Abstract: A controlled release oral formulation, for human vaccines, are formed in microspherical form. The vaccine is suspended in a polymer matrix. The polymer matrix is formed from at least two highly water soluble biodegradable polymers, selected for example from starch, crosslinked starch, ficoll, polysucrose, polyvinyl alcohol, gelatine, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl-ethyl cellulose, hydroxypropyl-methyl cellulose, sodium carboxymethyl cellulose, cellulose acetate, sodium alginate, polymaleic anhydride esters, polyortho esters, polyethyteneimine, polyethylene glycol, methoxypolyethylene glycol, ethoxypolyethylene glycol, polyethylene oxide,poly(1,3 bis(p-carboxyphenoxy) propane-co-sebacic anhydride, N,N-diethylaminoacetate, block copolymers of polyoxyethylene and polyoxypropylene. The microspheres are coated with a (d,1 lactide-glycolide) copolymer. The coating makes the microspheres more resistant to enzymatic degradation.

Abstract: Implantable poly(lactic acid)-based pharmaceutical composition which comprises at least one water soluble antibiotic in particle form with controlled dimensions, less than 100 .mu.m uniformly dispersed in an amorphous poly(lactic acid) matrix, said composition being in ground powder or thin film form. Application especially in initiating local internal antibiotic therapy by the gradual release of the antibiotic substance.

Abstract: A once-a-day controlled release diltiazem formulation is described which includes:(a) from 20 to 50% by weight of enteric polymeric membrane coated pellets comprising a polymer membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder; and a second layer which comprises a membrane comprising a pH dependent polymeric material; and(b) from 50% to 80% by weight of delayed pulse polymeric membrane coated pellets comprising a polymeric membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder and a second layer which comprises a polymeric membrane which will substantially maintain its integrity in the varying pH conditions of the gastrointestinal tract but is permeable to diltiazem; and(c) a unit dose containment system.

Abstract: Injectable nanoparticles or microparticles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified as necessary to achieve variable release rates or to target specific cells or organs as desired. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the injectable particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the injectable particles. The injectable particles include magnetic particles or radioopaque materials for diagnostic imaging.

Abstract: A method for producing sustained release microsphere preparation for water-soluble medicament, which has high incorporation efficiency of the medicament and low initial burst, which comprises dissolving water-soluble pharmaceutical active ingredient and water-insoluble biodegradable polymer in one or two solvents in which both can dissolve, removing the solvent to give a solid dispersion having the water-soluble pharmaceutical active ingredient dispersed into said biodegradable polymer at molecular level, and further, dissolving said solid dispersion in an organic solvent being water-immiscible and having a boiling point of below 100.degree. C., and adding the resulting oil phase into an aqueous phase containing emulsifying agent to give O/W emulsion, and followed by removing the organic solvent from the oil phase of the resulting emulsion.

Abstract: Particles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified to achieve variable release rates or to target specific cells or organs. The particles have a biodegradable solid core containing a biologically active material and poly(alkylene glycol) moieties on the surface. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the particles.

Abstract: A drug delivery system useful in aiding individuals in the cessation of smoking or chewing nicotine containing products is described. The delivery system includes a physical constraint modulation system (PCMS.TM.) containing lobeline. The drug delivery system is capable of delivering lobeline to an individual in a controlled, sustained release manner and providing long-term therapeutic levels of lobeline to the individual. The delivery of lobeline in such a manner reduces or eliminates the individual's smoking or chewing habit. The PCMS may be a biodegradable polymer containing the lobeline capable of subcutaneous or intramuscular injection or implantation into the individual or may be part of a transdermal patch containing lobeline. Also described are methods of using the drug delivery systems and kits containing the drug delivery systems.

Abstract: Nonaqueous pharmaceutical compositions for use in aqueous physiological systems are disclosed comprising drug delivery vehicles suspended in nonaqueous perfluorocarbon or fluorinated silicone liquid carriers. The suspended drug delivery vehicles may be water labile or water stable and incorporate therapeutic or diagnostic compounds which remain stable and pharmaceutically effective for extended periods. The pharmaceutical compositions have improved bioavailability, are capable of low dose volume delivery, and do not leach the incorporated therapeutic or diagnostic compounds into the liquid carriers making them well suited for multi-dose packaging and administration.

