JPH03227933A - Vasodepressor and anti-vasopressor agent - Google Patents

Abstract

PURPOSE:To provide the subject vasodepressor and anti-vasopressor agent composed of a bran-derived hemicelullose hydrolysate having a specified viscosity, showing a vasodepressor activity and an anti-vasopressor activity by a very small-quantity administration and ready to handle and take in. CONSTITUTION:A white and water soluble powdery vasodepressor and anti- vasopressor agent composed of a bran-derived hemicelullose hydrolysate 5wt.% aqueous solution of which is 5-30 centipoise, preferably especially about 5-20 centipoise at 25 deg.C in measurement by using an Ostwald's viscometer and ready to handle because of its low viscosity even in a high-concentration solution such as 5wt.% solution, capable of a large-amount administrate in a form of a high-concentration solution at a time therefor, capable of administration in a form of solid also without further processing and having a vasodepressor and anti-vasopressor activity equal to or higher than that of unhydrolyzed hemicelullose.

Description

[Detailed description of the invention] [Industrial application field] TECHNICAL FIELD The present invention relates to an agent for lowering and suppressing blood pressure increase.

[Prior art 1] In recent years, the effectiveness of dietary fiber has been re-recognized in terms of preventing adult diseases, lowering and suppressing cholesterol rise, regulating the intestines, and preventing colon cancer. As a result, various attempts have been made to actively intake dietary fiber. Examples of such attempts include (1) the use of rice bran and wheat bran, which have so far been mainly used as livestock feed, and (row) the use of gums such as guar gum, locust bean gum, tara gum, and tragaganth gum. , use of indigestible polysaccharides such as konjac mannan, etc.

However, in the case of (i) above, there is no effect unless a large amount of rice bran or wheat bran is ingested, and it is practically difficult to ingest a large amount of rice bran or wheat bran, which have poor texture. Therefore, as an improvement technique, there is a method of recovering the dietary fiber contained in rice bran, wheat bran, etc. and utilizing it.
Publication No. 216822 and the like describes that hemicellulose is extracted from rice bran, wheat bran, etc. and used as a substance for suppressing the rise in serum cholesterol, neutral fat, and liver cholesterol.

However, the extracted hemicellulose solution has a high viscosity and is difficult to handle.

Also, in the case of (ii) above, indigestible polysaccharides such as gums and konjac mannan are often used in aqueous solutions because they are less palatable and difficult to ingest as they are.
The aqueous solution is a highly viscous solution with poor palatability and ease of handling, and therefore has to be made into a low concentration aqueous solution of 1% or less. However, if a low concentration aqueous solution is used, a large amount of the aqueous solution must be ingested in order to ingest the desired amount of dietary fiber, and it is actually difficult to ingest a large amount of dietary fiber.

As a solution to the drawbacks of the prior art (■),
Partially hydrolyze the above indigestible polysaccharide with a plant fiber tissue disintegrating enzyme, prepare a 1% aqueous solution of the resulting hydrolyzate to have a pressure of 10 mPa-8 or less, and use it as dietary fiber. It has been reported that
3-269993). In this case, a 1% aqueous solution of the hydrolyzate certainly exhibits a low viscosity of lomPa-3 or less, but if it is made into a highly concentrated aqueous solution (for example, a 5% aqueous solution), the viscosity becomes extremely high and the handling and texture are greatly affected. This makes it difficult to use high-concentration solutions and hinders intake of the required amount of dietary fiber. Furthermore, because the main chain of indigestible polysaccharides such as gums is mainly hydrolyzed and cleaved there, the resulting hydrolyzate has a much smaller molecular weight than the one before decomposition, and can be used as dietary fiber. Its functionality was also significantly inferior.

[Contents of the Invention] The present inventors have conducted research on improving the physical properties and effective utilization of hemicellulose derived from bran.

As a result, the hydrolyzate obtained by partially hydrolyzing hemicellulose derived from bran showed a low viscosity even when made into a high concentration aqueous solution of 5%, and was easy to handle and ingest. The molecular weight is not significantly lower than that of hemicellulose before hydrolysis.
It has been found that in addition to suppressing the rise in serum cholesterol, triglyceride and liver cholesterol, it has a blood pressure lowering effect and a blood pressure rise suppressing effect. This discovery of the present invention is completely unexpected in view of the conventional knowledge that agents that suppress increases in cholesterol and triglycerides do not immediately lower blood pressure or suppress increases in blood pressure.

