JPH03190820A - Cerebral function improver - Google Patents

Abstract

PURPOSE:To obtain a cerebral fiction improver useful for preventing and treating cerebral function disorder such as cerebral infarct or dementia, containing dried powder or extract of tuber of Stachys sieboldii Miq. CONSTITUTION:A cerebral function improver containing dried powder prepared by grinding tuber of Stachys sieboldii Miq into <=200 meshes or an extract thereof prepared by using water, an alcohol, ethyl acetate or a mixture thereof, preferably hydrous alcohol an extractant. 1 pt.wt. ground material of raw material is used based on 2-10 pts.wt. solvent, immersed in the solvent at 5-40 deg.C, preferably 15-25 deg.C for 15 days, preferably 2-3 days and filtered to give filtrate. The filtrate is concentrated at <=40 deg.C to give an essence. A dose of the improver is 500-5,000mg/day calculated as dried substance.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a brain function improving agent, particularly to a brain function improving agent effective in preventing and treating brain dysfunction such as cerebral infarction and dementia.

[Prior art] In recent years, with changes in dietary habits and aging of the population in Japan, the number of patients with brain dysfunction such as cerebral infarction and dementia has increased, resulting in a burden on families and an increase in medical institutions. Countermeasures such as increasing the number of facilities are attracting a lot of attention as a social issue.

Currently, the main treatments for these diseases are synthetic drugs.
Long-term treatment: 1 Not preferred as it usually involves side effects. Therefore, crude drugs with few side effects are generally preferred as therapeutic agents.

JP-A-59-164717 discloses an agent for improving stress-induced dysfunction containing iridoid (or its glycoside) as an active ingredient. Furthermore, JP-A No. 62-4,5526 discloses a composition containing phenylpropanoid glycoside as an active ingredient.

Although the drugs described in the above-mentioned publications have been shown to improve brain function to some extent, even higher efficacy is expected.

[Problems to be Solved by the Invention] An object of the present invention is to provide a therapeutic agent that is highly effective in preventing and treating brain dysfunction such as cerebral infarction and dementia and has no side effects.

[Means for Solving the Problems] In order to achieve the above object, it was discovered that a powder or extract of the tubers of Chorogi exhibits excellent pharmacological effects, and the present invention was completed.

That is, the present invention provides a brain function improving agent containing a dry powder or extract of the tuber part of Chorogi.

Stachys 5ieb used in the present invention
Oldii anus) is a plant of the Lamiaceae family native to China, and is only used as food in Japan.

In the present invention, the above-mentioned tuber part of Chorogi is used as a raw material.

The dry product or extract of the Chorogi tuber part used as a raw material is blended into the improving agent of the present invention. The dry product of Chorogi tuber is preferably crushed to 200 mesh pieces or less.

In addition, extracts such as liquid extracts and tinctures are prepared by the usual method according to the 11th edition of the Japanese Pharmacopoeia, "General Rules for Preparations." For example, the following method is exemplified as a method for preparing a liquid extract.

The coarsely ground material of the above raw material is chilled in an extraction solvent and filtered to obtain a filtrate. For the residue, repeat the above cooling and filtration process 2 to 3 times. The obtained filtrates are combined and concentrated by distilling off the extraction solvent to obtain an extract. In addition, it is preferable to stir occasionally during cooling.

Examples of the above-mentioned extraction solvent include water, alcohols such as methanol and ethanol, ethyl acetate, acetone, and mixtures thereof, and may be used depending on the form of the therapeutic agent. It is prepared as For example, when the improving agent is a solid such as a tablet, excipients, lubricants, etc. are added, and when the improving agent is a liquid, solubilizers, solubilizers, preservatives, etc. are added.

Examples of the excipients include microcrystalline cellulose, lactose,
Examples include white sugar, corn starch, and silicic anhydride. Examples of the lubricant include talc, magnesium stearate, and silica.

Examples of solubilizers include Niracol HCO-60 (manufactured by Nippon Zurfactant Industries) and Uniox HC-6.
0 (manufactured by NOF), etc. Examples of solubilizing agents include ethanol and glycerin.

Furthermore, examples of preservatives include ethyl roseoxybenzoate, benzoic acid, and mixtures thereof.

In the composition of the brain function improving agent of the present invention, the total weight of the liquid extract or tincture is 2 to 20% by weight, preferably 5 to 10% by weight of the improving agent.

