JP5674984B1 - Epithelial sodium channel inhibitor - Google Patents

Abstract

The present invention provides an ENaC inhibitor and a salty taste inhibitor that have an ENaC inhibitory action and are effective in reducing salty taste. SOLUTION: An epithelial sodium channel inhibitor and salty taste suppressant containing an octenyl sulfate ester represented by the following formula (1) or a salt thereof (wherein the wavy line indicates either cis or trans configuration) as an active ingredient. . [Selection figure] None

Description

  The present invention relates to an epithelial sodium channel inhibitor that inhibits epithelial sodium channel (hereinafter also referred to as “ENaC”) and has a salty taste suppressing effect and the like.

  Salt is widely contained in many natural foods, and there is almost no fear of deficiency in normal life. However, if you sweat a lot due to sports, vomiting or diarrhea, or if you have heat stroke, a lot of sodium is lost and the amount of blood sodium decreases. Accordingly, it is necessary to appropriately supply minerals such as sodium. For example, to prevent heat stroke, the Ministry of Health, Labor and Welfare is instructed to take water frequently and take appropriate salt.

  However, when a mineral component is blended in a food or drink, there is a problem that when the concentration is increased, the saltiness becomes stronger and the palatability is lowered. Therefore, a means for suppressing such salty taste is required. For example, a method of masking salty taste by adding a saccharide such as inulin (Patent Document 1) or D-psicose (Patent Document 2) is known. .

  As one of such salty oral receptors, a voltage-independent sodium channel (ENaC) whose activity is suppressed by amiloride has recently been found. It is known that amiloride suppresses the saltiness of the front of the tongue, but does not suppress the saltiness of the back of the tongue and only suppresses about half of the saltiness as a sensation in the entire oral cavity (Non-patent Document 1). From this, it is considered that salty taste receptors that are insensitive to amiloride exist in addition to ENaC in the oral taste of salty taste, and it is suggested that bitterness and sour taste receptors are involved as the receptors. Specifically, it is considered that ENaC is involved in a salty taste with a low concentration of 100 mM or less, and a bitter or sour receptor is involved in a salty taste with a high concentration (Non-patent Document 2). Therefore, it is considered that inhibiting ENaC is effective in suppressing low-concentration salty taste.

  In addition to miso, ENaC is expressed in many human epithelial tissues (kidney, bladder, lung, respiratory tract, salivary gland, sweat gland, etc.) and serves as an inflow route for sodium ions (Non-patent Document 3). For example, in the kidney, it is known to precisely control the amount of sodium in the body by reabsorbing sodium in the renal cortical collecting duct, and it plays a very important role in regulating body fluid volume, plasma osmotic pressure, blood pressure, etc. have. Furthermore, ENaC overexpression and hyperfunction are associated with diseases such as hypertension and renal function deterioration, cystic fibrosis, pulmonary edema, ulcerative colitis, diarrhea, etc. It is reported that it is useful for prevention / improvement of the disease (see Non-Patent Document 3).

On the other hand, alkenyl sulfate is a kairomone-like substance in which cis / trans-3-decenyl sulfate induces morphological change induction of green algae (Non-patent Documents 4 and 5), and trans-3-decenyl sulfate is It has been reported that it has antibacterial activity (Non-patent Document 6).
However, no alkenyl sulfate having an ENaC inhibitory action or a salty taste inhibitory action has been known so far.

JP 2007-209268 A Japanese Patent No. 5314207

Ninomiya, Y. Proceedings of the National Academy of Science of the United States of America, 1998, 95, 5347-5350. Oka, Y .; et al. Nature, 494, 472-475 (2013) Bhalla, V .; et al. Journal of American Society of Nephrology. 2008, 19, 1845-1854. Yasumoto, K .; et al. Chemical & Pharmceutical Bulltein, 2008, 56 (1), 133-136. Yasumoto, K .; et al. Tetrahedron Letters, 2005, 46, 4765-4767. La, M-P .; et al. CHEMISTRY & BIODIVERSITY, 2012, 9, 1166-1171

  The present invention relates to providing an ENaC inhibitor and a salty taste inhibitor that have an ENaC inhibitory action and are effective in reducing salty taste.

