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Biological activity of pigment epithelium-derived factor and methods of use

A homologous, angiogenesis technology, applied in the analysis of biological materials, medical preparations containing active ingredients, drug combinations, etc., can solve the problem of PEDF lacking protease inhibitory activity and other problems

Inactive Publication Date: 2007-08-08
THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although PEDF has a legendary protease-sensitive loop, unlike typical serine protease inhibitors (such as αl-antichymotrypsin (ACT)), PEDF lacks protease inhibitory activity

Method used

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  • Biological activity of pigment epithelium-derived factor and methods of use
  • Biological activity of pigment epithelium-derived factor and methods of use
  • Biological activity of pigment epithelium-derived factor and methods of use

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0126] Formulations of the pharmaceutical compositions described herein may be prepared by any of the methods known or later developed in the art of medicine. In general, such preparation methods include the steps of bringing into association the active ingredient with the carrier or one or more other additional ingredients, and then, if necessary or more appropriate, shaping or packaging the product into desired single or multiple forms. dosage unit.

[0127] Although the description of the pharmaceutical compositions provided herein is primarily directed to pharmaceutical compositions suitable for administration to humans by prescription, those skilled in the art will appreciate that such compositions are generally suitable for administration to all species of animals . Known and generally skilled veterinary pharmacologists, if necessary, can only use any ordinary experiments to design and modify the pharmaceutical composition suitable for administration to humans in order ...

Embodiment 1

[0177] Example 1: PEDF qualitatively inhibits VEGF-induced retinal vascular permeability

[0178] Luciferin angiography is a clinical diagnostic technique that allows us to visualize the effects of factors that regulate VEGF-induced permeability. Decreased fluorescence in one eye relative to the other eye on the contralateral side may be attributable to agents injected into both eyes. Vascular permeability due to VEGF 28 , so as expected, compared with the fellow eye injected with saline, receiving VEGF 164 (human VEGF in mouse 165 Eyes with an ortholog) showed increased luciferin leakage (Fig. 1a). When PEDF and VEGF 164 When co-injected, no VEGF-induced vascular permeability was observed (Fig. 1b).

[0179] To show that the antivascular permeability activity is specific for PEDF, we tested the effect of ACT and HSP47 in the same assay. ACT and HSP47 are two subfamilies from the serine protease inhibitor (serpin) superfamily 29 , which is different from the subfamily...

Embodiment 2

[0180] Example 2: PEDF Quantitatively Inhibits VEGF-Induced Retinal Vascular Permeability

[0181] To quantify and confirm the ability of PEDF to inhibit VEGF-induced vascular permeability, we used a modified Evans blue assay 32 . Mice injected intravitreally as in luciferin angiography experiments received Evans blue intravascularly 24 hours later. PEDF almost terminated (95.6±21.2%) VEGF-induced vascular permeability, while ACT and HSP47 had no discernible effect (3.4±18.2% and 19.4±22.3% inhibition, respectively) ( FIG. 2 ). These data quantitatively confirm what we observed qualitatively by luciferin angiography: PEDF inhibits VEGF-induced vascular permeability.

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Abstract

The present invention relates to method of treating a patient with a condition involving increased vascular permeability or increased angiogenesis comprising administering to the patient a therapeutically effective amount of PEDF, PEDF 44 AA peptide, a homolog of the PEDF 44 AA peptide, a homolog of the PEDF 44 AA peptide wherein amino acid residues glutamateat the (101) amino acid position, isoleucine at the (103) amino acid position, leucine at the (112) and serine at the (115) amino acid position are unchanged, or an agent that activates the PEDF receptor. Conditions for treatment include, but are not limited to, sepsis acute respiratory distress syndrome, nephrotic syndrome, diabetic neuropathy, preproliferative diabetic retinopathy, cancer or proliferative diabetic retinopathy.

Description

technical field [0001] The field of the invention is that of compositions and methods for the treatment or prevention of conditions involving vascular permeability, angiogenesis and / or neurological diseases. [0002] priority [0003] The present application claims priority to US Provisional Application No. 60 / 515,374, filed October 29, 2003. Background of the invention [0004] Vascular permeability and its regulatory control are very important for homeostasis. Increased vascular permeability is important in hypotension associated with sepsis, acute respiratory distress syndrome, and nephrotic syndrome. ), diabetic nephropathy and the development of diabetic retinopathy play an important role. Although the physiological importance of maintaining normal vascular integrity is well understood, how it is maintained and how vascular permeability is negatively regulated remains poorly understood. [0005] The activity of vascular endothelial growth factor (VEGF) has been shown...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K
CPCG01N2800/28G01N2800/125G01N2800/08A61K38/1709G01N33/6893G01N33/574G01N2800/26G01N2800/164G01N2333/811A61P1/04A61P11/02A61P11/16A61P13/12A61P17/00A61P19/02A61P25/00A61P27/02A61P29/00A61P31/00A61P31/04A61P35/00A61P35/02A61P35/04A61P43/00A61P7/04A61P7/10A61P9/10A61P9/14A61P3/10
Inventor P·童H·刘
Owner THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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