JPH11240841A - Inhibitor of hypertension - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a preparation useful for prevention or treatment of hypertension or a disease caused by the hypertension by including psyllium as an active ingredient. SOLUTION: This therapeutic agent or prevention agent for hypertension and a disease caused by the hypertension (apoplexy, hypertensive heart disease, hypertensive renal disease, hypertensive retinopathy or the like) is obtained by including psyllium of a natural gum gathered from a seed of a plant belonging to the genus Plantago of the family plantain (e.g. Indian species of Plantago ovata Forskal) as an active ingredient. Preferably, the daily dose of the psyllium is about l-30 g/adult expressed in terms of the dried weight and administered by dividing the dose into 1-2 times. A food capable of persistently preventing the hypertension is obtained by allowing the food to include the before active ingredient, for example, when the food is a powdered juice, by regulating the content so as to be 1-50 wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an agent for preventing or treating hypertension and diseases caused by hypertension (for example, stroke, hypertensive heart disease, hypertensive renal disease, hypertensive retinopathy) and a food for prevention.

[0002]

BACKGROUND OF THE INVENTION Antihypertensive drugs are used to lower the blood pressure of hypertensive patients to a normal range, not to increase organ damage, and to control side effects within a range that can be safely tolerated. In addition, those with a reliable and slow action and few side effects are selected.

[0003] Chitosan has been proposed as such an antihypertensive drug (for example, Monthly Food Chemical 1995-2 p.33-3).
8; Food and Development Vol.29, No.3 (1994)). Chitosan has no problem with side effects, but there is room for improvement in its antihypertensive effect.

[0004] Hypertension causes diseases such as stroke (cerebral hemorrhage and cerebral infarction), hypertensive heart disease, and hypertensive retinopathy.

An object of the present invention is to provide an antihypertensive agent having a strong antihypertensive action and a food having an antihypertensive action without causing any side effects even when taken for a long time.

Another object of the present invention is to provide an agent for preventing or treating hypertension and diseases caused by hypertension and a food for preventing the same.

[0007]

Means for Solving the Problems The present inventor has proposed an intestinal regulating action,
Serum lipid lowering action, blood sugar rise inhibitory action is known,
In addition, we have been studying psyllium, which is also used as a diet food.

It has been reported that psyllium, when taken by hypercholesterolemic patients with normal blood pressure, lowers blood cholesterol but has no blood pressure lowering effect (Bell et al., Am J. . Clin. Nutr., 52, 10
Despite 20-1026 (1990), especially Table 2 on page 1022), it was found that when administered to a subject with hypertension, it showed a strong hypotensive effect.

[0009] Furthermore, it has been found that psyllium can prevent diseases caused by hypertension and can greatly extend the life span of hypertensive mammals such as humans, rats, dogs and cats.

[0010] In particular, the intake of psyllium can suppress the occurrence of stroke (cerebral hemorrhage, cerebral infarction), and this effect was notable for chitosan, which is known to have a hypotensive effect.

The present invention relates to the following items 1 to 8.

Item 1. An agent for preventing or treating hypertension and diseases caused by hypertension, comprising psyllium as an active ingredient.

Item 2. A pharmaceutical composition comprising psyllium and a pharmaceutically acceptable carrier, which has an effect of preventing or treating hypertension and diseases caused by hypertension.

Item 3. A food having a phyllium-containing preventive action on hypertension and diseases caused by hypertension.

Item 4. If the disease caused by high blood pressure is stroke,
Item 4. The food according to item 3, which is hypertensive heart disease, hypertensive renal disease and hypertensive retinopathy.

Item 5. An agent for preventing or treating stroke, comprising psyllium as an active ingredient.

Item 6. Stroke-preventing foods containing psyllium.

Item 7. A food that contains psyllium and has an effect of continuously preventing hypertension.

Item 8. A persistent antihypertensive agent containing psyllium as an active ingredient.

Psyllium is a natural plant gum obtained from the seeds of the plantago genus Plantago. Plantago genus plants are more than 200 kinds and are not particularly limited, for example, Pl
antago psyllium L., plantago indica L. and other French and Spanish species (plaque psyllium), plantago o
Examples include Indian species such as vata Forskal (Indian psyllium or blonde psyllium). Psyllium can be obtained, for example, from the hull (seed coat, husk) that surrounds the seeds of the planta plant.

Psyllium can be easily obtained as a commercial product.

Psyllium is used as a drug or as a food including beverages (eg, health food, food for specified health use) (including food additives) in order to exert its antihypertensive action and preventive action against diseases caused by hypertension. , Can be taken.

In particular, psyllium is useful for the prevention of stroke (cerebral hemorrhage, cerebral infarction (including cerebral softening)) in people (animals) with a history of hypertension or other genetically predisposed individuals. It can be a drug or food.

