Microfluidization of calcium/oxyanion-containing particles
AssigneeMallinckrodt Medical, Inc.
InventorsLinda Meeh, William P. Cacheris
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Abstract
Methods of preparing solid apatite particles using a microfluidizer, for use in medical diagnostic imaging such as magnetic resonance imaging, X-ray, and ultrasound. The desired apatite particles are synthesized, passed through a microfluidizer, and purified to remove excess base, salts, and other materials used to synthesize the particles. The microfluidizer causes two high pressure streams to interact at ultra high velocities in a precisely defined microchannel. Microfluidization of preparations causes small (<5 .mu.m) and uniform particles to be formed. Coating and purifying (especially by tangential flow filtration) the particles improves particle stability.
Claims41
A method of preparing a calcium/oxyanion-containing particle for use in medical diagnostic imaging of body organs and tissues comprising the steps of:
- (a) obtaining calcium/oxyanion-containing particles having the following general formula:
- Ca.sub.n M.sub.m X.sub.r Y.sub.s
- wherein M is a paramagnetic metal ion or stoichiometric mixture of paramagnetic metal ions, X is a simple anion, Y is an oxyanion, tetrahedral oxyanion, carbonate, or mixtures thereof, n is from 1 to 10, m is from 1 to 10, s is.gtoreq.1, and r is adjusted as needed to provide charge neutrality;
- and
- (b) passing the calcium/oxyanion-containing particles through a microfluidizer.
A method of preparing apatite or apatite precursor particles for use in magnetic resonance imaging of body organs and tissues comprising the steps of:
- (a) obtaining particles having the following general formula:
- Ca.sub.n Mn.sub.m (OH).sub.2 (PO.sub.4).sub.6
- wherein m is from 1 to 10, n is from 1 to 10, and m+n=10;
- (b) passing the particles through a microfluidizer;
- and
- (c) purifying the particles from base and salts used to synthesize the particles.
A method of preparing apatite or apatite precursor particles for use in magnetic resonance imaging of body organs and tissues comprising the steps of:
- (a) obtaining apatite particles comprising apatite or apatite precursor particles, a paramagnetic metal species adsorbed to the surface of the apatite particle, and a di- or polyphosphonate coating agent;
- (b) passing the apatite particles through a microfluidizer;
- and
- (c) purifying the apatite particles from base and salts used to synthesize the apatite particles.
A method of preparing apatite or apatite precursor particles for use in magnetic resonance imaging comprising the steps of:
- (a) preparing apatite or apatite precursor particles having a particle size in the range from about 5 nm to about 50 .mu.m;
- (b) adsorbing a bifunctional coating agent capable of forming a chelate complex with a paramagnetic metal ion onto the apatite particle surface;
- (c) forming a chelate complex between the bifunctional coating agent and the paramagnetic metal ion;
- and
- (d) passing the apatite particles through a microfluidizer;
- and
- (e) purifying the apatite particles from base and salts used to synthesize the apatite particles.
Dependencies are inferred from the claim text.