  The present inventor has found that octenyl sulfate ester or a salt thereof has an ENaC inhibitory action and a salty taste inhibitory action, and can be used as an ENaC inhibitor and a salty taste inhibitor.

That is, the present invention relates to the following 1) to 3).
1) An epithelial sodium channel inhibitor containing an octenyl sulfate ester or a salt thereof represented by the following formula (1) as an active ingredient.
2) A salty taste inhibitor containing as an active ingredient an octenyl sulfate ester represented by the following formula (1) or a salt thereof.
3) The salty taste suppression method which uses the salty taste inhibitor of said 2) with respect to a salty substance containing composition.

(Where, wavy lines indicate either cis or trans configuration)

The ENaC inhibitor or salty taste suppressant of the present invention can reduce the salty taste without harming safety by using it for oral compositions containing salty substances such as sodium chloride, foods and the like. As a result, it is possible to enhance the product value such as improving the feeling of use of the oral composition and improving the taste of food.
Further, the ENaC inhibitor of the present invention prevents diseases that develop due to overexpression (hyperfunction mutation) of ENaC, such as hypertension, cystic fibrosis, pulmonary edema, ulcerative colitis, diarrhea and the like Or it can be used for improvement.

The figure which shows ENaC inhibitory effect.

  The octenyl sulfate ester represented by the general formula (1) of the present invention (referred to as octenyl sulfate ester (1)) is trans-3-octenyl sulfate (1a) represented by the following formula, and cis-3-octane. Although it is tenyl sulfate (1b), the trans form is preferable from the viewpoint of ENaC inhibitory action and salty taste suppression.

  Suitable salts of the octenyl sulfate ester (1) of the present invention are pharmaceutically acceptable salts such as alkali metal salts (for example, sodium salts, potassium salts and the like), alkaline earth metal salts (for example, Metal salts such as magnesium salts, calcium salts, etc.), ammonium salts, or trimethylamine, triethylamine, tributylamine, pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, N, N-dimethylaniline, N-methylpiperidine, Nitrogen-containing organic bases such as N-methylmorpholine, diethylamine, cyclohexylamine, procaine, dibenzylamine, N-benzyl-β-phenethylamine, 1-ephamine, N, N′-dibenzylethylenediamine, N-methyl-D-glucamine Lysine, arginine, It may be mentioned salts with basic amino acids such as carnitine. Of these, alkali metal salts are preferable, and sodium salts and potassium salts are more preferable.

  The octenyl sulfate ester (1) or a salt thereof of the present invention can exist not only as an unsolvated type but also as a hydrate or a solvate. Accordingly, in the present invention, all crystal forms and hydrates or solvates thereof are included.

  The octenyl sulfate ester (1) of the present invention is obtained by, for example, reacting trans-3-octen-1-ol (2) or cis-3-octen-1-ol (3) with a sulfating reagent in an organic solvent. Can be produced by sulfate esterification.

The sulfating reagent used here is not particularly limited as long as it can sulfate alcohols. For example, sulfur trioxide pyridine complex, sulfur trioxide trimethylamine complex, sulfur trioxide triethylamine complex, sulfur trioxide dimethyl Examples include formamide complex, sulfuric acid-dicyclohexylcarbodiimide, chlorosulfuric acid, concentrated sulfuric acid, sulfamic acid, and the like. Among these, sulfur trioxide pyridine complex is preferable.
The reaction solvent is not limited as long as it does not interfere with the esterification reaction, and examples of suitable solvents include tetrahydrofuran, acetonitrile, dimethylformamide, dichloromethane, chloroform, ether, carbon tetrachloride and the like.
The reaction temperature may be from room temperature to around the boiling point of the solvent, but is preferably -20 to 200 ° C, more preferably 0 to 100 ° C. The reaction time is 0.1 to 48 hours, preferably 1 to 12 hours.

