Antihypertensives

Abstract

To provide a novel antihypertensive agent.SOLUTION: Provided is an antihypertensive agent containing a decomposition extract of bagasse as an active ingredient. The antihypertensive agent in which the decomposition extract of bagasse is a decomposition treatment liquid obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment, micro-pulverization treatment and explosive-shattering treatment, and containing, as an active ingredient, a fraction obtained by passing the decomposition treatment liquid through a column packed with a solid carrier. The antihypertensive agent in which the solid carrier is a synthetic adsorbent or an ion exchange resin.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to antihypertensive agents. [Background technology]

[0002] Hypertension is a condition in which blood pressure is maintained above the normal range. Hypertension is a lifestyle-related disease and is a major problem because it can cause complications in major organs such as the brain, heart, and kidneys.

[0003] In recent years, naturally occurring substances with antihypertensive activity have been sought. For example, Patent Document 1 discloses an antihypertensive agent containing mung bean protein hydrolysate. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-219420 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a novel antihypertensive agent. [Means for solving the problem]

[0006] The present inventors have found through in vitro tests that a decomposed extract of bagasse has antihypertensive effects.

[0007] In one aspect, the present invention provides an antihypertensive agent containing a decomposed extract of bagasse as an active ingredient. The antihypertensive agent of the present invention has an excellent antihypertensive effect due to the inclusion of a decomposed extract of bagasse as an active ingredient.

[0008] The decomposition extract of bagasse may be a decomposition treatment liquid obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment, pulverization treatment, and explosion treatment.

[0009] The decomposed extract of bagasse may be a fraction obtained by passing the decomposition treatment liquid through a column packed with a fixed carrier, which is preferably a synthetic adsorbent or an ion exchange resin.

[0010] When the fixed carrier is a synthetic adsorbent, the decomposed extract of bagasse may be a fraction obtained by eluting the components adsorbed by the synthetic adsorbent with at least one solvent selected from the group consisting of water, methanol, ethanol, and mixtures thereof.

[0011] The synthetic adsorbent is preferably an aromatic resin, an acrylic acid-based methacrylic resin, or an acrylonitrile-aliphatic resin.

[0012] The decomposed extract of bagasse may be a fraction obtained by passing the decomposition treatment liquid through a column packed with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. In this case, the synthetic adsorbent is an unsubstituted aromatic resin, the column temperature may be 20 to 60°C, and the volume ratio of ethanol to water (ethanol / water) in the mixed solvent may be 50 / 50 to 60 / 40.

[0013] In another aspect, the present invention provides an angiotensin-converting enzyme inhibitor containing a decomposed extract of bagasse as an active ingredient. [Effects of the Invention]

[0014] According to the present invention, a novel antihypertensive agent can be provided. DETAILED DESCRIPTION OF THE INVENTION

[0015] Hereinafter, embodiments of the present invention will be described, but the present invention is not limited to the following embodiments.

[0016] The antihypertensive agent of the present invention has an antihypertensive effect. The antihypertensive effect may be an effect of suppressing an increase in blood pressure.

[0017] There are various blood pressure regulation mechanisms in the body. Angiotensin II has the effect of constricting blood vessels and increasing blood volume by suppressing the excretion of sodium and water in the kidneys, thereby raising blood pressure. Angiotensin II is produced when angiotensin I is converted by angiotensin-converting enzyme (ACE). Therefore, by inhibiting ACE and suppressing the production of angiotensin II, it is possible to suppress an increase in blood pressure.

[0018] The antihypertensive agent of the present invention has an ACE inhibitory effect, thereby suppressing the production of angiotensin II and, as a result, suppressing an increase in blood pressure. That is, the antihypertensive agent of the present invention can be said to be based on the inhibitory effect of angiotensin converting enzyme, or on the effect of suppressing the production of angiotensin II. In addition, the present invention can also be said to provide an angiotensin converting enzyme inhibitor.

[0019] An antihypertensive agent according to one embodiment contains a decomposed extract of bagasse as an active ingredient. The decomposed extract of bagasse preferably contains at least one selected from the group consisting of phenylpropanoids such as p-coumaric acid, ferulic acid, caffeic acid, and vanillin, as well as lignin and its decomposition products.

