JPH0429646B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a blood cholesterol level increase inhibitor containing a low-viscosity polysaccharide as an active ingredient, which has physical properties that are extremely easy to handle in formulation, etc., specifically, a 1.5% aqueous solution of 20
The present invention relates to a low-viscosity blood cholesterol level increase inhibitor containing a polysaccharide having a viscosity of 200 centipoise or less at °C as an active ingredient. It has been known that natural polysaccharides such as pectin, konjac mannan, guar gum, carrageenan, sodium alginate, and microbial polysaccharides have the effect of suppressing increases in serum and liver cholesterol ("Dietary fiber", Japanese Dietetic Association). ed., 136-140.
page). However, since these natural polysaccharides are originally polymers, they have high viscosity, and to take advantage of their ability to suppress increases in cholesterol levels, they are mixed into food and feed in order to suppress increases in cholesterol levels in humans and animals. It has been extremely difficult to prepare the compound itself into a dosage form suitable for oral or parenteral administration. Therefore, the present inventors have conducted extensive research with the aim of reducing the viscosity of a natural polysaccharide that has an effect of suppressing the rise in cholesterol, thereby obtaining a formulation suitable for administration to humans, animals, and the like. In general, it has not yet been elucidated which component of the polysaccharide exerts the effect of suppressing the rise in cholesterol levels of natural polysaccharides. Therefore, it is completely unclear whether simply emulsifying and dispersing these polysaccharides can maintain the effect of polysaccharides in suppressing increases in cholesterol levels, and conventional thinking suggests that polysaccharide molecules will be randomly fragmented. Therefore, it was generally assumed that the same effect could not be achieved. Furthermore, the viscosity of the natural polysaccharide could not be reduced using a commonly used homogenizer, and a polysaccharide having a viscosity that was easy to form into a formulation could only be obtained using a high-pressure homogenizer. Surprisingly, the inventors have discovered that the low-viscosity polysaccharide can be used as a cholesterol level increase inhibitor without any decrease in its cholesterol level increase inhibitory effect, and have completed the present invention. In the present invention, the viscosity of a 1.5% aqueous solution at 20°C is 200%.
It is a low-viscosity blood cholesterol level increase inhibitor suitable for preparations containing as active ingredients polysaccharides having a viscosity of centipoise or less, particularly preferably polysaccharides such as konjac mannan, guar gum, and xanthan gum produced by microorganisms. The polysaccharides used in the present invention include various natural polysaccharides known to suppress increases in cholesterol levels;
These include polysaccharides produced by microorganisms, scientifically modified polysaccharides, and the like, among which konjac mannan, xanthan gum, guar gum, Bacillus polymyxa polysaccharide, etc. are preferred. Low viscosity (200 centipoise or less) of the high viscosity polysaccharide of the present invention can be achieved by homogenizing the high viscosity polysaccharide under conditions that apply high energy of 0.1 KW/hr or more to 1 kg of the same solution. be able to. This reduction in viscosity can be achieved by high-pressure homogenizer treatment, ultrasonic treatment, or the like. To describe an example of using a high-pressure homogenizer, the stock solution is fed into the stock solution inlet 1 shown in the attached drawing using a plunger pump, and the stock solution is ejected radially from the fine gap between the valve 2 and the valve seat 3, causing pressure and acceleration. , shearing, cavitation, impact, etc. are applied to the stock solution as one action that integrates various factors. By pressing the valve 2 to the left side and further narrowing the gap between the valve seats 3 and 2, the stock solution is treated with high energy. This pressure is around 600-1200Kg/ ^cm2 . The raw liquid is pumped by a plunger pump, first hits the surface of the valve 2, converts the flow to 90 degrees, and squirts out with explosive pressure to the low pressure part, and then collides with the inner surface of the impact ring 4 in front. , and is discharged as a low-viscosity homogenized liquid 5. This working time is about 9/100000
This is an extremely short time of 0 seconds. By repeating this operation several times, a low-viscosity polysaccharide of the present invention having a viscosity of 200 centipoise or less at 20°C of a 1.5% aqueous solution is obtained. Next, Table 1 below shows the values for pressure, flow rate, power consumption, and energy amount when the high-pressure homogenizer was used.

