JP7602313B2 - Antihypertensives - Google Patents

Description

The present invention relates to an antihypertensive agent.

Hypertension is a condition in which blood pressure remains 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.

In recent years, naturally occurring substances with antihypertensive properties have been sought. For example, Patent Document 1 discloses an antihypertensive agent containing mung bean protein hydrolysate.

JP 2006-219420 A

The object of the present invention is to provide a novel antihypertensive agent.

The inventors have found through in vitro testing that a decomposed extract of bagasse has an antihypertensive effect.

In one aspect, the present invention provides an antihypertensive agent containing a decomposition extract of bagasse as an active ingredient. The antihypertensive agent of the present invention has excellent antihypertensive effects due to the inclusion of a decomposition extract of bagasse as an active ingredient.

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

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

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

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

The decomposition 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 temperature of the column is 20 to 60°C, and the volume ratio of ethanol and water in the mixed solvent (ethanol/water) may be 50/50 to 60/40.

In another aspect, the present invention provides an angiotensin-converting enzyme inhibitor that contains a decomposed extract of bagasse as an active ingredient.

The present invention provides a novel antihypertensive agent.

The following describes an embodiment of the present invention. However, the present invention is not limited to the following embodiment.

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.

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.

The antihypertensive agent of the present invention has an ACE inhibitory effect, and therefore suppresses the production of angiotensin II, and as a result, suppresses the rise in blood pressure. In other words, the antihypertensive agent of the present invention can be said to be based on the inhibitory effect of angiotensin converting enzyme, and can also be said to be based on the effect of suppressing the production of angiotensin II. The present invention can also be said to provide an angiotensin converting enzyme inhibitor.

An antihypertensive agent according to one embodiment contains a decomposition extract of bagasse as an active ingredient. The decomposition 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.

"Bagasse" typically refers to bagasse discharged during the sugar manufacturing process in the raw sugar manufacturing process. The bagasse discharged during the sugar manufacturing process in a raw sugar factory includes not only the final bagasse that leaves the final press, but also shredded sugarcane that is eaten into the subsequent presses, including the first press. A suitable bagasse is bagasse discharged after the sugar juice is compressed in the compression process in a raw sugar factory. The moisture, sugar content, and composition ratio of the bagasse vary depending on the type of sugarcane, harvest time, etc., but in the present invention, any of these bagasses can be used. Furthermore, in this embodiment, as in the raw sugar factory, bagasse remaining after sugarcane compression discharged from, for example, a brown sugar manufacturing factory, or bagasse after sugar juice is compressed from sugarcane in a small-scale laboratory-level implementation can also be used as the raw bagasse.

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 an alkali treatment, a hydrothermal treatment, an acid treatment, a subcritical water treatment, a fine pulverization treatment, and an explosion treatment. From the viewpoint of facilitating the production of a decomposition extract of bagasse, the decomposition treatment is preferably an alkali treatment or a hydrothermal treatment.

The alkaline 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 bagasse is sprinkled with the alkaline solution, 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 in a mixture of the bagasse and the alkaline solution while being stirred.

Examples of alkaline solutions include aqueous sodium hydroxide solutions, aqueous potassium hydroxide solutions, and aqueous ammonia solutions. 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 manufacturing processes, the alkaline solution is preferably an aqueous sodium hydroxide solution.

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 shortening the processing time of the decomposition process. 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, from the viewpoint of not leaving polysaccharides in the decomposition process liquid.

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.

Hydrothermal treatment may be a process in which bagasse is brought into contact with high-temperature water or steam under high pressure. More specifically, hydrothermal treatment may be a method in which water is added so that the solids concentration of the bagasse 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 applied pressure is preferably 0.1 to 0.5 MPa higher than the saturated steam pressure of water at each temperature.

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 of 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.

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. There are no particular limitations on the conditions for the subcritical water treatment, 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.

