The development of allergy in a patient is a complex process. Allergic responses may be effected by antibodymediated (immediate) hypersensitivity, or cell-mediated (delayed) hypersensitivity or a combination of both. Immediate type, or Type I, hypersensitivity reactions result when immunologlobulin E ("IgE") antibodies bind to mast cells or basophils and an allergan (or antigen) binds to that antibody, thus perturbing the cell membrane and triggering a calcium ion influx across the membrane. Microtubule formation and movement of granules to the cell membrane leads to fusion of granule and plasma membrane (degranulation) and release of granule-associated mediators into the intercellular space.
Changes in the cell membrane associated with cell activation, i.e., the calcium influx, activates mast cells both to degranulate and to activate phospholipase A, in parallel. Degranulation releases histamines and hydrolytic enzymes into the system. Activated phospholipase A.sub.2 hydrolyzes free arachidonic acid, a fatty acid, which then acts as a substrate for two enzyme systems which form the mediators; for example, leukotrienes and prostaglanins. Prostaglandin A.sub.2 and thromboxane A.sub.2 (cyclo-oxygenase pathway), and SRS (which is leukotriene LTC.sub.4 +LTD.sub.4) and chemotactic LTB.sub.4 (lipoxygenase pathway) are among the newly synthesized products which result from the metabolysis of the acid. An alternative route independent of phospholipase A.sub.2 is believed to lead to the production of histamine, proteolytic enzymes, heparin and chemotactic factors. Of the products of these processes, at least histamine and/or leukotrienes are believed to mediate allergic diseases 5-lipoxygenase acts as a catalyst in the hydrolysis of aracidonic acid to form leukotrienes. Leukotrienes are mediators which are far more active than histamine or prostaglandins. These mediators have potent contractile effects on the respiratory tract. Sneezing and respiratory problems are caused by contractions of smooth muscle of the respiratory tract. Other symptoms are a result of inflammation caused by increased vascular permeability and the attraction of leukocytes. The metabolism of arachidonic acid has been suggested as part of the mechanism of other diseases, i e., rheumatism and psoriasis. 5-lipoxygenase activity may affect these conditions, as well as inflammatory responses.
Allergies have typically been treated by a variety of chemical agents directed toward counteracting their symptoms. Such treatments have only short-term utility and are often accompanied by adverse reactions. For example, antihistamines are often used to alleviate temporarily the general discomfort caused by histamine release. Such drugs, however, cause drowsiness and therefore are often not recommended. Corticosteroids are also used to treat severe allergic reactions. However, these compounds immunosuppress the patient and thereby increase susceptibility to infectious disease. Inhaled salbutamol (or albuterol) is commonly used by asthma patients. However, like other symphathomimetic agents, salbutamol can cause side reactions such as hypertension, angina, vomiting, vertigo, and insomnia.
In view of the disadvantatges of such prior allergy treatments, conventional means for treating allergies remain disappointing to the patient, as well as to the clinician. Therefore, the need exists for a process which avoids these disadvantages and provides effective treatment for allergies, as well as other conditions which result from the metabolism of arachidonic acid.
USPTO Backgrounds
USPTO Backgrounds