JP2024064610A - Uncoupling protein-1 (UCP-1) mRNA expression promoter - Google Patents

Abstract

The present invention provides a UCP-1 mRNA expression promoter that contains a substance having an effect of promoting UCP-1 mRNA expression as an active ingredient.
The UCP-1 mRNA expression promoter of the present invention uses 3-(4-hydroxy-3-methoxyphenyl)propionic acid as an active ingredient.
[Selection diagram] None

Description

The present invention relates to an agent for promoting the expression of uncoupling protein-1 (UCP-1) mRNA.

In recent years, the diet of Japanese people has become increasingly high in calories, and the high proportion of fat intake has become a problem. Excessive fat intake can lead not only to obesity, but also to diseases such as diabetes, myocardial infarction, and cerebral infarction. The fat accumulated as a result of excessive fat intake, particularly visceral fat, is known to not only be stored as energy, but also to secrete physiologically active substances that cause damage to blood vessels, which can lead to arteriosclerosis and other conditions.

In order to prevent obesity and the various diseases associated with obesity, it is believed that it is effective to promote the burning of fat ingested through food and fat stored as body fat.

The adipose tissue of mammals, including humans, is mainly composed of white adipose tissue and brown adipose tissue. Fat cells contain mitochondria that produce ATP, and uncoupling proteins (UCPs) are present in the inner mitochondrial membrane. UCPs are known to burn neutral fats, specifically, they significantly enhance the oxidation of substrates such as fatty acids without synthesizing ATP, activating heat production. Among UCPs, UCP-1 is present in brown adipose tissue, which is thought to be involved in thermoregulation. In addition, it was thought that the gene expression of UCP-1 was at a lower level in white adipose tissue compared to brown adipose tissue, but recent studies have detected gene expression of UCP-1 in human white adipose tissue (beige cell formation), which is thought to lead to the suppression of increased fatty acid oxidation and obesity.

3-Hydroxymethyl-7-methylocta-1,6-dien-3-ol, which is obtained from mango ginger extract, and other substances are known to have the effect of enhancing UCP-1 gene expression and burning fat (see Patent Document 1).

JP 2011-241195 A

The present invention aims to discover a substance that has the effect of promoting UCP-1 mRNA expression and to provide a UCP-1 mRNA expression promoter that contains the substance as an active ingredient.

In order to solve the above problems, the UCP-1 mRNA expression promoter of the present invention is characterized by having 3-(4-hydroxy-3-methoxyphenyl)propionic acid as an active ingredient.

According to the present invention, by using 3-(4-hydroxy-3-methoxyphenyl)propionic acid as an active ingredient, it is possible to provide a highly effective UCP-1 mRNA expression promoter.

Hereinafter, an embodiment of the present invention will be described.
The UCP-1 mRNA expression promoter of this embodiment contains 3-(4-hydroxy-3-methoxyphenyl)propionic acid as an active ingredient.

[3-(4-hydroxy-3-methoxyphenyl)propionic acid]
3-(4-Hydroxy-3-methoxyphenyl)propionic acid (hereinafter sometimes abbreviated as "HMPA") is a cinnamic acid analogue represented by the following formula (I).

HMPA may be in the form of a conjugate. A conjugate is a compound obtained by binding a water-soluble substance through a phase II reaction (conjugation reaction) in a living body.
The water-soluble substance forming the above-mentioned conjugate of HMPA is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include sulfuric acid, glucuronic acid, glutathione, amino acids such as glycine, etc., among which sulfuric acid and glucuronic acid are preferred. The bond molar ratio between HMPA and the above-mentioned water-soluble substance is not particularly limited and can be appropriately selected depending on the purpose.
The site of HMPA to which the water-soluble substance binds may be a phenolic hydroxy group at the 4-position of the benzene ring or a carboxy group of the propionic acid moiety, with the phenolic hydroxy group at the 4-position being preferred.

Among the conjugates of HMPA, a particularly suitable one is a sulfate conjugate in which the phenolic hydroxy group at the 4-position is conjugated with sulfuric acid. Such a sulfate conjugate is a compound represented by the following formula (II).

