JPH10287575A - Antiobestic drug - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antiobestic drug that can inhibit the increase in blood sugar with a reduced amount of ingestion without side-effect by admixing a crude drug selected from a dry powder, an aqueous extract and alcohol extract obtained from D-xylose and a specific naturally occurring substance. SOLUTION: This antiobestic preparation is prepared by formulating D-xylose that has inhibitory action on enzymes hydrolyzing oligosaccharides, a crude drug having inhibitory action on absorption of oligosaccharides and monosaccharides from intestinal tracts. This crude drug is, for example, the root bark, tree bark and buds of Japanese angelica tree, root of beet, root of spinach, root of Achyranthes japonica, root of Swiss chard, seeds of Kochia scoparia and conker, laves of Gymnema sylvestre R. Br. and fruits and seeds of Momordica Charantia and they are dried and powdered or extracted with water or an alcohol and these extracts are used. One pt.wt. of d-xylose is mixed with 1-3 pts.wt. of the crude drug and prepared to a powdery or solid preparation or a solution preparation. The daily dose of this drug is orally 50-300 mg for adult.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to D-xylose having an inhibitory effect on an enzyme that degrades oligosaccharides and one or two types having an inhibitory effect on intestinal absorption of oligosaccharides and monosaccharides. The present invention relates to an anti-obesity agent prepared by combining the above crude drugs.

[0002]

2. Description of the Related Art As is well known, when food is taken into a living body, carbohydrates in the food are decomposed into oligosaccharides such as sucrose and maltose by the action of various enzymes.
It undergoes enzymatic degradation by glucosidase and the like to become monosaccharides such as glucose. Only after being broken down into monosaccharides is blood sugar absorbed from the intestinal tract, but postprandial hyperglycemia involves a large amount of insulin secretion. This insulin has a function of lowering the blood glucose level in a living body, but in a state where insulin is constantly secreted in a large amount, that is, in a state of overeating, the blood glucose lowering effect of insulin becomes slow. As a result, glycogen is synthesized from the monosaccharide to increase adipose tissue, and if the adipose tissue is not digested with energy, it accumulates and causes obesity. A high insulin condition causes arteriosclerosis, and a hyperglycemic condition causes diabetes.

[0003] As anti-obesity agents, D-xylose, L-arabinose, D-glucono-1,5-lactone and the like, which are generally extracted from natural drugs such as acarbose or the like, which inhibit the action of degrading enzymes such as α-glucosidase. Are used, and drugs such as ephedrine that consume calories are used.

[0004]

However, taking an anti-obesity drug in which a plurality of drugs such as acarbose and ephedrine are combined does not prevent the side effects of exciting the sympathetic nerve and affecting the cardiovascular system and the central nervous system. There was a problem that it was accompanied by the side effect of excitement. In addition, although D-xylose, L-arabinose, D-glucono-1,5-lactone, and the like are extracts from natural products, taking large amounts of them has been regarded as a problem.

[0005] Therefore, the present inventor has proposed that the bark of cod (Aralia etara, Ascididae) is effective for diabetes, and saponin contained in the leaves of gymnema (Gymnema sylvestre, Potato) and the bark of cod is in vivo. Focusing on inhibiting the absorption of monosaccharides, as a technical problem to provide an anti-obesity agent capable of suppressing a rise in blood glucose with a small amount of intake without using the drug, other than the cod and gymnema If there is a natural product having the monosaccharide absorption inhibitory action, research on a number of plants, repeating D-xylose and one or two or more natural products having different mechanisms of action in repeated experiments, small amounts The present inventors have obtained remarkable knowledge that there is a more effective inhibitory effect on blood sugar rise than the use of each substance alone, and achieved the above technical problem.

[0006]

