Abstract: An edible dry-powder formulation of a film coating for pharmaceuticals and confectionaries using gum acacia as a low-cost film former is provided. A cellulosic polymer such as hydroxypropyl methylcellulose is used in addition to the gum acacia. A plasticizer such as propylene glycol is also added. The resulting formulation is a dry, free flowing powder that can be put into solution and applied to a tablet or other substrate without an extended waiting period. The resulting film coating is clear, shiny, durable and extremely economical. Because the formulation is a dry powder, it has along shelf life and low shipping costs.

Abstract: Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, i.e. undesirable components, from the peptide or protein. In a preferred embodiment, a peptide, such as insulin, containing one or more impurities, e.g., zinc ions, is entrapped in diketopiperazine to form a precipitate of peptide/diketopiperazine/impurity, which is then washed with a solvent for the impurity to be removed, which is a nonsolvent for the diketopiperazine and a nonsolvent for the peptide. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration.

Abstract: A process is described for preparing dry powders of one or more oxygenated carotenoids by a) dispersing one or more oxygenated carotenoids in an aqueous molecular dispersion or colloidal dispersion of a protecting colloid and b) converting the dispersion formed into a dry powder by removing the water and any solvents additionally used and drying, in the presence or absence of a coating material, which comprises using as protecting colloid in process step a) at least one partially hydrolyzed soybean protein having a degree of hydrolysis greater than 5%.

Abstract: A polymer is prepared by self-assembly of a plurality of monomeric polypeptide units. The polymer tends to form a nanotube and is capable of encapsulating a particular drug molecule. Once encapsulated in the polymer of the present invention, the drug molecule may be delivered to a particular location of human body to effectively cure a disease or treat a symptom.

Abstract: A method of making fine dry particles of substances is provided by forming a composition comprising a substance of interest and a supercritical or near critical fluid; rapidly reducing the pressure on said composition, whereby droplets are formed; and passing said droplets through a flow of heated gas. The process does not require any organic solvent.

Abstract: Antitumor formulation based on nanoparticles of paclitaxel and human serum albumin as obtained by the addition of a biocompatible acid to an aqueous albumin solution before this is mixed with paclitaxel during the nanoparticle production process, the injectable solutions of this formulation having a pH between 5.4 and 5.8 and having stability and inalterability with time.

Abstract: A process for producing nanoparticles of paclitaxel and albumin having antitumor properties, by which a mixture obtained by adding paclitaxel in powder form to an aqueous solution of albumin with chloroform is subjected to high pressure homogenization treatment.

Abstract: The invention is directed to self-assembling, polymer-based delivery systems for proteins. The delivery systems comprises an active agent and a polyol ester of the invention, having a linear polyol containing six or more hydroxyl groups as a central backbone and biodegradable hydroxy carboxylic ester groups attached to the central backbone.

Abstract: This invention relates to an immunostimulating composition comprising encapsulating microspheres, which may contain a pharmaceutically-acceptable adjuvant, wherein said microspheres having a diameter between 1 nanometer (nm) to 10 microns (um) are comprised of (a) a biodegradable-biocompatible poly(DL-lactide-co-glycolide) as the bulk matrix, wherein the relative ratio between the amount of lactide and glycolide components are within the range of 40:60 to 0:100 and wherein said poly (DL-lactide-co-glycolide) is present in an uncapped form and an end-capped form wherin a ratio of uncapped to end-capped forms is 99/1 to 1/99, and (b) an immunogenic substance comprising Colony Factor Antigen (CFA/II), hepatitis B surface antigen (HbsAg), or a physiologically similar antigen that serves to elicit the producton of antibodies in animal subjects. The preparation of its composition and its use as a vaccine is also disclosed.

Abstract: A process for preparing nanoparticles, microparticles and nanoencapsulated products using the PIN process is provided. The invention involves using additives to reduce the aggregation or coalescence of the PIN nanoparticles, microparticles, or nanoencapsulated products during their formation and collection and to facilitate the recovery of said nanoparticles, microparticles, or nanoencapsulated products.

Abstract: Provided by the present invention are topical formulations of Interleukin-11 and methods for treating a variety of disorders, including inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, inflammatory skin disorders (e.g., psoriasis, atopic dermatitis, and contact hypersensitivity), aphthous ulcers, pharyngitis, esophagitis, peptic ulcers, gingivitis, periodontitis, and ocular diseases (e.g., conjunctivitis, retinitis, and uveitis).

