Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1996-03-05
2000-08-15
Weber, Jon P.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 2, 530324, 530380, A61K 3804, A61K 3822, A61K 3836, C07K 14575, C07K 14745
Patent
active
061036919
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The invention relates to the utilization, sometimes referred to as utilisation of angiogenin and/or .alpha..sub.1 -microglobulin and/or complement factor D to inhibit or prevent the secretion of proteins. The invention further relates to a therapeutic agent for the abovementioned utilization, sometimes referred to as utilization.
BACKGROUND OF THE INVENTION
Leucocytes, particularly granulocytes, particularly after stimulation through non-physiological surfaces, by means of chemotaxins such as formylpeptides, complementary components, leucotrienes etc, secrete enzymes, particularly proteases, into their environment. These enzymes (collagenases and gelatinases), serve to enable passage of a cell through the tissue, the removal of destroyed tissue during wound healing, and the decomposition of penetrating foreign bodies. The proteolytic enzymes (collagenase, gelatinase, elastase, cathepsin G and B and others) are normally rapidly inhibited in their local effect by inhibitors (TIMP-1, TIMP-2, a-Proteinase inhibitor, .alpha..sub.1 -antichymotrypsin, cystatines, .alpha..sub.1 -macroglobulin and others) of the tissue, serum and blood plasma.
In the case of a massive leucocyte invasion as for example in reactions to inflammations, a condition may arise in which the local inhibitor potential insufficient and the excessive enzyme potential leads to considerable damage to the tissue naturally occurring in the body. Syndromes with such inflammatory derailments are for example emphysema of the lung, inflammatory rheumatoid arthritis, and lupus erythematodes among others. Also, however, haemodialysis in patients with chronic kidney insufficiency leads in the dialyser on the surface of the dialytic membrane to massive activation of the leucocytes with corresponding release of the named enzymes. The same occurs during extra-corporeal circulation in operations (e.g. on the open heart). The enzymes used then lead to considerable (up to 50%) proteolytic destruction of important blood plasma proteins (.sup..alpha..sub.1 -protease inhibitor, .sup..alpha..sub.1 -antichymotrypsin, C1-esterase inhibitor among others). Previous therapeutic action in the case of such inflammatory degenerative ailments, e.g. emphysema of the lungs, concentrated on reinstatement of the enzyme/inhibitor balance by therapeutic reinforcement of the inhibitor potential, e.g. infusion of corresponding enzyme inhibitors (Land, H. and Greiling, H. (Hrsg.) Pathobiochemie der Entzundung, Springer verlag, Berlin (1983)).
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a angiogenin (SEQ ID NO:4) used according to the invention.
FIGS. 2, 3 , and 4 show the protein inhibiting effect of angiogenin, .alpha..sub.1 -microglobulin, and complement factor D, respectively.
SUMMARY OF THE INVENTION
Proceeding from this basis, the purpose of the present invention is to indicate known and/or new active ingredients, which will prevent or at least severely limit the secretion of proteins, particularly enzymes, from leucocytes,
This purpose is fulfilled in that it is firstly proposed, in order to prevent or limit the secretion of proteins, to use materials with a secretion-inhibiting effect. Such materials were firstly discovered as blood plasma proteins, and identified with their novel method of operation. Among these are angiogenin and/or .alpha..sub.1 microglobulin and/or complement factor D or its fragments, or peptides with the biological effective sequential ranges of these peptides. The protection-inhibiting effect appears particularly clearly in the inhibition curves depicted in FIGS. 2 to 4 for the three proteins. There is simultaneously proposed a new therapeutic agent, as characterised in claims 3 to 8. The secondary claims reveal advantageous further developments.
It was surprisingly discovered that, by means of the use of angiogenin and/or .sup..alpha..sub.1 -microglobulin, and/or complement factor D and/or its fragments or peptides with the biologically effective sequential ranges of these peptides, the evacuation of the enzymes fr
REFERENCES:
Ngo et al. In: The Protein Folding Problem and Tertiary Structure Prediction Mioz et al (eds.) Birkhauser, Boston, pp. 433, 492-495.
Moore (1994) Trerd. Pharm. Sci 15: 124-129.
Mender (1986) PNAS 83: 1472-1475.
Hempelmann Ute
Tschesche Harald
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