Trans-3-octen-1-ol (2) used as a raw material can be obtained, for example, by reacting 1-heptene and paraformaldehyde in the presence of an organoaluminum compound such as dimethylaluminum chloride (Snider , BB; et al. Journal of American Chemical Society, 1982, 104, 555-563.).
Cis-3-octen-1-ol (3) is generally available, but can be obtained, for example, by subjecting 3-octin-1-ol to a catalytic hydrogenation reaction using a Lindlar catalyst. (See Mayer, SF; et al. European Journal of Organic Chemistry, 2001, 4537-4542.)

  The salt of octenyl sulfate (1) of the present invention includes basic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonia, trimethylamine, triethylamine, tributylamine, pyridine, quinoline, piperidine, imidazole. , Picoline, dimethylaminopyridine, N, N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, cyclohexylamine, procaine, dibenzylamine, N-benzyl-β-phenethylamine, 1-ephenamine, N, N Octenyl sulfate ester (1) is heated at room temperature or appropriately in the presence of nitrogen-containing organic bases such as' -dibenzylethylenediamine and N-methyl-D-glucamine, and basic amino acids such as lysine, arginine and ornithine. It can be obtained by the. Alternatively, the octenyl sulfate (1) can be obtained by adsorbing to a basic anion exchange resin and eluting with an eluent containing the basic compound.

  Isolation and / or purification of the octenyl sulfate ester (1) of the present invention or a salt thereof obtained by the above reaction can be performed by, for example, filtration, washing, drying, recrystallization, various chromatography and the like.

The octenyl sulfate ester (1) of the present invention inhibits the inflow of sodium ions from ENaC into cells and effectively suppresses the salty taste caused by sodium chloride, as shown in the Examples below.
Therefore, the octenyl sulfate (1) or a salt thereof can be an ENaC inhibitor or a salty taste suppressor, and the octenyl sulfate (1) or a salt thereof is used for producing an ENaC inhibitor or a salty taste suppressor. be able to.

  In the present invention, “ENaC inhibition” means inhibiting the inflow of sodium ions into cells from epithelial sodium channels. ENaC inhibitory activity can be tested by measuring the inhibitory effect on ENaC in an appropriate cell-based assay. For example, single cell or confluent epithelium designed to endogenously or overexpress ENaC can be used to assess channel function using electrophysiological techniques ( The journal of biological chemistry, 284 (2): pages 792-798 (2009)).

ENaC is expressed in miso and functions as an amiloride-sensitive salty taste receptor. ENaC is also expressed in many human epithelial tissues such as kidney, bladder, lung, airway, salivary gland, sweat gland (non-patent document 3), and is responsible for regulation of body fluid volume, plasma osmotic pressure, blood pressure, etc. Overexpression of ENaC (hyperfunction mutation) is known to cause diseases such as hypertension, cystic fibrosis, pulmonary edema, ulcerative colitis, and diarrhea (Non-patent Document 3).
Therefore, octenyl sulfate ester (1) or a salt thereof can be used to inhibit ENaC for the purpose of preventing or ameliorating the above diseases. Here, the “use” may be a use in a human or non-human animal or a sample derived therefrom, and may be a therapeutic use or a non-therapeutic use. Further, “non-therapeutic” means a concept that does not include medical practice, that is, a concept that does not include a method for operating, treating, or diagnosing a human. It is a concept that does not include a method of performing surgery, treatment or diagnosis.

That is, the composition containing the ENaC inhibitor of the present invention becomes a drug, quasi-drug, or food that exhibits ENaC inhibition or the above-described prevention or improvement effect for each disease, and the ENaC inhibitor is a drug, quasi-drug. Or it is useful as a raw material or a formulation for mix | blending with a foodstuff. The food includes foods that indicate ENaC inhibition and improvement of symptoms of the above-mentioned diseases, functional foods, foods for the sick, foods for specified health use, and supplements.
The pharmaceutical, quasi-drug, and food preparation forms are not particularly limited, and can be prepared by appropriately combining an acceptable carrier and octenyl sulfate (1) or a salt thereof.

