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Photochemical therapy to affect mechanical and/or chemical properties of body tissue

A tissue and compound technology, applied in the direction of drug devices, drug devices, other medical devices, etc.

Inactive Publication Date: 2009-12-02
CALIFORNIA INST OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this regard the use of photoactivated riboflavin appears to be advisable; however, UVA light is potentially cytotoxic, and comparable exposure of the cornea for the treatment of keratoconus requires 30 minutes of irradiation (Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006; 17(4): 356-60)

Method used

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  • Photochemical therapy to affect mechanical and/or chemical properties of body tissue
  • Photochemical therapy to affect mechanical and/or chemical properties of body tissue
  • Photochemical therapy to affect mechanical and/or chemical properties of body tissue

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0166] Following the teachings of US Published Application No. 20050271590, the present inventors used Eosin Y / TEOA as a selective photoinitiator for PEGDM crosslinking for reinforcement of scleral tissue. It was surprisingly found that Eosin Y / TEOA was comparable effective in enhancing the strength of scleral tissue in the absence of the target crosslinker (eg PEGDM). It is particularly unexpected that Type II photoinitiators are able to strengthen the sclera to a therapeutically useful extent with irradiation times of about 30 minutes or less. Without wishing to be bound by any theory, it is believed that Eosin Y may be sufficient to promote the direct cross-linking of collagen and other scleral components to directly increase the strength of scleral tissue. While this does not rule out the co-action of cross-linkers such as PEGDM, the results for Eosin Y suggest that simpler formulations are possible utilizing reagents already approved by the US Food and Drug Administration...

Embodiment 2

Dose response and mechanical properties of treated tissues

[0167] A number of different techniques have been used to initially assess scleral tissue enhancement, including tensile testing, oscillatory shear measurements, and eye dilation analysis discussed more fully below.

[0168] The ability of the initiators with and without crosslinking compounds to strengthen the sclera was initially assessed using rheological analysis of tissue sections. Scleral sections (8 mm diameter) were excised from porcine eyes and tested on a TA Instruments AR1000 rheometer (using a tethered parallel plate geometry) to quantify the change in modulus before and after treatment. Two example photoinitiators were chosen for initial evaluation. 2959 (2-Hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone and Eosin Y with triethanolamine (Eosin Y / TEOA). 2959 (12959) is a UV photoactivatable photoinitiator that has shown low toxicity in cell encapsulation studies. Eosin Y / TEOA was chosen a...

Embodiment 3

Eye shape in an inflated model of myopia and keratoconus

[0169] Stabilization of eye shape was assessed in vitro using pairs of eyes enucleated from young (1-2 weeks) New Zealand white rabbits, one eye being treated and the companion eye serving as a control. In order to simulate and accelerate the loading geometry that exists in vivo, intact eyeballs are mechanically tested by imposing elevated intraocular pressure: a syringe connects the intraocular fluid to the elevated reservoir of Dulbecco's (DPBS), while the exterior of the eye is immersed in the In DPBS ( figure 1 ). Eyes enucleated from young rabbits provide a model of expandable corneal and scleral tissue: when subjected to elevated intraocular pressure in vitro, the cornea progressively bulges outward and the scleral wall expands ( figure 2 and 3 ).

[0170] Eyeball size and shape were recorded over time from two perpendicular viewpoints. To prepare the eye for testing, the epithelium is removed from the co...

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PUM

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Abstract

The disclosure concerns altering the mechanical and / or chemical property of a body tissue, particularly an ocular tissue. In specific cases, it concerns altering or stabilizing the shape of the cornea, such as in a subject suffering or at risk for ectasia or keratoconus. In other specific cases, it concerns strengthening the sclera in a subject suffering or at risk for myopia. The invention employs light irradiation of a photoactivatable compound, such as one that applies crosslinking to the tissue, for example.

Description

[0001] Related applications [0001] This application claims priority from U.S. Provisional Patent Application No. 60 / 853,949, filed on October 24, 2006, and U.S. Provisional Patent Application No. 60 / 954,541, filed on August 07, 2007. Statement Regarding Federally Sponsored Research or Development [0002] This invention was developed, at least in part, with funds from the National Institutes of Health Grant R41EY017484. The United States Government may have certain rights in this invention. Technical field [0003] The fields of the invention relate, for example, to pharmacology, anatomy, cell biology or molecular biology. In particular, the field of the invention relates to ophthalmic drugs, including ophthalmology. Background of the invention [0004] Keratoconus [0005] Keratoconus (Rabinowitz, 1998; Krachmer et al, 1994; Bron, 1988) is the most common corneal dystrophy, affecting 1 in 2000 individuals. Keratoconus causes thinning of the cornea and is named after...

Claims

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Application Information

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IPC IPC(8): A61M35/00A61M31/00
Inventor D·M·施沃茨M·S·梅特森J·A·科恩菲尔德R·K·马罗尼R·H·格鲁布斯
Owner CALIFORNIA INST OF TECH
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