[(2R)-2,3-di(octadecanoyloxy)propyl] 2-(trimethylazaniumyl)ethyl phosphate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.27 mg DSPC (1:1 initial L:D ratio) and 1.73 mg cholesterol (7:3 mole % ratio DSPC: cholesterol), both in chloroform, were transferred to a 50 ml round bottom flask. The lipids were dried to a film under vacuum using rotoevaporation. The lipids were then solubilized in 0.500 ml methanol with heating for 1-2 mins. in a 60° C. water bath. Ten milligrams of calcitonin (Mitsubishi Chemical Co., Japan MCI-536) was solubilized in 0.100 ml sodium acetate buffer. This solution was added to the solvent mixture. The solvent was removed under vacuum, using rotoevaporation in a 60° C. water bath. Once the solvent was removed, the lipid/drug film was resuspended in 0.5 ml 60° C. sodium acetate buffer. The preparation was washed by addition of 0.5 ml of 60° C. sodium acetate buffer followed by centrifugation at 12,100×g for 10 minutes. The supernatant was decanted and the liposomal pellet resuspended with 1 ml of 60° C. sodium acetate buffer. The suspension was again centrifuged at 12,100×g for 10 minutes and resuspended. The resuspended DSPC-cholesterol lipomes containing calcitonin were administered s.c. to mice to compare retention of the liposomal preparation to that of free calcitonin. Free calcitonin was undetectable after one hour in mice. The calcitonin of liposomes of the instant invention was at least about 70% present one day after administration and persisted for about 3 to 7 days disclosing a substantial increase in retention time over free calcitonin. The lipids were dried to a film under vacuum with heating for 1-2 mins in a 60° C. This solution was added to the solvent mixture The solvent was removed under vacuum in a 60° C. Once the solvent was removed was resuspended in 0.5 ml 60° C. sodium acetate buffer The preparation was washed by addition of 0.5 ml of 60° C. sodium acetate buffer The supernatant was decanted resuspended with 1 ml of 60° C. sodium acetate buffer g for 10 minutes The resuspended DSPC-cholesterol lipomes containing calcitonin retention of the liposomal preparation to that of free calcitonin was at least about 70% present one day persisted for about 3 to 7 days

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.27 mg DSPC (1:1 initial L:D ratio) and 1.73 mg cholesterol (7:3 mole % ratio DSPC: cholesterol), both in chloroform, were transferred to a 50 ml round bottom flask. The lipids were dried to a film under vacuum using rotoevaporation. The lipids were then solubilized in 0.500 ml methanol with heating for 1-2 mins. in a 60° C. water bath. Ten milligrams of calcitonin (Mitsubishi Chemical Co., Japan MCI-536) was solubilized in 0.100 ml sodium acetate buffer. This solution was added to the solvent mixture. The solvent was removed under vacuum, using rotoevaporation in a 60° C. water bath. Once the solvent was removed, the lipid/drug film was resuspended in 0.5 ml 60° C. sodium acetate buffer. The preparation was washed by addition of 0.5 ml of 60° C. sodium acetate buffer followed by centrifugation at 12,100×g for 10 minutes. The supernatant was decanted and the liposomal pellet resuspended with 1 ml of 60° C. sodium acetate buffer. The suspension was again centrifuged at 12,100×g for 10 minutes and resuspended. The resuspended DSPC-cholesterol lipomes containing calcitonin were administered s.c. to mice to compare retention of the liposomal preparation to that of free calcitonin. Free calcitonin was undetectable after one hour in mice. The calcitonin of liposomes of the instant invention was at least about 70% present one day after administration and persisted for about 3 to 7 days disclosing a substantial increase in retention time over free calcitonin. The lipids were dried to a film under vacuum with heating for 1-2 mins in a 60° C. This solution was added to the solvent mixture The solvent was removed under vacuum in a 60° C. Once the solvent was removed was resuspended in 0.5 ml 60° C. sodium acetate buffer The preparation was washed by addition of 0.5 ml of 60° C. sodium acetate buffer The supernatant was decanted resuspended with 1 ml of 60° C. sodium acetate buffer g for 10 minutes The resuspended DSPC-cholesterol lipomes containing calcitonin retention of the liposomal preparation to that of free calcitonin was at least about 70% present one day persisted for about 3 to 7 days

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 8.27 mg DSPC (1:1 initial L:D ratio) and 1.73 mg cholesterol (7:3 mole % ratio DSPC: cholesterol), both in chloroform, were transferred to a 50 ml round bottom flask. The lipids were dried to a film under vacuum using rotoevaporation. The lipids were then solubilized in 0.500 ml methanol with heating for 1-2 mins. in a 60° C. water bath. Ten milligrams of calcitonin (Mitsubishi Chemical Co., Japan MCI-536) was solubilized in 0.100 ml sodium acetate buffer. This solution was added to the solvent mixture. The solvent was removed under vacuum, using rotoevaporation in a 60° C. water bath. Once the solvent was removed, the lipid/drug film was resuspended in 0.5 ml 60° C. sodium acetate buffer. The preparation was washed by addition of 0.5 ml of 60° C. sodium acetate buffer followed by centrifugation at 12,100×g for 10 minutes. The supernatant was decanted and the liposomal pellet resuspended with 1 ml of 60° C. sodium acetate buffer. The suspension was again centrifuged at 12,100×g for 10 minutes and resuspended. The resuspended DSPC-cholesterol liposomes containing calcitonin were administered s.c. to mice to compare retention of the liposomal preparation to that of free calcitonin. Free calcitonin was undetectable after one hour in mice. The calcitonin of liposomes of the instant invention was at least about 70% present one day after administration and persisted for about 3 to 7 days disclosing a substantial increase in retention time over free calcitonin. The lipids were dried to a film under vacuum with heating for 1-2 mins in a 60° C. This solution was added to the solvent mixture The solvent was removed under vacuum in a 60° C. Once the solvent was removed was resuspended in 0.5 ml 60° C. sodium acetate buffer The preparation was washed by addition of 0.5 ml of 60° C. sodium acetate buffer The supernatant was decanted resuspended with 1 ml of 60° C. sodium acetate buffer g for 10 minutes The resuspended DSPC-cholesterol liposomes containing calcitonin retention of the liposomal preparation to that of free calcitonin was at least about 70% present one day persisted for about 3 to 7 days

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A tobramycin sulfate dry powder composition is prepared according to the following procedure. Sterile Water for Irrigation (SWFI) is heated above the gel to liquid crystal temperature (about 80° C.) of disteroyl phosphatidylcholine (DSPC). DSPC and calcium chloride dihydrate are then added to the heated water. The resulting lipid dispersion is mixed in an UltraTurrax T-50 (IKA Labortechnik) at 8,000 rpm for 5 min. Perfluorooctyl bromide (PFOB) is then added dropwise (15 ml/min) to the lipid dispersion under mixing. After the addition is complete the resulting PFOB-in-water emulsion is mixed for an additional 10 min at 10,000 rpm. Emulsification in the UltraTurrax produces droplets in the micron-size range. Tobramycin sulfate is then dissolved in the continuous phase of the emulsion and the resulting dispersion is used as the feedstock for spray drying. The feedstock is then spray dried to obtain a dry powder formulation having the composition set forth in Table 1 below. A tobramycin sulfate dry powder composition is prepared The resulting lipid dispersion is mixed in an UltraTurrax T-50 (IKA Labortechnik) at 8,000 rpm for 5 min under mixing After the addition is mixed for an additional 10 min at 10,000 rpm Emulsification in the UltraTurrax produces droplets in the micron-size range drying The feedstock is then spray dried to obtain a dry powder formulation