The fine pulverization process may be a process in which bagasse is pulverized to a size 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 suddenly opening a valve installed in a pressure-resistant reaction vessel, for example.

After the above-mentioned decomposition process, the decomposition liquid may be subjected to a process for separating the solid and liquid components. In this case, the liquid obtained after the separation may be used as the decomposition liquid. The method for separating the solid and liquid components may be separation using a strainer, filtration, centrifugation, decantation, etc.

In the decomposition treatment liquid, polymeric components such as polysaccharides may be removed by membrane separation. In this case, the liquid after membrane separation can be used as the decomposition treatment liquid. There are no particular limitations on the separation membrane 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, and more preferably 2,500 to 5,000.

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.

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

The ultrafiltration membrane may be of any suitable type, such as flat membrane, spiral, tubular, hollow fiber, etc. 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; the HFM-180, HFM-183, HFM-251, HFM-300, HFK-131, HFK-328, MPT-U20, MPS-U20P, and MPS-U20S from KOCH; the SPE1, SPE3, SPE5, SPE10, SPE30, SPV5, SPV50, and SOW30 from Synder; the Microza (registered trademark) UF series from Asahi Kasei Corporation, which has a molecular weight cutoff of 3,000 to 10,000; and the NTR7410 and NTR7450 from Nitto Denko Corporation.

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 effect (active ingredients) in the decomposition treatment liquid are adsorbed onto the fixed carrier, and most of the sugars and inorganic salts flow out as they are.

The above-mentioned decomposition treatment liquid can be passed through the column directly or after being adjusted to any concentration with water. The pH of the decomposition treatment liquid may be adjusted before passing through the column. From the viewpoint of improving the adsorption rate, it is preferable that the decomposition treatment liquid is adjusted to a pH of 6 or less. The pH of the decomposition treatment liquid may be more than 4.5 and 6 or less.

The fixed carrier is preferably either a synthetic adsorbent or an ion exchange resin.

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.

Examples of aromatic resins include styrene-divinylbenzene resins. Examples of aromatic resins include porous resins such as aromatic resins with hydrophobic substituents, unsubstituted aromatic resins, and aromatic resins that have been specially treated to be unsubstituted. Of these, unsubstituted aromatic resins and aromatic resins that have been specially treated to be unsubstituted are preferred.

Synthetic adsorbents that are commercially available include Diaion (trademark) HP-10, HP-20, HP-21, HP-30, HP-40, HP-50 (all unsubstituted aromatic resins, all trade names, manufactured by Mitsubishi Chemical Corporation); SP-825, SP-800, SP-850, SP-875, SP-70, 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, XAD-2000 (aromatic resins, all trade names, manufactured by Organo Corporation); Diaion Examples of such resins include POLY(TM) SP-205, SP-206, and SP-207 (aromatic resins having hydrophobic substituents, all trade names, manufactured by Mitsubishi Chemical Corporation); HP-2MG and EX-0021 (aromatic resins having hydrophobic substituents, all trade names, manufactured by Mitsubishi Chemical Corporation); Amberlite(TM) XAD-7 and XAD-8 (acrylic ester resins, all trade names, manufactured by Organo Corporation); Diaion(TM) HP1MG and HP2MG (acrylic acid methacrylic resins, all trade names, manufactured by Mitsubishi Chemical Corporation); Sephadex(TM) LH20 and LH60 (crosslinked dextran derivatives, all trade names, manufactured by Pharmacia Biotech Co., Ltd.). Among these, aromatic resins without substituents (e.g., HP-20) or aromatic resins that have been specially treated with an unsubstituted type (e.g., SP-850) are preferred.

The amount of synthetic adsorbent to be packed into the column can be determined appropriately depending on the size of the column, the type of synthetic adsorbent, etc.

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 h ^{- 1.} Note that SV (Space Velocity) is a unit that indicates how many times the resin volume the liquid is passed per hour.