HMPA can form a salt with a cation by dissociating a hydrogen ion from a carboxy group (-COOH) in the molecule and exchanging it with another cation. In addition, when a conjugate of HMPA is used as HMPA, a carboxy group or sulfate group derived from a water-soluble substance can also form a salt. In this embodiment, a salt of HMPA or a conjugate of HMPA may be used as HMPA.
Examples of cations capable of forming a salt with HMPA or a conjugate thereof include sodium ion, potassium ion, ammonium ion, magnesium ion, calcium ion, etc., and among these, sodium ion, potassium ion, and ammonium ion are preferred.

Here, the sodium salt of HMPA is a compound represented by the following formula (III). The sodium salt of the above sulfate conjugate of HMPA is a compound represented by the following formula (IV).

HMPA can be produced, for example, by synthesis, or by purification and isolation from a plant extract containing HMPA. In this case, such a plant extract containing HMPA can be obtained by a method commonly used for plant extraction. Examples of plants that contain HMPA include rice, barley, wheat, soybeans, adzuki beans, and corn.

HMPA can also be produced by, for example, fermenting 3-(4-hydroxy-3-methoxyphenyl)propenoic acid or a derivative thereof, or a composition containing the same (for example, crushed plant material or extract, etc.) with a microorganism having phenolic acid reductase, converting the 3-(4-hydroxy-3-methoxyphenyl)propenoic acid to HMPA, and then extracting, purifying, and isolating the resulting fermentation product. Examples of compositions containing 3-(4-hydroxy-3-methoxyphenyl)propenoic acid include crushed plant material and extracts of plants such as coffee, wheat, corn, tomato, yerba mate, mugwort, and burdock. In addition, since 3-(4-hydroxy-3-methoxyphenyl)propenoic acid is a component of lignin in woody plants and herbaceous plants, lignin or a composition containing the same may be used as the fermentation raw material. On the other hand, examples of microorganisms having phenolic acid reductase include lactic acid bacteria such as Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus crispatus, Lactobacillus acidophilus, Lactobacillus amylovorus, Lactobacillus delbrueckii, Lactobacillus buchneri, Lactobacillus kefiranofaciens, Lactobacillus gallinarum, and Enterococcus faecalis.

The method for extracting, purifying and isolating HMPA from the above-mentioned plant or fermented product is not particularly limited, and can be carried out according to a conventional method. For example, the extraction process can be carried out by drying the above-mentioned plant or fermented product as the extraction raw material, and then subjecting it to extraction with an extraction solvent, either as is or after crushing using a crusher. Drying can be carried out in the sun or using a commonly used dryer. In addition, the product can be used as the extraction raw material after pretreatment such as degreasing with a nonpolar solvent such as hexane. By carrying out pretreatment such as degreasing, extraction with a polar solvent can be carried out efficiently.

As the extraction solvent, it is preferable to use a polar solvent, such as water or a hydrophilic organic solvent, which is preferably used alone or in combination of two or more at room temperature or at a temperature below the boiling point of the solvent.

Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, etc., as well as water that has been subjected to various treatments. Treatments that can be applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, etc. Therefore, water that can be used as an extraction solvent in this embodiment also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered physiological saline, etc.

Examples of hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic alcohols with 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; polyhydric alcohols with 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin; and lower aliphatic ketones, such as acetone and methyl ethyl ketone.

When a mixture of two or more polar solvents is used as an extraction solvent, the mixture ratio is arbitrary and can be adjusted appropriately. For example, when a mixture of water and a hydrophilic organic solvent is used as an extraction solvent, the mixture ratio can be arbitrarily adjusted, that is, between more than 0:100 and less than 100:0 (volume ratio, hereinafter the same).
For example, when a mixture of water and a lower aliphatic alcohol is used as the extraction solvent, the mixing ratio (volume ratio) of water to lower aliphatic alcohol can be 9:1 or more, or can be 7:3 or more, or the mixing ratio of water to lower aliphatic alcohol can be 1:9 or less, or can be 2:8 or less. When a mixture of water and a polyhydric alcohol is used, the mixing ratio of water to polyhydric alcohol can be 8:2 or more, or can be 1:9 or less, and when a mixture of water and a lower aliphatic ketone is used, the mixing ratio of water to lower aliphatic ketone can be 9:1 or more, or can be 2:8 or less.

