Abstract: Two or more hydrophilic polymers that are not soluble in each other at a particular concentration and temperature, but which have a positive spreading coefficient in solution, are used to form multi-layered polymeric microspheres. The multi-layer microspheres produced by the method are distinguished by extremely uniform dimensioned polymer layers and actual incorporation of a substance to be delivered into the polymer layers. In the preferred embodiment of the method, two polymers are dissolved in an aqueous solvent, the substance to be incorporated is dispersed or dissolved in the polymer solution, the mixture is suspended in an organic solvent or polymer/water mixture and stirred, and the solvent is slowly evaporated, creating microspheres with an inner core formed by one polymer and an outer layer formed by the second polymer.

Abstract: A self-binding, glycerine-free tablettable composition has a saccharide carrier and the sugar alcohols sorbitol and xylitol.

Abstract: The foregoing invention relates to a new microbubble preparation and thrombolytic therapy which relies on microbubbles and ultrasound for its lytic activity. The pharmaceutical composition of the invention comprises a liquid solution of microbubbles with an internal atmosphere enhanced with the perfluorocarbon gas which cavitate in the presence of an ultrasound field following intravenous injection or infusion of said composition into said host. For thrombolysis the area of a thrombus is exposed to an ultrasound field in the presence of the microbubbles and significant lysis is experienced. The method and pharmaceutical composition of the invention exhibit thrombolytic properties similar to those of other thrombolytic agents such as urokinase and are less toxic and are clot specific in that they do not introduce a systemic lytic state to a said animal.

Abstract: A dry powder that contains carotenoids produced by grinding a mixture of carotenoids and oil to reduce the carotenoid particle size, emulsifying the mixture with an encapsulating mixture, and drying the emulsification. The encapsulating mixture includes a starch encapsulating agent, a sugar, and an anti-oxidant. The resulting water-dispersible powder contains a high concentration of carotenoids, yet is protected from oxidation.

Abstract: Liquisolid systems are acceptably flowing and compressible powdered forms of liquid medications. According to the concept of liquisolid systems, liquid lipophilic drugs, or water-insoluble solid drugs dissolved in suitable non-volatile solvents, may be converted into free-flowing and readily compressible powders by a simple admixture with selected powder excipients referred to as the carrier and coating materials. Various grades of microcrystalline or amorphous cellulose may be used as carriers, whereas very fine particle size silica powders may be used as coating materials. Based on the theory that the carrier and coating materials can retain only certain amounts of liquid and at the same time maintain acceptable flow and compression properties, a new formulation-mathematical model is provided to calculate the optimum quantities of carrier and coating materials required to yield acceptably flowing and compressible liquid/powder admixtures.

Abstract: Amine functionality-containing materials such as cationic cellulose-based compositions are coated to suppress their tendency to generate "amine odors" in an alkaline pH environment. Further provided are effervescent compositions, liquid or solid soap formulations, fabric softeners, shampoos and the like comprising such materials coated with a suitable coating composition.

Abstract: Hollow polymer microcapsules are made by the method of dissolving a film-forming polymer in a volatile nonaqueous solvent; dispersing into the polymer solution finely divided particles of a volatilizable solid core material; inducing formation of a solid polymer coating on the particulate solid core material in the nonaqueous liquid mixture to produce polymer microcapsules having an encapsulated core of particulate core material; recovering the polymer microcapsules from the nonaqueous liquid mixture; and removing the encapsulated core material from the microcapsules to make hollow polymer microcapsules. Gas-filled polymer microcapsules that are made according to the method of this invention are useful in medical applications such as imaging contrast agents because they may be prepared to precisely controlled size specifications.

Abstract: The use of complex coacervates of two or more biopolymer materials, preferably at least one of these being gelatin, as a fat-replacing ingredient. The complex coacervates may be used in foods and cosmetics and preferably are of substantially spherical or elliptical shape and have an average D.sub.3,2 particle size, of from 0.2 to 100 microns.

Abstract: Microspheres comprising a gelified polar core which is optionally surrounded by concentric and alternating superimposed n lipidic bilayers or n aqueous liquid layers and n gelified polar layers, n being an integer. The microspheres of the invention are obtainable by delipidation of liposomes designated as liposomes having a gelified polar core, of the type comprising at least one outer lipidic bilayer and at least one inner polar aqueous phase containing a gelified substance.

Abstract: The invention relates to pharmaceutical compositions for the intranasal administration of dihydroergotamine, apomorphine and morphine comprising one these pharmacologically active ingredients in combination with a cyclodextrin and/or a disaccharide and/or a polysaccharide and/or a sugar alcohol.

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: Compositions and methods for treating periodontal disease and other related disorders utilizing a therapeutic treatment composition, including at lease one chemotherapeutic agent in combination with at least one carrier agent, are disclosed. Oral care products and a method preventing periodontal disease and related disorders are also provided.

