JP2007191398A - Therapeutic agent for eye disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new therapeutic agent for eye diseases having high therapeutic effect for various eye diseases. <P>SOLUTION: The therapeutic agent for eye diseases comprises trichostatin A as an active ingredient. The invention expresses effect for effectively treating various eye diseases. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a novel therapeutic agent for eye diseases.

  As the information society and the aging society progress more advanced, various eye diseases such as glaucoma and cataract are increasing, and the prevention and treatment of these eye diseases are urgently needed. However, the conventional techniques have not been able to effectively treat these eye diseases.

Trichostatin A has been reported to have an antifungal action, an antiprotozoal action, an anticancer action, and a histone deacetylase inhibitory action, and is used to treat dermatitis, eczema, leukemia, and thyroid cancer. Also known as an agent for treating fibrosis.
However, there is no report that trichostatin A is effective in the treatment of eye diseases.

  An object of the present invention is to provide a novel therapeutic agent for eye diseases that is highly effective in the treatment of various eye diseases.

  The present invention is an eye disease therapeutic agent containing trichostatin A as an active ingredient.

  The present invention has an effect that various eye diseases can be effectively treated.

  The active ingredient in the present invention is trichostatin A which is 7- [4- (dimethylamino) phenyl] -N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadieneamide. Trichostatin A is a metabolite of Streptomyces actinomycetes and can be purified and isolated from the culture. For example, it can also be purchased from Wako Pure Chemical Industries, Ltd.

  Trichostatin A can be used by dissolving or dispersing in water, but it can also be used as an inclusion product with an inclusion agent such as cyclodextrin. The content of trichostatin A in the therapeutic agent can vary depending on the type of eye disease, administration route, single dose, and patient, and can be appropriately determined by those skilled in the art. In the case of eye drops, 0.01 mg to 500 mg, particularly about 0.1 mg to 100 mg of trichostatin A can be contained in 1 L of water, and preferably included with 10 mg to 50 g of cyclodextrin.

  The present invention is a therapeutic agent for various eye diseases. Eye diseases include glaucoma, high-tension glaucoma, normal-pressure glaucoma, narrow-angle glaucoma, angiogenic senile macular degeneration, senile macular degeneration, central choroiditis, macular degeneration, senile macular degeneration , Macular hole, cataract, senile cataract, fundus hemorrhage, central retinal artery occlusion, fundus arteriosclerosis, photopathia, diabetic retinopathy, retina choroidal atrophy, fundus lesion by myopia, retina and choroidal neovascular lesion , Retinoblastoma, malignant melanoma or other malignant tumors, cataracts by removal of ovaries, cataracts by TGFβ, macular fibroproliferation (macular macular), central retinal vein (branch) obstruction, retinal tear, retinal detachment, Proliferative retinopathy, retinitis pigmentosa, keratitis, corneal opacity, corneal bilan, corneal epithelial detachment, corneal ulcer, morens corneal ulcer, corneal endothelial cell degeneration or loss, corneal degeneration, epidemic keratoconjunctivitis, chalazion, iris Flame Uveitis, autoimmune disease, choroiditis, iridocyclitis, eye strain, visual field stenosis due to various diseases, optic nerve atrophy, optic neuritis, ischemic optic neuropathy, decreased dynamic vision, color blindness, presbyopia, myopia, There are various eye diseases such as refractive errors such as hyperopia and astigmatism. The present invention is particularly effective in treating glaucoma, normal-tension glaucoma, narrow-angle glaucoma, cataract, and myopia.

  The dosage form of the therapeutic agent of the present invention may be conventional, for example, eye drops, tablets, capsules, solutions, syrups, injections, haps, ointments, suppositories, and the like.

  The administration route of the therapeutic agent of the present invention may be local administration (for example, instillation, subconjunctival injection, intraocular injection), oral administration, parenteral administration (injection, etc.), and local administration, particularly instillation is preferred.

  Examples of the present invention are shown below.

Example 1 Preparation of ophthalmic solution for treatment of eye diseases 1 mg of trichostatin A (manufactured by Wako Pure Chemical Industries, Ltd.) is dissolved in 1 L of distilled water, and 1 g of γ-cyclodextrin (manufactured by Sigma) is dissolved in the solution. In addition, the eye drop was prepared by stirring.

