Methods for coating invasive devices with inhibitors of thrombin

Details Methods for coating invasive devices with inhibitors of thrombin Methods for coating invasive devices with inhibitors of thrombin

1995-05-02

1996-05-07

Lusignan, Michael

Coating processes

Medical or dental purpose product; parts; subcombinations;...

Implantable permanent prosthesis

424 169, 427 23, 514 18, 530330, A01N 102

Patent

active

055144098

ABSTRACT:
This invention relates to coating invasive devies with novel biologically active molecules which bind to and inhibit thrombin. These molecules comprise a catalytic site directed moiety (CSDM) of the formula: ##STR1## wherein X is hydrogen or is characterized by a backbone chain consisting of from 1 to 100 atoms; R.sub.1 is selected from the group consisting of unsubstituted, mono-substituted, di-substituted and tri-substituted saturated ring structures; R.sub.2 is a bond or is characterized by a backbone chain consisting of from 1 to 5 atoms; R.sub.3 is a bond or is characterized by a backbone chain consisting of from 1 to 3 atoms; R.sub.4 is any amino acid; R.sub.5 is any L-amino acid which comprises a guanidinium- or amino-containing side chain group; R.sub.6 is a non-amide bond; and Y is characterized by a backbone chain consisting of from 1 to 9 atoms; or the formula: ##STR2## wherein R.sub.1 ' is selected from the group consisting of unsubstituted, mono-substituted, di-substituted and tri-substituted ring structures; R.sub.4 ' is any amino acid comprising a side chain group characterized by the capacity to accept a hydrogen bond at a pH of between about 5.5 and 9.5; and X, R.sub.2, R.sub.3, R.sub.5, R.sub.6 and Y are defined as above. Preferred thrombin inhibitors are further characterized by a anion binding exosite associating domain (ABEAM) and a linker portion of between 18 .ANG. and 42 .ANG. in length which connects the Y to the ABEAM.

REFERENCES:
patent: 4971953 (1990-11-01), Krstenansky
patent: 5240913 (1993-08-01), Maraganore et al.
patent: 5425936 (1995-06-01), Maraganore et al.

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