Abstract: A method of encapsulating a pesticide with an ultraviolet protectant comprises the steps of forming a slurry of a pesticide and a lignin-containing material, and spraying a stream of acid and the slurry into contact with one another to precipitate the lignin-containing material onto the pesticide and form a protective coating on the pesticide. The pesticide is preferably a biopesticide, and the lignin-containing material is preferably kraft lignin. The method is easily adapted to industrial processes currently used for pesticide production by simply changing the spray drier from a single nozzle system to a dual spray nozzle and then adding the acid stream to the dual nozzle.

Abstract: A multidose transdermal drug delivery system comprises a laminate composite with a plurality of compartments. Each compartment is a reservoir for a unit dose of a drug active to be transdermally administered. The assembly is adhesively secured to the skin of a patient. Individual seals are provided for resealably enclosing the drug active in each of the reservoirs. The individual enclosing seals are removable to release the unit dose into contact with the skin of the patient and are actuable to control the transdermal absorption of the drug actives. Provisions are also made to automatically indicate the activation of the drug and to prevent an accidental release of medicament.

Abstract: Pectins from gel and rind cell wall fibers of Aloe vera are extracted, isolated and identified. Two classes of Aloe pectin are obtained: the high-molecular-weight (HMW) pectin and the low-molecular-weight (LMW) pectin. Aloe pectins have a low methoxyl (LM) content. Aloe pectins form gel in the presence of calcium, and they, especially, the HMW pectin, form monovalent cation-based gels at low temperature, which revert back to solution when brought to room temperature. The HMW Aloe pectin-calcium gel is used for controlled release. The monovalent cation-based gel is used as a matrix for storing pharmacological substances and also for antigen and antibody precipitation reaction.

Abstract: A pharmaceutical composition comprising a physiologically active polypeptide, an absorption promoting agent consisting of a combination of an organic acid and a fatty acid sucrose ester in admixture with a pharmaceutically acceptable carrier or diluent, which is suitable for oral administration and for application to the oral cavity, by which the polypeptide can sufficiently be absorbed through the intestinal tract or the mucous membrane in the oral cavity and exhibit the physiological activities without being suffered from enzymolysis.

Abstract: The present invention relates to contrast agents comprising water-soluble microbubble-generating carbohydrate microparticles in admixture with at least 10% w/w relative to the overall composition of a non-surface active material which is less water soluble than the carbohydrate. The contrast agents exhibit useful levels of contrast efficiency and/or stability and may be used in diagnostic applications such as ultrasound and MR imaging.

Abstract: The invention relates to microspheres which are suitable for biomedical uses which have a diameter in the range of 10 nm to 2 mm and which comprise a substantially spherical core particle of a non-water-soluble polymer and an outer surface layer consisting substantially of a water-soluble polymer. The water-soluble polymer is conjugated to polyethylene glycol and the non-water-soluble core particle is attached to the water-soluble polymer by the polyethylene glycol moiety. The microspheres are prepared by dissolving the non-water-soluble polymer in a suitable first solvent, dispersing the polymer solution in a solution of the PEG/water-soluble polymer conjugate and evaporating the first solvent to form microspheres in which the PEG anchors the water-soluble polymer to the core particle.

Abstract: A method of distinguishing between microorganisms having different attributes comprises the steps of: encapsulating one or more cells within a polymeric bead; incubating the cell(s) within the bead in a growth-supporting medium for a time period sufficient for multiplication of viable cells within the bead; then non-invasively physically examining the bead or the adjacent vicinity of the bead for physical characteristics associated with the differing attributes of cells within the bead. Various forms of apparatus for carrying out the process are descried.

Abstract: A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets and the like comprises polyvinyl alcohol, soya lecithin, and optionally a flow aid, a colorant, and/or a suspending agent. A liquid coating solution or dispersion for forming a moisture barrier film coating for pharmaceutical tablets and the like comprises polyvinyl alcohol, soya lecithin, water, and optionally a flow aid, a colorant, and/or a suspending agent. A method of coating pharmaceutical tablets and the like with a moisture barrier film coating comprises forming a liquid coating solution or dispersion for forming a moisture barrier film coating for pharmaceutical tablets and the like comprising polyvinyl alcohol, soya lecithin, water, and optionally a flow aid, a colorant, and/or a suspending agent, applying the coating solution or dispersion onto the tablets to form a film coating on the tablets, and drying the film coating on the tablets.

Abstract: The invention concerns a freeze-dried emulsion composition containing an active substance and which can be reconstituted using water to give the original emulsion, plus a method for producing the freeze-dried composition. The reconstituted emulsion is suitable for parenteral use.

