JPH08325143A - Medicine for curing damage of corneal parenchyma - Google Patents

Abstract

PURPOSE: To obtain a safe corneal prenchyma damage-curing medicine capable of reducing corneal opacity and pain caused in a process for healing the damaged corneal parenchyma, capable of healing the damage to the normal state in an early stage, and free from side effects such as those of steroid medicines. CONSTITUTION: A corneal parenchyma damage-curing medicine contains taurine in an amount of 0.1-3wt.% as an active ingredient. Since an antiseptic agent (e.g. benzalkonium chloride) usually used as an essential ingredient on the preparation of an ophthalmic solution is not used, the irritation of an eye with the antiseptic agent on the application of the corneal parenchyma-curing medicine to the eye can be prevented. The corneal parenchyma medicine is suitably compounded with other ingredients for ophthalmic solutions and subsequently prepared by a conventional method. The daily administration of the corneal parenchyma medicine is performed several times, preferably 3-6 times. The usual ingredients for the ophthalmic solutions include methyl nestigmine sulfate, an antiinflammatory agent (e.g. glycyrrhizinic acid dipotassium salt), an antihistaminic agent (e.g. diphnhydramin hydrochloride), an afflux- removing agent (e.g. naphanoline hydrochloride), a vitamin (e.g. active type vitamin B2 ), an amino acid, a refreshing agent, a polymeric additive, a stabilizer, and a preservative.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to the use of taurine for treating corneal stroma damaged by corneal refractive surgery and the like.

[0002]

2. Description of the Related Art The cornea, which controls the visual field, is composed of epithelium, parenchyma, and endothelium in order from the outside.

Conventionally, treatment of the cornea when keratitis, a wound, infection with bacteria and viruses, and deterioration of visual acuity occur depends on the degree of symptoms, but in mild cases, the outermost epithelium of the cornea is treated. The treatment was carried out by eye drops, and in severe cases, treatment was carried out by full-thickness corneal transplantation (transplanting all of the corneal epithelium, parenchyma, and endothelium). As described above, in the conventional eye diseases, the corneal epithelium is treated except when the symptoms are severe.

However, in recent years, due to an increase in superficial keratitis and myopia, the cornea is damaged to treat or correct them.
Curative surface corneal resection surgery and corneal refractive surgery (AR
K and excimer laser) are performed, and when such an operation is performed, not only the corneal epithelium but also the parenchyma that plays the most important role in the cornea is damaged.

When the corneal stroma is damaged, it is forced to suffer pain and inconvenience with temporary corneal opacity and pain. Conventionally, as a means for recovering such corneal stroma damage, there is a natural healing inherent in humans. I left it to you.

[0006]

However, if it is left to the natural healing, the complete repair of the cornea will be slow, and the pain and inconvenience caused by it will be great. It has been desired to reduce the period of time required for treatment of cornea or to shorten the period itself required for corneal injury, but until now there have been no effective drugs and attempts have been made to administer some steroids, but side effects are severe,
It has not been put to practical use.

[0007]

Means for Solving the Problems As a result of intensive research for solving the above-mentioned problems, the inventors of the present invention reduced the pain of the corneal stroma damaged by taurine and the period required for repairing the corneal stroma damage. The present invention has been completed by finding out that it has the action of shortening the drug action, and that it has no side effects as in the case of administering a steroid drug. That is, the present invention is a therapeutic agent for corneal stroma using taurine as an active ingredient.

The repair promoter for corneal parenchymal damage of the present invention is used by blending with an eye drop. Here, the content of taurine in the eye drop is 0.1 to 3% by weight. If the amount of taurine is too small, the effect is insufficient, and if the amount is too large, it causes irritation to the eyes.

In the present invention, the above eye drop is, for example, 1
By filling in a single-use type unit dose container, preservatives (eg benzalkonium chloride, boric acid, etc.), which are the essential ingredients when preparing eye drops, are not added, and when preserving It is preferable to eliminate eye irritation in order to enhance the effect of the present invention.

Eye drops include taurine and neostigmine methylsulfate, anti-inflammatory agents (eg dipotassium glycyrrhizinate, epsilon aminocaproic acid, allantoin,
Berberine chloride, berberine sulfate, sodium azulene sulfonate, zinc sulfate, zinc lactate, lysozyme chloride, etc.), antihistamines (eg diphenhydramine hydrochloride, chlorpheniramine maleate etc.), decongestants (naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride etc.) , Various vitamins [eg active vitamin B ₂ (flavin adenine dinucleotide sodium), vitamin B ₆ (pyridoxine hydrochloride), vitamin B ₁₂ (cyanocobalamin), vitamin A acetate (retinol acetate), vitamin E acetate (acetic acid) Tocopherol), panthenol, calcium pantothenate, sodium pantothenate, etc.], amino acids (magnesium potassium L-aspartate, potassium L-aspartate, L-aspa) Magnesium laginate, sodium chondroitin sulfate, etc., cooling agent (eg menthol, borneol, camphor, peppermint oil etc.), polymer additive (eg polyhydric alcohol, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose) Etc.), stabilizers (eg ethylenediaminetetraacetate etc.), preservatives (benzalkonium chloride, methylparaben, sorbic acid etc.), sulfa agents etc. used in an amount which does not impair the effects of the present invention. It can be prepared by a conventional method.

The eye drop thus prepared is administered several times a day, preferably 3 to 6 times.

