JP6454661B2 - Blood pressure increasing agent - Google Patents

Description

  The present invention relates to a blood pressure raising agent.

  Low blood pressure is considered as one of the causes of various symptoms such as coldness, hypothermia, dizziness, dizziness on standing up. Particularly in recent years, the number of people with low blood pressure has increased due to changes in lifestyle habits. About such low blood pressure, it is required to improve easily without burden by daily intake of functional components and the like.

  For example, Non-Patent Documents 1 and 2 disclose that monoglycosyl hesperidin has a function of maintaining body temperature by improving blood flow.

http: // www. caa. go. jp / foods / pdf / A130-kihon. pdf http: // www. caa. go. jp / foods / pdf / A130-kinou. pdf

  However, according to Non-Patent Documents 1 and 2, monoglycosyl hesperidin has an effective daily dose of 170 to 340 mg, and since it was necessary to take a large amount, daily intake such as a decrease in palatability, etc. It was a burden to do.

  This invention is made | formed in view of the above situation, and it aims at providing the blood pressure raising agent which can raise a blood pressure, without ingesting a large quantity.

  The present inventors have found that anthocyanins, which are generally said to have an effect of preventing and improving eye strain, surprisingly have a blood pressure increasing action, and have completed the present invention. More specifically, the present invention provides the following.

  (1) An antihypertensive agent containing anthocyanins.

  (2) The blood pressure increasing agent according to (1), comprising a tea leaf extract.

  (3) An antihypertensive agent comprising Saint Rouge (variety registration number 21262) or a subsequent tea leaf extract.

  (4) The blood pressure increasing agent according to any one of (1) to (3), which is used for improving or preventing hypotension.

  (5) The blood pressure increasing agent according to any one of (1) to (4), which is used for improving or preventing coldness.

  (6) The blood pressure increasing agent according to any one of (1) to (5), wherein the total intake amount of anthocyanins per day is 0.1 to 100 mg.

  (7) The blood pressure increasing agent according to any one of (1) to (6), which is in the form of a food or drink.

  According to the present invention, blood pressure can be increased without taking a large amount.

It is a graph which shows the variation | change_quantity of the systolic blood pressure at the time of getting up. It is a graph which shows the variation | change_quantity of the diastolic blood pressure at the time of getting up. It is a graph which shows the variation | change_quantity of the systolic blood pressure at the time of bedtime. It is a graph which shows the variation | change_quantity of the diastolic blood pressure at the time of bedtime.

  Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited to the following embodiments, and can be implemented with appropriate modifications within the scope of the object of the present invention.

  The antihypertensive agent according to the present invention contains anthocyanins. Alternatively, the blood pressure increasing agent according to the present invention contains Saint Rouge (variety registration number 21262) or a tea leaf extract of its progeny.

  The reason for this is not clear, but it has been found that anthocyanins have the effect of increasing blood pressure even if they are not consumed in large amounts. The blood pressure increasing action is suitable for the improvement or prevention of symptoms such as low blood pressure, coldness due to low blood pressure, hypothermia, dizziness, dizziness on standing up.

  Anthocyanins are present in plants in the form of glycosides in which anthocyanins, which are flavonoids, are linked to sugars and sugar chains as aglycones. Depending on their structure, delphinidins, cyanidins, pelargonidins, and auranthidines , Luteolinidine, peonidin, malvidin, petunidin, europeinidine, rosinidine and the like. The component of anthocyanin is not particularly limited, but preferred examples include delphinidin-based anthocyanins and cyanidin-based anthocyanins.