(1) An agent for preventing or treating hypertension and diseases caused by hypertension, in particular, an agent for preventing stroke, psyllium, is used as a usual oral preparation such as tablets, capsules, granules, fine granules, powders, pills and the like. It can be administered without any particular restrictions. In these preparations, excipients, diluents, carriers and the like usually used in the field of medicine are appropriately used in addition to the active ingredient.

The dosage of psyllium varies depending on symptoms, age, body weight and the like.
1 g to 30 g, preferably 3 g to 2 in dry weight per day
5 g, more preferably 3 g to 20 g, particularly preferably 3 g
About 10 to 10 g is administered once or in two or more divided doses. The administration of psyllium is preferably in an amount such that weight loss falls within an acceptable range.

In the present invention, hypertension refers to a case where the blood pressure corresponds to either systolic blood pressure of 140 mmHg or more or diastolic blood pressure of 90 mmHg or more. The antihypertensive agent of the present invention shows a particularly effective antihypertensive effect to hypertensive subjects,
It has an ideal antihypertensive property that does not affect the blood pressure of a normal or hypotensive subject.

Normal blood pressure means that the systolic blood pressure is 140 mmH
g and the diastolic blood pressure is less than 90 mmHg.

Examples of diseases caused by hypertension include stroke (cerebral hemorrhage, cerebral infarction), hypertensive heart disease, hypertensive renal disease and hypertensive retinopathy. Here, hypertensive retinopathy is a disease in which sclerosis of the fundus arterioles occurs due to hypertension, causes ischemic / bleeding lesions, and causes visual impairment and the like.

According to the agent for preventing or treating diseases caused by hypertension according to the present invention, by taking psyllium for a long period of time, it is possible not only to lower the blood pressure of a hypertensive subject, to suppress a further increase in blood pressure, but also to prevent normal blood pressure Can be prevented from becoming hypertensive or a disease caused by hypertension.

In addition, those who have a history of hypertension or the like,
It is extremely effective as a use for reducing the risk of the onset of stroke (cerebral hemorrhage, cerebral infarction) in people with a genetic predisposition to hypertension, etc., and is useful as a preventive agent and method for stroke.

The therapeutic or prophylactic agent of the present invention is suitable for ingestion by normotensive or hypertensive healthy persons or patients having risk factors (such as genetic predisposition) for hypertension or diseases caused by hypertension.

(2) Food The food having the antihypertensive action and the preventive action against diseases caused by hypertension according to the present invention, which is used as a health food or a food for specified health use, may be a solid or semi-solid food. It may be a liquid (beverage). The above-mentioned active ingredient (psyllium) is blended with the food. The mixing ratio of psyllium to food varies depending on the form and material of the food. For example, in the case of powdered juice and the like, it may be close to 100%, but usually contains about 1 to 50% by weight. The point is that the total daily intake of psyllium is 1 g to 30 g, preferably 3 g, in dry weight per adult per day.
２５25 g, more preferably 3 g-20 g, particularly preferably about 3-10 g. The intake of psyllium is preferably in an amount such that weight loss falls within an acceptable range.

The food of the present invention may be composed only of psyllium, but is usually produced in the form of an existing food together with other food ingredients. Specific foods include corn flakes, noodles (buckwheat, udon, Chinese noodles), biscuits, powdered drinks, jellies, breads, and the like.

The food of the present invention is suitably used as pet food and the like.

The food of the present invention can be produced according to a conventional method by mixing an appropriate amount of psyllium with a food material.

The food of the present invention can not only suppress a further increase in blood pressure of a hypertensive subject but also prevent a normal blood pressure subject from becoming hypertensive or a disease caused by hypertension.

In addition, a person having a history of hypertension or the like,
It is extremely effective as a food for reducing the risk of developing stroke (cerebral hemorrhage, cerebral infarction) in people with a genetic predisposition to hypertension, and is useful as a food for preventing stroke.

The food of the present invention is suitable for ingestion by normotensive or hypertensive subjects having risk factors (such as genetic predisposition) for hypertension or diseases caused by hypertension.

[0039]

EFFECTS OF THE INVENTION Psyllium is effective as an agent for preventing or treating high blood pressure and diseases caused by high blood pressure, since it exhibits a particularly effective antihypertensive effect on persons with high blood pressure in such an amount that does not reduce body weight. It is particularly useful as a food (including food additives) having a preventive effect on hypertension and diseases caused by hypertension.

In addition, those who have a history of hypertension or the like,
It is also useful as a prophylactic and food for reducing the risk of developing stroke (cerebral hemorrhage, cerebral infarction) in people with a genetic predisposition to hypertension.

Further, a therapeutic / prophylactic agent containing psyllium,
The food can also have an intestinal effect such as improvement of bowel movement, a blood neutral fat, a blood cholesterol lowering effect, and a blood sugar rise suppressing effect.

