JP7727671B2 - Homocysteine derivative, its production method, composition, and anti-inflammatory agent - Google Patents

Description

The present invention relates to homocysteine derivatives and methods for producing them, compositions containing them, and anti-inflammatory agents containing them.

Compositions with anti-inflammatory properties have been known to date, such as cosmetics that have the effect of inhibiting MMP-9 production (see, for example, Patent Documents 1 and 2).

However, there are a wide variety of applications and target populations for which anti-inflammatory effects are required, and there is a need to develop new anti-inflammatory agents.

Japanese Patent Application Laid-Open No. 2005-298391 JP 2015-24985 A

In light of these circumstances, the present invention aims to provide novel homocysteine derivatives and methods for producing the same, compositions containing the compounds, and anti-inflammatory agents containing them, etc.

As a result of intensive research to solve the above problems, the inventors succeeded in creating the novel homocysteine derivative shown below, and discovered that the above objectives could be achieved with the above compound, thereby completing the present invention.

That is, the present invention provides the compounds listed below.

Item 1.
A compound represented by the following formula 1:

Item 2.
Item 1. The compound according to item 1, represented by the following formula 2:

Item 3.
Item 3. The compound according to item 1 or 2, which is represented by the following formula 3:

The present invention also provides the compositions described below.

Item 4.
A composition comprising the compound according to any one of items 1 to 3.

Item 5.
Item 5. The composition according to Item 4, further comprising L-ergothioneine (hereinafter also referred to as "EGT").

Item 6.
Item 6. The composition according to Item 5, wherein the content of the compound is 50 parts by mass or less per 100 parts by mass of the L-ergothioneine.

Section 7.
Item 7. The composition according to Item 5 or 6, wherein the content of the compound is 0.0001 parts by mass or more per 100 parts by mass of the L-ergothioneine.

The present invention also relates to the inflammation inhibitors listed below.

Section 8.
Item 4. An anti-inflammatory agent comprising the compound according to any one of Items 1 to 3.

Item 9.
Item 8. An anti-inflammatory agent comprising the composition according to any one of Items 4 to 7.

The present invention also relates to the manufacturing method described below.

Item 10.
Item 4. A method for producing the compound according to any one of Items 1 to 3, comprising a step of reacting ribosylhomocysteine (hereinafter also referred to as "SRH") with a reducing agent.

Item 11.
Item 11. The method according to Item 10, wherein the reducing agent comprises lithium borohydride, sodium borohydride, or zinc borohydride.

The compounds of the present invention or compositions containing them can be suitably used, for example, as anti-inflammatory agents.

In addition, by using the method for producing the compound of the present invention, the above compound or composition can be easily obtained.

In addition, the inflammation inhibitor of the present invention may be able to exert an inflammation inhibitory effect that leads to the maintenance of retinal pigment epithelial cells, for example.

FIG. 1 is a graph showing the evaluation results of the anti-inflammatory effect in Example 2.

The following describes in detail the embodiments of the present invention.

[Compound]
The homocysteine derivative of the present invention is a compound represented by the following formula 1:

The homocysteine derivative is, for example, a compound represented by the following formula 2:

The homocysteine derivative is, for example, a compound represented by the following formula 3:

The above homocysteine derivatives also include derivatives such as substitution products in which part or all of the structure is substituted, and solvates such as hydrates, as appropriate.

In the above homocysteine derivatives, some or all of the hydroxyl groups may be appropriately substituted with, for example, alkyl ether groups, aryl ether groups, or ester groups.

In addition, in the above homocysteine derivatives, the carboxyl group may be appropriately substituted with an ester group, an amide group, an acid anhydride, a salt, etc.

In addition, in the above homocysteine derivatives, the amino group may be appropriately substituted with an alkylated form, an amide group, a salt, etc.

In addition, in the above homocysteine derivatives, the sulfide group may be appropriately substituted with an alkylated salt, sulfoxide, or sulfone.

[Method for producing compounds]
The homocysteine derivatives can be produced by any known method, but it is preferable to use a production method including a step of reducing ribosylhomocysteine or the like.

