Abstract: The present invention relates to novel compositions comprising microspheres and/or nanospheres containing condensed polyanionic bioactive agents, such as DNA. The polyanionic bioactive agent in the microspheres and/or nanospheres is preferably condensed using a polycationic condensing agent, such as poly-L-lysine. The present invention further relates to methods for producing the microspheres and/or nanospheres containing condensed polyanionic bioactive agents.

Abstract: A method for preparing biodegradable, biocompatible microparticles. A first phase is prepared that includes a biodegradable, biocompatible polymer, an active agent, and a solvent. A second phase is prepared. The first and second phases are combined to form an emulsion in which the first phase is discontinuous and the second phase is continuous. The discontinuous first phase is separated from the continuous second phase. The residual level of solvent in the discontinuous first phase is reduced to less than about 2% by weight.

Abstract: Methods for preparing microspheres containing imidazole derivatives are provided. Also provided is the use of imidazole derivatives containing microspheres for treating fungal infections. Oral dosage forms for oral administration are also provided.

Abstract: A method of producing a thermally expansive microcapsule that is excellent in heat resistance and solvent resistance, narrow in breadth of the distribution of particle size, and extremely low in secondary cohesion of the particles when heated, wherein a polymer obtained from the component comprising not less than 80 weight % of monomer of nitrile series, less than weight % of monomer of non-nitrile series, and 0.05-1 weight % of at least tetrafunctional cross-linking agent and/or of long side chain of cross-linking agent is used to micro-encapsulate a volatile expanding agent that comes into its gaseous state at a temperature equal to or less than a softening point of the polymer.

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

Abstract: A method is provided for the formation of liposomes of 0.1 &mgr;m to 50 &mgr;m in diameter having unilamella or multilamella structure and containing water insoluble or undissolved particulate materials comprising (a) forming liposomes and removing substantially all of any organic solvent used in their preparation, (b) freeze drying the liposomes so formed and then (c) rehydrating them in intimate admixture with the particulate material. Preferred encapsulated materials are particulate materials, most preferably microorganisms, plant or animal cells or water insoluble structures having organic solvent labile biochemical or immunological activity, but any water insoluble particulate may be encapsulated using the method. For example catalysts or drugs that are sparingly soluble may also be so incorporated such that slow release into the a patients body may be provided while release of detergents included in the many liposome preparation protocols may be avoided.

Abstract: The present invention provides a method for preparing submicron sized particles of an organic compound, the solubility of which is greater in a water-miscible first solvent than in a second solvent which is aqueous, the process including the steps of: (i) dissolving the organic compound in the water-miscible first solvent to form a solution, (ii) mixing the solution with the second solvent to define a pre-suspension; and (iii) adding energy to the pre-suspension to form particles having an average effective particle size of 400 nm to 2 microns.

Abstract: This invention provides methods of loading preformed liposomes by transmembrane permeation induced by alcohols. Solutes loaded into liposomes by this ethanol mediated process include both small nonpolar molecules and larger species, such as proteins and carbohydrates.

Abstract: Microencapsulated medicine of ox adrenal medulla pheochromocyte (BBC) for treating pain is prepared through the following steps: 1. suspending BBC in solution of sodium alginate; 2. dispersing the suspension in solution of calcium chloride to form calcium alginate bead deposit; 3. mixing the deposit with solution of polylysine to form a coating and depositing; 4. mixing the deposit with sodium alginate to form a coating; 5. displacing the calcium ions in deposit with sodium citrate for microencapsulating BBC; 6. transferring the microencapsulated BBC into culture liquid for storage. The medicine can release analgesic substance for several months after it be implanted into human body.

Abstract: The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having the desired activity using a change in the optical properties of the genetic elements. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.

Abstract: The present invention relates to a method of making a liposome, the method comprising the steps of: (a) mixing a lipophilic phase and a hydrophilic phase, the lipophilic phase comprising an amphiphilic bilayer-forming substance; and (b) applying a shear force to the mixture to form the liposome; wherein the shear force is created by passing the mixture by a member at a velocity sufficient to create turbulence in the mixture.

Abstract: A method for preparing microparticles having a selected polymer molecular weight. The hold time and temperature of a solution containing a nucleophilic compound and a polymer having a starting molecular weight are controlled in order to control the molecular weight of the polymer in the finished microparticle product. In this manner a selected polymer molecular weight in the finished microparticle product can be achieved from a variety of starting material molecular weights.

