CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to U.S. Provisional Patent Application No. 62/839,564, filed April 26, 2019; U.S. Provisional Patent Application No. 62/845,231, filed May 8, 2019; U.S. Patent Application No. 16/408,428, filed May 9, 2019; U.S. Provisional Patent Application No. 62/860,224, filed June 11, 2019; and U.S. Provisional Patent Application No. 62/942,442, filed December 2, 2019, each of which is incorporated by reference in its entirety.

BACKGROUND

Cannabidiol exists as a crystalline solid at room temperature, which has a melting point of 151 degrees Fahrenheit (66 degrees Celsius). Crystalline cannabidiol lacks robust bioavailability, for example, because the human body is incapable of melting it. The pharmaceutical EPIDIOLEX® contains cannabidiol dissolved in sesame seed oil to increase bioavailability.

Consumers also vaporize and inhale cannabidiol to increase bioavailability. Cannabidiol crystallization confounds vaporization in electronic cigarettes and vaporizers because

crystallization inhibits the flow of cannabidiol toward a heating element. Prior art methods to inhibit the crystallization of cannabidiol for use in electronic cigarettes and vaporizers include the dissolution of cannabidiol in organic solvents such as propylene glycol and triglycerides. Organic solvents dilute the cannabidiol, however, and present unknown health risks. Improved cannabidiol formulations are therefore desirable.

SUMMARY

Various aspects of this patent document relate to compositions comprising liquid cannabidiol, which have either a freezing point or a glass-liquid transition temperature of less than the melting point of pure cannabidiol. In preferred embodiments, the freezing point or the glass-liquid transition temperature is less than either 70 degrees Fahrenheit or 21 degrees Celsius.

DETAILED DESCRIPTION

This patent document discloses that the melting point of cannabidiol can be lowered— or eliminated— by dissolving small amounts of specific solutes in liquid cannabidiol. The melting point of cannabidiol can be reduced to less than 70 degrees Fahrenheit (or less than 21 degrees Celsius), for example, to provide concentrated cannabidiol compositions that are liquids at room temperature. This discovery allows novel products including concentrated cannabidiol vape oil.

Various aspects of this patent document relate to a composition, comprising (i) cannabidiol at a concentration of at least 70 percent and no greater than 99.5 percent by mass, and (ii) one or more solutes selected from terpenes, terpene alcohols, terpenoids, and terpene oxidation products at a combined concentration of at least 0.5 percent and no greater than 30 percent by mass, in which: the one or more solutes comprise a terpene and a terpene oxidation product; the terpene is humulene; the terpene oxidation product is either bicyclohumuladiol, tricyclohumuladiol, tricyclohumuladiol II, humulenol II, humulene epoxide I, humulene epoxide II, or humulene epoxide III; the composition comprises the humulene and the terpene oxidation product at a ratio of at least 1 : 10 and no greater than 10,000: 1 by mass; the cannabidiol is a liquid; the one or more solutes are dissolved in the cannabidiol; and either (i) the composition has a freezing point of less than 21 degrees Celsius, and the composition lacks a glass-liquid transition temperature, or (ii) the composition has a glass-liquid transition temperature of less than 21 degrees Celsius, and the composition lacks a freezing point.

In some preferred embodiments, the terpene oxidation product is bicyclohumuladiol.

In some preferred embodiments, the terpene oxidation product is tricyclohumuladiol.

In some preferred embodiments, the terpene oxidation product is tricyclohumuladiol II.

In some preferred embodiments, the terpene oxidation product is humulenol II.

In some preferred embodiments, the terpene oxidation product is humulene epoxide I.

In some preferred embodiments, the terpene oxidation product is humulene epoxide II.

In some preferred embodiments, the terpene oxidation product is humulene epoxide III.

Various aspects of this patent document relate to a composition, comprising (i) cannabidiol at a concentration of at least 70 percent and no greater than 99.5 percent by mass, and (ii) one or more solutes selected from terpenes, terpene alcohols, terpenoids, and terpene oxidation products at a combined concentration of at least 0.5 percent and no greater than 30 percent by mass, wherein: the one or more solutes comprise a terpene and a terpene oxidation product; the terpene is beta- caryophyllene; the terpene oxidation product is caryophyllene oxide; the composition comprises the beta-caryophyllene and the caryophyllene oxide at a ratio of at least 1 : 10 and no greater than 10,000: 1 by mass; the cannabidiol is a liquid; the one or more solutes are dissolved in the cannabidiol; and either (i) the composition has a freezing point of less than 21 degrees Celsius, and the composition lacks a glass-liquid transition temperature, or (ii) the composition has a glass- liquid transition temperature of less than 21 degrees Celsius, and the composition lacks a freezing point.