For example, the method for producing the compound of the present invention preferably includes a step of reacting ribosylhomocysteine with a reducing agent.

Ribosylhomocysteine (SRH) is a homocysteine derivative in which homocysteine (2-amino-4-sulfanylbutanoic acid) is S-ribosylated, and its structure is represented by the following formula.

SRH can be obtained by known methods such as synthesis, extraction, and fermentation.

SRH may be in the free form or in the form of a salt. The salt of SRH may be a salt formed with the carboxyl group in these structures, or a salt formed with the amino group. Ribosylhomocysteine or a ribosylhomocysteine analog may also be a solvate such as a hydrate.

Salts of SRH are not particularly limited as long as they are pharmacologically or physiologically acceptable, but specific examples include organic acid salts, inorganic acid salts, and salts with organic or inorganic bases. Examples of organic acid salts include monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; polycarboxylic acid salts such as fumarate, maleate, succinate, and malonate; hydroxycarboxylic acid salts such as lactate, tartrate, and citrate; and organic sulfonates such as methanesulfonate, toluenesulfonate, and tosylate. Examples of inorganic acid salts include hydrochloride, sulfate, nitrate, hydrobromide, and phosphate. Examples of salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine, and ethylenediamine. Examples of salts with inorganic bases include ammonium salts; salts with alkali metals such as sodium or potassium, alkaline earth metals such as calcium or magnesium, and metals such as aluminum. These salts may be used alone or in any combination of two or more. "Pharmaceutically or physiologically acceptable salts" may include solvates or hydrates of the salts.

Any reducing agent can be used as long as it can reduce ribosylhomocysteine to produce the compound. Examples of reducing agents include lithium borohydride, sodium borohydride, and zinc borohydride. Among these, sodium borohydride is a particularly suitable reducing agent.

The reducing agent can be used in the reduction step using known techniques, as appropriate. For example, ribosylhomocysteine dissolved or dispersed in a solvent such as water can be reacted in a system containing, for example, 0.01 to 1000 mol % of the reducing agent at a temperature range of -10°C to 30°C for, for example, 10 minutes to 48 hours.

The above compound can be produced, for example, according to the following reaction scheme.

Furthermore, after the above reaction, a step of removing salts by electrodialysis or the like may be included.

[Composition]
The composition of the present invention contains the above-mentioned compound. These compounds may be contained alone or in combination of two or more.

In the composition of the present invention, the content of the above-mentioned compound is adjusted appropriately depending on the intended use of the composition, the type and content of other components, etc., and is not limited to, for example, 0.000001% by mass or more, 0.000005% by mass or more, 0.00001% by mass or more, 0.00005% by mass or more, 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, etc., relative to the total amount of the composition. Furthermore, the content of the above-mentioned compound can be, for example, 99.999% by mass or less, 99.9% by mass or less, 99.5% by mass or less, 99% by mass or less, 98.5% by mass or less, 98% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, 1% by mass or less, etc. In another embodiment, for example, when prepared as a liquid composition or liquid formulation, the content of the compound can be, for example, but not limited to, 80% by mass or less, relative to the total amount of the composition, and examples include 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, and 1% by mass or less.

The above composition may also contain L-ergothioneine (EGT).

EGT is a histidine derivative (N,N,N-trimethyl-L-2-thiohistidine) and its structure is represented by the following formula:

EGT can be obtained by known methods such as synthesis, extraction, and fermentation, or it can be obtained as a commercially available product.

An example of a commercially available EGT product is ^Ergonine® (manufactured by Tetraedron Co., Ltd.).

EGT may be in the free form or in the form of a salt. The salt of EGT may be a salt formed with the carboxyl group in these structures, or a salt formed with the trimethylamino group. Furthermore, L-ergothioneine or an L-ergothioneine analog may be a solvate such as a hydrate.

