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Corneal neuritogenesis promoter containing PACAP and its derivative

A technology of derivatives and neurites, applied in the field of reagents for improving corneal sensitivity and therapeutic agents for corneal epithelial damage, can solve the problems of no indication or indication, no indication or indication indication, etc., so as to improve corneal sensitivity reduction and dryness. Effects of eye symptoms

Inactive Publication Date: 2007-07-11
SENJU PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, they did not show or suggest that the derivatives have corneal sensitivity-improving effects, tear secretion-promoting effects, or corneal epithelial damage-treating effects
[0008] Although WO 03 / 020281 discloses that a compound that promotes neuron regeneration or axon elongation can be used to treat corneal nerve damage after LASIK surgery, etc., and an example of the compound is neotrophin (which is a neurotrophic factor stimulating substance), there is no Statement indicating or suggesting VIP, PACAP or its derivatives

Method used

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  • Corneal neuritogenesis promoter containing PACAP and its derivative
  • Corneal neuritogenesis promoter containing PACAP and its derivative
  • Corneal neuritogenesis promoter containing PACAP and its derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] peptide synthesis

[0113] Peptide No. 3 having the amino acid sequence shown in SEQ ID No. 19 was prepared by a conventional method for solid-phase peptide synthesis.

[0114] The hydrochloride (polystyrene-1% divinylbenzene copolymer, 100-200 mesh) of MBHA resin is placed in artificial synthesis reactor (made by glass, 6.0cm (diameter) * 29.5cm (height)) , wash with methanol 2-3 times the volume of the resin while stirring, and then wash with diaminomethane (2-3 times the volume of the resin) while stirring to expand the resin. The resin was neutralized with 10% triethylamine in diaminomethane by using dicyclohexylcarbodiimide and N-hydroxybenzotriazole with approximately 2 equivalents of Boc-Arg (Tos )-OH for condensation. After the condensation reaction proceeded for about 2 hours (with stirring), the resin was washed with methanol and dichloromethane. After disappearance of the α-amino group was confirmed by the Kaiser test, the resin was treated with 50% triflu...

Embodiment 9

[0326] Facilitating effect on the treatment of rabbit corneal epithelial injury

[0327] 1. Animals used

[0328] Male Japanese white rabbits weighing 2.0-2.5 kg purchased from Kitayama Labes Co., Ltd. were used. Each animal was placed in a separate cage indoors, which maintained a temperature of 23 ± 3°C and a humidity of 55 ± 10%, and was illuminated for 12 hours a day (lighting started at 8:00 and light ended at 20:00), and the experiment was carried out after arrival. Rearing until the last day of testing. Animals were given 100 g of solid feed (Labo R Stock, Nosan Corporation) per day, with free access to tap water.

[0329] 2. Test substance

[0330] PACAP27 was used as test substance. The test substances were dissolved in the following vehicle solutions at a concentration of 10 μM or 100 μM to prepare eye drops. As a control, the following vehicle solutions without test substances were used.

[0331] The formulation of the carrier solution:

[0332] Sodium dihydr...

Embodiment 2

[0352] Examples of pharmaceutical formulations are described below.

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Abstract

It is intended to provide a corneal neuritogenesis promoter containing PACAP, a PACAP derivative or a pharmaceutically acceptable salt thereof, in particular, a corneal neuritogenesis promoter aiming at improving corneal perception, treating dry eye and treating corneal epithelial injury due to an effect of promoting corneal neuritogenesis. This corneal neuritogenesis promoter is useful as a drug for ameliorating reduction in corneal perception following corneal surgeries such as laser keratonomy (LASIK) and corneal grafting or cataract surgery, reduction in corneal perception accompanying corneal neurodegeneration and dry eye symptom and corneal epithelial injury accompanying such reduction in corneal perception. Moreover, it is useful as a drug for ameliorating dry eye symptom, reduction in corneal perception and corneal epithelial injury in patients with dry eye, and a drug for ameliorating corneal epithelial injury and dry eye symptom and reduction in corneal perception accompanying therewith.

Description

technical field [0001] The present invention relates to an agent for promoting corneal neurite formation, an agent for improving corneal sensitivity, a therapeutic agent for dry eye, and a therapeutic agent for corneal epithelial damage. The present invention also relates to an agent for promoting corneal neurite formation, which can improve corneal sensitivity, treat dry eye, and treat corneal epithelial damage based on the neurite formation promoting effect. Background technique [0002] Corneal sensitivity is generally thought to develop after corneal surgery, such as photorefractive keratectomy (PRK), laser-assisted in situ keratomileusis (LASIK), or keratoplasty due to surgical severing of the corneal nerve, and persist for about 3 Well to 1 year. For example, corneal nerves are significantly severed after LASIK (see Linna, Tuuli U et al., Experimental EyeResearch, 1998, vol.66, p755-763), nerve images cannot be observed in the cornea or nerve bundles are too short to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61P27/02A61K38/22
CPCA61K38/2278A61P25/00A61P27/02A61K38/00
Inventor 高山美子中村义邦井上优薮田知穗东光佳尾上诚良
Owner SENJU PHARMA CO LTD
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