Abstract: Processes for making microparticles, preferably containing an active agent, are provided. In a preferred embodiment, the process involves preparing (1) a dispersed phase containing an agent in a solution of polymer and a first solvent; (2) a continuous phase containing a surfactant, and a second solvent that is totally or partially immiscible with the first solvent; and (3) an extraction phase that is a nonsolvent for the polymer, a solvent for the continuous phase components, and a solvent for the first solvent, wherein the first solvent has solubility in the extraction phase of between about 0.1% and 25% by weight. Then, the dispersed phase and the continuous phase are mixed to form an emulsion, and the emulsion is then briefly mixed with a suitable quantity of extraction phase to induce skin formation at the interface of the dispersed and continuous phases. Remaining solvent is removed by an evaporation process step.

Abstract: Preparation of particles of an active substance having a layer of an additive at the particle surfaces, by dissolving both the active substance and the additive in a vehicle to form a target solution, and contacting the target solution with an anti-solvent fluid using a SEDS™ particle formation process, to cause the active substance and additive to coprecipitate. The additive is typically a protective additive, in particular a taste and/or odour masking agent. Also provided is a particulate coformulation made by the method, which has a finite gradient in the relative additive concentration, which concentration increases radially outwards from the active-rich core to the additive-rich surface of the particles.

Abstract: Methods for preparing microparticles having improved flowability to facilitate processing in automated equipment. Microparticles are maintained at a conditioning temperature for a period of time. The conditioning temperature and period are selected so that the angle of repose of the microparticles is less than about 28°.

Abstract: Submicron particles of a biologically active agent are prepared by atomizing using multifluid atomization a dispersed system comprising at least one biologically active agent and at least one solvent to produce droplets, freezing the droplets to produce frozen droplets, lyophilizing the frozen droplets to obtain microstructures capable of being further fragmented into submicron particles by techniques such as probe sonication. The submicron particles can be incorporated into sustained release compositions having a reduced initial release of biologically active agent. The sustained release compositions can be administered to a human or animal.

Abstract: The present invention provides novel encapsulation compositions and methods. In particular, the invention relates to fluorescent capsule compositions, which consists of a layer of a polymer shell enclosing one or more fluorescent materials such as fluorescent microspheres and which are capable of emitting at least two distinct fluorescent signals. Also provided are methods for their preparation. The compositions and methods of this invention are useful in a variety of applications, including preparation of multiplexed arrays for industrial, chemical, immunological, and genetic manipulation and analysis especially as related but not limited to flow cytometry.

Abstract: The present invention relates to pharmaceutical compositions for the sustained release of pharmacologically active compounds, and methods of their manufacture and use. The pharmaceutical compositions contain microcrystals of pharmacologically active compounds which are encapsulated within a phospholipid layer which contain a unique combination of phospholipids. The pharmaceutical compositions may be rendered suitable for injection. The microcrystals are of varying sizes. At least 50 percent of the microcrystals are from 0.5 &mgr;m and 3.0 &mgr;m in diameter, at least ten percent of the microcrystals are from 3.0 &mgr;m to 10 &mgr;m in diameter, and the composition may contain microcrystals which are greater than 10 &mgr;m in diameter. Methods of manufacturing the composition are disclosed, as well as various methods of administration.

Abstract: A method of making a substrate in which sets of optically anisotropic spheroidal balls are disposed, as for use in an electrical twisting ball display. First and second sets of spheroidal balls, are deposited on a receiving surface composed of an elastomer substrate material in an adhesive state, the spheroidal balls thus deposited adhering to the receiving surface. Balls of the first and second sets are physically distinguishable from one another. Balls of the first set can be deposited in a first arrangement, and balls of the second set, in a second arrangement. Each ball of each set has an optical anisotropy and an anisotropy for providing an electrical dipole moment, the electrical dipole moment rendering the ball electrically responsive such that when the ball is rotatably disposed in an electric field while the electrical dipole moment of the ball is provided, the ball tends to rotate to an orientation in which the electrical dipole moment aligns with the field.