Example 2 Treatment of Normal Tension Glaucoma One drop (about 50 μL) of trichostatin A ophthalmic solution prepared in Example 1 was applied to the left eye of an 88-year-old female patient diagnosed with normal tension glaucoma twice a day. (8 am and 5 pm) Instilled for 10 days. Changes in the visual field of the patient before and after 10 days of instillation were observed using a static perimeter (Octopus 1-2-3). FIG. 1 shows a static visual field before instillation, and FIG. 2 shows a static visual field after 10 days of instillation. 1 and 2, it was confirmed that the visual field was improved by instillation of trichostatin A. Instillation of trichostatin A ophthalmic solution confirmed the therapeutic effect of visual field narrowing due to normal pressure glaucoma.

Example 3 Treatment of Narrow Angle Glaucoma One drop (about 50 μL) of trichostatin A ophthalmic solution prepared in Example 1 was applied to the eyes of a 73 year old female patient with narrow angle glaucoma and hypothyroidism. Was instilled twice a day (8 am and 5 pm) for 10 days. Changes in the visual field of the patient before and after 10 days of instillation were observed using a static perimeter (Octopus 1-2-3). 3 and 4 show the static visual fields of the right eye and the left eye before instillation, and FIGS. 5 and 6 show the static visual fields of the right eye and the left eye after instillation for 10 days. From FIGS. 3-6, the visual field improvement by instillation of trichostatin A was confirmed. Instillation of trichostatin A ophthalmic solution confirmed the therapeutic effect of visual field constriction due to narrow-angle glaucoma accompanied by hypothyroidism.

Example 4 Treatment of Cataract and Normal Tension Glaucoma One drop (about 50 μL) of trichostatin A ophthalmic solution prepared in Example 1 was applied to the eyes of a 69-year-old female patient with both cataract and normal pressure glaucoma. Twice a day (8 am and 5 pm), they were instilled for 10 days to observe the course of visual acuity and visual field. Corrected visual acuity before instillation (right eye: 0.7 and left eye: 0.7) improved to corrected visual acuity of right eye: 0.8 and left eye: 0.8 after 10 days of instillation, and opacity of cataract However, it was confirmed that it was improved by observation with a slit lamp microscope. Changes in the visual field of the patient before and after 10 days of instillation were observed using a static perimeter (Octopus 1-2-3). 7 and 8 show the static visual fields of the right eye and the left eye before instillation, and FIGS. 9 and 10 show the static visual fields of the right eye and the left eye after instillation for 10 days. As shown in FIGS. 7 to 10, narrowing of the visual field due to cataract and glaucoma was improved by instillation of trichostatin A ophthalmic solution.

Example 5 Treatment of Myopia and Glaucoma Performed on the eyes of a 23-year-old male patient with concurrent myopia and glaucoma (this patient uses an ortho-ke contact lens to temporarily improve myopia) One drop (about 50 μL) of trichostatin A ophthalmic solution prepared in Example 1 was instilled once a day (8 am) for 14 days. Instillation improved vision as follows.
Right eye before instillation: Vd = 1.2 (1.5x-0.5D)
Left eye: Vs = 1.0 (1.5x−0.5D)
Right eye after instillation: Vd = 1.5 (n.c)
Left eye: Vs = 1.5 (n.c)

Subsequently, when one drop (about 50 μL) of trichostatin A ophthalmic solution prepared in Example 1 was instilled into this patient twice a day (8 am and 5 pm) for 10 days, FIGS. As shown, the number of corneal endothelial cells increased as follows.
Right eye Left eye Before instillation 2770 2808
After instillation 2857 2849

  Moreover, the change of the visual field of the patient before instillation and after instillation for 24 days was observed using the static perimeter (Octopus 1-2-3). 15 and 16 show the static visual fields of the right eye and left eye before instillation, and FIGS. 17 and 18 show the static visual fields of the right eye and left eye after instillation for 24 days. 15-18, it can be seen that the visual field constriction is improved.

  Instillation of trichostatin A ophthalmic solution confirmed improvement in visual acuity, protection and regeneration of endothelial cells, and improvement in visual field narrowing due to glaucoma.

