JP2019038750A - Composition for preventing/improving deterioration of blood vessel flexibility and preventing/improving arteriosclerosis - Google Patents

Abstract

To provide a composition having the actions of preventing/improving deterioration of blood vessel flexibility and preventing/improving arteriosclerosis, containing ampelopsin as an active ingredient.SOLUTION: The present invention provides a composition for preventing/improving deterioration of blood vessel flexibility and preventing/improving arteriosclerosis, containing ampelopsin as an active ingredient.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a composition for preventing or improving vascular flexibility and preventing or improving arteriosclerosis, which contains amperopsin as an active ingredient.

  The average blood pressure as an index of peripheral vascular resistance is a pressure generated by a steady flow without pulsation, and the steady flow without pulsation indicates peripheral vascular resistance beyond the arteriole. For this reason, if the thickening or narrowing of the peripheral blood vessel occurs, the total peripheral blood vessel resistance increases and the average blood pressure rises. When average blood pressure rises, symptoms of high blood pressure appear, but this high blood pressure is often in the pattern of high blood pressure that appears in the early stages from the thirties, and is considered to be caused by an increase in peripheral vascular resistance.

  In clinical trials for hypertensive subjects, it has been clarified that when the subject ingests salt, the mean blood pressure and systolic blood pressure, which are indicators of peripheral vascular resistance, increase. This is considered to be hypertension that appears because the peripheral blood vessels are stimulated by salt and the peripheral vascular resistance increases. It is predicted that the increase in peripheral vascular resistance is one factor in the hypertension caused by the intake of salt.

As described above, high blood pressure and peripheral vascular resistance are closely related, but it is clear that there is also a close relationship between peripheral vascular resistance and arteriosclerosis.
There are three types of arteriosclerosis: atherosclerosis (atherosclerosis), arteriole sclerosis, and medial calcification sclerosis (Menkeberg sclerosis). Generally speaking, "arteriosclerosis" refers to atherosclerosis. Often points. However, in recent years, arteriosclerosis that affects peripheral vascular resistance, that is, sclerosis of peripheral blood vessels, has attracted attention.
Arteriosclerosis that affects peripheral vascular resistance is a symptom in which the elasticity of peripheral arterial blood vessels is lost due to aging of the blood vessel wall. In this case, since the blood vessels do not have elasticity, the blood vessels tend to rupture when the blood pressure increases, and in particular, when the rupture occurs in the brain, the body functions suddenly, causing a stroke, which is a dangerous disease. It is said that there is no definitive solution other than taking drugs that lower blood pressure.
Pulse wave velocity (PWV) is used as an index as an index of arteriosclerosis including arteriosclerosis that affects peripheral vascular resistance, and evaluation of blood vessel flexibility and blood vessel age. Patent Document 1 describes that a dipeptide contained in a processed product obtained by treating rice protein or rice-derived brewed protein with a proteolytic enzyme improves the pulse wave velocity (PWV).

As described above, PWV has already been widely used as an index of arteriosclerosis such as arteriosclerosis, which affects peripheral vascular resistance, and an index of blood vessel flexibility and blood vessel age. It has been confirmed that there is a correlation between an increase in PWV accompanying aging and aging and hardening of the arterial wall. For this reason, it is recommended in the medical community to incorporate the measurement of PWV into the diagnosis as a blood vessel aging index.
For example, a joint research team of 10 internal medicine societies such as the Japanese Circulation Society established guidelines for PWV measurement (see Non-Patent Document 1) to noninvasively diagnose vascular flexibility and arteriosclerosis. As an important technology.
For the measurement of PWV, an apparatus for clinical examination is commercially available, which makes it easy to measure. As commercially available measuring devices, the device described in Patent Document 2, form PWV / ABI (made by OMRON Colin), measuring device VaSera (made by Fukuda Denshi Co., Ltd.) for arterial stiffness index CAVI, and the like are widely used.
The present inventors are also researching substances that affect vascular flexibility and arteriosclerosis using a PWV measurement device.

