초록 ▼

Novel burst-free, sustained release biocompatible and biodegrable microcapsules which can be programmed to release their active core for variable durations ranging from 1-100 days in an aqueous physiological environment. The microcapsules are comprised of a core of polypeptide or other biologically

Novel burst-free, sustained release biocompatible and biodegrable microcapsules which can be programmed to release their active core for variable durations ranging from 1-100 days in an aqueous physiological environment. The microcapsules are comprised of a core of polypeptide or other biologically active agent encapsulated in a matrix of poly(lactide/glycolide) copolymer having a molar composition of lactide/glycolide from 90/10 to 40/60, which may contain a pharmaceutically-acceptable adjuvant, as a blend of uncapped free carboxyl end group and end-capped forms ranging to ratios from 100/0 to 1/99.

대표청구항 ▼

1. 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 contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncap and end-capped biodegradable-bioc

1. 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 contains pharmaceutically-acceptable adjuvant, comprised of a blend of uncap and end-capped biodegradable-biocompatible copolymer wherein said composition comprises a capacity to completely release histatin in an aqueous physiological environment within from 1 to 40 days with a 99/1 blend of uncapped and end-capped poly(lactide/glycolide) having a L/G ratio of 48/52 to 52/48, and a molecular weight less than 15,000.2. The composition of claim 1 wherein the histatin can be completely released within 18 to 40 days and the molecular weight of the poly(lactide/glycolide) is within the range of 28,000 to 40,000.3. 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.4. 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.5. 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. 6. 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.7. The composition of claim 6 wherein the entrapped polypeptide consists of peptide antigens of molecular weight range of about 800-5000 daltons for immunization against enterotoxigenic E. coli (ETEC).8. The composition of claim 7 wherein the entrapped polypeptide is selected from the group consisting of an antigenic synthetic peptide containing CFA/I pilus protein T-cell epitopes; B-cell spitopest or mixtures thereof.9. 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.10. 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.11. 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.12. 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.13. 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.14. 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.15. 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.16. 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.17. 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.18. 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.19. 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.20. A process for preparing controlled release compositions characterized by burst-free, sustained, programmable release of biologically active agents, comprising: dissolving biodegradable poly(lactide/glycolide), in uncapped form in methylene chloride, and dissolving a biologically active agent or active core in water; adding the aqueous layer to the polymer solution and emulsifying to provide an inner water-in-oil (w/o) emulsion; stabilizing the w/o emulsion in a solvent-saturated aqueous phase containing a oil-in-water (o/w) emulsifier; adding said w/o emulsion to an external aqueous layer containing oil-in-water emulsifier to form a ternary emulsion; and stirring the resulting water-in-oil-in-water (w/o/w) emulsion for sufficient time to remove said solvent, and rinsing hardened microcapsules with water and lyophilizing said hardened microcapsules.21. The process of claim 20 wherein a solvent-saturated external aqueous phase is added to emulsify the inner w/o emulsion prior to addition of the external aqueous layer, to provide microcapsules of size distribution range between 0.05-500 um.22. The process of claim 20 wherein a low temperature of about 0-4 degree C. is provided during preparation of the inner w/o emulsion, and a low temperature of about 4-20 degree C. is provided during preparation of the w/o/w emulsion to provide a stable emulsion and high encapsulation efficiency.23. A process for preparing controlled release compositions characterized by burst-free, sustained, programmable release of biologically active agents, comprising:dissolving biodegradable poly(lactide/glycolide) uncapped and end-capped form in methylene chloride, and dissolving a biologically active agent or active core in water; adding the aqueous layer the polymer solution and emulsifying to provide an inner water-in-oil emulsion; stabilizing the w/o emulsion in a solvent-saturated aqueous phase containing a oil-in-water (o/w) emulsifier; adding said w/o emulsion to an external aqueous layer containing oil-in-water emulsifier to form a ternary emulsion; and stirring a resulting water-in-oil-water (w/o/w) emulsion for sufficient time to remove said solvent; and rinsing heardened microcapsules with water; and lyophilizing said hardened microcapsules. 