Polymer-lipid microencapsulated gases for use as imaging agents
First Claim
1. A method for making microparticles for diagnostic imaging, wherein the microparticles are formed of a biocompatible polymer and have incorporated therein gas, the improvement comprising(a) incorporating into the polymer a hydrophobic compound by either dissolving the polymer and hydrophobic compound in an organic solvent or melting the polymer with the hydrophobic compound, prior to forming the microparticles, and(b) forming the microparticles by either removing the polymer solvent or cooling the polymer,wherein the hydrophobic compound is mixed with the polymer in the microparticle in an amount effective to increase the echogenicity of the microparticle as compared to the echogenicity of the microparticle without the hydrophobic compound andwherein the hydrophobic compound is selected from the group consisting of fatty acids, fatty acid alcohols, fatty acid anhydrides, hydroxy fatty acids, prostaglandins, phospholipids, sphingolipids, steroids and steroid derivatives, fat soluble vitamins, terpenes, tryptophan, tyrosine, isoleucine, leucine, valine, alkyl paraben, and benzoic acid.
3 Assignments
0 Petitions
Accused Products
Abstract
It has been discovered that the incorporation of gases, especially fluorinated gases such as perfluorocarbons, into microparticles formed from the combination of a natural or synthetic polymer and lipid have significantly enhanced echogenicity as compared with microparticles not including the lipid. Compounds other than lipids which are hydrophobic and limit the penetration and/or uptake of water into the microparticles can also be incorporated into the microparticles to enhance echogenicity. In the preferred embodiment, the polymers are synthetic biodegradable polymers. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter of between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens. Preferred polymers are polyhydroxy acids such as polylactic acid-co-glycolic acid, most preferably conjugated to polyethylene glycol or other materials inhibiting uptake by the reticuloendothelial system (RES). The most preferred lipids are phospholipids, preferably dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), diarachidoylphosphatidylcholine (DAPC), dibehenoylphosphatidylcholine (DBPC), ditricosanoylphosphatidylcholine, dilignoceroylphatidylcholine (DLPC), incorporated at a ratio of between 0.01-30 (w lipid/w polymer), most preferably between 0.1-10 (w lipid/w polymer). Microparticles for imaging using other detectable agents can be similarly manufactured.
161 Citations
28 Claims
-
1. A method for making microparticles for diagnostic imaging, wherein the microparticles are formed of a biocompatible polymer and have incorporated therein gas, the improvement comprising
(a) incorporating into the polymer a hydrophobic compound by either dissolving the polymer and hydrophobic compound in an organic solvent or melting the polymer with the hydrophobic compound, prior to forming the microparticles, and (b) forming the microparticles by either removing the polymer solvent or cooling the polymer, wherein the hydrophobic compound is mixed with the polymer in the microparticle in an amount effective to increase the echogenicity of the microparticle as compared to the echogenicity of the microparticle without the hydrophobic compound and wherein the hydrophobic compound is selected from the group consisting of fatty acids, fatty acid alcohols, fatty acid anhydrides, hydroxy fatty acids, prostaglandins, phospholipids, sphingolipids, steroids and steroid derivatives, fat soluble vitamins, terpenes, tryptophan, tyrosine, isoleucine, leucine, valine, alkyl paraben, and benzoic acid.
-
13. A composition for diagnostic imaging comprising biocompatible polymeric microparticles incorporating a gas which are formed by the steps of
(a) dissolving the polymer and a hydrophobic compound in an organic solvent or melting the polymer and the hydrophobic compound, prior to forming the microparticles, (b) forming the microparticles by removing the solvent or cooling the polymer, wherein the hydrophobic compound is mixed with the polymer in the microparticle in an amount effective to increase the echogenicity of the microparticle as compared to the echogenicity of the microparticle without the hydrophobic compound, and wherein the hydrophobic compound is selected from the group consisting of fatty acids, fatty acid alcohols, fatty acid anhydrides, hydroxy fatty acids, prostaglandins, phospholipids, sphingolipids, steroids and steroid derivatives, fat soluble vitamins, terpenes, tryptophan, tyrosine, isoleucine, leucine, valine, alkyl paraben, and benzoic acid.
-
27. In a method for increasing the hydrophobicity of microparticles formed of a biocompatible hydrophobic polymer and having incorporated therein a gaseous imaging agent, the improvement comprising
dissolving the polymer and a hydrophobic compound in an organic solvent or melting the polymer and a hydrophobic compound, removing the solvent or cooling the polymer to form the microparticles, wherein the hydrophobic compound is mixed with the polymer in the microparticle in an amount effective to increase the echogenicity of the microparticle as compared to the echogenicity of the microparticle without the hydrophobic compound.
Specification