JP-2022534291-A5 -

Dates

Publication Date

20230529

Application Date

20200529

Description

[Invention 1001](a) Therapeutic agents,(b) Ionization stabilizing excipient,(c) Aprotic polar solvents,(d) Water with a concentration of approximately 10% v/v to approximately 50% v/vA non-protic polar solvent formulation containing and compatible with the flow path of a container and/or injection device.[Invention 1002]A formulation of the present invention 1001, wherein the components of the device channel include rubber, thermoplastics, thermosetting plastics, polystyrene, polyvinyl alcohol, polyvinylpyrrolidone, polyalkylene oxide, acrylamide, acrylic acid, cellulose, cellulose ether, cellulose ester, celluloseamide, polyvinyl acetate, polycarboxylic acid, polyamide, polyacrylamide, maleic acid/acrylic acid copolymer, polysaccharide, or natural gum, or a combination of two or more thereof.[Invention 1003]A formulation of the present invention 1002, wherein the components of the device flow path include polycarbonate (PC), acrylonitrile butadiene styrene (ABS), methacrylonitrile butadiene styrene (MABS), methylcellulose, sodium carboxymethylcellulose, dextrin, ethylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, maltodextrin, polymethacrylate, polystyrene (PS), polyisobutylene (PIB), polymethyl methacrylate (PMMA), ethylene vinyl acetate (EVA), polyvinyl chloride (PVC), thermoplastic polyurethane (TPU), hydroxypropyl methylcellulose (HPMC), high-density polyethylene (HDPE), low-density polyethylene (LDPE), polyurethane, or a blend thereof.[Invention 1004]A formulation of the present invention 1001, wherein the therapeutic agent is a peptide.[Invention 1005]A formulation of the present invention 1004, wherein a peptide or a salt thereof is dissolved in an amount ranging from approximately 0.1 mg/mL to the maximum solubility limit of the peptide or salt thereof.[Invention 1006]A formulation of the present invention 1004, wherein the peptide is a glucagon peptide, a glucagon analog, a glucagon mimetic, or a salt thereof.[Invention 1007]The formulation of the present invention 1001, wherein an ionization-stabilizing excipient is included in the formulation in an amount that maintains the physical stability of the therapeutic agent.[Invention 1008]A formulation of the present invention 1001, wherein the ionization-stabilizing excipient is present in a concentration of 0.01 mM or more and less than 200 mM.[Invention 1009]A formulation according to the present invention 1001, wherein the ionization stabilizing excipient is an inorganic acid.[Invention 1010]A formulation according to the present invention 1005, wherein the inorganic acid is selected from the group consisting of hydrochloric acid, sulfuric acid, and nitric acid.[Invention 1011]A formulation according to the present invention 1001, wherein the aprotic polar solvent is DMSO.[Invention 1012]A formulation according to the present invention 1001, wherein the ionization stabilizing excipient is hydrochloric acid and the aprotic solvent is DMSO.[Invention 1013]A formulation according to the present invention 1001, having a water content of 20% v/v to 40% v/v.[Invention 1014]A formulation of the present invention 1001, further comprising a preservative in less than approximately 10%, less than approximately 5% w/v, or less than approximately 3% w/v.[Invention 1015]A formulation of the present invention 1014, wherein the preservative is metacresol.[Invention 1016]A formulation of the present invention 1001, further comprising disaccharides in a w/v concentration of less than approximately 10%, less than approximately 5%, or less than approximately 3%.[Invention 1017]A formulation of the present invention 1016, wherein the disaccharide is trehalose.[Invention 1018]A formulation of the present invention 1001 having a freezing point of approximately 0°C or less.[Invention 1019]A formulation of the present invention 1018 having a freezing point of approximately -20°C or less.[Invention 1020]A formulation according to the present invention 1018, having a freezing point of approximately -50°C to approximately -80°C.[Invention 1021]A formulation according to the present invention 1001, wherein the container or injection device channel is an infusion set or pump that can administer the formulation parenterally.[Invention 1022]A method for treating hypoglycemia by introducing an effective amount of the formulation of the present invention 1001 to a subject in need.[Invention 1023]A method according to the present invention 1022, wherein a formulation is introduced into a target by injection.[Invention 1024]The method of the present invention 1023, wherein the injection is achieved by pump injection.[Invention 1025]The method of the present invention 1024, wherein the pump injection includes continuous pump injection, bolus pump injection, or a combination thereof.[Invention 1026]A step of mixing at least one ionization-stabilizing excipient, at least one aprotic polar solvent, glucagon, and enough water to result in a formulation water content of