24. The process of claim 20 wherein a 100/0 blend of uncapped and end-capped polymer in used to provide release of the active core in a continuous and sustained manner without a lag phase.25. The process of claim 23 wherein a solvent-saturated external aqueous phase is added to emulsify the inner w/o emulsion prior to addition of the external aqueous layer, to provide microcapsules of narrow size distribution range between 0.05-500 um.26. The process of claim 23 wherein a low temperature or about 0-4 degree C. is provided during preparation or the inner w/o emulsion, and a low temperature of about 4-20 degree C. is provided during preparation of the w/o/w emulsion to provide a stable emulsion and high encapsulation efficiency.27. 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 1/99.28. The method of claim 27 wherein the poly(lactide/glycolide) is a blend of uncapped and end-capped forms in ratios ranging from 90/10 to 40/60.29. The method of claim 27 wherein the infection is a bacterial infection.30. The method of claim 27 where the synthetic peptide contains an epitope selected from the group consisting of CFA/I pilus protein T-cell epitopes, B-cell epitopes or mixtures thereof.31. The method of claim 27 wherein the infection is a viral infection.32. The method of claim 27 wherein the infection is parasitic infection.33. The method of claim 27 wherein the infection in a fungal infection.34. The method of claim 29 wherein the bacterial infection is caused by a bacteria selected from the group consisting of Salmonella typhi, Shigella Sonnei, Shigella Flexneri, Shigella dysenteriae, Shigella boydii, Escheria coli, Vibrio cholera, Group D-2, Group E, Group G, Group I, Group 1, Listseria, Erysipelothrix, Mycobacterium, Aerobic pathogenic Actinomycetales, Enterobacteriaceae, Vibrio, aeromonas, Plesiomonas, Helicobacter, W. succinogenes, Acineto bacter spp., Foavobacterium, Pseudomonas, Legionella, Brucella, Haemophilus, Bordetalla, Mycoplasmas, Gardnerella, Streptobacillus, Spirillum, Calymmatobacterium, Clostridium, Treponema, Borrelia, Leptospira, Anaerobic Gram-negative Bacteria including bacilli and Cocci, Anaerobic gram-Postive Nonsporeforming Bacilli and Cocci, versinia, staphylococcus, clostridium, Enteroccus, Streptoccus, Aerococcus, Planococcus, Stomatococcus, Micrococcus, Lactoccus, Germella, Pediococcus, Leuconostoc, Bacillus, Neisseria, Branhamella, Coryne bacterium, campylobacter, Arcanobacterium haemolyticum, Rhodococcus spp., Rhodococcus, Group A-4.35. The method in accordance with claim 27 wherein said antigenic synthetic peptide is present in the amount of 0.1 to 1%.36. 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.37. The vaccine according to claim 36 wherein the polymeric substance is poly(DL-lactide-co-glycolide).38. The vaccine according to claim 37 wherein the relative ratio between the lactide and glycolide (L/G) component is within the range of 40/60 to 0/100.39. The vaccine according to claim 38 wherein the relative ratio between the amount of lactide and glycolide component is within the range of 90/10 to 40/60.40. A vaccine according to claim 36 wherein the pathogenic organisms are bacterial.41. A vaccine according to claim 36 wherein the pathogenic organisms are viral.42. A vaccine according to claim 36 wherein the pathogenic organisms are fungal.43. A vaccine according to claim 36 wherein the pathogenic organisms are parasitic.44. The vaccine according to claim 36 wherein the material is an antigenic synthetic peptide is selected from the group consisting essentially of Synthetic Peptides Containing CFA/I Pilus Protein T-cell Epitopes (Starting sequence I given)4(Asn-Ile-Thr-Val-Thr-Ala-Ser-Val-Asp-Pro), 8(Thr-Ala-Ser-Val-Asp-Pro-Val-Ile-Asp-Leu), 12(Asp-Pro-Val-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 15(Ile-Asp-Leu-Lou-Gln-Ala-Asp-Gly-Asn-Ala), 20(Ala-Asp-Gly-Asn-Ala-Leu-Pro-Ser-Ala-Val), 26(Pro-Ser-Ala-Val-Lys-Leu-Ala-Tyr-Ser-Pro), 72(Leu-Asn-Ser-Thr-Val-Gln-Met-Pro-Ile-Ser), 78(Met-Pro-Ile-Ser-Val-Ser-Trp-Gly-Gly-Gln), 87(Gln-Val-Leu-Ser-Thr-Thr-Ala-Lys-Glu-Phe), 126(Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr), and 133(Gly-Asn-Tyr-Ser-Gly-Val-Val-Ser-Leu-Val), and mixtures thereof; Synthetic Peptides, Containing CFA/I Pilus Protein B-cell (antibody) Eptiopes (Starting Sequence # given) 3(Lys-Ana-Ile-Thr-Val-Thr-Ala-Ser-Val), 11(Val-Asp-Pro-Val-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 