In the present invention, for example, “delphinidin-based anthocyanin” refers to a glycoside of delphinidin in which the substituent R ¹ is an OH group in the following formula (1). The glycoside of delphinidin refers to one in which at least one of the hydroxyl groups in delphinidin is substituted with a substituent having a sugar structure (galactose, glucose, etc.). The “cyanidine-based anthocyanin” refers to a cyanidin glycoside in which the substituent R ¹ is a hydrogen atom in the following formula (1). The glycoside of cyanidin refers to one in which at least one of the hydroxyl groups in cyanidin is substituted with a substituent having a sugar structure (galactose, glucose, etc.). Examples of the “petunidin-based anthocyanins” include petunidin glycosides in which the substituent R ¹ is an OCH ₃ group in the following formula (1). The glycoside of petunidin refers to one in which at least one of the hydroxyl groups in petunidin is substituted with a substituent having a sugar structure (galactose, glucose, etc.).

In the following formula (1), R ² is preferably at least one of a hydrogen atom, a group represented by the following formula (I), or a group represented by (II). In formulas (I) and (II), R ³ is a hydrogen atom, a p-coumaroyl group (trans) represented by formula (III), a p-coumaroyl group (cis) represented by formula (IV), or malonyl It is preferably at least one of the groups.

  Specifically, as delphinidin-based anthocyanins, for example, delphinidin-3-O-β-galactopyranoside (D3Ga), delphinidin-3-O-β- (6-trans-p-coumaroyl) galactopyranoside ( DCGa), delphinidin-3-O-β- (6-cis-p-coumaroyl) galactopyranoside (DCZGa), delphinidin-3-O-β-glucopyranoside (D3G), delphinidin-3-O-β- ( 6-trans-p-coumaroyl) glucopyranoside (DCG), and the like. In particular, delphinidin-based anthocyanin is a galacside delphinindi-type anthocyanin (delphinidin-3-O-β-galactopyranoside, delphinidin-3-yl) because it exhibits extremely high effects in improving eye strain or body fatigue. O-β- (6-trans-p-coumaroyl) galactopyranoside, delphinidin-3-O-β- (6-cis-p-coumaroyl) -β-galactopyranoside) and the like are preferable.

  Anthocyanins other than delphinidin-based anthocyanins are not particularly limited. For example, cyanidin-based anthocyanins include cyanidin-3-O-β-galactopyranoside (C3Ga), cyanidin-3-O-β- (6-trans -P-coumaroyl) -β-galactopyranoside (CCGa), cyanidin-3-O-β- (6-cis-p-coumaroyl) galactopyranoside (CCZGa), cyanidin-3-O-β-glucopyranoside (C3G), cyanidin-3-O-β- (6-trans-p-coumaroyl) -β-glucopyranoside (CCG) and the like. Examples of petunidin-based anthocyanins include petunidin-3-O-β- (6-trans-p-coumaroyl) -β-galactopyranoside (PCGa).

  The anthocyanin may be an anthocyanin extracted from any plant body, or an anthocyanin extracted from tea leaves. Therefore, the blood pressure increasing agent according to the present invention may contain a tea leaf extract. When the blood pressure increasing agent according to the present invention contains a tea leaf extract, the anthocyanin may be derived from the tea leaf extract, and the anthocyanin may be added separately from the tea leaf extract.

  In the present invention, the “tea leaves” are not particularly limited as long as they are leaves of Camellia sinensis. Saint Rouge tea (variety registration number 21262, application number 23800) in the present invention is a tea leaf belonging to Camellia sinensis (L.) Kuntze. For example, a blood pressure increasing action can be obtained by obtaining a tea leaf extract from a tea leaf of San Rouge or its progeny.

  Further, the tea leaf extract may or may not contain catechins, but preferably contains catechins. Catechin has carcinogenesis suppression, arteriosclerosis prevention, suppression of fat metabolism abnormality, suppression of blood pressure increase, platelet aggregation suppression action, antiallergy, antiviral, antibacterial, prevention of bad teeth, prevention of bad breath, normalization of intestinal flora, It is known to have an action of scavenging active oxygen and free radicals, an antioxidant action, and an antidiabetic effect.