Arteriosclerosis that affects peripheral vascular resistance is known to cause an increase in blood pressure. Although the mechanism of its occurrence is not necessarily elucidated, it is said that excessive intake of salt is involved. That is, dietary excess salt intake results in an increase in extracellular fluid volume and circulating blood volume, an increase in cardiac output due to an increase in venous return, and blood pressure increases. In addition, excessive sodium intake increases sodium transport inhibitory factors, increases the sodium concentration in arteriole smooth muscle cells, causes vasoconstriction, and further increases blood pressure. This can be said to be a temporary increase in peripheral vascular resistance and arteriosclerosis.
The present inventors are conducting research while paying attention to the phenomenon of temporary rise in blood pressure due to excessive intake of salt. In addition, we are continuously researching foods and drinks to prevent and improve arteriosclerosis including arteriole sclerosis, which affects peripheral vascular resistance, and vascular flexibility.

  Against such a background, the present inventors have continuously searched for a substance that lowers PWV that can evaluate the flexibility and age of blood vessels of natural products and natural extracts. They discovered that Fuji tea, a traditional food in China and Southeast Asia, has an inhibitory effect on PWV elevation. It is known that Fuji tea has various medicinal effects. The action is diverse, such as the effect of treating liver diseases such as acute hepatitis (Patent Document 3), the antibacterial effect (Patent Document 4), and the anti-pigmentation effect (Patent Document 5). However, it has never been known until now that Fuji tea has the effect of suppressing the increase in PWV, suppressing the decrease in vascular flexibility and arteriosclerosis, and improving treatment.

JP 2009-167127 A JP 2003-126058 A JP 2003-26584 A Japanese Patent Application Laid-Open No. 2002-1559566 JP 2002-65201 A

“Guidelines for diagnosis and treatment of cardiovascular disease (reported by the 2011-2012 Joint Research Team) Guidelines for non-invasive evaluation of vascular function: Guidelines for non-invasive basic function test (JCS 2013)” [online] Japan Circulation Society , Japanese Society of Hypertension, Japanese Society of Cardiology, Japanese Society of Nephrology, Japanese Society of Ultrasonic Medicine, Japanese Society of Diabetes, Japanese Arteriosclerosis Society, Japanese Vascular Society, Japanese Society of Clinical Physiology, Japanese Society of Geriatrics, Internet <URL: http: //www.j-circ.or.jp/guideline/pdf/JCS2013_yamashina_h.pdf>

The present inventors have conducted research based on the background art as described above, and Fuji tea extract has a strong PWV lowering action, and a preventive / improving effect on vascular flexibility and an arteriosclerosis preventing / ameliorating action. I discovered that. As a result of further research, it was discovered that a substance exhibiting an effect of preventing or improving vascular flexibility and preventing or improving arteriosclerosis was amperopsin, which is a kind of flavonoid contained in Fuji tea. I did it.
That is, an object of the present invention is to provide a composition for preventing or improving vascular flexibility and preventing or improving arteriosclerosis comprising amperopsin as an active ingredient.

The main configuration of the present invention is as follows.
(1) A composition for preventing / improving vascular flexibility and preventing / ameliorating arteriosclerosis comprising amperopsin as an active ingredient.
(2) A composition for preventing / improving vascular flexibility and preventing / ameliorating arteriosclerosis, comprising 10% by mass or more of amperopsin.
(3) The composition for preventing or improving the decrease in vascular flexibility and preventing or improving arteriosclerosis according to (1) or (2), wherein amperopsin is derived from Fuji tea extract.
(4) A composition for preventing / improving vascular flexibility and preventing / ameliorating arteriosclerosis, comprising Fuji tea extract.
(5) Wisteria tea extract-containing food or beverage composition for preventing or improving vascular flexibility and preventing or improving arteriosclerosis.
(6) The food / beverage product composition according to (5), which contains 10% by mass or more of amperopsin.
(7) The composition according to any one of (1) to (6), wherein the decrease in vascular flexibility and arteriosclerosis are arteriole sclerosis of peripheral blood vessels and capillaries.

  The present invention provides a composition for preventing or improving the decrease in vascular flexibility and preventing or improving arteriosclerosis. Moreover, it can be set as the food-drinks composition for prevention and improvement of vascular flexibility reduction and prevention and improvement of arteriosclerosis.