Therefore, the present invention is a bran-derived hemicellulose hydrolyzate, which comprises a bran-derived hemicellulose hydrolyzate, the viscosity of which in a 5% aqueous solution is 5 to 30 centipoise when measured at 25°C using an Ostwald viscometer. It is a blood pressure lowering and increasing suppressant.

The "bran-derived hemicellulose hydrolyzate" used in the present invention has a viscosity of 5 to 30 centiboise (
(hereinafter referred to as rcPJ), and if the viscosity of the 5% aqueous solution is lower than 5 cP, the function as a blood pressure lowering and increase suppressing agent will be reduced or lost. Furthermore, if the viscosity of the 5% aqueous solution is higher than 30 cP, the viscosity will be too high, making it difficult to ingest, and the handling properties will be poor. From the viewpoint of ease of ingestion, ease of handling, etc., it is particularly preferable that the viscosity of the 5% aqueous solution is about 5 to 20 cP.

The bran-derived hemicellulose hydrolyzate used in the present invention is disclosed in, for example, Japanese Patent Application No. 1-169 filed by the present applicant.
As described in No. 849, hemicellulose derived from wheat bran obtained by extracting wheat bran from wheat, barley, oats, rye, oats, etc. with alkali is partially hydrolyzed with enzymes, acids, alkalis, etc. It can be prepared by processing.

Among these, partial hydrolysis treatment using an enzyme is preferable because it can efficiently purify a hydrolyzate exhibiting a desired viscosity under mild conditions without causing excessive hydrolysis or insufficient hydrolysis.

Enzymes for partially hydrolyzing hemicellulose derived from bran include hemicellulase (for example, “
Plant fiber tissue-disintegrating enzymes such as "Onozuka", pectolyase manufactured by Donishin Seiyaku Co., Ltd.), and cellulase can be used. In this case, the enzyme may be used in a free state or immobilized on a carrier. Also, partially hydrated The decomposition treatment may be carried out in a continuous or batch method.The type of hemicellulose derived from bran, whether the enzyme is used in a free state or immobilized, and it is carried out in a continuous or batch method. It is best to perform partial hydrolysis by selecting the type of enzyme, the amount used, temperature, pressure, pH, time, etc. during partial hydrolysis depending on the situation. can be produced in a short time, but if the amount is too large, low-molecular substances with an average molecular weight of about 1000 or less, such as monosaccharides and oligosaccharides, which do not have the function of lowering or suppressing blood pressure increase, are produced. For example, when partially hydrolyzing hemicellulose derived from wheat bran using the above-mentioned "Paonozuka" manufactured by Yakult, an approximately 1 to 5% by weight aqueous solution of hemicellulose derived from wheat bran (pH approximately 3.
5 to 7.0) and add about 1 to 50 ppm to this aqueous solution.
The desired hydrolyzate can be obtained by adding (w/v) "Onozuka" and hydrolyzing it at a temperature of about 40 to 60°C for about 5 minutes to 1 hour. In this hydrolysis reaction,
The viscosity of the bran-derived hemicellulose aqueous solution initially decreases rapidly and then gradually decreases, but by stopping the hydrolysis reaction once the rapid viscosity decrease has finished, the average viscosity can be reduced even though the viscosity is low. It is possible to obtain a bran-derived hemicellulose hydrolyzate having a high molecular weight and retaining its functions as a blood pressure lowering and blood pressure increase suppressing agent without significantly lowering the molecular weight. If the hydrolysis reaction is continued even after the rapid viscosity decrease has ended, the viscosity decrease will not proceed much or the molecular weight of the hemicellulose hydrolyzate will decrease, making it impossible to obtain the desired product. In this case, "the point at which the rapid viscosity decrease ends" refers to a point within 30 minutes from the point at which the rapid viscosity decrease stops and shifts to a gradual viscosity decrease.

For example, when looking at hemicellulose derived from wheat bran, the Brookfield viscosity of a 5% aqueous solution at 25°C is usually about 150 to 180 cP before hydrolysis.
In contrast, the viscosity of the hydrolyzate used in the present invention is 5 to 30 cP as mentioned above, indicating that the viscosity is extremely low due to hydrolysis.

