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US 2019 / 0216870 A1 Witowski Et Al US 20190216870A1 ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 / 0216870 A1 Witowski et al. ( 43 ) Pub . Date: Jul. 18 , 2019 ( 54 ) ENCAPSULATED CANNABINOID A61K 9 / 107 ( 2006 .01 ) FORMULATIONS FOR TRANSDERMAL A61K 9 /00 (2006 . 01) DELIVERY (52 ) U .S . CI. CPC . .. .. .. A61K 36 / 185 (2013 .01 ) ; A61K 9 / 0014 (71 ) Applicant: Nutrae , LLC , Sarasota , FL (US ) (2013 .01 ) ; A61K 9 / 1075 (2013 .01 ) ; A61K ( 72 ) Inventors : Christopher G . Witowski, Tampa , FL 9 / 7084 ( 2013 . 01) (US ) ; Jacqueline L . Salm , Tampa, FL ( US ) (57 ) ABSTRACT ( 73 ) Assignee : Nutrae , LLC , Sarasota , FL (US ) Preparation of cannabinoid formulations containing: 19 - tet ( 21 ) Appl. No. : 16 / 246, 411 rahydrocannabinol (49 - THC ) , A8 - tetrahydrocannabinol ( A8 - THC ) , A9 - tetrahydrocannabinolic acid ( THCa ) , canna (22 ) Filed : Jan . 11 , 2019 bidiol (CBD ) , cannabidiolic acid (CBDa ) , cannabigerol Related U . S . Application Data (CBG ) , cannabichromene (CBC ) and cannabinol (CBN ) , either alone or in combinations henceforth known as can (60 ) Provisional application No. 62 /617 ,003 , filed on Jan . nabis , have been created using an emulsification process to 12 , 2018 . encapsulate cannabinoids . The aqueous -based method involves micellular encapsulation of cannabinoids, a method Publication Classification that has been used to increase the bioavailability of poorly ( 51 ) Int. Cl. permeable , lipophilic drugs . The present invention demon A61K 36 / 185 (2006 .01 ) strates the viability of transdermal delivery with gels and A61K 9 / 70 ( 2006 .01 ) patches for consistent and sustained cannabinoid dosing . Permeability(*1045cm/hr) + . + . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . + . + . 50 100 150 200 250 Time (hrs ) Patent Application Publication Jul. 18 , 2019 Sheet 1 of 6 US 2019 / 0216870 A1 FIG.1 ce Patent Application Publication Jul. 18 , 2019 Sheet 2 of 6 US 2019 / 0216870 A1 CBDTransdermal FIG.2 Topical/TransdermalComparison *MembraneRetentionReceiverPermeability 11111111111111 424444444444444444444444444444444444444444444 12.00 Patent Application Publication Jul. 18 , 2019 Sheet 3 of 6 US 2019 / 0216870 A1 . )w/ingredient%(Active .191421111 .41 FIG.3 CBDOTHC . 80%70% ) 4 ( Efficiency Encapsulation Patent Application Publication Jul. 18 , 2019 Sheet 4 of 6 US 2019 / 0216870 A1 408 402 407 403 V 401 404 406 409 FIG.4B FIG.4A 405 407 Patent Application Publication Jul. 18 , 2019 Sheet 5 of 6 US 2019 / 0216870 A1 . www . * . * . ($Ju)aw . SDI . ms . " Patent Application Publication Jul. 18 , 2019 Sheet 6 of 6 US 2019 / 0216870 A1 . ActiveIngredient. FIG.6 CBD ) %( Efficiency Encapsulation US 2019 /0216870 A1 Jul. 18 , 2019 ENCAPSULATED CANNABINOID [0007 ] It is well known in cosmeceutical and pharmaceu FORMULATIONS FOR TRANSDERMAL tical preparations that above the critical micelle concentra DELIVERY tion of one or more surfactants that micelles will be formed during emulsification . The micelles can take many shapes CROSS -REFERENCE TO RELATED ( spherical, cylinders , or other arrangements ) , structures ( uni APPLICATIONS lamellar or multilamellar ) , and names ( liposomes , niosomes , and ethosomes among others ) . Various reports have con [ 0001] This application claims priority to U . S . Provisional cluded that these micelles can also be used to encapsulate Patent Application Ser. No . 62/ 617 , 003 , filed on Jan . 12 , active ingredients for delivery of pharmaceuticals (Hung et 2018 , entitled “ ENCAPSULATED CANNABINOID FOR al. 2001; Narang et al . 2007 : Kwon , 2012 ) as well as MULATIONS ” of which is hereby incorporated herein by increase the bioavailability of drugs with poor water solu reference in their entirety for all purposes . bility (Keller et al. 1999 ; Touitou et al. 2000 ; O 'Driscoll et [0002 ] This application includes material that is subject to al. 2008 ) . copyright protection . The copyright owner has no objection [0008 ] Transdermal delivery allows for direct absorption to the facsimile reproduction by anyone of the patent dis into the bloodstream without a hepatic first pass effect that closure , as it appears in the Patent and Trademark Office files significantly reduces the bioavailability of cannabinoids . or records, but otherwise reserves all copyright rights what Despite efforts to create highly soluble and bioavailable soever . cannabinoid formulations , there remains a need in the art for cannabinoid formulations that have increased bioavailability FIELD and which are conducive to use with traditional drug deliv [0003 ] The present disclosure relates in general to the field ery methods. of drug delivery formulations . In particular , the present disclosure provides for the encapsulation of poorly