US 2003.0099756A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0099756A1 GOW et al. (43) Pub. Date: May 29, 2003 (54) METHOD OF PRODUCING A PROCESSED Publication Classification KAVA PRODUCT HAVING AN ALTERED KAVALACTONE DISTRIBUTION AND (51) Int. Cl." ....................................................... A23K 1100 PROCESSED KAVA PRODUCTS PRODUCED (52) U.S. Cl. .............................................................. 426/615 USING THE SAME (76) Inventors: Robert Gow, Naples, FL (US); John (57) ABSTRACT Pierce, Moreno Valley, CA (US); Brian A method of producing a processed kava product involves Pierce, Thousand Oaks, CA (US); using an extraction Solvent, Such as liquid CO, to prefer William Birdsall, Naples, FL (US) entially extract different kavalactones from the Source mate Correspondence Address: rial at different rates. By controlling the extraction param CLIFFORD CHANCE US LLP eters and Stopping the extraction before all of the kavalactones have been extracted or allowing the extracted 200 PARKAVENUE kavalactones to be preferentially precipitated in one or more NEW YORK, NY 10166 (US) collection environments, a processed kava product can be (21) Appl. No.: 10/263,579 produced that has a kavalactone distribution profile that can differ Substantially from that of the source material. As a (22) Filed: Oct. 3, 2002 result, roots from a leSS desirable kava cultivar can be used to produce a processed kava product which has a kavalac Related U.S. Application Data tone distribution profile that is similar to that of a highly desired cultivar. The kava paste can be further processed to (60) Provisional application No. 60/326,928, filed on Oct. produce a dry flowable powder Suitable for use in, e.g., a 3, 2001. Provisional application No. 60/369,889, filed tableting formula. A rapid dissolve tablet formulation for use on Apr. 3, 2002. in the delivery of kavalactones is also disclosed. Patent Application Publication May 29, 2003 Sheet 1 of 7 US 2003/0099756A1 JeA}|no emey nenue/Wyo edAL Patent Application Publication May 29, 2003 Sheet 2 of 7 US 2003/0099756A1 Suemino emey nenueAgo JedunN US 2003/0099756A1 (p) uemey I uemeyoupAuO Patent Application Publication May 29, 2003 Sheet 4 of 7 US 2003/0099756A1 -- „KeG-OWLeJeA?InO säsv=š0?dae.(WHG+W)º...……………………………………………………ººº!V.-?---- sasv=sQNI(»Hq.+x)GNv.»||W| --·1-·||-·}.|- 0 Patent Application Publication May 29, 2003 Sheet 5 of 7 US 2003/0099756A1 -#-,--v•- briti?benxazoo | "OIHS o O wr c S S v v effeueoued ufeW (A) uuofue + (ANC) uuofueMAXOueused Patent Application Publication May 29, 2003 Sheet 6 of 7 US 2003/0099756A1 080/ 9"OIH ºqNWHq.+x)sasväg?NI uo?oeulxezoopinbl-? (A+Awa)sasv?Hoad O O w e5eue3.edu.6éMY (A)vm uluofueve + (ANC) uuofueMAXOueused Patent Application Publication May 29, 2003 Sheet 7 of 7 US 2003/0099756A1 Z1021)XEZOOb?T– /'OIH US 2003/0099756 A1 May 29, 2003 METHOD OF PRODUCING A PROCESSED KAVA “two-day”, “medicinal', and “no drink”. “Daily kava cul PRODUCT HAVING AN ALTERED KAVALACTONE tivars are generally consumed daily and have relatively DISTRIBUTION AND PROCESSED KAVA short-term effects. “Custom kava cultivars tend to be used PRODUCTS PRODUCED USING THE SAME for ritual and ceremonial purposes. “Two-day kava culti vars tend to have pronounced physiological effects and are CROSS-REFERENCE TO RELATED known as “two day” because the drinker is usually affected APPLICATIONS: for two days. “Medicinal kava cultivars are specific for the treatment of ailments like rheumatism. "No Drink' kava 0001. This application is claims priority under 35 U.S.C. cultivars are not recommended for consumption because S 119 to U.S. Provisional Patent Application Serial No. they tend to induce nausea and other undesirable effects. 60/326,928 entitled “Methods For Processing Kava Root (Piper Methysticum) And Kava-Derived Products Generated 0007 More recently, there have been concerns associat By These Methods Having Controllable Kavalactone ing kava with occurrences of liver damage, although these Ratios', filed on Oct. 3, 2001, and U.S. Provisional Appli reports are primarily anecdotal. Studies done in the 1970s cation Serial No. 60/369,889 entitled “Dry Flowable Kava and 1980s have found that “two day” kava cultivars have Extract Powder And Fast-Dissolve Kava Extract Composi particularly high concentrations of methysticin and dihy tion For Oral Delivery”, filed on Apr. 3, 2002. The entire dromethysticin. These kavalactones contain a methylene contents of both of these applications are hereby expressly dioxyphenyl functional group which, when activated incorporated by reference. through metabolic activity, forms intermediary compounds that can inactivate multiple P450 enzymes. There are some FIELD OF THE INVENTION(S) suggestions that inhibition of P450 enzymes can interfere with the metabolism of many pharmaceuticals. The Solution 0002 This invention is related to methods for processing proposed in the prior art is the development of new kava kava to produce a kava extract with particular kavalactone cultivars with reduced amounts of methysticin and dihy concentration profile, a processed kava product, Such as a dromethysticin and increased kavain content. dry flowable kava extract powder, and the use of Such a powder in a rapid-dissolve tablet for oral delivery. 