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Therapeutic agent (Y - 39983) for corneal endothelial dysfunction

A technology for corneal endothelial dysfunction, applied in the direction of cell culture active agents, medical preparations containing active ingredients, nervous system cells, etc., can solve the in vivo effects of Y-27632 and fasudil, and the impact of corneal endothelial cells Issues not considered

Inactive Publication Date: 2012-11-07
SENJU PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Patent Document 1 does not describe the in vivo effects of Y-27632 and Fasudil
In addition, the effects of Rho kinase inhibitors other than Y-27632 and fasudil on corneal endothelial cells were not considered

Method used

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  • Therapeutic agent (Y - 39983) for corneal endothelial dysfunction
  • Therapeutic agent (Y - 39983) for corneal endothelial dysfunction
  • Therapeutic agent (Y - 39983) for corneal endothelial dysfunction

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0197] Preparation of corneal endothelial cell layer

[0198] The cell suspension of corneal endothelial cells can be prepared according to collection and in vitro culture of corneal endothelial cells and subculture of the above-mentioned corneal endothelial preparation. The cell suspension is seeded onto a substrate such as a collagen sheet or the like, and cultured. Here, the number of seeded cells is controlled so that the corneal endothelial preparation finally produced has a cell layer with a desired cell density. Specifically, cells are seeded to form cells with about 1,000 to about 4,000 cells / mm 2 The cell layer of the cell density. The culture can be performed under conditions similar to the above-mentioned primary culture and the like. Although the culture time varies depending on the condition of the cells used, it is, for example, 3 to 30 days. By adding the compound of the present invention, preferably compound (Ia) ((R)-(+)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)...

Embodiment 1

[0228] Embodiment 1: the effect of compound (I) in rabbit corneal endothelial wound model

[0229] 1. Test substances and reference substances

[0230] As a test substance, (R)-(+)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4-(1-aminoethyl)benzamide monohydrochloride was used (compound (I)). Compound (I) was prepared according to the methods described in WO95 / 28387 and WO2002 / 083175.

[0231] In this example, a 0.95 mM (0.03 w / v %) compound (I) infusion obtained by diluting the above-mentioned infusion with the above-mentioned excipient and 0.32 mM (0.01 w / v %) of the compound (I) were used Instillation.

[0232] As positive control substances, Y-27632 dihydrochloride (Wako Pure Chemical Industries, Co., Ltd., Cat. #253-00513) and hydrated fasudil hydrochloride injection (Eril (registered trademark) intravenous Injection solution, Asahi Kasei Pharma) was instilled, and Y-27632 and fasudil were each adjusted to 10 mM with phosphate buffered saline (PBS, Invitrogen, Cat. #14190). In...

Embodiment 2

[0254] Embodiment 2: the effect of administration of high concentration compound (I) on rabbit corneal endothelial wound model

[0255] The effect could be demonstrated in a rabbit corneal endothelial loss model by instillation of 0.05 w / v% (1.58 mM) of compound (I) (topical instillation; 6 times a day for 2 days).

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PUM

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Abstract

The present invention aims to provide a means for effectively and conveniently treating diseases wherein corneal endothelial cells poor in proliferative capacity in vivo are damaged. The present invention provides a therapeutic agent for corneal endothelial dysfunction containing (R) - ( + ) -N- (lH-pyrrolo [2, 3 -b] pyridin-4-yl) -4- (1 -aminoethyl) benzamide (Y- 39983) or a pharmacologically acceptable salt thereof (compound (Ia) ) as active ingredient, an agent for promoting adhesion of corneal endothelial cells, containing compound (Ia), a culture medium for corneal endothelial cells, containing the agent for promoting adhesion, an implant for corneal endothelial keratoplasty, containing corneal endothelial cells, scaffold and compound (Ia), and a production method of a corneal endothelial preparation, including a step of cultivating corneal endothelial cells using the culture medium.

Description

technical field [0001] The present invention relates to therapeutic agents for corneal endothelial dysfunction. In particular, the therapeutic agent for corneal endothelial dysfunction of the present invention is used for healing corneal endothelial wounds or adhesion, maintenance or preservation of corneal endothelial cells. Background technique [0002] When light entering from the cornea (the transparent tissue at the front of the eyeball) reaches the retina to stimulate retinal neuron cells, visual information is recognized, and the developed electrical signal is transmitted to the visual cortex of the brain via the optic nerve. In order to have good visual acuity, the cornea needs to be transparent. The transparency of the cornea is maintained by maintaining the homeostasis of the 3-layer structure of the corneal epithelium, stroma, and endothelium. Among them, corneal endothelial cells maintain the water content of the cornea at a constant level and are important cel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/437A61P27/02A61P43/00A61K9/00
CPCA61K9/0048A61K9/08A61K31/437C12N5/0621C12N2501/999A61P27/02A61P43/00
Inventor 高桥浩昭坂本雄二喜田彻郎樽井毅
Owner SENJU PHARMA CO LTD
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