In addition, the wheat bran-derived hemicellulose hydrolyzate used in the present invention usually has an average molecular weight of about 70% by weight when its average molecular weight is measured by the method described below.
The average molecular weight is in the range of about 700,000 to 1,500,000,
On the other hand, about 85-95% by weight of bran-derived hemicellulose before hydrolysis usually has an average molecular weight in the range of about 700,000 to 1,500,000, so comparing the two, the hydrolyzate used in the present invention is It can be seen that although the viscosity of the 5% aqueous solution is kept extremely low, its average molecular weight is not much different from the average molecular weight of the bran-derived hemicellulose before hydrolysis.

However, the method for preparing the bran-derived hemicellulose hydrolyzate described above is only one example, and the agent of the present invention is not limited to that prepared as described above. In the present invention, a hydrolyzate of hemicellulose derived from bran is used, which has a viscosity of 5 to 5% when made into a 5% aqueous solution.
Any material within the range of 30 cP can be used, and its preparation method is not limited.

The antihypertensive and antihypertensive agent of the present invention comprising a hemicellulose hydrolyzate derived from bran is a water-soluble white powder that is administered in small amounts to humans and various animals (for example, pets such as dogs and cats). By doing so, it is possible to lower the blood pressure of hypertensive humans and animals, and furthermore it is possible to suppress the increase in blood pressure.

In addition, the agent for lowering and suppressing blood pressure increase of the present invention can contain potassium, which is known to be involved in lowering blood pressure and suppressing increase in blood pressure, together with bran-derived hemicellulose hydrolyzate, and the combination of potassium can lower blood pressure. and the effect of suppressing the rise in blood pressure is further enhanced. Potassium in this case is preferably used in the form of an inorganic potassium salt such as potassium chloride, potassium carbonate, potassium phosphate, or an organic potassium salt.

The preferred dosage of the antihypertensive and antihypertensive agent of the present invention is as follows:
This naturally depends on various conditions such as the age, weight, sex, symptoms, and type of animal of the human or animal being administered, but for example,
For humans, it is approximately 0.00 kg per kg of body weight per day. O1~0.
It can be administered at a rate of 5 g and in animals at a rate of about 0.1 to Log per kg body weight per day.

The agent for lowering and suppressing blood pressure increase of the present invention is administered orally. Furthermore, the antihypertensive and antihypertensive agents of the present invention may be administered alone, together with solid carriers or liquid carriers commonly used in the pharmaceutical industry, or mixed with other drugs. Can be used alone or in combination. Its dosage forms include tablets, pills,
It can be used in any form such as granules, capsules, powders, and aqueous solutions.

Furthermore, the agent for lowering and suppressing blood pressure increase of the present invention can be added to or administered together with foods and feeds.

The present invention will be specifically explained below by giving examples, but the present invention is not limited thereto. All percentages in the examples below are by weight.

In addition, the average molecular weights of the bran-derived hemicellulose and its hydrolyzate in the following examples and above were measured as follows.

[Method for Measuring Average Molecular Weight] Purified hemicellulose or its hydrolyzate is dissolved in ultrapure water to form a 1% aqueous solution.

20 μg of the aqueous solution was collected and injected into a high performance liquid chromatography separation column (Ultra Hydrogel 1000: manufactured by Waters, USA) kept at 80°C.
An eluent consisting of ultrapure water was flowed there at a flow rate of 0.5 m12/min, and the differential refractive index, which is the difference between the refractive index of the eluate (ultrapure water) and the refractive index of the effluent from the column, was plotted as a chart. Measurements are recorded over time.

On the other hand, prepare five types of pullulans with known average molecular weights (with average molecular weights between 20,000 and 1,500,000), flow them out of the separation column in the same manner as above, and measure the differential refractive index of Char 1 over time. A calibration curve was prepared from the relationship between the average molecular weight and the appearance time of five peaks corresponding to pullulan of each average molecular weight appearing on the chart and used as a standard.

The average molecular weight of hemicellulose and its hydrolyzate was determined by comparing the appearance time of the peak in the above-mentioned 1 chart, in which the differential refractive index accompanying the outflow of hemicellulose or its hydrolyzate was recorded over time, with the standard calibration curve described above. .

