Patents Assigned to Liposome Technology, Inc.
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Patent number: 5534259Abstract: A composition of polymer-coated particles, and a polymer compound used in forming the particles are disclosed. The polymer compound is composed of a hydrophilic polymer attached to a lipophilic moiety through a linking segment which contains chemical groups through which the compound can be crosslinked to other such compounds. The particles in the composition are prepared by forming lipid structures containing ordered arrays of the polymer compounds, and crosslinking the compounds through their chemical groups. The particles are used for parenteral administration of a pharmaceutical compound which is entrapped in the particles.Type: GrantFiled: July 8, 1993Date of Patent: July 9, 1996Assignee: Liposome Technology, Inc.Inventors: Samuel Zalipsky, Francis J. Martin
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Patent number: 5395619Abstract: A lipid-polymer conjugate for use in forming long-circulating liposomes is disclosed. The conjugate includes a vesicle-forming lipid having covalently attached to its polar head group, one of the polymers: polyvinylpyrrolidone, polyvinylmethylether, polyhydroxypropyl methacrylate, polyhydroxypropylmethacrylamide, polyhydroxyethyl acrylate, polymethacrylamide, polydimethylacrylamide, polymethyloxazoline, polyethyloxazoline, polyhydroxyethyloxazoline, polyhydroxypropyloxazoline, or polyaspartamide. A method for preparing liposomes containing the lipid-polymer conjugate is also disclosed.Type: GrantFiled: March 3, 1993Date of Patent: March 7, 1995Assignee: Liposome Technology, Inc.Inventors: Samuel Zalipsky, Martin C. Woodle, Danilo D. Lasic, Francis J. Martin
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Patent number: 5356633Abstract: A method of and composition for concentrating a therapeutic agent in an inflamed dermal region are disclosed. The composition, which is also used in the method, is a liposomal composition. The liposomes contain the therapeutic agent in entrapped form and are composed of vesicle-forming lipids including a vesicle-forming lipid derivatized with hydrophilic biocompatible polymer. After intravenous administration, the liposomes are taken up by the inflamed region within 24-48 hours, for site-specific release of entrapped compound into the inflamed region.Type: GrantFiled: October 7, 1992Date of Patent: October 18, 1994Assignee: Liposome Technology, Inc.Inventors: Martin C. Woodle, Francis J. Martin, Shi K. Huang
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Patent number: 5340587Abstract: A method and system for treating bronchial constriction. The system includes a liposome composition containing a .beta..sub.2 -adrenoreceptor agonist in a liposome-entrapped form, and a device for aerosolizing a metered quantity of the composition. The drug in liposome aerosol form is substantially more effective in bronchodilation, over a substantially longer time, than the same amount of drug in free-drug aerosol form.Type: GrantFiled: June 13, 1989Date of Patent: August 23, 1994Assignee: Liposome Technology, Inc.Inventors: Paul J. Mihalko, Robert M. Abra, Ramachandran Radhakrishnan
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Patent number: 5225212Abstract: A liposome composition for extended release of a therapeutic compound into the bloodstream. The liposomes are composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with hydrophilic polymer, have sizes in a selected size range between 0.1 and 0.4 microns, and contain the therapeutic compound in liposome-entrapped form. The dosage form of the composition contains at least about three times the dose of the compound required for intravenous injection in free form. Also disclosed in a method for extending to at least 24 hours the period in which an intravenously administered therapeutic compound is therapeutically active in the bloodstream, and novel liposomes compositions for practicing the method.Type: GrantFiled: December 10, 1990Date of Patent: July 6, 1993Assignee: Liposome Technology, Inc.Inventors: Francis J. Martin, Martin C. Woodle, Carl Redemann, Annie Yau-Young, Ramachandran Radhakrishnan
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Patent number: 5213804Abstract: A liposome composition for localizing an anti-tumor compound to a solid tumor via the bloodstream. The liposomes, which contain the agent in entrapped form, are composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with hydrophilic biocompatible polymer, and have sizes in a selected size range between 0.07 and 0.12 microns. After intravenous administration, the liposomes are taken up by the tumor within 24-48 hours, for site-specific release of entrapped compound into the tumor. In one composition for use in treating a solid tumor, the compound is an anthracycline antibiotic drug which is entrapped in the liposomes at a concentration of greater than about 50 .mu.g agent/.mu.mole liposome lipid. The method results in regression of solid colon and breast carcinomas which are refractory to anthracycline antibiotic drugs administered in free form or entrapped in conventional liposomes.Type: GrantFiled: January 15, 1991Date of Patent: May 25, 1993Assignee: Liposome Technology, Inc.Inventors: Francis J. Martin, Martin C. Woodle, Carl Redemann, Annie Yau-Young
