Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-07-12
1997-07-08
Schain, Howard E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
424 851, 424 852, 514 21, 530351, 530324, A61K 3819
Patent
active
056461178
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a therapeutic agent for treating wounds.
BACKGROUND ART
Several factors having chemotactic properties to monocytes are known. Among these, monocyte chemotactic and activating factor (hereinafter referred to as "MCAF") also known as MCP-1 (monocyte chemoattractant protein-1) or GDCF (glioma-derived monocyte chemotactic factor), is a protein consisting of 76 amino acids, which has 4 cysteine residues. It is known that this protein has a strong chemotactic activity to monocytes and a strong monocyte-activating property.
Identification and gene cloning of MCAF, MCP-1 and GDCF are described in the following references: and reference: as MCAF, described in the References 1) and 2).
It is known that MCAF strongly attracts and activates monocytes, and uses exploiting immunopotentiation and anti-tumor properties are suggested in the above-mentioned references. Further, as a general concept, it is known that monocytes which have gathered in a wound play a role in the natural healing of the wound. However, it is not known that MCAF has an activity to directly promote therapy of wounds.
It is known that several proteinous growth factors promote healing of wounds. For example, growth factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor (TGF-.alpha., TGF-.beta.), platelet-derived growth factor (PDGF), endothelial cell growth factor (ECGF) and keratinocyte growth factor are expected to have therapeutic activities for wounds (Reference 6). (IL-1) has a therapeutic effect for wounds.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide a therapeutic agent for treating wounds, which does not employ the growth factors or proteins inducing growth factors, but has properties and actions totally different from these substances, and which has a strong therapeutic effect.
That is, the present invention provides a therapeutic agent for treating wounds comprising as an effective ingredient MCAF or a variant thereof having a monocyte-chemotactic activity or a derivative of MCAF or saidvariation thereof.
By the present invention, a useful therapeutic agent which promotes healing of wounds such as traumatic ulcers caused by burn, trauma, surgery and the like, and basic disorder ulcers caused by endogenous factors (digestive fluid) and the like was provided.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows tensile strengths of skin samples at 7 days after wounding;
FIG. 2 shows tensile strengths of skin samples at 14 days after wounding;
FIG. 3 shows therapeutic effects of MCAF for wounds in comparison with those by other growth factors; and
FIG. 4 shows therapeutic effects of MCAF for wounds.
BEST MODE FOR CARRYING OUT THE INVENTION
MCAF is a protein consisting of 76 amino acids, which attracts and activates monocytes, as described in the above-mentioned References 1) to 5). The amino acid sequence of MCAF is shown in SEQ ID NO. 1 in the Sequence Listing.
In the present invention, variants of MCAF, which substantially have the amino acid sequence of MCAF, and which attract and activate monocytes can also be used as the effective ingredient. Here, the term "variants of MCAF" means that it substantially has the amino acid sequence of MCAF, and the term includes those compounds in which amino acids in the amino acid sequence of MCAF are naturally or artificially deleted, added or substituted to the extent that the monocyte-attracting property of MCAF is not lost. Sequences in the N-terminal and C-terminal regions of naturally occurring and recombinant MCAF may vary (increase or decrease in amino acid residues) depending on the production conditions and these are included in the scope of the present invention. Further, in the present invention, derivatives obtained by chemically or biochemically modifying MCAF or the above-mentioned MCAF variants (e.g., those obtained by chemically linking polyethylene glycol or an analogue thereof; those obtained by attaching phosphate or sulfate groups; those treated w
REFERENCES:
patent: 5202118 (1993-04-01), Gillis et al.
Robinson et al. PNAS USA, 86, 1850-1854 (1989).
Matsushima Kouji
Naruto Masanobu
Schain Howard E.
Toray Industries Inc.
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