AU2019100190A4

AU2019100190A4 - An innovative formulation of very high kavalactone, non-toxic Kava extract derived from a water isolate of Kava (Piper methysticum)

Info

Publication number: AU2019100190A4
Application number: AU2019100190A
Authority: AU
Inventors: Alex Bezruchko; Simon Angelo Cichello; Wael Khudruj; Evan Wood; Reese Wood
Original assignee: Wholesale Group International Pty Ltd; Nurturcare Inc
Current assignee: Wholesale Group International Pty Ltd; Nurturcare Inc
Priority date: 2019-02-20
Filing date: 2019-02-20
Publication date: 2019-03-28
Anticipated expiration: 2027-02-20

Abstract

The present invention relates to a process for the water extraction of very high levels of kavalactone from Kava (Piper methysticum). Said extract may be used for its anxiolytic effect to the central nervous system.

Description

Editorial Note 2019100190

There is only Six pages of Description AUSTRALIA Patents Act 1990

An innovative formulation of very high kavalactone, non-toxic extract derived from a water isolate of Kava (Piper methysticum)

Patent Description - The patent is described in the following statements

The present innovation patent relates to a technological invention that improves the extraction of kavalactones from Kava (Piper methysticum) grown in Vanuatu, and the associated physiological effects of ingestion of encapsulated a water extract of Kava.

What is Kava

Kava Piper methysticum (Latin "pepper" and Latinized Greek "intoxicating"), has been consumed by South Pacific islanders for thousands of years. It is the domesticated variety of P. subbullatum which is native to New Guinea and the Philippines and spread by Papuans eastward across the Pacific (Ross & Malcolm 2008). Moreover, Kava has historically grown only in the Pacific islands of Hawaii, Federated States of Micronesia, Vanuatu, Fiji, the Samoas and Tonga where over 40 other species of Kava grow, some medicinal, some not including P. wichmannii which grows in Papua New Guinea, the Solomon Islands, and Vanuatu.

This is not to be confused with the Kawakawa (P. excelsum) plant, known also as "Maori kava"

Traditional Use

It was traditionally consumed for its “peace offering effects”, chiefly anxiolytic effects by chieftans to settle disputes between tribes, reducing warfare and cannibalism. The quality of kava and kava beverage can vary, and is determined by the content of six major kavalactones including methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin and desmethoxyyangonin. Also the absence of toxins found in the aerial stem of the plant (Pipermethystine) (Wang et. al. 2013).

Kava(-kava) is derived from the from Tongan and Marquesan language to mean "bitter". Other names include ‘awa’ (Hawaii), ‘ava’ (Samoa), yaqona (Fiji), sakau (Pohnpei), and malok/ malogu (parts of Vanuatu). Traditionally consumed as an entheogenic drink with sedative, anesthetic, and euphoriant properties, it is now promoted as a pharmaceutical and consumed as a capsule. The root is used safely even though some people persist to promote the use of the aerial stem (2016213700) which contain and toxin Piperemethystine.

Toxicity

There has been great concern regarding the consumption and speculation that Kava is dangerous to consume. This has been largely proliferated by the sale and consumption of poor-quality Kava and also use of solvent extraction systems (non-aqueous) (Kuchta & Mathias 2015). The WHO has deemed water extraction of Kava to be "acceptably low level of health risk" (WHO 2016). Our extract does not contain these toxic compounds especially the absence of Piperemethystine.

The plant grows in isolated, specific climates of loose, well-drained soils where plenty of air reaches the roots where rainfall is over 78 inches or 2,000 mm/yr and 21-35 °C and 70-100% relative humidity propagation is asexually via stem cutting or rhizome with the roots/ rhizome harvested in plants >4 years of age. The distinction between Kava varieties and previous art (2016213700) is that this patent clearly distinguishes against the noble and non-noble varieties of Kava.

The physical composition of the kava root contains 43% starch (dried root) 20% dietary fiber (dried root) 15% kavalactones (dried root) 12% water (dried root) 3.2% sugars (dried root) 3.6% protein (dried root) 3.2% vitamins & minerals (dried root) <1% Kavalactones, dihydrokavain, methysticin, and dihydromethysticin also present

Pharmacology

Constituents A total of 18 different kavalactones (or kavapyrones) have been identified, 15 being pharmacologically active, with six [kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin] being responsible for at least 96% of the pharmacological activity. Less desirable compounds include three chalcones, flavokavain A, flavokavain B, and flavokavain C as well as a toxic alkaloid (not present in the consumable parts of the plant pipermethystine (of which the last four compounds mentioned are absent from our extract).

Pharmacodynamics

The following pharmacological actions have been reported for kava and/or its major active constituents - Potentiation of GABAa receptor activity ((GABAAR) (by kavain, dihydrokavain, methysticin, dihydromethysticin, and yangonin). GABAAR action is based on ligand (endogenous ligand; γ-aminobutyric acid (GABA))-gated ion channel (Cl ). - Inhibition of the reuptake of norepinephrine (i.e. kavain and methysticin) (regulate mood related neurotransmitters) and dopamine [by kavain and desmethoxyyangonin] - Binding to the CB1 receptor [Cannabinoid receptors] (by yangonin) [anxiolytic effects] (Ligresti et. al. 2012) - Inhibition of voltage-gated sodium channels and voltage-gated calcium channels (by kavain and methysticin) - Monoamine oxidase B reversible inhibition (by all six of the major kavalactones) (inhinbits MAOI’s that oxidize monamines such as dopamine) - Weak interaction with the 5-HT6 and 5-HT7 receptors (binds endogenous neurotransmitters i.e. serotonin [5-hydroxytryptoamine] (Dinh et. al. 2001). - Potentiation of GABAA receptor activity (i.e. anxiolytic effects) - Elevation of dopamine levels in the nucleus accumbens (i.e. psychotropic effects) - Changes in 5-HT neuron activity (i.e. sleep-inducing action)

Summary

The previous art includes a standard patent 2016213700 “PREPARATION OF MILD TASTING AND HIGH YIELDING KAVA POWDER” (Australia) which has a number of deficiencies arise from this patent including but not limited to; - lack of description of the Genus and species - the patent describes using all parts of the root and also aerial stem which has been shown to contain toxic compounds i.e. Pipermethystine, which is an ingredient from aerial stem peelings (Wang et. al. 2013).

