of promoting the mRNA expression of ABC transporters).

[0202] [Table 6A]

[0203]

[0204] [Table 6B]

[0205]

[0206] [Example 7]

[0207] Evaluate the protein expression levels of ABCA1 and ABCG1. Specifically, the cultured cells were recovered in the same manner as in Example 6, SDS-PAGE and blotting were performed using 10% microgels shown in Table 7A. After blocking, the protein expression levels were determined by Western blotting using a primary antibody (anti-mouse monoclonal ABCA1 (KM3110) or anti-rabbit polyclonal ABCG1 (H65) (Novus) and anti-actin (Sigma) as a loading control (n = 3)). The quantification of the protein expression levels was performed using CS Analyzer 4 (Bio-Rad). The protein expression levels of ABCA1 and ABCG1 were corrected with the protein expression level of actin.

[0208] The results are shown in Figure 2 , Table 7B and Table 7C. It should be noted that in Tables 7B and 7C, the "protein expression level" is the relative value when the value without adding 10-hydroxypalmitic acid (when only DMSO used as the dilution solvent of 10-hydroxypalmitic acid is added) is set to 1. In addition, in Tables 7B and 7C, "*" and "**" indicate that the protein expression levels of ABCA1 and ABCG1 are significantly higher statistically compared with the case without adding 10-hydroxypalmitic acid (*: P < 0.05, **: P < 0.01, both are student t-tests).

[0209] As shown in Tables 7B and 7C, it was confirmed that 10-hydroxypalmitic acid has the activity of promoting the expression of ABC transporters (the activity of promoting the protein expression of ABC transporters).

[0210] [Table 7A]

[0211] Gel composition for Western blotting

[0212]

[0213] [Table 7B]

[0214]

[0215] [Table 7C]

[0216]

[0217] The above results indicate that 10-hydroxy palmitic acid promotes the excretion of cholesterol by promoting the expression of ABC transporters.

[0218] [Example 8]

[0219] In the same manner as in Example 5A, the cholesterol excretion-promoting activities of 10-hydroxy palmitic acid and other hydroxy palmitic acids (2-hydroxy palmitic acid (Tokyo Chemical Industry), 3-hydroxy palmitic acid (Sigma-Aldrich), 16-hydroxy palmitic acid (Tokyo Chemical Industry), 10-hydroxy palmitic acid), and palmitic acid without added hydroxy group (Sigma) contained in Camembert cheese were evaluated (n = 6 - 11).

[0220] The results are shown in Table 8. Note that in Table 8, the "cholesterol excretion amount" is the relative value when the value without adding hydroxy palmitic acid or palmitic acid (when only adding EtOH used as the dilution solvent for hydroxy palmitic acid or palmitic acid) is set to 1.

[0221] As shown in Table 8, it was confirmed that 10-hydroxy palmitic acid and 16-hydroxy palmitic acid have cholesterol excretion-promoting activities.

[0222] [Table 8]

[0223]

[0224] From the above results, it was confirmed that the Camembert cheese extract has cholesterol excretion-promoting activity. In addition, it was confirmed that the 10-hydroxy palmitic acid and / or 16-hydroxy palmitic acid contained in Camembert cheese exerts cholesterol excretion-promoting activity by promoting the expression of ABC transporters.

[0225] [Example 9]

[0226] In a 24-well plate at 1.0×10 6 Human macrophage-like THP-1 cells were inoculated at a density of [[number of cells]] cells / well and differentiated for 72 hours. Subsequently, the medium was replaced with RPMI 1640 medium containing 0.02% (w / w) BSA (Bovine serum albumin), dimethyl sulfoxide (DMSO), or 20 μg / mL 10-hydroxy palmitic acid, 50 μg / mL oxidized LDL (oxLDL) (Invitrogen), 50 μg / mL acetylated LDL (acLDL) (Invitrogen), 5 μM T0901317 + 5 μM 9-cis retinoic acid (T0+RA), or 1 μg / mL lipopolysaccharide (LPS) (Sigma), or RPMI 1640 medium containing 0.02% (w / w) BSA, DMSO, or 20 μg / mL 10-hydroxy palmitic acid and not containing any of oxLDL, acLDL, T0+RA, and LPS (control), and cultured for 24 hours to induce inflammation in the macrophage-like cells. Subsequently, the medium was replaced with DMEM medium (Dulbecco's modified Eagle's medium) containing 0.02% (w / w) BSA and 6 mM sodium taurocholate, and cultured for 4 hours. Subsequently, the cells were recovered, and the mRNA expression levels of IL-1 and IL-6, which are inflammatory markers (inflammatory cytokines), were measured by real-time PCR as in Example 6 (n = 4 - 6).

