Method for the prophylaxis and/or treatment of medical disorders

a medical disorder and prophylaxis technology, applied in the field of medical disorders, can solve the problems of affecting a significant proportion of the population, and not being completely effective, and being free of adverse side effects

Inactive Publication Date: 2005-11-24
WRAIGHT CHRISTOPHER +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013] According to this preferred embodiment, there is provided a method for ameliorating the effects of a medical disorder such as a proliferative and / or inflammatory skin disorder in a mammal, said method comprising contacting the proliferating and / or inflamed skin or skin capable of proliferation and / or inflammation or a cell otherwise involved with said medical disorder with an effective amount of a nucleic acid molecule or chemical analogue thereof capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation and / or inflammation and / or other medical disorder.
[0014] According to this embodiment, there is provided a method for ameliorating the effects of a proliferative and / or inflammatory skin disorder such as psoriasis said method comprising contacting the proliferating and / or inflamed skin or skin capable of proliferation and / or inflammation with effective amounts of UV treatment and a nucleic acid molecule or chemical analogue thereof capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation and / or inflammation.

Problems solved by technology

Psoriasis and other similar conditions are common and often distressing proliferative and / or inflammatory skin disorders affecting or having the potential to affect a significant proportion of the population.
Whilst a range of treatments have been developed, none is completely effective and free of adverse side effects.

Method used

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  • Method for the prophylaxis and/or treatment of medical disorders
  • Method for the prophylaxis and/or treatment of medical disorders
  • Method for the prophylaxis and/or treatment of medical disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0118] The differentiated human keratinocyte cell line, HaCaT [9] was used in the in vitro assay. Cells at passage numbers 33 to 36 were maintained as monolayer cultures in 5% V / V CO2 at 37° C. in Keratinocyte-SFM (Gibco) containing EGF and bovine pituitary extract as supplied. Media containing foetal calf serum were avoided because of the high content of IGF-I binding proteins in serum.

[0119] Feeder layer plates of lethally irradiated 3T3 fibroblasts were prepared exactly as described by Rheinwald and Green [10].

example 2

[0120] Cells were grown to 4 days post confluence in 2 cm2 wells with daily medium changes of Keratinocyte-SFM, then the medium was changed to DMEM (Cytosystems, Australia), with the following additions: 25 mM Hepes, 0.19% w / v, sodium bicarbonate, 0.03% w / v glutamine (Sigma Chemical Co, USA), 50IU / ml penicillin and 50 μg / ml streptomycin (Flow Laboratories). After 24 hours, IGF-I or tIGF-I was added to triplicate wells, at the concentrations indicated, in 0.5 ml fresh DMEM containing 0.02% v / v bovine serum albumin (Sigma molecular biology grade) and incubated for a further 21 hours. [3H]-Thymidine (0.1 μCi / well) was then added and the cells incubated for a further 3 hours. The medium was then aspirated and the cells washed once with ice-cold PBS and twice with ice-cold 10% v / v TCA. The TCA-precipitated monolayers were then solubilized with 0.25M NaOH (200 μl / well), transferred to scintillation vials and radioactivity determined by liquid scintillation counting (Pharmacia Wallac 1410 ...

example 3

[0121] HaCaT conditioned medium (250 μl) was concentrated by adding 750 μl cold ethanol, incubating at −20° C. for 2 hours and centrifuging at 16,000 g for 20 min at 4° C. The resulting pellet was air dried, resuspended thoroughly in non-reducing Laemmli sample buffer, heated to 90° C. for 5 minutes and separated on 12% w / v SDS-PAGE according to the method of Laemmli (1970).

[0122] Separated proteins were electrophoretically transferred to nitrocellulose membrane (0.45 mm, Schleicher and Schuell, Dassel, Germany) in a buffer containing 25 mM Tris, 192 mM glycine and 20% v / v methanol. IGFBPs were then visualised by the procedure of Hossenlopp et al [11], using [125I]-IGF-I, followed by autoradiography. Autoradiographs were scanned in a BioRad Model GS-670 Imaging Densitometer and band densities were determined using the Molecular Analyst program.

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Abstract

The present invention relates generally to a method for the prophylaxis and / or treatment of skin disorders, and in particular proliferative and / or inflammatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a most preferred embodiment, a method for the prophylaxis and / or treatment of psoriasis.

Description

CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Application Ser. No. 60 / 140,345, the disclosure of which is incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates generally to a method for the prophylaxis and / or treatment of medical disorders, and in particular proliferative and / or inflammatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on cells such as epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a particularly preferred embodiment, a method for the prophylaxis and / or treatment of psoriasis or neovascularization conditions such as neovascularization of the retina. The present invention is further directed to the subject genetic molecules in adjunctive therapy for ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00C12N15/113
CPCA61K38/00C12N15/113C12N2310/335C12N15/1138C12N2310/315C12N15/1136
Inventor WRAIGHT, CHRISTOPHERWERTHER, GEORGEEDMONDSON, STEPHANIE
Owner WRAIGHT CHRISTOPHER
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