The PWV measurement result between the right upper arm artery and the right ankle in the human test is shown. The PWV measurement result between the left brachial artery and the left ankle in the human test is shown. The measurement result of the mean blood pressure (MBP) which is a parameter | index of the change of the peripheral vascular flexibility for 12 weeks of the test food administration group containing an ampelpsin and a placebo administration group is shown.

The present invention relates to a composition for preventing or improving vascular flexibility and preventing or improving arteriosclerosis comprising amperopsin as an active ingredient.
Fuji tea is a plant belonging to the genus Ganoderma genus, and its Chinese name is called dentition gabion. The scientific name is Ampelopsis grossedentata. It is mainly distributed in provinces and autonomous regions of China such as Guangxi, Guangdong, Yunnan, Guizhou, Hunan, Hubei, Jiangxi, Fujian. Chinese and Chinese provinces such as Guangxi, Hunan and other autonomous and barbaric people regularly use beverages made from these stems and leaves and are used for colds and sore throats. Amperopsin has been identified as the active body of the therapeutic and antibacterial effects of liver diseases exhibited by Fujicha.

  Ampelopsin is represented by the following formula.

  Ampelopsins are, for example, wisteria tea (Ampelopsis glossedentata), Ampelopsis megaphyllilla, Ampelopsis gantoni umf (Emperissis tantonis) It can be isolated and purified from an extract of a plant selected from wig (Cerciphyllum japonicum). Among these, Fuji tea is preferable.

Specifically, amperopsin can be obtained as follows from Fuji tea (Amelopsis grossedenta), a plant belonging to the genus Ampelopsis.
That is, the extract obtained by extracting the dried leaves and leaves of wisteria tea with water-containing ethanol was concentrated, and subjected to column chromatography using, for example, a porous resin (DIAION (registered trademark) HP-20), and with 80% by volume water-containing methanol. Ampelopsin is obtained in the eluted fraction. This can be further purified by reverse phase silica gel column chromatography or recrystallization. Purified amperopsin is also sold as a reagent and can be used.

The composition of the present invention can be used as long as it contains 10% by mass or more of the above-mentioned amperopsin. In order to obtain such a composition from Fuji tea, the following operation is performed.
Using dried wisteria tea leaf or stalk pulverized material or powder as an extraction raw material, it is poured into water, a hydrophilic organic solvent or a mixed solvent thereof, and extracted using an arbitrary apparatus at a temperature between room temperature and the boiling point of the solvent. Can be obtained.

Examples of organic solvents used for extraction include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene glycol, propylene glycol, Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as propylene glycol and glycerin.
Moreover, a mixed solvent of these hydrophilic organic solvents and water can be used. In the case of using a mixed solvent of water and a hydrophilic organic solvent, 30 to 90 parts by mass with respect to 10 parts by mass of water in the case of a lower alcohol, and 10 parts by mass of water in the case of a lower aliphatic ketone. In contrast, 10 to 40 parts by mass, and in the case of polyhydric alcohol, 10 to 90 parts by mass are preferably added to 10 parts by mass of water.

  Into a treatment tank filled with the extraction solvent, dried and pulverized product of Fuji tea is added, and the mixture is left to stand for 30 minutes to 2 hours with occasional stirring. , And the extractant is distilled off from the extract and dried to obtain an extract. The amount of the extraction solvent is preferably 5 to 15 times the mass of the extraction raw material (mass ratio), and the extraction conditions are usually 50 to 95 ° C. for about 1 to 4 hours when water is used as the extraction solvent. It is. Moreover, when using the mixed solvent of water and ethanol as an extracting solvent, it is about 30 minutes-about 4 hours at 40-80 degreeC normally.

When the extraction solvent is distilled off from the obtained extract, a paste-like concentrate is obtained. When further dried, a solid extract is obtained. In the present invention, as long as the content of amperopsin is 10% by mass or more, preferably 20% by mass or more, the extract or the concentrated solution thereof may be used. These may be used after being purified by a method such as activated carbon treatment, adsorption resin treatment, ion exchange resin, liquid-liquid countercurrent distribution or the like.
Therefore, an extract obtained by extracting from the above-mentioned wisteria tea and increasing the concentration of amperopsin can also be used as the composition of the present invention.
In addition, amperopsin can reduce PWV and suppress arteriole sclerosis in a dose-dependent manner.

