Abstract: The invention relates to a method of treating psychotic disorders comprising a biodegradable and biocompatible microparticle composition comprising a 1,2-benzazole of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof.

Abstract: A method for preparing biodegradable, biocompatible microparticles. A first phase is prepared that includes a biodegradable, biocompatible polymer, an active agent, and a solvent. An immiscible second phase is prepared. The first and second phases are combined to form an emulsion in which the first phase is discontinuous and the second phase is continuous. The two phases are immersed in a quench liquid that includes a quench medium and a quantity of the solvent. The quantity of the solvent is selected to control a rate of extraction of the solvent from the first phase. The first phase is isolated in the form of microparticles. Also disclosed is a microencapsulated active agent prepared by the method for preparing biodegradable, biocompatible microparticles.

Abstract: The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical or diagnostic agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of an antibody-neuropharmaceutical or diagnostic agent conjugate wherein the antibody is reactive with a transferrin receptor and the antibody is a chimera between the variable region from one animal source and the constant region from a different animal source. Other aspects of this invention include a delivery system comprising an antibody reactive with a transferrin receptor linked to a neuropharmaceutical or diagnostic agent and methods for treating hosts afflicted with a disease associated with a neurological disorder.

Abstract: The present invention relates to a polymer-based sustained release device, and methods of forming and using the device for the sustained release of an active agent. The improved method of the invention for forming a polymer-bases sustained release device comprises forming a polymer/active agent solution by mixing a polymer, a continuous phase, and an active agent. The continuous phase can comprise one or more polymer solvents, a polymer solvent/polymer non-solvent mixture, or a polymer solvent/active agent non-solvent mixture. When the continuous phase comprises a polymer solvent/active agent non-solvent, the active agent can also be present as a microparticulate rather than in solution. The continuous phase is then removed from the polymer/active agent solution, thereby forming a solid polymer/active agent matrix.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of a ligand-neuropharmaceutical agent fusion protein wherein the ligand is reactive with a brain capillary endothelial cell receptor. Other aspects of this invention include a delivery system comprising a ligand reactive with a brain capillary endothelial cell receptor which has formed a fusion protein with a neuropharmaceutical agent. The fusion proteins are also aspects of this invention.

Abstract: The invention relates to a pharmaceutical composition comprising a biodegradable and biocompatible microparticle composition comprising a 1,2-benzazole of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, within a polymeric matrix.

Abstract: The present invention relates to a method for forming microparticles of a material from microdroplets of a solution, wherein the solution comprises the material dissolved in a solvent. The method includes the steps of directing the microdroplets into a freezing zone, whereby the microdroplets freeze. The frozen microdroplets are then contacted with a liquid non-solvent to extract the solvent into the non-solvent, thereby forming the microparticles.

Abstract: A method for preparing biodegradable, biocompatible microparticles. A first phase is prepared that includes a biodegradable, biocompatible polymer, an active agent, and a solvent. An immiscible second phase is prepared. The first and second phases are combined to form an emulsion in which the first phase is discontinuous and the second phase is continuous. The two phases are immersed in a quench liquid that includes a quench medium and a quantity of the solvent. The quantity of the solvent is selected to control a rate of extraction of the solvent from the first phase. The first phase is isolated in the form of microparticles. Also disclosed is a microencapsulated active agent prepared by the method for preparing biodegradable, biocompatible microparticles.

Abstract: Composition for the sustained release of a biologically active agent in vivo. The composition comprises microcarriers containing a first solid-phase biocompatible material and a biologically active agent, wherein said microcarriers sustain the in vivo release of the biologically active agent. The composition also contains particles of a second biocompatible solid-phase material wherein the second solid-phase material further sustains the in vivo release of the biologically active agent.The invention also relates to a method for sustaining effective serum levels of a biologically active agent in a subject, including forming an injectable dose containing an effective amount of a biologically active agent, wherein the agent is contained in a microcarrier, with a release-period sustaining amount of a solid-phase material. The method further includes administering the injectable dose to the subject.

Abstract: The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution.