  The catechins are not particularly limited as long as they are catechins or derivatives thereof. For example, as catechin, catechin (C), gallocatechin (GC), catechin gallate (CG), gallocatechin gallate (GCG), epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epi Gallocatechin gallate (EGCG), epigallocatechin-3- (3 "-O-methyl) gallate (EGCG3" Me), gallocatechin-3- (3 "-O-methyl) gallate (GCG3" Me), epicatechin- 3- (3 ″ -O-methyl) gallate (ECG3 ″ Me), catechin-3- (3 ″ -O-methyl) gallate (CG3 ″ Me) can be mentioned.

  The tea leaf extract of the present invention can be obtained by extracting tea leaves with a solvent, and conventionally known methods can be employed. From the viewpoint of extracting active ingredients such as anthocyanins and catechins, the tea leaves are preferably extracted by pulverization. Since it is preferable that the pulverized tea leaves have a uniform size, the crushed material may be sieved.

  The extraction solvent may be any non-toxic solvent, and examples of the solvent used in the solvent extraction method include water, a hydrophilic solvent, and a mixture thereof. In the solvent extraction method, water used for the extraction solvent is not particularly limited, and examples thereof include tap water, distilled water, pure water, and ion exchange water. Examples of the hydrophilic solvent used as the extraction solvent in the solvent extraction method include lower alcohols such as methanol, ethanol, propyl alcohol, and isopropyl alcohol, lower aliphatic ketones such as acetone and methyl ethyl ketone, 1,3-butylene glycol, and propylene glycol. And polyhydric alcohols such as glycerin. Considering the recovery rate of catechins in the extract, it is preferable to use a solvent containing ethanol. The extraction temperature is preferably 20 ° C to 100 ° C, more preferably 50 ° C to 100 ° C. The extraction pH is preferably 1.0 to 7.0, and more preferably 1.5 to 6.5. The extraction may be performed a plurality of times by collecting the residue once extracted. The extraction may use a method generally used as a chemical separation and purification method. For example, liquid-liquid distribution, thin layer chromatography, adsorption column chromatography, distribution column chromatography, gel filtration column chromatography, ion exchange column chromatography, electrophoresis, high performance liquid chromatography and the like can be used. Moreover, you may carry out combining these isolation | separation purification means as needed.

  Since the blood pressure increasing agent according to the present invention has an action of increasing blood pressure as described above, it is preferably used for improvement or prevention of hypotension. Moreover, it is preferable that the blood pressure increasing agent which concerns on this invention is used for improvement or prevention of symptom, such as cooling property by hypotension, hypothermia, dizziness, and standing dizziness.

  The total intake amount of anthocyanins per day is not particularly limited, but specifically, it is preferably 0.1 mg or more, more preferably 2 mg or more, because the above-described blood pressure increasing action can be obtained. More preferably, it is 10 mg or more. On the other hand, a sufficient blood pressure raising effect can be obtained without taking a large amount. From this viewpoint, the upper limit of the total intake amount of anthocyanins per day is preferably 100 mg or less, more preferably 50 mg or less, and further preferably 40 mg or less. If the total intake amount of anthocyanin is 100 mg or less, the influence on the taste and flavor can be reduced when added to foods and drinks that are blood pressure increasing agents.

  Monoglycosyl hesperidin has an effective daily dose of 170 to 340 mg and needs to be ingested in large amounts. On the other hand, anthocyanins can obtain a sufficient blood pressure increasing effect even in a small amount such as 100 mg or less.

  The total intake amount of catechins per day is not particularly limited, but is preferably 300 mg or more per day, more preferably 400 mg or more, and further preferably 500 mg or more. By containing 300 mg or more, a sufficient blood pressure increasing action can be obtained. On the other hand, as an upper limit, the dose per day is preferably 2000 mg or less, more preferably 1500 mg or less, and even more preferably 1000 mg or less. If it is 1000 mg or less, there is little influence on the taste and flavor of the food and drink when blended into the food and drink.