The content of amperopsin in the composition can be analyzed by a known analysis method such as HPLC. The outline of the quantification method is as follows.
-Preparation of sample solution About 20 mg of a sample (extract) is precisely weighed, distilled water is added and sonicated to dissolve, and the volume is made exactly 50 mL. 2 mL of this solution is accurately diluted to 50 mL to obtain a sample solution.
・ Preparation of standard solution and preparation of calibration curve
2.00 mg of a standard product (manufactured by Dihydromyricin SIGMA-ALDRICH) is precisely weighed, and 100% acetonitrile is added in an appropriate amount to be sonicated to dissolve, and further acetonitrile is added to make exactly 25 mL. Prepare. This standard stock solution is diluted exactly 5 times with distilled water to prepare a 16 μg / mL amperopsin standard solution. The injection amount to HPLC is 10, 20, and 40 μL, and a calibration curve is created based on the peak of amperopsin.
-HPLC measurement conditions Set the conditions in Table 1 below.

The composition for preventing / ameliorating arteriosclerosis of the present invention is formulated as it is or by adding various excipients. Examples of the preparation include granules, tablets, and capsules.
Further, the composition can be used as it is or after being formulated into a food or drink.
In the preparation, excipients and other active ingredients can be used as long as the purpose of the composition of the present invention is not impaired. Specifically, cyclodextrin, hemicellulose, lignin, guar gum, konjac mannan, isagor, alginic acid, agar, carrageenan, chitin, carboxymethylcellulose, polydextrose and other dietary fibers and thickeners, edible oil, calcium, iron, Minerals such as sodium, zinc, copper, potassium, phosphorus, magnesium, iodine, manganese, selenium; fat-soluble or water-soluble such as vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, niacin, folic acid, pantothenic acid Emulsifiers and dispersants such as vitamins, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, phospholipid, gum arabic, xanthan gum, tragacanth gum, locust bean gum, Quantities, excipients, preservatives / antioxidants, flavor modifiers and flavors, flavoring agents such as sodium chloride, sodium glutamate, glycine, succinic acid, sodium lactate, citric acid, sodium citrate, acetic acid, adipic acid Acidulants such as fumaric acid and malic acid, low calorie sweeteners such as maltitol and aspartame, and coloring agents.
The composition for preventing / ameliorating arteriosclerosis of the present invention is prepared so as to contain 10 to 500 mg, preferably 50 to 300 mg, particularly preferably 100 to 200 mg of amperopsin.

The production examples of the composition of the present invention and test examples using this composition are shown below to further explain the present invention.
<Example of production of Fuji tea extract>
An extract was obtained with 70% EtOH in an amount 10 times the weight of dry wisteria tea. Thereafter, the extract was concentrated and filtered while removing impurities using activated carbon. An appropriate amount of γ-cyclodextrin was added to the concentrate, and the composition of the present invention was produced by spray drying.
15 parts of water was added to 1 part by weight (200 g) of dried wisteria tea, heated to 90 ° C., extracted for 1 hour and filtered to obtain No. 1 extract. Next, 12 times the amount of water was added to the residue, heated to 90 ° C., and then filtered to obtain No. 2 extract. Both extracts were added together and concentrated under reduced pressure. About 300 mL of the concentrated solution was frozen at −40 ° C. and further dried with a freeze-drying apparatus to obtain a dried product. This was pulverized and sieved with a 60-mesh sieve, and 85 g of passing material was used as a composition for preventing and improving arteriosclerosis. The amperopsin content in this composition was 65.8% by mass.

<Manufacture example 2 of Fuji tea extract>
A 15% amount of 50% aqueous ethanol solution was added to 1 part by weight (200 g) of dried wisteria tea, heated with a reflux condenser, extracted for 1 hour and filtered to obtain No. 1 extract. Next, 12 times the amount of 50% aqueous ethanol solution was similarly added to the residue, heated to 90 ° C., extracted for 30 minutes and filtered to obtain No. 2 extract. Both extracts were added together and concentrated under reduced pressure. About 300 mL of the concentrated solution was frozen at −40 ° C. and further dried with a freeze-drying apparatus to obtain a dried product. This was pulverized and sieved with a 60-mesh sieve, and 78.1 g of the passing material was used as a composition for preventing and improving arteriosclerosis. The amperopsin content in this composition was 52.9% by mass.