The technical problem can be solved by the present invention as described below. That is, the anti-obesity agent according to the present invention comprises D-xylose and dry powder of cod tree root bark, water extract of cod tree root bark, alcoholic extract of cod tree root bark, dry powder of cod tree bark Water extract of cod tree bark, alcoholic extract of cod tree bark, dry powder of cod tree bud, water extract of cod tree bud, alcoholic extract of cod tree bud, sugar beet root Dried powder of sugar beet, water extract of sugar beet root, alcoholic extract of sugar beet root, dried powder of spinach root, water extract of spinach root, alcoholic extract of spinach root, corn root Dried powder, water extract of root of Inoschiko, alcohol extract of root of Inoschiko, dry powder of root of chard, water extract of root of chard, alcohol of root of chard Exudates, dried powder of Butterfly seeds, water extract of Butterfly seeds, alcoholic extract of Butterfly seeds, dry powder of conker seeds, water extract of conker seeds, alcoholic extract of conker seeds , Dried powder of Gymnema leaf, aqueous extract of Gymnema leaf, alcoholic extract of Gymnema leaf, dry powder of bitter melon fruit, aqueous extract of bitter melon fruit,
Alcohol extract of bitter melon fruit, dry powder of bitter melon seed, water extract of bitter melon seed, alcoholic extract of bitter melon seed, dry powder of namban callura berry fruit, water extract of namban callura berry fruit, Extracts of alcoholic fruits of Namamba Callas Uri, dried powder of seeds of Namban Callas Uri, aqueous extracts of seeds of Namban Callas Uri, alcoholic extracts of seeds of Namban Callas Uri, dry powder of Senega root, water extraction of Senega root Extract, Senega root alcoholic extract, onion root dry powder, onion root water extract, onion root alcoholic extract, oak nut tree bark dry powder, oak nut bark Combined with one or more crude drugs selected from water extract and alcoholic extract of oak nut bark It is made of Te.

[0007] The present invention also relates to the anti-obesity agent,
One part by weight of D-xylose is mixed with 1 to 3 parts by weight of a crude drug.

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS As D-xylose, a commercially available product (for example, manufactured by Eisai Co., Ltd.) may be used. Further, an extract from a plant (for example, a decomposition product from paddy) may be used.

[0009] Crude drugs include cod tree root bark, bark and buds, sugar beet root, spinach root, wild locust root, chard root, euphorbia seed, conker seed, gymnema leaf, bitter melon fruit and seed, Fruit and seeds of Namban callas uri, Senega root, Onji root and oak nut bark (hereinafter collectively referred to as "natural products") are dried powder or extracted with water or alcohol. Use the extract extracted. In addition, the said crude drug can also be used in combination of 2 or more types.

As the dry powder, the above-mentioned various natural products may be sufficiently dried and then pulverized to a mesh of 200 to 300 using a pulverizer or the like.

[0011] Extracts with water and alcohols are obtained by thoroughly drying the above-mentioned various natural products and cutting them into coarse pieces, and then adding 1.5 to 2.0 liters of a solvent (water, methanol, ethanol, propyl) to 1 kg of the above-mentioned crude products. Alcohol, butanol, etc.)
In the case of warming, the mixture may be left at 80 to 90 ° C. for 3 hours, and in the case of cold temperature, may be left at room temperature and shaken occasionally, filtered, and then concentrated under reduced pressure at 45 ° C. or lower to obtain a dry extract. According to the heating, the water extract yield was 22 to 28%, the methanol extract yield was 15 to 18%, the ethanol extract yield was 12 to 15%, n
The yield of -propyl alcohol extract is 7 to 11%, the yield of n-butanol extract is 8 to 10%, and the cold immersion reduces the yield by 20% when heated. Further, the dried extract may be used by dissolving it in a solvent such as water.

The anti-obesity agent is preferably a mixture of 1-3 parts by weight of a crude drug with respect to 1 part by weight of D-xylose. If it is 1 or less, the effect is weak, and if it is 3 or more, the flavor is changed. It becomes difficult. More preferably, the crude drug is 1 part by weight based on 1 part by weight of D-xylose. The antiobesity agent may be any of a powder, a solid, and a liquid.

The dosage of the anti-obesity agent varies depending on the age, sex, symptoms, number of administrations, etc., but it is an anti-obesity agent comprising a combination of D-xylose and the above crude drug, which does not cause any side effects with modest effects. In general, it can be administered orally, and the range of 50 to 300 mg / day for an adult is appropriate.

[0014]

【Example】

 Examples 1 to 8, Comparative Examples 1 to 17.

The dried product of the bud, root bark and bark of the cod tree was crushed to obtain a powder of 200 to 300 mesh, which was used as a powdered crude drug.

