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W O 2014/093127 a 2 19 June 2014 (19.06.2014) W P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2014/093127 A 2 19 June 2014 (19.06.2014) W P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A24F 47/00 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/US2013/073346 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 5 December 2013 (05.12.2013) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (84) Designated States (unless otherwise indicated, for every (30) Priority Data: 13/7 15,028 14 December 2012 (14. 12.2012) US kind of regional protection available): ARIPO (BW, GH, 13/871,213 26 April 2013 (26.04.2013) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (72) Inventors; and TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (71) Applicants : FUISZ, Richard C . [US/US]; 1238 Coldwa- EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, FT, LT, LU, LV, ter Canyon Drive, Beverly Hills, CA 90210 (US). FUISZ, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Joseph M . [US/US]; 116 Byron Avenue, Surfside, FL TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 33 154 (US). KM, ML, MR, NE, SN, TD, TG). (74) Agent: SCHIAVELLI, Alan E.; Antonelli, Terry, Stout & PPuubblliisshheedd: Kraus, LLP, 1300 North 17th Street, Suite 1800, Arling — witho'uuti i s r a to be republished ton, VA 22209 (US). i n ti e r n a t i o n a l e a r c hn t e p o rt ti unnda upon receipt of that report (Rule 48.2(g)) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, < (54) Title: ENHANCED DELIVERY OF NICOTINE, THC, TOBACCO, CANNABIDIOL OR BASE ALKALOID FROM AN ELECTRONIC CI GARETTE OR OTHER VAPOR OR SMOKE PRODUCING DEVICE THROUGH USE OF AN ABSORPTION CONDITIONING UNIT (57) Abstract: A method for the administration of nicotine, THC, tobacco, cannabidiol or a base alkaloid includes administering in the oral or nasal cavity an absorption conditioning unit having at least two agents selected from the group consisting of (a) a buffer agent, (b) a capturing agent, (c) a penetration agent, and (d) a thermal agent, to the mammal, and then administering by inhalation a bioactive agent selected from the group consisting of nicotine, THC, cannabidiol and a base alkaloid. The absorption conditioning unit may be in a dosage form not containing a drug. The absorption conditioning unit may create a pH in the oral cavity or nasal cav - ity of 7.8-10 for a period of ten minutes or more after administration, the dosage form not containing an acid and not containing a drug. ENHANCED DELIVERY OF NICOTINE, THC, TOBACCO, CANNABIDIOL OR BASE ALKALOID FROM AN ELECTRONIC CIGARETTE OR OTHER VAPOR OR SMOKE PRODUCING DEVICE THROUGH USE OF AN ABSORPTION CONDITIONING UNIT BACKGROUND Electronic vapor devices are increasingly popular with consumers. Such devices comprise electronic cigarettes, electronic pipes, electronic hookahs, personal vaporizers and other inhalator embodiments, both electronic and mechanical. UBS estimates that US e-cigarette sales will reach $500 million by the end of 2012, representing 100% growth from the preceding year (See UBS Tobacco Analyst Nik Modi's May 14, 2012 report entitled "Clearing the Smoke on E-Cigarettes," the entirety of which is incorporated herein by reference). Arguably, the most well-respected tobacco analyst, Bonnie Herzog of Wells Fargo, has gone so far as to suggest in discussing Loriilard: "We remain very encouraged by blu [Lorillard's e-cigarette brand] and see huge upside potential given our belief ecigs could overtake traditional cigarettes in 10 years." See Wells Fargo Loriilard Equity Research dated October 24, 2012, the entirely of which is incorporated herein by reference. British American Tobacco Chief Financial Officer Nicandro Durante stated in an interview with the Financial Times in September 2012 that the size of the market for tobacco alternatives like the e-cigarette could account for as much as 40% of BAT's revenues (which were £15bn in 201 1) in 20 years' time. "It will be sizeable in 20 years' time ... it's going to grow," he said. Despite this rapid sales growth, it is understood that electronic cigarettes fail to deliver a steeply peaked blood plasma delivery of nicotine like the conventional cigarette does. Still, there are good reasons for using the e-cigarette as compared with cigarettes. The level of toxicants from the electronic cigarette is a small fraction as compared with a conventional cigarette. See, e.g., John