[Table] The viscosity can also be reduced by ultrasonication. 50g of the stock solution is irradiated with ultrasonic waves at a frequency of 10KHz, an amplitude of 40 microns, and a transducer input of 300W for 12 minutes to reduce the viscosity. (190 centipoise) Energy amount: 1.2 KW·hr/Kg The results of measuring the blood cholesterol level of the low-viscosity polysaccharide obtained as above are shown below. 1 Test method: 80 5-week-old SD male rats were divided into 10 groups, and each group received 22% casein and 10% lard.
%, salt mixture 3.5%, vitamin mixture 1.0%, choline chloride 1.0%, sucrose 63.35% as the basal feed, (1) basal feed only (cholesterol-free diet), (2) 0.5% cholesterol in the basal feed. and feed containing 0.35% sodium cholate (cholesterol diet), (3) feed containing 1.0% polysaccharide (17400 centipoise) produced by Bacillus polymyxa to cholesterol diet [BP (unprocessed product) diet], (4) ) Feed containing 1.0% low-viscosity polysaccharides (170 centipoise) added to the cholesterol diet (low-viscosity BP diet), (5) konjac flour (20,000 centipoise) to the cholesterol diet
Feed with 1.0% added [konjac flour (unprocessed product) food], (6) cholesterol food with low viscosity konjac flour (200 centipoise)
Feed with 1.0% added (low viscosity konjac flour food), (7) Feed with 1.0% xanthan gum (1800 centipoise) added to cholesterol food [xanthan gum (unprocessed product) food], (8) Low xanthan gum added to cholesterol food. Feed with 1.0% viscosity (100 centipoise) added (low viscosity xanthan gum diet), (9) Feed with 1.0% guar gum (13200 centipoise) added to cholesterol diet [guar gum (unprocessed product) diet], (10 )
The rats were fed a cholesterol diet with 1.0% of low-viscosity guar gum (60 centipoise) added (low-viscosity guar gum diet) and raised for 18 days. Afterwards, the rats in each group were decapitated and blood was collected from the neck. , Blood cholesterol levels were measured using Determiner TC (manufactured by Kyowa Hakko Co., Ltd.). The results were as shown in Table 2 below.

[Table] The viscosity was measured using a Tokyo Keiki Seisakusho Co., Ltd. B-type viscometer (model BM) at 30 rpm. As is clear from the above results, the effect of the polysaccharide, which has the effect of suppressing the increase in blood cholesterol level, is almost unchanged even though the viscosity thereof is reduced. Furthermore, the low viscosity makes it extremely useful in formulation. The blood cholesterol level elevation inhibitor of the present invention is formulated by blending it with a commonly used pharmaceutical carrier. It may also be mixed with human or animal food or feed and administered orally. When producing solid dosage forms for oral use, add low-viscosity polysaccharide excipients, binders, disintegrants, lubricants, corrigents, etc., and then form into tablets, granules, capsules, etc. using conventional methods. I can do it. When manufacturing parenteral preparations such as injections, add PH regulators, buffers, stabilizers, isotonic agents, etc. to the low-viscosity polysaccharide and obtain subcutaneous or intravenous injections using conventional methods. I can do it. The dosage of low-viscosity polysaccharide varies depending on the symptoms, but
For adults, administer 450 to 900 mg in 3 to 4 divided doses a day. Next, a formulation example of the blood cholesterol level increase inhibitor of the present invention will be shown. Example 1 Low viscosity BP (170 centipoise) 10 parts, lactose 20 parts
1 part, 20 parts of corn starch, and 2 parts of magnesium stearate are mixed and made into tablets of 500 mg each using a tablet machine.

[Brief explanation of drawings]

The drawing is a diagram showing the principle of a homogenizer for producing a low-viscosity polysaccharide, which is an active ingredient of the present invention. 1: Stock solution input part, 2: Valve, 3: Valve seat, 4: Impact ring, 5: Low viscosity liquid.

Claims (1)

[Scope of Claims] 1. A low-viscosity blood cholesterol level increase inhibitor characterized by containing as an active ingredient a polysaccharide having a viscosity of 200 centipoise or less at 20°C in a 1.5% aqueous solution. 2. The low-viscosity blood cholesterol level increase inhibitor according to claim 1, wherein the polysaccharide is a polysaccharide produced by a microorganism, konjac mannan, or guar gum. 3 The active ingredient is a polysaccharide whose viscosity at 20°C of a 1.5% aqueous solution is 200 centipoise or less, which is obtained by homogenizing the high viscosity polysaccharide under conditions that apply high energy of 0.1 KW/hr or more to 1 kg of the high viscosity polysaccharide solution. The low viscosity blood cholesterol level increase inhibitor according to claim 1.