(12) Patent Application Publication (10) Pub. No.: US 2009/0198145 A1 CHOW (43) Pub
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US 20090 198145A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0198145 A1 CHOW (43) Pub. Date: Aug. 6, 2009 (54) COMPOSITIONS, METHODS, AND SYSTEMS A 6LX 3/557 (2006.01) FOR RAPID INDUCTION AND A6II 3/4468 (2006.01) MAINTENANCE OF CONTINUOUS REM A 6LX 3/573 (2006.01) SLEEP A6II 3/478 (2006.01) A6IB5/0476 (2006.01) (76) Inventor: Harrison CHOW, Saratoga, CA A6IB 5/II (2006.01) (US) A6M 3L/00 (2006.01) Correspondence Address: (52) U.S. Cl. ......... 600/544; 514/731: 514/647: 514/400; LEVNE BAGADE HAN LLP 514/130: 514/2: 514/646; 514/626; 514/220; 2400 GENG ROAD, SUTE 120 514/329; 514/180: 514/397; 600/546; 600/595; PALO ALTO, CA 94.303 (US) 6O4/5OO (21) Appl. No.: 12/330,427 (57) ABSTRACT (22) Filed: Dec. 8, 2008 Compositions, kits, methods, and systems to induce, main tain, monitor, and interpret a continuous, un-fragmented Related U.S. Application Data REM sleep state in humans, generate dreams, recover sleep, create brain neuronal plasticity and activate the brain for (60) Provisional application No. 61/026,696, filed on Feb. cognition enhancement and mood stabilization are described. 6, 2008. If potentially combined with other medications, a platform is provided to develop new researchand therapies in many fields Publication Classification treating the human brain. The procedure reliably and quickly (51) Int. Cl. generates a Continuous REM Sleep cycle of pre-determined A6 IB5/0488 (2006.01) time or indefinite duration depending on therapeutic goals, A6 IK3I/05 (2006.01) allowing the patient to experience a qualitatively Superior A6 IK3I/35 (2006.01) dream sleep in a shortened period of time compared to a A6 IK 3/4164 (2006.01) natural sleep cycle. Profuse positive (pleasant) dreams are A6 IK3I/661 (2006.01) produced as well. REM sleep, dreams and sleep recovery can A6IP 25/00 (2006.01) be reliably generated, and various sleep, psychological and A6 IK 38/02 (2006.01) neurological illnesses and disorders can be treated or pre A6 IK3I/37 (2006.01) vented either solely by this method or in combination with A6 IK3I/I67 (2006.01) additional agents. DREAM MACHINE WITH "R" (REM) SENSOR Patent Application Publication Aug. 6, 2009 Sheet 1 of 7 US 2009/O1981.45 A1 Figure 1 Proposed Neuronal Mechanism of Activation for Continuous REM Sieep GABA-A Agoaist (propofol, arrestineties) REMi-O Netroits suppressed Riwi-O-N Sesos activated REM sieep and deans Patent Application Publication Aug. 6, 2009 Sheet 2 of 7 US 2009/O1981.45 A1 Figure 2 Flow Chart of Hypnotic Agent induction, Maintenance and Termination of Continuous REM Sleep Cycle Awake Subject GABA-A againist botas Aseep Subject, i.O.C. s. 60% (REMi-OFF Reurons suppressed) GABA-A agonist iafisie: * aduatict edicatiris Asleep Subject, 68%-LOC<88% {REM-ON eurons activated) CiABA-A age:histiafiasion Asleep Subject. 70%-I.OCs.88% {REM-ON eurors maintained active GABA-A agonist cessatio: Awake Sabject, OC -85% {REvi-QF aerons active) Patent Application Publication Aug. 6, 2009 Sheet 3 of 7 US 2009/O1981.45 A1 09 99 e?nu?IN09uogobesoqlogodoud-£aun61-I (6x01)aloÁOdeæISINEX,snonu?uo'o (seqnu?IN)au?1 o report f O O C. C. O O O c C CO C { C CO. N. CO () wi ve (fylfotu) effesocopodoid Patent Application Publication Aug. 6, 2009 Sheet 4 of 7 US 2009/O1981.45 A1 JO19A9"|---- (OOT)|6u?ung SnOnu??uOOg deeÍSWEx} e?oÁO e?nu?IN09uog96equeouedOOT-†7eun61 eloÁodeæISWExaesnonu?uo'o ssºusno?osuo.O|—/??????•………--%08• 09GG0?70€0||9 (segnu?IN)au?L. tiedle OOT }}}}}}}}}|%0 Patent Application Publication Aug. 6, 2009 Sheet 5 of 7 US 2009/O1981.45 A1 Patent Application Publication Aug. 6, 2009 Sheet 6 of 7 US 2009/O1981.45 A1 DREAM MACHINE WITH "R" (REM) SENSOR Patent Application Publication Aug. 6, 2009 Sheet 7 of 7 US 2009/O1981.45 A1 Figure 7 Flow Chart of Continuous REM Sleep Treatment. Using Cognition Enhancers or Neurologicai and Psychological disorders Awake patient with nelsiologicai (; psychologica disorder Continuous RENi Sieep induction REM-dependent reusal pathways activated Continuous REM Skeep maintenance Enhanced Reurona activity and synaptic efficacy Continuous REM Sleep mainterarce and added cognition enhancers Enhancerneat of anemory consolidation, estiniag, mood stabilization processes Continuous REM Sleep Ferminated Awake patient, assessment of memory, earning and nxod changes US 2009/O 1981.45 A1 Aug. 6, 2009 COMPOSITIONS, METHODS, AND SYSTEMS believed that continuous and un-fragmented REM sleep has FOR RAPID INDUCTION AND not previously been selectively induced or maintained using MAINTENANCE OF CONTINUOUS REM anesthetics or other pharmacological agents. SLEEP 0007 Stanford University psychiatrist and sleep researcher, Dr. William Dement, postulated that sleep can be CROSS-REFERENCE TO RELATED delayed for long periods of wakefulness but “sleep debt APPLICATIONS eventually needs to be “repaid” in equivalent linear amounts of sleep time in order to achieve psychological sleep recovery. 