Each of the dried products is roughly pulverized.
Coarse particles of 50-300 mesh were obtained. Subsequently, 2 l of 95% ethanol was added to each of the buds, root bark and bark coarse particles, and the mixture was refluxed at a temperature of 90 ° C. for about 3 hours to obtain an extract. After filtering the extract with filter paper, the filtrate was completely evaporated under reduced pressure at a temperature of 40 to 45 ° C. to obtain an ethanol extract of cod tree buds, root bark and bark by heating, and The extract was used as a crude drug. The ethanol extract yield of cod tree buds is 8.
5%.

Further, 2 l of 100% n-butanol was added to the buds, root bark and bark coarse particles at a temperature of 90 ° C.
The mixture was refluxed for about 3 hours to obtain an extract. After the extract was filtered through filter paper, the filtrate was completely evaporated under reduced pressure at a temperature of 40 to 45 ° C. to remove cod tree buds, root bark and bark by heating to extract n-butanol extract. Obtained as extract crude drug. The n-butanol extract yield of cod tree buds is 4.3
%Met.

Further, 2 l of water was added to each of the coarse particles of the bud, root bark and bark, and the mixture was heated at 90 ° C. for about 3 hours to obtain an extract. After filtering the extract with filter paper,
The filtrate was completely evaporated in a reduced pressure environment at a temperature of 40 to 45 ° C. to obtain an extract of cod tree buds, root bark and bark extracted by heating to obtain an extract crude drug. The water extract yields of cod tree bud, root bark and bark are 15.2%, 13.3% and
10.2%.

The above-mentioned bud powder, bud ethanol extract and commercially available D-xylose are mixed in appropriate amounts respectively to obtain an anti-obesity agent (Examples 1 to 8). Was tested for the effect of The comparative examples 1 to 17 used D-xylose, bud powder, bud ethanol extract, bud n-butanol extract, bud water extract, root bark water extract and bark water extract alone.

In the measurement of the blood sugar level, a hyperglycemia model based on a sugar load was used as an index for knowing the amount of sugar absorbed from the digestive tract. As a hyperglycemia model, male Wistar rats weighing 150 to 180 g were used. Sucrose was used as a substitute for oligosaccharide. Thirty minutes after the administration of the above-mentioned anti-obesity agent, 0.05 g / 100 g of body weight sucrose was orally administered, and 30 minutes later, blood was collected to evaluate the inhibition of blood glucose elevation as an index. In addition, the blood glucose level was shown by the inhibition rate (%) with the control group by the glucose-oxidase method. Table 1 shows the results.

In the test of the effect on weight gain, a male ddy mouse weighing 13 to 14 g was weighed on the same day, 6 days and 12 days after addition of a normal feed and 2 to 6% of the aforementioned anti-obesity agent to the feed. At the same time, the rate of increase after 12 days was calculated. Table 2 shows the results.

[0022]

[Table 1]

[0023]

[Table 2]

As shown in Table 1, in rats administered with D-xylose in combination with each of the above crude drugs, a high inhibitory rate was exhibited even at a small dose, and a rise in blood glucose level was strongly suppressed. In addition, regarding the change in body weight, usually, a mouse takes about 2-2.5 g of feed per day and becomes about twice as heavy as a comparative mouse (see Table 2) in 12 days. Despite normal intake, body weight gain is about 30-40%, about half. In addition, the target mouse grew well similarly to the comparative example mouse.

This has an inhibitory effect on the intestinal absorption of D-xylose, which has an inhibitory effect on the enzyme that degrades oligosaccharides, and oligosaccharides and monosaccharides having a different mechanism of action from the D-xylose. This is because herbal medicines effectively act to suppress excessive secretion of insulin and prevent fat accumulation.

According to Tables 1 and 2, a sufficient effect was obtained when the blending ratio of D-xylose and crude drug was 1: 1.
It is considered to be effective as an antiobesity agent.

Examples 9 to 20, Comparative Examples 18 to 33.

The dried product of the seeds of Thrush was obtained in the same manner as in Examples 1 to 8 to obtain powder of Thonburi, ethanol extract of Thonburi, n-butanol extract of conker, and n-butanol extract of root of Fudanso. The extract was used as a crude drug. The extract yields are 7.8%, 7.5% and 5.
3%.

Antiobesity agents (Examples 9 to 20) by mixing appropriate amounts of each of the aforementioned Thonburi powder, Thonburi ethanol extract, conker n-butanol extract, Fudanso root n-butanol extract and commercially available D-xylose. age,
A test was conducted to determine the effect of the administration of the anti-obesity agent on blood glucose levels and weight gain. The results are shown in Tables 3 to 8. It should be noted that Comparative Examples 18 to 33 used the single use of the thrombus powder, the thrombus ethanol extract, the conker n-butanol extract, and the root n-butanol extract of Swiss chard.

