JPH0643338B2 - Anti-cataract eye drops - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION "Industrial field of use" The present invention relates to an anti-cataract eye drop containing oxidized glutathione or a salt thereof as a main component.

“Prior Art, Problems to be Solved by the Invention and Means for Solving the Problems” Cataract is one of intractable eye diseases in which the crystalline lens of the eye becomes cloudy. A reduction in the amount of reduced glutathione in the lens has been reported in patients with cataracts (metabolic 17 , 2173 (1
980)), which is considered to cause clouding of the lens due to a decrease in the ability to protect against oxidative damage accompanying a decrease in reduced glutathione (lens lens biochemical mechanism edited by Shuzo Iwata, Medical Aoi Publishing). Therefore, reduced glutathione eye drops have been used as an anti-cataract agent.

However, the reduced glutathione has poor stability in the preparation, and in the case of eye drops, it has been necessary to dissolve the reduced glutathione tablets and granules before use.

Therefore, the present inventors diligently studied a method of increasing stability and an amount of reduced glutathione in the lens.

DISCLOSURE OF THE INVENTION The present invention relates to an anti-cataract eye drop containing oxidized glutathione or a salt thereof as a main component. As the above-mentioned salt, any pharmaceutically acceptable salt may be used, such as sodium,
It includes metal salts such as potassium, calcium and magnesium, and organic amine salts.

Reduced glutathione plays an important role in maintaining transparency in the lens, for example, when reduced glutathione in the lens decreases, the ability to protect against oxidative damage decreases,
As a result, it is believed that the lens becomes cloudy and cataracts occur. Therefore, reduced glutathione eye drops have been used as a therapeutic agent for cataracts. However, since reduced glutathione has poor stability in the preparation, it is necessary to dissolve the reduced glutathione tablets and granules in the eye drops before use.

Therefore, the present inventors diligently studied a method of increasing the amount of reduced glutathione in the lens that is excellent in stability. As a result, they have found that the use of oxidized glutathione or salts thereof (generally referred to as oxidized glutathione unless otherwise specified) provides an excellent anticataract therapeutic agent satisfying the above conditions.

The eye drop of the present invention is very stable as described in the section of the stability test, and the residual rate of an aqueous solution of reduced glutathione is about 90% at room temperature for 1 month, whereas the residual rate is almost the same under the same conditions. Was not observed. Further, it was found that when the eye drop of the present invention is administered, oxidized glutathione is changed to reduced glutathione by the action of glutathione reductase in the lens to increase the amount of reduced glutathione in the lens, thus completing the purpose of the present invention. It was (Refer to the section on pharmacological test) The concentration of oxidized glutathione in the eye drop of the present invention may be such that the effect can be exerted, preferably 0.5 to 5%, but may be appropriately selected depending on symptoms, age and the like. .

The pH may be within the range acceptable for ophthalmic preparations,
A range of 7 is preferred.

Additives that are usually used in this preparation as eye drops, for example, preservatives such as paraoxybenzoate, benzalkonium chloride and chlorobutanol, isotonic agents such as sodium chloride and potassium chloride, buffers such as sodium phosphate. Agents, stabilizers such as sodium edetate, and pH adjusters such as sodium hydroxide can be used as necessary.

The dosage form of the eye drop of the present invention may be either an eye drop or an eye ointment. The formulation examples are given below as examples.

"Example" Example 1 (ophthalmic solution) Formulation 1 In 100 ml Oxidized glutathione 2.0 g ε-aminocaproic acid 0.2 g Sodium chloride 0.6 g Benzalkonium chloride 0.005 g Sodium hydroxide A suitable amount Sterile purified water 〃 Manufacturing method Sterile purified water 80 ml Oxidized glutathione, ε-aminocaproic acid, sodium chloride and benzalkonium chloride are added and dissolved, and the pH is adjusted to 5.0 with sodium hydroxide. Add sterile purified water to bring the total volume to 100 ml.

Ophthalmic solutions of Formulations 2 to 4 were prepared using the same method as described above.

