# US 2021/0275470 A1 · Packaged, sealed container system for stable storage of an oxygen sensitive pharmaceutical formulation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275470 A1 - Document ID: US20210275470A1 - Status: Published application - Kind: A1 - Application number: 17/249,642 - Filed: 2021-03-08 - Published: 2021-09-09 - Earliest claimed: 2020-03-06 - Assignees: Baxter International Inc.; Baxter Healthcare S.A. - Applicants: Baxter International Inc.; Baxter Healthcare SA - Inventors: Steven M. Cope; Allan E. Titus - Web page: https://patentgrep.com/patent/US20210275470A1 ## CPC - A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} - A61J 1/10: Bag-type containers - A61J 1/1468: {Containers characterised by specific material properties} - A61J 1/16: Holders for containers - A61M 5/002: {Packages specially adapted therefor, e.g. packages for syringes or needles or kits for diabetics} - B65D 75/28: Articles or materials wholly enclosed in composite wrappers, i.e. wrappers formed by associating or interconnecting two or more sheets or blanks - B65D 81/266: {for absorbing gases, e.g. oxygen absorbers or desiccants (B65D51/244, B65D51/30 take precedence)} - A61J 1/14: Details; Accessories therefor (A61J7/00 takes precedence; openers B65D, B67B7/00) - A61J 1/1475: {Inlet or outlet ports} - A61M 1/14: Dialysis systems; Artificial kidneys; Blood oxygenators (semi-permeable membranes characterised by the material, manufacturing processes therefor B01D71/00){; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis} - A61M 5/14: Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor - 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) - A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - B65D: CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES ## Abstract A packaged, sealed container system for stable storage of a formulation of an oxygen-sensitive pharmaceutical compound, the packaged, sealed container system comprising a primary container including therein a formulation of an oxygen-sensitive pharmaceutical compound, a secondary outer container comprising a first flexible sheet layer, an opposing second flexible sheet layer, and a seal disposed along a common peripheral edge of the first and second flexible sheet layers, such that the primary container is disposed between and enclosed by the first and second flexible sheet layers of the secondary outer container. An oxygen scavenger is also disposed between and enclosed by the first and second flexible sheet layers of the secondary outer container. The oxygen scavenger is in fluid communication with the contents of the primary container. ## Claims ### Claim 1 A packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation, the packaged, sealed container system comprising: a primary container comprising a ready-to-use, stable norepinephrine formulation therein, the ready-to-use, stable norepinephrine formulation comprising: 0.01 mg/ml to less than 0.04 mg/ml norepinephrine; an aqueous tonicity adjusting agent; a pH between 3.4 and 4.0; wherein the ready-to-use, stable norepinephrine formulation is free of an antioxidant; a secondary container comprising a first flexible sheet layer, an opposing second flexible sheet layer, and a seal disposed along a common peripheral edge of the first and second flexible sheet layers, wherein the primary container is disposed between and enclosed by the first and second flexible sheet layers of the secondary container; and, an oxygen scavenger disposed between and enclosed by the first and second flexible sheet layers of the secondary container, the oxygen scavenger being in fluid communication with the contents of the primary container. ### Claim 2 (canceled) ### Claim 3 (canceled) ### Claim 4 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the primary container is a plastic bag with a single port, the single port comprising an administration port for delivering the ready-to-use, stable norepinephrine formulation to a patient. ### Claim 5 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the primary container is a plastic bag comprising a third flexible sheet layer, an opposing fourth flexible sheet layer, and a primary container seal disposed along a common peripheral edge of the third and fourth flexible sheet layers. ### Claim 6 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the primary container is a plastic bag comprising a third flexible sheet layer folded and arranged such that first and second faces of the sheet layer are opposing one another and a primary container seal disposed along a common peripheral edge of the first and second faces. ### Claim 7 (depends on 5) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 5, wherein the third or the third and fourth flexible sheets are coextruded film laminates comprising a polypropylene layer. ### Claim 8 (depends on 7) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 7, wherein the coextruded film laminates further comprise a polyamide layer. ### Claim 9 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the first flexible sheet layer comprises a coextruded film including a metal foil. ### Claim 10 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the opposing second flexible sheet layer comprises a transparent coextruded film configured to allow visual inspection into the secondary container. ### Claim 11 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the opposing second flexible sheet layer is colored to protect the ready-to-use, stable norepinephrine formulation from light. ### Claim 12 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the second flexible sheet layer has a water transmission rate less than 3.0 g/m2/day. ### Claim 13 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the oxygen scavenger comprises iron powder, iron oxide powder, or a mixture thereof. ### Claim 14 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the concentration of norepinephrine is between about 0.015 mg/ml and about 0.035 mg/ml. ### Claim 15 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the concentration of norepinephrine is between about 0.015 mg/ml and about 0.020 mg/ml. ### Claim 16 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the concentration of norepinephrine is between about 0.030 mg/ml and about 0.035 mg/ml. ### Claim 17 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the norepinephrine is in the form of norepinephrine bitartrate monohydrate. ### Claim 18 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the aqueous tonicity agent is selected from the group comprising sodium chloride, potassium chloride, calcium chloride, mannitol, glycerol, sorbitol, propylene glycol, dextrose, sucrose, and mixtures thereof. ### Claim 19 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the aqueous tonicity adjusting agent is dextrose. ### Claim 20 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the aqueous tonicity agent is sodium chloride. ### Claim 21 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the pH is between about 3.5 and about 3.9. ### Claim 22 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the pH is between about 3.6 and about 3.8. ### Claim 23 (depends on 1) The packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1, wherein the ready-to-use, stable norepinephrine formulation has a dissolved oxygen level of less than 1 ppm after storage for, for 30 days, for/10 days, for 60 days, for 90 days, for 150 days, for 180 days, and/or at least 1 year at 25° C. ### Claim 24 (depends on 1) A method of treating hypotension in a subject, the method comprising: opening the packaged, sealed container system for stable storage of a ready-to-use, stable norepinephrine formulation according to claim 1; administering to a subject a therapeutically effective amount of the ready-to-use, stable norepinephrine formulation, wherein the subject is in need of treatment for hypotension. ### Claim 25 (depends on 24) The method of claim 24 wherein the subject has a condition selected from one or more of pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, myocardial infarction, septicemia, blood transfusion, and drug reactions. ### Claim 26 (depends on 24) The method of claim 24 wherein the subject has a condition selected from one or more of cardiac arrest and profound hypotension. ### Claim 27 A packaged, sealed container system for stable storage of a formulation of an oxygen-sensitive pharmaceutical compound, the packaged, sealed container system comprising: a primary container comprising a formulation of an oxygen-sensitive pharmaceutical compound therein; a secondary container comprising a first flexible sheet layer, an opposing second flexible sheet layer, and a seal disposed along a common peripheral edge of the first and second flexible sheet layers, wherein the primary container is disposed between and enclosed by the first and second flexible sheet layers of the secondary container; and, an oxygen scavenger disposed between and enclosed by the first and second flexible sheet layers of the secondary outer container. ### Claim 28 (depends on 27) The packaged, sealed container system according to claim 27, wherein the oxygen-sensitive pharmaceutical compound comprises a catechol amine. ### Claim 29 A ready-to-use norepinephrine formulation comprising about 0.01 mg/ml to about 0.04 mg/ml norepinephrine, an aqueous tonicity adjusting agent, a pH between about 3.4 and about 4.0, wherein the formulation is free of an antioxidant is provided.