Abstract: A process for producing microparticles containing biologically active substance, in which process an aqueous solution of the said substance is prepared, this solution is mixed with an aqueous solution of PEG such that the substance is concentrated and/or solidified, the substance is optionally washed, the substance is mixed with an organic polymer solution, the composition obtained is mixed, after the admixture of said polymer solution, with an aqueous polymer solution, thereby forming an emulsion of droplets of first mentioned polymer as the internal phase, said droplets are solidified into microparticles, the microparticles are dried and a release-controlling shell is optionally applied to these.

Abstract: The present invention relates to novel nonpolymeric compounds and compositions that form liquid, high viscosity materials suitable for the delivery of biologically active substances in a controlled fashion, and for use as medical or surgical devices. The materials can optionally be diluted with a solvent to form a material of lower viscosity, rendering the material easy to administer. This solvent may be water insoluble or water soluble, where the water soluble solvent rapidly diffuses or migrates away from the material in vivo, leaving a higher viscosity liquid material.

Abstract: In order to form liposomes with a longer half-life in blood, use is made of defined with the general formula (A)

Abstract: A microcapsule characterized by comprising a solid pesticide as a core material coated with a wall material which is a resin formed by polycondensation of a sparingly water-soluble melamine-formaldehyde resin type prepolymer (said sparingly water-soluble melamine-formaldehyde resin type prepolymer dissolves 2000 g or less of water therein per 100 g of solid component of the prepolymer at ±25° C.) in the presence of a dispersant which is a condensation product of naphthalenesulfonic acid and/or alkylnaphthalenesulfonic acid and formaldehyde or a salt thereof, a method for producing said microcapsule, and a method for applying said microcapsule are disclosed.

Abstract: A novel method for introduction of an exogenous genetic substance or a physiologically active compound into cells is provided according to this invention. This method can realize introduction of an exogenous genetic substance or a physiologically active compound of large size with a large amount. Such substance is immobilized to beads of sphere fine particles having a particle size of 0.01 &mgr;m to 10 &mgr;m, and bio-beads thus produced are introduced into cells. Bio-beads comprising calcium alginate are particularly useful for the purpose of the present invention.

Abstract: A process for producing microparticles containing biologically active substance, in which process an aqueous solution of the said substance is prepared, this solution is mixed with an aqueous solution of PEG such that the substance is concentrated and/or solidified, the substance is optionally washed, the substance is mixed with an aqueous starch solution, the composition obtained is mixed, after the admixture of the starch solution, with a polymer solution, thereby forming an emulsion of starch droplets in the polymer solution, the starch droplets are solidified into microparticles, the microparticles are dried and a release-controlling shell is optionally applied to these.

Abstract: The invention relates to microcapsules for which the walls comprise reaction products of polyisocyanates, guanidine compounds, and optionally amines, wherein the polyisocyanates have an isocyanurate content of at least 30% by weight, based on polyisocyanate, and the walls comprise on average less than 9% by weight, based on the total weight of the microcapsule.

Abstract: Methods and compositions are described for nonliposomal lipid complexes in association with toxic hydrophobic drugs such as the polyene antibiotic amphotericin B. Lipid compositions are preferably a combination of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in about a 7:3 mole ratio. The lipid complexes contain a bioactive agent, and may be made by a number of procedures, at high drug:lipid ratios. These compositions of high drug:lipid complexes (HDLCs) may be administered to mammals such as humans for the treatment of infections, with substantially equivalent or greater efficacy and reduced drug toxicities as compared to the drugs in their free form. Also disclosed is a novel liposome-loading procedure, which may also be used in the formation of the HDLCs.

Abstract: A particle resistant to storage of at least one first and at least one second component, wherein

Abstract: Disclosed is a method for preparing a water soluble iron-containing microcapsule by use of fatty acid ester, which is advantageous in terms of shortened preparation process of emulsion and microcapsule, the use of tasteless and odorless fatty acid ester as emulsifier, and increased preparation yield of 95% or more while the microcapsule has the size of 2-5 &mgr;m. The method comprises preparing a mixture of a coating agent and iron by mixing polyglycerin stearate with ferric ammonium sulfate in the ratio of 5:1-25:1 and stirring at 500-1200×g for 30 seconds to 2 minutes, said polyglycerin stearate having been mixed with a predetermined amount of water and allowed to stand at 45-60° C. for 5-20 minutes, said polyglycerin stearate and ferric ammonium sulfate serving as the coating agent and iron, respectively; spraying said mixture to a dispersion of 0.01-0.1% surfactant in purified water of 5-10° C.

