JP2729340B2 - Dementia treatment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to useful in the treatment of dementia Bae
The present invention relates to a pharmaceutical composition containing oniflorin as an active ingredient.

[0002]

BACKGROUND OF THE INVENTION Paeoniflorin has the formula

[0003]

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[0004] It is known that glycosides mainly contained in crude drugs such as shakuyaku, which exhibit extremely mild sedative action, anti-inflammatory action, vasodilatory action, smooth muscle motility inhibitory action and the like. However, no effect of paeoniflorin on dementia has been reported so far. Also, no effect on dementia has been reported for a peony drug known as a crude drug rich in paeoniflorin.

[0005]

[Problems to be solved by the invention] With the aging of the population,
As the number of senile dementia patients continues to increase and is attracting much attention as a kind of social problem, various anti-dementia drugs have been developed and marketed. However, there are few satisfactory ones, and there are various types of dementia according to the cause and symptom, etc., and the maximum therapeutic effect according to each type is obtained. The emergence of different types of drugs is expected.

[0006]

Means for Solving the Problems The present inventor has sought out various compounds having an anti-dementia effect in order to solve the above-mentioned problems, and as a result of diligent studies, as a result, it has been known as a herbal medicine for menstrual irregularities, chills and the like. It has been found that Shimotsu-to, or its main drug Shakuyaku, has an anti-dementia effect, and filed a patent application ( Japanese Patent Application No. 3-120717, Japanese Patent Application Laid-Open No. 4-275224).
No. ). As a result of repeated studies on these active ingredients, the present inventors have found that paeoniflorin, which is a main component of the peony, is extremely effective for the treatment of dementia, leading to the present invention.

That is, the present invention provides a therapeutic agent for dementia comprising paeoniflorin as an active ingredient. Paeoniflorin, which is an active ingredient of the therapeutic agent for dementia of the present invention, shows a very excellent effect on the omnidirectional radial maze task using scopolamine-induced amnesic rats. Also,
Paeoniflorin is 9.5 g / kg LD ₅₀ in acute toxicity studies in intravenous administration 3.5 g / kg, intraperitoneally administered in mice, toxicity is very weak enough hardly viewed deaths oral administration, Very useful as a pharmaceutical.

[0008] Paeoniflorin, which is an active ingredient of the therapeutic agent for dementia of the present invention, can be obtained as a commercial product, but can be easily obtained by extraction and purification from a peonyiflorin-containing crude drug such as a peony. In the case of using paeoniflorin extracted and fractionated from a crude drug in the therapeutic agent for dementia of the present invention, a crude paeoniflorin extract that has only been crudely extracted and fractionated without particular purification may be used.

[0009] Pharmaceutical compositions of the present invention after paeoniflorin or <br/> other plus extracted from paeoniflorin containing crude drugs, the fractionated paeoniflorin extracts it is or suitable pharmaceutical additives appropriate, customary formulations biological techniques To prepare various dosage forms, for example, oral preparations such as powders, granules, tablets, capsules, syrups and the like or parenteral administrations such as injections or suppositories .

The dosage of the therapeutic agent for dementia of the present invention varies depending on the age, sex, weight and degree of disease of the patient, but is usually about 0.1 as peoniflorin per adult per day.
Take about 10 g in 1 to several divided doses.

[0011] specifically described by way of further example the contents of the present invention, but the invention is not intended to be limiting thereof.

【Example】

[0012] Example 1 Peony the (Yamato production) was suspended in an excess of water methanol extract obtained by extraction with hot methanol, fat low polarity with diethyl ether or chloroform, removing the non-glycoside, etc. did. After butanol was added to the aqueous layer for extraction, the butanol layer was dried over sodium sulfate and concentrated under reduced pressure to obtain a butanol extract. The butanol extract was eluted with a large amount of acetone to remove insolubles, and then the acetone layer was concentrated. The obtained acetone extract is applied to a silica gel column (elution solvent:
Chloroform / methanol = 9/1), and fractions containing only paeoniflorin were collected while checking by thin-layer chromatography (silica gel plate, developing solvent: chloroform / methanol = 5/1) and liquid chromatography. The solvent of the collected fractions was distilled off to obtain paeoniflorin as a white powder (about 1% yield from the raw material Shakuyaku). The measurement results of the obtained paeoniflorin by thin layer chromatography, infrared absorption spectrum and nuclear magnetic resonance spectrum were the same as those of the standard.

[0013] The paeoniflorin 100g microcrystalline cellulose 10g and magnesium stearate 2g obtained in Example 1 was added,
The mixture was mixed well, and the mixture was tableted to produce 1,000 tablets containing 100 mg of paeoniflorin in each tablet.

[0014] In elevated radial arm maze as a Experiment eight arm radial improvement eight arms spatial cognitive impairment in maze task (selection) from the platform of the octagonal established a Esasara the tip of all options, each Approximately 45 mg of food was placed and left free for rats. Training once a day, the first 7
The selection is successively a correct selection (entering an unselected option), and the next one selection is also a correct selection or one incorrect selection (re-entering the already selected option) and then the positive selection is performed. Based on this, each rat was trained until at least 5 consecutive trials meeting this criterion.

[0015] Using the rats achieved the standards in the training trials, the paeoniflorin test start 1 hour 30 minutes before administering 0.001 to 1 mg / kg orally, further scopolamine 0.3 mg / kg in the test 30 minutes before the start of Was administered intraperitoneally. After that, a test was performed, and those that again achieved the above criteria were regarded as pass, and the pass rate was examined. The results of these experiments are as follows. In addition, scopolamine 0.1.
In the control group administered 3 mg / kg 30 minutes before the start of the test, the pass rate was confirmed to be 0%.

[0016]

[Table 1]

Claims (2)

(57) [Claims] 1. A therapeutic agent for dementia comprising paeoniflorin as an active ingredient. 2. The therapeutic agent for dementia according to claim 1, comprising a crude paeoniflorin extract extracted and fractionated from a crude drug containing paeoniflorin as an active ingredient.