Salts of EGT are not particularly limited as long as they are pharmacologically or physiologically acceptable, but specific examples include organic acid salts, inorganic acid salts, and salts with organic or inorganic bases. Examples of organic acid salts include monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; polycarboxylic acid salts such as fumarate, maleate, succinate, and malonate; hydroxycarboxylic acid salts such as lactate, tartrate, and citrate; and organic sulfonates such as methanesulfonate, toluenesulfonate, and tosylate. Examples of inorganic acid salts include hydrochloride, sulfate, nitrate, hydrobromide, and phosphate. Examples of salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine, and ethylenediamine. Examples of salts with inorganic bases include various salts with alkali metals such as sodium or potassium, alkaline earth metals such as calcium or magnesium, and metals such as aluminum. These salts may be used alone or in any combination of two or more. "Pharmaceutically or physiologically acceptable salts" may include solvates or hydrates of the salts.

In addition, the content of EGT in the composition of the present invention is adjusted appropriately depending on the use of the composition, the type and content of other components, etc., and is not limited to, for example, 0.000001% by mass or more, such as 0.000005% by mass or more, 0.00001% by mass or more, 0.00005% by mass or more, 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, etc., relative to the total amount of the composition. In addition, the content of EGT can be, for example, 99.999% by mass or less, such as 99.9% by mass or less, 99.5% by mass or less, 99% by mass or less, 98.5% by mass or less, 98% by mass or less, etc., relative to the total amount of the composition. In another embodiment, when prepared as a liquid composition or liquid formulation, the content of EGT can be, for example, but is not limited to, 80% by mass or less, relative to the total amount of the composition, and examples thereof include 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, and 1% by mass or less.

When using a composition containing EGT, the daily intake (application amount) can be an effective amount that allows EGT to exert its inherent physiological activity. For example, when ingested (applied) by a healthy adult, the daily intake (application amount) of EGT can be, for example, 0.005 to 4,000 mg, preferably 0.1 to 3,000 mg, or 0.5 to 2,000 mg, 1 to 1,000 mg, 2 to 500 mg, 5 to 30 mg, etc.

The pH of the composition of the present invention is set appropriately depending on the type and content of other formulated ingredients, intended use, formulation, method of use, etc., and is not limited as long as it is within a pharmaceutically or physiologically acceptable range, but can be, for example, pH 2 to 10. From the perspective of stably exerting the effects of the present invention, the pH of the composition of the present invention can be, for example, pH 2 to 10, pH 2 to 9, pH 2 to 8, pH 2 to 7, pH 3 to 10, pH 3 to 9, pH 3 to 8, pH 3 to 7, pH 4 to 10, pH 4 to 9, pH 4 to 8, pH 4 to 7, pH 5 to 10, pH 5 to 9, pH 5 to 8, pH 5 to 7, pH 6 to 10, pH 6 to 9, pH 6 to 8, pH 6 to 7, etc.

[Application]
The composition of the present invention can further be appropriately blended with active ingredients and additives that can be used in foods and beverages, functional foods, foods for specified health uses, quasi-drugs, pharmaceuticals, cosmetics, daily necessities, feed, etc., and can be appropriately formulated using known formulation methods used for the relevant items.

It can be formulated into cosmetics and daily necessities, such as lotion, emulsion, gel, serum, cream, sunscreen cream, pack, mask, foundation, powder, bath additive, body lotion, shampoo, rinse, hair treatment, hair conditioner, hair styling product, hair tonic, toothpaste, mouthwash, etc.

Furthermore, for example, when the above composition contains EGT, it can be suitably used for the physiological activities that EGT inherently possesses, such as antioxidant, brain function improvement, anti-aging, eye disease treatment, whitening, UV absorption, melanin production inhibition, elimination of reactive oxygen species, elastase activity inhibition, wrinkle formation inhibition, skin sagging inhibition, skin blemish formation inhibition, dark circles around the eyes inhibition, UV-induced skin damage reduction (photoaging inhibition), dry skin, sensitive skin, hair improvement, and autophagy promotion.

〔formulation〕
The compositions of the present invention can be administered orally or parenterally (including topically) in the form of solid preparations such as tablets, capsules, granules, and powders; or liquid preparations such as solutions, syrups, injections, creams, lotions, pastes, ointments, emulsions (oil-in-water emulsions, water-in-oil emulsions, multiple emulsions, microemulsions, PET emulsions, and Pickering emulsions), gels (hydrogels and alcohol gels), and suspensions. Solid preparations may contain excipients, lubricants, binders, and disintegrants; liquid preparations may contain solvents, solubilizers, emulsifiers, emulsion stabilizers, thickeners, humectants, suspending agents, isotonic agents, buffers, and soothing agents. Additives such as preservatives, antioxidants, colorants, sweeteners, and flavors may also be used, if necessary.