22(Gly-Asn-Ala-Leu-Pro-Ser-Ala-Val), 32(Ala-Tyr-Ser-Pro-Ala-Ser-Lys-Thr-Phe-Lys-Thr-Phe-Glu-Ser-Tyr-Arg-Val), 32(Ala-Tyr-Ser-Pro-Ala-Ser-Lys-Thr-Phe) 38(Lys-Thr-Phe-Glu-Ser-Tyr-Arg-Val), 66(Pro-Gln-Leu-Thr-Asp-Val-Leu-Asn-Ser) 93(Ala-Lys-Glu-Phe-Glu-Ala-Ala-Ala), 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr) 127(Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and mixtures thereof; and Synthetic Peptides Containing CFA/I Pilus Protein T-cell and B-cell (antibody) Epitopes (Starting Sequence # given) 3(Lys-Asn-Ile-Thr-Val-Thr-Ala-Ser-Bal-Asp-Pro), 8(Thr-Ala-Ser-Val-Asp-Pro-Val-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 11(Bal-Asp-Pro-Bal-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 20(Ala-Asp-Gly-Asn-Ala-Leu-Pro-Ser-Ala-Val), 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and 126(Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and mixtures thereof. 45. The vaccine according to claim 40 wherein the bacteria is selected from the group consisting essentially of Salmonella typhi, Shigella Sonnei, Shigella Flexneri, Shigella dysenteriae, Shigella boydii, Escheria coli, Vibrio cholera, Group D-2, Group E, Group G, Group I, Group 1, Listseria, Erysipelothrix, Mycobacterium, Aerobic pathogenic Actinomycetales, Enterobacteriaceae, Vibrio, aeromonas, Plesiomonas, Helicobacter, W. succinogenes, Acineto bacter spp., Foavobacterium, Pseudomonas, Lepionella, Brucella, Haemophilus, Bordetalla, Mycoplasmas, Gardnerella, Streptobacillus, Spirillum, Calymmatobacterium, Clostridium, Treponema, Borrelia, Leptospira, Anaerobic Gram-negative Bacteria including bacilli and Cocci, Anaerobic gram-Postive Nonsporeforming Bacilli and Cocci, versinia, staphylococcus, clostridium, Enteroccus, Streptoccus, Aerococcus, Planococcus, Stomatococcus, Micrococcus, Lactoccus, Germella, Pediococcus, Leuconostoc, Bacillus, Neisseria, Branhamella, Coryne bacterium, campylobacter, Arcanobacterium haemolyticum, Rhodococcus spp., Rhodococcus, Group A-4.46. The vaccine according to claim 40 wherein the antigenic synthetic peptide is selected from the group consisting of4(Asn-Ile-Thr-Val-Thr-Ala-Ser-Val-Asp-Pro), 8(Thr-Ala-Ser-Val-Asp-Pro-Val-Ile-Asp-Leu), 12(Asp-Pro-Val-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 15(Ile-Asp-Leu-Leu-Gln-Ala-Asp-Gly-Asn-Ala), 20(Ala-Asp-Gly-Asn-Ala-Leu-Pro-Ser-Ala-Val), 26(Pro-Ser-Ala-Val-Lys-Leu-Ala-Tyr-Ser-Pro), 72(Leu-Asn-Ser-Thr-Val-Gln-Met-Pro-Ile-Ser), 78(Met-Pro-Ile-Ser-Val-Ser-Trp-Gly-Gly-Gln), 87(Gln-Val-Leu-Ser-Thr-Thr-Ala-Lys-Glu-Phe), 126(Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr), and 133(Gly-Asn-Tyr-Ser-Gly-Val-Val-Ser-Leu-Val), and mixtures thereof. 47. The vaccine according to claim 46 wherein the antigenic synthetic peptide is 4(Asn-Ile-Thr-Val-Thr-Ala-ser-Val-Asp-Pro).48. The vaccine according to claim 46 wherein the antigenic synthetic peptide is 8(Thr-ala-ser-val-Asp-Pro-Val-I,la-asp-Leu).49. The vaccine according to claim 40 wherein the antigenic synthetic peptide is 12(Asp-Pro-Val-Ile-Asp-Lau-Lau-Gln-Ala-Asp).50. The vaccine according to claim 40 wherein the antigenic synthetic peptide is 15(Ile-Asp-Leu-Lou-Gln-Ala-Asp-Gly-Asn-Ala).51. The vaccine according to claim 40 wherein the antigenic synthetic peptide is 20(Ala-Asp-Gly-Asn-Ala-Leu-Pro-Ser-Ala-Val).52. The vaccine according to claim 40 wherein the antigenic synthetic peptide is 26(Pro-Ser-Ala-Val-Lys-Leu-Ala-tyr-Ser-Pro).53. The vaccine according to claim 40 wherein the antigenic synthetic peptide is 72(Leu-Asn-Ser-Thr-Val-Gln-Met-Pro-Ile-Ser).54. The vaccine according to claim 40 wherein the antigenic synthetic peptide is 78(Met-Pro-Ile-Ser-Val-Ser-Trp-Gly-Gly-Gln).55. The vaccine according to claim 40 wherein the antigenic synthetic peptide in 87(Gln-Val-Leu-Ser-Thr-thr-Ala-Lys-Glu-Phe).56. The vaccine according to claim 40 wherein the antigenic synthetic peptide is 126(Ala-Gly-Thr-Ala-pro-Thr-Ala-Gly-Asn-Tyr).57. The vaccine according to claim 46 wherein the antigenic synthetic peptide is 133 (Gly-Asn-Tyr-Ser-Gly-Val-Val-Ser-Leu-Val).58. The vaccine according to claim 44 wherein the antigenic synthetic peptide is selected from the group consisting essentially of 3(Lys-Ana-Ile-Thr-Val-Thr-Ala-Ser-Val),11(Val-Asp-Pro-Val-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 22(Gly-Asn-Ala-Leu-Pro-Ser-Ala-Val), 32(Ala-Tyr-Ser-Pro-Ala-Ser-Lys-Thr-Phe-Lys-Thr-Phe-Glu-Ser-Tyr-Arg-Val), 32(Ala-Tyr-Ser-Pro-Ala-Ser-Lys-Thr-Phe), 38(Lys-Thr-Phe-Glu-Ser-Tyr-Arg-Val), 66(Pro-Gln-Leu-Thr-Asp-Val-Leu-Asn-Ser), 93(Ala-Lys-Glu-Phe-Glu-Ala-Ala-Ala), 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr), 127(Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and mixtures thereof. 59. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 3(Lys-Ana-Ile-Thr-Val-Thr-Ala-Ser-Val).60. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 11(Val-Asp-Pro-Val-Ile-Asp-Lau-Leu-Gln-Ala-Asp).61. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 22(Gly-Asn-Ala-Lou-Pro-Ser-Ala-Val).62. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 32(Ala-Tyr-Ser-Pro-Ala-Ser-Lys-Thr-Phe-Lys-Thr-Phe-Glu-Ser-Tyr-Arg-Val).63. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 32(Ala-Tyr-Ser-Pro-Ala-Ser-Lys-Thr-Phe).64. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 38(Lys-Thr-Phe-Glu-Ser-Tyr-Arg-Val).65. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 66(Pro-Gln-Leu-Thr-Asp-Val-Leu-Asn-Ser).66. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 93(Ala-Lys-Glu-Phe-Glu-Ala-Ala-Ala).67. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr).68. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 127(Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser).69. The vaccine according to claim 58 wherein the antigenic synthetic peptide is 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser).70. The vaccine according to claim 44 wherein the antigenic synthetic peptide in selected from the group consisting essentially of 3(Lys-Asn-Ile-Thr-Val-Thr-Ala-Ser-Bal-Asp-Pro),8(Thr-Ala-Ser-Bal-Asp-Pro-Bal-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 11(Bal-Asp-Pro-Bal-Ile-Asp-Leu-Leu-Gln-Ala-Asp), 20(Ala-Asp-Gly-Asn-Ala-Lau-Pro-Ser-Ala-Val), 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and 126(Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser), and mixtures thereof. 71. The vaccine according to claim 70 wherein the antigenic synthetic peptide is 3(Lys-Asn-Ile-Thr-Val-Thr-Ala-Ser-Bal-Asp-Pro).72. The vaccine according to claim 70 wherein the antigenic synthetic peptide is 8(Thr-Ala-Ser-Bal-Asp-Pro-Bal-Ile-Asp-Leu-Leu-Gln-Ala-Asp).73. The vaccine according to claim 70 wherein the antigenic synthetic peptide is 11(Bal-Asp-Pro-Bal-Ile-Asp-Leu-Leu-Gln-ala-Asp).74. The vaccine according to claim 70 wherein the antigenic synthetic peptide is 20(Ala-Asp-Gly-Asn-Ala-Leu-Pro-Ser-Ala-Val).75. The vaccine according to claim 70 wherein the antigenic synthetic peptide is 124(Lys-Thr-Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser).76. The vaccine according to claim 70 wherein the antigenic synthetic peptide is 126(Ala-Gly-Thr-Ala-Pro-Thr-Ala-Gly-Asn-Tyr-Ser).77. The method of claim 31, wherein the viral infection is caused by a virus selected from the group consisting of hepatitis A, hepatitis B, hepatitis C, Varicella-Zoster virus, Epstein-Barr virus, Rotaviruses, polio virus, human immunodeficiency virus (HIV), herpes simplex virus type 1, human retroviruses, herpes simplex virus type 2, Ebola virus, cytomegalo viruses, Herpes Simplex viruses, Human cytomegalovirus, Varicella-Zoster Virus, Epstein-Barr Virus, Poxvirus, Influenza viruses, Parainfluenza viruses, Respiratory Syncytial virus, Rhinoviruses, coronaviruses, Adenoviruses, Measles virus, Mumps virus, Robella Virus, Human Parvoviruses, Arboviruses, Rabies virus, Enteroviruses, reoviruses, viruses Causing gastroenteritis Hepatitis Viruses, Filoviruses, Arenaaviruses, Papillomaviruses, Polyomaviruses, Human Immunodeficiency viruses, Human Retroviruses, and Spongirorm Encephalopathies.78. The method in accordance with claim 27 wherein said peptides is an antigen in the amount or 0.1 to 1%.79. 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.80. The vaccine according to claim 79 wherein the polymer is a blend of end-capped and uncapped polymers.81. The vaccine according to claim 80 wherein the relative ratio between the lactide and glycolide component is within the range of 90/10 to 40/60.82. The vaccine according to claim 80 wherein the relative ratio between the amount of lactide and glycolide component is within the range of 48/52 to 52/48.83. The vaccine according to claim 79 wherein the antigen is a bacteria or derivatives thereof.84. The vaccine according to claim 80 wherein the antigen is a virus or derivatives thereof.85. The vaccine according to claim 80 wherein the antigens is a parasite or derivative thereof.86. The vaccine according to claim 80 wherein the antigen is fungus or derivative thereof.87. The vaccine according to claim 83 wherein the bacteria is selected from the group consisting of Salmonella typhi, Shigella Sonnei, Shigella Flexneri, Shigella dysenteriae, Shigella boydii, Escheria coli, Vibrio cholera, Group D-2, Group E, Group G, Group I, Group 1, Listseria, Erysipelothrix, Mycobacterium, Aerobic pathogenic Actinomycetales, Enterobacteriaceae, Vibrio, aeromonas, Plesiomonas, Helicobacter, W. succinogenes, Acineto bacter spp., Foavobacterium, Pseudomonas, Lepionella, Brucella, Haemophilus, Bordetalla, Mycoplasmas, Gardnerella, Streptobacillus, Spirillum, Calymmatobacterium, Clostridium, Treponema, Borrelia, Leptospira, Anaerobic Gram-negative Bacteria including bacilli and Cocci, Anaerobic gram-Postive Nonsporeforming Bacilli and