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Therapeutic agent for corneal sensory nerve damage containing semaphorin inhibitor as active ingredient

An active ingredient, sensory nerve technology, applied in the field of therapeutic agents, can solve problems such as no inhibitory experiments, no description of sensory nerve function, etc.

Active Publication Date: 2013-10-30
KEIO UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this publication, no inhibitory experiments have been performed and there is no description of sensory nerve function

Method used

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  • Therapeutic agent for corneal sensory nerve damage containing semaphorin inhibitor as active ingredient
  • Therapeutic agent for corneal sensory nerve damage containing semaphorin inhibitor as active ingredient
  • Therapeutic agent for corneal sensory nerve damage containing semaphorin inhibitor as active ingredient

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0160] Vinaxanthone promotes corneal sensory nerve regeneration in keratoplasty in a mouse keratoplasty model role in life

[0161] In this experiment, genetically modified mice (P0-Cre / Floxed-EGFP mice) in which corneal parenchymal cells, corneal endothelial cells, and nerves express green fluorescent protein (GFP), a type of fluorescent protein in the cornea, were used. Using these mice, corneal sensory nerve fibers traveling in the cornea can be easily visualized by removing a layer of corneal endothelial cells.

[0162] Corneas derived from syngeneic wild-type mice were implanted into each of the mice listed above. Thereafter, 50 ul of vinaxanthone (which had been dissolved in Rinderon (1 mg / ml betamethasone sodium phosphate injection) to a concentration of 0.1 mg / mL) was administered to the mice by subconjunctival injection immediately after completion of the operation, followed by administration of 1 times, a total of 11 times. Only the drug-free solvent was admini...

Embodiment 2

[0169] Evaluation of retention of vinaxanthone formulations in corneal tissue

[0170] Apply 50 μL of vinaxanthone (0.5, 1.5 and 5.0 mg / mL) in PBS solution (0.12 M phosphate buffer saline (pH7.4)), and then closed his eyes for 30 seconds. Thereafter, at 0.5, 2 and 6 hours after administration, the rabbits were euthanized, and then the excised eyeballs were washed with physiological saline. Thereafter, corneas were harvested from each eyeball. Homogenize the cornea, then extract vinaxanthone from it. Use HPLC to examine the content and concentration of vinaxanthone in corneal tissue over time.

[0171] From Figure 4 , 5 As demonstrated in the results shown in 6 and 6, vinaxanthone was transferred into corneal tissue in an applied concentration / dose dependent manner. In the 5.0 mg / mL vinaxanthone solution administration group, it was confirmed that even 6 hours after the completion of the operation, the retention of vinaxanthone in the cornea was greater than the IC obt...

Embodiment 3

[0174] Production of xanthone compound represented by formula (1)

[0175] The xanthone compound represented by the formula (1) of the present invention is a well-known compound and is disclosed in International Publication No. WO02 / 09756 (Patent Document 1 cited above), International Publication No. WO03 / 062243 (Patent Document 2 cited above) , International Publication No. WO03 / 062440 (Patent Document 3 cited above), JP2006-335683A and JP2008-13530A. The xanthone compound of the present invention can be produced by culturing, chemical general synthesis or chemical transformation of the SPF-3059 strain. In addition to the production method, the physicochemical properties of the compound are also disclosed in the patent documents cited above. The details of the production method and the like are as follows.

[0176] Already adjusted containing 2% glucose, 5% sucrose, 2% cottonseed meal, 0.1% sodium nitrate, 0.1% L-histidine, 0.05% dipotassium hydrogen phosphate, 0.07% pota...

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Abstract

A compound represented by formula (1) (wherein R1 represents a hydrogen atom or a carboxyl group, R2 represents a hydrogen atom or a hydroxy group, R3 represents a hydrogen atom or a carboxyl group, and R4 represents a hydrogen atom or a hydroxy group) or a pharmaceutically acceptable salt thereof is effective as a therapeutic agent or a prophylactic agent for a corneal disease or sensory nerve damage due to corneal surgery, and as a regeneration accelerator for corneal sensory nerves.

Description

technical field [0001] The present invention relates to a therapeutic agent for sensory neuropathy caused by corneal disease or corneal surgery, or eye dryness associated therewith, wherein the therapeutic agent comprises a xanthone compound having semaphorin inhibitory activity as an active agent. Background technique [0002] The cornea is a transparent membrane covering the front of the eye and has the function of introducing light into the eye and then refracting it together with the lens to focus the eye. In addition, because the surface of the cornea is always covered with tears, the cornea also has the function of preventing dry eyes or bacterial infections in the eyes. This cornea can become weakened or degenerated by injury or disease, with the result that the functions listed above may be lost. To treat this symptom, medications are first used. In addition, normal corneas are transplanted into weakened or degenerated corneas in cases where this drug fails to brin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P27/02A61P27/04A61P43/00C07D311/86
CPCC07D407/04C07D311/86A61K31/352A61P25/02A61P27/02A61P27/04A61P43/00A61K31/35
Inventor 冈野荣之坪田一男榛村重人大本雅弘岸野晶祥前田美穗
Owner KEIO UNIV
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