JP2780201B2 - Antihypertensive and antihypertensive - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to an antihypertensive and antihypertensive agent.

[Prior art] In recent years, the effectiveness of dietary fiber (dietary fiber) has been re-recognized in terms of prevention of adult diseases, suppression of cholesterol lowering and elevation, intestinal control, prevention of colorectal cancer, and the like. Accompanying this, various attempts have been made to actively ingest dietary fiber. Examples of such attempts include (i) the use of rice bran and wheat bran, which have been mainly used as livestock feeds, and (ii) gums such as guar gum, locust bean gum, tara gum, tragagant gum and the like. And the use of indigestible polysaccharides such as konjac mannan.

However, in the case of the above (i), there is no effect unless a large amount of rice bran or wheat bran is consumed, and it is practically difficult to consume a large amount of rice bran or wheat bran having poor texture. Therefore, as an improvement technique, there is a method of recovering and utilizing dietary fiber contained in rice bran, wheat bran and the like, and Japanese Patent Publication No. 62-6691 and Japanese Patent Application Laid-Open No. 63-2168.
No. 22 discloses that hemicellulose is extracted from rice bran, wheat bran, and the like, and is used as a substance that suppresses increases in serum cholesterol, neutral fat, and liver cholesterol. However, the hemicellulose solution extracted therefrom had a high viscosity and was difficult to handle.

Also, in the case of the above (ii), indigestible polysaccharides such as gums and konjac mannan are inferior in taste as they are and are difficult to be ingested.
The aqueous solution is a viscous, high-viscosity solution with poor palatability and handling properties, and therefore must be a low-concentration aqueous solution of 1% or less. However, when a low-concentration aqueous solution is used, a large amount of aqueous solution must be taken in order to take in a desired amount of dietary fiber, and it is practically difficult to take in large amounts of dietary fiber.
Then, as a method for solving the disadvantage of the conventional technology (ii),
The indigestible polysaccharide is partially hydrolyzed by a plant fiber tissue-disintegrating enzyme, and a 1% aqueous solution of the resulting hydrolyzate is prepared to be 10 mPa · S or less and used as a dietary fiber. (Japanese Patent Laid-Open No. 63-26)
No. 9993). In this case, a 1% aqueous solution of the hydrolyzate certainly shows a low viscosity of 10 mPa · S or less, but a high-concentration aqueous solution (for example, a 5% aqueous solution) has a very high viscosity, and the handleability and texture are greatly increased. The use of high-concentration solutions became difficult, and the intake of the required amount of dietary fiber was hindered. In addition, the main chain of the indigestible polysaccharide, such as gums, is mainly hydrolyzed and cleaved, so that the resulting hydrolyzate has a much smaller molecular weight than that before decomposition, and as a dietary fiber The functionality was also much worse.

[Description of the Invention] The present inventors have studied on improvement of physical properties and effective use of hemicellulose derived from bran.

As a result, the hydrolyzate obtained by partially hydrolyzing the bran-derived hemicellulose exhibits a low viscosity even in the case of a high-concentration aqueous solution of 5%, and is easy to handle and ingest. The molecular weight is not much lower than the molecular weight of hemicellulose before hydrolysis, and it has been found to have a blood pressure lowering effect and a blood pressure increase suppressing effect in addition to the serum cholesterol, triglyceride and liver cholesterol increase suppressing effects. . Such an invention of the present invention is completely unexpected from the conventional knowledge that cholesterol and neutral fat elevation inhibitors do not immediately exhibit blood pressure lowering and blood pressure elevation suppressing effects.

Accordingly, the present invention comprises a bran-derived hemicellulose hydrolyzate, wherein the 5% aqueous solution has a viscosity of 5 to 30 centipoise when measured at 25 ° C. using an Ostwald viscometer. It is an antihypertensive and antihypertensive agent.

The “fuma-derived hemicellulose hydrolyzate” used in the present invention may have a 5% aqueous solution having a viscosity of 5 to 30 centipoise (hereinafter referred to as “cP”) when measured at 25 ° C. using an Ostwald viscometer. If the viscosity of the 5% aqueous solution is lower than 5 cP, the function as an antihypertensive and antihypertensive agent is reduced or lost. On the other hand, if the viscosity of the 5% aqueous solution is higher than 30 cP, the viscosity becomes too high, making it difficult to ingest and the handling property is poor. From the viewpoint of ease of ingestion and handling, the viscosity of the 5% aqueous solution is particularly preferably about 5 to 20 cP.