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Patent number: 5194266Abstract: An amphotericin B composition containing particles of amphotericin B and cholesterol sulfate, in a molar ratio of between about 1:1 to 2:1. The particles, when stored in lyophilized form and reconstituted in an aqueous suspension, have particle sizes predominantly between about 50-250 nm. The composition has stable particle sizes in an aqueous suspension over a several-day storage period. The composition is significantly less toxic and more effective in treating fungal infection than prior amphotericin B formulations.Type: GrantFiled: December 19, 1991Date of Patent: March 16, 1993Assignee: Liposome Technology, Inc.Inventors: Robert Abra, Luke S. S. Guo
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Patent number: 5192528Abstract: A method for delivering a therapeutic dosage of corticosteroid drug to the lungs, for treating a lung condition or disease. An aqueous suspension of sized liposomes containing the drug in liposome-entrapped form is aerosolized under conditions which produce aerosol particle sizes favoring particle deposition in a selected region of the respiratory tract, and the aerosol is administered in an amount which delivers the thereapeutic dosage level to the selected lung region.Type: GrantFiled: December 1, 1989Date of Patent: March 9, 1993Assignee: Liposome Technology, Inc.Inventors: Ramachandran Radhakrishnan, Paul J. Mihalko, Robert M. Abra
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Patent number: 5185154Abstract: This invention describes a simple, fast, reproducible economic, and convenient method of preparation of very large unilamellar liposome vesicles of uniform size distribution. The populations of these vesicles are homogeneous and suitable for encapsulation of water and lipid soluble compounds.Type: GrantFiled: February 28, 1990Date of Patent: February 9, 1993Assignee: Liposome Technology, Inc.Inventors: Danilo D. Lasic, Andrej Belic
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Patent number: 5180713Abstract: A method of administering a liposome/amphotericin B composition having a predetermined size distribution in 0.2-0.5 micron size range. The method includes preparing a suspension of heterogeneously sized amphotericin B liposomes in an aqueous solution containing at least about 0.5% w/v of membrane-stabilizing agent. After sizing to the desired size distribution, and before the liposome sizes change substantially, the suspension is lyophilized for storage. After reconstituting the lyophilized material, the resulting suspension is administered before a substantial size changes in the liposomes occur.Type: GrantFiled: December 14, 1990Date of Patent: January 19, 1993Assignee: Liposome Technology, Inc.Inventors: Robert Abra, Francis C. Szoka
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Patent number: 5064655Abstract: A liposome gel composition and method of preparing the same. The composition is composed of charged liposomes, at a relatively low lipid concentration, in a low-conductivity medium. The composition preferably contains a zwitterionic compound at its isoelectric point. The liposomes can be designed for cosmetic use, transdermal drug delivery, or enhanced retention on mucosal tissues, such as for ophthalmic use.Type: GrantFiled: May 23, 1989Date of Patent: November 12, 1991Assignee: Liposome Technology, Inc.Inventors: Paul S. Uster, Jacqueline K. Morano, Francis J. Martin
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Patent number: 5049389Abstract: A non-conventional lipid particle formulation for the sustained release and delivery of steroids into deep lung is disclosed. The formulation provides prolonged release of the drug, improved therapeutic ratio, lower toxicity, reduced systemic side effects, and stability for several months. The formulation is in particular suitable for treatment of interstitial lung diseases.Type: GrantFiled: December 1, 1989Date of Patent: September 17, 1991Assignee: Liposome Technology, Inc.Inventor: Ramachandran Radhakrishnan
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Patent number: 5043165Abstract: This invention relates to a novel, non-conventional liposome formulation for the sustained release and delivery of steroids. The formulation provides prolonged release of the drug, improved therapeutic ratio, lower toxicity, reduced systemic side effects and is stable for up to three months. The formulation is suitable for sustained delivery of steroid via inhalation, parenteral, intrathecal, intraarticular, topical, ophthalmic, and oral administration.Type: GrantFiled: December 14, 1988Date of Patent: August 27, 1991Assignee: Liposome Technology, Inc.Inventor: Ramachandran Radhakrishnan