<Manufacture example 3 of Fuji tea extract>
In the same manner as in Production Example 1, 15 times the amount of water was added to 1 part by weight of dry wisteria tea, heated to 90 ° C., extracted for 1 hour and filtered to obtain No. 1 extract. Next, 12 times the amount of water was added to the residue, heated to 90 ° C., extracted for 30 minutes and filtered to obtain No. 2 extract. Both extracts were added together and concentrated under reduced pressure to obtain about 300 mL of the concentrated solution. Further, 78 g of the guar gum decomposition product was added per concentrated solution, frozen at −40 ° C., and further dried with a freeze-drying apparatus to obtain a dried product. This was pulverized and sieved with a 60-mesh sieve, and 163.1 g of the passing material was used as a composition for preventing and improving arteriosclerosis. The amperopsin content in this composition was 24.7% by mass.

<Human test 1>
It was confirmed by human tests that amperopsin is effective in reducing vascular flexibility and arteriole sclerosis due to salt intake. The subjects were tested in healthy volunteers with the background described in Table 2 below and in which atherosclerosis was not observed.

(1) Test product (hereinafter referred to as “test food”)
An ampelopsin-containing extract produced according to Production Example 1 was used.
1) Instant noodles containing 6.6 g of salt 2) Instant noodles containing 6.6 g of salt + Fujicha extract 2500 mg
(Containing 700 mg of amperopsin)
3) Instant noodles containing 6.6 g of salt + 1250 mg of γ cyclodextrin

(2) PWV measuring apparatus It measured using the product name "form PWV / ABI (made by OMRON Colin Co., Ltd.)".

(3) Test protocol On the day before the test, supper shall be completed by 20:00 (with the same amount of supper for each test as much as possible), and on the day of the test, a 12-hour fast (only water allowed) will come to the medical facility. Place. The day before the test and the day of the exam, refrain from exercising and set the sleeping time of the previous day to 7 hours (align bedtime and wake-up time as much as possible).
In the test, 30 minutes after eating instant noodles containing 6.6 g of salt, the test food was taken (no test food, Fujicha extract 2500 mg (amperopsin 700 mg), γ cyclodextrin 1250 mg), and 1 hour and 2 hours after meal. PWV was measured twice. The measurement was performed according to the use manual of the apparatus, and PWV was measured between the right upper arm artery and the right ankle and between the left upper arm artery and the left ankle.

(4) Results The measurement results are shown in FIG. 1 (between right upper arm artery and right ankle: right) and FIG. 2 (between left brachial artery and left ankle: left). In addition, the measurement result was represented by the PWV increase% value with respect to the measured value before ingesting the test food.
In both the right and left measurement results, when a test food containing 6.6 g of food salt and a test food containing 6.6 g of salt and 1.25 g of γ-dextrin were ingested, a significant increase in PWV was confirmed until 120 minutes after the meal. It was.
On the other hand, when a test food containing 6.6 g of salt and a food containing 700 mg of amperopsin were ingested, PWV did not increase until 120 minutes after ingestion.
(5) Consideration When 2500 mg (ampelopsin 700 mg), which is the test food of this test, was ingested simultaneously with the salt-containing food, the results of suppressing the increase in PWV due to the salt-containing food could be obtained. This result is considered to be a phenomenon manifested by preventing or improving arteriole sclerosis through a decrease in vascular resistance caused by overdose of 6.6 g of salinity, with 2500 mg of Fujicha extract (700 mg of amperopsin). It was.

<Human test 2>
From the results of human test 1, it was inferred that 700 mg of amperopsin could improve the decrease in vascular flexibility and arteriosclerosis. Therefore, the effect of amperopsin on the flexibility of peripheral blood vessels was further evaluated. Since peripheral blood vessel flexibility can be evaluated by measuring mean blood pressure (MBP) (see Non-Patent Document 1), a human test was conducted by a double blind method.

1. Test Method (1) Test Product (hereinafter “Test Food”)
As the test food, 150 mg of amperopsin-containing capsule (500 mg of Fuji tea extract powder) and 500 mg of starch as a placebo capsule were used.