The extraction process is not particularly limited as long as the soluble components contained in the extraction raw material can be dissolved in the extraction solvent, and can be carried out according to conventional methods. For example, the extraction raw material is immersed in an extraction solvent in an amount 5 to 15 times (by mass) the amount of the extraction raw material, and the soluble components are extracted at room temperature or under reflux heating, and then the extraction residue is removed by filtration to obtain an extract. The solvent is distilled off from the obtained extract to obtain a paste-like concentrate, and this concentrate is further dried to obtain a dry product.

The method for purifying and isolating HMPA from the extract obtained as described above, the concentrate of the extract, or the dried product of the extract is not particularly limited and can be carried out by conventional methods.

On the other hand, a conjugate of HMPA can be obtained by subjecting HMPA obtained by the above-mentioned method to a conjugation reaction. Such a conjugation reaction can be carried out by a known method, and examples of such methods include in vitro enzymatic synthesis using an enzyme that catalyzes the conjugation reaction; biosynthesis using recombinant yeast or the like that expresses the enzyme; and organic synthesis, and any of these may be used. As the enzyme that catalyzes the conjugation reaction, sulfotransferase (SULT), UDP-glucuronosyltransferase, glutathione-S-transferase, and the like can be appropriately used depending on the type of water-soluble substance that forms the conjugate.
The method for purifying and isolating the HMPA conjugate from the reaction solution obtained in the conjugation reaction is not particularly limited, and can be carried out by a conventional method.

In this embodiment, the active ingredient of the UCP-1 mRNA expression promoter may be at least one of HMPA (neither a conjugate nor a salt); a conjugate of HMPA; or a salt thereof, and two or more of these (when the conjugate or the salt is a different type) may be used in appropriate combination.
In the following specification, when the term "HMPA" is used, it includes not only HMPA but also its conjugates and salts thereof, unless otherwise specified.

[UCP-1 mRNA expression promoter]
The HMPA obtained as described above has an excellent uncoupling protein-1 (UCP-1) mRNA expression promoting effect, and can therefore be used as an active ingredient of a UCP-1 mRNA expression promoting agent. In other words, HMPA can be used to produce a UCP-1 mRNA expression promoting agent.

The UCP-1 mRNA expression promoter of this embodiment can be used for a wide range of applications, such as medicines, quasi-drugs, cosmetics, and oral compositions. Here, the UCP-1 mRNA expression promoter of this embodiment is preferably an agent labeled with information regarding the UCP-1 mRNA expression promoting effect of HMPA.

When HMPA is used as the active ingredient of the UCP-1 mRNA expression promoter of this embodiment, a composition containing HMPA may be used instead of isolated HMPA. Here, the "composition containing HMPA" in this embodiment includes an extract obtained using a natural product containing HMPA as an extraction raw material, a processed natural product containing HMPA, and an extract obtained using the processed natural product as an extraction raw material.

In addition, when an HMPA conjugate is used as the active ingredient of the UCP-1 mRNA expression promoter of this embodiment, a composition containing an HMPA conjugate may be used instead of an isolated HMPA conjugate. Here, the "composition containing an HMPA conjugate" in this embodiment includes a culture containing an HMPA conjugate, and an extract obtained using the culture as an extraction raw material.

In this embodiment, the term "extract" includes the extract obtained by the extraction process, a dilution or concentrate of the extract, or a dried product obtained by drying the extract.

The UCP-1 mRNA expression promoter of this embodiment may consist of HMPA alone, or may be a formulation of HMPA.
The UCP-1 mRNA expression promoter of this embodiment can be formulated into any dosage form, such as powder, granules, tablets, liquid, etc., in accordance with a conventional method using a pharma- ceutically acceptable carrier such as dextrin, cyclodextrin, or any other auxiliary agent. In this case, examples of auxiliary agents that can be used include excipients, binders, disintegrants, lubricants, stabilizers, flavorings, and odorants. The UCP-1 mRNA expression promoter can be used by being blended with other compositions (e.g., skin topical agents, oral compositions, etc.), and can also be used as ointments, topical liquids, patches, etc.