Formulation 2 in 100 ml (pH 6.0) Oxidized glutathione 2.0 g Sodium acetate 0.2 g Sodium chloride 0.6 g Benzalkonium chloride 0.005 g Sodium edetate 0.01 g Dilute hydrochloric acid or sodium hydroxide Appropriate amount of sterilized purified water 〃 Formula 3 in 100 ml (pH 5. 0) Oxidized glutathione 2.0 g Sodium acetate 0.2 g Glycerin 2.0 g Methyl paraoxybenzoate 0.005 g Propyl paraoxybenzoate 0.01 g Sodium hydroxide or dilute hydrochloric acid Appropriate amount of sterilized purified water 〃 Formula 4 100 ml (pH5.2) Oxidized glutathione 2.0 g Polyvinyl alcohol 1.0 g Mannitol 3.5 g Benzalkonium chloride 0.005 g Sodium hydroxide A suitable amount of sterile purified water Example 2 Formulation 5 (eye ointment) in 100 g Oxidized glutathione 2.0 g Liquid paraffin 10 g White petrolatum 88 g Manufacturing method Oxidized in liquid paraffin Type gluta On the addition to disperse. This is added to white paraffin heated to 80 ° C., and the mixture is gently stirred while being deaerated, and cooled to room temperature.

Stability test In order to investigate the stability of the eye drop of the present invention, a 2% aqueous solution of oxidized glutathione and an aqueous solution of reduced glutathione adjusted to pH 6 were prepared and stored at room temperature for 1 month, after which the residual rate was measured. .

As a result, the residual rate of the reduced glutathione aqueous solution was about 90.
%, On the other hand, almost no decrease in the residual ratio was observed in the oxidized glutathione aqueous solution.

From this, it is understood that the eye drop of the present invention is far superior in stability to the reduced glutathione eye drop.

Pharmacological test The change in the amount of reduced glutathione in the lens upon administration of oxidized glutathione was measured using the rat lens.

1) Effect on lens immediately after extraction The lens of Wistar male rat was removed and incubated with a glucose-containing Ringer's solution containing 15 mM oxidized glutathione for 5 hours, and then the amount of reduced glutathione in the lens was measured.

Results The results are shown in Table 1.

As shown in Table 1, it is clear that the addition of oxidized glutathione increases the amount of reduced glutathione in the lens.

2) Effect on sugar cataract lens The extracted lens is pre-incubated with a solution containing 55.6 mM glucose to make a sugar cataract lens (Can.J.
Ophthalmol. 16 , 32 (1981)). On the other hand, an experiment was performed using the same method as in 1) to measure the amount of reduced glutathione in the lens.

Results The results are shown in Table 2.

As shown in Table 2, in the cataract lens, the reduced glutathione level is lower than that in the normal lens shown in Table 1. Against this, the lens incubated with the solution containing oxidized glutathione is reduced. An increase in the amount of type glutathione was observed.

Toxicity test 5 week-old Slc: ddY mice (6 mice) were administered 10% aqueous solution of oxidized glutathione (neutralized with 1N sodium hydroxide solution) to the tail vein at 2000 mg / Kg, but death was observed. I couldn't do it. From these results, it was found that oxidized glutathione is a highly safe compound.

“Effect of the invention” As described above, when oxidized glutathione is administered to both normal lens and pathological model of cataract, the amount of reduced glutathione increases. Therefore, oxidized glutathione acts as a prodrug of reduced glutathione. It is clear that they are useful as anti-cataract agents.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A 64-26516 (JP, A) JP-A 62-126125 (JP, A) JP-A 56-147715 (JP, A) JP-A 55- 92315 (JP, A) JP-A-2-502189 (JP, A) All revised drug handbook edited by Osaka Prefectural Hospital Pharmacists Association P. 258,259 Published by Yakuhin Jikho Co., Ltd. 1986

Claims (1)

[Claims] 1. An anti-cataract eye drop containing oxidized glutathione or a salt thereof as a main component.