Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,...
Patent
1993-09-27
1997-09-02
Scheiner, Toni R.
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
4241451, 5303871, 53038824, 5303911, 5303917, A61K 39395, A61K 3944, C07K 1622, C07K 1704
Patent
active
056629044
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the healing of wounds and no agents and techniques for facilitating repair and healing of animal tissue, especially, but not exclusively, skin or other epithelial tissue, that has been damaged by, for example, wounds resulting from accidental injury, surgical operations or other trauma. The invention has particular reference to the healing of wounds in humans and other vertebrates.
As is well known, the healing of wounds in tissue such as skin generally involves, at least in adult humans and other mammals, a process of extra-cellular matrix (ECM) biosynthesis, turnover and organisation which commonly leads to the production of fibrous, connective tissue scars and consequential loss of normal tissue function.
In the realm of surgery scar tissue formation and contraction is a major clinical problem for which there is no entirely satisfactory solution at present. Likewise, scarring and fibrosis following accidental burning or other injuries or trauma, particularly in children, often has serious results, leading to impaired function, defective future growth, and to unsightly aesthetic effects, and again presents a major problem.
In regard to unsightly aesthetic effects produced by scars, there also commonly arises a need for cosmetic treatment or operations to attempt to remove these disfigurements in order to improve appearance. Additionally, a similar need for cosmetic treatment often arises in connection with unwanted tatoos and other skin blemishes. At present, however, it is difficult or impossible to carry out such cosmetic treatment or operations satisfactorily since a certain amount of surgery is generally involved which in itself is likely to result in wounds producing fresh unsightly scar tissue.
In adult humans and other mammalian vertebrates, wound healing in tissues such as skin is generally a reparative process, in contrast to a regenerative process which appears to take place in healing of fetal and embryonic tissue. The outcome of a wound repair process appears no be influenced by a number of different factors, including both intrinsic parameters, e.g. tissue oxygenation; and extrinsic parameters, e.g. wound dressings. There is, however, considerable evidence indicating that the overall process of healing and repair of wound damaged tissue, including the necessary innercellular communication, is regulated in a coordinated manner in adult humans and other mammals by a number of specific soluble growth factors which are released within the wound environment (especially by degranulating platelets and incoming macrophages) and which, amongst other things, appear to induce neovascularisation, leucocyte chemotaxis, fibroblast proliferation, migration and deposition of collagen and other extracellular matrix molecules within the wounds. Such growth factors that have been identified and isolated are generally specialised soluble proteins or polypeptides and include transforming growth factor alpha (TGF-.alpha.), transforming growth factor beta (TGF-.beta.1, TGF-.beta.2, TGF-.beta.3 etc), platelet derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factors I and II (IGFI and IGFII) and acidic and basic fibroblast growth factors (acidic FGF and basic FGF). Many of these growth factors have already been made by genetic engineering using recombinant DNA technology.
General reviews of these growth factors are to be found in articles by Mary H McGrath in Clinics in Plastic Surgery, Vol. 17, No. 3, July 1990, pp 421-432, and by George A Ksander in Annual Reports in Medicinal Chemistry, 1989, Vol. 24, pages 223-32 (published by Academic Press, Inc.) of which the contents are incorporated herein by reference.
The recognition of the importance of the role of such growth factors in the control of wound healing has led to numerous proposals for their clinical use and application as exogenous growth factor agents in treatment for acceleration and promotion of healing of wounds, especially in cases of defective wound healing states (see for example Sporn et al,
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Ferguson Mark William James
Foreman David Michael
Shah Mamta
Johnson Nancy A.
Scheiner Toni R.
The Victoria University of Manchester
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