Abstract: A nanoparticle delivery vehicle, comprising a nanoparticle, an active agent and a nuclear localization signal and methods of modulating gene expression and protein expression employing the nanoparticle delivery vehicle. A representative method includes providing a nanoparticle delivery vehicle comprising a nanoparticle having a diameter of about 30 nm or less, an active agent and a nuclear localization signal; and contacting a target cell with the nanoparticle delivery vehicle, whereby an active agent is delivered to the nucleus of a target cell. Another representative method includes providing a nanoparticle delivery vehicle comprising a nanoparticle having a diameter greater than or equal to about 30 nm, an active agent and a nuclear localization signal; and contacting a target cell with the nanoparticle delivery vehicle, whereby an active agent is delivered to the cytoplasm of a cell.

Abstract: A novel method for introduction of an exogenous 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 mm to 10 mm, and bio-active beads thus produced are introduced into cells. Bio-active beads comprising calcium alginate are particularly useful for the purpose of the present invention.

Abstract: The invention relates to an opsonized micro-particle complex comprising: a micro-particular vector encapsulating at least one antigen, and at least one antibody or fragment thereof, with said antibody being a human or humanized antibody or an antibody binding to human FcR with substantially the same affinity and avidity as the ones of a human antibody and with said antibody or fragment thereof having the carboxy terminal end of its Fc portion external with respect to the opsonized micro particle complex.

Abstract: A process is described for preparing microspheres, films and coatings from protein or modified protein in which the protein product is stabilized by carrying out the preparation in the presence of an aqueous solution of at least one &agr;-hydroxy acid. The microspheres, films and coatings so produced have improved stability in aqueous solution.

Abstract: A process for preparing ultrafine powders of biological macromolecules comprises atomizing liquid solutions of the macromolecules, drying the droplets formed in the atomization step, and collecting the particles which result from drying. By properly controlling each of the atomization, drying, and collection steps, ultrafine dry powder compositions having characteristics particularly suitable for pulmonary delivery for therapeutic and other purposes may be prepared.

Abstract: A stable cross-linked alginate gel such as in the form of alginate gel beads encapsulating transplant materials is produced by binding surplus multivalent cations remaining after cross-linking alginate with the cations. A cross-linked alginate gel containing the surplus cations is contacted with a solution of multivalent anions such as sodium sulfate solution to bind the surplus cations. Preferably, a dehydration preventing agent such as protein, bone powder or implant substances is present during cross-linking. A hydrophobic substance such as a perfluoro hydrocarbon or an emulsion may be present during cross-linking to fill spaces between alginate chains. Alginate gel beads produced by the process have long term stability after transplanting.

Abstract: A controlled release preparation of insulin and its method are provided. The controlled release preparation of insulin contains microparticles obtained by microencapsulation of uniform microcystals of insulin using biodegradable polymeric materials. Since the denaturation of insulin that may occur during microencapsulation is reduced, the stability of the preparation can be increased. Also, the ratio of insulin to a polymer carrier is increased, which is suitable for pulmonary delivery. Further, the controlled release preparation of insulin can continuously exhibit pharmaceutical efficacy in vivo in a stable manner for an extended period of time.

Abstract: Amine functionalized magnetic nanoparticle compositions and processes for synthesizing the same are described. The process consists of obtaining a carboxylated polymer in substantially pure form, which is used to prepare a substantially size homogeneous, polymer coated carboxyl, functionalized magnetic nanoparticle. The carboxyl groups are converted to reactive primary amino groups by the use of a water-soluble carbodiimide followed by reaction of a large excess of a diamine. The amine-terminated nanoparticles are then reacted with bifunctional crosslinking agents and with various biomolecules to make nanoparticles for in vitro assays, cell sorting applications and target specific MR contrast agents.

Abstract: Fas ligand (CD95L) induces apoptosis in activated T cells through the process of Activation Induced Cell Death (AICD). Gelatin nanoparticles are virus sized gelatin-protein-DNA complexes which can encapsulate multiple DNA vectors and proteins, and which are thought to act by increasing in vivo transfection of antigen presenting cells. By injecting mice with gelatin nanoparticles containing a murine Fas ligand (CD95L) DNA vector and a &bgr;-galactosidase (LacZ) model antigen vector, the T cell response specific for &bgr;-gal was ablated without effecting the response to a secondary antigen. In effect, this “tolerization” injection induced antigen specific peripheral tolerance in study mice, and is applicable to the treatment of autoimmune diseases when self-antigens such as Myelin Basic Protein are co-delivered with the fas ligand.