0001. This application claims the benefit of priority to However recent evidence suggests that REM sleep-rich naps U.S. Prov. Pat. App. 61/026,696 filed Feb. 6, 2008, which is may quickly provide sleep recovery and psychological ben incorporated herein by reference in its entirety. efits of sleep in a much shorter time. 0008. The mental and physical disruptions of poor sleep BACKGROUND OF THE INVENTION caused by sleep deprivation, stressors, or psychological dis turbances are well documented, and often lead to negative 0002 Sleep is postulated to be a state of natural rest and health, personal, and financial consequences. Acute and physiological recovery, and is seen in all mammals, and chronic sleep disturbances have been strongly implicated as a throughout the animal kingdom. Sleep in humans is charac causal factor in traffic and other operator-dependent acci terized by a reduction in voluntary body movement, dents, jet-lag, and decreased employee productivity; they decreased reaction to external stimuli, and loss of conscious may also play a significant role in illnesses connected to ness. Sleep has been implicated in learning, memory forma psychological conditions, including but not limited to post tion, cellular restoration, brain development, mood regulation traumatic stress disorder (PTSD), depression, anxiety disor and stress relief in humans. ders, and chronic pain. 0009 REM sleep disturbances have been documented as 0003. There are five internationally recognized stages of contributing to the psychological symptoms of sleepiness, sleep, as characterized by a sleeping individual's electroen memory loss, and mood instability associated with obstruc cephalogram (EEG). Non-rapid eye movement sleep tive sleep apnea, restless leg syndrome and anxiety disorders (NREM) ranges in sleep depth from Stage 1 (light sleep) such PTSD. Though the effects of REM sleep deprivation in through Stage 4 (deepest sleep). Stage 1 sleep is drowsiness, humans are still unclear, prolonged REM sleep deprivation in in which the EEG displays a lower voltage, more mixed animal populations has led to death. frequencies, and a deterioration of alpha rhythm, relative to 0010. The relationship of human cognition processes, the EEG exhibited when an individual is awake. In Stage 2, learning and memory, to sleep currently is of great interest to background activity similar to that of Stage 1 is experienced, researchers. Neurons in the brainstem, hippocampus, cortex, with slightly higher frequency 'sleep spindles' and sporadic and neocortex are thought to be active in storing and consoli higher amplitude of slow wave complexes. Stage 3 and Stage dating memories or learning during sleep. REM sleep, in 4 sleep, also known as slow wave sleep (SWS), display particular, is postulated to have a primary role in changes increasingly higher amplitude slow wave activity and are (plasticity) in the brain and the neuronal synaptic efficacy considered “deep sleep”. Typically, the vast majority of total involved in storing new memories from awake experiences, sleep time is spent in NREM sleep. Rapid eye movement consolidating, and re-consolidating old memories into stable (REM) sleep cycles are often brief and fragmented compared memories, and Supporting new learning. 0011 Current pharmaceutical development for learning to other sleep cycles with the majority of dreams occurring and memory therapy is mostly in investigative stages. Col during REM sleep. lectively, Such drugs or “cognition enhancers', to-date have 0004 Dreams have historically been a source of keen had limited if any demonstrated effectiveness in rehabilitat interest and inspiration in many human cultures and are ing degenerative memory and learning losses associated with thought to occur primarily during REM sleep. Dreams are Alzheimer's disease, senile dementia, Parkinson's, and defined as an experience involving a sequence of images, stroke. New directions, which may be further advanced by Sounds, ideas, emotions or other sensations occurring during this invention, involve altering the presence, concentration or sleep. efficacy of neurotransmitters (glutamate, serotonin, dopam 0005 REM sleep is characterized by high frequency, low ine etc) at specific receptors (NMDA/AMPA etc) at neuronal amplitude, desynchronized EEG waves, rapid ocular muscle synapses of neural networks of the brain affecting mood and movements and low muscle tone. The function of dreams cognition (memory and learning) processes. remain unclear with many researchers postulating that 0012 Current pharmacological sleep recovery therapy is dreams produced during REM sleep have a critical role in focused on using oral sedatives such as benzodiazepines (in neural processes involving learning, memory consolidation, cluding diazepam (e.g., VALIUM(R)) and cyclopyrrones (in and mood regulation. REM sleep is also considered funda cluding Zolpidem (e.g., AMBIENR)) to initiate or promote mental to providing sleep recovery and psychological rest. sleep cycle induction. The use of oral sedatives, however, may Neurologically, REM sleep originates from neurons in the be limited by rapid tolerance, abuse, and overdose potential.