[0030]

[Table 3]

[0031]

[Table 4]

[0032]

[Table 5]

[0033]

[Table 6]

[0034]

[Table 7]

[0035]

[Table 8]

Examples 9 to 20 are all examples 1 to 8
Had the same effect as.

Examples 21 to 36 and Comparative Examples 34 to 66.

Dried fruits and seeds of Namambakarasuri, spinach root, Gymnema leaves, bitter melon fruits and seeds, Senega root, Inokozuchi root and oak nut tree bark are the same as in Examples 1 to 8. According to the method, ethanol extract of fruit of Namban callus uri (extract yield: 6.5%) and ethanol extract of seed (extract yield: 8.8%), spinach root n-butanol extract (extract yield: 5.9%), ethanol of Gymnema leaf Extract (extract yield: 8.1%), bitter melon fruit extract (extract yield: 7.0%) and seed ethanol extract (extract yield: 6.0%), Senega root ethanol extract (extract yield: 3.9%), Ino Kozuchi root ethanol extract (extract yield: 4.0%), oak nut tree bark ethanol extract (extract : To obtain a 7.3%), and the extract herbal medicine.

An antiobesity agent (Examples 21 to 3) was prepared by mixing each extract crude drug and commercially available D-xylose in appropriate amounts.
6), and a test was conducted to determine the effect of the administration of the anti-obesity agent on blood glucose and the effect of weight gain. The results are shown in Tables 9 to 22.
Shown in In addition, the ethanol extract of Namban callus berries and seeds, the spinach root n-butanol extract,
Comparative Examples 34 to 66 were the sole use of Gymnema leaf ethanol extract, bitter melon fruit / seed ethanol extract, Senega root ethanol extract, Inokokochi root ethanol extract, and oak nut tree bark ethanol extract.

[0040]

[Table 9]

[0041]

[Table 10]

[0042]

[Table 11]

[0043]

[Table 12]

[0044]

[Table 13]

[0045]

[Table 14]

[0046]

[Table 15]

[0047]

[Table 16]

[0048]

[Table 17]

[0049]

[Table 18]

[0050]

[Table 19]

[0051]

[Table 20]

[0052]

[Table 21]

[0053]

[Table 22]

Examples 21 to 36 are all examples 1 to 8
Had the same effect as.

Examples 37 to 40, Comparative Examples 67 to 74.

Approximately 1 kg of each of the dried sugar beet roots and dried onion roots was coarsely ground to obtain coarse particles of 50 to 300 mesh. Subsequently, 2 liters of 95% ethanol was added to the coarse powder of sugar beet root and the coarse particles of radish, respectively, left to stand at room temperature, and occasionally shaken, followed by filtration after about 3 hours. The filtrate was concentrated under reduced pressure at a temperature of 45 ° C. or less to obtain an ethanol extract of sugar beet root and onji root extracted by cold soaking, and used as an extract crude drug. The extract yields were 5.0% and 4.8%, respectively.

The above-mentioned ethanol extract of sugar beet and cold-soaked ethanol extract of onji and commercial D-
Xylose and an appropriate amount of each were mixed to prepare an anti-obesity agent (Examples 37 to 40), and a test was conducted on the measurement of blood glucose and the effect of weight gain by administration of the anti-obesity agent. The results are shown in Tables 23 to 26. It should be noted that Comparative Examples 67 to 74 used single use of the sugar beet root cold soaked ethanol extract and the onji root cold soaked ethanol extract.

[0058]

[Table 23]

[0059]

[Table 24]

[0060]

[Table 25]

[0061]

[Table 26]

Examples 37 to 40 are all examples 1 to 8
Had the same effect as.

[0063]

As described above, according to the present invention, D
-Since xylose and a crude drug obtained from a specific natural product are blended and used as an anti-obesity agent, D-xylose and the crude drug having a different mechanism of action from D-xylose are effective. Sufficient effects can be obtained with a smaller dose, and there is no concern about side effects even if taken.

Therefore, it can be said that the industrial applicability of the present invention is very high.