The preventive effect of psyllium on diseases caused by hypertension can be confirmed by the long-term ingestion of psyllium, which significantly extends the lifespan compared to the case without psyllium.

[0043]

The present invention will be described more specifically below with reference to examples.

Example 1 A group of five to six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP; sales agency, Funabashi Farm Co., Ltd.) was divided into five groups, and the following four groups were provided according to the composition of the diet. Was.

(1) A control group that receives a commercial diet (SP (powder): Funabashi Farm Co., Ltd.); (2) 3% psyllium (commercial name: Foodmate p-100: Shikishima Boseki Co., Ltd.) (3) Chitosan (trade name: chitosamine, 3%) in commercial diet
A chitosan group to which Nippon Kayaku Food Techno Co., Ltd.) was added; and (4) a cellulose group to which 10% cellulose (cellulose ion exchanger for thin-layer chromatography; distributor, Nacalai Tesque, Inc.) was added to a commercial diet. In the case of the psyllium group and the chitosan group, the mixing of each additive component in the diet is performed by 30 g of psyllium (or chitosan).
470 g of the above commercial feed was powder-mixed several times and mixed well, and then 500 g of the above commercial feed was further added and thoroughly mixed again.

In the case of the cellulose group, after sufficiently mixing 750 g of the above commercial feed with 100 g of cellulose,
Further, the above commercial feed was added so that the total amount was 1 kg, and the mixture was thoroughly mixed again.

The feeding method was free intake, and the drinking water was given a 0.5% NaCl aqueous solution in order to promote an increase in blood pressure. The breeding period of this test was 29 days, and the breeding period was 22 days.
The body weight was measured after day 29 and after day 29, and the respective average values were determined. Blood pressure was measured immediately before food intake (day 0), 15 days.
The measurements were taken after day 29 and day 29, and the respective average values were determined.

Table 1 shows the measurement results of body weight. The measurement results of the blood pressure are shown in Table 2 and FIG.

[0049]

[Table 1] * Indicates that there is a significant difference (p <0.05) from the control group.

[0050]

[Table 2] * Indicates that there is a significant difference (p <0.05) from the control group.

As shown in Table 2, psyllium exhibited a significant blood pressure lowering effect on the control group.
It was proved to be a stronger antihypertensive than cellulose and chitosan.

Example 2 Five to six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP; vendor, Funabashi Farm Co., Ltd.) were grouped into five rats, and the following four groups were provided according to the diet composition. Was.

(1) A control group that receives a commercial diet (SP (powder): Funabashi Farm); (2) 10% psyllium (trade name: Foodmate p-100: Shikishima Boseki Co., Ltd.) (3) Chitosan group to which 10% chitosan (trade name: chitosamine: manufactured by Nippon Kayaku Food Techno Co., Ltd.) was added to a commercial diet; and (4) 10% cellulose to commercial diet (Cellulose ion exchanger for thin-layer chromatography; sales agent, Nacalai Tesque, Inc.) 10% psyllium, chitosan and cellulose in 10% of cellulose group
In 0 g of psyllium, chitosan or cellulose, 750
g of the above commercial feed, and then the total amount is 1k.
g, and the above commercial feed was added thereto, and the mixture was mixed well again.

The feeding method was free intake, and the drinking water was given a 0.5% NaCl aqueous solution in order to promote an increase in blood pressure. The breeding period of this test was 197 days.
The systolic blood pressure and body weight were measured 5 days and 29 days later, and the respective average values were determined. In the group other than 10% psyllium, it was easily inferred from observation that a stroke was occurring due to an increase in blood pressure after 29 days. Therefore, in order to avoid death at the time of blood pressure measurement, blood pressure measurement was performed. Did not do.

The relationship between the systolic blood pressure and the dietary fiber intake period is shown in Table 3 and FIG.

The relationship between the survival rate and the intake period is shown in Table 4 and FIG.

[0057]

Table 3 Fluctuation of systolic blood pressure (mmHg) after ingestion of dietary fiber Intake period (days) 3 15 29 197 control 174 ± 6 211 ± 7 234 ± 4-10% psyllium 168 ± 4 190 ± 4 * 210 ± 4 * 207 ± 9 10% chitosan 165 ± 3 184 ± 6 * 213 ± 2 * − 10% cellulose 170 ± 3 211 ± 7 238 ± 4 −

[0058]

[Table 4] Survival rate after dietary fiber intake (%) Intake period (days) 0 40 60 80 100 120 140 160 197 Control 100 100 60 20 0 0 0 0 0 10% psyllium 100 100 100 100 100 100 100 100 100 10% Chitosan 100 100 100 60 60 20 20 0 0 10% Cellulose 100 100 20 20 20 20 0 0 0 As is clear from the above results, psyllium suppresses the increase in blood pressure and causes diseases associated with increased blood pressure. And significantly prolonged the life of the rat.