Moreover, the salty taste suppression using the ENaC inhibitor or salty taste inhibitor of the present invention can suppress the salty taste by using these for a composition containing a salty substance (salt taste-causing substance). .
Here, “suppression of salty taste” includes reducing salty taste and inhibiting salty taste.
Examples of the salty substance-containing composition include oral compositions and foods. Examples of the salty substance include metal ions derived from minerals such as sodium, potassium, calcium, magnesium, and phosphorus, chloride ions, and one or more metal chlorides composed of the metal ions and chloride ions. Typical examples include sodium chloride and potassium chloride.

When the ENaC inhibitor or salty taste suppressant of the present invention is used for salty taste suppression, the ENaC inhibitor or salty taste suppressant is added to the salty substance-containing composition, The combined use is mainly mentioned.
For the combined use with a salty substance-containing composition, for example, an aqueous solution of the ENaC inhibitor or salty taste inhibitor is prepared, and this is previously contained in the oral cavity, and then the salty substance-containing composition is orally ingested, or the like Examples include a method in which an aqueous solution of an ENaC inhibitor or a salty taste inhibitor and a salty substance-containing composition are orally ingested at the same time.

  The ENaC inhibitor or salty taste inhibitor of the present invention may contain only the octenyl sulfate (1) or a salt thereof, such as water, starch, protein, fiber, carbohydrate, lipid, fatty acid, vitamin. One or a plurality of raw materials and / or raw materials usually used in pharmaceuticals and foods such as minerals, flavoring agents, coloring agents, sweeteners, seasonings, preservatives, preservatives, and antioxidants may be blended. Moreover, the form is arbitrary and any of solution form, suspension form, syrup form, powder form, granule form, particle form, etc. may be sufficient, and it can shape | mold into a desired shape.

  The salty substance-containing composition (for example, oral composition, food, etc.) is in the form of a liquid or paste such as an aqueous solution, suspension or emulsion, or a solid such as powder, granule or particle. Either is acceptable. Food includes soft drinks, tea-based beverages, coffee beverages, fruit juice beverages, carbonated beverages, sports drinks, juices, jelly, wafers, biscuits, bread, noodles, sausages and other general food and beverages, nutritional foods, functional foods, etc. Any kind may be sufficient. Examples of the oral composition include dentifrice, mouthwash, gingival massage cream, and the like. Suitable salty substance-containing compositions include various solid foods, beverages, dentifrices, mouthwashes and the like containing salty substances.

  When the ENaC inhibitor or salty taste suppressant of the present invention is applied to such a composition, if the composition is in the form of a liquid or paste such as an aqueous solution, suspension or emulsion, the ENaC of the present invention. A method of adding an inhibitor or a salty taste inhibitor and sufficiently stirring and dispersing can be applied. Moreover, when the form of the composition is a solid such as a powder, a method of simply adding and mixing the ENaC inhibitor or salty taste inhibitor of the present invention can be applied.

  When the ENaC inhibitor or salty taste suppressant of the present invention is used for a salty substance-containing composition, the ENaC inhibitor or salty taste suppressant is octenyl sulfate ester (1 ) Or a salt thereof is preferably 0.001 part by mass or more, preferably 0.01 part by mass or more and 90 parts by mass or less, preferably 10 parts by mass or less. Moreover, it is more preferable to use 0.001-90 mass parts, Preferably 0.01-10 mass parts is used.

  The content of octenyl sulfate (1) or a salt thereof in a pharmaceutical, quasi-drug or food containing the octenyl sulfate (1) or a salt thereof of the present invention is not particularly limited, but is 0. 1 mass% or more, preferably 1 mass% or more, more preferably 10 mass% or more, and 99 mass% or less, preferably 90 mass% or less, more preferably 50 mass% or less. Moreover, 0.1-99 mass%, Preferably it is 1-90 mass%, More preferably, 10 mass%-50 mass% is mentioned.