Our Kava extraction process to produce a highly safe, and effective water only extract is processed from fresh Kava or village dried, noble Kava from lateral rots only, that is 5-30 years in maturity from a specific genus and species (Piper methysticum).

References

Dinh, L.D., Simmen, U., Bueter, K.B., Bueter, B., Lundstrom, K.,

Schaffner, W. (2001). "Interaction of various Piper methysticum cultivars with CNS receptors in vitro". Planta Med. 67(4), 306-11. doi:10.1055/s-2001-14334. PMID 11458444.

Kuchta, K.S., Mathias, N.S. (2015). "German Kava Ban Lifted by Court:

The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics". Planta Medica. 81(18), 1647-1653. doi:10.1055/s-0035-1558295. ISSN 1439-0221. PMID 26695707.

Ligresti, A., Villano, R., Allara, M., Ujvary, I., Di Marzo, V. (2012). "Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CBi receptor ligand". Pharmacol. Res. 66(2), 163-9. doi:10.1016/j.phrs. 2012.04.003.

Ross, Malcolm (2008). "Other cultivated plants". In Ross, Malcolm; Pawley, Andrew; Osmond, Meredith. The lexicon of Proto Oceanic: The culture and environment of ancestral Oceanic society. Volume 3: Plants. Pacific Linguistics, p. 389-426. ISBN 9780858835894.

Wang, J., Qu, W.Y., Bittenbender, H.C., and Qing X. Li (2015). Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents. J Food Sci Technol. 52(2), 1164-1169. doi: 10.1007/s13197-013-1047-2 WHO (2016). Kava: a review of the safety of traditional and recreational beverage consumption" (PDF). Food and Agriculture Organization of the United Nations and World Health Organization, Rome, Italy.

Claims

1. The Kava is either processed fresh from Kava harvested in the prior 3 days or;

2. Our patent herein only uses the lateral roots (rhizome) and undergoes a traditional drying system first. We also differentiate from the above-mentioned patent (patent 2016213700) in that we use noble Kava (only P. methysticum) that is 5-30 years in maturity.

3. Moreover, we specifically refer to a water extract of the Kava and not a water and or solvent based extraction as per the previous patent (patent 2016213700)

4. Moreover, our process is differentiated and in commercial production and can use both wet (fresh Kava) as well as traditionally dried roots and processed at the source in Vanuatu rather than transport and extraction of the Kava in Australia, EU, USA, Canada

5. After the Kava is sorted and only the lateral roots (rhizomes) are extracted, the roots are chopped into 100mm square cubes

6. The roots are soaked in distilled and filtered water (20pm filtered) for 5 minutes

7. Then the kava blocks are dried for 36 hours at 42°C to a relative humidity of 33%

8. They are then powdered three times using a hammer mill with sieve sizes of 200, 100, and 75 mesh size in sequential order

9. The Kava which now is of particle size 50-100pm in size is then rehomogenized in distilled and filtered water, and made into a paste and further fiber is collected via ultracentrifugation at 10,000 rpm for 10 minutes to further remove fiber and also starch.

10. The Kava is then analyzed using an acetone test to ensure only noble Kava is used (460nm) derived by Vincent LeBot to ensure only non-toxic Kava is processed and sold, and confirmed with HPLC testing[3] >30% transmission (basal roots) >17% transmission (lateral roots/ rhizomes) HPLC analysis Confirming the presence of the Kavalactone(s) herein mentioned as well as absence of Pipermethystine (toxic alkaloid).

11 .The Kava is then encapsulated into a 400mg vegetable-based capsule

12. Typically, Kavalactones are present at a 8-15% total composite in the final product include (w/w) of the capsule; Yangonin, 10-methoxyyangonin, 11-methoxyyangonin, 11-hydroxyyangonin, Desmethoxyyangonin, 11-methoxy-12-hydroxydehydrokavain, 7,8-dihydroyangonin, Kavain, 5-hydroxykavain, 5,6-dihydroyangonin, 7,8-dihydrokavain, 5,6,7,8-tetrahydroyangonin, 5,6-dehydromethysticin, Methysticin, 7,8-dihydromethysticin

13. The Kava extract does not contain basal root or aerial parts and thus does not contain the toxin Pipermethystine, which is an ingredient from aerial stem peelings, nor heavy metals (confirmed by HPLC detection & use of ICP-OES (inductively coupled plasma optical emission spectrometry), and Ultraviolet-Visible spectrometer. We note that the previously mentioned patent (2016213700) contains aerial stem and thus the toxin Pipermethystine.

14. Further, all extract material is tested for microbiological contamination including by not limited to specific plate count (aerobic plate count), Coliforms, Escherichia coli, Coagulase-positive staphylococci, Campylobacter spp, Salmonella spp., Listeria monocytogenes (<10 colony forming units per gram) and Yeasts and Moulds/ Molds (Fungi) (<100 per gram of test material).

15. The instant kava is effective within 7-10 minutes of consumption causing an anxiolytic effect to the central nervous system.