The adsorbed components (active ingredients) adsorbed to the synthetic adsorbent can be eluted with a solvent (elution solvent). From the viewpoint of recovering the adsorbed components more efficiently, 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 decomposition extract of bagasse.

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 with a volume ratio of 50/50 to 60/40 (ethanol/water) from the viewpoint of enabling the adsorbed components to be eluted more efficiently at room temperature.

When a synthetic adsorbent is used as the fixed carrier, the temperature of the column 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, and the adsorbed components can be eluted more efficiently. The temperature is preferably 20 to 60°C, and more preferably 40 to 60°C. The inside of the column may be under normal pressure or under pressurized conditions.

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 is preferably SV=0.1 to 10 hr ^-1 .

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

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).

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.).

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

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 passing is 100 to 300% of the ion exchange resin, and the column temperature is 40 to 90° C. The inside of the column may be at normal pressure or under pressure.

When an ion exchange resin is used as the fixed carrier, the decomposed extract of bagasse may be a fraction obtained by passing the extract through a column packed with an 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.

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 distillation of the solvent 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 components may be used as the decomposition extract of bagasse.

A decomposition extract of bagasse can be obtained, for example, as follows. A 1% by mass aqueous solution of sodium hydroxide is added to the bagasse so that the solid concentration is 0.1 to 50%, and the bagasse is boiled at 100°C to obtain a decomposition treatment liquid (alkaline treatment liquid). The decomposition treatment liquid is ultrafiltered using a UF membrane with a molecular weight cutoff of 2500 to 5000, and the obtained filtrate is adjusted to be acidic and then passed through a column packed with an unsubstituted aromatic resin at a column temperature of 20 to 60°C. The components adsorbed in the column are then eluted with a mixed solvent of ethanol and water (elution solvent) with a volume ratio of 50/50 to 60/40 (ethanol/water) at a column temperature of 20 to 60°C, and the fraction in which the amount of elution liquid 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 collected. The recovered fractions (fractions containing components with antihypertensive activity) can be collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a decomposition extract of bagasse. The decomposition extract of bagasse thus obtained can be stored as a liquid or powder extract concentrated to a solid content of 30% by mass or more. When the extract is in liquid form, it is preferably stored in a refrigerator.

As another example, the decomposition extract of bagasse can be obtained, for example, as follows. That is, water is added to bagasse so that the solid concentration is 0.1 to 50%, and hydrothermal treatment is performed with water at 130 to 250°C under a pressure of 0.2 to 4.0 MPa, and a decomposition treatment liquid (hydrothermal treatment liquid) is obtained by solid-liquid separation by filtration. The obtained hydrothermal treatment liquid is passed through a column filled with aromatic resin that has been specially treated to be unsubstituted at a temperature of 20 to 60°C, and the components adsorbed in the column are eluted with a mixed solvent of ethanol and water (elution solvent) with a volume ratio of 50/50 to 60/40 (ethanol/water) at a column temperature of 20 to 60°C, and the fraction eluted in which the amount of elution liquid collected from the start of elution with the mixed solvent of ethanol and water is within 5 times the wet volume of the aromatic resin is recovered. The recovered fractions (fractions containing components with antihypertensive activity) can be collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a decomposition extract of bagasse. The decomposition extract of bagasse thus obtained can be stored as a liquid or powder extract concentrated to a solid content of 30% by mass or more. When the extract is in liquid form, it is preferably stored in a refrigerator.

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

The antihypertensive agent can be used as a food composition, a medicine, 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, etc.

The antihypertensive agent may consist only of the active ingredient, a decomposed extract of bagasse, or may further contain ingredients that can be used in food compositions, quasi-drugs, or medicines. There are no particular limitations on the ingredients that can be used in food compositions, quasi-drugs, or medicines, but examples of such ingredients include amino acids, proteins, carbohydrates, oils and fats, sweeteners, minerals, vitamins, flavorings, excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, suspending agents, etc.