[0020] "Bagasse" typically refers to bagasse discharged during the sugar refining process in the raw sugar production process. Bagasse discharged during the sugar refining process in a raw sugar factory includes not only the final bagasse that leaves the final compressor, but also shredded sugarcane that has been consumed by subsequent compressors, including the first compressor. A suitable bagasse is bagasse discharged after the sugar juice is extracted in the extraction process in a raw sugar factory. The moisture content, sugar content, and composition ratio of the bagasse vary depending on the type of sugarcane, harvest time, etc., but any of these bagasse can be used in the present invention. Furthermore, in this embodiment, the raw bagasse can also be bagasse remaining after sugarcane extraction in a brown sugar production factory, for example, or bagasse remaining after sugarcane is extracted from sugarcane in a small-scale laboratory experiment, just like in a raw sugar factory.

[0021] In one embodiment, the decomposition extract of bagasse may be a decomposition treatment liquid of bagasse (and / or a processed product thereof). The decomposition treatment liquid can be obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment, pulverization treatment, and explosion treatment. From the viewpoint of facilitating the production of a decomposition extract of bagasse, alkali treatment or hydrothermal treatment is preferred as the decomposition treatment.

[0022] The alkali treatment may be a treatment in which the bagasse is brought into contact with an alkaline solution. Examples of methods for bringing the bagasse into contact with the alkaline solution include a method in which the alkaline solution is sprinkled on the bagasse, and a method in which the bagasse is immersed in the alkaline solution. In the method in which the bagasse is immersed in the alkaline solution, the bagasse may be immersed while stirring a mixture of the bagasse and the alkaline solution.

[0023] Examples of the alkaline solution include an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution, and an aqueous ammonia solution. The alkaline solution may be one of these solutions alone or a mixture of two or more of them. From the viewpoints of being inexpensive and easily usable in food production processes, the alkaline solution is preferably an aqueous sodium hydroxide solution.

[0024] From the viewpoint of shortening the treatment time of the decomposition treatment, the temperature of the alkaline solution (liquid temperature) is preferably 40° C. or higher, more preferably 100° C. or higher, and even more preferably 130° C. or higher. From the viewpoint of preventing polysaccharides from remaining in the decomposition treatment liquid, the temperature of the alkaline solution is preferably 250° C. or lower, more preferably 200° C. or lower, and even more preferably 150° C. or lower.

[0025] The alkali treatment may be carried out under normal pressure or under pressure. When pressure is applied, the pressure may be 0.1 MPa or more, or 0.2 MPa or more, and may be 4.0 MPa or less, 1.6 MPa or less, or 0.5 MPa or less.

[0026] The hydrothermal treatment may be a treatment in which bagasse is brought into contact with high-temperature water or steam under high pressure. More specifically, the hydrothermal treatment may be a method in which water is added to the bagasse so that the solids concentration is 0.1 to 50%, and decomposition treatment is carried out under high-temperature and high-pressure conditions. The temperature of the water or steam is preferably 130 to 250°C, and the pressure applied is preferably 0.1 to 0.5 MPa higher than the saturated steam pressure of water at the respective temperatures.

[0027] The acid treatment may be a treatment in which the bagasse is brought into contact with an acidic solution. Examples of the acidic solution include dilute sulfuric acid. The method for bringing the bagasse into contact with the acidic solution, the temperature of the acidic solution in the acid treatment, and the pressure conditions in the acid treatment may be the same as the method or conditions in the alkali treatment described above.

[0028] The subcritical water treatment may be a treatment in which subcritical water is brought into contact with bagasse. The method for bringing subcritical water into contact with bagasse may be the same as the method for the alkaline treatment described above. The conditions for the subcritical water treatment are not particularly limited, but it is preferable that the temperature of the subcritical water is 160 to 240°C and the treatment time is 1 to 90 minutes.

[0029] The pulverization process may be a process in which bagasse is pulverized to sizes of several μm to several hundred μm by compression, impact, shear, friction, etc. The explosion process may be a process in which the insoluble xylan contained in the bagasse is decomposed to a certain extent by hydrothermal treatment, and then the bagasse is pulverized by instantly releasing it to atmospheric pressure by, for example, suddenly opening a valve provided in a pressure-resistant reaction vessel.