Other additives include, for example, flavoring agents and sweeteners, preferably aqueous ethanol. The amount of the extraction solvent used is 2 to 10 parts by weight, preferably 4 to 5 parts by weight, per 1 part by weight of the coarsely ground raw material. If it is less than 2 parts by weight, the extract will not be extracted sufficiently, and if it is more than 10 parts by weight, the extraction effect will be poor and it will be economically disadvantageous.

The above cooling temperature and time are 5 to 40°C, preferably 1
The temperature is 5 to 25°C for 1 to 5 days, preferably 2 to 3 days. If the temperature is lower than 5°C or shorter than 1 day, the extract will not be extracted sufficiently. If the temperature is higher than 40°C, decomposition of the contents will easily occur, and if it is longer than 3 days, a chemical reaction may occur between the contents and the solvent, which is not preferable.

The above concentration operation may be carried out under normal pressure or reduced pressure, but it is preferably carried out at a concentration temperature of 40° C. or lower. 40℃
Higher concentrations are not preferable because the heat-labile active ingredients may be agitated and affect the medicinal efficacy.

The form of the brain function improving agent of the present invention is not particularly limited, and for example, pills, tablets, granules, capsules, liquid preparations, coloring agents, etc. may be blended.

The brain function improving agent of the present invention may be prepared by a conventional method. For example, when compressing into tablets, the above-mentioned ingredients are uniformly mixed with corn starch, etc., and the mixture is heated in a tablet molding machine, etc. Quiet, preferably 100-200m9
It may be formed into tablets.

In addition, when preparing a liquid preparation, a liquid preparation of 10 to 100 λσ, preferably 25 to 50 leaves, obtained by uniformly stirring and mixing each of the above ingredients with nilacol etc., is placed in a suitable container, such as a glass bottle, and then the therapeutic agent is prepared. It's good as well.

The dosage of the improving agent of the present invention is 500 to 5000 m9/day in terms of dried tuber part for adults. If the dose is less than 500x9/day, the therapeutic effect of the present invention cannot be obtained, and if the dose is more than 5000xg/day, there will be no side effects, but it will be uneconomical because it will be excreted in vain.

[Effect] According to the analysis conducted by the present inventors, both the powder and extract of Chiyorogi contain iridoids, their glycosides, and acteozide compounds, which have been reported to have an effect on improving functional disorders caused by stress. I understood what to do. However, as we analyzed this in more detail, we found that an extract containing mainly the above-mentioned known iridoid compounds and acteozide compounds (referred to as fraction 2 in the following examples) and a fraction containing most of them. Extract containing a sugar called stachyose (fraction 1)
When fraction 2 was divided into two fractions, a much higher effect on improving brain function was observed when both were added than fraction 2 or alone. That is,
Although fractions 1 and 2 alone produced only normal effects, when fractions 1 and 2 were added together, a high synergistic effect on improving brain function was observed.

[Effect of the invention] A treatment that is extremely effective in preventing and treating brain dysfunction such as cerebral infarction and dementia, and has no side effects, by containing all of iridoid glycosides, phenylethanoid glycosides, and saccharides. 300m of the above extract
9. Nikkolt IC60120, 0.05% of chili pepper tincture, 59% of white sugar, 0.5xρ of ethanol, 24vrg of ethyl hydroxybenzoate, and 2mg of benzoic acid were mixed well to obtain a homogeneous solution. Thirty amounts of this solution were placed in an ampoule bottle to obtain a liquid preparation.

Fractionation of Chorogi tuber extract and its component analysis As shown in Figure 1, Chorogi tuber extract (domestic commercial product) 5 kg
Cut into pieces and extract at room temperature 3 times with methanol at 20C.
x3), the extracts were combined and concentrated under reduced pressure at 40°C to obtain 500 g of methanol extract. Dissolve the extract in 10ν of water,
The column was passed through a column filled with 5ρ of Amberlite XAD2 (manufactured by Organo), eluted with 5Q of water, and then further eluted with 3Q of methanol. The water-soluble mountain part and the methanol-eluted part were each distilled off under reduced pressure to obtain Suiko Kiss (Fraction 1), 42o@
, 55 g of methanol extract (fraction 2) was obtained. Next, fraction 2 was subjected to silica gel column chromatography packed with Wako Gel C-300 (manufactured by Wako Pure Chemical Industries, Ltd.) 5007, and chloroform/methanol/water (70; However, the present invention is not limited to these examples.