soluble SUMMARY OF THE DISCLOSURE cannabinoids for efficient transdermal delivery to a subject . [ 0009 ] It is therefore an object of the present disclosure to provide water - soluble cannabinoid formulations that are BACKGROUND surfactant- stabilized and that have increased bioavailability . [ 0010 ] In one aspect of the present disclosure , various [0004 ] Cannabis is an annual, primarily dioecious , flow preparations are presented to produce an oil- in -water emul ering herb . The genera Cannabis is considered to be mono sion in which the hydrophilic - lipophilic balance (HLB ) is specific (Cannabis sativa L . ) which is divided into several optimized to produce a stable emulsion . A blend of surfac subspecies ( C . sativa subsp . sativa , C . sativa subsp . indica , tants can increase the stability of emulsions and create C . sativa subsp . ruderalis , C . sativa subsp . spontanea , C . self - emulsifying drug delivery systems (SEDDS ) . During sativa subsp . kafiristanca ) . However , the chemical and mor emulsification , micelles are created which have the ability to phological distinctions by which cannabis has been split into capture cannabinoids and other cannabis - based ingredients these subspecies are often not readily discernible , appear to within the hydrophobic inner core . The encapsulation pro be environmentally modifiable , and vary in a continuous tects labile ingredients and the hydrophilic heads of the fashion . For most purposes, it will suffice to apply the name micellular outer shell increase drug delivery capabilities . Cannabis sativa to all cannabis plants encountered . [0011 ]. In one aspect of the present disclosure , a cannabi [0005 ] Cannabinoids are chemical compounds found in noid composition is provided , said composition comprising : the cannabis plant that interact with receptors in the brain a cannabinoid preparation ; at least one surfactant ; at least and body to create various effects . Cannabis contains over one co - solvent; and water ; wherein said cannabinoid com 400 compounds including over 100 cannabinoids, which are position yields the cannabinoid preparation capable of hav aryl - substituted meroterpenes unique to the plant genus ing increased bioavailability . In another aspect, the at least cannabis. The pharmacology ofmost of the cannabinoids is one surfactant comprises one or more , or alternatively , at largely unknown but the most potent psychoactive agent, least two surfactants . Further , the one or more surfactants A ' - tetrahydrocannabinol ( 4 - THC , or THC ) , has been iso have an HLB in the range of 1 to 8 and form a self lated , synthesized and much studied due to its abundance assembling emulsion . In another aspect , at least one surfac and psychoactive attributes . Other plant - based cannabinoids tant comprises an HLB in the range of 9 - 20 . In yet another include 4 ' - tetrahydrocannabinolic acid , 4° - THC , cannab aspect , the at least one surfactant is selected from a group igerol, cannabidiolic acid , and cannabidiol (CBD ) . These consisting of: oleic acid , sunflower oil, lecithin , phosphati and other cannabinoids have additive , synergistic or antago dylcholine , isopropyl myristate , stearic acid , medium and nistic effects with THC and may modify its actions when long chain triglycerides, Labrasol, polysorbate 20 , polysor cannabis products are consumed . bate 80 , or other ethoxylated surfactant, and sorbitan tri [0006 ] Cannabinoid containing extracts can be produced oleate , or other sorbitan surfactant. from a wide variety of methods ( sub / supercritical CO2, [0012 ] In another aspect of the present disclosure, the at hydrocarbons, alcohols , and by heated /pressurized means ) least one co - solvent is selected from a group consisting of: and can be further purified using winterization (precipita methanol, ethanol , isopropyl alcohol, butanol , pentanol , tion ) in alcohols , distillation , or chromatographic separation . hexanol, ethylene glycol, propylene glycol, dipropylene The resulting cannabinoids are highly lipophilic with Log P glycol, glycerol, erythritol, xylitol, mannitol , sorbitol, dieth values ranging from 5 to 9 , making them practically ylene glycol monoethyl ether ( Transcutol) , any derivative insoluble in water . These properties are not conducive to thereof, and combinations relating thereto . traditional pharmaceutical drug delivery methods, which is [ 0013 ] In one aspect cannabinoid preparation of the pres why smoking is still a preferred method for cannabis ent disclosure is encapsulated by surfactants to form consumption . micelles having uni- , bi- , or multi -lamellar structures. US 2019 /0216870 A1 Jul. 18 , 2019 [0014 ] In another aspect, the composition of the present [0019 ] It is another
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