Reference Example 1 [Preparation of wheat bran-derived hemicellulose 1 2 kg of selected wheat bran is dispersed in 20Ω of 50°C warm water and stirred for 5 minutes. After that, the solid content was collected by filtration with a centrifugal filter (manufactured by Tanabe Iron Works), and the obtained solid content was 7060,0.2 kg.
Add to N aqueous sodium hydroxide solution 204 and stir for 90 minutes. After cooling, 0.8N hydrochloric acid aqueous solution 5a is gradually added under stirring to neutralize. Neutralizing solution at 5,000 G for 10
Centrifuge for minutes. The supernatant liquid was separated and the total sugar content was 5.
Dilute with water to a concentration of mg/mQ, and keep the solution at a temperature of 50°C. The entire solution was passed through a tubular ultrafiltration membrane (Nitto Denko i: NT
U3520-PI3 type, membrane area 0-76m”, inner diameter 11
．． 5mm) at a pressure of 8kg/am” and a flow rate of 1
Treat for 3 hours under conditions of 3 Q/min. At this time, the same amount of water as the membrane permeation solution is constantly replenished into the tube to keep the membrane treatment liquid volume constant. After 3 hours, the water supply was stopped, and concentration was started under the same conditions as described above.Concentration was performed without considering the decrease in flux, and the sugar concentration of the aqueous solution was approximately 10 mg.
/ m Continue for about 1.5 hours until Q. The treatment liquid was 500cc of cation exchange resin IR-120E manufactured by Organo.
The sample was eluted at a flow rate of 10 times the exchange capacity of the ion exchange resin per hour, and then passed through an anion exchange resin IRA-93 manufactured by the same company at the same flow rate. After the ion exchange treatment, the resulting aqueous solution was freeze-dried in vacuum at a temperature of 30° C. and a vacuum of 0.1 Torr or less) to obtain a white hemicellulose powder (recovery rate near selected wheat bran, 5%).

The obtained product was completely dissolved in water at 25°C (0% water-insoluble content). Further, the content of each component and the breakdown of the total sugar content in the product were as shown in Table 1 below.

[Table-1] Component content Ash (%) Total nitrogen (%) Total sugar content (%) 0.12 4.8 93.6 Total (%) 100.0
In Table 1 above, the total sugar content was determined as follows. The content of each constituent component (xylose, arabinose, glucose, etc.) in the sugar was determined by the method of TARIO, BHATTI, etc. [Biochim,
Biophys, Acta, 222 (197
0)+339-347], followed by methylation, and the resulting product was analyzed using gas chromatography. All values in the table are calculated as dry matter.

[Method for measuring total sugar content] The aqueous solution containing sugars is diluted 100 times with distilled water.

Next, 0.5mρ of a 5% phenol aqueous solution was added to 0.5mQ of this diluted aqueous solution and stirred, followed by 3m4 of concentrated sulfuric acid.
was added and further stirred. After leaving it as it is for 20 minutes and cooling it in the air, absorbance at a wavelength of 490 nm is measured. The total sugar content was determined by comparing the measured values with a standard curve using xylose as a substrate.

Reference Example 2 [Preparation of partial hydrolyzate of hemicellulose derived from wheat bran] 5 g of the hemicellulose prepared in Reference Example 1 above was added to an acetate buffer aqueous solution (acetate content: 50 mmol, pH 5.5).
) A 5% aqueous solution of hemicellulose was prepared by dissolving it in 100 mff (liquid A).

The viscosity of this A liquid was measured at 25°C using an Ostwald viscometer.
When measured, it was 182 cP.

Next, after preheating the above solution A at 40°C for 10 minutes, 25 cPg of plant fiber tissue disintegrating enzyme "Onozuka" (manufactured by Yakult Co., Ltd.) was added and kept at the same temperature to partially hydrolyze hemicellulose. When the viscosity was measured over time in the same manner as above, the results shown in the figure were obtained.

From the results shown in the figure, it can be seen that the viscosity of the liquid decreases rapidly until 30 minutes after the start of hydrolysis, and then decreases only gradually. That is, here, about 30 to 30 minutes after the start of hydrolysis
The period of 60 minutes corresponds to the point at which the rapid viscosity decrease ends.