Abstract: Lamellar particles are provided comprising a biodegradable and biocompatible polymer and carrying a cationic charge on their surface. These particles are prepared by mixing a preformed negatively charged lamellar particle with a positively charged material. Compositions using these particles may include genetic material or antigens, for example, and may be used as a drug delivery system, such as a sustained release system.

Abstract: A liposomal vesicular preparation with good encapsulation efficiency for active ingredients, based on homogeneous unilamellar liposomal vesicular lipids, has a substantially tightly packed vesicular structure and forms carriers of active ingredients. At least 20% by weight relative to the total weight of the liposomal vesicular preparation of the active ingredient (drug substances, vaccines, diagnostics, vectors) are present in encapsulated form inside the homogeneous unilamellar liposomal vesicular lipids. The liposomal vesicular preparation is a semi-solid liposomal vesicular lipid gel. The membrane forming amphiphiles can be members of from the group consisting of lipids, phospholipids and synthetic amphiphiles.

Abstract: The invention relates to microcapsules for which the walls comprise reaction products of polyisocyanates with guanidine compounds and amines.

Abstract: The invention relates to a method for the preparation of microencapsulated colloidal systems such as liposomes, i.e., microspheres which comprise colloidal systems. These microencapsulated colloidal systems can be used as controlled release systems for the delivery of active ingredients in in vivo and in vitro applications. A method is provided in which the colloidal systems are added to a phase which comprises a water soluble crosslinkable polymer followed by formation of microspheres.

Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.

Abstract: The present invention relates to pharmaceutical compositions for delivery of drugs intended to reside in the nose, compositions for nasal administration of drugs, e.g., antiviral agents, and particularly antiviral agents comprising the human major rhinovirus receptor, also known as intercellular adhesion molecule-1 (ICAM-1); to methods of making said nasal drug compositions, and to an improved process for the removal of residual solvent from pharmaceutical matrices.

Abstract: Microcapsules prepared by encapsulating an aqueous solution of a protein, drug or other bioactive substance inside a semi-permeable membrane by are disclosed. The microcapsules are formed by interfacial coacervation under conditions where the shear forces are limited to 0-100 dynes/cm2 at the interface. By placing the microcapsules in a high osmotic dewatering solution, the protein solution is gradually made saturated and then supersaturated, and the controlled nucleation and crystallization of the protein is achieved. The crystal-filled microcapsules prepared by this method can be conveniently harvested and stored while keeping the encapsulated crystals in essentially pristine condition due to the rugged, protective membrane. Because the membrane components themselves are x-ray transparent, large crystal-containing microcapsules can be individually selected, mounted in x-ray capillary tubes and subjected to high energy x-ray diffraction studies to determine the 3-D structure of the protein molecules.

Abstract: This invention provides a stable aqueous/aqueous emulsion system which is prepared with a hydrophilic polymer. This invention also provides the method of preparing a stable aqueous/aqueous emulsion. Finally, this invention provides an encapsulation comprising the emulsion system which is prepared with a hydrophilic polymer.

Abstract: A method of sizing liposomes by passing a suspension of liposomes through an aluminum oxide porous film under pressure is disclosed. In a preferred embodiment, the porous film is a branched-pore type anodic aluminum oxide porous film. The process produces a population of liposomes substantially free of liposomes above a predetermined maximum size. Also disclosed is an apparatus for carrying out the invention.

Abstract: A method is described for the formation of microcapsules which contain a liquid composition in the core, which is surrounded by a polymeric shell, membrane, or coating. The microcapsules are produced by simultaneously extruding the liquid core material along with a polymerizable liquid through concentrically-aligned nozzles to form spherically-layered biliquid droplets, followed by energy input in the form of heat or light which causes polymerization of the outer layer. The capsules formed by this method are capable of containing a variety of liquid materials having a composition ranging from completely aqueous to completely non-aqueous.

Abstract: The subject of the invention is to prepare carotenoid beads with high concentration and with less bleeding.

