Arterial stiffness increase inhibitor

Abstract

To provide an artery stiffness increase inhibitor that can inhibit an increase in artery stiffness due to the ingestion of food.SOLUTION: An artery stiffness increase inhibitor contains isomaltulose as an active ingredient.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an agent for inhibiting an increase in arterial stiffness. [Background technology]

[0002] Arterial stiffness refers to the physical hardness of the arterial wall, and has been reported to be a predictor of vascular disease independent of blood pressure. Therefore, in order to prevent arteriosclerosis (aging of blood vessels) and early vascular disorders, it is important to control arterial stiffness as well as blood pressure.

[0003] Suppressing the increase in arterial stiffness is expected to improve arteriosclerosis (aging of blood vessels) and other early vascular disorders. Therefore, various studies have been conducted on ingredients for suppressing or improving arterial stiffness. For example, Patent Document 1 discloses that cocoa polyphenols are useful as an active ingredient in a composition for improving arterial stiffness. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2017 / 026471 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of one aspect of the present invention is to provide an agent for suppressing an increase in arterial stiffness, which is capable of suppressing an increase in arterial stiffness caused by food intake. [Means for solving the problem]

[0006] The present inventors have found that in humans or animals, the ingestion of a meal temporarily increases arterial stiffness, but that the ingestion of isomaltulose inhibits this increase in arterial stiffness. The present invention is based on this novel finding.

[0007] That is, a first aspect of the present invention provides an agent for suppressing an increase in arterial stiffness, which comprises isomaltulose as an active ingredient.

[0008] In a first aspect, the agent for inhibiting an increase in arterial stiffness may be administered to a human who does not have diabetes.

[0009] In a second aspect, the present invention provides an agent for suppressing an increase in pulse wave velocity, which contains isomaltulose as an active ingredient.

[0010] In a third aspect, the present invention provides an agent for suppressing an increase in cardio-ankle vascular index, which comprises isomaltulose as an active ingredient. [Effects of the Invention]

[0011] According to the present invention, an agent for suppressing an increase in arterial stiffness can be provided, which is capable of suppressing an increase in arterial stiffness. [Brief explanation of the drawings]

[0012] [Figure 1] 1 is a graph showing the time course of measured values ​​of baPWV, hbPWV, and CAVI in an example. [Figure 2] 1 is a graph showing the time course of changes in measured values ​​of baPWV, hbPWV, and CAVI in an example. DETAILED DESCRIPTION OF THE INVENTION

[0013] Hereinafter, embodiments of the present invention will be described, but the present invention is not limited to the following embodiments.

[0014] As used herein, "arterial stiffness" refers to the physical stiffness (physical flexibility) of the arterial wall. The arterial wall has a three-layer structure: the intima, the media, and the adventitia. However, arterial stiffness refers to the stiffness of the entire arterial wall, including all three layers, and is not evaluated based on the stiffness of any one layer. Furthermore, arterial stiffness indicates the physical stiffness of the arterial wall, and is an index different from the arteriosclerosis index, which is calculated from the cholesterol level in the blood.

[0015] The agent for inhibiting an increase in arterial stiffness of the present invention has the effect of inhibiting an increase in arterial stiffness when administered before arterial stiffness increases, and further has the effect of reducing arterial stiffness when administered after arterial stiffness increases. It has been found that arterial stiffness temporarily increases due to food intake (mainly carbohydrate intake), but the agent for inhibiting an increase in arterial stiffness of the present invention is novel in that it has the effect of inhibiting the temporary increase in arterial stiffness due to food intake.

[0016] Arterial stiffness can be evaluated by measuring, for example, pulse wave velocity (PWV) or cardio-ancle vascular index (CAVI), which are indicators of cardiovascular risk. PWV may be brachial-ankle pulse wave velocity (baPWV) or heart-brachial pulse wave velocity (hbPWV). The greater the degree of arterial stiffness, the higher the PWV and CAVI.

[0017] That is, the present invention can be said to provide an agent for suppressing an increase in pulse wave velocity, which contains isomaltulose as an active ingredient, or an agent for suppressing an increase in cardio-ankle vascular index, which contains isomaltulose as an active ingredient.Furthermore, the present invention can be said to provide an agent for suppressing an increase in brachial-ankle pulse wave velocity, and an agent for suppressing an increase in heart-brachial pulse wave velocity, which contain isomaltulose as an active ingredient.

[0018] An agent for inhibiting an increase in arterial stiffness according to one embodiment contains isomaltulose as an active ingredient.

[0019] Isomaltulose is a compound also known as 6-O-α-D-glucopyranosyl-D-fructose. Isomaltulose is also known as palatinose. "Palatinose" is a registered trademark of Mitsui Sugar Co., Ltd.

