THE MAIN TEA ETA USA 20180169172A1EL MATTITAULI MALI MALTA ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0169172 A1 Kariman (43 ) Pub . Date : Jun . 21 , 2018 ( 54 ) COMPOUND AND METHOD FOR A61K 31/ 437 ( 2006 .01 ) REDUCING APPETITE , FATIGUE AND PAIN A61K 9 / 48 (2006 .01 ) (52 ) U . S . CI. (71 ) Applicant : Alexander Kariman , Rockville , MD CPC . .. .. .. .. A61K 36 / 74 (2013 .01 ) ; A61K 9 / 4825 (US ) (2013 . 01 ) ; A61K 31/ 437 ( 2013 . 01 ) ; A61K ( 72 ) Inventor: Alexander Kariman , Rockville , MD 31/ 4375 (2013 .01 ) (US ) ( 57 ) ABSTRACT The disclosed invention generally relates to pharmaceutical (21 ) Appl . No. : 15 /898 , 232 and nutraceutical compounds and methods for reducing appetite , muscle fatigue and spasticity , enhancing athletic ( 22 ) Filed : Feb . 16 , 2018 performance , and treating pain associated with cancer, trauma , medical procedure , and neurological diseases and Publication Classification disorders in subjects in need thereof. The disclosed inven ( 51 ) Int. Ci. tion further relates to Kratom compounds where said com A61K 36 / 74 ( 2006 .01 ) pound contains at least some pharmacologically inactive A61K 31/ 4375 ( 2006 .01 ) component. pronuPatent Applicationolan Publication manu saJun . decor21, 2018 deSheet les 1 of 5 US 2018 /0169172 A1 reta Mitragynine 7 -OM - nitragynine *** * *momoda W . 00 . Paynantheine Speciogynine **** * * * ! 1000 co Speclociliatine Corynartheidine Figure 1 Patent Application Publication Jun . 21, 2018 Sheet 2 of 5 US 2018 /0169172 A1 - + - + - + - - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + Akslaid REE 3 Elect . 1 . 2 . 2 . 1 . 1 . 2 .22 . 2 .22 . 2 . 474 . 4 . 4 . 4 . 4 . 4 . 4 4 . 4 . 4 . 4 . 4 . 4 . 4 . 4 4 . 4 4 . 4 . 4 . 4 4 . 4 4 . 4 . 4 . 4 . 4 4 . 4 . 4 . 4 4 . Mimaginile Axloesic antitussive , anidae 2010ergic , antimalanal Hayonchaine Smooth musclo iclaxor Speciogynine Smiooth tuscte relaxer - } { yd?XTítagne 25 Analgesic , antitussive , antidiarrhea Speciarilatine 4 Weak opioid agonist Nitroxylline < ix Vasodilator zatilaypertensive , muscle relaxer , diuretic antiamesic , W unostimulant anti- lendemic Isontitnap?ylline * 21 stivuiant, unti laukerfic Speciophylline * ????{{ ?? Rhynchophyllite * Vasodilator antihypertensive, calcium channelblocker , antiagregant, anti- iffamatory , antipyretic . anti - arrhythmic , antithelinuntio Isorbiyachapisyiline K1X Nunostimulant Ajmalicine Cerebrocirculant, antiaggregant, ni- adrenergie sedative anticonvulsant smooth muscle relaxer Corynantheidine 171 1 ?gin CorynoxiBe * I Calcium chanel blocker, anti - locomotive Corynoxiße & < x Arb - focomotiva Mitzoliac < 1 % somitrafolne Oxindala A Oxindole B Søeciofolint Analgesic , antitussive 130 pectofoline Olispizviline Kik Analyesic , antitussive Miscillatina Mitragynaline < 1 % Mtazy13 !inte acid Colynantheidzlinic acid Figure 2 Patent Application Publication Jun . 21, 2018 Sheet 3 of 5 US 2018 / 0169172 A1 PercentageofMitragyninereleased(%) m momoon ?? momotionation … … egggggg , , , , , , ??? : :4 4 : / / tit* #* # * # * #* # * #* -* - * -* - *- * -* - * -* -* - *- * -* - *- * -* - *- * -* - * | ??????? Figure 3 Patent Application Publication Jun . 21, 2018 Sheet 4 of 5 US 2018 /0169172 A1 8 8 * Concentration(ng/mL) 8*. 8 $ 8 KY 11 , 9 . irror 15 * 20 * 28 Time (hours ) * * * Concentration(ng/mL) " . : : * * * *. * . *. * . *. * . *. * . * * * * * * ** * * ** * * m . * * * * ** * * * * ** * * * * * * 177 DO ????????? ???? ?? ?? ? ? ? ?? ? ? ? ?? ? ? ? ? ? ?? ? ? ? ?? ? ?? ? ? ? ?? ? ? ? ?? ?10 ?? ? ? ? ?? ? ? ? ?? ? ?? ? ? ? ? ? ? ?? ? ? ? ?? 15 ? ? ? ?? ? ?? ? ? ? ?? ? ? ? ?? ? ?? ? ? ?? ?20 ? ? ? ? ?? ? ? ? ?? ? ? ? ? ? ? ?? ? ? ? ?? ? ?25 ??? Time (hours ) Figure 4 Patent Application Publication Jun . 21, 2018 Sheet 5 of 5 US 2018 /0169172 A1 Semach . : : : : . mostra 200 mgmitragynine 6 mg 7- hydroxymitragynine Lipid carrier 10 % > Other alkaloids and Soft gelatin capsule substances Figure 5 US 2018 /0169172 A1 Jun . 