Oral Formulations of Kava

This application is a continuation-in-part of U.S. application Ser. No. 18/669,480, filed May 20, 2024, the disclosure of which is incorporated herein by reference in its entirety.

Nicotine is an alkaloid that may be derived from the leaves ofspp. plants (colloquially “tobacco plants”). Nicotine has been used by adult humans for its stimulant and anxiolytic effects. Conventionally, nicotine has been delivered to users via smoking or chewing tobacco leaves, which has many well-known negative health consequences, such as exposing tissue of the oral cavity, throat, and lungs to carcinogenic substances.

In recent years, alternative nicotine delivery systems that can bypass the aforementioned negative health consequences have been developed. Such alternative nicotine delivery systems include oral formulations that contain non-tobacco-derived sources of nicotine, such as nicotine salts. Recent clinical studies confirm that these alternative nicotine delivery systems, however, can suffer from disadvantages including an inadequate relief of nicotine cravings, which significantly increases the likelihood that nicotine users will discontinue the use of an alternative nicotine delivery system for a conventional tobacco-containing nicotine delivery system. A 2024 clinical study by Keller-Hamilton et al., for example, found that oral nicotine pouches failed to provide adequate relief of nicotine cravings compared to cigarettes, which significantly increased the likelihood that nicotine users would discontinue the use oral nicotine pouches and resume their use of cigarettes. See Keller-Hamilton et al.,2024; 119 (3): 464-475 (the disclosure of which is hereby incorporated by reference in its entirety).

To address these shortcomings, the present invention relates to oral nicotine formulations that contain kavalactones derived from the Pacific Island crop(colloquially “kava”). As disclosed herein, the oral nicotine formulations contain both a nicotine composition (comprising one or more nicotine salts) and a kava composition (comprising one or more kavalactones). Surprisingly, the inventions disclosed herein address aforementioned problems associated with alternative nicotine delivery systems can be overcome by delivering nicotine and kavalactones from the oral nicotine formulations disclosed herein.

The present disclosure also developed oral nicotine-free formulations that contain kavalactones derived from kava, alone or in combination with, kratom alkaloids derived from the Asian crop(colloquially “kratom”). As disclosed herein, the foregoing oral nicotine-free formulations contain a kava composition (comprising one or more kavalactones), alone or in combination with, a kratom composition (comprising one or more kratom alkaloids). Surprisingly, the inventions disclosed herein address aforementioned problems with alternative nicotine delivery systems can be overcome by delivering kavalactones, alone or in combination with, kratom alkaloids from the oral nicotine-free formulations disclosed herein.

The disclosure further describes oral tobacco formulations that contain kavalactones derived from kava. As disclosed herein, the foregoing oral tobacco formulations contain both a tobacco leaf composition and a kava composition (comprising one or more kavalactones). Surprisingly, the inventions disclosed herein address aforementioned problems with alternative nicotine delivery systems can be overcome by delivering nicotine and kavalactones from the oral tobacco formulations disclosed herein.

Embodiments of the present disclosure relate to oral formulations comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to an oral formulation formulated as a chewable tablet comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to an oral formulation formulated as a lozenge comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to an oral formulation formulated as a chewing gum comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to an oral formulation formulated as a dissolvable oral strip comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to an oral formulation formulated as a pouch comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to methods of making oral formulations comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to methods of making an oral formulation formulated as a chewable tablet comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to methods of making an oral formulation formulated as a lozenge comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to methods of making an oral formulation formulated as a chewing gum comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to methods of making an oral formulation formulated as a dissolvable oral strip comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to methods of making an oral formulation formulated as a pouch comprising a nicotine composition and a kava composition.

Embodiments of the present disclosure relate to methods of using an oral formulation comprising a nicotine composition and a kava composition to prevent or reduce the risk of developing cancer in a subject that smokes tobacco.

Embodiments of the present disclosure relate to methods of using an oral formulation comprising a nicotine composition and a kava composition to prevent or reduce the risk of developing cancer in a subject that chews tobacco.

Embodiments of the present disclosure relate to methods of using an oral formulation comprising a nicotine composition and a kava composition to prevent or reduce the formation of DNA adducts in a subject.

Embodiments of the present disclosure relate to methods of using an oral formulation comprising a nicotine composition and a kava composition to inhibit enzymes in a subject.

Embodiments of the present disclosure relate to methods of using an oral formulation comprising a nicotine composition and a kava composition to inhibit metabolic and/or signaling pathways in a subject.

Embodiments of the present disclosure relate to methods of using an oral formulation comprising a nicotine composition and a kava composition to regulate gene expression in a subject.