[0030] After the decomposition treatment, the decomposition treatment liquid may be subjected to a process for separating the solid and liquid components. In this case, the liquid component obtained after the separation may be used as the decomposition treatment liquid. The method for separating the solid and liquid components may be separation using a strainer, filtration, centrifugation, decantation, or the like.

[0031] High molecular weight components such as polysaccharides may be removed from the decomposition treatment liquid by membrane separation. In this case, the liquid fraction after membrane separation can be used as the decomposition treatment liquid. The separation membrane is not particularly limited as long as it is an ultrafiltration membrane (UF membrane). The molecular weight cutoff of the ultrafiltration membrane is preferably 2,500 to 50,000, more preferably 2,500 to 5,000.

[0032] Materials that can be used for the ultrafiltration membrane include polyimide, polyethersulfone (PES), polysulfone (PS), polyacrylonitrile (PAN), polyvinylidene fluoride (PVDF), regenerated cellulose, cellulose, cellulose ester, sulfonated polysulfone, sulfonated polyethersulfone, polyolefin, polyvinyl alcohol, polymethyl methacrylate, and polytetrafluoroethylene.

[0033] The filtration method of the ultrafiltration membrane may be dead-end filtration or cross-flow filtration, but from the viewpoint of suppressing membrane fouling, cross-flow filtration is preferred.

[0034] The ultrafiltration membrane may be of any suitable type, such as a flat membrane type, a spiral type, a tubular type, or a hollow fiber type. More specifically, examples include the GE series, GH series, and GK series from GE Power & Water; the G-5 type, G-10 type, G-20 type, G-50 type, PW type, and HWSUF type from DESAL; HFM-180, HFM-183, HFM-251, HFM-300, HFK-131, HFK-328, MPT-U20, MPS-U20P, and MPS-U20S from KOCH; SPE1, SPE3, SPE5, SPE10, SPE30, SPV5, SPV50, and SOW30 from Synder; those equivalent to the molecular weight cutoff of 3,000 to 10,000 in the Microza (registered trademark) UF series manufactured by Asahi Kasei Corporation; and NTR7410 and NTR7450 manufactured by Nitto Denko Corporation.

[0035] In another embodiment, the decomposition extract of bagasse may be a fraction obtained by passing the above-mentioned decomposition treatment liquid through a column packed with a fixed carrier. By passing the decomposition treatment liquid through the column, the components having antihypertensive activity (active ingredients) in the decomposition treatment liquid are adsorbed onto the fixed carrier, and most of the sugars and inorganic salts are eluted as they are.

[0036] The decomposition treatment liquid described above can be passed through the column directly or after adjusting the concentration with water to a desired level. The pH of the decomposition treatment liquid may be adjusted before passing through the column. From the viewpoint of improving the adsorption rate, the decomposition treatment liquid is preferably adjusted to a pH of 6 or less. The pH of the decomposition treatment liquid may be greater than 4.5 and equal to or less than 6.

[0037] The solid support is preferably either a synthetic adsorbent or an ion exchange resin.

[0038] The synthetic adsorbent is preferably a synthetic porous adsorbent. As the synthetic adsorbent (synthetic porous adsorbent), an organic resin is preferably used. The organic resin is preferably an aromatic resin, an acrylic acid-based methacrylic resin, or an acrylonitrile-aliphatic resin.

[0039] Examples of aromatic resins include styrene-divinylbenzene resins. Examples of aromatic resins include porous resins such as aromatic resins having hydrophobic substituents, unsubstituted aromatic resins, and aromatic resins specially treated to be unsubstituted, among which unsubstituted aromatic resins and aromatic resins specially treated to be unsubstituted are preferred.