(2) Test subjects Volunteers selected at random were selected to meet the following selection criteria.
1) Selection criteria (1) Blood pressure (systole) in screening test is 130mmHg or more and 160mmHg
Less than a is a person (2) Visit possible persons age at obtaining informed consent is less than 80 years of age or 20 years of age (3) BMI is 18.5 kg / ^{m 2} or more 30.0 kg / ^{m 2} less than's (4) Article agree Who got

2) Exclusion criteria (1) Severe gastrointestinal diseases, liver diseases, kidney diseases, cardiovascular diseases, blood diseases, endocrine diseases,
Those who are suspected or have a history of malignant neoplasms (2) Those who have been diagnosed with renal impairment or left ventricular hypertrophy (3) Those who have secondary hypertension (4) Allergies to vines (5) Those who are currently taking antihypertensive drugs or who are receiving antihypertensive treatment by a doctor (6) Those who are scheduled to receive treatment or medication by a doctor during the study period (7) Specified health care during the study period Foods, functional labeling foods and other supplements
(8) Eating habits (number of meals, meal content, alcohol intake) may change during the test period
(9) Persons whose lifestyle may change during the test period (night work, long trips,
Duty)
(10) Those who are currently smoking or have a history of smoking within the past year. (11) Estimated daily salt intake is 8.0 for men in the screening test from time to time.
(g) Women less than 7.0 g (12) Women who are pregnant or likely to become pregnant or breastfeeding (13) Those who plan to participate in other clinical trials during the study period (14) Other persons judged inappropriate by the doctor in charge

(3) Evaluation items 1) Main evaluation items Mean blood pressure (peripheral vascular resistance)
Based on the following formula, it is calculated from the measured values of systolic blood pressure and diastolic blood pressure.
Mean blood pressure = (systolic blood pressure / 3) + (2 × diastolic blood pressure / 3)
* Can evaluate the flexibility of peripheral blood vessels far from the heart.

2) Safety evaluation items Adverse events, laboratory values

(4) Administration study 1) Study design Double-blind parallel group comparison study 2) Study period (14 weeks)
The initial observation period is before taking Fujicha extract powder. Thereafter, the subjects are randomly divided into two groups and ingested with 500 mg of Fujicha extract powder or placebo for 12 weeks.
There are 5 visits: screening test, start date of intake, 4 weeks after intake, 8 weeks after intake, and 12 weeks after intake.
Initial observation period / ingestion period (all 14 weeks)

3) Intake method After confirming that the selection and exclusion criteria are not violated, start taking the test food (Fujicha extract powder) once a day after breakfast.

Ingestion period 12 weeks Ingestion method Take 3 tablets once a day after breakfast after breakfast Test foods Fujicha extract powder packed in capsules is taken as test food, and starch packed in capsules is placed in placebo.

4) Concomitant drugs / combination therapy Use of concomitant drugs and combination therapy are prohibited in principle. However, treatment can be started as necessary at the discretion of the doctor. Investigate drug use, dosage, duration, etc. regarding the use of drugs.

5) Survey items (1) Background survey
Screening tests will investigate age, gender, current medical history, past medical history, and life history (smoking, drinking, medication status, use of health food usage).

(2) Home blood pressure (HPM)
A blood pressure monitor for this test that is rented at the test facility within 1 hour after waking up (after urination and before breakfast) and twice after resting for 1 to 2 minutes before going to bed from the start of the screening test to the end of the test 12 weeks after ingestion Use to measure sitting blood pressure.

(3) Blood pressure and pulse at visit
After taking a rest for 3 minutes or more at the outpatient clinic at the study site, the brachial blood pressure was measured in the sitting position, and the average value of the two times that showed a stable value (difference in measured value less than 5 mmHg) To do. Conduct each visit during the study period.