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, soy oil, safflower oil, olive oil, and palm oil. Examples of sweeteners include sugars such as glucose, sucrose, fructose, glucose-fructose liquid sugar, and fructose-glucose liquid sugar; 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, vitamin B, biotin, niacin, etc. Examples of excipients include dextrin, starch, lactose, crystalline cellulose, etc. Examples of binders include polyvinyl alcohol, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, etc. Examples of lubricants include magnesium stearate, calcium stearate, talc, etc. Examples of disintegrants include crystalline cellulose, agar, gelatin, calcium carbonate, sodium bicarbonate, dextrin, etc. 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, lecithin, etc. Examples of bases include cetostearyl alcohol, lanolin, polyethylene glycol, etc. Examples of solubilizing agents include polyethylene glycol, propylene glycol, sodium carbonate, sodium citrate, etc. Examples of suspending agents include glycerin monostearate, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxymethylcellulose, sodium alginate, etc. These may be used alone or in combination of two or more.

When the antihypertensive agent is blended with other materials, the content of the active ingredient, the decomposition extract of bagasse, may be appropriately set depending on the form and intended use of the antihypertensive agent described below, but from the viewpoint of more effectively exerting the antihypertensive effect, 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 preferably 50% by mass or less, more preferably 40% by mass or less, and even more preferably 30% by mass or less, as solid content.

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

Antihypertensive agents may be administered orally or parenterally, such as intravenously.

When the antihypertensive agent is orally administered, the dosage is, for example, preferably 50 μg/kg (body weight) or more of the decomposition extract of bagasse per administration, more preferably 100 μg/kg (body weight) or more, and even more preferably 150 μg/kg (body weight) or more. Also, the decomposition extract of bagasse is preferably administered at a dose of 150 μg/kg (body weight) or more per day, more preferably 300 μg/kg (body weight) or more, and even more preferably 450 μg/kg (body weight) or more. Also, the decomposition extract of bagasse is preferably administered at a 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. In addition, the bagasse decomposition extract is preferably administered at a daily dose of 3000 mg/kg (body weight) or less, more preferably 2000 mg/kg (body weight) or less, and even more preferably 1000 mg/kg (body weight) or less. Within this range, a sufficient blood concentration can be achieved, and the antihypertensive effect can be better expressed.

When the antihypertensive agent is administered parenterally, the dosage is, for example, preferably 100 μg/kg (body weight) or more of the decomposition 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. Also, the decomposition extract of bagasse is preferably administered at a dose of 200 μg/kg (body weight) or more per day, more preferably 300 μg/kg (body weight) or more, and even more preferably 400 μg/kg (body weight) or more. Also, the decomposition extract of bagasse is preferably administered at a 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. In addition, the bagasse decomposition extract is preferably administered at a daily dose of 4000 mg/kg (body weight) or less, more preferably at a daily dose of 3000 mg/kg (body weight) or less, and even more preferably at a daily dose of 2000 mg/kg (body weight) or less. Within this range, a sufficient blood concentration can be achieved, and the antihypertensive effect can be better expressed.

Antihypertensive agents can also be used as feed or feed additives. Examples of feed include companion animal feed such as dog food and cat food, livestock feed, poultry feed, and farmed fish and shellfish feed. "Feed" includes anything that animals take orally for nutritional purposes. More specifically, when classified in terms of nutrient content, it includes roughage, concentrated feed, inorganic feed, and special feed, and when classified in terms of official standards, it includes compound feed, mixed feed, and single feed. When classified in terms of feeding method, it includes all feeds that are fed directly, mixed with other feeds, or added to drinking water to supplement nutrients.

Specific aspects of the angiotensin-converting enzyme inhibitor according to one embodiment may be similar to 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.

The present invention will be described below with reference to examples, but the present invention is not limited to these examples. Hereinafter, the decomposition extract of bagasse may be simply referred to as the "extract."