The bran-derived hemicellulose hydrolyzate used in the present invention is, for example, Japanese Patent Application No. 1-13838, filed by the present applicant.
As described in No. 49, wheat, barley, oats,
It can be prepared by partially hydrolyzing a bran-derived hemicellulose obtained by extracting a wheat bran such as rye and oats with an alkali using an enzyme, acid, alkali or the like.

Among them, the partial hydrolysis treatment with an enzyme is preferable because a hydrolyzate having a desired viscosity can be efficiently purified under mild conditions without excessive hydrolysis or insufficient hydrolysis.

As the enzyme for partially hydrolyzing the bran-derived hemicellulose, plant fiber tissue-disintegrating enzymes such as hemicellulase (for example, "Onozuka" manufactured by Yakult Co., Ltd. and Pectlyase manufactured by Seishin Pharmaceutical Co., Ltd.) and cellulase can be used. At that time, the enzyme may be used in a free state or immobilized on a carrier. The partial hydrolysis treatment may be performed by a continuous method or a batch method. Depending on the type of bran-derived hemicellulose, whether the enzyme is used in a free state or immobilized, is used in a continuous method, or is performed in a batch method, etc., the type of enzyme, the amount used, and during partial hydrolysis The partial hydrolysis may be carried out by selecting the temperature, pressure, pH, time, etc. In that case, a larger amount of the enzyme can generate a hydrolyzate in a shorter time, but if the amount is too large, a monosaccharide or an oligosaccharide having no function as a blood pressure lowering and increasing inhibitor, This is undesirable because low molecular weight substances having an average molecular weight of less than about 1000 are formed. For example, hemicellulose derived from wheat bran can be converted to "Onozuka" manufactured by Yakult.
When partial hydrolysis is performed using an aqueous solution, about 1 to 5% by weight aqueous solution of hemicellulose derived from wheat bran (pH about 3.5 to 7.0)
Is prepared, and about 1 to 50 ppm (w / v) of "Onozuka" is added to this aqueous solution and hydrolyzed at a temperature of about 40 to 60 ° C. for about 5 minutes to 1 hour to obtain a desired hydrolyzate. it can. In this hydrolysis reaction, the viscosity of the aqueous solution of bran-derived hemicellulose suddenly decreases at first, and then gradually decreases. Nevertheless, it is possible to obtain a bran-derived hemicellulose hydrolyzate having a high molecular weight which retains the function as a blood pressure lowering and increasing inhibitor without a significant decrease in the average molecular weight. When the hydrolysis reaction is continued even after the rapid decrease in viscosity is completed, the decrease in viscosity does not proceed so much, but the molecular weight of the hemicellulose hydrolyzate decreases, and the desired product cannot be obtained. In this case, “the point at which the rapid decrease in viscosity is completed” refers to a point in time at which the rapid decrease in viscosity stops and shifts to a gradual decrease in viscosity, and a point within 30 minutes thereafter.

For example, regarding the wheat bran-derived hemicellulose, the Brookfield viscosity at 25 ° C. of a 5% aqueous solution thereof before hydrolysis is usually about 150 to 180 cP, whereas that of the hydrolyzate used in the present invention is As described above, the viscosity is 5 to 30 cP, indicating that the viscosity is extremely low due to hydrolysis.

Further, when the average molecular weight of the bran-derived hemicellulose hydrolyzate used in the present invention is measured by the method described below, usually about 70% by weight or more is about 700,000 to 150%.
While the average molecular weight is in the range of 10,000, about 85-95% by weight of the bran-derived hemicellulose before hydrolysis is usually
Since the average molecular weight is in the range of about 700,000 to 1.5 million, the hydrolyzate used in the present invention has an average molecular weight of about 700,000 to 1.5 million even though the viscosity of the 5% aqueous solution is kept extremely low. It can be seen that the average molecular weight of the bran-derived hemicellulose before hydrolysis does not change much.

However, the above-mentioned method for preparing a bran-derived hemicellulose hydrolyzate is merely an example, and the agent of the present invention is not limited to the above-prepared one. In the present invention, a hydrolyzate of bran-derived hemicellulose, which has a viscosity of 5% when converted to a 5% aqueous solution, is as described above.
Anything within the range of ~ 30 cP can be used,
The preparation method does not matter.

The antihypertensive and antihypertensive agent comprising the bran-derived hemicellulose hydrolyzate of the present invention is a water-soluble white powder, which is administered in a small amount to humans and various animals (for example, pets such as dogs and cats). Thus, the blood pressure of a hypertensive human or animal can be reduced, and an increase in blood pressure can be further suppressed.