  The blood pressure increasing agent of the present invention may or may not contain other components other than the above-mentioned anthocyanins and catechins. As other components, the blood pressure increasing agent of the present invention can contain, for example, caffeine (for example, 50 to 300 mg) which is a polyphenol component other than anthocyanins and catechins. The blood pressure increasing agent of the present invention can obtain the above-described blood pressure increasing action even when caffeine is included.

  Furthermore, the intake period of the blood pressure-elevating agent described above is not particularly limited, but it is preferably taken continuously for a long period of time, specifically, preferably 4 weeks or more, and 8 weeks or more. Is more preferable, and it is further more preferable that it is 12 weeks or more. By ingesting for 4 weeks or more, a sufficient blood pressure increasing effect can be obtained. Moreover, it is preferable to take every day during these periods, and it is particularly preferable that the total intake amount of anthocyanins per day is within the numerical range described above.

  The form of the blood pressure raising agent of the present invention may be any form, for example, a form of food or drink. The antihypertensive agent of the present invention may be composed of anthocyanin or a tea leaf extract containing the anthocyanin, and may contain other components depending on the purpose. When the blood pressure increasing agent of the present invention is applied as a food or drink, the tea leaf extract containing anthocyanin may be ingested as it is as a tea beverage, or various beverage materials or food materials such as confectionery, health food, and supplements. May be ingested. The property of the improving agent or the preventive agent of the present invention is solid or liquid, and when it is solid, for example, tea leaf extract containing anthocyanin is an agent such as tablets, capsules, granules, syrups, troches, etc. It may be processed into a mold. In addition, when the improver or preventive agent of the present invention is applied as a food or drink, a gelling agent, a saccharide, a fragrance, a sweetener, an oil, a base, an excipient, a food additive, a secondary material, a bulking agent, etc. are appropriately used. You may mix | blend.

  Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

[Example 1]
100 ml of 80 ° C. water is poured into 2.5 g of Saint Rouge tea leaves and left for 20 minutes to obtain a tea leaf extract. After adding excipients to this tea leaf extract, it is spray-dried and dried. After the liquid was obtained, this tea leaf extract was freeze-dried to prepare Saint Rouge powder tea (hereinafter referred to as "Saint Rouge tea"). The delphinidin-based anthocyanin content in the saint rouge tea was 70% with respect to the total anthocyanin content. The intakes of the main components of anthocyanins and catechins per day for San Rouge tea are as follows.
Anthocyanin: 11.2 mg / day Delphinidin-3-O-β- (6-trans-p-coumaroyl) -galactopyranoside: 4.1 mg / day Delphinidin-3-O-β-galactopyranoside: 2 .4 mg / day Cyanidin-3-O- (6-trans-p-coumaroyl) -β-galactopyranoside: 1.8 mg / day Cyanidin-3-O-β-galactopyranoside: 0.9 mg / day Delphinidin-3-O-β-glucopyranoside: 0.8 mg / day Delphinidin-3-O-β- (6-cis-p-coumaroyl) -galactopyranoside: 0.6 mg / day cyanidin-3-O-β -Glucopyranoside): 0.3 mg / day Cyanidin-3-O- (6-trans-p-coumaroyl) -β-galactopyranoside): 0.3 mg / day Russia gallate (EGCG) + epigallocatechin gallate (GCG): 322mg / day - caffeine: 185mg / day

[Comparative Example 1 (placebo)]
A barley tea extract was obtained by hot water extraction of roasted Rojo barley, an excipient was added to the barley tea extract, and then spray-dried to prepare barley tea powdered tea (hereinafter referred to as barley tea). Barley tea does not contain any of anthocyanins, catechins, or caffeine.