Embodiments of the present disclosure relate to oral nicotine-free formulations comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to an oral nicotine-free formulation formulated as a chewable tablet comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to an oral nicotine-free formulation formulated as a lozenge comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to an oral nicotine-free formulation formulated as a chewing gum comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to an oral nicotine-free formulation formulated as a dissolvable oral strip comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to an oral nicotine-free formulation formulated as a pouch comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to methods of making oral nicotine-free formulations comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to methods of making an oral nicotine-free formulation formulated as a chewable tablet comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to methods of making an oral nicotine-free formulation formulated as a lozenge comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to methods of making an oral nicotine-free formulation formulated as a chewing gum comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to methods of making an oral nicotine-free formulation formulated as a dissolvable oral strip comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to methods of making an oral nicotine-free formulation formulated as a pouch comprising a kava composition, alone or in combination with, a kratom composition.

Embodiments of the present disclosure relate to methods of using an oral nicotine-free formulation comprising a kava composition, alone or in combination with, a kratom composition to prevent or reduce the risk of developing cancer in a subject that smokes tobacco.

Embodiments of the present disclosure relate to methods of using an oral nicotine-free formulation comprising a kava composition, alone or in combination with, a kratom composition to prevent or reduce the risk of developing cancer in a subject that chews tobacco.

Embodiments of the present disclosure relate to methods of using an oral nicotine-free formulation comprising a kava composition, alone or in combination with, a kratom composition to prevent or reduce the formation of DNA adducts in a subject.

Embodiments of the present disclosure relate to methods of using an oral nicotine-free formulation comprising a kava composition, alone or in combination with, a kratom composition to inhibit enzymes in a subject.

Embodiments of the present disclosure relate to methods of using an oral nicotine-free formulation comprising a kava composition, alone or in combination with, a kratom composition to inhibit metabolic and/or signaling pathways in a subject.

Embodiments of the present disclosure relate to methods of using an oral nicotine-free formulation comprising a kava composition, alone or in combination with, a kratom composition to regulate gene expression in a subject.

Embodiments of the present disclosure relate to oral tobacco formulations comprising a tobacco leaf composition and a kava composition.

Embodiments of the present disclosure relate to methods of making oral tobacco formulations comprising a tobacco leaf composition and a kava composition.

Embodiments of the present disclosure relate to methods of using an oral tobacco formulation comprising a tobacco leaf composition and a kava composition to prevent or reduce the risk of developing cancer in a subject that chews tobacco.

Some embodiments provide an oral formulation comprising an amount of a nicotine composition and an amount of a kava composition.

Some embodiments provide an oral nicotine-free formulation comprising an amount of a kava composition, and optionally, an amount of a kratom composition.

In certain embodiments, a nicotine composition, as described herein, may comprise an amount of one or more compounds selected from nicotine, nicotine acetate, nicotine benzoate, nicotine bitartrate, nicotine bitartrate dihydrate, nicotine citrate, nicotine dihydrochloride, nicotine formate, nicotine hydrochloride, nicotine lactate, nicotine laurate, nicotine levulinate, nicotine malate, nicotine polacrilex, nicotine pyruvate, nicotine salicylate, nicotine sorbate, nicotine succinate, nicotine sulphate, nicotine tartrate, nicotine zinc chloride monohydrate, and any combination thereof.

In certain embodiments, a nicotine composition, as described herein, may comprise an amount of nicotine. In some embodiments, a nicotine composition, as described herein, may comprise between about 0.1 mg and about 20 mg of nicotine, such as, for example, 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2.0 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3.0 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4.0 mg, 4.1 mg, 4.2 mg, 4.3 mg, 4.4 mg, 4.5 mg, 4.6 mg, 4.7 mg, 4.8 mg, 4.9 mg, 5.0 mg, 5.1 mg, 5.2 mg, 5.3 mg, 5.4 mg, 5.5 mg, 5.6 mg, 5.7 mg, 5.8 mg, 5.9 mg, 6.0 mg, 6.1 mg, 6.2 mg, 6.3 mg, 6.4 mg, 6.5 mg, 6.6 mg, 6.7 mg, 6.8 mg, 6.9 mg, 7.0 mg, 7.1 mg, 7.2 mg, 7.3 mg, 7.4 mg, 7.5 mg, 7.6 mg, 7.7 mg, 7.8 mg, 7.9 mg, 8.0 mg, 8.1 mg, 8.2 mg, 8.3 mg, 8.4 mg, 8.5 mg, 8.6 mg, 8.7 mg, 8.8 mg, 8.9 mg, 9.0 mg, 9.1 mg, 9.2 mg, 9.3 mg, 9.4 mg, 9.5 mg, 9.6 mg, 9.7 mg, 9.8 mg, 9.9 mg, 10.0 mg, 10.1 mg, 10.2 mg, 10.3 mg, 10.4 mg, 10.5 mg, 10.6 mg, 10.7 mg, 10.8 mg, 10.9 mg, 11.0 mg, 11.1 mg, 11.2 mg, 11.3 mg, 11.4 mg, 11.5 mg, 11.6 mg, 11.7 mg, 11.8 mg, 11.9 mg, 12.0 mg, 12.1 mg, 12.2 mg, 12.3 mg, 12.4 mg, 12.5 mg, 12.6 mg, 12.7 mg, 12.8 mg, 12.9 mg, 13.0 mg, 13.1 mg, 13.2 mg, 13.3 mg, 13.4 mg, 13.5 mg, 13.6 mg, 13.7 mg, 13.8 mg, 13.9 mg, 14.0 mg, 14.1 mg, 14.2 mg, 14.3 mg, 14.4 mg, 14.5 mg, 14.6 mg, 14.7 mg, 14.8 mg, 14.9 mg, 15.0 mg, 15.1 mg, 15.2 mg, 15.3 mg, 15.4 mg, 15.5 mg, 15.6 mg, 15.7 mg, 15.8 mg, 15.9 mg, 16.0 mg, 16.1 mg, 16.2 mg, 16.3 mg, 16.4 mg, 16.5 mg, 16.6 mg, 16.7 mg, 16.8 mg, 16.9 mg, 17.0 mg, 17.1 mg, 17.2 mg, 17.3 mg, 17.4 mg, 17.5 mg, 17.6 mg, 17.7 mg, 17.8 mg, 17.9 mg, 18.0 mg, 18.1 mg, 18.2 mg, 18.3 mg, 18.4 mg, 18.5 mg, 18.6 mg, 18.7 mg, 18.8 mg, 18.9 mg, 19.0 mg, 19.1 mg, 19.2 mg, 19.3 mg, 19.4 mg, 19.5 mg, 19.6 mg, 19.7 mg, 19.8 mg, 19.9 mg, 20.0 mg, or any value in between any two of the preceding amounts.