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

The preferred dosage of the antihypertensive and antihypertensive agent of the present invention is the age, weight, sex, symptoms, and age of the human or animal to be administered.
Naturally, it varies depending on various conditions such as the type of animal. For example, in the case of humans, at a rate of about 0.01 to 0.5 g per kg of body weight per day, and in the case of animals, about 0.1 to 0.5 g per kg of body weight per day.
It can be administered at a rate of 10 g.

And the antihypertensive and antihypertensive agent of the present invention is administered orally. Furthermore, the antihypertensive and antihypertensive agents of the present invention may be administered alone, together with a solid carrier or liquid carrier commonly used in the pharmaceutical industry, or mixed with other drugs. Or in combination. The dosage form can be used in any form such as tablets, pills, granules, capsules, powders, and aqueous solutions.

Further, the antihypertensive and antihypertensive agents of the present invention can be added to foods or feeds or administered together therewith.

Hereinafter, the present invention will be described specifically by way of examples, but the present invention is not limited thereto. All percentages in the examples below are by weight.

The average molecular weight of the bran-derived hemicellulose and the hydrolyzate thereof in the following examples and above was measured as follows.

[Measurement Method of Average Molecular Weight] Purified hemicellulose or a hydrolyzate thereof is dissolved in ultrapure water to form a 1% aqueous solution.

12 μl of the aqueous solution was collected and injected into a high performance liquid chromatography separation column (Ultra Hydrogel 1000: manufactured by Waters, USA) maintained at 80 ° C., and the eluate composed of ultrapure water was flowed at a flow rate of 0.5 ml / min. The differential refractive index, which is the difference between the refractive index of the eluate (ultra pure water) and the refractive index of the effluent from the column, was measured and recorded over time as a chart.

On the other hand, five types of pullulan having a known average molecular weight are prepared (those having an average molecular weight of between 20,000 and 1.5 million), and are allowed to flow out of the separation column in the same manner as described above, and the differential refractive index chart is recorded over time. Then, a calibration curve was prepared from the relationship between the appearance time of five peaks corresponding to pullulan of each average molecular weight shown in the chart and the average molecular weight, and was 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 chart in which the differential refractive index accompanying the outflow of hemicellulose or its hydrolyzate was recorded with time with the above standard calibration curve.

Reference Example 1 [Preparation of Wheat Bran-Derived Hemicellulose] 2 kg of carefully selected wheat bran was dispersed in warm water 20 at 50 ° C and stirred for 5 minutes. Thereafter, the solid content was collected by filtration with a centrifugal filter (manufactured by Tanabe Iron Works), and 3 kg of the obtained solid content was filtered at 70 ° C. and 0.2N
Place in aqueous sodium hydroxide solution 20 and stir for 90 minutes.
After allowing to cool, a 0.8N aqueous hydrochloric acid solution 5 is gradually added with stirring to neutralize. Centrifuge the neutralization solution at 5,000 G for 10 minutes. The supernatant is collected, diluted with water so that the total sugar content is 5 mg / ml, and kept at a liquid temperature of 50 ° C. The whole solution was subjected to a tubular ultrafiltration membrane (Nitto Denko: NTU3520-P18 type, membrane area 0.76 m ² , inner diameter 11.
5 mm) through a tube, and treated for 3 hours under the conditions of a pressure of 8 kg / cm ² and a flow rate of 13 / min. At this time, the same amount of water as the membrane permeating solution is always replenished into the tube, and the amount of the membrane treatment solution is kept constant. After 3 hours, supply of water is stopped, concentration is started under the same conditions as described above, concentration is performed without considering a decrease in flux, and the concentration is performed for about 1.5 hours until the sugar concentration of the aqueous solution becomes about 10 mg / ml. The treated solution is eluted at a flow rate of 10 times the ion exchange resin exchange capacity per hour into 500 cc of a cation exchange resin IR-120E manufactured by Organo Corporation, and then flown at the same flow rate into an anion exchange resin IRA-93 manufactured by the company. After the ion exchange treatment, the resulting aqueous solution was freeze-dried in vacuum (at a temperature of 30 ° C. and a degree of vacuum of 0.1 Torr or less) to obtain a white hemicellulose powder (recovery rate for selected wheat bran: 7.5%).

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

In Table 1 above, the total sugar amount was determined as follows.
The content of each component (xylose, arabinose, glucose, etc.) in the sugar is determined by the method of TARIO, BHATTI, etc. [Biochim. Biophys. Acta., 222 ].
(1970), 339-347], followed by methylation, which was determined by analysis using gas chromatography. All values in the table are values converted as dry matter.