Abstract: The invention relates to sustained-release biodegradable lice repelling preparations comprising as active ingredient a lice repelling agent comprising at least one natural oil selected from the group consisting of citronella oil, rosemary oil and eucalyptus oil, or at least one natural oil component selected from the group consisting of citronellal and geraniol or mixtures thereof and further comprising an anionic emulsifier and chitosan, optionally further comprising dermatologically acceptable additives, carriers or diluents. The preparations may be in the form of an aqueous emulsion or chitosan microcapsules, preferably prepared by the processes of the invention.

Abstract: A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g.

Abstract: A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g.

Abstract: A pharmaceutical composition comprising a shaped enteric material having distributed therethrough preferably substantially uniformly, pharmaceutical loaded particles, said particles having a size no greater than about 10 microns in any dimension and being alkali insoluble and the method of delivering pharmaceuticals to Peyer's glands.

Abstract: The present invention relates to a sustained-release suppository preparation characterized by comprising an acidic drug or a salt thereof which can be absorbed by rectal administration and an acidic compound or a pH buffering agent. The sustained-release suppository preparation of the present invention exhibits no rapid increase in blood concentration immediately after the administration and maintains its action for a long period of time. Thus, it is safer and exhibits a better therapeutic effect.

Abstract: Encapsulation of active materials in chitosan beads of uniform size and improved mechanical and chemical stability. The active material is suspended in an acidic aqueous solution of a chitosan having a molecular weight of less than 250,000, the suspension is added dropwise to a crosslinking solution of diphosphate and glyoxal hydrate and the resulting beads are cured. It is possible to coat the active material with oil prior to suspension.

Abstract: A drug delivery system useful in treating an individual for a drug dependence is described. One embodiment of the system is useful for aiding individuals in the cessation of smoking or chewing nicotine containing products is described. The delivery system includes a physical constraint modulation system (PCMS.TM.) containing lobeline. The drug delivery system is capable of delivering lobeline to an individual in a controlled, sustained release manner and providing long-term therapeutic levels of lobeline to the individual. The delivery of lobeline in such a manner reduces or eliminates the individual's smoking or chewing habit. The PCMS may be a biodegradable polymer containing the lobeline capable of subcutaneous or intramuscular injection or implantation into the individual or may be part of a transdermal patch containing lobeline. Also described are methods of using the drug delivery systems in treating other drug dependencies and kits containing the drug delivery systems.

Abstract: Gepirone compositions having extended release properties contain a gepirone salt, a cellulosic polymer matrix and suitable quantities of pharmaceutical excipients. Dosage forms based thereon require 18 to 24 hours for release of 90 to 95% of gepirone.

Abstract: The subject of the present invention is a process for preparing microparticles of the microsphere type of a water-soluble substance and a biocompatible and biodegradable polymer controlling the kinetics of release of the said substance consisting of a matrix of the said polymer within which the said water-soluble substance is regularly dispersed, characterized in thata) the said polymer is dissolved in a first volatile organic solvent immiscible with water,b) the said water-soluble substance is dissolved in a second solvent which is miscible with the said first solvent, is a solvent for the polymer, and miscible with water,c) the solution of the said substance and the solution of the said polymer are mixed,d) an organic phase of the polymer and of the said substance is obtained which is then emulsified in an immiscible dispersant medium consisting of an aqueous phase containing an emulsifying agent,e) the two solvents are then removed from the microspheres being formed with stirring, the first solvent being r

Abstract: A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.

Abstract: A new method of producing paucilamellar lipid vesicles has been developed. The vesicles are made of non-phospholipid surfactants. The paucilamellar lipid vesicles have 2-8 lipid bilayers surrounding a central cavity which may be filled with either an aqueous-based solution or an oil or wax.