Examples of excipients include sugar alcohols such as sorbitol, mannitol, and xylitol; sugars such as glucose, sucrose, lactose, and fructose; crystalline cellulose, carmellose sodium, croscarmellose sodium, calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, beta-cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminum metasilicate, talc, kaolin, and olive oil.

Examples of binders include cellulose derivatives such as methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, and propylene glycol alginate.

Disintegrants include, for example, starch, low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, partially pregelatinized starch, etc.

Solvents include, for example, water, alcohol, propylene glycol, macrogol, sesame oil, corn oil, etc.

Examples of lubricants include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetearyl alcohol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, and white beeswax.

Examples of solubilizing agents include polyethylene glycol, propylene glycol, mannitol, benzyl benzoate, ethanol, tris(hydroxymethyl)aminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, etc.

Examples of suspending agents and emulsifiers include surfactants such as stearylamine, triethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glycerin monostearate; hydrophilic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose; and waxes such as shellac wax, beeswax, carnauba wax, spermaceti, lanolin, liquid lanolin, reduced lanolin, hard lanolin, cyclic lanolin, lanolin wax, candelilla wax, Japan wax, montan wax, and rice wax.

Examples of isotonic agents include sodium chloride, glycerin, D-mannitol, etc.

Examples of buffering agents include buffer solutions such as phosphate, acetate, carbonate, and citrate.

Examples of preservatives include parahydroxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, etc.

Examples of antioxidants include sulfites, ascorbic acid, etc.

When the composition of the present invention is made into a solid formulation, manufacturing methods known in the art can be used. Examples include a method in which the composition is kneaded and passed through a screen to form an extruded granule, which is then pulverized and sized; and a method in which kneading water is added to the composition and the mixture is granulated using a vertical granulator, followed by pulverization and sieving using a Comil. Another example is a method in which the formulation composition is compressed using a roller compactor, pulverized using a roll granulator, and sieved. Another example is a method in which the mixture is granulated using a fluidized bed, followed by fluidized bed drying. For example, when manufacturing by direct compression, the composition can be mixed and then directly placed in a tablet press for tableting.

[Inflammatory suppressant]
The inflammation suppressant of the present invention contains the above-mentioned compound. These compounds may be contained alone or in combination of two or more.

Other anti-inflammatory agents of the present invention include the above-mentioned compositions. These compositions may be contained alone or in combination of two or more types.

The above-mentioned anti-inflammatory agent may, for example, exhibit an anti-inflammatory effect that leads to the maintenance of retinal pigment epithelial cells.

[Food and beverages]
The composition of the present invention can also be used as a food or drink composition, and can be provided by being contained in a food or functional food. Examples of such foods or functional foods include cooked rice; various noodles including soba, udon, vermicelli, Chinese noodles, instant noodles, and cup noodles; beverages such as soft drinks, carbonated drinks, energy drinks, fruit drinks, lactic acid drinks, and sports drinks; curry roux, stew, and various soups; frozen desserts such as ice cream, ice sherbet, and shaved ice; sweets such as candy, cookies, candy, gum, chocolate, candy tablets, snacks, biscuits, jelly, jam, cream, and other baked goods; processed seafood and livestock foods such as kamaboko, hanpen, ham, and sausage; 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; condiments such as sauces, dressings, miso, soy sauce, and tare sauces; soups, stews, salads, side dishes, furikake, and pickles; and various other forms of health and nutritional supplements, functional foods, and foods for specified health uses.

Supplements (powders, granules, soft capsules, hard capsules, tablets, chewable tablets, rapid-disintegrating tablets, syrups, liquids, etc.) containing the compositions of the present invention may also be prepared.

The composition of the present invention can also be added to food for animals such as pets.