[0040] Commercially available synthetic adsorbents include Diaion (trademark) HP-10, HP-20, HP-21, HP-30, HP-40, and HP-50 (all unsubstituted aromatic resins, all trade names, manufactured by Mitsubishi Chemical Corporation); SP-825, SP-800, SP-850, SP-875, SP-70, and SP-700 (all unsubstituted aromatic resins that have been specially treated, all trade names, manufactured by Mitsubishi Chemical Corporation); SP-900 (aromatic resin, trade name, manufactured by Mitsubishi Chemical Corporation); Amberlite (trademark) XAD-2, XAD-4, XAD-16, and XAD-2000 (aromatic resins, all trade names, manufactured by Organo Corporation); and Diaion (trademark). Examples of suitable resins include: POLY(R) SP-205, SP-206, and SP-207 (all aromatic resins having a hydrophobic substituent, all trade names, manufactured by Mitsubishi Chemical Corporation); HP-2MG and EX-0021 (aromatic resins having a hydrophobic substituent, all trade names, manufactured by Mitsubishi Chemical Corporation); Amberlite(R) XAD-7 and XAD-8 (acrylic ester resins, all trade names, manufactured by Organo Corporation); Diaion(R) HP1MG and HP2MG (acrylic acid methacrylic resins, all trade names, manufactured by Mitsubishi Chemical Corporation); and Sephadex(R) LH20 and LH60 (crosslinked dextran derivatives, all trade names, manufactured by Pharmacia Biotech Co., Ltd.). Among these, unsubstituted aromatic resins (e.g., HP-20) and unsubstituted aromatic resins that have been specially treated (e.g., SP-850) are preferred.

[0041] The amount of synthetic adsorbent packed in the column can be determined appropriately depending on the size of the column, the type of synthetic adsorbent, and the like.

[0042] When a synthetic adsorbent is used as the fixed carrier, the flow rate of the decomposition treatment liquid can be appropriately changed depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but is preferably SV = 1 to 30 hours. -1 SV (Space Velocity) is a unit that indicates how many times the resin capacity the liquid passes through per hour.

[0043] The adsorbed components (active ingredients) adsorbed to the synthetic adsorbent can be eluted with a solvent (elution solvent). From the viewpoint of more efficiently recovering the adsorbed components, it is preferable to wash away the sugars and inorganic salts remaining in the column with water before eluting the adsorbed components. In this case, the eluted components can be used as a decomposed extract of bagasse.

[0044] When a synthetic adsorbent is used as the fixed carrier, the elution solvent may be at least one selected from the group consisting of water, methanol, ethanol, and mixtures thereof. The elution solvent is preferably a mixed solvent of alcohol and water, more preferably a mixed solvent of ethanol and water, and even more preferably a mixed solvent of ethanol and water in a volume ratio of 50 / 50 to 60 / 40 (ethanol / water) from the viewpoint of enabling more efficient elution of the adsorbed components at room temperature.

[0045] When a synthetic adsorbent is used as the fixed carrier, the column temperature during elution (column temperature) may be room temperature, but by increasing the column temperature above room temperature, the mixing ratio of ethanol in the mixed solvent of ethanol and water can be reduced, allowing the adsorbed components to be eluted more efficiently. The temperature is preferably 20 to 60°C, more preferably 40 to 60°C. The inside of the column may be under normal pressure or under pressurized condition.

[0046] When a synthetic adsorbent is used as the fixed carrier, the elution rate can be appropriately set depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but preferably, SV=0.1 to 10 hours. -1 is.

[0047] Ion exchange resins are classified into gel-type resins and porous resins such as porous, microporous, or hyperporous resins based on the resin form, but there are no particular limitations. The ion exchange resin is preferably an anion exchange resin. As the anion exchange resin, a strongly basic anion exchange resin or a weakly basic anion exchange resin may be used. When an alkaline processing liquid is used as the raw material, a strongly basic anion exchange resin is preferably used, but when a decomposition processing liquid from other processes is used as the raw material, there are no particular limitations.

[0048] Examples of commercially available strong basic anion exchange resins include Diaion (trademark) PA306, PA308, PA312, PA316, PA318L, HPA25, SA10A, SA12A, SA11A, SA20A, and UBA120 (all manufactured by Mitsubishi Chemical Corporation), Amberlite (trademark) IRA400J, IRA402B1, IRA404J, IRA900J, IRA904, IRA458RF, IRA958, IRA410J, IRA411, and IRA910CT (all manufactured by Organo Corporation), and Dowex (trademark) Marathon A, Marathon MSA, MONOSPHERE550A, and Marathon A2 (all manufactured by Dow Chemical Japan Ltd.).

