SBIR-STTR Award

While standard oral sedative/soporific medication for treatment of insomnia and other sleep disorders is a multi-million dollar industry, substantial numbers of patients would be best managed via non-oral routes. This includes the very young or very old, those with protracted nausea due to pregnancy, chemotherapy, or other medical conditions, and those with oral intake restricted while they are awaiting surgery. In these settings it would also be of benefit to be able to interrupt dosing should untoward sensitivities or reactions occur. Melatonin is a natural human product, which is known to be involved in the regulation of sleep cycles and circadian rhythms. Oral melatonin is widely used over the counter in the belief that it can improve or shift sleep patterns. Studies confirm that melatonin can indeed have such effects. However, marketed oral forms of melatonin tend to be absorbed quickly and unreliably, and so fail to mimic the smooth nocturnal rise and fall of the natural melatonin cycle over a period of several hours. With its background in transdermal delivery, Biotek Inc, concluded that the natural melatonin cycle might be better simulated by transdermal delivery than by oral dosing. However, they recognized the need for therapeutic quantities of melatonin to be delivered through the skin from a patch of comfortable size. Melatonin has not been found to impair cognitive and motor functions, and administration of a natural hormone at physiologically normal levels should not evoke tolerance or pose a teratogenic risk. This project deals with a new and highly promising method for the transdermal administration of melatonin which should be able to achieve a dose profile more closely resembling the normal human nocturnal secretion pattern than oral dose forms. This method utilizes a new transdermal formulation discovered by Biotek that delivers melatonin through the skin much faster than previously investigated media, a delivery both non-oral and non-invasive.

BIOTEK has developed a transdermal melatonin formulation capable of producing flux levels high enough to allow a small patch to deliver a night-time melatonin pulse similar to that of healthy young adults. Such delivery should foster drowsiness, restful sleep, and alert waking more effectively than available oral dose forms and would also be more easily administered to impaired or uncooperative subjects. Because transdermal melatonin provides non-invasive delivery of a human hormone at natural levels, it should not lead to tolerance or harmful side effects. Transdermal melatonin may be of value to night shift workers, elderly individuals who lack an endogenous high-amplitude melatonin cycle, long distance air travelers, and those with sleep or seasonal affect disorders. In Phase I GMP patches were made and characterized, stability studies were initiated, a human Clinical Protocol was developed with the Brigham and Women's Sleep Center in Boston, MA, and a draft IND was prepared. Phase II will conduct a human clinical study aimed at establishing safety and testing efficacy under well-controlled conditions. PROPOSED COMMERCIAL APPLICATION: A melatonin patch should encourage development of transdermal systems for other cyclic hormones, leading to products capable of modifying or restoring other types of hormone-mediated behavior.

Thesaurus Terms:
hormone regulation /control mechanism, melatonin, sleep disorder, technology /technique development, transdermal drug delivery circadian rhythm, dosage, skin absorption, skin irritation /irritant, wakefulness clinical research, human subject