Cocci, versinia, staphylococcus, clostridium, Enteroccus, Streptoccus, Aerococcus, Planococcus, Stomatococcus, Micrococcus, Lactoccus, Germella, Pediococcus, Leuconostoc, Bacillus, Neisseria, Branhamella, Coryne bacterium, campylobacter, Arcanobacterium haemolyticum, Rhodococcus spp., Rhodococcus, Group A-4.88. The vaccine of claim 84 wherein the virus is selected from the group consisting of hepatitis A, hepatitis B, hepatitis C, Varicella-Zoster virus, Epstein-Barr virus, Rotaviruses, polio virus, human immunodeficiency virus (HIV), herpes simplex virus type 1, human retroviruses, herpes simplex virus type 2, Ebola virus, cytomegalo viruses, Herpes Simplex viruses, Human cytomegalovirus, Varicella-Zoster Virus, Epstein-Barr Virus, Poxvirus, Influenza viruses, Parainfluenza viruses, Respiratory Syncytial virus, Rhinoviruses, coronaviruses, Adenoviruses, Measles virus, Mumps virus, Robella Virus, Human Parvoviruses, Arboviruses, Rabies virus, Enteroviruses, reoviruses, viruses Causing gastroenteritis Hepatitis Viruses, Filoviruses, Arenaaviruses, Papillomaviruses, Polyomaviruses, Human Immunodeficiency viruses, Human Retroviruses, and Spongirorm Encephalopathies.89. 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.90. An immunostimulating composition according to claim 89 wherein the amount of said immunogenic substance is within the range of 0.1 to 1.5% based on the volume of said bulk matrix.91. An immunostimulating composition according to claim 89 wherein the immunogenic substance comprises Colony Factor Antigen (CFA/II), hepatitis B surface antigen (HBsAg), and a mixture thereof physiologically similar antigen.92. An immunostimulating composition according to claim 89 wherein the relative ratio between the lactide and glycolide component is within the range of 48/52 to 52/48.93. An immunostimulating composition according to claim 89 wherein the size of more than 50% of said microspheres is between 5 to 10 um in diameter by volume.94. An immunostimulating composition according to claim 89 wherein the immunogenic substance is the synthetic peptide representing the peptide fragment beginning with the amino acid residue 63 through 78 of Pilus Protein CS3, said residue having the amino acid sequence, 63(Ser-Lys-Asn-Gly-Thr-Val-Thr-Try-Ala-His-Glu-Thr-Asn-Asn-Ser-Ala).95. A vaccine comprising an immunostimulating composition of claim 89 and a sterile, pharmaceutically-acceptable carrier therefor.96. A vaccine comprising an immunostimulating composition of claim 95 wherein said immunogenic substance is Colony Factor Antigen (CFA/II).97. A vaccine comprising an immunostimulating composition of claim 96 wherein said immunogenic substance is hepatitis B surface antigen (HBsAg).98. A method for the vaccination against bacterial infection comprising administering to a human in need thereof, an antibactericidally effective amount of a composition of claim 95.99. A method according to claim 98 wherein the bacterial infection is caused by a bacteria selected from the group consisting of Salmonella typhi, Shigella Sonnei, Shigella Flexneri, Shigella dysenteriae, Shigella boydii, Escheria coli, Vibrio cholera, Group D-2, Group E, Group G, Group I, Group 1, Listseria, Erysipelothrix, Mycobacterium, Aerobic pathogenic Actinomycetales, Enterobacteriaceae, Vibrio, aeromonas, Plesiomonas, Helicobacter, W. succinogenes, Acineto bacter spp., Foavobacterium, Pseudomonas, Lepionella, Brucella, Haemophilus, Bordetalla, Mycoplasmas, Gardnerella, Streptobacillus, Spirillum, Calymmatobacterium, Clostridium, Treponema, Borrelia, Leptospira, Anaerobic Gram-negative Bacteria including bacilli and Cocci, Anaerobic gram-Postive Nonsporeforming Bacilli and Cocci, versinia, staphylococcus, clostridium, Enteroccus, Streptoccus, Aerococcus, Planococcus, Stomatococcus, Micrococcus, Lactoccus, Germella, Pediococcus, Leuconostoc, Bacillus, Neisseria, Branhamella, Coryne bacterium, campylobacter, Arcanobacterium haemolyticum, Rhodococcus spp., Rhodococcus, Group A-4.100. A method for the vaccination against viral infection comprising administering to a human in need thereof, an antivirally effective amount of a composition of claim 89.101. 