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Bismuth-containing compounds for modulating properties of biologically active agents

A bioactive agent and bismuth compound technology, applied in the field of regulating the pharmacokinetic properties of bioactive agents, can solve problems such as unsatisfactory pharmacokinetic properties and restrictions on marketed drugs

Inactive Publication Date: 2013-09-18
SYNTHONICS CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] Unfavorable pharmacokinetic properties can also limit the use, safety or effectiveness of marketed drugs

Method used

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  • Bismuth-containing compounds for modulating properties of biologically active agents
  • Bismuth-containing compounds for modulating properties of biologically active agents
  • Bismuth-containing compounds for modulating properties of biologically active agents

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Experimental program
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Embodiment

[0148] General synthesis operations and spectra: Stable metal complexes were prepared as described below. The proposed structure of the compound is based on 1 HNMR spectroscopy, and chelation positions were determined from observed chemical shift changes and line broadening, theoretical calculations from known coordination complexes of similar composition, and mass spectral data. Note that for comparison purposes, the proton NMR spectrum of DOPA is: ( 1 H NMR,D 2 O): δ6.90(d;J=8.2Hz;1H),6.82(d;J=2.2Hz,1H),6.74(dd;J=8.2Hz,J=2.2Hz;1H),3.92(dd; J=7.8Hz, J=5.2Hz; 1H), 3.16(dd; J=14.6Hz, 5.2Hz; 1H), 2.99(dd; J=14.6Hz, 7.8Hz; 1H). The metal coordination complexes were neither salts nor mixtures as indicated by the stability observed on the solid phase extraction (SPE) column. Magnesium and zinc salts were not retained on the SPE column, whereas LD was retained on the SPE column much more strongly than the metal coordination complex.

[0149] Mg(dopa) 2 Synthesis: Equip...

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Abstract

Bismuth-containing compounds include bismuth and a biologically active agent coordinated to the bismuth. The biologically active agent includes at least one heteroatom configured for coordination with the bismuth. Coordination polymers include a polymer matrix that contains a bismuth-containing compound. Methods for modulating a pharmacokinetic property of a biologically active agent include coordinating the biologically active agent to bismuth to form a bismuth-containing compound, and administering the bismuth-containing compound orally to a patient. Methods for treating Parkinson's disease, methods for treating hypothyroidism, methods for treating ulcerative colitis, and methods for treating cancer each include administering a bismuth-containing compound to a patient.

Description

[0001] References to earlier filed applications [0002] This application claims the benefit of US Patent Application Serial No. 12 / 941,599, filed November 8, 2010, which is incorporated herein by reference in its entirety. [0003] Federally funded research or development [0004] This invention was made with Government support under Grant No. 1R43NS065572-01A1 awarded by the National Institutes of Health. The government has certain rights in this invention. [0005] technical field [0006] The present invention relates generally to bismuth-containing compounds, methods of therapeutic use in treating patients, and methods of modulating the pharmacokinetic properties of biologically active agents. Background technique [0007] Often, the efficacy of a promising agent is diminished due to one or more undesirable pharmacokinetic properties exhibited by the agent when administered to a patient in vivo. Indeed, achieving an optimal balance between the various pharmacokin...

Claims

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Application Information

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IPC IPC(8): A61K33/24
CPCA61P1/00A61P1/04A61P5/14A61P25/16A61P29/00A61P35/00A61P43/00C07C229/76C07F9/005C07H23/00C08B37/003C08B37/0084
Inventor 约翰·D·普赖斯托马斯·皮卡列洛罗伯特·A·奥伯莱德米夏埃拉·E·马尔哈雷斯科特·B·帕尔默
Owner SYNTHONICS CALIFORNIA
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