[0049] Examples of commercially available weakly basic anion exchange resins include Diaion (trademark) WA10, WA20, WA21J, and WA30 (all manufactured by Mitsubishi Chemical Corporation), Amberlite (trademark) IRA478RF, IRA67, IRA96SB, IRA98, and XE583 (all manufactured by Organo Corporation), and Dowex (trademark) Marathon WBA, 66, MONOSPHERE 66, and MONOSPHERE 77 (all manufactured by Dow Chemical Japan Ltd.).

[0050] The amount of ion exchange resin packed in the column can be determined appropriately depending on the size of the column, the type of ion exchange resin, etc., but is preferably 2 to 10,000 times, and more preferably 5 to 500 times, the wet volume of the solid content of the decomposition treatment liquid.

[0051] The liquid passing conditions can be appropriately set depending on the type of pretreatment liquid, the type of ion exchange resin, etc. Preferably, the flow rate is SV=0.3 to 30 h -1 The amount of liquid passed through the column is 100 to 300% of the ion exchange resin, and the column temperature is 40 to 90° C. The pressure inside the column may be normal or pressurized.

[0052] When an ion exchange resin is used as the fixed carrier, the decomposed extract of bagasse may be a fraction obtained by passing it through a column packed with the ion exchange resin and eluting it with an eluent such as a salt, an acid, an alcohol, or a mixed aqueous solution of these. The eluent may be degassed.

[0053] In one embodiment, the decomposition extract of bagasse may be a concentrate obtained by concentrating the above-mentioned decomposition treatment liquid or fraction. The concentration method may be a known method, such as solvent distillation under reduced pressure or freeze-drying. When concentration is performed, the decomposition treatment liquid or fraction may be concentrated 15 to 30 times, and the concentrated component may be used as the decomposition extract of bagasse.

[0054] A decomposition extract of bagasse can be obtained, for example, as follows. A 1% by mass aqueous solution of sodium hydroxide is added to bagasse so that the solids concentration is 0.1 to 50%, and the mixture is boiled at 100°C to obtain a decomposition treatment liquid (alkali treatment liquid). The decomposition treatment liquid is ultrafiltered using a UF membrane with a molecular weight cutoff of 2500 to 5000. The resulting filtrate is acidified and then passed through a column packed with an unsubstituted aromatic resin at a column temperature of 20 to 60°C. The components adsorbed on the column are then eluted with a mixed solvent (elution solvent) of ethanol and water in a volume ratio of 50 / 50 to 60 / 40 (ethanol / water) at a column temperature of 20 to 60°C, and the fraction eluted when the amount of eluate collected from the start of elution with the mixed solvent of ethanol and water is within 45 times the wet volume of the aromatic resin is recovered. The recovered fractions (fractions containing components with antihypertensive activity) can be combined and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a decomposed extract of bagasse. The decomposed extract of bagasse obtained in this manner can be stored as a liquid or powder extract concentrated to a solids content of 30% by mass or more. When the extract is in liquid form, it is preferably stored refrigerated.

[0055] Another example of a bagasse decomposition extract can be obtained as follows: Water is added to bagasse to a solids concentration of 0.1 to 50%, followed by hydrothermal treatment with water at 130 to 250°C under a pressure of 0.2 to 4.0 MPa. A decomposition-treated solution (hydrothermally treated solution) is obtained by solid-liquid separation via filtration. The resulting hydrothermally treated solution is passed through a column packed with an aromatic resin that has been specially treated to be unsubstituted at a temperature of 20 to 60°C. The components adsorbed on the column are then eluted with a mixed solvent (elution solvent) of ethanol and water in a volume ratio of 50 / 50 to 60 / 40 (ethanol / water) at a column temperature of 20 to 60°C. The fraction eluted in an amount of eluate collected from the start of elution with the mixed solvent of ethanol and water within 5 times the wet volume of the aromatic resin is recovered. The recovered fractions (fractions containing components with antihypertensive activity) can be combined and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a decomposed extract of bagasse. The decomposed extract of bagasse obtained in this manner can be stored as a liquid or powder extract concentrated to a solids content of 30% by mass or more. When the extract is in liquid form, it is preferably stored refrigerated.