When the UCP-1 mRNA expression promoter of this embodiment is formulated, the content of HMPA is not particularly limited and can be set appropriately depending on the purpose.

The UCP-1 mRNA expression promoter of this embodiment can use only HMPA as the active ingredient for promoting UCP-1 mRNA expression, and if necessary, other natural extracts or the like having the effect of promoting UCP-1 mRNA expression can be mixed with HMPA and used as active ingredients.

Methods for administering the UCP-1 mRNA expression promoter of this embodiment to a patient include transdermal administration and oral administration, and a method suitable for prevention, treatment, etc. may be appropriately selected depending on the type of disease. The dosage of the UCP-1 mRNA expression promoter of this embodiment may also be appropriately increased or decreased depending on the type and severity of the disease, individual differences between patients, administration method, administration period, etc.

The UCP-1 mRNA expression promoter of this embodiment can promote fat burning in, for example, white adipose tissue or brown adipose tissue and prevent or improve obesity through the UCP-1 mRNA expression promoting effect of the active ingredient HMPA. However, in addition to these uses, the UCP-1 mRNA expression promoter of this embodiment can be used for all uses in which it is meaningful to exert an effect of promoting UCP-1 mRNA expression.

In addition, since the UCP-1 mRNA expression promoter of this embodiment has an excellent UCP-1 mRNA expression promoting effect, it is suitable for incorporation into, for example, topical skin preparations and oral compositions described below. In this case, HMPA may be incorporated as is, or a UCP-1 mRNA expression promoter formulated from HMPA may be incorporated.

In addition, since the UCP-1 mRNA expression promoter of this embodiment has an excellent UCP-1 mRNA expression promoting effect, it can be suitably used as a reagent for research on the mechanism of action of these.

[Incorporation into topical skin preparations]
HMPA has an excellent UCP-1 mRNA expression promoting effect, and is therefore suitable for incorporation into topical skin preparations. In this case, HMPA may be incorporated as is, or a UCP-1 mRNA expression promoting agent prepared by formulating HMPA may be incorporated. This makes it possible to provide a topical skin preparation suitable for promoting UCP-1 mRNA expression. In other words, incorporation into topical skin preparations is one of the suitable uses of the UCP-1 mRNA expression promoting agent.

Here, topical skin preparations are not limited to specific categories and include a wide range of drugs, quasi-drugs, cosmetics, etc. that are used transdermally, and specific examples include ointments, creams, milky lotions, skin toners, beauty serums, lotions, gels, beauty oils, packs, foundations, lip balms, bath additives, hair tonics, hair lotions, soaps, body shampoos, etc.

The amount of the active ingredient in the topical skin preparation can be adjusted as appropriate depending on the type of topical skin preparation, but for example, a suitable content rate of HMPA (calculated as the mass of HMPA) is 0.0001 to 10% by mass, and a particularly suitable content rate is 0.001 to 1% by mass. Here, the conversion to the mass of HMPA means that when a conjugate or salt of HMPA is used as HMPA, it is converted to the mass of an equimolar amount of HMPA (neither a conjugate nor a salt), and the same applies below.

The topical skin preparation of this embodiment can be used in combination with main agents, auxiliary agents, or other ingredients used in the manufacture of ordinary topical skin preparations, such as astringents, germicides/antibacterial agents, whitening agents, UV absorbers, moisturizers, cell activators, anti-inflammatory/anti-allergic agents, antioxidants/active oxygen removers, oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, fragrances, etc., so long as the effect of promoting UCP-1 mRNA expression by HMPA is not hindered. By using such a combination, a more general product can be obtained, and the synergistic effect with the other active ingredients used in combination can bring about a superior effect than would normally be expected.

The topical skin preparation of this embodiment can promote fat burning in white and brown adipose tissues through the UCP-1 mRNA expression promoting effect of HMPA, thereby preventing or ameliorating obesity.

Incorporation into oral compositions
HMPA has an excellent UCP-1 mRNA expression promoting effect, and is therefore suitable for incorporation into an oral composition. In this case, HMPA may be incorporated as is, or a UCP-1 mRNA expression promoting agent formulated from HMPA may be incorporated. This makes it possible to obtain an oral composition suitable for promoting UCP-1 mRNA expression. In other words, incorporation into an oral composition is one of the suitable uses of the UCP-1 mRNA expression promoting agent.