[0012]

INDUSTRIAL APPLICABILITY According to the present invention, a safe cornea that reduces corneal opacification and pain that occur during the healing process of damaged corneal stroma, restores damaged corneal stroma early and normal, and does not have side effects such as steroids It has become possible to provide a therapeutic agent for parenchymal injury.

[0013]

EXAMPLES The present invention will be described in more detail with reference to Examples and Test Examples. (Example 1) Taurine 500 mg, sodium chloride 65
0 mg, 120 mg of potassium chloride and 10 mg of sodium hydrogen carbonate were dissolved in 95 ml of sterilized purified water, the pH was adjusted to 7.4 with sodium hydroxide, and sterilized purified water was added to bring the total volume to 100 ml to prepare an eye drop. This is 0.
It was filled in a 5 ml polyethylene unit dose container. (Example 2) Taurine 1000 mg, sodium chloride 5
After dissolving 00 mg, 100 mg of potassium chloride and 10 mg of sodium hydrogen carbonate in 95 ml of sterile purified water and adjusting the pH to 7.4 with sodium hydroxide, sterile purified water was added to bring the total volume to 100 ml to prepare an eye drop. This was filled in a 0.5 ml polyethylene unit dose container.

(Example 3) 3000 mg of taurine, 100 mg of sodium chloride, 20 mg of potassium chloride and 10 mg of sodium hydrogen carbonate were dissolved in 95 ml of sterile purified water,
After adjusting the pH to 7.4 with sodium hydroxide, sterile purified water was added to bring the total volume to 100 ml to prepare an eye drop. This was filled in a 0.5 ml polyethylene unit dose container. (Example 4) Taurine 1000 mg, sodium chloride 5
00 mg, potassium chloride 100 mg, benzalkonium chloride 4 mg, sodium hydrogencarbonate 10 mg were dissolved in sterile purified water 95 ml, the pH was adjusted to 7.4 with sodium hydroxide, and sterile purified water was added to bring the total volume to 100 ml. An eye drop was prepared. This was filled in a 14 ml polyethylene terephthalate container.

(Example 5) Taurine (1000 mg), sodium chloride (300 mg), potassium chloride (60 mg), boric acid (500 mg) and sodium hydrogencarbonate (10 mg) were dissolved in sterile purified water (95 ml), and the pH was adjusted to 7.4 with sodium hydroxide. Sterile purified water was added to bring the total volume to 100 ml to prepare an eye drop. This was filled in a 14 ml polyethylene terephthalate container. (Comparative Example) Sodium chloride 750 mg, potassium chloride 1
60 mg, sodium hydrogencarbonate 20 mg, sterile purified water 9
After dissolving in 5 ml and adjusting the pH to 7.4 with sodium hydroxide, sterilized purified water is added to bring the total volume to 100 ml,
An eye drop was prepared. This was filled in a 0.5 ml polyethylene unit dose container.

(Test Example 1) Japanese white rabbits (male, body weight 3.0 to 3.5 kg, age 8 to 12 weeks) were used as one group consisting of 6 birds. After general anesthesia, eye anesthesia was performed, and excimer laser irradiation was performed with the eyelid opener attached to remove the corneal epithelium and a part of the parenchyma. Thereafter, the eye drops prepared in the example were applied to the right eye of the rabbit, and the eye drops prepared in the comparative example were applied to the left eye 0.1 ml each 4 times / day at the time of observation (after 2, 4 and 7 days after the treatment). It was instilled until. At the time of observation (2, 4 and 7 days after the treatment), the corneal parenchymal lesion was cured by observing the corneal opacification state of the tested rabbit, and then preparing a strong corneal section for immunohistological examination. It was observed by staining (proliferating cell nuclear antigen, hematoxylin / eosin, collagen type III, heat shock protein, etc.) or a scanning electron microscope. As a result, at each observation, the ophthalmic solution of Example showed significant suppression of corneal opacity and wound healing effect as compared with the ophthalmic solution of Comparative Example, and the effect was highest in Example 3, followed by The order of Example 2, Example 1, Example 5, and Example 4 was followed.

Test Example 2 Japanese white rabbits (male, body weight 3.0 to 3.5 kg, age 8 to 12 weeks) were used as one group consisting of 6 birds. After general anesthesia, eye anesthesia was performed, and a filter paper having a diameter of 6.0 mm in which n-heptanol was infiltrated with the eyelid opener was allowed to act on the central portion of the cornea of the rabbit for 1 minute and washed with 20 cc of physiological saline. Then, the eye drop prepared in the example to the right eye of the rabbit, the eye drop prepared in the comparative example to the left eye,
0.1 ml each 4 times / day, during observation (after treatment 2,
The eye drops were applied until 4 and 7 days later. At the time of observation (2, 4 and 7 days after the treatment), the corneal parenchymal lesion was cured by observing the corneal opacification state of the tested rabbit, and then preparing a strong corneal section for immunohistological examination. It was observed by staining (proliferating cell nuclear antigen, hematoxylin / eosin, collagen type III, heat shock protein, etc.) or a scanning electron microscope. As a result, at each observation, the ophthalmic solution of Example showed significant suppression of corneal opacity and wound healing effect as compared with the ophthalmic solution of Comparative Example, and the effect was highest in Example 3, followed by The order of Example 2, Example 1, Example 5, and Example 4 was followed.

Claims (1)

[Claims] 1. A therapeutic agent for corneal stroma, which comprises taurine as an active ingredient.