  When the octenyl sulfate ester (1) of the present invention or a salt thereof is used in combination with pharmaceuticals or supplements, the dosage may vary according to the condition, body weight, sex, age or other factors of the subject, but oral administration In this case, the daily dose per adult is usually 0.1 mg or more, preferably 1 mg or more, more preferably 5 mg or more, and 10 g or less, preferably octenyl sulfate (1) or a salt thereof. 1 g or less, more preferably 500 mg or less. Moreover, 0.1 mg-10 g, Preferably 1 mg-1 g, More preferably, 5-500 mg is mentioned.

  The above-mentioned preparation can be administered according to an arbitrary administration schedule, but is preferably divided into once to several times a day and continuously administered for several weeks to several months. In addition, the administration or ingestion target is a human who needs or desires it, for example, a human who needs or desires prevention or improvement of a disease caused by overexpression of ENaC such as hypertension or renal dysfunction. Is mentioned.

With respect to the above-described embodiment, the following aspects are disclosed in the present invention.
<1> An epithelial sodium channel inhibitor comprising an octenyl sulfate ester represented by the following formula (1) or a salt thereof as an active ingredient.
<2> A salty taste suppressant containing, as an active ingredient, an octenyl sulfate ester represented by the following formula (1) or a salt thereof.
<3> Use of an octenyl sulfate ester represented by the following formula (1) or a salt thereof for producing an epithelial sodium channel inhibitor.
<4> Use of an octenyl sulfate ester represented by the following formula (1) or a salt thereof for producing a salty taste inhibitor.
<5> Octenyl sulfate represented by the following formula (1) or a salt thereof for use in epithelial sodium channel inhibition.
<6> An octenyl sulfate ester represented by the following formula (1) or a salt thereof for use in salty taste suppression.
<7> An epithelial sodium channel inhibition method comprising administering or ingesting an octenyl sulfate ester represented by the following formula (1) or a salt thereof in an effective amount to a subject in need thereof.
<8> A salty taste suppressing method using the ENaC inhibitor of <1> or the salty taste inhibitor of <2> for a salty substance-containing composition.
<9> The method of <8>, wherein an ENaC inhibitor or a salty taste suppressant is used in a salty substance-containing composition. <10> A metal ion and / or chloride ion derived from a mineral, or <10> The method according to <8> or <9>, which is a composition containing a metal chloride composed of the metal ion and chloride ion.
<11> The method according to <10>, wherein the mineral is one or more metals selected from sodium, potassium, calcium, magnesium and phosphorus.
<12> The method according to any one of <8> to <11>, wherein the composition is a food or an oral composition.
<13> The octenyl sulfate ester (1) or a salt thereof is 0.001 part by mass or more, preferably 0.01 part by mass or more and 90 parts by mass or less, preferably 10 parts by mass with respect to 1 part by mass of the salty substance. The method according to any one of <8> to <12>, which is used below or 0.001 to 90 parts by mass, preferably 0.01 to 10 parts by mass.

(Where, wavy lines indicate either cis or trans configuration)

Production Example 1 Synthesis of trans-3-octenyl sulfate Methylene chloride (6 mL) and paraformaldehyde (60 mg, 2 mmol) were added to 1-heptene (196 mg, 2 mmol), cooled to 0 ° C., and 1.08 M dimethyl An aluminum chloride-hexane solution (2.77 mL, 3 mmol) was added dropwise, and the mixture was warmed to room temperature and stirred overnight. Subsequently, a saturated aqueous sodium dihydrogen phosphate solution (2 mL) and a 1 M aqueous hydrochloric acid solution (3 mL) were added, and extraction was repeated three times with ether (10 mL). The obtained ether layer was dried with sodium sulfate, concentrated under reduced pressure, Trans-3-octen-1-ol (190 mg, 1.48 mmol) was obtained. Subsequently, tetrahydrofuran (15 mL) and sulfur trioxide pyridine (421 mg, 1.63 mmol) were added to the obtained trans-3-octen-1-ol (190 mg, 1.48 mmol) and stirred overnight. Subsequently, 1M NaOH aqueous solution was added to make the reaction system basic, and then dry nitrogen was blown to remove tetrahydrofuran. The residue was passed through ODS (Cosmo Seal 140C18 OPN, 10 g, manufactured by Nacalai Tesque), washed with water and eluted with 20% aqueous acetonitrile, and the resulting eluate was concentrated to dryness under reduced pressure. -3-Octenyl sulfate (115 mg) was obtained.