Here, an oral composition refers to a composition that is unlikely to be harmful to human health and is taken orally or by administration through the digestive tract in normal social life, and is not limited to administrative classifications such as food, medicine, and quasi-drug. Therefore, the "oral composition" in this embodiment broadly includes general foods, health foods, health functional foods (foods for specified health uses, foods with nutritional functions, foods with functional claims), quasi-drugs, medicines, etc. that are taken orally. The oral composition according to this embodiment is preferably an oral composition that can display the favorable effects of HMPA on the oral composition or its packaging, and is particularly preferably a health functional food (foods for specified health uses, foods with functional claims, foods with nutritional functions), quasi-drugs, and medicines.

When HMPA or a UCP-1 mRNA expression promoter formulated from HMPA is incorporated into an oral composition, the amount of active ingredient can be appropriately changed taking into consideration the purpose of use, symptoms, sex, etc., but taking into consideration the general intake of the oral composition to which it is added, it is preferable that the daily intake of HMPA (calculated as the mass of HMPA) for adults is about 1 to 1000 mg. Note that when the oral composition to which it is added is a granular, tablet, or capsule-shaped oral composition, the amount of HMPA or a UCP-1 mRNA expression promoter formulated from HMPA added (calculated as the mass of HMPA) is usually 0.1 to 100% by mass, and preferably 5 to 100% by mass, of the oral composition to which it is added.

The oral composition of this embodiment may be any oral composition in which HMPA is incorporated so as not to interfere with its activity, or may be a dietary supplement containing HMPA as a main ingredient.

When producing the oral composition of this embodiment, any auxiliary agent can be added, such as sugars such as dextrin and starch; proteins such as gelatin, soy protein, and corn protein; amino acids such as alanine, glutamine, and isoleucine; polysaccharides such as cellulose and gum arabic; and fats and oils such as soybean oil and medium-chain fatty acid triglycerides, to form an oral composition of any shape.

Oral compositions that can contain HMPA are not particularly limited, but specific examples include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (including concentrated concentrates and powders for adjusting these beverages); frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, vermicelli, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; sweets such as candy, chewing gum, candies, gum, chocolate, tablet candy, snacks, biscuits, jellies, jams, creams, and baked goods; processed seafood and livestock foods such as kamaboko, ham, and sausages; dairy products such as processed milk and fermented milk; oils and fats and oil-based processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; seasonings such as sauces and sauces; soups, stews, salads, side dishes, and pickles; health and nutritional supplements in various forms; tablets, capsules, and energy drinks. When HMPA is added to these oral compositions, commonly used auxiliary ingredients and additives can be used in combination.

The UCP-1 mRNA expression promoter of this embodiment is preferably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as the respective action effects are exerted.

The present invention will be specifically explained below with test examples and formulation examples, but the present invention is not limited to the following examples. In the test examples and formulation examples below, Sample 1 below was used as HMPA, and Sample 2 below was used as the sulfate conjugate (sodium salt) of HMPA.

[Test Example 1] Test for promoting effect of UCP-1 mRNA expression HMPA (sample 1) and dihydroferulic acid sulfate conjugate (sample 2) were tested for their promoting effect of UCP-1 mRNA expression as follows.

Human visceral preadipocytes (Lonza) were precultured in a 75 ^cm2 flask using growth medium (PGM-2 Bullet Kit, Lonza) at 37°C and 5% _CO2 , and the cells were harvested by trypsinization. The harvested cells were diluted with PGM-2 Bullet Kit medium, and then seeded at 7.5 x ¹⁰⁴ cells/well on a collagen-coated 6-well plate (IWAKI) and cultured at 37°C and 5% _CO2 until confluent.

