CONTROLLED RELEASE NASAL TESTOSTERONE GELS, METHODS AND PRE-FILLED MULTI-DOSE APPLICATOR SYSTEMS FOR PERNASAL ADMINISTRATION

The present invention relates to intranasal testosterone gels for the controlled release of testosterone into the systemic circulation of males and females for providing constant effective testosterone blood levels, without inducing undesired testosterone spike in blood levels, following pernasal administration. The intranasal testosterone gels of the present invention are safe, convenient to use, well tolerated, stable and easily and reproducibly manufactured on scale up. Moreover, because supra- normal and sub-normal testosterone blood levels are believed to be essentially kept to a minimum or avoided and the testosterone serum levels are believed to remain essentially constant during dose life, i.e., the intranasal testosterone gels of the present invention mimic or restore testosterone blood levels to normal physiologic daily rhythmic testosterone levels, the novel intranasal testosterone gels of the present invention are uniquely suited for testosterone replacement or supplemental therapy and effective for treating males diagnosed with, for example, male testosterone deficiency, such as, low sexual libido, low sexual drive, low sexual activity, low fertility, low spermatogenesis, aspermatogenesis, depression and/or hypogonadism, and females who are diagnosed with, for example, female sexual dysfunction, such as, low sexual libido, low sexual drive, low sexual activity, low amygdala reactivity, low sexual stimulation, hypoactive sexual desire disease ("HSDD"), female sexual arousal disorder and/or anorgasmia. The present invention also relates to methods and pre- filled multi-dose airless applicator systems for pernasal administration of the nasal testosterone gels of the present invention. L'invention concerne des gels intranasaux de testostérone permettant une libération prolongée de testostérone dans la circulation systémique d'hommes et de femmes pour obtenir des taux sanguins efficaces constants de testostérone, sans induire de pic de testostérone non voulu dans les taux sanguins suite à l'administration pernasale. Les gels intranasaux de testostérone selon l'invention sont sans danger, pratiques à utiliser, bien tolérés, stables et peuvent être fabriqués facilement et reproductible à grande échelle. En outre, puisque les taux sanguins de testostérone supra-normaux et sous-normaux sont supposés être sensiblement maintenus à un minimum ou empêchés, et que les taux sériques de testostérone sont supposés rester sensiblement constants pendant la vie d