Properties: white powder, mp 159 ° C (decomposition);
¹ H NMR (600 MHz, CD ₃ OD): δ 0.90 (3H, t, J = 7.5 Hz, H-8), 1.29-1.38 (4H, m, H-6, 7), 2 .01 (2H, dtt, J = 6.8, 6.8, 1.2 Hz, H-5), 2.35 (2H, dtd, J = 6.8, 6.8, 1.2 Hz, H− 2), 3.97 (2H, t, J = 6.8 Hz, H-1), 5.44 (1H, dtt, J = 15.3, 6.8, 1.2 Hz, H-3), 5 .55 (1H, dtt, J = 15.3, 6.8, 1.2 Hz, H-4)

¹³ C NMR (150 MHz, CD ₃ OD): δ 14.28 (C-8), 23.23 (C-7), 32.78 (C-6), 30.40 (C-5), 33.72 (C-2), 68.89 (C-8), 126.62 (C-3), 134.22 (C-4)

Production Example 2 Synthesis of cis-3-octenyl sulfate

  Tetrahydrofuran (20 mL) and sulfur trioxide pyridine (600 mg, 2 mmol) were added to cis-3-octen-1-ol (manufactured by Tokyo Chemical Industry Co., Ltd., 256 mg, 2.00 mmol) and stirred overnight. Subsequently, 1M NaOH aqueous solution was added to make the reaction system basic, and then dry nitrogen was blown to remove tetrahydrofuran. The residue was passed through ODS (Cosmo Seal 140C18 OPN, 10 g, manufactured by Nacalai Tesque), washed with water and eluted with 20% acetonitrile aqueous solution, and the resulting eluate was concentrated to dryness under reduced pressure. -3-Octenyl sulfate (81 mg) was obtained.

Properties: white powder, melting point 185 ° C (decomposition);
¹ H NMR (600 MHz, CD ₃ OD): δ 0.92 (3H, t, J = 7.8 Hz, H-8), 1.33-1.37 (4H, m, H-6, 7), 2 .08 (2H, m, H-5), 2.42 (2H, tdddd, J = 7.2, 7.2, 1.0, 1.0 Hz, H-2), 3.96 (2H, t , J = 7.2 Hz, H-1), 5.40 (1H, dtt, J = 10.7, 7.2, 1.2 Hz, H-3), 5.49 (1H, dtt, J = 10). .7, 7.7, 1.0 Hz, H-4)

¹³ C NMR (150 MHz, CD ₃ OD): δ 14.33 (C-8), 23.25 (C-7), 27.99 (C-6), 28.55 (C-5), 32.98 (C-2), 68.57 (C-8), 125.69 (C-3), 133.46 (C-4)