Abstract: The present invention relates to a microcapsule having a core material encapsulated with a capsule wall obtained by coagulating the fine colloidal particles by using an electrolyte, and a process for producing such microcapsules. In the present invention, inorganic and/or organic colloidal particles are used as the wall material and such particles are coagulated by using an electrolyte to form the capsule wall, so that it is possible to produce the microcapsules under mild conditions and with simple operations, and in addition, even the physically and/or chemically instable core materials can be easily encapsulated.

Abstract: A preparation for reducing intraocular pressure consisting essentially of a therapeutically effective amount of the fixed combination of dipivalylepinephrine and carbachol (preparation 1) or dipivalylepinephrine and beta-blocker (preparation 2). The preparations may be prepared both as a solution and as a suspension. Either preparation is administered twice daily.

Abstract: A method for encapsulating a biological substance is biocompatible microcapsules is disclosed, said method comprising:a) maintaining a coating-forming liquid film sheet comprising a solution of a soluble organic polymer in an organic solvent,b) causing droplets comprising biological substance is an aqueous medium to pass through said sheet to form microcapsules comprising cores of said droplets coated by said liquid film, andc) permitting said microcapsules to pass through said sheet so that a portion of said polymer precipitates in the presence of water in said droplets while evaporating a portion of said solvent to form a continuous permeable polymer coating of sufficient structural that said microcapsules are self-supporting.

Abstract: The present invention is directed to a novel sustained release matrix and oral dosage form comprising a homogeneous matrix formed from a wet granulation containing an effective amount of a medicament and a polymer blend of hydroxypropyl cellulose and hydroxyethyl cellulose. The present invention also discloses a novel process for making a sustained release oral dosage form comprising wet granulating a medicament with a polymer blend of hydroxypropyl cellulose and hydroxyethyl cellulose to form a homogeneous matrix, wherein the polymer blend is provided in an amount effective to control the release of said medicament, then forming the homogenous matrix into a solid oral dosage form.

Abstract: A pharmaceutical composition is prepared in the form of microparticles or of an implant comprising a biodegradable polymer selected from poly-1,4-butylene succinate, poly-2,3-butylene succinate, poly-1,4-butylene fumarate and poly-2,3-butylene succinate, incorporating as the active substance the pamoate, tannate, stearate or palmitate of a natural or of a synthetic peptide comprising 3 to 45 amino acids, such as LH-RH, somatostatin, GH-RH or calcitonin, or one of their synthetic analogues or homologues. The preparation comprises dry blending the ingredients in the form of powders, pre-compressing and preheating the mixture and then extruding the pre-compressed and pre-heated mixture. The product resulting from the extrusion step can then be comminuted and finally sieved.

Abstract: The invention concerns a method for the production of microscopic particles made of hydrolytically decomposable polymers, in particular copolymers, and containing active substances, using fluid gas with a uniform particle-size distribution and by the addition of biologically compatible amino acids. The microscopic particles produced by this method can be used as drugs for the treatment of humans or animals.

Abstract: ACTH polymeric controlled release systems are described wherein the ACTH retains good biological activity and is released over an extended period of time following administration by injection. In the preferred embodiment, the ACTH polymeric microspheres are made using very cold temperatures to freeze the polymer-ACTH mixtures into polymeric microspheres with very high retention of biological activity and material. Sustained release of biologically active ACTH is achieved when the microspheres are tested in vitro, extending over a period of greater than one day to several months. Altered release can be achieved by inclusion of degradation modifiers, pore forming agents, and stabilizers of the ACTH.

Abstract: A drug delivery system useful in aiding individuals in the cessation of smoking or chewing nicotine containing products is described. The delivery system includes a physical constraint modulation system (PCMS.TM.) containing lobeline. The drug delivery system is capable of delivering lobeline to an individual in a controlled, sustained release manner and providing long-term therapeutic levels of lobeline to the individual. The delivery of lobeline in such a manner reduces or eliminates the individual's smoking or chewing habit. The PCMS may be a biodegradable polymer containing the lobeline capable of subcutaneous or intramuscular injection or implantation into the individual or may be part of a transdermal patch containing lobeline. Also described are methods of using the drug delivery systems and kits containing the drug delivery systems.

