Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – X-ray contrast imaging agent
Patent
1994-05-16
1998-12-22
Lovering, Richard D.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
X-ray contrast imaging agent
252312, 252314, 424 189, 424 937, 424 94, 514744, 514938, 514941, A61K 4900, B01J 1300
Patent
active
058515100
ABSTRACT:
A heat and shelf-stable oil-in-water emulsion useful as a tissue or cell-selective delivery vehicle. Radioactive or stable, synthetic or semi-synthetic polyhalogenated triglycerides, such as phenyl acetate, can be incorporated into the lipophilic core of a lipoprotein-like emulsion particle. The lipophilic core is surrounded by a phospholipid membrane comprising cholesterol and apolipoproteins. For hepatocyte-selective delivery, the emulsion is chylomicron remnant-like by being in a size range of 50 to 200 nm as measured by number weighting analysis with a narrow size distribution (<2% greater than 300 nm) and having a composition simulating naturally-occurring chylomicron remnants. Use of cholesterol in the emulsion formula facilitates association of apolipoproteins, especially Apo E which are recognized by liver cells and necessary for binding and uptake. Stability and size constraints can be achieved by using ultra high energy mixing equipment, such as such as the MicroFluidizer (Microfluidics Corp., Newton, Mass.) to form the emulsion. In preferred embodiments, osmolality of the emulsion is controlled by glycerol rather than normal saline.
REFERENCES:
patent: Re32393 (1987-04-01), Wretlind et al.
patent: 3992513 (1976-11-01), Petkau et al.
patent: 4073943 (1978-02-01), Wretlind et al.
patent: 4309289 (1982-01-01), Head
patent: 4816247 (1989-03-01), Desai et al.
patent: 4873075 (1989-10-01), Counsell et al.
patent: 4917880 (1990-04-01), Wretlind et al.
patent: 4957729 (1990-09-01), Counsell et al.
patent: 4970209 (1990-11-01), Wretlind et al.
patent: 5004756 (1991-04-01), Ogawa et al.
patent: 5039527 (1991-08-01), Tabibi
patent: 5055303 (1991-10-01), Riley, Jr.
patent: 5080885 (1992-01-01), Long, Jr.
patent: 5093042 (1992-03-01), Counsell et al.
patent: 5093044 (1992-03-01), Wretlind et al.
patent: 5098606 (1992-03-01), Nakajima et al.
patent: 5116599 (1992-05-01), Rogers, Jr., et al.
patent: 5152923 (1992-10-01), Weder et al.
patent: 5171737 (1992-12-01), Weiner et al.
patent: 5234680 (1993-08-01), Rogers et al.
patent: 5445811 (1995-08-01), Norrlind et al.
Clark, et al., "Phosphatidylcholine Composition of Emulsions Influences Triacylglycerol Lipolysis and Clearance from Plasma," Biochimica et Biophysica Acta, vol. 920, pp. 37-46 (1987).
Cooper, et al., "Rates of Removal and Degradation of Chylomicron Remnants by Isolated Perfused Rat Liver," J. Lipid Research, vol. 19, pp. 635-643 (1978).
Cooper, "Hepatic Clearance of Plasma Chylomicron Remnants," vol. 12, No. 4, pp. 386-396 (1992).
Counsell et al., "Lipoproteins as Potential Site-Specific Delivery Systems for Diagnostic and Therapeutic Agents," J. Med. Chem., vol. 25, No. 10, pp. (1982).
Damle et al., "Potential Tumor-or organ-imaging Agents XXIV: Chylomicron Remnants as Carrier for Hepatographic Agents," J. Pharm. Science., vol. 72, No. 8, pp. 898-901 (1983).
Gardner et al., "Comparison of the Metabolism of Chylomicrons and Chylomicron Remnants by the Perfused Liver," Biochem. J., vol. 170, pp. 47-55 (1978).
Grimes, "Formulation and Evaluation of Ethiodized Oil Emulsion for Intravenous Hepatography," J. Pharm. Sci., vol. 68, No. 1, pp. 52-56 (1979).
"Handbook of Chemistry and Physics," 58th edition, CRC Press, B-303-B-305 (1977-1978).
Hamilton et al., "Apolipoprotein E Localization in Rat Hepatocytes by immunogold Labeling of Cryothin Sections," J. Lipid Research, vol. 31, pp. 1589-1603 (1990).
Ivancev et al., "Effect of Intravenously Injected Iodinate Lipid Emulsions on the Liver," Acta Radiologica, vol. 30, Fasc. 3, pp. 291-297 (1989).
Ivancev et al., "Experimental Investigation of a New Iodinated Lipid Emulsion for Computed Toography of the Liver," Acta Radiologica, vol. 30, Fasc. 4, pp. 407-412 (1989).