[Measurement Method of Total Sugar Content] An aqueous solution containing a saccharide is diluted 100 times with distilled water.
Next, 0.5 ml of a 5% aqueous phenol solution was added to 0.5 ml of the diluted aqueous solution, and the mixture was stirred, and then 3 ml of concentrated sulfuric acid was added, followed by further stirring. After leaving it for 20 minutes and air cooling, wavelength 490n
Measure absorbance at m. The measured value was compared with a standard curve using xylose as a substrate to determine the total sugar amount.

Reference Example 2 [Preparation of partially hydrolyzed hemicellulose derived from wheat bran] 5 g of the hemicellulose prepared in Reference Example 1 above was used in 100 ml of an acetate buffer aqueous solution (acetate content 50 mmol, pH 5.5).
To prepare a 5% aqueous solution of hemicellulose (A
liquid).

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

Then, after previously heating the above solution A at 40 ° C. for 10 minutes,
Plant fiber tissue-disintegrating enzyme "Onozuka" (Yakult)
250 μg was added, hemicellulose was partially hydrolyzed at the same temperature, and the viscosity was measured over time in the same manner as described 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 rapidly decreases until 30 minutes after the start of hydrolysis, and thereafter decreases only gradually. That is, here, about 30 to 60 after the start of hydrolysis.
The period of minutes corresponds to the time point at which the rapid decrease in viscosity ends.

In the above-mentioned hydrolysis apparatus, one part of the hydrolyzed liquid (solution B) is 30 minutes after the time when the viscosity of the liquid does not rapidly decrease (about 30 minutes), that is, 60 minutes after the start of hydrolysis. ) Was collected and its viscosity was measured in the same manner to find that it was 25 cP.

Further, one part (liquid C) of the liquid 120 minutes after the start of hydrolysis was sampled, and its viscosity was measured in the same manner to be 10.5 cP.

The average molecular weight of the hemicellulose before hydrolysis contained in the liquid A and the average molecular weight of the hemicellulose hydrolyzate contained in the liquids B and C were measured by the above-described method, and are shown in Table 2 below. It was as follows.

From the above results, although the wheat bran-derived hemicellulose hydrolyzate (namely, solution B) obtained in Reference Example 2 had a much lower viscosity than the hemicellulose (solution A) before hydrolysis, It can be seen that the decrease in the average molecular weight is small. In addition, when the hydrolysis is continued without stopping even after the end of the rapid hydrolysis (solution C), the viscosity does not decrease much more but the average molecular weight is greatly reduced.

EXAMPLES Test meals A to C having the compositions shown in Table 3 below were prepared.

In the test meals A and B, each of the unhydrolyzed hemicellulose of Reference Example 1 and the hydrolyzed hemicellulose of Reference Example 2 was blended so that the dietary fiber content in the test meal was 3%.

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

The rats in each group were allowed to freely ingest each of the test foods A to C for 6 days.

The blood pressure of the rats in each group initially and 6 days later, and
The average body weight after day was measured and was as shown in Table 4 below.

From the results in Table 4 above, in the rats of the group to which the test meal C containing neither the unhydrolyzed hemicellulose nor the hydrolyzed hemicellulose 4 was administered, the blood pressure hardly decreased, whereas the unhydrolyzed hemicellulose and Test meals A and B containing hydrolyzed hemicellulose
It can be seen that the blood pressure was reduced in the rats of the group to which the test food A was administered, and the blood pressure of the rats to which the test meal A containing hydrolyzed hemicellulose was administered was particularly large.

[Effect of the Invention] The antihypertensive and antihypertensive agent comprising the bran-derived hydrolyzed hemicellulose of the present invention can exert an antihypertensive action and an antihypertensive action with an extremely small amount of administration,
Moreover, such a blood pressure lowering and increasing suppressing effect is equal to or higher than that of non-hydrolyzed hemicellulose.

The antihypertensive and antihypertensive agent of the present invention derived from the bran-derived hemicellulose hydrolysis is a white water-soluble powder, and has a low viscosity even in the case of a high-concentration aqueous solution (for example, a 5% aqueous solution). It can be administered in large amounts at a time in a highly concentrated solution, or can be administered as it is in a solid form.

[Brief description of the drawings]

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

Claims (1)

(57) [Claims] 1. A blood pressure comprising a bran-derived hemicellulose hydrolyzate, the viscosity of a 5% aqueous solution of which is 5 to 30 centipoise when measured at 25 ° C. using an Ostwald viscometer. Descent and rise inhibitors.