Therapeutic treatment and prevention of infections with a bioactive material(s) encapuslated within a biodegradable-bio-compatable polymeric matrix

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active material and (2) a carrier which may contain pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein said active material is histatin and wherein said composition is characterized by a capacity to release up to 90% of the histatin in an aqueous physiological environment from 28-70 days with a 1/99 blend of uncapped and end-capped poly(lactide/glycolide) having a L/G ratio of 48/52 to 52/48 and a molecular weight range of 10,000-40,000 daltons.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active material and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein said active material is histatin and wherein said composition is characterized by the capacity to release up to 80% of histatin in an aqueous physiological environment from 56-100 days with a 1/99 blend of uncapped and end-capped poly(lactide/glycolide) having a L/G ratio or 75/25 and a molecular weight of less than 15,000 daltons.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) a biologically active agent and (2) a cattier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer wherein the biologically active agent comprises a polypeptide leutinizing hormone releasing hormone (LHRH) that is a decapeptide of molecular weight 1182 in its acetate form, and having the structure:
• p-EHWSYGLRPG.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active material comprising a polypeptide and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncupped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein the entrapped polypeptide is any of the vaccine agents against enterotoxigenic E. coli (ETEC) selected from the group consisting of CFA/I, CFA/II, CS1, CS3,CS6 and CS17, ETEC-related enterotoxins, and combinations thereof.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein said agent is selected from the group consisting of water-soluble hormone drugs, antibiotics, antitumor agents, and inflammatory agents, antipyretics, analgesics antitussivess expectorants, sedatives, muscle relaxants, antiepileptics, antiulcer agents, antidepressants, antiallergic drugs, cardiotonics, antiarrhythmic drugs, vasodilators, antihypertensives, diuretics, anticoagulants, antinarcotics, in the molecular weight range of 100-100,000 daltons.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an entrapped polypeptide as an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biogradable-biocompatible poly(lactide/glycolide) copolymer, wherein the entrapped polypeptide is active at a low pH, and comprises LHRH, adrenocorticotropic hormone, epidermal growth factor, or calcitonin released polypeptide.

A composition for the burst-free, sustained, progammable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an entrapped polypeptide as an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein when the entrapped polypeptide is inactive at a low pH, a non-ionic surfactant such an polyoxyethylene sorbitan fatty acid esters (Tween 80, Tween 60 and Tween 20) and polyoxyethylene—polyoxypropylene block copolymers (Fluronics) is added to the inner aqueous phase to maintain biological activity of the released polypeptide.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an entrapped polypeptide as an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein when the entrapped polypeptide such as histatin is inactive at a low pH, a pH-stabilizing agent of inorganic salts is added to the inner aqueous phase to maintain biological activity of the released peptide, and further wherein placebo spheres loaded with the pH-stabilizing agents are coadministered with polypeptide-loaded spheres to maintain the solution pH around the microcapsules and preserve the biological activity of the released peptide in instances where the addition of pH-stabilizing agents in the inner aqueous phase is undesirable for the successful encapsulation of the acid pH sensitive polypeptide.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an entrapped polypeptide as an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein when the entrapped polypeptide is inactive at a low pH, a non-ionic surfactant such an polyoxyethylene sorbitian fatty acid esters (Tween 80, Tween 60 and Tween 20) and polyoxyethylene-polyoxypropylene block copolymers (Flutonics) is added to the inner aqueous phase to maintain biological activity of the released polypeptide, and further wherein placebo spheres loaded with non-ionic surfactant are coadministered with polypeptide-loaded spheres to maintain biological activity of the released peptide where the addition of non-ionic surfactants in the inner aqueous phase is undesirable for successful encapsulation of the acid pH sensitive polypeptide.

A composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide copolymer), wherein complete solubilization of the copolymer leaves no residual polymer at the site of administration and occurs concurrently with the complete release of the entrapped agent.

A process of treating humans with a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, said process comprising administering said composition via parenteral route selected from intramuscular and subcutaneous.

A process of treating humans with a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, said process comprising administering said composition via topical route.

A process of treating humans with a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, said process comprising administering said composition via oral routes.

A process of treating humans with a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, said process comprising administering said composition via nasal, transdermal, rectal, and vaginal routes.

A process of treating humans with a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, said process comprising administering said composition in the form of an oral or nasal inhalant for the respiratory tract.

A method for the protection against infection of a mammal in need thereof by pathogenic organisms comprising administering orally to said mammal an immunogenic amount of an immunostimulating composition comprising an antigenic synthetic peptide encapsulated within a poly(lactide/glycolide) matrix, wherein said poly(lactide/glycolide) matrix comprises a blend of uncapped and end-capped forms, in a ratio of 100/0 to 1/99.

A vaccine for the immunization of a mammal in need thereof against infection caused by pathogenic organisms prepared from a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer.

A vaccine for the immunization of a mammal in need thereof, against infection by pathogenic organisms comprising an antigen in the amount of 0.1 to 1% encapsulated within a biodegradable-biocompatible polymeric poly(DL-lactide-coglycolide) matrix wherein the polymer is uncapped or a blend of uncapped and end-capped polymers.

An immunostimulating composition comprising encapsulating-microspheres, which may contain a pharmaceutically-acceptable adjuvant, wherein said microspheres having a diameter between 1 nanogram (ng) to 10 microns (um) are comprised of (a) a biodegradable-biocompatible poly(DL-lactide-co-glycolide) as the bulk matrix, wherein the copolymer (lactide to glycolide L/G) ratio for uncapped and end-capped polymer is 100/0 to 1/99 and (b) an immunogenic substance comprising a bacteria, virus, fungus, parasite, or derivative thereof, that serves to elicit the production of antibodies in animal subjects.

A diagnostic assay for bacterial infections comprising a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) a biologically active agent and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer.

A method for the protection against or therapeutic treatment of bacterial infection in the soft tissue or bone of a mammal in need thereof comprising administering locally to said mammal a bactericidally-effective amount of a composition for the burst-free, sustained, programmable release of active material(s) over a period from 1-100 days, which comprises:

• (1) an active material and (2) a carrier which contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncapped and end-capped biodegradable-biocompatible poly(lactide/glycolide) copolymer, wherein the active material is an antibiotic which is controlled release within a period of about 1 to 100 days.