Abstract: An improved method for preparing microparticles that exhibit controlled release of an effective amount of an active agent over an extended period of time. More particularly, a method is provided for preparing microparticles having a selected release profile for release of active agent contained in the microparticles. By adjusting the degree of drying that is performed during the preparation of the microparticles, the release profile can be controlled. By performing no intermediate drying, an initial burst and a substantially linear release profile is achieved. By performing substantially complete intermediate drying, an initial lag phase and a substantially sigmoidal release profile is achieved.

Abstract: A method of preparing microparticles of one or more phytosterols, phytostanols or mixtures of both comprises:

Abstract: A microencapsulated adhesive and a method for producing that microencapsulated adhesive is disclosed. The adhesive is produced from an alkyl acrylate or methacrylate monomer having about 4 to about 12 carbon atoms, or a mixture thereof. The monomer is encapsulated by interfacial polymerization, gelatin/gum arabic coacervation or melamine/formaldehyde encapsulation. The microcapsules may be polyamide or polyurea. The monomer is polymerized in the microcapsules by heating to form an adhesive that is non-tacky, but becomes tacky upon application of external forces, such as shearing. The microencapsulated adhesive composition may be used, among other applications, as an adhesive for stamps or envelopes.

Abstract: Methods are provided for forming a dispersion of substantially uniform droplets. An internal phase that includes a plurality of particles suspended in a first fluid is provided and an external phase including a second fluid is provided. The internal phase is vibrated and the internal phase is applied to the external phase. Either the internal phase or a combination of the internal and external phases form a series of droplets or complex droplets of substantially uniform size.

Abstract: The present invention relates to a continuous method to prepare encapsulated cyclopropenes, a method to purify cyclopropene gas, and a method to prepare an &agr;-cyclodextrin/cyclopropene complex.

Abstract: A process for producing parenterally administrable microparticles, in which an at least 20% by weight aqueous solution of purified amylopectin-based starch of reduced molecular weight is prepared, the solution is combined with biologically active substance, an emulsion of starch droplets is formed in an outer phase of polymer solution, the starch droplets are made to gel, and the gelled starch particles are dried. A release-controlling shell is optionally also applied to the particles.

Abstract: The present invention is directed to a composition for gene transfer which composition contains a quaternary ammonium salt represented by formula (1): wherein A represents (wherein each of R1, R2, R3, R4 and R5, which are identical to or different from one another, represents a C9-C17 aliphatic group); X1 represents a halogen atom; and n is an integer from 1 to 10 inclusive; and a method for introducing a gene into a cell by use of the composition. The composition enables effective delivery and expression of a gene which previously could not be effectively expressed in cells due to the low ratio at which the gene is delivered into cells. Therefore, the composition is advantageously used as a gene transfer reagent or a pharmaceutical.

Abstract: Single phase preparations of hydrophilic species, in particular macromolecular compounds such as proteins or glycoproteins in a hydrophobic solvent such as an oil can be obtained by preparing a hydrophile/amphiphile array in which the hydrophilic head groups of the amphiphile are orientated towards the hydrophilic species and bringing the array into contact with the hydrophobic solvent. The preparations of the invention can be used alone or can be combined with an aqueous phase to form emulsions in which the hydrophilic species is present in the hydrophobic phase. The compositions of the present invention are versatile and have application in the pharmaceutical, food, cosmetic, chemical and agricultural industries.

Abstract: A microcapsule capable of thoroughly encapsulating environmentally-sensitive or volatile core materials and capable of releasing said core material on contact with water. A process for manufacture of water soluble microcapsules comprising the admixture of a water soluble cellulosic material, a water soluble glucopyranosidyl material, at least two surfactants and core material, subjecting said mixture to an abrupt pressure change and drying the pressure-treated mixture.

Abstract: A composition and method of fabrication are presented with which nanoparticles may be used as a tool to deliver drugs to a specific target within or on a mammalian body Specifically, by using stabilizers other than Dextran 70.000 during the polymerization process, according to the present invention, surfactants, which were deemed necessary coating material in the prior art, are no longer required. This is a significant simplification of the fabrication procedure. Many substances are useful as stabilizers, but the preferred stabilizers comprise Dextran 12.000 or polysorbate 85. In the present invention a drug is either incorporated into or adsorbed onto the stabilized nanoparticles. This drug/nanoparticle complex is then administered to the organism on any route such as by oral application, injection or inhalation, whereupon the drug exerts its effect at the desired site of pharmacological action.