Abstract: Dispersibility of a respirable powder, administrable by inhalation, is increased by including a pharmaceutically acceptable water-soluble polypeptide.

Abstract: Hydrophobic ion pairing (HIP) is applied to solubilize proteins and/or adjuvants in an organic medium. A polymer is cosolubilized in the medium and microspheres encapsulating the protein and/or adjuvant can be produced by a single emulsion method. Microspheres prepared by this method exhibit low initial burst of the protein and gradual release over time, and elicit a strong and comprehensive immune response. Compositions comprising a protein and an adjuvant co-encapsulated in microspheres are provided.

Abstract: A process is provided for making dry, micronized particles of an agent, such as a drug. The method includes (a) dissolving a macromolecular material, preferably a polymer, in an effective amount of a solvent, to form a solution; (b) dissolving or dispersing the agent in the solution to form a mixture; (c) freezing the mixture; and (d) drying by vacuum the mixture to form solid particles of the agent dispersed in solid macromolecular material. The micronization in this process occurs directly in a macromolecular matrix and hardening of the particles of agent by solvent removal takes place by lyophilization of the bulk matrix, which stabilizes the drug particles during hardening and prevents coalesence, thereby resulting in smaller final drug particles. The method is particularly preferred for protein agents. The process can be used in conjunction with a standard microencapsulation technique, typically following separation of the agent from the macromolecular matrix.

Abstract: Conditioning of the surface of silica-based glass or ceramic by differential immersion in a serum protein-containing solution, and the resultant microporous Ca-P surface layer having serum-protein like organic molecules, as defined herein intermingled throughout, is described.

Abstract: The present invention relates to a sustained release composition for the targeted delivery of biologically active agents to specific tissues and cells. The composition comprises microparticles containing a biocompatible polymer, a water-soluble polymer and a biologically active agent. In one embodiment, the biologically active agent is an antigen or an immunomodulator. In another embodiment, the biologically is a labile agent. The microparticles have a number median diameter of greater than 20 microns upon administration. The water-soluble polymer is present in the sustained released composition in at least about 20% of the dry weight of the microparticle. The sustained release composition provides for the dissolution of the water-soluble polymer of the composition upon hydration, at a much greater rate than the degradation of the biocompatible polymer.

Abstract: Method and system of producing microparticles loaded with biologically active drugs, including proteins such as ICAM-1, for controlled release of the drugs in a nasal passageway. The method includes introducing a drug/polymer feed solution and an emulsifier into a first mixing chamber to create an emulsion, then mixing a cross-linking agent together with the emulsion under controlled conditions to create microparticles loaded with the drug. The system includes a first mixing chamber, in which the emulsion is created, having a first port for introducing the drug/polymer solution, and a second port angled substantially perpendicular to the first port for introducing the emulsifier. A second mixing chamber adjacent to the first mixing chamber receives the emulsion and either contains a cross-linking agent or receives a stream of a cross-linking agent to solidify the microparticles.

Abstract: The present invention pertains to a pharmaceutical conjugate comprising an insoluble carrier to which first and second active agents are bound, respectively via a first linker to a first functional group on the carrier and via a second linker to a second functional group on the carrier. For example, fibrinogen and Factor VIII can be independently linked to albumin microcapsules.

Abstract: In one aspect, biocompatible matrices such as sol-gels encapsulating a reaction center may be administered to a subject for conversion of prodrugs into biologically active agents. In certain embodiments, the biocompatible matrices of the present invention are sol-gels. In one embodiment, the enzyme L-amino acid decarboxylase is encapsulated and implanted in the brain to convert L-dopa to dopamine for treatment of Parkinson's disease.

Abstract: The present invention relates to gene preparations comprising desired genes or vectors containing desired genes integrated there into and carriers for supporting the same.

Abstract: Compositions useful in treating immune modulated disease comprising an anticytokine antibody or immune active drug capable of modifying cytokine activity or modulating the immune system microencapsulated with a biodegradable nonantigenic material, such as albumin or PLGA. When the composition is introduced into a subject, it is phagocytosed by the target organ, the target organ digests the microsphere, releasing the drug or an active form or fragment thereof intracellularly. The drug then modifies the target organ function, thereby modulating it's activity. A method is disclosed for preparation of the microencapsulated composition.