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.102. A method of preparing an immunotherapeutic agent against infections caused by a bacteria comprising the steps of (1) immunizing a plasma donor with a vaccine according to claim 40 such that a hyperimmune globulin is produced which contains antibodies directed against the bacteria; (2) separating the hyperimmune globulin and (3) purifying the hyperimmune globulin.103. A method preparing an immunotherapeutic agent against infections caused by a virus comprising the step of immunizing a plasma donor with a vaccine according to claim 41 such that hyperimmune globulin is produced which contains antibodies directed against the hepatitis B virus.104. An immunotherapy method comprising the step of administering to a subject an immunostimulatory amount of hyperimmune globulin prepared according to claim 102.105. An immunotherapy method comprising the step of administering to a subject an immunostimulatory amount of hyperimmune globulin prepared according to claim 103.106. A method for the protection against infection of a subject by enteropathogenic organisms or hepatitis B virus comprising administering to said subject an immunogenic amount of an immunostimulating composition of claim 89.107. A method according to claim 104 wherein the immunostimulating composition is administered orally.108. A method according to claim 104 wherein the immunostimulating composition is administered parenterally.109. A method according to claim 104 wherein the immunostimulating composition is administered in four separate doses on day 0, day 7, day 14, and day 28.110. 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.111. The method according to claim 110 wherein the biodegradable (lactide/glycolide) is a blend of uncapped and end-capped forms having a relative ratio between the amount of lactide and glycolide component within the range of 100/0 to 1/99.112. A method according to claim 111 wherein the bacterial infection is (1) a subcutaneous infection secondary to contaminated abdominal surgery, (2) an infection surrounding prosthetic devices and vascular grafts, (3) ocular infections, (4) topical skin infections, (5) orthopedic infections, including osteomyelitis, or (6) oral infections.113. The method according to claim 112 wherein the oral infections are pericoronitis or periodontal disease.114. The method according to claim 111 wherein the administration is effected prior to infection.115. The method according to claim 111 wherein the administration is effected subsequent to infection.116. The method according to claim 111 wherein said animal is a human.117. The method according to claim 111 wherein said animal is a nonhuman.118. The method in accordance with claim 111 comprising applying to the soft tissue or bone tissue of said animal a bactericidally-effective amount of said antibiotic, selected from the group consisting of a beta-lactam, aminoglycolide, polymyxin-b, Amphotericin B, Aztreonam, cephalosporins, chloramphenicol, fusidans, lincosamides, macrolides, methronidazole, nitro-furation, Imipenem/cilastin, quinolones, refampin, polyenes, tetracycline, sulfonamides, trimethoprim, vancomycin, teicoplanin, imidazoles, and erythromycin, encapsulated within a ,biodegradable polymeric matrix of said copolymer wherein the amount of the lactide and glycolide (L/G) component is within the range of 48/52 to 52/48 based on the weight of said polymeric matrix which is present in the amount of from 40 to 95 percent, resulting in the controlled release of a bacteriacidal amount of the said antibiotic over a period of from 1 to 100 days.119. The method of claim 118 wherein the polymeric matrix consists essentially of a poly(DL-lactide-co-glycolide) wherein the relative ratio between the amount of lactide and glycolide (L/G) component is within the range of 48/52 to 52/48.120. The method of claim 118 wherein the bacterial infection is caused by a resistant or non-resistant bacteria selected from the group consisting of Enterobacteriaceae; Klebsiella spp.; Bacteroides sp. Enterococci; Proteus sp.; Streptococcus sp.; Staphylococcus sp.; Pseudomonas sp.; Neisseria sp.; Pedptostreptococcus sp.; fusobacterium sp.; Actinomyces sp.; Mycobacterium sp.; Listeria sp.; Corynebacterium sp.; Proprionibacterium sp.; Actinobacillus sp.; Aerobacter sp.; Borrelia sp.; Campylobacter sp.; cytophaga sp.; Pasteurella sp.; Clostridium sp., Enterobacter aerogenes, Peptococcus sp.; Proteus vulgaris, Proteus morganii, Staphylococcus aureus, Streptococcus pyogenes, Actinomyces sp., Campylobacter fetus, and Legionella pneumophila, ampilllin-resistant strain of S. aureus, and methicillin-resistant strain of S. aureus. 121. The method of claim 118 wherein the antibiotic is selected from the group consisting essentially of a beta-lactam, aminoglycolide, polymyxin-B, amphotericin B, aztreonam, cephalosporine, chloramphenicol, fusidans, lincosamides, macrolides, methronidazole, nitro-furantoin, Imipenem/cilastin, quinolones, rifampin, polyenes, tetracycline, sulfonamides, trimethoprim, vancomycin, teicoplanin, imidazoles, and erythromycin.122. The method of claim 121 wherein the beta-lactam is cephalosporin.123. The method of claim 121 wherein the beta-lactam is penicillin.124. The method of claim 121 wherein the aminoglycolide is gentamicin.125. The method of claim 121 wherein the aminoglycolide is amikacin.126. The method of claim 121 wherein the aminoglycolide is tobramycin.127. The method of claim 121 wherein the aminoglycolide is kanamycin.128. The method of claim 121 wherein