Abstract: Gadolinium based contrast agents (GCA) incorporating linear ligand chelation are fundamentally different from GCAs incorporating macrocyclic ligands. The macrocyclic GCAs are synthesized by pathways characterized by the formation of a sequence of metastable complexes before obtaining the final stable complex. The synthesis of linear GCAs do not form metastable complexes. Commercial macrocyclic GCAs contain unstable metastable complexes. These metastable species are not regulated and quickly release free Gd3+ ions upon administration into the body. Gadolinium based contrast agents with near zero metastable species content and methods of synthesizing the same are disclosed. Gadolinium based contrast agents with long dissociation time in the body, and low free Gd3+ ion formation are obtained using a synthesis method which departs in novel ways from the traditional free Gd3+-based synthesis methods.

Abstract: Gadolinium based contrast agents (GCA) incorporating linear ligand chelation are fundamentally different from GCAs incorporating macrocyclic ligands. The macrocyclic\GCAs are synthesized by pathways characterized by the formation of a sequence of metastable complexes before obtaining the final stable complex. The synthesis of linear GCAs do not form metastable complexes. Commercial macrocyclic GCAs contain unstable metastable complexes. These metastable species are not regulated and quickly release free Gd3+ ions upon administration into the body. Gadolinium based contrast agents with near zero metastable species content and methods of synthesizing the same are disclosed. Gadolinium based contrast agents with long dissociation time in the body, and low free Gd3+ ion formation are obtained using a synthesis method which departs in novel ways from the traditional free Gd3+-based synthesis methods.

Abstract: Macrocyclic gadolinium-based contrast agents (GCA) are synthesized by pathways characterized by the formation of a sequence of metastable complexes before obtaining the final stable complex. Commercial macrocyclic GCAs contain unstable metastable complexes. These metastable species quickly release free Gd3+ ions upon delivery into the body. Aqueous or dry/solid GCA with near zero metastable species content and methods of synthesizing the same are disclosed.

Abstract: Disclosed herein are complexes of gadolinium metal, ligand and meglumine that are substantially free of non-aqueous solvents. In particular, solvent-free complexes of 1) gadopentetate dimeglumine and 2) gadoterate meglumine are disclosed and methods of their preparation are disclosed. In addition, methods are disclosed for purifying reactants, monitoring and controlling pH, quantifying the free gadolinium content, quantifying the concentration of gadolinium-ligand complex in aqueous solution, and procedures for producing a drug product in one step. The one step process eliminates the need to dry the gadolinium-ligand complex, which is typically highly hygroscopic. The one step process includes purification steps that do not require the use of non-aqueous solvents.

Abstract: Disclosed herein are complexes of gadolinium metal, ligand and meglumine that are substantially free of non-aqueous solvents. In particular, solvent-free complexes of 1) gadopentetate dimeglumine and 2) gadoterate meglumine are disclosed and methods of their preparation are disclosed. In addition, methods are disclosed for purifying reactants, monitoring and controlling pH, quantifying the free gadolinium content, quantifying the concentration of gadolinium-ligand complex in aqueous solution, and procedures for producing a drug product in one step. The one step process eliminates the need to dry the gadolinium-ligand complex, which is typically highly hygroscopic. The one step process includes purification steps that do not require the use of non-aqueous solvents.

Abstract: The device includes an accelerometer for sensing a parameter of movement, such as direction and/or magnitude. A pre-recorded sound is played in response to the sensed movement. The speed and/or pitch at which the pre-recorded sound is played is a function of the sensed movement parameter. There may be one or more pre-recorded sounds from which playback is chosen. In one embodiment, hardwired circuits set the characteristics of the generated sound in accordance with the accelerometer output. In a second embodiment, the software selects which pre-recorded sound to play and sets the characteristics of the sound based upon parameters sensed by the accelerometer.

Abstract: The device includes an accelerometer for sensing movement in more than one direction, a sound chip for generating a pre-recorded sound in response to the sensed movement and a circuit for controlling the speed at which the pre-recorded sound is generated in response to the sensed movement, as a function of the direction of the sensed movement. The accelerometer senses the magnitude of movement. The sound chip generates sound in response to movement of a magnitude exceeding a pre-set level. The accelerator senses movement in at least two, preferably three directions. The sound chip includes an oscillator which determines the speed at which a pre-recorded sound is processed. The control means provides a control signal which sets the sound chip to generate the sound signal with a speed which is a function of the number of directions of sensed movement.