[Comparative Example 2]
After pouring 100 ml of 100 ° C hot water into 2.5 g of Yabukita tea leaves and leaving it for 30 minutes to obtain a tea leaf extract, an excipient was added to this tea leaf extract, followed by spray drying and drying. Powdered tea (hereinafter referred to as Yabukita tea) was prepared. The intake of each component per day of this Yabukita tea is as follows.
Anthocyanins: 0 mg / day Catechin epigallocatechin gallate (EGCG) + gallocatechin gallate (GCG): 324 mg / day Caffeine: 203 mg / day

[Evaluation]
A placebo-controlled double-blind parallel group for the purpose of clarifying the blood pressure-elevating effect by continuously ingesting the sun rouge tea of Example 1, the barley tea of Comparative Example 1, and the Yabukita Tea of Comparative Example 2 every day for 12 weeks. An intercomparison test was conducted.

(subject)
The subjects were 120 Japanese men and women who were between 20 and 60 years old. The number of subjects who took Example 1 (Saint Rouge tea) who completed Test Method 1 and Test Method 2 was 39, and the number of subjects who took Comparative Example 1 (Barley Tea) was 37, and Comparative Example 2 (Babuki The number of subjects who took the tea was 38. It does not include those who are judged to be ineligible for study participation by the supervising physician, such as those who are currently receiving continuous treatment for some disease.

(test)
The subject must stay in a sitting position at the time of waking up and at bedtime on a predetermined examination day, and then use a brachial cuff type automatic sphygmomanometer (hereinafter referred to as an automatic sphygmomanometer) for systolic and diastolic blood pressure. Was measured. Then, changes in blood pressure after 4 weeks, 8 weeks, and 12 weeks after blood intake before intake (0 week) of saint rouge tea of Example 1, barley tea of Comparative Example 1, and Yabukita Tea of Comparative Example 2 The amount was evaluated. Specifically, blood pressure was measured by the subject himself using an automatic sphygmomanometer, and in principle was measured with the upper arm opposite to the dominant arm. The measurement was performed before breakfast after urination within 1 hour after getting up and after urination before going to bed. After resting for 5 minutes each, the measurement was carried out three times in the sitting position, and the average value of two stable measurements among the three measurements was taken as the blood pressure value of each day (each day's blood pressure value). The evaluation is performed before ingestion, 4 weeks after ingestion, 8 weeks after ingestion, and 12 weeks after ingestion, and the average of blood pressure values for 5 days before each evaluation day is taken as the blood pressure value (evaluation day blood pressure value) on that evaluation day. did. In addition, in order to eliminate variation in the measurement technique between subjects, all the subjects were instructed to actually measure with an automatic sphygmomanometer before starting the test.

(result)
FIG. 1 shows the amount of change in systolic blood pressure when waking up. FIG. 2 shows the amount of change in diastolic blood pressure when waking up. FIG. 3 shows the amount of change in systolic blood pressure at bedtime. FIG. 4 shows the amount of change in diastolic blood pressure at bedtime. 1 to 4, * indicates a significant difference (p <0.05), and ** indicates a significant difference (p <0.01).

(Discussion)
1-4, Example 1 (Saint Rouge tea) shows a significantly higher value than Comparative Example 1 (Barley tea) and Comparative Example 2 (Yabukita tea), and blood pressure within the normal range. It was confirmed that there was an action to raise. Moreover, it was confirmed that such an action to increase blood pressure can be obtained by daily intake for 4 weeks or more, preferably 8 weeks or more. Since Example 1 (Saint Rouge tea) has such an effect of increasing blood pressure, it is considered preferable to be used for improving or preventing hypotension and coldness.

Claims (5)

An antihypertensive agent comprising a tea leaf extract of San Rouge (variety registration number 21262 ) . The blood pressure increasing agent according to claim 1, which is used for improvement or prevention of hypotension. The blood pressure increasing agent according to claim 1 or 2 , which is used for improving or preventing coldness. The blood pressure increasing agent according to any one of claims 1 to 3 , wherein the total intake amount of anthocyanin per day is 0.1 to 100 mg. The blood pressure increasing agent according to any one of claims 1 to 4 , which is in the form of a food or drink.

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