A61K49/106

Reduced metastable complex macrocyclic contrast agents
11419953 · 2022-08-23 · ·

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.

Lanthanide complex formulations

The present invention relates to a method of removal of metal ion impurities, such as calcium, from lanthanide metal complexes of macrocyclic chelators. The method uses a scavenger resin to remove metal ions, displaced from chelator, by an excess of lanthanide ions. Also provided is a method of preparation of MRI contrast agents, from the purified lanthanide metal complex, by the addition of a defined excess chelator.

Texaphyrin-Pt(IV) conjugates and compositions for use in overcoming platinum resistance

The present disclosure relates platinum(IV) and texaphyrin linked conjugates and compositions comprising a texaphyrin and a platinum(IV) agent. The present disclosure also provides pharmaceutical compositions of the conjugates and compositions. Also, provided herein are methods of using the instant compounds in the treatment of cancer such as a platinum resistant cancer.

CYCLEN BASED COMPOUNDS, COORDINATION COMPOUNDS, PEPTIDES, PHARMACEUTICAL PREPARATION, AND USE THEREOF

Cyclen based compounds of general formula (I) are disclosed. X is nitrogen and Y, Z are —CH—, or X, Z are —CH— and Y is nitrogen, or X, Y are —CH— and Z is nitrogen. R.sup.1 is independently selected from H; COOH; benzyloxycarbonyl; fluorenylmethyloxycarbonyl; tert-butoxycarbonyl; methylcarbonyl; trifluoromethylcarbonyl; benzyl; triphenylmethyl; tosyl; mesyl; benzyloxymethyl; phenylsulfonyl; ethoxycarbonyl; 2,2,2-trichloroethyloxycarbonyl; methoxycarbonyl; methoxymethyloxycarbonyl; R.sup.2 is selected from H; methylcarbonyl; tert-butyldimethylsilyl; (C1-C4)alkyl; R.sub.3 is independently selected from H; (C1-C6)alkyl.

Polarisation transfer via a second metal complex

There is described a method for preparation of an imaging medium via transfer from a hyperpolarised singlet state that is not parahydrogen, said method comprising the steps of: (i) preparing a system containing: parahydrogen; a magnetisation transfer complex, with a molecular symmetry that allows the creation of a singlet state between spin pairs within it, said complex including a reversibly bound small molecule transference substrate; applying a magnetic field such that hyperpolarisation is transferred into the transfer complex, including the reversibly bound small molecule transference substrate; (ii) introducing a recipient complex capable of binding the small molecule transference substrate, said recipient complex including a recipient substrate, such that the recipient complex and recipient substrate, including the bound transference substrate, is hyperpolarised.

SOLVENT FREE GADOLINIUM CONTRAST AGENTS

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.

NARROW EMISSION DYES, COMPOSITIONS COMPRISING SAME, AND METHODS FOR MAKING AND USING SAME

Provided are chlorin derivatives with narrow band emission. In some embodiments, the bacteriochlorin derivatives are PEGylated. In some embodiments, the chlorin derivatives have high water solubility (e.g., 10 mg/mL or more). In some embodiments, the chlorin derivatives are PEGylated and have high water solubility. The chlorin derivatives can include bioconjugatable groups for forming conjugates, for example, with antibodies and nanoparticles. The chlorin derivatives and their conjugates can be used in imaging and therapeutic applications. Methods of synthesizing the chlorin derivatives are also provided.

NARROW EMISSION DYES, COMPOSITIONS COMPRISING SAME, AND METHODS FOR MAKING AND USING SAME

Provided are bacteriochlorin derivatives with narrow band emission. In some embodiments, the bacteriochlorin derivatives are PEGylated. In some embodiments, the bacteriochlorin derivatives have high water solubility (e.g., 10 mg/mL or more). In some embodiments the bacteriochlorin derivatives are PEGylated and have high water solubility. The bacteriochlorin derivatives can include bioconjugatable groups for forming conjugates, for example, with antibodies and nanoparticles. The bacteriochlorin derivatives and their conjugates can be used in imaging and therapeutic applications. Methods of synthesizing the bacteriochlorin derivatives are also provided.

IMAGING WITH LIPOSOME-BASED CONTRAST AGENTS BASED ON MODULATION OF MEMBRANE WATER PERMEABILITY

The present disclosure provides imaging and contrast agents, and methods of using the agents. According to some embodiments of the disclosure, agents and methods for magnetic resonance imaging and related technologies are provided.

Modified biotin, streptavidin mutant, and usage of them

An object of this invention is to provide a streptavidin mutant reduced in affinity to the naturally-occurring biotin, and to provide a modified biotin which shows a high affinity to such streptavidin mutant reduced in affinity to the naturally-occurring biotin. This invention can provide a compound composed of a dimer of modified biotin, a streptavidin mutant, and usage of them.