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Methods and pharmaceutical compositions for healing wounds

a technology of pharmaceutical compositions and wound healing, applied in the field of methods and pharmaceutical compositions, can solve the problems of insufficient healing of wounds, inability to properly function, and inability to properly heal wounds, and achieve the effect of accelerating the healing process of skin wounds

Inactive Publication Date: 2008-11-13
TENNENBAUM TAMAR +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides a method and pharmaceutical composition for inducing or accelerating the healing process of a skin wound. The method involves administering to the skin wound an agent that modulates the production or activity of protein kinase C (PKC), such as insulin or an insulin secreting cell. The pharmaceutical composition includes insulin or a nucleic acid construct designed to produce and secrete insulin. The method and pharmaceutical composition can be used to promote skin wound healing, particularly in cases of ulcers, burns, lacerations, and surgical incisions."

Problems solved by technology

Wound healing is impaired when these components, either individually or as a whole, do not function properly.
Yet skin ulceration in diabetic patients takes a staggering personal and financial cost (29, 30).
However, other mechanisms whereby the diabetic state associated with abnormal insulin signaling impairs wound healing and alter the physiology of skin has not been elucidated.
There is also a common problem of wound healing following surgical procedures in various parts of the body, the surgery succeeds but the opening wound does not heal.
The limitations for investigating the role of distinct PKC isoforms in skin cells proliferation and / or differentiation has been hampered as result of the difficulty in introducing foreign genes efficiently into primary cells, by conventional methods.
The short life span, differentiation potential and the inability to isolate stable transformants do not allow efficient transduction of foreign genes into primary skin cells.
However, none of these patent applications teaches the use of insulin for treating chronic, Grade II or deep wounds.
However, the use of insulin in combination with another biologically active agent capable of modulating the expression and / or activation of PKC is not taught nor suggested in this application.
However, this patent application fails to teach the use of insulin for the purpose of treating diabetes non-related wounds.
However, the application of insulin on wounds in vivo is not taught by these patents.
Furthermore, the prior art fails to teach or suggest utilizing nucleic acid constructs or genetic transformation techniques for providing insulin to wounds, so as to accelerate the healing process of the wounds.

Method used

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  • Methods and pharmaceutical compositions for healing wounds
  • Methods and pharmaceutical compositions for healing wounds
  • Methods and pharmaceutical compositions for healing wounds

Examples

Experimental program
Comparison scheme
Effect test

example 1

Effective Over-Expression of PKC Isoforms Utilizing Recombinant Adenovirus Vectors

[0193]By utilizing a recombinant β-galactosidase adenovirus a high infection rate was achieved with more than 90% of the cultured keratinocyte population expressing the recombinant protein. The recombinant β-galactosidase adenovirus infection did not affect cell viability or cell growth. Furthermore, β-galactosidase expression was sustained for up to two weeks of culture and was used as a control infection in following experiments. The efficiency of recombinant PKC adenovirus constructs to induce protein expression and be activated properly in mouse keratinocyte cultures was examined. As seen by Western blotting in FIG. 1, 24 hours following a 1 hour infection with recombinant PKC adenovirus constructs, a dramatic increase in specific PKC protein expression was observed five to ten fold above the endogenous expression levels of the specific isoforms. Recombinant protein could be detected in infected ke...

example 2

Over-Expressed PKC Isoforms are Activated by PKC Activators

[0194]Recombinant proteins of the PKC isoforms responded typically to PKC activators. As seen in FIG. 2, treatment with bryostatin 1 induced translocation of PKCα and δ proteins to the membrane fraction, with a lesser effect on PKCη and ζ isoforms, similarly to results obtained with the endogenous isoforms and as expected from their cofactor requirements.

example 3

Over-Expressed PKC Isoforms are Active in their Native Form

[0195]As early as 18 hours following infection, PKC kinase assays revealed that immunoprecipitates of distinct PKC isoforms were enzymatically active without further need of stimulation by PKC activators (FIG. 3).

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Abstract

A pharmaceutical composition and method for inducing or accelerating a healing process of a skin wound are described. The pharmaceutical composition contains, as an active ingredient, a therapeutically effective amount of at least one agent for modulating PKC production and / or activation, and a pharmaceutically acceptable carrier. The method is effected by administering the composition to a wound.

Description

[0001]This is a continuation of U.S. patent application Ser. No. 10 / 644,775 filed Aug. 21, 2003, pending, which is a continuation-in-part of U.S. patent application Ser. No. 10 / 169,801, filed Jul. 9, 2002, which is a National Phase of PCT / IL01 / 00675, filed Jul. 23, 2001, which claims priority of U.S. patent application Ser. No. 09 / 629,970, filed Jul. 31, 2000, now abandoned. This application also claims the benefit of priority of U.S. provisional patent application No. 60 / 486,906, filed Jul. 15, 2003.FIELD AND BACKGROUND OF THE INVENTION[0002]The present invention relates to a method and a pharmaceutical composition for inducing and / or accelerating cell proliferation, and / or cell differentiation and thereby accelerating the healing process of wounds. More particularly, the present invention relates to the use of modulated expression and / or activation, e.g., as initiated by membrane translocation, of serine / threonine protein kinases, also known as PKCs, for inducing and / or accelerati...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/28A61P17/02A61KA61K31/74A61K38/45C12N15/54
CPCA61K31/785A61K38/1858A61K38/28A61K38/30A61K38/45A61K45/06C12N2799/022A61K2300/00A61P1/02A61P1/04A61P15/02A61P17/02A61P17/06A61P27/02A61P31/18A61P43/00A61P9/14A61P3/10A61K31/74
Inventor TENNENBAUM, TAMARSAMPSON, SANFORDKUROKI, TOSHIOADDY, ALTSHEN, SHIOMZION
Owner TENNENBAUM TAMAR
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