the beta-lactam is an ampicillin.129. The method of claim 121 wherein the polymeric matrix consists essentially of a poly(DL-lactide-co-glycolide), wherein the relative ratio between the amount of lactide and glycolide (L/G) component is within the range of 48/52 to 58/42.130. The method of claim 128 wherein the ampicillin is present in an amount of from 5 to 60 percent and the amount of polymeric matrix is from 40 to 95 percent.131. The process comprising treating humans in need, thereof, suffering from diseases and/or ailments selected from the group consisting of: viral infections; bacterial infections; fungal infections; parasitic infections and more specific diseases and/or ailments; such as, aids; alzheimer's dementia; angiogenesis diseases; aphthour ulcers in AIDS patients; asthma; atopic dermatitis; psoriasis; basal cell carcinoma; benign prostatic hypertrophy; blood substitute; blood substitute in surgery patients; blood substitute in trauma patients; breast cancer; breast cancer; cutaneous & metastatic; cachexia in AIDS; campylobacter infection; cancer; pnemonia; sexually transmitted diseases (STDs); cancer; viral dieases; candida albicians in AIDS and cancer; candidiasis in HIV infection; pain in cancer; pancreatic cancer; parkinson's disease; peritumoral brain edema; postoperative adhesions (prevent); proliferative diseases; prostate cancer; ragweed allergy; renal disease; restenosis; rheumatoid arthritis; rheumatoid arthritis; allergies;/rotavirus infection; scalp psoriasis; septic shock; small-call lung cancer; solid tumors; stroke; thrombosis; type I diabetes; type I diabetes w/kidney transplants; type II diabetes; viseral leishmaniasis; malaria; periodontal or gum disease; cardiac rthythm; disorders; central nervous system diseases; central nervous system disorders; cervical dystonia (spasmodic torticollis); choridal neovascularization; chronic hepatitis c, b and a; colitis associated with antibiotics; colorectal cancer; coronary artery thrombosis; cryptosporidiosis in AIDS; cryptosporidiun, paryum diarrhea in AIDS; cystic fibrosis; cytomegalovirus disease; depression; social phobias; panic disorder; diabetic complications; disabetic eye disease; diarrhea associated with antibiotics; erectile dysfunction; genital herpes; graft-vs host disease in transplant patients; growth hormone deficiency; head and neck cancer; head trauma; stroke; heparin neutralization after cardiac bypass; hepatocallular carcinoma; HIV; HrV infection; huntington's disease; CNS diseases; hypercholesterolemia; hypertension; inflammation; inflammation and angiogensis; inflammation in cardiopulmonary bypass; influenza; migrain head ache; interstitial cystitis; kaposion sarcoma; kaposils coma in AIDS; lung cancer; melanoma; molluscum contagiosum in AIDS; multiple sclerosis; neoplastic meningitis from solid tumors; non-small call lung cancer; organ transplant rejection; osteoarthritis; rheumatoid arthritis; osteoporosis; drug addiction; shock; ovarian cancer; Amebiasis; Babesiasis; Chagas' disease (Trypanosoma cruzi); Cryptosporidiosis; Cysticetcosis; Fascioliasis; Filariasis; Echinococcosis; Giardiasis; Leishmaniasis; Malaria; Paragonimiasis; Toxoplasmosis; Trichinellosis; Trichomoniasis; yeast infection; and pain, 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 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.132. A vaccine prepared from a composition for the burst-free, sustained, programmable release of active martials(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 to prevent the occurrence in humans in need thereof of diseases and/or ailments selected from the group consisting of viral infections; bacterial infections; fungal infections; parasitic infections and more specific diseases and/or ailments; such as, aids; alitimer's dementia; angiogenesis diseases; aphthour ulcers in AIDS patients; asthma; atopic dermatitis; psoriasis; basal call carcinoma; benign prostatic hypertrophy; blood substitute; blood substitute in surgery patients; blood substitute in trauma patients; breast cancer; breast cancer; cutaneous & metastatic; cachexia in AIDS; campylobacter infection; cancer; pneumonia; sexually transmitted diseases (STDs); cancer; viral diseases; candida albicians in AIDS and cancer; candidiasis in HIV infection; pain in cancer; pancreatic cancer; parkinson's disease; periturmoral brain edema; postoperative adhesions (prevent); proliferative diseases; prostate cancer; ragweed allergy; renal disease; restenosis; rheumatoid arthritis; rheumatoid arthritis; allergies; rotavirus infection; scalp psoriasis; septic shock; small-cell lung cancer; solid tumors; stroke; thrombosis; type I diabetes; type I diabetes w/kidney transplant; type II diabetes; viseral leishmaniasis; malaria; periodontal or gun disease; cardiac rthythm disorders; central nervous system diseases; central nervous