Preparation of brain function improving agent (Example 1) Dried tubers of Chorogi crushed to 200 mesh or less 5
Corn starch powder 109g, lactose powder 20g
, carboxymethyl cellulose calcium powder 109.
40g of microcrystalline cellulose, 5g of polyvinylpyrrolidone powder
9 and 10 g of talc powder were added, mixed uniformly, and wet granulated using a conventional method.
u tablets were prepared.

(Example 2) Shredded dry tubers of Chorogi 51? was cold soaked in 30 mQ of 50% ethanol at room temperature for 3 days with occasional stirring. Then, it was filtered and the filtrate was collected. This operation was repeated three times, the filtrates were combined, and the solvent was distilled off at 40° C. or lower under reduced pressure of 1,100 ml to obtain an extract.

30:5 to 60:40:10). This operation is repeated to separate and purify martinocide (
1) 0.89.8-acetylharpaguide (2) 1.5
g, 0.7 g of lecosceptozyde FA (3), 3.0 g of acteozide (4), 2.19 g of Harpaguide (5), and 2.59 g of melitozide (6) were obtained. The presence of stachyose (7) (85% content) in fraction 1 was confirmed by high performance liquid chromatography.

Physical test dd for potassium cyanide-induced lethal model
Y strain male mice (5 to 6 weeks old, 10 mice per group) were orally administered with the test drugs shown in Table 1, and 60 minutes later, potassium cyanide 3, 2 rI9/9 was administered intravenously. In addition, the control group was not given any drug at all.

The average time until respiratory arrest after administration of potassium cyanide (average survival time) and the comparison (survival number) of mice that did not reach respiratory arrest even after 180 seconds were recorded. These results are shown in Table-1.

0- Table-1 1): ] Number of survivors per 00 animals.

In the Chorogi tuber extract administration group, survival time was prolonged and the number of survivors increased compared to the control. On the other hand, the group administered with Fraction 1 (sugar fraction), which is a fractionated product of tuber extract, did not show any effect. In the fraction 2 (glycoside fraction) administration group, a trend toward longer survival time and increased number of survivors was observed compared to the control, but no significant effect over tuber extract was observed.

Therefore, the improvement effect of hypoxic brain damage caused by potassium cyanide shown by the tuber extract is due to the glycoside components of Chorogi.
This is thought to be due to the additive effect of stachyose, a sugar component unique to chorogi.

The achievement rate of response latency (300 seconds) exceeded that of the control, indicating that the drug had a promoting effect on memory acquisition.

Even in amnestic mice, administration of the test drug restored memory acquisition ability to the level of normal mice, demonstrating the drug's ability to improve memory impairment.

Toxicity test A toxicity test was carried out by orally administering the drugs of Examples 1 and 2 at a dose of 3000 x g/9 for 1 week to 2 groups of ddY male mice, each group consisting of 10 mice, given free access to water and feed. .

As a result of observing the mice for one week, there were no cases of death, and
Since no toxic symptoms were observed, the drug of the present invention was found to be non-toxic.

[Brief explanation of drawings]

FIG. 1 shows a diagram of fractionation and identification of Chorogi tuber extract. a... Methanol extraction, b... Amberlite XA
Separation using D2 packed column, C. High performance liquid chromatography analysis, d... Silica gel column chroma), Graphic separation and purification. Effect on step-through passive avoidance response Normal mice and amnestic mice were placed in the light room of a step-through passive avoidance test box, the floor of one dark room was energized, and the mice were placed inside the dark room. The children were given five minutes to learn that if they entered the room, they would receive an electric shock. After acquisition of learning, methanol extract of Chorogi tuber part was orally administered, and 30 minutes later, mice were placed back into the light room of the experimental box. Mice that remained in the light room for 300 seconds or more were considered as an example of achieving the standard response latency (300 seconds). The ratio was calculated. Note that nothing was administered to control mice. The results are not shown in Table 2. ],) ddY male mice (6-7 weeks old, 10 mice per group)
. 2) Mice in which scopolamine hydrobromide (lay/ni 9) was subcutaneously administered to normal mice. The test drug administration group was normal mice based on the reference counterprocedural amendment February 14, 1990, Patent Application No. 329319 of 1999.

Claims (1)

[Claims] (1) A brain function improving agent containing dry powder or extract of Chorogi tuber.