<Production of bagasse decomposition extract>
[Production Example 1]
15 kg of bagasse (water content 50% by mass), which is sugarcane pomace, and 100 L of 0.5% (w/w) aqueous sodium hydroxide solution were mixed and subjected to an alkali treatment under the condition of 150 ° C. The mixture after the alkali treatment was separated into a solid portion and a liquid portion, and about 100 L of the liquid portion was obtained. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500, and 80 L of filtrate was obtained. 1 liter of synthetic adsorbent (manufactured by Mitsubishi Chemical Corporation, HP-20) was filled in a resin tower (inner diameter 80 mm, height 400 mm), and the above filtrate was passed through it at a flow rate of 10 liters / hour (SV = 10.0 (hour ^-1 )) after adjusting the pH to 6.

Subsequently, 5 liters of purified water was passed through the resin tower at a flow rate of 10 liters/hour (SV=10.0 (hour ^-1 )) to wash the resin tower. Next, 2 liters of 60% aqueous ethanol solution (ethanol/water=60/40 (volume/volume)) was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour ^-1 )) as an elution solvent. Subsequently, 2 liters of purified water was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour ^-1 )) to elute the components adsorbed to the synthetic adsorbent. The fraction eluted from the resin tower was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and then freeze-dried overnight to obtain 20 g of a brownish powder as a decomposition extract of bagasse. This was designated as Extract A.

[Production 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 a solid and a liquid, and about 88 L of the liquid was obtained. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500, and 70 L of filtrate was obtained. 1 L of synthetic adsorbent (Mitsubishi Chemical Corporation, SP-850) was packed in a resin tower (inner diameter 80 mm, height 400 mm), and 25 L of the above filtrate was passed through it at a flow rate of 20 L/hour (SV = 20.0 (hour ^-1 )).

Subsequently, 3.3 liters of purified water was passed through the resin tower at a flow rate of 20 liters/hour (SV=20.0 (hour ^-1 )) to wash the resin tower. Next, 2 liters of 60% aqueous ethanol solution (ethanol/water=60/40 (volume/volume)) was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour ^-1 )) as an elution solvent. Subsequently, 2 liters of purified water was passed through the resin tower at a flow rate of 2 liters/hour (SV=2.0 (hour ^-1 )) to elute the components adsorbed to the synthetic adsorbent. The fraction eluted from the resin tower was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and then freeze-dried overnight to obtain 40 g of a brownish powder as a decomposition extract of bagasse. This was designated as Extract W.

<Angiotensin-converting enzyme inhibition test>
An angiotensin-converting enzyme inhibition test was carried out based on the method of Nakano et al. (Nakano et al., Biosci. Biotechnol. Biochem., 70, 1118-1126 (2006)).
1.0 g each of Extract A and Extract W was extracted with 20 ml of 50% (V/V) ethanol solution, and then appropriately diluted with 0.1 mol/L Hepes buffer (pH 8.3) to prepare test solutions with the concentrations shown in Table 1. 25 μL each of 0.1 mol/L Hepes buffer (untreated group) or the test solution was added to a 96-well microplate, and 25 μL of 20 mU/mL ACE solution was added and incubated at 37° C. for 5 minutes. 25 μL of 8 mmol/L substrate (Hippuryl-L-histidyl-L-leucine; Hip-His-Leu) solution was further added thereto and reacted at 37° C. for 30 minutes. Thereafter, 25 μL of 0.1 mol/L sodium hydroxide aqueous solution was added to stop the reaction, and 25 μL of 1 mass% orthophthalaldehyde (OPA) aqueous solution was further added and left 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.

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

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

As shown in Table 1, ACE inhibitory effects were observed in Extract A and Extract W. The _IC50 of Extract A was 0.95 mg/mL based on the total amount of the test solution (final concentration based on the total amount of the measurement specimen: 0.16 mg/mL), and the _IC50 of Extract W was 0.52 mg/mL based on the total amount of the test solution (final concentration based on the total amount of the measurement specimen: 0.087 mg/mL).

Claims (2)

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. 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.