Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1986-11-20
1990-09-18
Draper, Garnette
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 8, 514 21, 514 2, 530330, 530380, 530381, 530382, 530383, 530384, 530806, 530829, 435 13, C07K 510, C12Q 137, A61K 3718
Patent
active
049579037
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a solubilizable, fibrin based composition which is based on a specific combination of a certain fibrin derivative and a low molecular peptide containing a certain amino acid sequence. The peptide referred to has, surprisingly, proved to give a complete solubilization of said specific fibrin derivative, which opens completely new possibilities of using such a composition when assaying important fibrinolytic parameters, or at least drastically improves the opportunity to perform accurate and reproducible analyses within this field. Hence, the invention also relates to certain especially interesting applications or uses of said composition.
BACKGROUND OF THE INVENTION
Systematic studies in fibrinolysis (those own systems of the body which are involved in the solubilization of fibrin, the protein from which blood clots are built up) has been hampered by difficulties in manipulating its target substance, fibrin. For further information on the fibrinolytic system see Collen D, 1980, Thrombosis and heamostasis 43: 77-86. The possibilities of replacing, for a model purpose, fibrin, which spontaneously forms a gel, with more easily handled substances, such as casein or albumin, are limited. This is due to the fact that fibrin, except from being the target substance, also has important regulatory functions in the fibrinolytic system. These can not be replaced by model proteins.
The demand for a soluble and hence easily handled fibrin derivative is substantial. Therefore, considerable research efforts have been made in order to satisfy this demand. In 1955, Donelly et al described in Arch. Biochem. Biophys. 56: 369-387, how fibrin can be solubilized in 1 mole/l of NaBr at pH 5.3. Further, in 1976, it was described by Haverkate and Timan in Progress in Chemical Fibrinolysis and Thrombolysis 2: 67-71, that fibrin can be solubilized with 10 mole/l of acetic acid, while in 1982 Ranby et al described in Thrombosis Research 27: 743-749, the solubilization of desAA-fibrin in 3.5 mole/l of urea.
However, neither of these methods has been widely used which confirms that they are not fully satisfactory. Thus, the described methods cause denaturation of the fibrin, which is expressed as a tendency of the fibrin to form, after having been brought back to physiological conditions, a precipitate instead of a gel. Furthermore, the described compositions of soluble fibrin do not stand being frozen/thawed or lyophilized/reconstituted with preserved properties.
As concerns prior art reference is also made to Chem. Abstracts 98 (1983), 69 554, which discloses a retardation of the polymerization of desAA-fibrin and desAABB-fibrin in the presence of Gly-Pro-Arg. However, the present invention is based on the fact that it has very unexpectedly turned out that there is a special type of tetrapeptide which does not only retard but also completely and permanently prevents the polymerization of a certain type of fibrin, viz. desAA-fibrin. This prevention has made it possible to prepare a practical useful preparation of soluble fibrin and even to find completely new areas of applications.
Furthermore, Chem. Abstracts 99 (1983), 118 035, discloses that ".alpha.-chain peptide" inhibits the polymerization of "thrombin-induced fibrin", i.e. desAABB-fibrin. Thus, said article is not relevant in connection with the present invention, according to which the above-mentioned tetrapeptide forms in combination with desAA-fibrin a stable, non-polymerizing composition.
Chem. Abstracts 101 (1984), 106 025, merely discloses that Gly-Pro-Arg-Pro retards the fibrin polymerization by being bound to fibrinopeptide A. Thus, this article is not either relevant in connection with the present invention; see above with reference to C.A. 99 (1983), 118 035.
SUMMARY OF THE INVENTION
According to the present invention it has unexpectedly turned out that the addition of a low molecular weight peptide containing the specific amino acid sequence -L-prolyl-L-arginyl- to a certain fibrin derivative, namely desAA-fibrin,
REFERENCES:
patent: 3966701 (1976-06-01), Dorman et al.
patent: 4455290 (1984-06-01), Olexa et al.
Lewis et al., J. Biol. Chem., 260(18), 10192-9, (1985).
Hurlet-Jenson et al., Thrombosis Res., 27, 419-27, 1982.
Castellino et al., Ann., N.Y. Acad. Sci., 408, 595-601, (1983).
Furlan et al., Bioch. Biophys. Acta., 742, 25-32, (1983).
Laudano et al., P.N.A.S., 75(7), 3085-9, (1978).
Bale et al., P.N.A.S., 82, 1410-13, (Mar. 1985).
Weimer et al., Biol. Abs., 82(1): 1168, (1986 (Jul.)).
Belitser et al., Biokhymia, 50(8), 1336-41, (1985).
Ranby et al., Thromb. Res. 27, 743-9, (1982).
Laudano, Andrew P., and Doolittle, Russell F., Biochemistry 19, pp. 1013-1019 (1980).
Verheijen. J. H., Mullaart, E. et al., "A Simple, Sensitive Spectrophotometric Assay for Extrinsic (Tissue-Type) Plasminogen Activator Applicable to Measurements in Plasma", Thromb. Haemostas (Stuttgart) 48(3), 266-269 (1982).
Laudano et al., "Synthetic Peptides Modeled on Fibrin Polymerization Sites", Ann. N.Y. Acad. Sci. 408, pp. 315-329 (1983).
Chemical Abstracts vol. 98 (1983) Abstract No. 69 554, Biochyem. Biophys. Acta 1983, 742(1), 25-32.
Chemical Abstracts vol. 99 (1983), Abstract No. 118 035, Ann. N.Y., Acad. Sci. 1983, 408 (Mol. Biol. Fibrinogen Fibrin), 315-29.
Chemical Abstracts vol. 101 (1984), Abstract No. 106 025 Proc. Natl. Acad. Sci., U.S.A., 1984, 18 (14), 4339-42.
Chemical Abstracts vol. 88 (1983), Abstract No. 158 988a, Proc. Natl. Acad. Sci., U.S.A., 1978, 75(7), 3085-9.
Chemical Abstracts vol. 92 (1980), Abstract No. 125 912e, Biochemistry, 1980, 19(5), 1013-9.
Chemical Abstracts vol. 99 (1983) Abstract No. 118 035 Ann. N.Y., Acad. Sci., 1983, 408 (Mol. Biol. Fibrinogen Fibrin), 315-29.
Biopool International, Inc.
Draper Garnette
Kushan Jeff
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