Abstract: There is provided a matrix preparation produced by dispersing a pharmaceutically active ingredient into a matrix which is solid at ambient temperature and comprised of a fatty acid ester of a polyglycerol. The preparation has stable release controlling ability, can be processed to fine granules, granules, capsules, tablets etc., and contributes to reduction of the administration times of the active ingredient and side effects of the ingredient.

Abstract: The present invention relates to method for preventing or treating cachexia in a mammal based on the administration of a therapeutically effective amount of an anti-cachexia agent. Suitable agents include ADP-ribose-polymerase inhibitors, ADP-ribose-transferase inhibitors, NADase inhibitors, nicotinamide benzamide, theophylline, thymine and analogs thereof.

Abstract: The present invention relates to a sustained-release injection, which comprises a suspension of a powder comprising an active ingredient and a pharmaceutically acceptable biodegradable carrier (e.g. proteins, polysaccharides and synthetic high molecular compounds, preferably collagen, atelocollagen, gelatin, and a mixture thereof) in a viscous solvent for injection (e.g. vegetable oils, polyethylene glycol, propylene glycol, silicone oil, and medium-chain fatty acid triglycerides). The sustained-release injection can release the active ingredient at an effective level for a long period of time when injected.

Abstract: This invention provides a method and compositions for increasing the permeability of epithelial cells to a chloride ion in a subject comprising administering a permeability enhancing amount of a composition comprising a nontoxic, nonionic surfactant having (1) a critical micelle concentration of less than about 10 mM and a hydrophile-lipophile balance number of from about 10 to 20 and (2) a suitable hydrophobic organic group joined by a linkage to a suitable hydrophilic polyol.

Abstract: New solid, porous unitary form comprising micro-particles and/or nano-particles, made by lyophilization are useful for the administration of therapeutically active substances, nutrition agents, diagnostic agents or cosmetic agents.

Abstract: A pharmaceutical composition comprising a shaped enteric material having distributed therethrough preferably substantially uniformly, pharmaceutical loaded particles, said particles having a size no greater than about 10 microns in any dimension and being alkali insoluble and the method of delivering pharmaceuticals to Peyer's glands.

Abstract: A process for conveniently producing microcapsules containing a gelatin wall crosslinked with quinone and a core of an active compound such as a fouling reducing agent, particularly a tributyl tin chloride, involves use of a simple or complex coacervation technique. The quinone crosslinking provides microcapsules of excellent strength, storage stability, and resistance to aqueous exposure, such that the rate of release of the fouling reducing agent can be controlled with precision.

Abstract: The present invention relates to oral compositions in the form of microcapsules which reduce oral bacteria and provide long lasting breath protection.

Abstract: Oral compositions for the local administration of a therapeutic agent to a periodontal pocket of a patient for alleviating dental disease comprise a plurality of dry, discrete microparticles each of which comprise an effective amount of at least one therapeutic agent dispersed in a matrix comprising a biocompatible and biodegradable polymer. Apparatus and methods are also provided for the dispensing of the dry microparticles to the periodontal pocket whereby they become tacky and adhere to the involved tissue so as to induce long term therapeutic benefits.

Abstract: The present invention relates to polymeric microspheres as injectable, drug-delivery systems for use to deliver bioactive agents to sites within the central nervous system, and for the stimulation of nerve fiber growth by implanting such microspheres within the central nervous system of a patient.

Abstract: Microcapsules can be prepared in an energy-saving manner by using a polyisocyanate which consists exclusively or partially of reaction products of isocyanates having a functionality of 2 or more with polyethylene oxide alcohols.

Abstract: Pharmaceutical compositions comprising a cyclosporin, e.g. Ciclosporin or [Nva].sup.2 -Ciclosporin, in "microemulsion pre-concentrate" and microemulsion form. The compositions typically comprise (1.1) a C.sub.1-5 alkyl or tetrahydrofurfuryl di- or partial-ether of a low molecular weight mono- or poly-oxy-alkane diol, e.g. Transcutol or Glycofurol, as hydrophilic component. Compositions are also provided comprising a cyclosporin and (1.1) and, suitably, also a saccharide monoester, e.g. raffinose or saccharose monolaurate. Dosage forms include topical formulations and, in particular, oral dosage forms.