Abstract: A method of preparing an oral preparation, especially in the form of hard gelatin capsules, tablets or pellets, for use by the administration of drugs or supplementary nutrients for human beings or animals, said preparation on its outer side being provided with an enteric coating which contains or comprises a calcium salt of a polysaccharide. A moisture-resistant layer containing a protein, especially zein, can be provided between the material to be coated and the enteric coating. The enteric coating is formed in situ by spraying the liquid coating substances in a fluidized bed. The present invention also pertains to oral preparations which is prepared by the method.

Abstract: The invention relates to accurately meterable shaped articles, for example granules or pellets, containing hydrophilic macromolecules, active compounds and optionally further pharmaceutically acceptable structure-forming substances and auxiliaries, the active compound being present in a matrix in dissolved, suspended or emulsified form, and a novel process for the production of these shaped articles, the process being particularly economically and ecologically acceptable, and use of the shaped articles as medicaments, in which the bioavailability, shelf life and tolerability is increased. Using the shaped articles or mixtures according to the invention, intermediates or final products for pharmacy, cosmetics, diagnosis, analysis or dietetics (healthcare) can additionally be advantageously prepared.

Abstract: The present invention is a method of entrapping an additive within carbohydrate bodies. The additive is drawn into the internal structure as a fluid during transformation of the bodies from a substantially amorphous state to a crystalline state. The present invention is also a delivery system including a carbohydrate body having an internal free volume space defined by an at least partially crystalline structure at equilibrium conditions, and an additive loaded within the carbohydrate body.

Abstract: Medical materials for use in treating maladies in living beings, such as ulcers and other conditions of the digestive tract. In one form, a container is provided for a medication which container also contains an adhesive material which is operatively released from the container or exposed at the surface thereof upon biodegradation or dissolution of a protective coating or wall portion of the container under the effects of fluid in the digestive tract in which the container is exposed, such as by swallowing, to permit such adhesive to temporarily bond and retain the container at a select location in the digestive tract so that it may slowly release its contents thereafter to a select portion of the digestive tract. In another form, a multitude of microcapsules, each containing a small quantity of medication, is mixed with an adhesive material, such as a sulcralfate other material which may be swallowed as a tablet or dissolved in a liquid such as water.

Abstract: The invention relates to compositions useful for making tablets which can be formed using conventional tableting machines and which disintegrate rapidly when placed in the mouth. The compositions typically include partially hygroscopic shearform matrices which may be recrystallized using crystallization promoters.

Abstract: A solid form of oral administration of isosorbide 5-mononitrate with a controlled, pH-independent release of the active substance in the gastro-intestinal tract is constituted by a pellet coated with a depot layer and a release prolonging lacquer layer. The lacquer layer contains ethyl cellulose and polymethacrylate in a weight ratio from 3:1 to 3:2. The new form of administration is characterized in that it is less costly to produce.

Abstract: This invention provides compositions for fair-skin containing the phosphorylated polysaccharides produced by lactic acid bacteria as an effective ingredient. The phosphorylated polysaccharides are expressed, for example, by the following formula and contained in the compositions for fair-skin at concentrations of 0.01-20 weight % and are used such as creams, emulsions and toilet lotions.The compositions for fair-skin exhibit fair-skin effect by inhibiting activities to melanoma proliferation and melanin formation. ##STR1## (wherein, Glc, Gal and Rha represent glucose, galactose and rhamnose residues, respectively. Numerals shown by other than subscript represent the respective binding sites and n represents the degree of polymerization of 1,000-5,000).

Abstract: A colonic delivery system for delivering a drug to the colon is provided. The system comprises a drug in combination with a matrix, wherein the matrix comprises a saccharide-containing polymer. According to the invention, the matrix is resistant to chemical and enzymatic degradation in the stomach and small intestine. The matrix is degraded in the colon by bacterial enzymatic action, and the drug is released. The system is useful for targeting drugs to the colon in order to treat colonic disease. The system is also useful for enteric administration of drugs such as proteins and peptides which are otherwise degraded in the stomach and small intestine.

Abstract: Provided is a drug carrier comprising particles of at least one pure active compound which is insoluble, only sparingly soluble or moderately soluble in water, aqueous media and/or organic solvents, wherein said active ingredient is solid at room temperature and has an average diameter, determined by photon correlation spectroscopy (PCS) of 10 nm to 1,000 nm, the proportion of particles larger than 5 .mu.m in the total population being less than 0.1% (number distribution determined with a Coulter counter), and, when introduced into water, aqueous media and/or organic solvents, the active compound has an increased saturation solubility and an increased rate of dissolution compared with powders of the active compound prepared using an ultrasonic probe, a ball mill or a pearl mill, the solid particles having been comminuted, without prior conversion into a melt, by using cavitation or shearing and impact forces with introduction of a high amount of energy.

