Compositions and their use to treat complications of aneurysmal subarachnoid hemorrhage

#The present invention relates to a system for therapeutic agents delivered locally to the cerebral arteries to prevent or reduce the incidence or severity of adverse consequences of subarachnoid hemorrhage (SAH) resulting from a disease, disorder, condition, or injury.

#1. Central Nervous System

#The central nervous system is a bilateral and essentially symmetrical structure with seven main parts: the spinal cord, medulla oblongata, pons, cerebellum, midbrain, diencephalon, and the cerebral hemispheres. FIG. 1 shows a lateral view of the human brain from Stedman's Medical Dictionary, 27th Edition, plate 7 at A7 (2000).

#FIG. 1 shows an illustrative lateral view of the human brain (Stedman's Medical Dictionary, 27th Edition, plate 7 at A7 (2000)).

#FIG. 2 shows an illustrative sagittal view of the human brain (Correlative Neuroanatomy & Functional Neurology, 18th Ed., p. 46 (1982)).

#FIG. 3 shows an illustrative view of a cross section of the intact meninges from the inner surface of the skull (upper) to the external surface of the brain (lower). Collagen is present in the periosteal and meningeal dura (large dots, orientation of fibrils not indicated) and in the subarachnoid space (SAS), usually in folds of trabecular cells. The dural border cell layer has no extracellular collagen, few cell junctions, enlarged extracellular spaces (but no basement membrane), and fibroblasts that are distinct from those of the outer portions of the dura. The arachnoid barrier cell layer has essentially no extracellular space, numerous cell junctions, more plump appearing cells, and a comparatively continuous basement membrane on its surface toward the SAS. Note the continuity of cell layers from the arachnoid to the dura (no intervening space), the characteristic appearance of the arachnoid trabeculae, and the relationship of the pia (from Haines D E: On the question of subdural space. Anat Rec 230:3-21, 1991).

#The term “active” as used herein refers to the ingredient, component or constituent of the composition of the present invention responsible for the intended therapeutic effect.

#The terms “acute lethal dose” or “LD50” as used herein refers to the amount of a drug that when administered kills 50% of subjects.

#The term “additive effect”, as used herein, refers to a combined effect of two chemicals that is equal to the sum of the effect of each agent given alone.