Recent research has discovered the ubiquitous synthesis and use of nitric oxide (NO) throughout the biological systems of animals. For example, NO has been found to play a role in blood pressure regulation, blood clotting, neurotransmission, smooth muscle relaxation, and immune systems. For example, within the immune system, NO is believed both to inhibit key metabolic pathways, thereby inhibiting tumor growth, and to serve as an outright toxin that can be used to kill cells.
Furthermore, NO has been found to be a potent vasodilator within the bronchial circulation system of the lungs and is believed to play an important role in regulating pulmonary circulation. NO is also believed to relax the muscles within lung airways, thereby regulating breathing.
It is thus believed that the insufficient production of NO within various biological functions results in deleterious effects as manifested in various immune deficiencies, asthma, bacterial infections, impotence, and high blood pressure, to name a few. From a pharmacological standpoint, the delivery of NO to the body may serve as a remedy for ailments caused by the insufficient production of NO within the body.
Nitric oxide, however, as it is used within the enumerable biological functions of animals, is highly controlled and regulated because excess amounts of NO can be hazardous to living animals. For example, the introduction of NO into the blood stream can cause the irreversible lowering of blood pressure, ultimately leading to death. Thus, the introduction of NO into the body is not the simple solution to the effects caused by insufficient NO production within the body.
There are known pharmaceutical compositions capable of delivering NO. Namely, Keeffer et al, U.S. Pat. No. 5,039,705, teaches pharmaceutical compositions of the formula ##STR1## wherein R.sub.1 and R.sub.2 are independently chosen from straight chain and branched chain alkyl groups of 1 to 12 carbon atoms or benzyl, with the proviso that no branch occur on the alpha carbon of the alkyl groups, or R.sub.1 and R.sub.2 together with the nitrogen atom they are bonded to form a pyrrolidino, piperidino, piperazino or morpholino ring, M.sup.+x is a pharmaceutically acceptable cation, wherein x is the valence of the cation. Because this particular compound is a salt, the preferred method of administering this compound to animals is through injection into the bloodstream. It is also noteworthy that this particular compound is highly soluble in biological fluids thereby quickly releasing the NO which is loaded to the molecule.
Also, Keeffer et al, U.S. Pat. No. 5,366,997, teaches a similar pharmaceutical composition of the formula ##STR2## wherein R.sub.1 and R.sub.2 are independently chosen from C.sub.1-12 straight chain alkyl, C.sub.1-12 alkoxy or acyloxy substituted straight chain alkyl, C.sub.2-12 hydroxy or halo substituted straight chain alkyl, C.sub.3-12 branched chain alkyl, C.sub.3-12 hydroxy, halo, alkoxy, or acyloxy substituted branched chain alkyl, C.sub.3-12 straight olefinic and C.sub.3-12 branched chain olefinic which are unsubstituted or substituted with hydroxy, alkoxy, acyloxy, halo or benzyl. R.sub.1 and R.sub.2 can also comprise various heterocyclic ring molecules as described therein.
It should be appreciated that the molecules as taught by Keeffer et al are soluble within body fluids. Chemistry dictates as much, as do the teachings of Keeffer et al as it is recommended to administer these drugs intravenously. It should further be appreciated that upon the intravenous introduction of these chemicals to a living animal, NO will be introduced throughout the body as the soluble compound disseminates throughout the body. As discussed above, unwarranted or overexposure of NO can have many harmful effects on living animals.
Thus, there is a need for a pharmaceutical composition capable of the site specific delivery of NO within living animals.