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[Procedure amendment]

[Submission date] November 4, 1997

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0012

[Correction method] Change

[Correction contents]

[0012] Anti-obesity agents is preferably one herb formulated 1-3 parts by weight with respect to D- xylose 1 part by weight, in 1 or less, the action becomes weak, and because taking flavor turn into varying in 3 or more It becomes difficult. More preferably, D-xylose 1
1 part by weight of crude drug per part by weight. The antiobesity agent may be any of a powder, a solid, and a liquid.

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0029

[Correction method] Change

[Correction contents]

Antiobesity agents (Examples 9 to 20) by mixing appropriate amounts of each of the aforementioned Thonburi powder, Thonburi ethanol extract, conker n-butanol extract, Fudanso root n-butanol extract and commercially available D-xylose. A test was conducted on the measurement of blood glucose level and the effect of weight gain by administration of the anti-obesity agent. The results are shown in Tables 3 to 8. In addition, Thonburi powder, Thonburi ethanol extract,
Conker n-butanol extract and chard root n-
Butanol extract was used alone as Comparative Examples 18 to 33.

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0039

[Correction method] Change

[Correction contents]

Each of the above extract crude drugs and a commercially available D-xylose were mixed in appropriate amounts, respectively, to form an antiobesity agent (Examples 21 to 21).
36), and a test was conducted to determine the effect of administration of the antiobesity agent on blood glucose levels and the effect of weight gain. Table 9-
22. In addition, the ethanol extract of Namban callus berry fruit / seed, the spinach root n-butanol extract, the Gymnema leaf ethanol extract, the bitter melon fruit /
Seed ethanol extract, Senega root ethanol extract,
Comparative Examples 34 to 66 were the sole use of the root ethanol extract of Inokokochi and the bark ethanol extract of oak nut tree.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0057

[Correction method] Change

[Correction contents]

The above-mentioned ethanol extract of sugar beet and cold-soaked ethanol extract of onji and commercial D-
Appropriate amounts of xylose were mixed with each to prepare an anti-obesity agent (Examples 37 to 40), and a test was conducted to determine the blood glucose level and the effect of weight gain by administration of the anti-obesity agent. The results are shown in Tables 23 to 26. It should be noted that Comparative Examples 67 to 74 used the single use of the cold-soaked ethanol extract of sugar beet and the cold-soaked ethanol extract of Onji.

Claims (2)

[Claims] 1. D-xylose and dry powder of cod tree root bark, water extract of cod tree root bark, alcoholic extract of cod tree root bark, dry powder of cod tree bark, cod tree bark Water extract, cod tree bark alcohol extract, cod tree bud dry powder, cod tree bud water extract, cod tree bud alcohol extract, sugar beet root dry powder, sugar beet Water extract of sugar beet root, alcoholic extract of sugar beet root, dry powder of spinach root, water extract of spinach root, alcoholic extract of spinach root, dry powder of Inokozuchi root, Aqueous root extract, Alcoholic extract of Inochikozuki root, Dry powder of Swiss chard root, Aqueous extract of Swiss chard root, Alcoholic extract of Swiss chard root, Dry powder of seeds, water extract of Butterfly seeds, alcoholic extract of Butterfly seeds, dry powder of conker nuts, water extract of conker nuts, alcoholic extract of conker seeds, Gymnema leaf Dry powder, water extract of Gymnema leaf, alcoholic extract of Gymnema leaf, dry powder of bitter melon fruit, water extract of bitter melon fruit,
Alcohol extract of bitter melon fruit, dry powder of bitter melon seed, water extract of bitter melon seed, alcoholic extract of bitter melon seed, dry powder of namban callura berry fruit, water extract of namban callura berry fruit, Extracts of alcoholic fruits of Namamba Callas Uri, dried powder of seeds of Namban Callas Uri, aqueous extracts of seeds of Namban Callas Uri, alcoholic extracts of seeds of Namban Callas Uri, dry powder of Senega root, water extraction of Senega root Extract, Senega root alcoholic extract, Onji root dry powder, Onji root water extract, Onji root alcohol extract, Oak nut tree bark dry powder, Oak nut tree bark Combined with one or more crude drugs selected from water extract and alcoholic extract of oak nut bark Anti-obesity agent, characterized in that the. 2. Crude drug 1 to 1 part by weight of D-xylose
2. The anti-obesity agent according to claim 1, wherein the antiobesity agent is incorporated in an amount of 3 to 3 parts by weight.