Bioassay for thrombogenesis and rabbit model
AssigneeImmuno Aktiengesellschaft
InventorsJohann J. Eibl, Hans P. Schwarz, Ludwig Pichler
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Abstract
An in vivo assay for determining the potential thrombogenic activity of a test compound entails pre-treating an animal with both a hepatoxin and either a bacterial agent (whole bacteria or bacterial toxins, including endotoxins) or a bacterial agent-induced cytokine, which pre-treatment enhances sensitivity to thrombogenic substances. The sensitized animal can be used in identifying a thrombogenic substance even when it is a weak potentiator of thrombogenesis, and in detecting smaller amounts of a strong potentiator.
Claims14
An in vivo stasis assay method for detection of thrombogenic activity of a composition, comprising the steps of (A) injecting into a rabbit (i) a first compound that is a hepatoxin and (ii) a second compound that is an endotoxin, wherein said first compound and said second compound sensitize said animal to thrombogenesis without causing thrombogenesis;
- (B) injecting said composition into said rabbit;
- then (C) restricting flow through a circulatory vessel in said rabbit such that a volume of blood is isolated within a delimited portion of said vessel;
- and thereafter (D) determining the extent of thrombogenesis within said delimited portion of said vessel based upon an evaluation of visible thrombi.
A stasis rabbit model for detecting thrombogenic activity of a compound, comprising a rabbit that has been injected with effective amounts of a hepatoxin and an endotoxin to increase susceptibility of said rabbit to thrombogenesis without causing thrombogenesis.
A kit for in vivo detection of thrombogenic activity of a compound by a stasis rabbit model, comprising a first receptacle containing a hepatoxin, a second receptacle containing an endotoxin and a third receptacle containing a labeled thrombophilic substance, wherein said hepatoxin, said endotoxin and said thrombophilic substance can be injected into a rabbit to increase the susceptibility of said rabbit to thrombogenesis without causing thrombogenesis.
Dependencies are inferred from the claim text.