Various aspects of this patent document relate to a composition, comprising (i) cannabidiol at a concentration of at least 70 percent and no greater than 99.5 percent by mass, and (ii) one or more solutes selected from terpenes, terpene alcohols, terpenoids, and terpene oxidation products at a combined concentration of at least 0.5 percent and no greater than 30 percent by mass, wherein: the one or more solutes comprise a terpene and a terpene oxidation product; the terpene is alpha- bisabolol; the terpene oxidation product is either caryophyllene oxide or humulene epoxide II; the composition comprises the alpha-bisabolol and the terpene oxidation product at a ratio of at least 1 : 10 and no greater than 10,000: 1 by mass; the cannabidiol is a liquid; the one or more solutes are dissolved in the cannabidiol; and either (i) the composition has a freezing point of less than 21 degrees Celsius, and the composition lacks a glass-liquid transition temperature, or (ii) the composition has a glass-liquid transition temperature of less than 21 degrees Celsius, and the composition lacks a freezing point.

Various aspects of this patent document relate to a composition, comprising (i) cannabidiol at a concentration of at least 50 percent and no greater than 99.5 percent by mass and (ii) one or more solutes selected from terpenes, terpene alcohols, and terpenoids at a combined concentration of at least 0.5 percent and no greater than 40 percent by mass, in which: the one or more solutes are dissolved in the cannabidiol; the composition has either a freezing point or a glass-liquid transition temperature; and the freezing point or the glass-liquid transition temperature is either (i) at least 50 degrees Fahrenheit less than the freezing point of pure cannabidiol or (ii) at least 27 degrees Celsius less than the freezing point of pure cannabidiol. In some preferred embodiments, the composition comprises the cannabidiol at a concentration of at least 65 percent and no greater than 99.5 percent by mass, and the composition comprises the one or more solutes at a combined concentration of at least 0.5 percent and no greater than 35 percent by mass. In some specific preferred embodiments, the composition comprises the cannabidiol at a concentration of at least 70 percent and no greater than 99.5 percent by mass, and the composition comprises the one or more solutes at a combined concentration of at least 0.5 percent and no greater than 30 percent by mass.

In some very specific preferred embodiments, the composition comprises the cannabidiol at a concentration of at least 75 percent and no greater than 99.5 percent by mass, and the composition comprises the one or more solutes at a combined concentration of at least 0.5 percent and no greater than 25 percent by mass.

Formula IV. Beta-Caryophyllene *

Formula VI Humulene *

Formula VII. Bicyclohumuladiol *

Formula VIII. Tricyclohumuladiol *

Formula XV. Cannabichromene†

* Formulas IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, and XIV depict stereochemistry, but each Common Name as used both in this patent specification and in the patent claims encompasses both the depicted stereochemistry of a Chemical Formula and each stereoisomer of a Chemical Formula because a probability distribution of each stereoisomer exists in natural products and because accredited cannabinoid testing laboratories generally do not distinguish stereoisomers;

† Formula XV does not depict stereochemistry, and“cannabichromene” encompasses both stereoisomers of Formula XV. In some embodiments, the composition has a freezing point; the composition lacks a glass- liquid transition temperature; and the freezing point is less than either 70 degrees Fahrenheit or 21 degrees Celsius.

In some embodiments, the composition has a glass-liquid transition temperature; the composition lacks a freezing point; and the glass-liquid transition temperature is less than either 70 degrees Fahrenheit or 21 degrees Celsius.

In some embodiments, the composition lacks crystals of cannabidiol.

In some embodiments, the composition comprises cannabidiol at a concentration of at least 75 percent and no greater than 99 percent by mass.

In some embodiments, the composition lacks tetrahydrocannabinol at a concentration greater than 0.3 percent by mass.

In some embodiments, the composition comprises tetrahydrocannabinol at a concentration greater than 0.3 percent by mass; the tetrahydrocannabinol is dissolved in the cannabidiol; and the composition comprises the cannabidiol and the tetrahydrocannabinol at a ratio of at least 3: 1 and no greater than 200: 1 by mass.

In some embodiments, the composition comprises (6a,S ^, ,10ai?)-6,6,9-trimethyl-3-pentyl- 6a, 7, 8, 10a-tetrahydro-6H -benzo[c]chromen- l -ol at a concentration of at least 0.05 percent and no greater than 5 percent by mass, in which the (6aV, 10aR )-6,6,9-trimethyl-3-pentyl-6a,7,8, 10a- tetrahydro-6H -benzo[c]chromen- l -ol is dissolved in the cannabidiol.

In some embodiments, the composition comprises molecules having a boiling point of less than either 360 degrees Fahrenheit or 182 degrees Celsius at a combined concentration of at least 95 percent by mass.