Example 6 Treatment of Normal Pressure Glaucoma For a 65-year-old female patient with normal pressure glaucoma, one drop (about 50 μL) of trichostatin A ophthalmic solution prepared in Example 1 was administered twice a day for 10 days ( (8 am and 5 pm) Instillation was carried out, and 100 mg of the extract of red grape leaves extracted with 30% ethanol and dried was taken once a day and used in combination. Changes in the visual field of patients before and after instillation and after 10 days of instillation were observed using a static perimeter (Octopus 1-2-3). 19 and 20 show static visual fields of the right eye and left eye before instillation and internal use, and FIGS. 21 and 22 show static visual fields of the right eye and left eye after instillation and internal use for 10 days. FIGS. 19 to 22 show that combined use of trichostatin A instillation and oral extract of red grape leaf extract improves the narrowing of visual field due to normal-tension glaucoma, and is effective in treating normal-tension glaucoma. Was confirmed.

  The present invention has a high therapeutic effect for various eye diseases.

The static visual field by Octopus 1-2-3 before instillation of the trichostatin A ophthalmic solution of the left eye of a normal-tension glaucoma patient in Example 2 is shown. The static visual field by Octopus 1-2-3 after instillation of the trichostatin A ophthalmic solution of the left eye of the normal-tension glaucoma patient in Example 2 is shown. The static visual field by Octopus 1-2-3 before instillation of the trichostatin A ophthalmic solution of the right eye of the narrow-angle glaucoma patient with hypothyroidism in Example 3 is shown. The static visual field by Octopus 1-2-3 before instillation of the trichostatin A ophthalmic solution of the left eye of the narrow-angle glaucoma patient with hypothyroidism in Example 3 is shown. The static visual field by Octopus 1-2-3 after instillation of the trichostatin A ophthalmic solution of the right eye of the narrow-angle glaucoma patient with hypothyroidism in Example 3 is shown. The static visual field by Octopus 1-2-3 after instillation of the trichostatin A ophthalmic solution of the left eye of the narrow-angle glaucoma patient with hypothyroidism in Example 3 is shown. The static visual field by the octopus 1-2-3 before instillation of the trichostatin A ophthalmic solution of the right eye of the patient who has both cataract and normal-tension glaucoma in Example 4 is shown. The static visual field by Octopus 1-2-3 before instillation of the trichostatin A ophthalmic solution of the left eye of the patient in Example 4 who has both cataract and normal-tension glaucoma is shown. The static visual field by the octopus 1-2-3 after instillation of the trichostatin A ophthalmic solution of the right eye of the patient who has both cataract and normal-tension glaucoma in Example 4 is shown. The static visual field by the octopus 1-2-3 after instillation of the trichostatin A ophthalmic solution of the left eye of the patient who has the cataract and the normal-tension glaucoma in Example 4 is shown. The photograph of the endothelial cell by a specular microscope and the number of endothelial cells in Example 5 are shown (right eye before instillation). The photograph of the endothelial cell by a specular microscope and the number of endothelial cells in Example 5 are shown (left eye before instillation). The photograph of the endothelial cell by a specular microscope and the number of endothelial cells in Example 5 are shown (right eye after instillation for 10 days). The photograph of the endothelial cell by a specular microscope and the number of endothelial cells in Example 5 are shown (left eye after instillation for 10 days). The static visual field by Octopus 1-2-3 before instillation of the trichostatin A ophthalmic solution of a patient's right eye in Example 5 is shown. The static visual field by Octopus 1-2-3 before instillation of the trichostatin A ophthalmic solution of the patient's left eye in Example 5 is shown. FIG. 6 shows a static visual field by Octopus 1-2-3 after 24 days of injecting trichostatin A ophthalmic solution in the right eye of a patient in Example 5. FIG. FIG. 6 shows a static visual field with Octopus 1-2-3 after 24 days of instillation of trichostatin A ophthalmic solution in the left eye of a patient in Example 5. FIG. The static visual field by Octopus 1-2-3 of the right eye of the patient before instillation and internal use in Example 6 is shown. The static visual field by octopus 1-2-3 of the patient's left eye before instillation and internal use in Example 6 is shown. The static visual field by Octopus 1-2-3 of the right eye of the patient after instillation and internal use in Example 6 is shown. The static visual field by Octopus 1-2-3 of the patient's left eye after instillation and internal use in Example 6 is shown.

Claims (1)

  A therapeutic agent for ophthalmic diseases comprising trichostatin A as an active ingredient.