In certain embodiments, a nicotine composition, as described herein, may comprise an amount of nicotine acetate. In some embodiments, a nicotine composition, as described herein, may comprise between about 0.1 mg and about 20 mg of nicotine acetate, such as, for example, 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2.0 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3.0 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4.0 mg, 4.1 mg, 4.2 mg, 4.3 mg, 4.4 mg, 4.5 mg, 4.6 mg, 4.7 mg, 4.8 mg, 4.9 mg, 5.0 mg, 5.1 mg, 5.2 mg, 5.3 mg, 5.4 mg, 5.5 mg, 5.6 mg, 5.7 mg, 5.8 mg, 5.9 mg, 6.0 mg, 6.1 mg, 6.2 mg, 6.3 mg, 6.4 mg, 6.5 mg, 6.6 mg, 6.7 mg, 6.8 mg, 6.9 mg, 7.0 mg, 7.1 mg, 7.2 mg, 7.3 mg, 7.4 mg, 7.5 mg, 7.6 mg, 7.7 mg, 7.8 mg, 7.9 mg, 8.0 mg, 8.1 mg, 8.2 mg, 8.3 mg, 8.4 mg, 8.5 mg, 8.6 mg, 8.7 mg, 8.8 mg, 8.9 mg, 9.0 mg, 9.1 mg, 9.2 mg, 9.3 mg, 9.4 mg, 9.5 mg, 9.6 mg, 9.7 mg, 9.8 mg, 9.9 mg, 10.0 mg, 10.1 mg, 10.2 mg, 10.3 mg, 10.4 mg, 10.5 mg, 10.6 mg, 10.7 mg, 10.8 mg, 10.9 mg, 11.0 mg, 11.1 mg, 11.2 mg, 11.3 mg, 11.4 mg, 11.5 mg, 11.6 mg, 11.7 mg, 11.8 mg, 11.9 mg, 12.0 mg, 12.1 mg, 12.2 mg, 12.3 mg, 12.4 mg, 12.5 mg, 12.6 mg, 12.7 mg, 12.8 mg, 12.9 mg, 13.0 mg, 13.1 mg, 13.2 mg, 13.3 mg, 13.4 mg, 13.5 mg, 13.6 mg, 13.7 mg, 13.8 mg, 13.9 mg, 14.0 mg, 14.1 mg, 14.2 mg, 14.3 mg, 14.4 mg, 14.5 mg, 14.6 mg, 14.7 mg, 14.8 mg, 14.9 mg, 15.0 mg, 15.1 mg, 15.2 mg, 15.3 mg, 15.4 mg, 15.5 mg, 15.6 mg, 15.7 mg, 15.8 mg, 15.9 mg, 16.0 mg, 16.1 mg, 16.2 mg, 16.3 mg, 16.4 mg, 16.5 mg, 16.6 mg, 16.7 mg, 16.8 mg, 16.9 mg, 17.0 mg, 17.1 mg, 17.2 mg, 17.3 mg, 17.4 mg, 17.5 mg, 17.6 mg, 17.7 mg, 17.8 mg, 17.9 mg, 18.0 mg, 18.1 mg, 18.2 mg, 18.3 mg, 18.4 mg, 18.5 mg, 18.6 mg, 18.7 mg, 18.8 mg, 18.9 mg, 19.0 mg, 19.1 mg, 19.2 mg, 19.3 mg, 19.4 mg, 19.5 mg, 19.6 mg, 19.7 mg, 19.8 mg, 19.9 mg, 20.0 mg, or any value in between any two of the preceding amounts.