# US 11,026,938 B2 · Therapeutical composition containing apomorphine as active ingredient > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,938 B2 - Document ID: US11026938B2 - Status: Granted - Kind: B2 - Application number: 14/152,000 - Filed: 2014-01-10 - Published: 2014-05-08 - Granted: 2021-06-08 - Earliest claimed: 2011-07-11 - Assignees: Britannia Pharmaceuticals Limited - Applicants: Britannia Pharmaceuticals Ltd. - Inventors: Michael Dey; Joel Richard; Marie-Madeleine Baronnet; Nathalie Mondoly; Laurent Bertocchi; Jeremiah Harnett - Web page: https://patentgrep.com/patent/US11026938B2 ## CPC - A61K 31/473: ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines - A61K 9/0019: {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)} - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61P 25/16: Anti-Parkinson drugs - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A pharmaceutical composition contains apomorphine as the active pharmaceutical ingredient, a water-miscible co-solvent, an antioxidant, and water. The solution has a pH greater than 4. The pharmaceutical composition is suitable for parenteral administration for the treatment of Parkinson's disease. The process for the manufacture of the pharmaceutical composition includes weighing the apomorphine and introducing it into a container with the co-solvent and the antioxidant under agitation until complete dissolution takes place. ## Claims ### Claim 1 A pharmaceutical composition for parenteral administration by injection having an active substance and being provided in the form of a solution, the pharmaceutical composition comprising: i) apomorphine as the active substance; ii) a water miscible co-solvent; iii) an antioxidant; iv) water; v) optionally, a surfactant; and vi) optionally, a pH modifier; wherein a pH of the pharmaceutical composition is greater than 4, and wherein the pharmaceutical composition is administrable through a needle with a 27 Gauge or larger. ### Claim 2 (depends on 1) The composition of claim 1, wherein an amount of the active substance is between about 10 to 70 mg/ml. ### Claim 3 (depends on 1) The composition according to claim 1, wherein an amount of the water miscible co-solvent is between 0.1 to 80% (w:w) of the composition. ### Claim 4 (depends on 1) The composition according to claim 1, wherein the water miscible co-solvent is selected from the group consisting of an alcohol, a polyol, and a polyether or a mixture thereof. ### Claim 5 (depends on 1) The composition according to claim 1, wherein the co-solvent is selected from a diol, a triol, a cyclodextrin derivative, a polyethylene glycol, and a polyethylene glycol derivative or a mixture thereof. ### Claim 6 (depends on 1) The composition according to claim 1, wherein the antioxidant is selected from the group consisting of an acid, a salt thereof, a vitamin, a vitamin derivative, an amino acid, a sulphite, and a phenolic free radical scavenger. ### Claim 7 (depends on 1) The composition according to claim 1, wherein the antioxidant is selected from the group consisting of ascorbic acid and sodium metabisulfite. ### Claim 8 (depends on 1) The composition according to claim 1, wherein the pharmaceutical composition further comprises the surfactant. ### Claim 9 (depends on 8) The composition of claim 8 wherein the surfactant has a hydrophile lipophile balance (HLB) between 8 and 20. ### Claim 10 (depends on 8) The composition of claim 8, wherein the surfactant is selected from the group consisting of a polyoxyethylene sorbitan fatty ester, a polyethylene glycol derivative, and a poloxamer. ### Claim 11 (depends on 1) The composition according to claim 1, wherein an apomorphine:co-solvent ratio (w:w) is between 1:0.1 to 1:40. ### Claim 12 (depends on 1) The composition according to claim 1, wherein the pH of the composition is between 4 and 7. ### Claim 13 (depends on 1) The composition according to claim 1, wherein the composition further comprises the pH modifier. ### Claim 14 (depends on 13) The composition according to claim 13, wherein the pH modifier is selected from the group consisting of sodium hydroxide, sodium bicarbonate, potassium hydroxide, and magnesium hydroxide or a mixture thereof. ### Claim 15 A method of administering a pharmaceutical composition to a patient in need thereof, the composition having an active substance and being provided in the form of a solution, the pharmaceutical composition comprising: i) apomorphine as the active substance; ii) a water miscible co-solvent; iii) an antioxidant; iv) water; v) optionally, a surfactant; and vi) optionally, a pH modifier; wherein a pH of the composition is greater than 4, and wherein the pharmaceutical is administered through a needle with a 27 Gauge or larger. ### Claim 16 (depends on 1) A method of reducing “off episodes” in a patient with advanced Parkinson's disease comprising administering the composition according to claim 1. ### Claim 17 (depends on 1) An injection solution for the treatment of Parkinson's disease comprising the composition according to claim 1. ### Claim 18 (depends on 1) A process for the manufacture of the composition according to claim 1, the process comprising: i) providing a first container; ii) optionally, weighing a surfactant in the first container; iii) adding the co-solvent to the first container; iv) weighing the antioxidant in a second container and dissolving the antioxidant in degassed water to obtain an antioxidant solution; v) adding the antioxidant solution to the first container under agitation; vi) adding degassed water to the first container and adjusting the pH to about 7.5±0.5; vii) weighing the apomorphine and introducing the apomorphine to the first container under agitation until complete dissolution takes place; viii) controlling the pH of the solution in the first container within the range of 4 to 7 by adding a pH modifier as necessary to maintain the pH within the range; and, ix) adding a remaining quantity of degassed water to reach a predetermined volume of the solution. ### Claim 19 (depends on 1) The composition according to claim 1, wherein the composition is suitable for subcutaneous infusion. ### Claim 20 A pharmaceutical composition for parenteral administration by injection having an active substance and being provided in the form of a solution, the pharmaceutical composition comprising: i) apomorphine as the active substance; ii) a water miscible co-solvent; iii) an antioxidant; iv) water; v) optionally, a surfactant; and vi) optionally, a pH modifier; wherein a pH of the pharmaceutical composition is greater than 4, wherein the pharmaceutical composition is administrable through a needle with a 27 Gauge or larger, and wherein an amount of the active substance is between about 10 to 70 mg/ml.