[0020] Isomaltulose is naturally found in honey and is also present as a transfer product of sucrose when α-glucosyltransferase (isomaltulose synthase) derived from bacteria and yeast acts on sucrose. Industrially, isomaltulose is produced by the action of α-glucosyltransferase derived from bacteria such as Protaminobacter rubrum and Serratia plymuthica on sucrose.

[0021] Isomaltulose may be naturally occurring or synthesized by enzymatic action or the like. Commercially available isomaltulose may also be used. Examples of commercially available isomaltulose include crystalline palatinose (trade name "Crystalline Palatinose IC", manufactured by Mitsui Sugar Co., Ltd.), powdered palatinose (trade name "Palatinose ICP", manufactured by Mitsui Sugar Co., Ltd.), and palatinose syrup (trade names "Palatinose Syrup-ISN" and "Palatinose Syrup-TN", manufactured by Mitsui Sugar Co., Ltd.).

[0022] The agent for inhibiting an increase in arterial stiffness 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, etc. That is, according to the present invention, a food composition for inhibiting an increase in arterial stiffness, a pharmaceutical product for inhibiting an increase in arterial stiffness, or a quasi-drug for inhibiting an increase in arterial stiffness is provided.

[0023] The agent for inhibiting an increase in arterial stiffness may consist solely of the active ingredient isomaltulose, or may further contain a material that can be used in a food composition, quasi-drug, or pharmaceutical product. The material that can be used in a food composition, quasi-drug, or pharmaceutical product is 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.

[0024] 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 (excluding isomaltulose) 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 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.

[0025] When the inhibitor of arterial stiffness increase contains materials other than isomaltulose, the content of isomaltulose may be appropriately set depending on the form of the inhibitor of arterial stiffness increase, the purpose of use, etc. From the viewpoint of more effectively exerting the inhibitory effect on arterial stiffness increase, the content of isomaltulose is preferably 10% by mass or more, more preferably 20% by mass or more, even more preferably 30% by mass or more, and is preferably 70% by mass or less, more preferably 60% by mass or less, even more preferably 50% by mass or less, based on the total amount of the inhibitor of arterial stiffness increase.

[0026] The form of the agent for inhibiting an increase in arterial stiffness is not limited, and may be any form such as a solid (powder, granules, etc.), a liquid (solution, suspension, etc.), a paste, etc., and may be any dosage form such as a powder, pill, granules, tablet, capsule, troche, liquid, suspension, etc. A food composition, pharmaceutical product, or quasi-drug containing the agent for inhibiting an increase in arterial stiffness may be in the form of a fondant, granules, tablet, syrup, drink, soft drink, jelly drink, powdered drink, etc.

[0027] The subject of administration of the inhibitor of arterial stiffness increase may be a human or an animal, preferably a human. The subject of administration may be a human not suffering from diabetes (a healthy individual). The subject of administration may be an elderly person aged 60 or over, 65 or over, or 70 or over.

[0028] The agent for inhibiting an increase in arterial stiffness may be administered orally or parenterally, such as intravenously, but is preferably administered orally.

[0029] When the agent for inhibiting an increase in arterial stiffness is orally administered, for example, isomaltulose is preferably administered in an amount of 5 g or more per administration, more preferably 8 g or more, and even more preferably 10 g or more. Furthermore, isomaltulose is preferably administered in an amount of less than 50 g per administration, more preferably 30 g or less, and even more preferably 25 g or less. Within this range, a sufficient blood concentration can be achieved, and the inhibitory effect on the increase in arterial stiffness can be more effectively exerted. As described above, the agent for inhibiting an increase in arterial stiffness of this embodiment can effectively act on the arterial wall and inhibit the increase in arterial stiffness even when administered in a small amount, for example, less than 50 g.

[0030] The agent for inhibiting an increase in arterial stiffness may be administered only once before arterial stiffness increases or after arterial stiffness increases. The agent for inhibiting an increase in arterial stiffness according to this embodiment acts on the arterial wall with a single administration, without requiring continuous administration, and can inhibit an increase in arterial stiffness even after 60 minutes or more or 90 minutes or more have elapsed since administration. The agent for inhibiting an increase in arterial stiffness may be administered multiple times before arterial stiffness increases or after arterial stiffness increases, or may be administered continuously for two or more days.

[0031] When the agent for inhibiting an increase in arterial stiffness is administered to a human, in one embodiment, it may be administered by the following method. That is, the agent for inhibiting an increase in arterial stiffness may be administered once to a human without diabetes before a meal or simultaneously with a meal in an amount such that the amount of isomaltulose is less than 50 g. In this case, the agent for inhibiting an increase in arterial stiffness may be administered by replacing part or all of the carbohydrates contained in the meal.