Additives may be added to foods and beverages as needed. Examples of such additives include glucose, fructose, sucrose, maltose, sorbitol, trehalose, stevioside, rubusoside, corn syrup, lactose, mannitol, dextrin, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, surfactants, colorings, flavorings, and preservatives.

The composition of the present invention can be used for foods and beverages that are permitted to claim improvement, prevention, or amelioration of various symptoms or conditions. In this invention, foods and beverages that are permitted to claim improvement, prevention, or amelioration of symptoms or conditions are foods and beverages that have efficacy approved or designated by a country or public organization, such as functional foods, foods with health claims such as foods for specified health uses, and foods for special dietary uses. Although names and regulations change depending on the situation, the times, and the systems of each country, foods that are essentially the same are included in this invention.

In the present invention, the amount of the composition of the present invention is not particularly limited and may be appropriately determined depending on the purpose of application (such as the type of target disease or symptom), the target area of application, the gender and age of the recipient, the product form (e.g., food or beverage, functional food, food for specified health uses, quasi-drug, pharmaceutical, cosmetic, daily necessities or feed), the method and frequency of administration or ingestion of these, preferences, etc.

[Embodiment]
The present invention is not limited to the above-described embodiment, but discloses the following embodiments.

A compound represented by the following formula 1:

The compound represented by the following formula 2:

The compound represented by the following formula 3:

A composition comprising the compound described above.

The above composition further contains L-ergothioneine.

The composition, wherein the content of the compound is 50 parts by mass or less per 100 parts by mass of the L-ergothioneine.

The composition in which the content of the compound is 0.0001 parts by mass or more per 100 parts by mass of the L-ergothioneine.

The composition in which the content of the compound is 0.0001 parts by mass or more and 50 parts by mass or less per 100 parts by mass of the L-ergothioneine.

An anti-inflammatory agent comprising the above compound.

An anti-inflammatory agent comprising the above composition.

Use of the above compound for the manufacture of an anti-inflammatory agent.

Use of the above composition for the manufacture of an anti-inflammatory agent.

The above compound for use in suppressing inflammation.

The above composition for use in suppressing inflammation.

A method for producing the above compound, comprising the step of reacting ribosylhomocysteine with a reducing agent.

The above manufacturing method, wherein the reducing agent includes lithium borohydride, sodium borohydride, or zinc borohydride.

Next, the present invention will be explained in detail using examples, but the present invention is not limited to the following examples.

Example 1
(Preparation of SRH Reduced Form)
Ribosylhomocysteine (SRH) was prepared according to the method described in Carbohydrate Research, 2014, Vol. 394, p. 32.

To 20 mL of the ribosylhomocysteine (SRH) aqueous solution prepared above (containing 123 mg of SRH, 0.46 mmol), 17.4 mg (0.46 mmol) of sodium borohydride was added and stirred for 1 hour (pH 9-10). The reaction was monitored by HPLC, and it was found that most of the SRH had been converted to its reduced form. 5 mL of 10% NH ₄ Cl and 500 μL of 1N HCl were added to the reaction solution to adjust the pH to 6.7.

The reaction solution was desalted using an electrodialysis device (manufactured by Astom Corporation) and then concentrated to prepare 10 mL of an aqueous solution of SRH reduced form (1.08% SRH reduced form by qNMR, containing 108 mg).

(HPLC analysis conditions)
HPLC analysis was carried out under the following conditions.
Column: YMC-Pack ODS-AQ S-5 μM, 12 nm, 250 × 4.6 mm I.D.
Flow rate: 0.5mL/min, temperature: 30°C
Detector: PDA (210 nm)
Eluent: 0.1% formic acid aqueous solution Retention time: 6.2 minutes (reduced SRH), 6.6 minutes (SRH)

(High resolution mass spectrometry)
The results of liquid chromatography high resolution mass spectrometry (LC-HRMS) are shown below.
[M+H] ⁺ calculated for _{C9H20NO6S 270.1011 ;} found 270.1016
(LC-HRMS analysis conditions)
Apparatus: Agilent Technologies 6224 TOF LC/MS (Agilent Technologies)
Column: YMC-Pack ODS-AQ S-5 μM, 12 nm, 250 × 4.6 mm I.D.
Flow rate: 0.5mL/min, temperature: 30°C
Eluent: 0.1% formic acid aqueous solution Ionization conditions: ESI capillary voltage 3500 V fragmentor voltage 100 V
Retention time: 6.6 minutes (reduced SRH), 7.2 minutes (SRH)