In the above hydrolysis treatment, 30 minutes after the point at which rapid viscosity reduction of the liquid no longer occurs (approximately 30 minutes),
That is, 60 minutes after the start of hydrolysis, a portion of the hydrolysis solution (liquid B) was sampled and its viscosity was measured in the same manner and found to be 25 cP.

Furthermore, when a part of the liquid (liquid C) was collected 120 minutes after the start of hydrolysis and its viscosity was measured in the same manner, lo, 5.
It was cP.

In addition, the average molecular weight of the hemicellulose before hydrolysis contained in the above liquid A and the average molecular weight of the hemicellulose hydrolyzate contained in liquids B and C were measured by the above method, and as shown in Table 2 below. Met.

[Table 2] Solution 93% Solution B 89% Solution C 51% From the above results, the wheat bran-derived hemicellulose hydrolyzate obtained in Reference Example 2 (i.e. Solution B) has a high concentration of hemicellulose (A) before hydrolysis. It can be seen that although the viscosity is significantly lower than that of the liquid), the decrease in the average molecular weight is small. Furthermore, it can be seen that when the hydrolysis is continued without stopping even after the rapid hydrolysis has ended (Liquid C), the viscosity does not decrease much further, but the average molecular weight decreases significantly.

Example Test foods A to C having the compositions shown in Table 3 below were prepared.

[Table 3] Casein (%) L-methionine (%) Mineral mix (%) Vitamin mix (%) Sucrose (%) Lard (%) Salt (%) Total (%) 100 100
100 * Hemicellulose hydrolyzate contained in Solution B of Reference Example 2 In the above test meals A and B, the unhydrolyzed hemicellulose of Reference Example 1 was added so that the dietary fiber content in the test meals was 3%. and the hydrolyzed hemicellulose of Reference Example 2.

Next, three groups of spontaneously hypertensive rats (male, 15 weeks old) with 6 rats in each group were prepared.

Each group of rats received 6 doses of each of the above test meals A-C.
They were allowed to take it ad libitum for days.

The blood pressures of the rats in each group were measured at the beginning and after 6 days, and the average body weights at the beginning and after 6 days were as shown in Table 4 below.

[Table-4] Blood pressure (mmHg) Initially 203±7.7 203±8
．． 6 203±11.96 days later 184±14
．． 0 189±16.9 204±12.3 Average body weight (
g/mouse) Initially 268±8.1 277±4
．． 8 280±7.56 days later 269±6.2
279 ± 5.3 285 ± 7.5 From the results in Table 4 above, the blood pressure of rats in the group administered test food C, which did not contain either unhydrolyzed hemicellulose or hydrolyzed hemicellulose, hardly decreased. On the other hand, the blood pressure of rats in the groups administered test meals A and B containing unhydrolyzed hemicellulose and hydrolyzed hemicellulose decreased, especially in the group administered test meal A containing hydrolyzed hemicellulose. It can be seen that there is a large drop in blood pressure in rats.

[Effects of the Invention] The agent for lowering and suppressing blood pressure increase made of hydrolyzed hemicellulose derived from wheat bran of the present invention can exert a blood pressure lowering effect and suppressing effect on blood pressure increase with an extremely small amount of administration. is equivalent to or higher than that of non-hydrolyzed hemicellulose.

In addition, the agent for lowering and suppressing blood pressure increase made of hydrolyzed hemicellulose derived from wheat bran of the present invention is a white water-soluble powder that exhibits low viscosity even when made into a highly concentrated aqueous solution (for example, a 5% aqueous solution) and is easy to handle. It can be made into a highly concentrated solution and administered in a large amount to 0-, or it can be administered as it is in solid form.

[Brief explanation of drawings]

The attached drawing is a diagram showing the relationship between hydrolysis treatment time and viscosity change when wheat bran-derived hemicellulose is partially hydrolyzed using an enzyme.

Claims (1)

[Claims] Hemicellulose hydrolyzate derived from bran, part 5
A blood pressure lowering and increasing suppressant comprising a bran-derived hemicellulose hydrolyzate, the viscosity of which is an aqueous solution of 5 to 30 centipoise when measured at 25°C using an Ostwald viscometer.