In some embodiments, the composition lacks propylene glycol, glycerol, triglycerides, phospholipids, fatty acids, and waxes at a combined concentration greater than 5 percent by mass.

In some preferred embodiments, the composition lacks propylene glycol.

In some preferred embodiments, the composition lacks triglycerides.

In some preferred embodiments, the composition lacks phospholipids.

In some preferred embodiments, the composition lacks waxes.

In some embodiments, the composition is a liquid.

In some embodiments, the composition has a viscosity, and the viscosity is less than 100 pascal-seconds at a temperature of either 70 degrees Fahrenheit or 21 degrees Celsius. In some specific embodiments, the viscosity is at least 50 millipascal-seconds and no greater than 50 pascal-seconds at a temperature of either 70 degrees Fahrenheit or 21 degrees Celsius.

In some embodiments, the one or more solutes comprise one or more of alpha-bisabolol, alpha- phellandrene, alpha-pinene, alpha-terpinene, alpha-terpineol, beta-caryophyllene, beta-pinene, borneol, cadinene, camphene, camphor, caryophyllene oxide, citral, citron ellol, delta-3 -carene, eucalyptol, eugenol, gamma-terpinene, geraniol, guaiol, humulene, isopulegol, limonene, linalool, myrcene, nerol, nerolidol, ocimene, para-cymene, phytol, pulegone, terpineol, terpinolene, and valencene at a combined concentration of at least 0.5 percent and no greater than 40 percent by mass. In some specific embodiments, the one or more solutes comprise one or more of alpha- bisabolol, beta-caryophyllene, guaiol, humulene, limonene, myrcene, and terpinolene at a combined concentration of at least 0.5 percent and no greater than 40 percent by mass.

In some preferred embodiments, the one or more solutes comprise alpha-bisabolol.

In some preferred embodiments, the one or more solutes comprise beta-caryophyllene.

In some preferred embodiments, the one or more solutes comprise caryophyllene oxide.

In some preferred embodiments, the one or more solutes comprise humulene. In some very specific embodiments, the composition comprises cannabidiol at a concentration of at least 65 percent and no greater than 99 percent by mass; the composition lacks crystals of cannabidiol; the composition lacks tetrahydrocannabinol at a concentration greater than 0.3 percent by mass; the one or more solutes comprise one or more of alpha-bisabolol, beta-caryophyllene, guaiol, humulene, limonene, myrcene, and terpinolene at a combined concentration of at least 0.5 percent and no greater than 35 percent by mass; the composition comprises molecules having a boiling point lower than either 360 degrees Fahrenheit or 182 degrees Celsius at a combined concentration of at least 95 percent by mass; the composition lacks propylene glycol, glycerol, triglycerides, phospholipids, fatty acids, and waxes at a combined concentration of greater than 5 percent by mass; the composition has a glass-liquid transition temperature; the glass-liquid transition temperature is less than either 70 degrees Fahrenheit or 21 degrees Celsius; the composition lacks a freezing point; the composition is a liquid; the composition has a viscosity; and the viscosity is at least 50 millipascal-seconds and no greater than 50 pascal-seconds at a temperature of either 70 degrees Fahrenheit or 21 degrees Celsius.

In some very specific embodiments, the composition comprises cannabidiol at a concentration of at least 65 percent and no greater than 99 percent by mass; the composition lacks crystals of cannabidiol; the composition comprises tetrahydrocannabinol at a concentration of greater than 0.3 percent by mass; the tetrahydrocannabinol is dissolved in the cannabidiol; the composition comprises cannabidiol and tetrahydrocannabinol at a ratio of at least 3 : 1 and no greater than 200: 1 by mass; the one or more solutes comprise one or more of alpha-bisabolol, beta-caryophyllene, guaiol, humulene, limonene, myrcene, and terpinolene at a combined concentration of at least 0.5 percent and no greater than 35 percent by mass; the composition comprises molecules having a boiling point lower than either 360 degrees Fahrenheit or 182 degrees Celsius at a combined concentration of at least 95 percent by mass; the composition lacks propylene glycol, glycerol, triglycerides, phospholipids, fatty acids, and waxes at a combined concentration greater than 5 percent by mass; the composition has a glass-liquid transition temperature; the glass-liquid transition temperature is less than either 70 degrees Fahrenheit or 21 degrees Celsius; the composition lacks a freezing point; the composition is a liquid; the composition has a viscosity; and the viscosity is at least 50 millipascal-seconds and no greater than 50 pascal-seconds at a temperature of either 70 degrees Fahrenheit or 21 degrees Celsius.