system disorders; cervical dystonia (spasmodic torticoillis); choridal neovascularization; chronic hepatitis c, b and a; colitis associated with antibiotics; colorectal cancer, coronary artery thrombosis; cryptosporidiosis in AIDS; ryptosporidium paryum diarrhea in AIDS; cystic fibrosis; cytomegalovirus disease; depression; social phobias; panic disorder; diabetic complications; disabetic eye disease, diarrhea associated with antibiotics; erectile dysfunction; genital herpes; graft-vs host disease in transplant patients; growth hormone deficiency; head and neck cancer; head trauma; stroke; heparin neutralization after cardiac bypass; hepatocellular carcinoma; HIV; HIV infection; huntington's disease; CNS diseases; hypercholesterolemia; hypertension; inflammation; inflammation and angiogensis; inflammation in cardiopulmonary bypass; influenza; migrain head ache; interstitial cystitis; kaposils sarcoma; kaposils sarcoma in AIDS; lung cancer; melanoma; molluscum contagiosum in AIDS; multiple sclerosis; neoplastic meningitis from solid tumors; non-small call lung cancer; organ transplant rejection; ostsoarthritis; rheumatoid arthritis; osteoporosis; drug addiction; shock; ovarian cancer; Amebiasis; Babesiasis; Chagas' disease (Trypanosoma cruzi); Cryptosporidiosis; Cysticercosis; rascioliasis; Filariasis; Echinococcosis; Giardiasis; Leishmaniasis; Xalaria; Paragonimiasis; Pneunocystosis; Schistosomiasis; Strongylodiasis; Toxocariasis; Toxoplasmosis; Trichinellosis; Trichomoniasis; yeast infection; and pain.133. An immunostimulating composition of claim 89 wherein the immunogenic substance is derived from bacteria.134. A composition of claim 133 wherein the immunogenic substance is comprised of (i) a non-covalent complex between purified, detoxified LPS endotoxin derived from E. coli and (ii) purified outer membrane protein derived from N. meningitis. 135. A composition of claim 134, wherein said E. coli is strain J5 (Rc chemotype).136. A composition of claim 134, wherein said N. meningitis is group B strain.137. A composition of claim 134, wherein said purified LPS endotoxin of said non-covalent complex is also detoxified.138. A composition of claim 134, wherein said purified outer membrane protein to said purified LPS endotoxin in said non-covalent complex is between 1 and 2.139. An immunostimulating composition according to claim 133 wherein the amount of said immunogenic substance is within the range of 0.1 to 1.5% based on the volume of said bulk matrix.140. A vaccine according to claim 83, effective in actively immunizing a subject against infection by Gram-negative bacteria or against lipopolysaccharide (LPS) endotoxin-mediated pathology, comprising a non-covalent complex between purified LPS endotoxin derived from E. coli and purified outer membrane protein derived from N. meningitis. 141. A vaccine of claim 140, wherein said E. coli is strain J5 (Rc chemotype).142. A vaccine of claim 140, wherein said N. meningitis is group B strain.143. A vaccine of claim 140, wherein said purified LPS endotoxin of said no-covalent complex is also detoxified.144. A vaccine of claim 140, wherein the weight ratio of said purified outer membrane protein to said purified LPS endotoxin in said non-covalent complex is between 1 and 2.145. A method of actively immunizing a subject against infection by Gram-negative bacteria and LPS-induced pathology, comprising administering to said subject an effective amount of a vaccine of claim 140.146. A method of claim 145, wherein said E. coli is strain J5 (Rc chemotype).147. A method of claim 144, wherein said N. meningitis is group B strain.148. A method of claim 144, wherein said purified LPS endotoxin is detoxified.149. A method of claim 144, wherein said Gram-negative bacterial infection is a meningococcal infection.150. A method of passively conferring upon a second subject protection against infection by Gram-negative bacteria or LPS-mediated pathology, comprising the steps of:a) actively immunizing a first subject with a vaccine of claim 140 comprising a non-covalent complex between purified LPS endotoxin derived from E. coli and purified outer membrane protein derived from N. meningitis; b) collecting from said first subject a postimmune serum or plasma, or IgG isolated therefrom; and, c) administering to said second subject an amount of said serum or plasma or IgG isolated therefrom that is effective in conferring passive protection against a infection by Gram-negative bacteria and LPS-mediated pathology. 151. A method of claim 150, wherein said E. coli is strain J5 (Rc chemotype).152. A method of claim 150, herein said N. meningitis is group B strain.153. A method of claim 150, wherein said purified LPS endotoxin is detoxified.154. Serum, plasma or specific polyclonal antibody obtained from a subject immunized with a vaccine according to claim 140.