JPS6360727B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the following formula [] The present invention provides a therapeutic agent for eye diseases containing cyanidin chloride or a salt thereof as a main component. Cyanidin belongs to the anthocyanidins, a group of substances collectively called flavonoids, and is found in various flowers, fruits,
Cyanidin and cyanidin chloride exist mainly as glycosides in leaves, stems, roots, seed coats, etc., but no pharmacological effects have been reported for cyanidin and cyanidin chloride. Regarding certain flavonoids, Szent-Siorgyi et al. [Nature 138 , 27
(1936)] reported that it has the effect of so-called vitamin P factor, which restores the fragility of capillaries and bleeding. Later, anthocyanocytes, which are flavonoid compounds, were activated by Vicinium myilteilus (Blueberry). Extracted as a component, it is said to promote erythema regeneration and enhance dark adaptation. The present inventors have discovered that cyanidin chloride, a derivative of a specific flavonoid, is extremely effective against eye diseases, such as retinitis pigmentosa, dark adaptation inadaptation, and diabetes, as shown in the following pharmacological tests. It is effective as a therapeutic agent for sexual cataracts and the like. The pharmacological tests are shown below. Pharmacological test 1 Effect on retinitis pigmentosa In order to search for the therapeutic effect of retinitis pigmentosa, we used periodic acid, which is known as a drug that causes experimental retinitis pigmentosa, to inject cyanidin chloride (hereinafter referred to as this compound). ).
Matsushita et al.'s method [Journal of the Japanese Ophthalmological Society 73 , 285
(1969)], ERG (electroretinogram, retinal action potential) was measured on the first day in Wistar rats (male, body weight 100-120 g, 5 rats per group).
This compound was orally administered at 50 mg/Kg for 7 days from days 8 to 14 (control group was not administered), and both groups were
3% sodium periodate for 5 days until the 13th
It was administered intraperitoneally at a rate of 0.2 ml/100 g. ERG was measured again on the 15th day and compared with the ERG on the 1st day to determine the survival rate. The higher the ERG residual rate, the stronger the degeneration suppressing effect. The ERG measurement device used was ERG ModelRX-3T manufactured by Heiwa Electronics Industry Co., Ltd. As a result, as shown in the table, a higher ERG residual rate was observed in the group administered with this compound compared to the control group.

[Table] Pharmacological test 2 Effect on dark adaptation maladaptation Male Wistar rats weighing 100-120 g (5 animals per group) were orally administered 50 mg/Kg of this compound 1 hour before the start of dark adaptation (the control group (no administration). In the experiment, ERG was measured by sufficient photopic adaptation under a 500W white light at a distance of 50cm, and then scotopic measurement for b-waves was started using Tamaki's method [Journal of the Japanese Ophthalmological Society 71 , 2095 (1967)]. 5, 10, 15, 30 after the start of dark adaptation
And ERG at 60 minutes was measured using constant stimulation light of 510 g units. As a result, as shown in the table, excellent recovery of dark adaptation was observed in the group treated with this compound compared to the control group.

[Table] Each value represents the mean ± standard deviation Pharmacological test 3 Effect on diabetic cataracts Aldose reductase (AR) is involved in diabetic cataracts, and inhibiting AR may delay the appearance of diabetic cataracts. It is known that it is possible to suppress [Journal of the Japanese Ophthalmological Society 80 ,
1362 (1975)] This method was used in this study. From the rabbit lens, Hoyman et al. [J.Biol.Chem. 240 ,
877 (1965)], and the effect of this compound on AR was determined using Kinoshita's method [Invest.
Ophthal, 13 , 713 (1974)]. The total volume of the reaction solution for AR activity measurement is 3.0ml.
[0.007M phosphate buffer (PH6.2), 0.46M lithium sulfate, 5×10 ^-5 MNADPH, 4×10 ^-4 M DL-glyceraldehyde, 10U.AR enzyme, 10 ^-4 to ^{10 -7} M
This compound] and the absorbance at 340 mμ was measured. As a result, as shown in the table, the concentration of this compound required to suppress AR by 50% was 5.0 × 10 ^-6 M,
It was found to have a strong AR suppressing effect.

[Table] Toxicity test The acute toxicity of this compound to mice and rats is extremely weak as shown in Table 4.

[Table] As is clear from the above pharmacological and toxicity tests, this compound is useful as a therapeutic agent for eye diseases such as retinitis pigmentosa, dark adaptation incompatibility, and diabetic cataracts. The dosage ranges from 10 to 1000 mg per day by oral administration, preferably 300 to 1000 mg per day when used for adult treatment.
It is 900mg. The composition of the present invention is used for internal administration in the form of tablets, granules, powders, and capsules. For this purpose, customary additives such as binders such as ethylcellulose, polyvinylpyrrolidone, etc., excipients such as lactose, crystalline cellulose, etc., disintegrants such as carboxymethylcellulose calcium, lubricants such as talc, colloidal silica, etc. are used. may be used as appropriate. Next, the composition of the formulation will be illustrated. (1) Tablets Compound 100mg Ethyl cellulose 50mg Crystalline cellulose 80mg Calcium carboxymethyl cellulose 7mg Magnesium stearate 3mg Total 240mg This tablet can be coated with the usual film coating, and can also be coated with sugar. (2) Granules Compound 100mg Polyvinylpyrrolidone 25mg Lactose 365mg Talc 10mg Total 500mg (3) Powder Compound 100mg Lactose 500mg Starch 370mg Colloidal Silica 30mg Total 1000mg (4) Capsules Compound 100mg Lactose 32mg Crystalline cellulose 56mg Colloidal silica 2mg total 190mg

Claims (1)

[Claims] 1. A therapeutic agent for eye diseases containing cyanidin chloride or its salts as a main ingredient.