THETWO TONTTITUNTIVIUS 20180264013A1 DA TI ON AND MAIN ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0264013 A1 DILL ( 43 ) Pub . Date : Sep . 20 , 2018 ( 54 ) COMPOSITION AND METHODS FOR Publication Classification TREATING SLEEP DISORDERS (51 ) Int. CI. A61K 31 /60 (2006 . 01 ) ( 71 ) Applicant: WELLESLEY A61K 31 / 4025 ( 2006 .01 ) PHARMACEUTICALS , LLC , A61K 45 / 06 ( 2006 .01 ) Newtown , PA (US ) A61K 31 /616 ( 2006 . 01 ) A61K 31/ 4725 ( 2006 . 01 ) (72 ) Inventor : David A . DILL , Newtown , PA (US ) A61K 31 / 46 (2006 .01 ) A61K 31/ 405 ( 2006 .01 ) A61K 9 / 00 ( 2006 .01 ) (21 ) Appl. No. : 15 /985 ,315 A61K 31 /216 ( 2006 . 01 ) A61K 31 / 192 (2006 . 01 ) ( 22 ) Filed : May 21 , 2018 A61K 31 / 19 ( 2006 .01 ) A61K 31 / 167 (2006 . 01 ) A61K 31 / 12 ( 2006 .01 ) Related U . S . Application Data (52 ) U . S . CI. @(63 ) Continuation - in -part of application No. 14 / 172, 649 , CPC . .. .. A61K 31 /60 (2013 . 01 ) ; A61K 31 /4025 filed on Feb . 4 , 2014 , which is a continuation of ( 2013 .01 ) ; A61K 45 / 06 ( 2013 .01 ) ; A61K application No . 13 / 847 , 927 , filed on Mar. 20 , 2013 , 31 /616 ( 2013 . 01 ) ; A61K 31 /4725 ( 2013 .01 ) ; now Pat . No . 8 ,685 , 453 , which is a continuation of A61K 31/ 46 ( 2013 .01 ) ; A61K 2300 /00 application No. 13 / 560 ,607 , filed on Jul. 27 , 2012 , ( 2013 .01 ) ; A61K 9 /0002 ( 2013 . 01 ) ; A61K now Pat. No. 8 ,445 , 015 , which is a continuation of 31 / 216 ( 2013 .01 ) ; A61K 31/ 192 ( 2013 . 01 ) ; application No. 13 / 487, 348 , filed on Jun . 4 , 2012 , A61K 31/ 19 ( 2013 .01 ) ; A61K 31/ 167 now abandoned , which is a continuation - in -part of (2013 .01 ) ; A61K 31/ 12 ( 2013 .01 ) ; A61K application No . 13 /424 ,000 , filed on Mar. 19 , 2012 , 31/ 405 (2013 .01 ) now Pat. No. 8 , 236 ,857 , which is a continuation - in (57 ) ABSTRACT part of application No . 13 / 343, 332 , filed on Jan . 4 , A method for treating sleep disorders includes the step of 2012 , now abandoned , which is a continuation of administering to a subject in need therefor a pharmaceutical application No . 12 /956 ,634 , filed on Nov . 30 , 2010 , composition comprising one or more analgesic agents . Also now abandoned . disclosed is a pharmaceutical composition for treating sleep (60 ) Provisional application No . 61 / 362, 374 , filed on Jul. disorders . The pharmaceutical composition comprises one 8 , 2010 . or more analgesic agents and an anti- insomnia agent. Patent Application Publication Sep . 20 , 2018 US 2018 / 0264013 A1 00005.0 wenye 0005.0 005.0 LPSNSAID+ wawatu DoseofNSAID (5000-0.00005um) FIG.1B kamiliki Aspirin -ibuprofen Naproxen -0Acetaminophen www. * * 1 ww. www.w 00005.0 www. 0005.0 Aspirin osmos(Ep45???* -0Acetaminophen -Naproxen com DoseofNSAID (5000-0.00005uM) FIG.1A NSAIDalone www . 8 0 NSAID without control of Percent( cells + CD80 + CD40 US 2018 /0264013 A1 Sep . 20 , 2018 COMPOSITION AND METHODS FOR gesics , wherein each of the one or more analgesics is TREATING SLEEP DISORDERS administered in an amount of 5 mg to 2000 mg. [0008 ] Another aspect of the present application relates to [ 0001 ] This application is a continuation - in - part of U . S . a pharmaceutical composition for treating a sleep disorder, patent application Ser . No. 14 /172 ,649 , filed Feb . 4 , 2014 , comprising one or more analgesics , an anti - insomnia agent which is a continuation application of U . S . patent applica and a pharmaceutically acceptable carrier . In some embodi tion Ser . No. 13 /847 , 927 , filed on Mar . 20 , 2013 , now U . S . ments, the one or more analgesics comprise acetaminophen Pat . No . 8 ,685 , 453 , which is a continuation application of and ibuprofen , and the pharmaceutical composition is for U . S . patent application Ser . No. 13 / 560 ,607 , filed on Jul. 27 , 2012 , now U . S . Pat . No. 8 ,445 ,015 , which is a continuation mulated in the form of an orally disintegrating tablet application of U . S . patent application Ser. No . 13 /487 , 348 , filed Jun . 4 , 2012 , which is a continuation - in -part applica BRIEF DESCRIPTION OF DRAWINGS tion of U . S . patent application Ser . No . 13 / 424 , 000 , filed [0009 ] FIGS. 1A and 1B are diagrams showing that anal Mar. 19 . 2012 . now U . S . Pat . No . 8 , 236 ,857 , which is a gesics regulate expression of co - stimulatory molecules by continuation - in - part application of U . S . patent application Raw 264 macrophage cells in the absence (FIG . 1A ) or Ser. No . 13 / 343 , 332 , filed on Jan . 4 , 2012 , which is a presence (FIG . 1B ) of LPS . Cells were cultures for 24 hrs in continuation - in -part application of U . S . patent application the presence of analgesic alone or together with Salmonella Ser. No . 12 /956 ,634 , filed on Nov . 30 , 2010 , which claims typhimurium LPS ( 0 . 