JPH09278653A - Retinal disease-treating preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a retinal disease-treating preparation which contains tranilast and is effective for retinopathy, particularly effective for retinoangiopathy. SOLUTION: This treating preparation contains tranilast [2-(3,4-dimethoxy- cinnamoyl)aminobenzoic acid] or its salt as an active ingredient. It is useful for treating retinopathy such as occlusion of retinal blood vessel, for example, occlusion of retinal vein, retinal vasculitis or diabetic retinopathy, and amelioration of macular edema and recovery of eyesight are observed. Customary components are appropriately formulated to tranilast to prepare capsules, tablets, dust, eye drop, injection solution and the like. The daily dose is 100-1,000mg in portions once to several times in the case of oral administration and is 0.01-5 wt./vol.% in portions once to several times in the case of eye drop.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent for retinal diseases containing tranilast or a pharmaceutically acceptable salt thereof as an active ingredient.

[0002]

2. Description of the Related Art The retina has a function of receiving light from the outside and plays an important role in visual function.
Structurally, it is composed of 10 layers such as retinal pigment epithelium layer, inner granular layer, nerve fiber layer, and a thickness of 0.1.
It is a tissue of 0.5 mm.

The blood vessels of the retina are branches of the central retinal arteries and veins, run in the nerve fiber layer, and play a role of supplying oxygen and nutrients to the optic nerve.

When a retinal blood vessel is occluded or narrowed due to factors such as convulsions, thrombus, and emboli, the retinal circulation is impaired, and the supply of oxygen and nutrients to the retina is blocked. Retinal vascular disorders occupy a particularly important position in retinal diseases,
Representative examples of symptoms associated with retinal vascular disorders include retinal vascular occlusion, retinal vasculitis, diabetic retinopathy, and hypertensive retinopathy.

Retinal vascular occlusion includes central retinal vein occlusion in which retinal vein is occluded and branch retinal vein occlusion, central retinal artery occlusion in which retinal artery is occluded or narrowed, and central retinal artery occlusion. , The current treatments are as follows. Laser photocoagulation has been the main treatment method for central retinal vein occlusion and branch retinal vein occlusion (Am. J. Ophthalmol., 98 , 271-282).
(1984)). In addition, drug treatment with a fibrinolytic enzyme agent or an anticoagulant has been attempted. On the other hand, central retinal artery occlusion and central retinal artery branch occlusion are treated by eye massage, inhalation of amyl nitrite, administration of isosorbide nitrate, and the like. However, these treatment methods may not be able to be sufficiently treated, and the detailed treatment methods are currently in flux.

[0006] Retinal vasculitis is a kind of posterior uveitis manifested in intraocular malignant lymphoma and has poor reactivity to steroid drugs.

Diabetic retinopathy, which is a diabetic eye complication, develops as a part of systemic diabetic microangiopathy. Capillary aneurysm, petechiae / ecchymosis, and hard vitiligo occur first, followed by multiple soft vitiligo, resulting in intraretinal microvascular abnormalities. After that, new blood vessels are generated in the vitreous, causing vitreous hemorrhage and causing retinal detachment. When these symptoms are applied to the macula, macular edema occurs, which causes visual impairment. Many treatments have been attempted for macular edema. For example, drug treatment with prostaglandin production inhibitor, Sairei-to, acetazomirad, etc.,
Hyperbaric oxygen therapy has been reported (New Ophthalmology, 12 , 727-733 (1995)).

[0008] On the other hand, tranilast (2- (3,4-dimethoxycinnamoyl) aminobenzoic acid) has an action of suppressing the release of chemical mediators due to an allergic reaction, and causes allergic reactions such as bronchial asthma, allergic rhinitis and atopic dermatitis. It is disclosed that it is useful for the treatment of diseases caused by (Japanese Patent Publication No. 56-40710), and capsules, fine granules and dry capsules are commercially available as therapeutic agents for allergic diseases. In addition, it is caused by a therapeutic agent for diseases caused by hypersynthesis of collagen such as keloid (JP-A-5-163222), restenosis after percutaneous coronary angioplasty, and excessive proliferation of vascular intimal cells such as arteriosclerosis. Preventive and therapeutic agent for diseases (JP-A-6-135)
It is also disclosed that it is useful as (Japanese Patent No. 829). However, there are no reports on studies on the ophthalmological field, particularly on retinal diseases.

