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Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases

A technology of tubulin and binding agent, which is applied in the directions of drug combination, active ingredient of phosphorus compound, medical preparation containing active ingredient, etc.

Inactive Publication Date: 2007-01-24
OXIGENE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Additionally, delivering drugs to the eye without side effects remains a major challenge

Method used

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  • Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases
  • Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases
  • Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0131] Example 1. Topical administration with three routes of administration, study

[0132] Eye Irritation and Determination of Average Tolerance of CA4P

[0133] (i) Intravitreal medication

[0134] After intravitreal injection in rats, the test article CA4P was evaluated for possible intraocular irritation. After general anesthesia, 0.2 ml dose of CA4P was administered to the right eyes of 8 mice. Then, 0.2 ml dose of 0.9% sodium chloride USP solution was administered to the left eye of the rat as a negative control. Four different concentrations of CA4P were measured. Each of 4 concentrations (0.1 mg / ml, 1 mg / ml, 10 mg / ml, 100 mg / ml) was administered to the right eyes of 2 mice. Approximately 48 hours after administration, the eye was examined with a biomicroscopy slit lamp and an indirect ophthalmoscope. After recording the results, the experimental mice were euthanized. Immediately after euthanasia, a sample of the vitreous humor was aspirat...

example 2

[0146] Example 2. When using different routes of administration for topical administration in the eye

[0147] Evaluation of the in vivo distribution of CA4P

[0148] To effectively treat ocular neovascularization, extrasystemic drug delivery must pass through the relevant ocular structures to deliver effective doses of the drug to the diseased site. In order to confirm that different extrasystemic injections can produce effective distribution of CA4P in vivo, radioactive isotope tracer drug experiments were carried out.

[0149] method:

[0150] Unless stated below, each in vivo distribution experiment followed the protocol described below.

[0151] Will 14 C-CA4P (OxiGENE Inc. Watertown, MA) was suspended in 100 μl of saline solution, and then injected into anesthetized male New Zealand rats (4 months old, 1.8-2.5 kg, 3 vials per sample) with a 30G injection needle in the right eye. Corresponding to the use of 1, 5 and 5 μCi radioactive reagents, respec...

example 3

[0176] Example 3 adopts iontophoresis eye drug CA4P

[0177] CA4P can be ionized at physiological pH conditions, so it can be delivered by iontophoresis. The vision rabbit eye applicator (IOMED Inc, Salt Lake City, UT) was used to evaluate the delivery effect (transcleral) of iontophoresis when CA4P (10mg / ml) was administered. Consisting of connecting wires, and a monolayer hydrogel-impregnated polyvinyl acetal matrix, the 180 μl silicone vessel body is supported by a silver chloride-coated silver foil current distribution assembly. The contact surface area of ​​the applicator was 0.54 square centimeters. It was placed in the blind tube above the sclera of the right eye of New Zealand rabbits (3-3.5 kg, n=6 per treatment), 1-2 mm above the edge of the distal front of the corneal-scleral junction. Adopt trademark Phoresor II TM A PM700 (IOMED Inc. Salt Lake City, UT) power supply, using 2, 3, and 4 mA of each applicator, was subjected to DC anodic iontophoresis for 2...

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PUM

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Abstract

The present invention relates to the use of vascular targeting agents, especially tubulin-binding agents, for the treatment of eye angiogenesis, eye tumors, diabetic retinopathy, retinopathy of prematurity, retinoblastoma, and macular degeneration.

Description

[0001] related application [0002] This application is a continuation-in-part of US Patent Application 10 / 344,886, filed July 15, 2002, which is a national phase application of US02 / 22449, filed July 15, 2002, and claims the Priority of US patent application 60 / 386227. field of invention [0003] The present invention relates to the administration of vascular targeting agents, particularly tubulin-binding agents, for the treatment of ocular diseases. Background of the invention [0004] Eyes are one of the most important organs in life. The ability to maintain eye health is paramount due to age, disease, and other factors that impair vision. The main cause of blindness is the inability to introduce drugs or therapeutic agents into the eye and maintain an effective concentration of the drug or therapeutic agent in the eye. The drug is delivered systemically by oral administration of the drug, or by injection outside the eye. However, especially for the eye, systemic admi...

Claims

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Application Information

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IPC IPC(8): A61K31/66A61K31/00A61K31/09A61K31/135
CPCA61K31/00A61K31/66A61K31/135A61K31/09A61P27/02A61P43/00Y02A50/30
Inventor 戴维·谢里斯马克·伍德
Owner OXIGENE
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