Example 3 All of the rats that died in Example 2 (control group, psyllium-administered group, chitosan-administered group, cellulose-administered group, 5 animals per group) were dissected within several days after dying. hand,
Obtained brain findings.

As a result, one or both lesions of cerebral hemorrhage or cerebral infarction (cerebral softening) were observed in the brains of all rats except the psyllium-administered group, and all rats other than the psyllium-administered group had a stroke. It was confirmed that.

On the other hand, all the psyllium-administered groups survived on the 197th day of the final blood pressure measurement in Example 2, but died from 285 to 300 days from the test start date in Example 2 (5 (320 to 340 days including a pre-breeding period of ~ 6 weeks). Rat SH used in the present invention
It is said that the average lifespan of a normal breeding of RSP is about 280 days on average, so the lifespan of the psyllium-administered group was rather long. In the psyllium-administered group, no brain lesion (cerebral hemorrhage or cerebral infarction (cerebral softening)) was confirmed macroscopically in the brains of all five cases, indicating that it was useful for prevention of stroke.

Table 5 shows the findings of the brain of the dead rat. Note that a stroke corresponds to a case in which at least one of cerebral hemorrhage and cerebral infarction (cerebral softening) is observed.

[0063]

[Table 5] Production Example 1 (Pyrium-containing powdered drink) 400 g of psyllium was mixed with 520 g of sugar, 60 g of acidulant, and a small amount of sweetener, flavor, and colorant, and then granulated.
A powdered drink containing 4 g of psyllium in 0 g was prepared. 180 g of cold water was added to 10 g of the powder for eating, but the flavor was good.

Production Example 2 (Psyllium-containing corn flakes) 144 g of psyllium, 710 g of corn grits and sugar 9
After mixing 0 g and a small amount of salt and the like, a corn flake containing 35 g of psyllium in 35 g was prepared through steaming, forming, and drying steps. 200 for 35g of corn flakes
It was eaten with cc of milk, but the flavor was good.

Production Example 3 (Instant noodles containing psyllium) 760 g of flour, 65 g of vegetable protein,
It was mixed with 63 g of starch and the like, kneaded by adding kneading water, and then subjected to the steps of rolling, cutting out, steaming, and hot-air drying to prepare instant noodles containing 5 g of psyllium in 60 g. 500c
After boiling in boiling water of c for 3 minutes, soy sauce-based powdered soup was added and eaten, but the flavor was good.

Production Example 4 (Pharmaceutical formulation with psyllium) After mixing 420 g of sugar, 28 g of acidulant and a small amount of a sweetener with 530 g of psyllium, the mixture was granulated to prepare a powder formulation containing 4 g of psyllium in 7.5 g. 7.5 powder
The present invention, in which 180 cc of cold water was added to g, and the flavor was good, also relates to the following A to C.

A. A method for treating hypertension and a disease caused by hypertension, comprising administering psyllium to a hypertensive subject.

B. A method for preventing hypertension and diseases caused by hypertension, which comprises administering psyllium to a subject (hypertension or normotensive pressure).

C. Diseases caused by hypertension are stroke, cerebral hemorrhage, hypertensive cerebral hemorrhage such as cerebral infarction, hypertensive heart disease, hypertensive renal disease, and hypertensive retinopathy. The method described in.

[Brief description of the drawings]

FIG. 1 is a graph showing changes in blood pressure of each test group after breeding 0, 15, and 29 days.

FIG. 2 is a graph showing the relationship between systolic blood pressure and dietary fiber intake period.

FIG. 3 is a graph showing the relationship between the intake period and the survival rate.

Continued on the front page (72) Inventor Keisuke Obata 4-1-1 Nishinakajima, Yodogawa-ku, Osaka-shi, Osaka Nissin Foods Co., Ltd.

Claims (8)

[Claims] 1. An agent for preventing or treating hypertension and diseases caused by hypertension, comprising psyllium as an active ingredient. 2. A pharmaceutical composition comprising psyllium and a pharmaceutically acceptable carrier, which has a prophylactic or therapeutic effect on hypertension and diseases caused by hypertension. 3. A food containing psyllium, which has an effect of preventing hypertension and diseases caused by hypertension. 4. The food according to claim 3, wherein the diseases caused by hypertension are stroke, hypertensive heart disease, hypertensive renal disease and hypertensive retinopathy. 5. A preventive or therapeutic agent for stroke, comprising psyllium as an active ingredient. 6. A food for preventing stroke comprising psyllium. 7. A food containing psyllium and having an effect of continuously preventing hypertension. 8. A continuous prophylactic agent for hypertension containing psyllium as an active ingredient.