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Patent number: 5032582Abstract: An amphotericin B composition containing particles of amphotericin B and cholesterol sulfate, in a molar ratio of between about 1:1 to 1:4. The particles, when stored in lyophilized form and reconstituted in an aqueous suspension, have particle sizes predominantly between aobut 100-400 nm. The composition formed at a molar ratio of about 1:1 amphotericin B:cholesterol sulfate has stable particle sizes in an aqueous suspension over a several-day storage period. The composition is significantly less toxic and more effective in treating fungal infections than prior amphotericin B formulations.Type: GrantFiled: March 8, 1989Date of Patent: July 16, 1991Assignee: Liposome Technology, Inc.Inventor: Robert Abra
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Patent number: 5030442Abstract: An aqueous, noncrystalline minoxidil composition for topical use which has significantly improved flux of the drug through human cadaver skin. The composition contains minoxidil complexed with an amphipathic compound, oleic acid and with pharmaceutically acceptable excipients. The composition may be formulated in an aqueous vehicle, or dispersed in fluorochlorocarbon solvent for spray delivery from a self- propelled spray device.Type: GrantFiled: April 4, 1989Date of Patent: July 9, 1991Assignee: Liposome Technology, Inc.Inventors: Paul S. Uster, Yolanda P. Quinn
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Patent number: 5023087Abstract: A method for selectively controlling the rate of release of a liposome-entrapped compound from an intramuscular or subcutaneous injection site. The method includes selecting the average size, amount, and lipid composition of liposomes injected into the site to produce a desired half-life of release of the compound. A preferred composition used in practicing the invention includes an aqueous suspension of liposomes containing the compound in entrapped form, and having average particle sizes less than about 0.2 microns, and large amount of larger empty lipsomes present in an amount effective to increase the half-life of release of the compound from the injection site to a desired half-life between about 1-14 days.Type: GrantFiled: May 12, 1989Date of Patent: June 11, 1991Assignee: Liposome Technology, Inc.Inventor: Annie Yau-Young
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Patent number: 5013556Abstract: A liposome composition which contains between 1-20 mole percent of an amphipathic lipid derivatized with a polyalkylether, as exemplified by phosphatidylethanolamine derivatized with polyethyleneglycol. The derivatized lipid enchances the circulation time of the liposomes severalfold, and this enhancement is achieved with either fluid or membrane-rigidifying liposome components. Also disclosed are methods for delivering a drug for slow release from the bloodstream, and for targeting a selected tissue or cells with liposomes, via the bloodstream.Type: GrantFiled: October 20, 1989Date of Patent: May 7, 1991Assignee: Liposome Technology, Inc.Inventors: Martin C. Woodle, Francis J. Martin, Annie Yau-Young, Carl T. Redemann
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Patent number: 5000887Abstract: A method of forming liposomes with a uniform size distribution, and an average size of about 300 nm or less. Vesicles-forming lipids are dissolved in a water-miscible solvent, such as ethanol, and an aqueous medium is added to a water:solvent ratio at which lipid assembly first occurs. The water:solvent ratio is raised, under conditions which maintain the volume of the mixture substantially constant, until uniform-size liposomes are formed. The average size of the liposomes can be selectively varied by changing the ionic strength and lipid composition of the mixture. In one embodiment, the method is used to produce small unilamellar vesicles. Also disclosed are suspensions of liposomes which have a narrow, substantially symmetrical size distribution in a selected size range.Type: GrantFiled: May 17, 1988Date of Patent: March 19, 1991Assignee: Liposome Technology, Inc.Inventors: Renee A. Tenzel, David F. Aitcheson
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Patent number: 4994213Abstract: A method of forming lipid structures, such as liposomes is disclosed. Lipids are dissolved in a solvent system containing a water-miscible solvent, such as ethanol, and an aqueous medium. The water:solvent ratio is raised by removing water and solvent in a reverse osmosis system, and replacing lost solvent with added aqueous medium, preferably at a rate which just balances volume loss by reverse osmosis. In one embodiment, the method is used to produce uniform-size liposomes.Type: GrantFiled: May 17, 1988Date of Patent: February 19, 1991Assignee: Liposome Technology, Inc.Inventors: David F. Aitcheson, Renee A. Tenzel
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Patent number: 4952405Abstract: A method of selectively enhancing efficacy of gentamicin, when used in the treatment of Mycobacterium avium Complex (MAC), by intravenous administration of the drug in liposomal form. Gentamicin-liposomes are comparable to amikacinliposomes in activity against MAC infection in the bloodstream and substantially more effective against MAC infection residing in liver and spleen.Type: GrantFiled: October 20, 1988Date of Patent: August 28, 1990Assignee: Liposome Technology, Inc.Inventor: Annie Yau-Young