Abstract: The present invention relates to water-insoluble solid particles, especially pigments, which characteristically are coated with at least one layer of at least one product resulting from the reaction between at least one molecule capable of becoming hydrated in contact with water and at least one lipophilic molecule. It further relates to cosmetic, pharmaceutical and agricultural compositions comprising such particles and to the manufacture and use of said particles.

Abstract: This invention provides method for sustained release delivery of structurally delicate agents such as proteins and peptides. Using a unique emulsion system (Stable polymer aqueous-aqueous emulsion), proteins and peptides can be microencapsulated in polysacchride glassy particles under a condition free of any chemical or physical hazard such as organic solvents, strong interfacial tension, strong shears, elevated temperature, large amount of surfactants, and cross-linking agents. Proteins loaded in these glassy particles showed strong resistance to organic solvents, prolonged activity in hydrated state, and an excellent sustained release profile with minimal burst and incomplete release when being further loaded in degradable polymer microspheres. This invention provides a simple yet effective approach to address all the technical challenges raised in sustained release delivery of proteins.

Abstract: Methods for forming sustained release microspheres and the products produced thereby are provided. The microspheres have a smooth surface that includes a plurality of channel openings that are less than 1000 angstroms in diameter.

Abstract: The present invention provides fibrin microbeads that are biologically active and comprise extensively cross-linked fibrin(ogen), and a method for preparing the fibrin microbeads. The present invention also provides a composition comprising cells bound to the fibrin microbeads, and methods for culturing and separating cells using the fibrin microbeads of the present invention. Finally, the present invention provides methods for transplanting cells and engineering tissue using the fibrin microbeads of the present invention.

Abstract: The invention concerns a method for preparing mineral capsules consisting of aqueous liquid core enclosed in mineral coating, said method consisting in: 1) emulsifying an aqueous fluid in a phase non-miscible with said aqueous fluid so as to disperse it therein in the form of droplets; 2) contacting, in the resulting emulsion, at least a zirconium, silicon, aluminium and/or a transition metal capable of being hydrolysed or subjected to condensation polymerisation in temperature and pH conditions suitable for forming a precipitate consisting of the corresponding oxide or hydroxide; 3) recuperating the resulting mineral capsules and, if required, purifying them.

Abstract: The present invention provides for the treatment of an individual suffering from lupus erythematosus utilizing a serine protease inhibitor. The treatment includes the use of a corticosteroid that is administered separately or in combination. The serine proteases preferred are alpha 1-antitrypsin, secretory leucocyte protease inhibitor, alpha 2-macroglobulin or mixtures thereof.

Abstract: A process for the manufacturing of microcapsules for sustained release of water soluble peptides, with adjustable release periods of between 1 to 18 weeks. The microcapsule wall are made of a biodegradable polymer. The process is based on the formation of an intermediate complex water/oil/water emulsion. By evaporating the solvent in the emulsion by pressure reduction the microcapsules consolidate, retaining the active peptides in the polymeric matrix. The process produces the complex emulsion in a two mixer, continuous operation. In the first mixer a water/oil emulsion is formed and it is used to form the complex emulsion in the second mixer. By operating in a continuous manner, the process overcome the problems found in existing processes regarding particle size distribution, material losses and process control, among others.

Abstract: A method for luring animals, repelling animals and training animals and a product used therewith comprising microporous beads having animal attractant scents, animal repellant scents and animal training scents, respectively, imbibed within the beads. The beads with the animal attractant scents are configured to release the animal attractant scents in order to attract a predetermined animal. Likewise, the beads with the animal repellant scents are configured to release the animal repellant scents in order to repel a predetermined animal. Similarly, the beads with the animal training scents are placed onto a predetermined location and a predetermined animal is trained to perform a predetermined sequence using the beads.