Abstract: A process is disclosed for the microencapsulation of a substantially water-insoluble liquid material within a porous shell to effect a slow rate of release of said material through said shell which comprises (a) providing an organic solution comprising said material and an etherified urea-formaldehyde prepolymer dissolved therein in which from about 50% to about 98% of the methylol groups of said prepolymer have been etherified with a C.sub.4 -C.sub.

Abstract: Microcapsules are advantageously produced with high take-up of a water-soluble drug by preparing a W/O emulsion composed of a water-soluble drug-containing solution as the inner aqueous phase and a polymer-containing solution as the oil phase, dispersing said emulsion in an aqueous phase and subjecting the resulting W/O/W emulsion to an in-water drying, wherein the viscosity of the W/O emulsion used in preparing the W/O/W emulsion is adjusted to about 150 to about 10,000 centipoises.

Abstract: A new series of degradable polymeric matrices were prepared by blending polymers that degrade by hydrolysis such as poly(L-lactic acid)(PLA), and nonionic Pluronic.TM. surfactants, block copolymers of polyethyleneoxide (PEO) and polypropyleneoxide (PPO). The water content of the polymer blend films was controlled by mixing different types of block copolymers and by adjusting their amount. In aqueous solution, the blends revealed the typical liquid-crystalline phase transition of Pluronic.TM. polymers, suggesting the formation of a gel-like structure within the polymer skeleton. Poly(lactic acid) degradation rates were not affected by the blending procedure, although the hydration degree in these matrices was higher. When used as drug-releasing matrices, these blends extended protein release and minimized the initial protein burst, as compared to the pure polymer.

Abstract: A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g.

Abstract: A polymeric controlled delivery system is provided for use in treating periodontal disease. The delivery system in a variety of forms is placed directly in the infected gingival tissue where the chemotherapeutic agent is slowly released into the tissue and into the infected periodontal pocket by means of the gingival crevicular fluid originating in the gingival tissue.

Abstract: Ophthalmic product comprising nanocapsules, process for preparing it and application of the nanocapsules.The present invention relates to an ophthalmic product comprising nanocapsules, characterized by a central core of lipid nature surrounded by a polymeric membrane capable of adhering to biological tissues.The present invention also relates to its preparation and to the application of the nanocapsules for ophthalmic use.

Abstract: Microcapsules providing breath protection are described and claimed as well as methods of their use.

Abstract: Microcapsules are prepared by encapsulating a core material with a capsule shell wall containing glutamldehyde crosslinked gelatin and at least one water soluble plasticizer that reduces the permeability of the Crosslinked gelatin. Optionally, the capsule shell wall also contains a feeding deterrent that dissuades accidental ingestion of the microcapsule. Upon exposing the microcapsules to water, the plasticizer is removed malting the shell wall permeable whereby the encapsulated core material is released. Materials such as insecticides, herbicides, plant growth regulating agents, and fungicides may be encapsulated and released at a controlled location, time and rate.

Abstract: The present invention relates to oral compositions in the form of microcapsules which reduce oral bacteria and provide long lasting breath protection.

Abstract: A process for encapsulating a wide variety of target materials, including both hydrophilic and hydrophobic materials, employs condensation of two reactive compounds to form shells around core phase particles including target material dispersed in a continuous phase. One of the reactive compounds has at least two active methylene functional groups per molecule, the other being an active methylene-reactive crosslinking agent. Either type of the reactive compounds can be dispersed in the continuous phase, the other being dispersible in the core phase. Applications include controlled release microencapsulation of agriculture chemicals and biocides.

Abstract: Sustained release microcapsules including a water soluble drug and an organic basic substance as a drug retaining substance of this invention not only have a high rate of incorporation (trapping rate), but also show little initial release so that they can be administered safely and bring about persistent, stable sustained release.