[0056] The decomposed extract of bagasse in each of the above-described embodiments may be in a liquid or powder form. A powdered decomposed extract of bagasse can be produced, for example, by using a liquid decomposed extract of bagasse by a spray-drying method, a freeze-drying method, a fluidized bed granulation method, or a powdering method using an excipient.

[0057] The antihypertensive agent can be used as a food composition, a pharmaceutical product, or a quasi-drug. The food composition may be provided in the form of, for example, a health food, a food for specified health uses, a functional food, a food with nutrient function claims, a supplement, or the like.

[0058] The antihypertensive agent may consist solely of the active ingredient, a decomposed extract of bagasse, or may further contain ingredients usable in food compositions, quasi-drugs, or pharmaceuticals. The ingredients usable in food compositions, quasi-drugs, or pharmaceuticals are not particularly limited, and examples thereof include amino acids, proteins, carbohydrates, oils and fats, sweeteners, minerals, vitamins, flavorings, excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, suspending agents, etc.

[0059] Examples of proteins include milk casein, whey, soy protein, wheat protein, and egg white. Examples of carbohydrates include corn starch, cellulose, pregelatinized starch, wheat starch, rice starch, and potato starch. Examples of fats and oils include salad oil, corn oil, soybean oil, safflower oil, olive oil, and palm oil. Examples of sweeteners include sugars such as glucose, sucrose, fructose, glucose-fructose corn syrup, and fructose-glucose corn syrup; sugar alcohols such as xylitol, erythritol, and maltitol; artificial sweeteners such as sucralose, aspartame, saccharin, and acesulfame K; and stevia sweeteners. Examples of minerals include calcium, potassium, phosphorus, sodium, manganese, iron, zinc, magnesium, and salts thereof. Examples of vitamins include vitamin E, vitamin C, vitamin A, vitamin D, B vitamins, biotin, and niacin. Examples of excipients include dextrin, starch, lactose, and crystalline cellulose. Examples of binders include polyvinyl alcohol, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidone. Examples of lubricants include magnesium stearate, calcium stearate, and talc. Examples of disintegrants include crystalline cellulose, agar, gelatin, calcium carbonate, sodium bicarbonate, and dextrin. Examples of emulsifiers or surfactants include sucrose fatty acid esters, citric acid, lactic acid, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, and lecithin. Examples of bases include cetostearyl alcohol, lanolin, and polyethylene glycol. Examples of solubilizers include polyethylene glycol, propylene glycol, sodium carbonate, and sodium citrate. Examples of suspending agents include glycerin monostearate, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxymethylcellulose, sodium alginate, and the like.These may be used alone or in combination of two or more.

[0060] When the antihypertensive agent is blended with other materials, the content of the decomposed extract of bagasse, which is the active ingredient, may be appropriately set depending on the form, intended use, etc. of the antihypertensive agent, which will be described later. From the viewpoint of more effectively exerting the antihypertensive effect, however, the content is preferably 1% by mass or more, more preferably 3% by mass or more, even more preferably 5% by mass or more, and is preferably 50% by mass or less, more preferably 40% by mass or less, even more preferably 30% by mass or less, in terms of solid content.

[0061] The form of the antihypertensive agent is not limited, and may be any form such as a solid (powder, granules, etc.), a liquid (solution, suspension, etc.), or a paste, and may be any dosage form such as a powder, pill, granule, tablet, capsule, troche, liquid, or suspension.

[0062] The antihypertensive agent may be administered orally or parenterally, such as intravenously.

[0063] When the antihypertensive agent is orally administered, the dosage is, for example, preferably 50 μg / kg (body weight) or more of the bagasse decomposition extract per dose, more preferably 100 μg / kg (body weight) or more, and even more preferably 150 μg / kg (body weight) or more. The bagasse decomposition extract is preferably administered at a daily dose of 150 μg / kg (body weight) or more, more preferably 300 μg / kg (body weight) or more, and even more preferably 450 μg / kg (body weight) or more. The bagasse decomposition extract is preferably administered at a daily dose of 1000 mg / kg (body weight) or less, more preferably 800 mg / kg (body weight) or less, and even more preferably 600 mg / kg (body weight) or less. The bagasse decomposition extract is preferably administered at a daily dose of 3,000 mg / kg (body weight) or less, more preferably 2,000 mg / kg (body weight) or less, and even more preferably 1,000 mg / kg (body weight) or less. Within these ranges, a sufficient blood concentration can be achieved, and the antihypertensive effect can be more effectively exerted.