21, 2018 COMPOUND AND METHOD FOR erative diseases and disorders ; pain associated with cancer ; REDUCING APPETITE , FATIGUE AND PAIN trauma; athletic performance ; migraine ; surgical interven tion or medical treatment; stroke ; heart attack ; dental- related FIELD OF THE INVENTION pain ; abdominal pain ; bone pain , muscle pain ; neurological pain ; stomach ulcers - related pain ; gallbladder disease - re [0001 ] The present invention relates to pharmaceutical lated pain ; Central Pain Syndrome; chronic pain disorder and nutraceutical compounds and methods for reducing (nociceptive pain , neuropathic pain , chronic back or leg appetite , muscle fatigue and spasticity , enhancing athletic pain , painful neuropathies, Complex Regional Pain Syn performance, and treating pain associated with cancer , drome ) , and acute pain . trauma, medical procedure , and neurological diseases and [ 0006 ] The principal mechanism of Kratom ' s psychoac disorders in subjects in need thereof. tive action involves mu -opioid receptor partial agonism , and to a lesser extent, kappa - opioid receptor antagonism rela BACKGROUND OF THE INVENTION tively analogous to the drug buprenorphine . Other, less 10002 ] Mitragyna speciose (Kratom ) is an evergreen tree prominent, mechanisms of Kratom ' s action include : delta of the coffee (Rubiaceae ) family native to Indonesia , Malay opioid receptor antagonism , alpha - 2 receptor agonism , sia , Myanmar, Papua New Guinea , Indonesia , and Thailand . 5 -HT2A receptor antagonism , and adenosine A2A receptor It is best known for generating leaves that contain more than antagonism . Due to the aforesaid pharmacodynamics , when 40 distinct psychoactive compounds. Mitragyna speciosa ingested , most individuals report opioidergic and /or stimu plant is a 4 to 16 -meter -high tropical tree indigenous to latory effects . South East Asia but now cultivated elsewhere. In Thailand , [0007 ] The disclosed invention finds that a number of the tree and leaf - preparations from it are called Kratom . alkaloids contained in a Mitragyna speciosa plant could be Traditionally , fresh or dried Kratom leaves are chewed or used as a substitute for morphine , and have a potent anal made into a tea ; they are seldom smoked . At a low dose , gesic action . Mitragynine and 7 -hydroxymitragynine are the Kratom has stimulant effects and is used to combat fatigue two alkaloids mainly responsible for the analgesic effects . during long working hours . At high dosages , however , it has They are selective and full agonists of the u - subtype opioid sedative -narcotic effect . It is also used in traditional medi receptor (MOR ). In mice , 7 -hydroxymitragynine was sev cine and as an opium substitute . eral times more potent analgesic than morphine even upon [0003 ] As already mentioned , the phytochemicals isolated oral administration . The receptor agonist effect of Kratom from various parts of the tree include over 40 structurally alkaloids is antagonized by the opioid receptor antagonist related alkaloids as well as several flavonoids , terpenoid naloxone. In addition , 5 -HT2a and postsynaptic a2 -adren saponins , polyphenols , and various glycosides . The main ergic receptors , as well as neuronal Ca2 + channels are also psychoactive components in the leaves are mitragynine and involved in the unique pharmacological and behavioral 7 - hydroxymitragynine , both found only in Mitragyna spe activity of mitragynine . ciose . Kartom contains other central nervous system stimu [ 0008 ] In addition , the antinociceptive and cough - suppres lants and depressants that can act upon a variety of neu sant effects of mitragynine were comparable to those of rotransmitter systems within the human brain . As already codeine in animal studies . It has been reported that a mentioned , it has traditionally been consumed as a leaves methanol extract of Kratom leaf and a major alkaloid , decoction for its stimulant effects to counter fatigue , treat mitragynine, produced skeletal muscle relaxation . Thus, fever , diarrhea , as well as anesthetic , antinociceptive, anal mitragynine also has a direct effect on skeletal muscle by gesic and stimulating effects that help to combat fatigue and decreasing the muscle twitch . More so , Chittrakarn et al . suppress appetite . ( 2010 ) , report that Kratom extract had a greater effect at the [ 0004 ). This invention generally relates to pharmaceutical neuromuscular junction than on the skeletal muscle or compounds and methods for reducing appetite , muscle somatic nerve . It is possible that alkaloid components of the fatigue and spasticity , enhancing athletic performance , and Kratom extract other than , and including mitragynine , may treating pain associated with cancer, trauma, medical pro influence the compound action potential as provided below . cedure , and neurological diseases and disorders in subjects 10009 ) The concentration percentages shown below , and in need thereof, as well as a method of administering the potential activity effects are compiled from several therapeutically - effective amount