( ^1H -NMR measurement)
The results of the ¹ H-NMR measurement are shown below.
¹ H-NMR (400 MHz, D ₂ O) DSS-d ₆ was set to 0 ppm.
δ 3.88 (m, 2H), 3.79 (m, 2H), 3.67 (m, 2H), 2.94 (m, 1H), 2.71 (m, 3H), 2.16 (m, 2H)

Example 2
(Evaluation of anti-inflammatory effect)
Human retinal pigment epithelial cell line ARPE-19 was seeded onto a 6-well plate using 10% FBS-DMEM/F12 medium and cultured in a carbon dioxide incubator under conditions of 5% CO ₂ and 37° C. for 48 hours.

After confirming that the cells had reached confluence, the medium was replaced with fresh 10% FBS-DMEM/F12 medium (control group), 10% FBS-DMEM/F12 medium containing 5 g/L of fructose (metabolic stress model group), or 10% FBS-DMEM/F12 medium containing SRH reductant (4 mM) and 5 g/L of fructose (metabolic stress, SRH reductant test group), and the cells were continued to be cultured.

After 72 hours, the medium was removed and RNA was extracted using TRIzol (Thermo Fisher) according to the protocol. RNA was then prepared using a cDNA preparation kit (TAKARA) according to the protocol.

The results are shown in Figure 1. The primers used had the following sequences:
IL-12p40: (Forward) 5'-aaggaggcgaggttctaagc-3', (Reverse) 5'-aagagcctctgctgcttttg-3'
IL-1beta: (Forward) 5'-gggcctcaaggaaaagaatc-3', (Reverse) 5'-ttctgcttgagaggtgctga-3'
MMP-9: (Forward) 5'ttgacagcgacaagaagtgg-3', (Reverse) 5'-gccattcacgtcgtccttat-3'
TNFalpha: (Forward) 5'-tccttcagacaccctcaacc-3', (Reverse) 5'-caggatcaaagctgtaggc-3'
TBP: (Forward) 5'-tataatcccaagcggtttgc-3', (Reverse) 5'-gctggaaaacccaacttctg-3'

As shown in Figure 1, the elevated levels of IL-1b and TNF due to high fructose loading confirmed the occurrence of an inflammatory response. Furthermore, the elevated levels of IL-12 suggested the occurrence of a Th1-type response. In each formulation, the system containing 4 mM SRH reduced form exhibited an inhibitory effect on the above-mentioned responses. Furthermore, the basement membrane is essential for the maintenance of retinal pigment epithelial cells, and the SRH reduced form was also found to have the effect of inhibiting the increase in MMP-9, an enzyme that degrades the basement membrane. From the above, it was confirmed that the SRH reduced form has the effect of inhibiting inflammatory responses and may contribute to the maintenance of retinal pigment epithelial cells.

Claims (11)

A compound represented by the following formula 1:
The compound according to claim 1, represented by the following formula 2:
The compound according to claim 1 or 2, represented by the following formula 3:
A composition comprising a compound according to any one of claims 1 to 3. The composition described in claim 4, further comprising L-ergothioneine. The composition described in claim 5, wherein the content of the compound is 50 parts by mass or less per 100 parts by mass of L-ergothioneine. A composition described in claim 5 or 6, wherein the content of the compound is 0.0001 parts by mass or more per 100 parts by mass of L-ergothioneine. An inflammation suppressant comprising a compound according to any one of claims 1 to 3. An inflammation suppressant comprising the composition described in any one of claims 4 to 7. A method for producing the compound described in any one of claims 1 to 3, comprising a step of reacting ribosylhomocysteine with a reducing agent. The method of claim 10 , wherein the reducing agent comprises lithium borohydride, sodium borohydride, or zinc borohydride.