Low-Temperature Inhalation Administration of Cannabinoid Entities

A formulation comprising:

• (A)(i) an extract of a cannabinoid containing plant material, said extract containing one or more first cannabinoid active agent(s) or (ii) a combination of said extract and one or more additional cannabinoid active agent(s), said additional cannabinoid active agent(s) selected from the group consisting of (a) partially or completely purified cannabinoid compounds, (b) synthetic cannabinoid compounds, and (c) mixtures thereof;
• (B) a hydrofluoroalkane (HFA) propellant;
• and
• (C) a co-solvent selected from the group consisting of ethanol, propanol, isopropanol, propylene, glycol, polyethylene glycol, and mixtures thereof;
• said HFA propellant being present in an amount of from 50% by weight to 99.99% by weight based on the entire formulation;
• said co-solvent, being present in an amount of from 0% by weight up to 40% by weight based on the entire formulation;
• and
• said extract or said combination of said extract and said additional cannabinoid active agent(s) being present, in an amount based on the total of the two most predominantly present cannabinoid active agents of from 0.01 mg/100 ul to 20 mg/100 ul of total formulation;
• wherein said extract contains from 1 up to 5 major cannabinoid pairs, each major cannabinoid pair consisting of the Acid and non-Acid forms thereof, wherein to be considered a major cannabinoid pair, the cannabinoid pair must be at least 20% of the total cannabinoid content of the formulation,
• wherein said extract is obtained in the absence of applying heat at all or in the absence of applying heat greater than 50° C.

A formulation comprising:

• an active containing material selected from the group consisting of (a) an extract of a cannabinoid containing plant material, said extract containing one or more first cannabinoid active agent(s), (b) partially or completely purified second cannabinoid active agents, (c) synthetic second cannabinoid active agents, and (d) mixtures thereof;
• a hydrofluoroalkane (HFA) propellant;
• and a co-solvent, said co-solvent selected from the group consisting of ethanol, propanol, isopropanol, propylene glycol, polyethylene glycol, glycerol, and mixtures thereof;
• said HFA propellant being present in an amount of from 50% by weight to 99.99% by weight based on the entire formulation;
• said co-solvent, being present in an amount of from 0% by weight up to 40% by weight based on the entire formulation;
• and
• said active containing material being present, in an amount based on the total of the two most predominantly present cannabinoid active agents of 0.01 mg/100 ul to 20 mg/100 ul of total formulation;
• wherein said first cannabinoid active agent(s) and said second cannabinoid active agent(s) being independently selected from the group consisting of:
• (a) formula I
• (i) wherein R1 is —CH2(OH), —CH(OH)lower alkyl, —CHO, —C(═O)lower alkyl, or —COOH or a pharmaceutically acceptable ester or a pharmaceutically acceptable amide or a pharmaceutically acceptable salt of said —COOH or a pharmaceutically acceptable ester or pharmaceutically acceptable salt of any alcoholic OHs;
• R2 and R3 are independently H, lower alkyl, or together are ═CH2, or ═CH-lower alkyl, or ═C-(lower alkyl) (lower alkyl);
• R4 is H or lower alkyl;
• R5 and R6 are independently H or lower alkyl;
• R7-R8 are independently H, lower alkyl, —CH2OH, —CHO, —COOH, or a pharmaceutically acceptable ester or pharmaceutically acceptable amide or a pharmaceutically acceptable salt thereof;
• (ii) wherein R1 is lower alkyl, —CH2(OH), —CH(OH)lower alkyl, —CHO, —C(═O)lower alkyl, or —COOH or a pharmaceutically acceptable ester or a pharmaceutically acceptable amide or a pharmaceutically acceptable salt of said —COOH or a pharmaceutically acceptable ester or pharmaceutically acceptable salt of any alcoholic OHs;
• at least one of R2 and R3 are independently H, or together are ═CH2, or ═CH-lower alkyl, or ═C-( lower alkyl) (lower alkyl);
• R4 is H or lower alkyl;
• R5 and R6 are independently H or lower alkyl;
• R7-R8 are independently H, lower alkyl, —CH2OH, —CHO, —COOH, or a pharmaceutically acceptable ester or pharmaceutically acceptable amide or a pharmaceutically acceptable salt thereof;
• (iii) wherein R1 is lower alkyl, —CH2(OH), —CH(OH)lower alkyl, —CHO, —C(═O)lower alkyl, or —COOH or a pharmaceutically acceptable ester or a pharmaceutically acceptable amide or a pharmaceutically acceptable salt of said —COOH or a pharmaceutically acceptable ester or pharmaceutically acceptable salt of any alcoholic OHs;
• R2 and R3 are independently H, lower alkyl, or together are ═CH2, or ═CH-lower alkyl, or ═C-(lower alkyl) (lower alkyl);
• R4 is lower alkyl;
• R5 and R6 are independently H or lower alkyl;
• R7-R8 are independently H, lower alkyl, —CH2OH, —CHO, —COOH, or a pharmaceutically acceptable ester or pharmaceutically acceptable amide or a pharmaceutically acceptable salt thereof;
• (iv) wherein R1 is lower alkyl, —CH2(OH), —CH(OH)lower alkyl, —CHO, —C(═O)-lower alkyl, or —COOH or a pharmaceutically acceptable ester or a pharmaceutically acceptable amide or a pharmaceutically acceptable salt of said —COOH or a pharmaceutically acceptable ester or pharmaceutically acceptable salt of any alcoholic OHs;
• R2 and R3 are independently H, lower alkyl, or together are ═CH2, or ═CH-lower alkyl, or ═C-(lower alkyl) (lower alkyl);
• R4 is H or lower alkyl;
• at least one of R5 and R6 is lower alkyl;
• R7-R8 are independently H, lower alkyl, —CH2OH, —CHO, —COOH, or a pharmaceutically acceptable ester or pharmaceutically acceptable amide or a pharmaceutically acceptable salt thereof;
• (v) wherein R1 is lower alkyl, —CH2(OH), —CH(OH)lower alkyl, —CHO, —C(═O)lower alkyl, or —COOH or a pharmaceutically acceptable ester or a pharmaceutically acceptable amide or a pharmaceutically acceptable salt of said —COOH or a pharmaceutically acceptable ester or pharmaceutically acceptable salt of any alcoholic OHs;
• R2 and R3 are independently H, lower alkyl, or together are ═CH2, or ═CH-lower alkyl, or ═C-(lower alkyl) (lower alkyl);
• R4 is H or lower alkyl;
• R5 and R6 are independently H or lower alkyl;
• at least one of R7-R8 is lower alkyl, —CH2OH, —CHO, —COOH, or a pharmaceutically acceptable ester or pharmaceutically acceptable amide or a pharmaceutically acceptable salt thereof;
• wherein all recitations of “alkyl” without specific carbon length or modified by “lower” being C1-C10 in length;
• and all recitations of “alkyl” and “lower alkyl” being understood as being straight chain or branched chain;
• and
• (b) formulae II-IX below
• wherein R1 is lower alkyl, —CH2(OH), —CH(OH)lower alkyl, —CHO, —C(═O)-lower alkyl, or —COOH or a pharmaceutically acceptable ester or a pharmaceutically acceptable amide or a pharmaceutically acceptable salt of said —COOH or a pharmaceutically acceptable ester or pharmaceutically acceptable salt of any alcoholic OHs;
• R2 and R3 are independently H, lower alkyl, or together are ═CH2, or ═CH-lower alkyl, or ═C-(lower alkyl) (lower alkyl);
• R4 is H or lower alkyl;
• R5 and R6 are independently H or lower alkyl;
• R7-R10 are independently H, lower alkyl, —CH2OH, —CHO, —COOH, or a pharmaceutically acceptable ester or pharmaceutically acceptable amide or a pharmaceutically acceptable salt thereof;
• R11-R16 independently being H, or lower alkyl;
• wherein all recitations of “alkyl” without specific carbon length or modified by “lower” being C1-C10 in length;
• and all recitations of “alkyl” and “lower alkyl” being understood as being straight chain or branched chain;
• and
• (c) mixtures thereof;
• wherein said extract is obtained in the absence of applying heat at all or in the absence of applying heat greater than 50° C.

A formulation comprising:

• a combination of at least two cannabinoid active agent(s),
• at least one of said cannabinoid active agents is selected from such agents other than a group selected from (a)-(d) below:
• (a) tetrahydrocannabinoid (THC) and a pharmaceutically acceptable salt thereof,
• (b) THC, cannabidiol (CBD), and a pharmaceutically acceptable salt thereof,
• (c) THC, tetrahydrocannabinol Acid (THC Acid) and a pharmaceutically acceptable salt thereof, or
• (d) THC, THC Acid, CBD, Cannabidiol Acid (CBD Acid), and a pharmaceutically acceptable salt thereof;
• a hydrofluoroalkane (HFA) propellant;
• and a co-solvent, said co-solvent selected front the group consisting of ethanol, propanol, isopropanol, propylene glycol, polyethylene glycol, glycerol, and mixtures thereof;
• said HFA propellant being present in an amount of from 50% by weight to 99.99% by weight based on the entire formulation;
• said co-solvent, being present in an amount of from 0% by weight up to 40% by weight based on the entire formulation;
• and
• said active containing material being present, in an amount based on the total of the two most predominantly present cannabinoid active agents of 0.01 mg/100 ul to 20 mg/100 ul of total formulation.