[0009]

DISCLOSURE OF THE INVENTION It has been a very interesting subject to find a compound useful for the treatment of retinal vascular disorders which occupy a particularly important position in retinal diseases.

[0010]

[Means for Solving the Problems] The inventors of the present invention have conducted various studies to find a new therapeutic agent for retinal vascular disorders that occupy a particularly important position among retinal diseases, and as a result, have been treated for allergic diseases. The drug tranilast or a pharmaceutically acceptable salt thereof is a retinal vascular disorder, for example,
Retinal vascular occlusion, such as retinal vein occlusion, retinal vasculitis,
It has been found that it is effective for diabetic retinopathy and the like and is useful as a therapeutic agent for retinal diseases.

The pharmaceutically acceptable salt in the present invention is not particularly limited, and examples thereof include hydrochloride, sulfate, phosphate, lactate, maleate, fumarate, oxalate and the like.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The details of the effect of tranilast or a pharmaceutically acceptable salt thereof on retinal vascular disorders will be described in the section on human tests described below. However, tranilast is administered to humans with retinal vascular disorders. Upon administration, improvement in macular edema and recovery of visual acuity were observed.

The dosage forms of tranilast or a pharmaceutically acceptable salt thereof include commercially available capsules, fine granules and dry syrups, tablets, powders, eye drops,
Injectables and the like can be mentioned, and tranilast or a pharmaceutically acceptable salt thereof can be formulated by a commonly used technique. Regarding powders, tablets, and capsules, JP-A-5-163222 and JP-A-6-1358.
29, JP-A-1-2946 regarding aqueous preparations.
20 and Japanese Patent Laid-Open No. 2-264716. Also, for eye drops, sodium chloride,
Isotonic agents such as concentrated glycerin, buffering agents such as sodium phosphate, sodium acetate, polyoxyethylene sorbitan monooleate (hereinafter referred to as polysorbate 80), polyoxyl stearate 40, interfaces such as polyoxyethylene hydrogenated castor oil An active agent, a stabilizer such as sodium citrate and sodium edetate, a preservative such as benzalkonium chloride and paraben can be used as necessary to formulate, and the pH is within a range acceptable for ophthalmic preparations. However, the range of 4 to 8 is preferable.

The dose may be appropriately selected depending on the symptoms, age, dosage form, etc., but usually 100 to 100 per day for oral preparations.
1000 mg, preferably 300 to 600 mg, may be administered once or in several divided doses.
The amount of 01 to 5% (w / v), preferably 0.1 to 3% may be instilled once to several times a day.

The results of human tests are shown below, but these examples are for better understanding of the present invention,
It does not limit the scope of the invention.

[0016]

Example [Human test] To examine the usefulness of tranilast,
The effect of tranilast on retinal circulation disorder with macular edema was investigated by fluorescent fundus examination in humans.

(Results) As an example of the results in Table 1, in patients with central retinal vein occlusion (case A) and diabetic retinopathy (case B), both of which had macular edema, tranilast 1 was used.
The improvement degree of macular edema when 00 mg is administrated three times a day every day is shown. The degree of improvement shown in the table is as shown below.

-: No change, ±: Slightly improved, +: Improved, ++: Remarkably improved

[Table 1]

As is clear from Table 1, macular edema was improved 2 weeks after the administration of tranilast. There were also cases in which the eyesight was restored by the administration of tranilast.

[0020]

EFFECTS OF THE INVENTION From the results of the above-mentioned test in humans, improvement of macular edema and recovery of visual acuity were observed by administration of tranilast, and tranilast indicates retinal vascular occlusion such as retinal vein occlusion, retinal vasculitis, diabetic retinopathy. It was found that it is effective for retinal vascular disorders such as and is useful as a therapeutic agent for retinal diseases.

Claims (6)

[Claims] 1. A therapeutic agent for retinal diseases comprising tranilast or a pharmaceutically acceptable salt thereof as an active ingredient. 2. The retinal disease is retinal vascular disease.
The therapeutic agent described. 3. The therapeutic agent according to claim 2, wherein the retinal vascular disorder is retinal vascular occlusion. 4. The therapeutic agent according to claim 3, wherein the retinal vascular occlusion is retinal vein occlusion. 5. The therapeutic agent according to claim 2, wherein the retinal vascular disorder is retinal vasculitis. 6. The therapeutic agent according to claim 2, wherein the retinal vascular disorder is diabetic retinopathy.