Ivancev et al., "Clinical Trials With a New Iodinated Lipid Emulsion for Computed Tomography of the Liver," Acta Radiologica, vol. 30, Fasc. 5, pp. 449-457, Sep.-Oct. 1989.
Jones et al., "Uptake and Processing of Remnants of Chylomicrons and Very Low Density lipoproteins by Rat Liver," J. Lipid Res., vol. 25, pp. 1151-1158 (1984).
Kowal, et al., "Low Density Lipoprotein Receptor-related Protein Mediates Uptake of Cholesteryl Esters Derived from Apoprotein E-enriched Lipoproteins," Biochemistry, vol. 86, pp. 5810-5814 (1989).
Lange, et al., "Esophageal Anastomotic Leaks: Preliminary results of Treatment with Balloon Dilation," Radiology, vol. 165, pp. 45-47 (1987).
Longino, et al., "Importance of Emulsification Method on the Particle Size of Fluorotriglyceride Microemulsions for Hepatic .sup.19 F-MR Imaging," Book of Abstracts, vol. 2, Soc. of Magnetic Resonance, p. 820 (1989).
Longino, et al., Abstract, Association of University Radiologists, vol. 9(1):53 (1990).
Longino, et al., Abstract 8-7, Investigative Radiology, vol. 25, No. 12, p. 1357 (1990).
Nagata, et al., "Role of Low Density Lipoprotein Receptor-dependent and -Independent Sites in Binding and Uptake of Chylomicron Remnants in Rat Liver," J. Biol. Chem., vol. 263, No. 29, pp. 15151-15158 (1988).
Nilsson-Ehle and Schotz, "A Stable, Radioactive Substrate Emulsion for Assay of Lipoprotein Lipase," J. of Lipid Research, vol. 17, p. 536 (1976).
Pattniak, et al., "Effect of Size and Competition by Lipoproteins and Apolipoproteins on the Uptake of Chylomicrons and Chylomicron Remnants by Hepatoma Cells in Culture," Biochimica et Biophysica Acta, vol. 617, pp. 335-346 (1980).
Redgrave, et al., "Cholesterol is Necessary for Triacylglycerol-phospholipid Emulsions to Mimic the Metabolism of Lipoproteins," Biochimica et Biophysica Acta, vol. 921, pp. 154-157 (1987).
Redgrave, et al., "The Effect of Triacyl-sn-glycerol Structure on the Metabolism of Chylomicrons and Triacylglycerol-rich Emulsion in the Rat," J. Biol. Chem., vol. 263, pp. 5115-5123 (1988).
Schumacher, et al., "Experimental Data on the Problem of Specific Hepatosplenography with Radiodense Lipomicrons," Europ. J. Radiol., vol. 5, pp. 167-174 (1985).
Schwendner, et al., "Potential Organ or Tumor Imaging Agents. 32. A Triglyceride Ester of .rho.-Iodophenyl Pentadecanoic Acid as a Potential Hepatic Imaging Agent," Nucl. Med. Biol., vol. 19, No. 6, pp. 639-650 (1992).
Sherrill et al., "Characterization of the Sinusoidal Transport Process Responsible for Uptake of Chylomicron by the Liver," J. Biol. Chem., vol. 253, No. 6, pp. 1859-1867 (1978).
Stryer, Biochemistry, 2d Ed., pp. 213-214 and 470-471 (1981).
Sultan, et al., "Inhibition of Hepatic Lipase Activity Impairs Chylomicron Remnant-removal in Rats," Biochimica et Biophysica Acta, vol. 1042, pp. 150-152 (1990).
Vermess, et al., Development and Experimental Evaluation of a Contrast Medium for Computed Tomographic Examination of the Liver and Spleen, J. Computer Assisted Tomography, vol. 31, No. 1, pp. 25-31 (1979).
Washington and Davis, The Production of Parenteral Feeding Emulsions by Microfluidizer, Int'l. J. Pharm., vol. 44, pp. 169-176 (1988).
Weichert, et al., J. Med. Chem., vol. 29, pp. 1674 and 2457 (1986).
Weichert, et al., Abstract of 7th Annual SMRM, vol. 1, p. 484 (Aug. 22-26 1988).
Bakan Douglas A.
Counsell Raymond E.
Longino Marc A.
Weichert Jamey P.
Lovering Richard D.
The Board of Regents of the University of Michigan
LandOfFree
Hepatocyte-selective oil-in-water emulsion does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Hepatocyte-selective oil-in-water emulsion, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Hepatocyte-selective oil-in-water emulsion will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2043257