05 ug /ml ) . Results are mean relative % priority to 61/ 362 ,374 filed on Jul. 8 , 2010 . The entirety of of CD40 + CD80 + cells. the aforementioned applications are incorporated herein by reference . DETAILED DESCRIPTION [ 0010 ] The following detailed description is presented to FIELD enable any person skilled in the art to make and use the invention . For purposes of explanation , specific nomencla [0002 ] The present application generally relates to meth ture is set forth to provide a thorough understanding of the ods and compositions for the treatment of sleep disorders . present invention . However , it will be apparent to one skilled in the art that these specific details are not required to BACKGROUND practice the invention . Descriptions of specific applications 0003 ] Sleep disorders , such as insomnia , are common are provided only as representative examples. The present sleep problems that affect hundreds of millions of people . invention is not intended to be limited to the embodiments People with insomnia usually experience one or more of the shown, but is to be accorded the broadest possible scope following symptoms: fatigue, low energy , difficulty concen consistent with the principles and features disclosed herein . trating , mood disturbances , depression , and decreased per formance in work or at school. Method for Treating Sleep Disorders [0004 ] Medical literature has recognized four types of [ 0011 ] One aspect of the present application relates to a insomnia , including sleep onset insomnia ( e . g . , trouble fall method for treating sleep disorders or otherwise improving ing asleep at bedtime) , sleep maintenance insomnia ( e . g ., quality of sleep . The method comprises the step of admin disturbed sleep during the night ) , early morning awakening , istering to a person in need thereof an effective amount of a and transient insomnia ( e . g . , new environment, first night in pharmaceutical composition comprising one or more anal hotel syndrome) . Other types of insomnia include “ middle gesic agents . In some embodiments , the pharmaceutical of - the - night” insomnia , “ late night” insomnia , “ prolonged composition further comprises one or more active agents awakening after sleep onset ” insomnia , “ sleep maintenance " selected from the group consisting of anti - insomnia agents , insomnia , and insomnia that follows after “ middle -of - the antimuscarinic agents , antidiuretic agents , spasmolytics , night” awakening , each of which has a component of a - blockers , 5a - reductase inhibitors , phosphodiesterase type interrupted sleep . 5 ( PDE5 ) inhibitors and prostaglandin (PD ) pathway inhibi [ 0005 ] Currently available treatments for insomnia have tors In some embodiments , the sleeping disorder is insom side effects and their effectiveness may decrease over time. nia . In some embodiments , the pharmaceutical composition Accordingly , there exists a continued need for new drug comprises acetaminophen and ibuprofen . compositions and methods for treating insomnia . [0012 ] The pharmaceutical composition may be adminis tered via systemic administration or topical administration . SUMMARY Systemic administration includes oral administration and parenteral ( including subcutaneous ( subQ or SC ) , intramus [0006 ] One aspect of the present application relates to a cular ( IM ) , intraperitoneal ( IP ) , intravenous ( IV ) , intrathe method for treating a sleep disorder , comprising: adminis cal, intraventricular, etc . ) administration . Topical adminis tering to a subject in need thereof an effective amount of a tration includes administration to dermal and mucosal pharmaceutical composition comprising one or more anal tissues , such as transdermal administration , nasal adminis gesics, wherein the one or more analgesics are formulated in tration , buccal administration , and pulmonary administra an immediate - release formulation or a controlled - release tion . In some embodiments , the pharmaceutical composition formulation . In some embodiments , the sleep disorder is is administered by orally administration . In other embodi insomnia . ments , the pharmaceutical composition is administered by [ 0007 ] Another aspect of the present application relates to transdermal administration . a method for treating insomnia , comprising: administering [0013 ] As used herein , the term “ sleep disorder” refers to to a subject in need thereof an effective amount of a problems with the quality , timing and amount of sleep , pharmaceutical composition comprising one or more anal which cause problems with functioning and distress during US 2018 /0264013 A1 Sep . 20 , 2018 the daytime . There is a variety of different types of sleep cyclobarbital, pentobarbital,