Parenteral formulations

Patent metadata

Field	Value
Publication number	US-11229612-B2
Application number	US-201716314583-A
Country	US
Kind code	B2
Filing date	Jun 29, 2017
Priority date	Jul 1, 2016
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

The present invention relates to parenteral cannabinoid formulations, and more particularly to cannabinoid containing intravenous (IV) formulations. Preferably the parenteral containing formulation comprises a cannabinoid; an isotonic agent; a surfactant; and one or more stability enhancers. Furthermore the cannabinoid may be selected from one or more of cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerolpropyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV) and tetrahydrocannabivarinic acid (THCVA).

First claim

The invention claimed is:

1. An aqueous parenteral formulation comprising:
(i) about 0.3 mg/mL to about 50 mg/mL of a cannabinoid comprising cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarinic acid (THCVA), or combinations thereof;
(ii) about 5 mg/mL to about 50 mg/mL of an isotonic agent comprising glucose, polyethylene glycol, or glycerol;
(iii) about 5 mg/mL to about 500 mg/mL of a non-ionic surfactant comprising polyoxyethylene (20) sorbitan monooleate, macrogol 15 hydroxystearate, or polyoxamers; and
(iv) about 0.1 mg/mL to about 10 mg/mL of one or more stability enhancers comprising ascorbic acid, monothioglycerol, cysteine HCl, glutathione, disodium EDTA, calcium disodium EDTA, or combinations thereof;
wherein the formulation has an osmolality of from 100-500 mOsMol/Kg; and
wherein the formulation has a shelf-life of at least about 12 months.

2. The formulation of claim 1 , wherein the cannabinoid is CBD or CBDV.

3. The formulation of claim 1 , wherein the isotonic agent is glycerol or glucose.

4. The formulation of claim 1 , wherein the isotonic agent is glycerol.

5. The formulation of claim 1 , wherein the non-ionic surfactant is polyoxyethylene (20) sorbitan monooleate or macrogol 15 hydroxystearate.

6. The formulation of claim 1 , wherein the non-ionic surfactant is macrogol 15 hydroxystearate.

7. The formulation of claim 1 , wherein the one or more stability enhancers is ascorbic acid, monothioglycerol, or a combination thereof.

8. The formulation of claim 7 , wherein when the ascorbic acid is present, the ascorbic acid is present in an amount of from 0.5 to 10 mg/ml, or when monothioglycerol is present, the monothioglycerol is present in an amount of from 0.5 to 10 mg/ml.

9. The formulation of claim 1 , having a pH ranging from about 3.5 to about 4.13.

10. The formulation of claim 1 , having a pH of about 4.

11. The formulation of claim 1 , wherein the non-ionic surfactant is macrogol 15 hydroxystearate, the isotonic agent is glycerol, and the stability enhancer is ascorbic acid, monothioglycerol, calcium disodium EDTA, disodium EDTA, or combinations thereof.

12. The formulation of claim 1 , having a shelf life of at least about 18 months.

13. The formulation of claim 1 , having a shelf life of at least about 24 months.

14. The formulation of claim 1 , wherein the formulation is stable in climatic zones 1 and 2 for about 12-24 months.

15. The formulation of claim 1 , wherein the formulation is stable in climatic zones 3 and 4 for about 12-24 months.

16. The formulation of claim 1 , wherein the cannabinoid content remains within ±3% of the initial content when tested over 12 months at temperatures ranging from 5-40° C.

Assignees

• Gw Res Ltd

Inventors

• Wright Stephen
• Wilkhu Jitinder

Classifications

• A61K31/658 Primary

  o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title