[0032] When the inhibitor of arterial stiffness increase is used in animals, it can also be used as feed or a feed additive. Examples of feed include companion animal feed such as dog food and cat food, livestock feed, poultry feed, and feed for farmed fish and shellfish. The term "feed" includes all feeds that animals orally ingest for nutritional purposes. More specifically, when classified based on nutrient content, it encompasses all roughage, concentrated feed, inorganic feed, and special feed, and when classified based on official standards, it encompasses all compound feed, mixed feed, and single feed. Furthermore, when classified based on feeding method, it encompasses all feeds that are fed directly, mixed with other feeds, or added to drinking water to supplement nutrients.

[0033] Specific aspects of the inhibitor of an increase in pulse wave velocity and the inhibitor of an increase in cardio-ankle vascular index according to one embodiment may be the same as those of the bone metabolism improving agent described above. That is, the inhibitor of an increase in pulse wave velocity and the inhibitor of an increase in cardio-ankle vascular index according to one embodiment may be obtained by replacing "inhibitor of an increase in arterial stiffness" in the description of the inhibitor of an increase in arterial stiffness described above with "inhibitor of an increase in pulse wave velocity" or "inhibitor of an increase in cardio-ankle vascular index." [Example]

[0034] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to the following examples.

[0035] A test sample was prepared by dissolving 25 g of isomaltulose in 200 mL of water, while a comparative test sample was prepared by dissolving 25 g of glucose in 200 mL of water.

[0036] The subjects were 10 healthy individuals with a mean age of 74.3 ± 3.4 years (standard error) and no underlying illnesses. The entire test sample was administered to each subject on an empty stomach. Arterial stiffness was measured 30, 60, and 90 minutes after administration. Arterial stiffness was measured using pulse wave velocity at two locations using a blood pressure pulse wave monitor (Omron Colin Co., Ltd., form PWV / ABI) and a blood pressure pulse wave monitor (Fukuda Colin Co., Ltd., BP-203RPEII). Proximal aortic stiffness was measured by measuring the cardiac blood pressure waveform with a phonocardiograph and the brachial artery blood pressure waveform with an oscillometric sensor. hbPWV was calculated from the pulse wave propagation time obtained from these measurements and the propagation distance obtained from height measurements. Systemic arterial stiffness (baPWV) was calculated from the pulse wave propagation time obtained from the brachial artery and ankle blood pressure waveforms measured with an oscillometric sensor and the propagation distance obtained by measuring height. Additionally, cardiac blood pressure waveforms were measured with a phonocardiograph, and brachial artery blood pressure waveforms were measured with an oscillometric sensor. CAVI was calculated from the pulse wave propagation time obtained from these measurements and the propagation distance obtained by measuring height. After a sufficient period, the 10 subjects ingested a comparative test sample, and baPWV, hbPWV, and CAVI were measured using the same method. Figure 1 shows the time course of each index, and Figure 2 shows the time course of change from the pre-intake values. In Figures 1 and 2, ** indicates a significant difference (p<0.01) compared to the pre-intake value, and # or ## indicates a significant difference between isomaltulose and glucose (#: p<0.05, ##: p<0.01).

[0037] As shown in Figure 1, when a sample containing glucose was ingested, baPWV, hbPWV, and CAVI all significantly increased compared to before ingestion. On the other hand, when a sample containing isomaltulose was ingested, no significant increase was observed. Furthermore, as shown in Figure 2, the change in each value when a sample containing isomaltulose was ingested was significantly smaller than the change in each value when a sample containing glucose was ingested. In other words, when isomaltulose was ingested, the increase in arterial stiffness was more suppressed than when glucose was ingested.

Claims

1. An agent for suppressing an increase in arterial stiffness, which contains isomaltulose as an active ingredient and is administered to replace part or all of the carbohydrates contained in food, and which suppresses an increase in arterial stiffness caused by the intake of carbohydrates.

2. The agent for suppressing an increase in arterial stiffness according to claim 1, which is administered to a human not suffering from diabetes.

3. An agent for suppressing an increase in pulse wave velocity caused by the intake of carbohydrates, which contains isomaltulose as an active ingredient and is administered to replace part or all of the carbohydrates contained in food.

4. An inhibitor of an increase in cardio-ankle vascular index, which contains isomaltulose as an active ingredient and is administered to replace part or all of the carbohydrates contained in a meal, and which inhibits an increase in cardio-ankle vascular index caused by carbohydrate intake.

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