After the culture, the culture medium was removed and replaced with a differentiation induction medium (the above growth medium to which insulin, dexamethasone, indomethacin and isobutylmethylxanthine had been added), and the cells were cultured for 14 days at 37°C under 5% _CO2 to differentiate the preadipocytes into fat cells that had stored oil droplets. The medium was then removed, and the medium was replaced with a growth medium (PGM-2 Bullet Kit) containing the test samples (samples 1-2, see Table 2 below for sample concentrations) or a growth medium without the samples, and the cells were cultured for another 24 hours. After the culture, the culture medium was removed, and total RNA was extracted using ISOGEN II (manufactured by NIPPON GENE), the amount of RNA was measured from the absorbance at a wavelength of 260 nm, and total RNA was prepared to be 200 ng/μL.

The total RNA was used as a template to measure the expression levels of UCP-1 and the internal standard GAPDH mRNA. Detection was performed by a two-step real-time RT-PCR reaction using a real-time PCR device, Thermal Cycler ^Dice® Real Time System III (manufactured by TaKaRa), PrimeScript ^™ RT Master Mix (Perfect Real Time) and TB ^Green® Fast qPCR Mix (manufactured by TaKaRa). Perfect Real Time Primer (manufactured by Takara Bio) was used as the primer.
The expression level of UCP-1 mRNA was calculated based on the total RNA samples prepared from cells cultured with and without the addition of the test sample, and was corrected with the expression level of GAPDH mRNA. The UCP-1 mRNA expression promotion rate (%) was calculated from the obtained values according to the following formula.

UCP-1 mRNA expression promotion rate (%) = A / B × 100
A: UCP-1 mRNA expression level when test sample was added (corrected value)
B: UCP-1 mRNA expression level (corrected value) when no test sample was added
The results are shown in Table 2.

As shown in Table 2, it was confirmed that both HMPA (sample 1) and dihydroferulic acid sulfate conjugate (sample 2) have excellent UCP-1 mRNA expression promoting effects.

[Formulation Example 1]
According to the composition below, a milky lotion was prepared by a conventional method.
HMPA 0.01g
Jojoba oil 4.00g
1,3-butylene glycol 3.00g
Arbutin 3.00g
Polyoxyethylene cetyl ether (20E.O.) 2.50g
2.00g olive oil
Squalane 2.00g
Cetanol 2.00g
Glyceryl monostearate 2.00g
Polyoxyethylene sorbitan oleate (20E.O.) 2.00g
Methyl paraoxybenzoate 0.15g
Stearyl glycyrrhetinate 0.10g
Phellodendron extract 0.10g
Dipotassium glycyrrhizinate 0.10g
Ginkgo leaf extract 0.10g
Conchiolin 0.10g
Phellodendron bark extract 0.10g
Chamomile extract 0.10g
Fragrance 0.05g
Purified water Remainder (total amount is 100g)

[Formulation Example 2]
A cream having the following composition was prepared by a conventional method.
Sodium salt of HMPA sulfate conjugate 0.05g
Sophora root extract 0.1g
Scutellaria root extract 0.1g
Liquid paraffin 5.0g
White beeswax 4.0g
Squalane 10.0g
Cetanol 3.0g
Lanolin 2.0g
Stearic acid 1.0g
Polyoxyethylene sorbitan oleate (20E.O.) 1.5g
Glyceryl monostearate 3.0g
Oil-soluble licorice extract 0.1g
1,3-butylene glycol 6.0g
Methyl paraoxybenzoate 1.5g
Fragrance 0.1g
Purified water Remainder (total amount is 100g)

[Formulation Example 3]
Tablets having the following composition were prepared by a conventional method.
HMPA 5.0 mg
Dolomite (containing 20% calcium and 10% magnesium) 83.4 mg
Casein phosphopeptide 16.7mg
Vitamin C 33.4mg
Maltitol 136.8mg
Collagen 12.7mg
Sucrose fatty acid ester 12.0 mg

[Formulation Example 4]
An oral liquid preparation having the following composition was produced by a conventional method.
<Composition in 1 ampoule (100 mL per bottle)>
Sodium salt of HMPA sulfate conjugate 0.3% by mass
Sorbitol 12.0% by mass
Sodium benzoate 0.1% by mass
Fragrance 1.0% by mass
Calcium sulfate 0.5% by mass
Purified water Balance (100% by weight)

Claims (1)

An uncoupling protein-1 (UCP-1) mRNA expression promoter characterized by containing 3-(4-hydroxy-3-methoxyphenyl)propionic acid as an active ingredient.