H. Lauterbach, Murray Laugesen, James D. Ross, "Suggested protocol for estimation of harmful and potentially harmful constituents in mainstream aerosals generated by electronic delivery systems (ENDS)", SOT, San Francisco, CA, March 10-16, 2012 (http://cigtoxdoc.ehost- servicesl 13.com/sot201 2poster1860aspresented.pdf) hereby incorporated by reference). It is typically considered in the industry that electronic vapor device adoption by consumers would be enhanced by faster, improved nicotine delivery from an electronic vapor device. Thus, there is a need to improve nicotine delivery from an electronic vapor device to its user. There is in addition need for delivery improvement (faster and more efficient) in connection with the use of all vapor devices (mechanical and electronic), of any nicotine, tobacco, or marijuana actives. SUMMARY OF THE INVENTION The present invention relates, inter alia, to a method for the administration of nicotine, THC, tobacco, cannabidiol, cocaine or a base alkaloid or combination thereof to a mammal, e.g., a human. The method includes administering an absorption conditioning unit, comprising at least two agents selected from the group consisting of (a) a buffer agent, (b) a capture agent, (c) a penetration agent, and (d) a thermal agent, to the mammal, and then administering by inhalation a bioactive agent selected from the group consisting of nicotine, THC, cannabidiol and a base alkaloid. The present invention also relates to a method for the administration of nicotine, THC, cannabidiol or a base alkaloid to a mammal, including administering an absorption conditioning unit including at least at least one material that creates a pH in the oral cavity of 7.8-10 for a period often minutes or more after administration; and then administering by inhalation a bioactive agent selected from the group consisting of nicotine, THC, tobacco, cannabidiol and a base alkaloid. In one aspect of the present invention, an absorption conditioning unit includes a dosage form including at least two agents selected from the group consisting of (a) a buffer agent, (b) a capture agent, (c) a penetration agent, and (d) a thermal agent, wherein said absorption conditioning unit (i) does not have an essentially acidic character, (ii) does not contain a drug, (iii) does not contain THC or other Marijuana derived active ingredient (or any base alkaloid intended as an active ingredient), and (iv) does not contain tobacco except for trace amounts in flavor. In another aspect of the present invention, an absorption conditioning unit, includes a dosage form including at least at least one material that creates a pH in the oral cavity of 7.8-10 for a period of ten minutes or more after administration, the dosage form not containing an acid and not containing a drug. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for the oral or nasal administration of nicotine, THC, cannabidiol, cocaine or any base alkaloid to a mammal, especially to a human, and to a prior administered (and/or contemporaneously administered and/or post administered) absorption conditioning unit useful in such a method. Nicotine inhalers are known art. For example, Pfizer markets Nicotrol® in the United States. The Nicotrol® inhaler consists of a mouthpiece and a plastic cartridge delivering 4 mg of nicotine from a porous plug containing 0 mg nicotine. The cartridge is inserted into the mouthpiece prior to use. Nicotine is released when air is inhaled through the inhaler. No heating element is used - the product relies on the natural propensity of nicotine to sublime at room temperature. Despite the inhalation-route of administration by the user of Nicotrol® a buccal route of absorption is described in the Nicotrol® package insert despite the user's inhalation of nicotine from the product (the entire package insert for Nicotrol ® is incorporated herein by reference as if fully set forth). The Nicotrol® package insert describes its method of action: "Most of the nicotine released from the NICOTROL Inhaler is deposited in the mouth. Only a fraction of the dose released, less than 5%, reaches the lower respiratory tract. An intensive inhalation regimen (80 deep inhalations over 20 minutes) releases on the average 4 mg of nicotine content of each cartridge of which about 2 mg is systemically absorbed. Peak plasma concentrations are typically reached within 5 minutes of the end of inhalation.
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