In some embodiments, the composition comprises cannabichromene at a concentration of at least 0.1 percent and no greater than 10 percent by mass. In some specific embodiments, the composition comprises cannabichromene at a concentration of at least 0.81 percent and no greater than 8.1 percent by mass. In some very specific embodiments, the composition comprises cannabichromene at a concentration of at least 1.94 percent and no greater than 6.92 percent by mass. The combination of cannabichromene and one or more solutes selected from terpenes, terpene alcohols, terpenoids, and terpene oxidation products is more effective at reducing the freezing point of liquid cannabidiol than the one or more solutes alone.

In some embodiments, the composition comprises cannabigerol at a concentration of at least 0.1 percent and no greater than 10 percent by mass. In some specific embodiments, the

composition comprises cannabigerol at a concentration of at least 0.81 percent and no greater than 8.1 percent by mass. In some very specific embodiments, the composition comprises cannabigerol at a concentration of at least 1.94 percent and no greater than 6.92 percent by mass.

Various aspects of this patent document relate to a method to manufacture a cannabidiol product, comprising (i) providing a starting composition comprising liquid cannabidiol; and (ii) dissolving one or more terpenes, terpene alcohols, terpenoids, or terpene oxidation products in the liquid cannabidiol to produce a composition described anywhere in this patent document.

Various aspects of this patent document relate to a container comprising (i) a heating element and (ii) a chamber that contains at least 2 milligrams and no greater than 2 grams of a composition described anywhere in this patent document, wherein the heating element is in thermal

communication with the composition. In some specific embodiments, the container is configured to be connected to a battery such that the battery and the heating element are in electrical communication that allows the transfer of electrical energy from the battery to the heating element; the heating element is operable to convert the electrical energy into sufficient heat energy; and the sufficient heat energy is sufficient to heat the composition to a temperature greater than the boiling point of the cannabidiol. In some very specific embodiments, the container is connected to the battery such that the battery and the heating element are in electrical communication.

Various aspects of this patent document relate to a method to manufacture a cannabidiol product, comprising (i) providing a composition comprising cannabidiol and one or more solutes, wherein the cannabidiol is a liquid, and the one or more solutes are dissolved in the cannabidiol; (ii) providing a starting container comprising a heating element; and (iii) inserting at least 2 milligrams and no greater than 2 grams of the composition into the starting container to produce a container described anywhere in this patent document.

Various aspects of this patent document relate to a method to manufacture a cannabidiol product, comprising (i) providing a starting composition comprising liquid cannabidiol; (ii) dissolving one or more terpenes, terpene alcohols, terpenoids, or terpene oxidation products in the liquid cannabidiol to produce a composition described anywhere in this patent document; (iii) providing a starting container comprising a heating element; and (iv) inserting at least 2 milligrams and no greater than 2 grams of the composition into the starting container to produce a container described anywhere in this patent document.

The following example provides a framework to implement certain aspects of the disclosure, and this example does not limit the scope of this patent document or any claim that matures from the disclosure of this patent document.

Example 1. Production of compositions comprising cannabidiol that do not crystallize

Cannabinoids were extracted from organic industrial hemp using the system described in PCT Patent Application Publication No. 2016/161420 A1 to produce crude industrial hemp extract comprising 65-70% cannabidiol; 5-10% terpenes, terpene alcohols, and terpenoids; 2-3% tetrahydrocannabinol; and other volatile molecules including waxes and phospholipids. The crude industrial hemp extract formed crystals of cannabidiol when stored at room temperature for 24 hours.

The cannabinoids of the crude industrial hemp extract were separated from other molecules by distillation in a VTA Short Path Distillation Plant VKL 70 (Verfahrenstechnische Anlagen GmbH & Co. KG, Germany) to produce a cannabinoid distillate comprising approximately 90% cannabidiol and 5% tetrahydrocannabinol. 10 grams of the cannabinoid distillate was combined with 0.1 grams of a terpene, terpene alcohol, and terpenoid blend obtained from True Terpenes (Oregon, USA) with heating to produce a liquid composition. The blend contained beta- caryophyllene (41%), humulene (18%), linalool (13%), limonene, alpha-bisabolol, nerolidol, beta- pinene, citronellol, fenchol, and other molecules at lower concentrations.

The liquid composition was stored at room temperature for 1 year with intermittent exposure to light and air, and the composition produced no detectable crystals. Cooling the liquid below room temperature vitrified the composition into a glass without any detectable crystal formation.

This example demonstrates that small amounts of terpenes, terpene alcohols, and terpenoids can provide robust stabilization of cannabidiol in a liquid state and inhibit crystal formation over commercially -relevant timeframes, even when subjected to chemical stress, provided that lipids that comprise fatty acids are removed from the liquid state.