[0227] The results are shown in Tables 9A and 9B. In Tables 9A and 9B, the "mRNA expression level" is a relative value when the value obtained using RPMI 1640 medium containing 0.02% (w / w) BSA and DMSO and not containing any of oxLDL, acLDL, T0+RA, and LPS (hereinafter referred to as "DMSO-control") is set to 1. In addition, in Tables 9A and 9B, "*" and "***" indicate that the mRNA expression level of IL-1 or IL-6 is significantly lower statistically compared to the DMSO-control (*: p < 0.05, ***: P < 0.001, both by Student's t-test).

[0228] As shown in Tables 9A and 9B, it was confirmed that 10-hydroxy palmitic acid has an inhibitory activity on the production of inflammatory cytokines (especially inhibitory of the mRNA expression of inflammatory cytokines), and further has an anti-inflammatory effect.

[0229] [Table 9A]

[0230]

[0231] [Table 9B]

[0232]

[0233] [Example 10]

[0234] Human macrophage-like THP-1 cells were seeded in a 24-well plate at a density of 1.0×10 6 cells / well and differentiated for 72 hours. Then, the medium was replaced with RPMI 1640 medium containing 0.02% (w / v) BSA (Bovine serum albumin), dimethyl sulfoxide (DMSO), 20 μg / mL 10-hydroxy palmitic acid, 50 μg / mL oxidized LDL (oxLDL) (Invitrogen), 50 μg / mL acetylated LDL (acLDL) (Invitrogen), 5 μM T0901317 + 5 μM 9-cis retinoic acid (T0+RA), or 1 μg / mL LPS (Sigma), or RPMI 1640 medium containing 0.02% (w / v) BSA, DMSO, or 20 μg / mL 10-hydroxy palmitic acid and none of oxLDL, acLDL, T0+RA, and LPS (control), and the cells were cultured for 24 hours to induce inflammation in the macrophage-like cells. Then, the medium was replaced with DMEM medium (Dulbecco's Modified Eagle Medium) containing 0.02% (w / v) BSA and 6 mM sodium taurocholate, and the cells were cultured for 4 hours. Then, the medium was collected, and the amount of cholesterol excreted from the cells (cholesterol amount in the collected medium) was measured by fluorescence assay using Amplex Red to evaluate the cholesterol efflux promoting activity of 10-hydroxy palmitic acid in the inflamed state (n = 4).

[0235] The results are shown in Table 10. In Table 10, the "cholesterol efflux amount" is the relative value when the value obtained using RPMI 1640 medium containing 0.02% (w / v) BSA and DMSO and none of oxLDL, acLDL, T0+RA, and LPS (hereinafter referred to as "DMSO-control") is set to 1. In addition, in Table 10, "*" and "**" indicate that the cholesterol efflux amount is significantly higher statistically compared to the DMSO-control (*: p < 0.05, **: P < 0.01, both by Student's t-test).

[0236] As shown in Table 10, it was confirmed that 10-hydroxy palmitic acid also has cholesterol efflux promoting activity in the inflamed state and in the state where ABC transporter expression is induced by an external factor (T0+RA).

[0237] 10-Hydroxypalmitic acid has cholesterol efflux-promoting activity even in a state where ABC transporter expression is induced by external factors (T0+RA). Therefore, it was confirmed that 10-hydroxypalmitic acid exerts cholesterol efflux-promoting activity not only through ABC transporter expression-promoting activity but also independently of (i.e., separately from) ABC transporter expression-promoting activity.

[0238] [Table 10]

[0239] < / lc>

Claims

1. An ABC transporter expression promoter, which comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

2. The ABC transporter expression promoter according to claim 1, wherein, The ABC transporter expression promoter comprises a Camembert cheese extract, and the Camembert cheese extract comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

3. A cholesterol efflux promoter, which comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

4. The cholesterol excretion promoter according to claim 3, wherein, The cholesterol efflux promoter comprises a Camembert cheese extract, and the Camembert cheese extract comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

5. The cholesterol excretion promoter according to claim 3 or 4, wherein, The cholesterol efflux promoter is administered to a subject in an inflammatory state.

6. An inflammatory cytokine production inhibitor, which comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

7. The inhibitor of inflammatory cytokine production according to claim 6, wherein, The inflammatory cytokine production inhibitor comprises a Camembert cheese extract, and the Camembert cheese extract comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

8. An anti-inflammatory agent, which comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

9. The anti-inflammatory agent according to claim 8, wherein, The anti-inflammatory agent comprises a Camembert cheese extract, and the Camembert cheese extract comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

10. An arteriosclerosis preventive agent, which comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

11. The arteriosclerosis preventive agent according to claim 10, wherein, The arteriosclerosis preventive agent comprises a Camembert cheese extract, and the Camembert cheese extract comprises at least one selected from 10-hydroxy palmitic acid and 16-hydroxy palmitic acid.

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