Protein stabilized pharmacologically active agents, methods for

Details Protein stabilized pharmacologically active agents, methods for Protein stabilized pharmacologically active agents, methods for

1996-10-01

1999-06-29

Levy, Neil S.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Particulate form

424450, 424465, 424451, 424439, A61K 914

Patent

active

059165960

ABSTRACT:
In accordance with the present invention, there are provided compositions and methods useful for the in vivo delivery of substantially water insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacologically active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than about 1 micron. The use of specific composition and preparation conditions (e.g., addition of a polar solvent to the organic phase), and careful selection of the proper organic phase and phase fraction, enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry powder comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable (in the form of molecules bound to the protein), and part of the agent is present within particles without any polymeric matrix therein.

REFERENCES:
patent: 3959457 (1976-05-01), Speaker et al.
patent: 4073943 (1978-02-01), Wretlind et al.
patent: 4247406 (1981-01-01), Widder et al.
patent: 4572203 (1986-02-01), Feinstein
patent: 4671954 (1987-06-01), Goldberg et al.
patent: 4718433 (1988-01-01), Feinstein
patent: 4789550 (1988-12-01), Hommel et al.
patent: 4844882 (1989-07-01), Widder et al.
patent: 5059699 (1991-10-01), Kingston et al.
patent: 5110606 (1992-05-01), Geyer et al.
patent: 5145684 (1992-09-01), Liversidge et al.
patent: 5362478 (1994-11-01), Desai et al.
patent: 5439686 (1995-08-01), Desai et al.
patent: 5498421 (1996-03-01), Grinstaff et al.
patent: 5505932 (1996-04-01), Gristaff et al.
patent: 5508021 (1996-04-01), Grinstaff et al.
patent: 5512268 (1996-04-01), Grinstaff et al.
patent: 5560933 (1996-10-01), Soon-Shing et al.
patent: 5650156 (1997-07-01), Grinstaff et al.
patent: 5665382 (1997-09-01), Grinstaff et al.
Burgess et al., "Potential use of albumin microspheres as a drug delivery system. I. Preparation and in vitro release of steroids," International Journal of Pharmaceutics, 39:129-136 (1987).
Chen et al., "Comparison of albumin and casein microspheres as a carrier for doxorubicin," J. Pharm. Pharmacol., 39:978-985 (1987).
Feinstein et al., "Two-Dimensional Constrast Echocardiography. I. In Vitro Development and Quantitative Analysis of Echo Contrast Agents," JACC, 3(1):14-20 (1984).
Grinstaff & Suslick, "Nonaqueous Liquid Filled Microcapsules," Polym. Prepr., 32:255-256 (1991).
Gupta et al., "Albumin microspheres. III. Synthesis and characterization of microspheres containing adriamycin and magnetite," International Journal of Pharmaceutics, 43:167-177 (1988).
Ishizaka et al., "Preparation of Egg Albumin Microcapsules and Microspheres," Journal of Pharmaceutical Sciences, 70(4):358-363 (1981).
Klibanov et al., "Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes," FEBS, 268(1):235-237 (1990).
Koenig & Meltzer, "Effect of Viscosity on the Size of Microbubbles Generated for Use as Echocardiographic Contrast Agents," Journal of Cardiovascular ultrasonography, 5(1):3-4 (1986).
Molecular Biosystems, Inc., "ALBUNEX--Preclinical Investigator's Package".
Moseley et al., "Microbubbles: A Novel MR Susceptibility Contrast Agent," 10th Annual Meeting of Society of Magnetic Resonance in Medicine (1991).
Suslick & Grinstaff, "Protein Microencapsulation of Nonaqueous Liquids," J. Am. Chem. Soc., 112(21):7807-7809 (1990).
Willmott & Harrison, "Characterisation of freeze-dried albumin microspheres containing the anti-cancer drug adriamycin," International Journal of Pharmaceutics, 43:161-166 (1988).
-----, "Serum Albumin Beads: An Injectable, Biodegradable System for the Sustained Release of Drugs," Science, 213(10):233-235 (1981). C!-poly(latic acid) nanoparticles coated with albumin after parenteral adminstration to rats" Biomaterials, 13:1093-1102 (1992).
Boury et al., "Dilatational Properties of Absorbed Poly(D,L-lactide) and Bovine Serum Albumin Monolayers at the Dichloromethane/Water Interface" Langmuir, 11:1636-1644 (1995).
Calvo et al., "Comparative in Vitro Evaluation of Several Colloidal Systems, Nanoparticles, Nanocapsules, and Nanoemulsions, as Ocular Drug Carriers" J. Pharm. Sci., 85(5):530-536 (1996).
Cavalier et al., "The formation and characterization of hydrocortisone-loaded poly((+.sub.--)-lactide) microspheres" J. Pharm. Pharmacol., 38:249-253 (1985).
Kumar et al., "Binding of Taxol to Human Plasma, Albumin and--Acid Glycoprotein" Research Communications in Chemical Pathology and Pharmacology, 80(3):337-344 (1993).
Lee et al., "Serum Albumin Beads: An Injectable, Biodegradable System for the Sustained Release of Drugs" Science, 213:233-235 (1981).
Leucuta et al., "Albumin microspheres as a drug delivery system for epirubicin: pharmaceutical, pharmacokinetic and biological aspects" International Journal of Pharmaceutics, 41:213-217 (1988).
Liversideg-Merisko et al., "Formulation and Antitumor Activity Evaluation of Nanocrystalline Suspensions of Poorly Soluble Anticacer Drugs" Pharmaceutical Research, 13(2):272-278 (1996).
Mathew et al., "Synthesis and Evaluation of Some Water-Soluble Prodrugs and Derivatives of Taxol with Antitumor Activity" J. Med. Chem., 35:145-151 (1992).
Norton et al., Abstracts of the 2nd National Cancer Institute Workshop on Taxol & Taxus, Sep. 23-24, 1992).
Wani et al., "Plant Antitumor Agents. VI. The Isolation and Structure of Toxol, a Novel Antileukemic and Antitumor Agents from Taxus brevifolia.sup.1,2 " J. Am. Chem. Soc., 93:2325-2327 (1971).

Affiliated with

Also associated with

Rating

Protein stabilized pharmacologically active agents, methods for does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Protein stabilized pharmacologically active agents, methods for , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Protein stabilized pharmacologically active agents, methods for will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1373945