[0064] When the antihypertensive agent is administered parenterally, the dosage is, for example, preferably 100 μg / kg (body weight) or more of the decomposed extract of bagasse per administration, more preferably 150 μg / kg (body weight) or more, and even more preferably 200 μg / kg (body weight) or more. The decomposed extract of bagasse is preferably administered at a daily dose of 200 μg / kg (body weight) or more, more preferably 300 μg / kg (body weight) or more, and even more preferably 400 μg / kg (body weight) or more. The decomposed extract of bagasse is preferably administered at a daily dose of 2000 mg / kg (body weight) or less, more preferably 1500 mg / kg (body weight) or less, and even more preferably 1000 mg / kg (body weight) or less. The bagasse decomposition extract is preferably administered at a daily dose of 4000 mg / kg (body weight) or less, more preferably 3000 mg / kg (body weight) or less, and even more preferably 2000 mg / kg (body weight) or less. Within these ranges, a sufficient blood concentration can be achieved, and the antihypertensive effect can be more effectively exerted.

[0065] Antihypertensive agents can also be used as feed or feed additives. Examples of feed include companion animal feeds such as dog food and cat food, livestock feeds, poultry feeds, and feeds for farmed fish and shellfish. "Feed" includes all feeds that animals ingest orally for nutritional purposes. More specifically, based on nutrient content, it encompasses roughage, concentrated feeds, inorganic feeds, and specialty feeds. Based on official standards, it encompasses compound feeds, mixed feeds, and individual feeds. Based on feeding method, it encompasses feeds that are fed directly, mixed with other feeds, or added to drinking water for nutrient supplementation.

[0066] Specific aspects of the angiotensin-converting enzyme inhibitor according to one embodiment may be the same as those of the antihypertensive agent described above. That is, the angiotensin-converting enzyme inhibitor according to one embodiment may be obtained by replacing "antihypertensive agent" with "angiotensin-converting enzyme inhibitor" in the description of the antihypertensive agent described above. [Example]

[0067] The present invention will be described below with reference to examples, but the present invention is not limited to these examples. The decomposed extract of bagasse may be hereinafter simply referred to as the "extract."

[0068] <Production of bagasse decomposition extract> [Manufacturing Example 1] 15 kg of bagasse (water content 50% by mass), which is sugarcane pomace, was mixed with 100 L of 0.5% (w / w) aqueous sodium hydroxide solution and subjected to an alkali treatment at 150°C. After the alkali treatment, the mixture was separated into solid and liquid fractions, yielding approximately 100 L of liquid fraction. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500, yielding 80 L of filtrate. One liter of synthetic adsorbent (HP-20, manufactured by Mitsubishi Chemical Corporation) was packed into a resin tower (internal diameter 80 mm, height 400 mm), and the above filtrate was added to the resin tower at a flow rate of 10 L / h (SV = 10.0 (hr)). The pH was adjusted to 6. -1 )) was passed through.

[0069] Next, 5 liters of purified water was added at a flow rate of 10 liters / hour (SV = 10.0 (hours) -1 Next, 2 liters of a 60% aqueous ethanol solution (ethanol / water = 60 / 40 (volume / volume)) was passed through the resin column to wash it. -1 )) and then passed through the resin column. Subsequently, 2 liters of purified water was passed through the resin column at a flow rate of 2 liters / hour (SV=2.0 (hours)). -1The solution was passed through a resin column in the same manner as above, and the components adsorbed by the synthetic adsorbent were eluted. The fraction eluted from the resin column was concentrated under reduced pressure to approximately 10 times its original concentration using a rotary evaporator, and then freeze-dried overnight to obtain 20 g of a brown powder as a decomposed extract of bagasse. This was designated Extract A.

[0070] [Manufacturing Example 2] 30 kg of bagasse (water content 50% by mass), which is sugarcane pomace, was hydrothermally treated with 100 L of hot water at 200°C. The pretreated mixed liquid was separated into solid and liquid fractions, yielding approximately 88 L of liquid. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500, yielding 70 L of filtrate. One liter of synthetic adsorbent (Mitsubishi Chemical Corporation, SP-850) was packed into a resin tower (internal diameter 80 mm, height 400 mm), and 25 L of the filtrate was added to this at a flow rate of 20 liters / hour (SV = 20.0 (hours)). -1 )) was passed through.