Test Example 1 ENaC inhibitory activity of octenyl sulfate
According to the method described in The journal of biological chemistry, 284 (2): pages 792-798 (2009), the inhibitory activity of ENaC expressed in Xenopus oocytes was measured. Specifically, according to the following procedure, the trans-3-octenyl sulfate produced in Production Example 1 was added to an oocyte expressing the ENaC complex, and the activity of ENaC was analyzed electrophysiologically.
First, DNA sequences encoding human ENaCα, β, and γ were obtained by performing PCR using a plasmid vector (manufactured by Clontech) in which the same gene was cloned as a template. The obtained PCR amplified fragment was incorporated into a transcription vector pSP64 (manufactured by Promega) to prepare pSP64 / ENaCα, pSP64 / ENaCβ, and pSP64 / ENaCγ.
The plasmid DNA was linearized by digesting pSP64 / ENaCα and pSP64 / ENaCγ with EcoRI and pSP64 / ENaCβ with PvuII, respectively. By using SP6 RNA polymerase (manufactured by Takara) on these linearized DNAs, cRNA added with a polyA sequence for expressing ENaCα, ENaCβ, and ENaCγ was synthesized. The synthesized cRNA was treated with phenol / chloroform, and the resulting supernatant was collected. Further, isopropyl alcohol was mixed and centrifuged to precipitate cRNA. The precipitated cRNA was washed with 75% ethanol and then dissolved in distilled water to a concentration of 1 mg / mL.
Equal amounts of the obtained cRNA aqueous solutions encoding ENaCα, ENaCβ, and ENaCγ were mixed, and 50 ng was injected per Xenopus oocyte. Specifically, a glass capillary was filled with a cRNA aqueous solution using a manipulator (manufactured by NARISHIGE), and 50 nL was injected per oocyte. Thereafter, ENaC α, β, γ and the complex were expressed in the oocyte membrane over 2-3 days.
Two micro glass electrodes are inserted into the oocyte and the membrane potential is fixed at −60 mV. At this time, the inflow of Na ⁺ ions induced by the ENaC complex constantly in an active state was measured by replacing it with a change in the amount of current. That is, in a 115 mM NaCl solution (115 mM NaCl, 2.5 mM KCl, 1.8 mM CaCl ₂ , 1 mM NaHCO ₃ , 1 mM MgCl ₂ , 10 mM HEPES, pH 7.4), the oocyte causes an inward current Under the circumstances, trans-3-octenyl sulfate dissolved in the same solution was administered.

  As a result, as shown in FIG. 1, trans-3-octenyl sulfate suppressed the inward current of ENaC-expressing oocytes in a concentration-dependent range within the range of 3-30 mM. This effect was similar to the existing ENaC inhibitor amiloride. Moreover, since the effect of this trans-3-octenyl sulfate was not recognized in the oocyte which does not express ENaC, it was confirmed that it is with respect to ENaC.

Test example 2
Seven subjects presented with 0.6 w / v saline as a salty standard solution, and after putting it in the mouth for about 5 seconds, it was discharged and the salty intensity (0-10) felt was set to a median of 5.
Next, after each salt solution (0.6, 1.0 w / v%) was included in the mouth for about 5 seconds, it was exhaled and the intensity felt was 0 if not felt, 10 if it felt very strong, The answer was in the range of 1 to 10. Subsequently, a saline solution (0.6, 1.0 w / v%) containing 5 mM trans-3-octenyl sulfate was prepared and presented to the tester. Each was put in the mouth for about 5 seconds, then exhaled and the intensity felt was answered with a value from 0 to 10. The results are shown in Table 1.

  From Table 1, it was confirmed that the octenyl sulfate ester of the present invention has a salty taste suppressing action.

Claims (6)

An epithelial sodium channel inhibitor comprising an octenyl sulfate ester represented by the following formula (1) or a salt thereof as an active ingredient.
(Where, wavy lines indicate either cis or trans configuration) The salty taste inhibitor which uses the octenyl sulfate ester or its salt represented by following formula (1) as an active ingredient.
(Where, wavy lines indicate either cis or trans configuration)   The salty taste suppression method which uses the epithelial sodium channel inhibitor of Claim 1, or the salty taste inhibitor of Claim 2 with respect to a salty substance containing composition.   The method according to claim 3, wherein the salty substance-containing composition is a composition containing a metal ion and / or chloride ion derived from a mineral, or a metal chloride composed of the metal ion and chloride ion.   The method according to claim 4, wherein the mineral is one or more metals selected from sodium, potassium, calcium, magnesium and phosphorus.   The method according to any one of claims 3 to 5, wherein the composition is a food or an oral composition.