Abstract: The present invention relates to insoluble compositions comprising a protein selected from the group consisting of insulin, insulin analogs, and proinsulins; a derivatized protein selected from the group consisting of derivatized insulin, derivatized insulin analog, and derivatized proinsulin; a complexing compound; a hexamer-stabilizing compound; and a divalent metal cation. Formulations of the insoluble composition are suitable for both parenteral and non-parenteral delivery for treating hyperglycemia and diabetes. Microcrystal forms of the insoluble precipitate are pharmaceutically analogous to the neutral protamine Hagedorn (NPH) insulin crystal form. Surprisingly, it has been discovered that suspension formulations of such insoluble compositions possess unique and controllable dissolution properties that provide therapeutically advantageous glucodynamics compared with insulin NPH formulations.

Abstract: The present invention relates to an encapsulated unsaturated fatty acid substance in a form of a three-layered capsule, comprising an unsaturated fatty acid or a derivative thereof (11) as a content and a coating layer (10) mainly containing gelatin, encapsulating the content (11), wherein a water-soluble gel layer (12) containing an acid or an acid salt thereof is present between the coating layer (10) and the content (11). The encapsulated unsaturated fatty acid substance of the present invention is characterized by that it has neither insolubility nor deterioration with time, and that it is enteric.

Abstract: Synthetic membranes, micelles and vesicles are formed in response to the spontaneous orientation of hydrophobic and hydrophilic groups in aqueous media. The oligosaccharide moieties of glycoprotein molecules are oriented toward the aqueous environment. The micelles of the present invention are relatively stable in aqueous environments, and thus are useful for transporting substances that can be dissolved or suspended in lipids for inclusion in the micelles. Lipo-glycoprotein micelles are also useful for protecting substances contained within the hydrophobic compartment from dispersal or degradation until the micelle structure is disrupted.

Abstract: A formulation and methods for inducing sustained regional local anesthesia in a patient comprising a substrate comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material prolonging the release of the local anesthetic from the substrate to obtain a reversible local anesthesia when implanted or injected in a patient, and a pharmaceutically acceptable, i.e., non-toxic, non-glucocorticoid augmenting agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without the augmenting agent.

Abstract: Bioerodible polyorthoesters useful as orthopedic implants or vehicles for the sustained delivery of pharmaceutical, cosmetic and agricultural agents contain amine functionalities and &agr;-hydroxy acid-containing groups.

Abstract: This invention relates to a novel granulate and a novel oral solid dosage formulation, each comprising an active ingredient and one or more carriers prepared by a novel wet granulation method. This method provides that the mixture of active ingredient and carrier be kept below 40° C. during the granulation process such that a more stable formulation is obtained.

Abstract: A formulation and methods for inducing sustained regional local anesthesia in a patient comprising a substrate comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material prolonging the release of the local anesthetic from the substrate to obtain a reversible local anesthesia when inplanted or injected in a patient, and a pharmaceutically acceptable, i.e., non-toxic, non-glucocorticoid augmenting agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without the augmenting agent.

Abstract: A formulation and methods for inducing sustained regional local anesthesia in a patient comprising a substrate comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material prolonging the release of the local anesthetic from the substrate to obtain a reversible local anesthesia when implanted or injected in a patient, and a pharmaceutically acceptable, i.e., non-toxic, non-glucocorticoid augmenting agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without the augmenting agent.

Abstract: A method is provided for producing an impact resistant solid cosmetic such as cheek rouge, powder, foundation and two way foundation by compacting powder materials into a dish mold. The powder materials are compression molded into a dish mold under a pressure of 200-300 kgf/cm2 at a temperature of 10-30° C. The powder materials contain 0.1-50.0 wt % of a spherical organopolysiloxane elastomer having a JIS A hardness of 60-100, and a mean particle size of 0.1-200 &mgr;m. The cosmetic optionally contains 1.0-30.0 wt % of an oily ingredient.

Abstract: In accordance with the present invention, there are provided composition and methods useful for the in vivo delivery of a pharmaceutically active agent, wherein the agent is associated with a polymeric biocompatible material.

Abstract: Microparticles, obtainable by spray-drying a substantially pure solution of a therapeutic agent, consist essentially of the agent having its therapeutic activity when administered to the lung. In a preferred embodiment the agent is insulin.

Abstract: The invention relates to a method of producing an agglomerate of drug and solid binder. The process involves producing individual agglomerate particles and then converting the convertible amorphous content of same, following agglomeration, by the application of, for example, moisture. Agglomerates capable of conversion as well as the finished agglomerates and oral and nasal dosing systems including same are also contemplated. The process produces agglomerates which are rugged but which will produce an acceptable fine particle fraction during dosing.