[0071] Next, 3.3 liters of purified water was added at a flow rate of 20 liters / hour (SV = 20.0 (hours) -1 Next, 2 liters of a 60% aqueous ethanol solution (ethanol / water = 60 / 40 (volume / volume)) was passed through the resin column to wash it. -1 )) and then passed through the resin column. Subsequently, 2 liters of purified water was passed through the resin column at a flow rate of 2 liters / hour (SV=2.0 (hours)). -1 The solution was passed through a resin column in the same manner as above, and the components adsorbed by the synthetic adsorbent were eluted. The fraction eluted from the resin column was concentrated under reduced pressure to approximately 10 times its original concentration using a rotary evaporator, and then freeze-dried overnight to obtain 40 g of a brown powder as a decomposed extract of bagasse. This was designated Extract W.

[0072] <Angiotensin-converting enzyme inhibition test> An angiotensin-converting enzyme inhibition test was performed based on the method of Nakano et al. (Nakano et al., Biosci. Biotechnol. Biochem., 70, 1118-1126 (2006)). 1.0 g of each of Extract A and Extract W was extracted with 20 mL of 50% (V / V) ethanol and then diluted appropriately with 0.1 mol / L Hepes buffer (pH 8.3) to prepare test solutions with the concentrations shown in Table 1. 25 μL of 0.1 mol / L Hepes buffer (untreated group) or the test solution was added to a 96-well microplate, followed by 25 μL of 20 mU / mL ACE solution and incubation at 37°C for 5 minutes. 25 μL of 8 mmol / L substrate (hippuryl-L-histidyl-L-leucine; Hip-His-Leu) solution was then added and the reaction was continued at 37°C for 30 minutes. The reaction was then terminated by adding 25 μL of 0.1 mol / L aqueous sodium hydroxide solution, and 25 μL of 1% by weight ortho-phthalaldehyde (OPA) solution was added and the mixture was allowed to stand for 20 minutes. Then, 25 μL of 0.1 mol / L hydrochloric acid was added to prepare a measurement sample. The measurement sample was left at room temperature for 10 minutes, and the fluorescence intensity was measured using a microplate reader under the following conditions. Note that phosphate-buffered saline was used as a blank instead of the ACE solution.

[0073] (Microplate reader operating conditions) Model: SpectraMax M2e (Molecular Devices) Measurement conditions: Fluorescence, endpoint mode, bottom read Excitation wavelength: 355 nm Fluorescence wavelength: 460nm

[0074] The fluorescence intensity of each test solution was evaluated as the ACE inhibition rate, with the fluorescence intensity of the untreated group being taken as 100%. The results are shown in Table 1. [Table 1]

[0075] As shown in Table 1, Extract A and Extract W showed ACE inhibitory effects. 50 is 0.95 mg / mL based on the total volume of the test solution (final concentration based on the total volume of the test sample: 0.16 mg / mL), and the IC 50was 0.52 mg / mL based on the total volume of the test solution (final concentration based on the total volume of the measurement sample: 0.087 mg / mL).

Claims

1. An antihypertensive agent comprising a decomposed extract of bagasse as an active ingredient, The bagasse decomposition extract is a fraction obtained by passing a decomposition solution obtained by decomposing bagasse through a column packed with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. The bagasse decomposition treatment is an alkali treatment or a hydrothermal treatment, The synthetic adsorbent is a non-substituted aromatic resin, The volume ratio of ethanol and water in the mixed solvent (ethanol / water) is 60 / 40.

2. An angiotensin-converting enzyme inhibitor comprising a decomposed extract of bagasse as an active ingredient, The bagasse decomposition extract is a fraction obtained by passing a decomposition solution obtained by decomposing bagasse through a column packed with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. The bagasse decomposition treatment is an alkali treatment or a hydrothermal treatment, The synthetic adsorbent is a non-substituted aromatic resin, The angiotensin converting enzyme inhibitor, wherein the volume ratio of ethanol and water in the mixed solvent (ethanol / water) is 60 / 40.

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