(4) Blood test
General blood test (white blood cell, red blood cell count, hemoglobin, hematocrit, MCV, MCH, MCHC, platelet count), general biochemical test (TG, TC, HDL-C, LDL-C, blood glucose, HbA1c (NGSP), γ-GTP AST, ALT, total bilirubin, total protein, albumin, A / G ratio, ALP, LDH, CPK, creatinine, uric acid, urea nitrogen, Na, K, Cl, LAP), chymase, renin, and aldosterone.
The blood test will be performed on a fasting basis, twice a screening test and a test 12 weeks after ingestion.
For urinalysis, spot urine is used to measure urinary Na and urinary Cr. Estimated daily salt intake is calculated and examined monthly to observe changes in salt intake over time. In addition, urinary albumin is measured only for screening tests to confirm safety.

(5) Chest photography / load electrocardiogram, ABI, PWV
Conduct screening to confirm safety. The loading method in the ECG measurement is going up and down stairs.

(6) Meal survey
Investigate meals on the day before the visit on the day of the visit.

(7) Diary
Investigate the content of drinking, changes in eating habits, changes in physical condition, and intake of test foods.

6) Criteria for withdrawal ・ If the subject asks for withdrawal ・ If the investigator determines that it is not desirable to continue the study due to an adverse event ・ Other cases where the investigator determines that cancellation is necessary

7) Adverse events (1) Severity of adverse events
・ Mild: Adverse events that do not interfere with daily activities
・ Moderate: Adverse events that interfere with daily activities
・ Severe: Adverse event that disables daily activities

(2) Serious adverse events
・ Things leading to death
・ Life-threatening
Note: If the patient is at risk of death at the time of the event
It doesn't mean that it might have caused death if it was more severe
Yes.
・ Those requiring hospitalization or extension of hospital stay for treatment
・ Permanent or significant disability or malfunction
・ Things that cause birth defects
・ Other events or reactions judged to be medically important (3) Relevance to the test food
・ None: When there is no reasonable possibility with the test food
・ Yes: There is at least a reasonable possibility between the test food and the causal relationship is denied.
If you can't
・ Unknown: When the causal relationship with the test food cannot be determined due to lack of information

(4) Outcome
The outcome of adverse events is determined in the following 6 stages.
·recovery
・ Light
・ Not recovered
・ Recovered but with sequelae
·death
·unknown

(5) Reports when serious adverse events occur
After a serious adverse event has occurred and the investigator knows the adverse event, immediately report it to the head of the study site, contact the study personnel, and submit a report on the serious adverse event. Prepared and submitted to the head of the testing organization.

8) Statistical analysis Perform a two-way analysis of variance.

2. Number of test cases The final target number of cases that can be analyzed was 24 cases in 12 groups in each group.

3. Test results The test results are shown in FIG.
In the test food intake group, it was confirmed that the mean blood pressure (MBP) decreased and the blood vessel flexibility increased from 8 weeks after administration. Adverse events were not observed and no subjects discontinued.
4). Discussion It was confirmed that taking the Fujicha extract 500 mg (ampelopsin 150 mg), which is the test food of this study, for 12 weeks reduces the mean blood pressure for evaluating blood vessel flexibility from the 8th week compared to the initial value. It was.
This result is considered to be manifested by the improvement in blood vessel flexibility due to the ingestion of amperopsin and the decrease in mean blood pressure.
From human tests 1 and 2, it has been clarified that amperopsin has a function of relieving blood vessel tension caused by salt and the like and improving arteriosclerosis including peripheral blood vessels.

Claims (7)

  A composition for preventing / improving vascular flexibility and preventing / ameliorating arteriosclerosis comprising amperopsin as an active ingredient.   A composition for preventing or improving vascular flexibility and preventing or improving arteriosclerosis, comprising 10% by mass or more of amperopsin.   The composition for preventing or improving vascular flexibility and preventing or improving arteriosclerosis according to claim 1 or 2, wherein the amperopsin is derived from a Fuji tea extract.   A composition for preventing or improving decrease in vascular flexibility and preventing or improving arteriosclerosis, comprising Fuji tea extract.   Wisteria tea extract-containing food / beverage product composition for preventing or improving the decrease in vascular flexibility and preventing or improving arteriosclerosis.   The food-drinks composition of Claim 5 containing 10 mass% or more of amperopsin. The composition according to any one of claims 1 to 6, wherein the decrease in vascular flexibility and arteriosclerosis is arteriole sclerosis of peripheral blood vessels and capillaries.

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