0008 One of the most highly prized kava cultivars is a one-day cultivar that grows in Vanuatu. Relative to other cultivars, this cultivar is naturally low in methysticin and BACKGROUND dihydromethysticin and has a proportionally higher concen 0.003 Kava plants, a type of pepper plant also known as tration of kavain. However, this cultivar is not widely grown Piper methysticum, arc generally found in Polynesia, or available and most commercially available cultivars have Melanesia, and Micronesia. The kava plant contains high increased levels of methysticin and dihydromethysticin and concentrations of kavalactones (sometimes referred to as lower concentrations of kavain. Although breeding of new kavapyrones), including kavain, methysticin, yangonin, cultivars that can be widely grown and which have lower dihydromethysticin, desmethoxyyangonin, and dihy concentrations of methysticin and dihydromethysticin and drokavain, and has been used as an herbal medicine. The increased concentrations of kavain is possible, this can be a prized part of the kava plant is the root System because it time consuming proceSS and is not assured of Success. In contains the highest concentrations of the active kavalac addition, the kavalactones Suspected of producing toxic tones. Kavalactones are also found in other parts of the plant. effects when consumed by humans are also toxic to various General information about kava plants can be found in insects and microorganisms, Such as fungi. Thus, the hardi Vincent Lebot, et al., “Kava The Pacific Elixir; The Defini est cultivars are generally those which are least Suitable for tive Guide to its Ethnobotany, History, and Chemistry', human consumption. Inner Traditions Intl. Ltd. (March 1997). 0009. In a kava extraction process, the rate at which 0004. After a kava plant is harvested, the root is conven various kavalactone components are extracted varies tionally processed to generate a consumable product. In according to the extraction Solvent and extraction conditions conventional and historical methods, the root is dried and used. However, kava root extracts are conventionally Sold ground to a powder. This powder contains not only the based upon total kavalactone content. Thus, the focus of kavalactones but also plant oils, resins, and other Substances. conventional commercial extraction techniques has been to The powder can be mixed with water to form a beverage. extract as much of the kavalactone content from the root The resinous ground dried root can also be packaged into Source as possible and knowledge regarding different rates capsules or other forms of delivery. of extraction for different kavalactones is used to adjust the 0005 The effects of ingesting kava root extract will vary extraction proceSS or Select appropriate extraction Steps to from person to perSon. Common effects include a State of provide for the greatest total kavalactone extraction. relaxation and a reduction in muscle tenseneSS. Kava root 0010 Various extraction techniques have been used to has also been used to help Sufferers of insomnia. It can also process kava root. Such techniques include the use of produce a mild State of euphoria. The ratioS of the various Supercritical carbon dioxide (CO2) extraction, fluorocarbon kavalactones in the consumed product has a large impact on extraction, and the use of various other organic and non the effect experienced by the user. organic Solvents to remove the kavalactones from the dried 0006 There are a large number of different kava culti root. The resulting bulk extract is in the form of a paste. vars, each of which has differing ratios of the different 0011 Supercritical CO processes have been found to kavalactones. Through historical knowledge and experimen extract the largest quantity of kavalactones from the root and tation, various kava cultivars have been classified according thus conventional practice has been to focus on the use of to their effect, such as “daily” or “one-day”, “custom', Supercritical CO2 to extract all of the kavalactones from the US 2003/0099756 A1 May 29, 2003 root in the production of kava extracts. AS will be appreci use in a fast dissolve tablet and other applications, and which ated, bulk extracts of Substantially all of the kavalactones in as a kavalactone profile that is altered from the profile of the the root will generally contain kavalactones in the same or kava feedstock. The present methodologies also allow the nearly the Same proportions as present in the Source root. distribution of kavalactones to be altered or adjusted to Because of the differing effects produced by variations in the achieve a particular kavalactone profile wherein the effec kavalactone ratioS of different cultivars, producers of Such tiveness of the kava can be enhanced or the negative effects kava products are limited to specific kava cultivars as Source reduced.