Abstract: The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Abstract: The present invention pertains to a method for delivering a neuropharmaceutical or diagnostic agent across the blood brain barrier to the brain of a host. The method comprises administering to the host a therapeutically effective amount of an antibody-neuropharmaceutical or diagnostic agent conjugate wherein the antibody is reactive with a transferrin receptor. Other aspects of this invention include a delivery system comprising an antibody reactive with a transferrin receptor linked to a neuropharmaceutical or diagnostic agent and methods for treating hosts afflicted with a disease associated with a neurological disorder.

Abstract: A method for forming polymer/drug microparticles comprising the steps of (1) forming a polymer solution/drug mixture comprising a polymer dissolved in an organic solvent and a suspended labile drug; (2) removing the solvent from the polymer solution/drug mixture, thereby forming a solid polymer/drug matrix; and (3) fragmenting the polymer/drug matrix at a temperature below the glass transition temperature of the polymer/drug matrix, thereby forming polymer/drug matrix microparticles.In one embodiment, the solvent is removed from a polymer solution/drug mixture by freezing the polymer solution/drug mixture and extracting the solvent from the resulting solid polymer solution/drug matrix. The polymer can be a biocompatible polymer, such as poly(lactic acid-co-glycolic acid). The drug can be a labile drug, such as a protein, or a polynucleotide. Another embodiment of the present invention includes the polymer/drug matrix microparticles which are formed by the method outlined above.

Abstract: A method for preparing biodegradable, biocompatible microparticles. A first phase is prepared that includes a biodegradable, biocompatible polymeric encapsulating binder, and an active agent having limited water solubility dissolved or dispersed in a solvent. An aqueous second phase is prepared. The first and second phases are combined to form an emulsion in which the first phase is discontinuous and the second phase is continuous. The two phases are separated. The discontinuous first phase is washed with water, or an aqueous solution of water and a solvent for residual solvent in the first phase, to reduce the level of residual solvent in the microparticles to less than about 2% by weight of the microparticles. Also disclosed are a microencapsulated drug prepared by the method for preparing biodegradable, biocompatible microparticles, and a pharmaceutical composition that includes biodegradable and biocompatible microparticles in a pharmaceutically acceptable carrier.

Abstract: The instant invention is related to a sustained-release microparticle produced by dissolving in a solvent an active agent and a biodegradable and biocompatible polymer to form an organic phase.

Abstract: A delivery system for providing antiparasitic agents to animals is provided and a method of treating parasitic infections in animals using such delivery systems is described. The delivery system is particularly useful for treatment with avermectins and milbemycins in lactide/glycolide polymeric matrices.

Abstract: A composition, and methods of forming and using said composition, for the sustained release of non-aggregated, biologically active, erythropoietin (EPO). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, aggregation-stabilized EPO, wherein said particles are dispersed within the biocompatible polymer.The method of the invention for producing a composition for the sustained release of biologically active EPO, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, aggregation-stabilized EPO in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said EPO particles.The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated erythropoietin in a subject for a sustained period.

Abstract: This invention relates to a composition, and method of forming said composition, for the controlled release of interferon. The controlled release composition of this invention comprises a biocompatible polymer and particles of metal cation-stabilized interferon, wherein the particles are dispersed within the biocompatible polymer.The method of the invention, for producing a composition for the controlled release of interferon, includes dissolving a polymer in a polymer solvent to form a polymer solution, dispersing particles of metal cation stabilized-interferon particles in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of the interferon particles.

Abstract: A pharmaceutical composition comprising a biodegradable and biocompatible composition comprising a 1,2 benzazole within a polymeric matrix. The 1,2 benzazole composition, pharmaceutically acceptable acid addition salts thereof, are potent antagonists of a series of neurotransmitters, particularly serotonin and dopamine. A method of inhibiting both serotonergic overactivity and dopaminergic overstimulation in animals is provided by administration of a biodegradable and biocompatible microparticle composition comprising a 1,2 benzazole or a pharmaceutically acceptable acid addition salt thereof. A method of treating warm blooded animals suffering from psychotic disorders, and a method of preparing the biodegradable and biocompatible composition are also described.