Abstract: Disclosed herein is a double capsule for cosmetics obtained by matrix-double-encapsulation method which comprises steps of (a) first-encapsulating the fat-soluble active matrials with filming materials to give a microcapsule; (b) encapsulating the microcapsule of the step (a) with gellan gums, and a cosmetic composition containing the same.

Abstract: The present invention is a method of making discrete particles by subjecting an organic feedstock to liquiflash conditions whereby the feedstock is transformed instantaneously from solid to liquiform to solid. Liquiform is a transient condition wherein the feedstock has substantially unimpeded internal flow. Shear force is imparted to the liquiform feedstock in an amount sufficient to separate tiny masses of feedstock. The tiny masses solidify as discretized particles. The present invention also includes unique products resulting from the process, e.g., a monodispersed microsphere product and coated particles prepared therefrom.

Abstract: Stabilization of colloidal systems through the formation of lipid-polyssacharide complexes. Development of a procedure for the preparation of colloidal systems involving a combination of two ingredients: a water soluble and positively charged polyssacharide and a negatively charged phospholipid. Colloidal systems (submicron emulsions and polymeric nanoparticles and nanocapsules) are stabilized through the formation, at the interface, of an ionic complex: aminopolyssachride-phospholipid. These colloidal systems are characterized by their positive charge and their improved stability. Furthermore, they can be freeze-dried, stored in a dry state and hydrated when required. They can be interesting systems for the administration of drugs by the oral, transdermal, ocular, nasal and vaginal routes of administration. In addition, they can be of interest for cosmetic use.

Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.

Abstract: Nucleic acids are compacted, substantially without aggregation, to facilitate their uptake by target cells of an organism to which the compacted material is administered. The nucleic acids may achieve a clinical effect as a result of gene expression, hybridization to endogenous nucleic acids whose expression is undesired, or site-specific integration so that a target gene is replaced, modified or deleted. The targeting may be enhanced by means of a target cell-binding moiety. The nucleic acid is preferably compacted to a condensed state.

Abstract: Shearform compositions made without added glycerine are disclosed. The compositions are self-binding and exhibit excellent cohesivity when used in tableting compositions. Typically, xylitol is incorporated into a feedstock which is flash-flow processed to form a self-binding shearform matrix.

Abstract: The present invention relates to a new form of biocompatible materials (e.g., lipids, polycations, polysaccharides) which are capable of undergoing free radical polymerization, e.g., by using certain sources of light; methods of modifying certain synthetic and naturally occurring biocompatible materials to make polymerizable microcapsules containing biological material coated with said polymerizable materials, composites of said polymerizable materials, methods of making microcapsules and encapsulating biological materials therein, and apparatus for making microcapsules containing biological cells (particularly islets of Langerhans) coated with polymerizable alginate or with a composite thereof (e.g., alginate and PEG). The present invention also relates to drug delivery systems relating to the foregoing, as well as bioadhesives and wound dressings made utilizing the foregoing technology.

Abstract: A method is provided of preventing arterial restenosis of an animal after the arteries have been traumatized. The method comprises the administration of a therapeutically effective non-toxic amount of hyaluronic acid and/or pharmaceutically acceptable salts thereof to the animal to prevent narrowing of the arteries. The form of hyaluronic acid is selected from hyaluronic acid and pharmaceutically acceptable salts thereof having a molecular weight less than 750,000 daltons.

Abstract: The present invention provides methods and a device for producing minimal volume capsules containing viable cells or cellular aggregates. The methods and device use a two-phase aqueous emulsion system to form a dispersion of liquid capsule-forming materials in a continuous liquid phase to which is added a suspension of biological material. Alternatively, the biological material can be added to one or the other of the liquid phases. The composition of this emulsion is adjusted to promote the thermodynamically-driven process of particle engulfment by the dispersed droplets of liquid capsule-forming materials. Subsequently, the droplets engulf the biological material to form a liquid film surrounding the tissue and are converted to solid form, resulting in encapsulation of the biological material in minimum volume capsules.

Abstract: Biocompatible microcapsules useful for transplanting foreign material into an animal body, and the method of their production, are described, wherein the microcapsules contain an outermost layer of water soluble non-ionic polymers such as PEO to create resistance to cell adhesion on the surface of the microcapsules.

Abstract: A solid oral dosage form for the treatment of gastrointestinal disorders comprising a therapeutically effective amount of a therapeutically effective amount of guanidinothiazole compound; and a therapeutically effective amount of an antacid wherein the pharmaceutical and an antacid are separated by a barrier which is substantially impermeable to an antacid.

Abstract: This invention provides a microcapsule designed for zero order release of a physiologically active polypeptide over a period of at least two months, which is produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing about 20 to 70% (w/w) of said polypeptide and an oil layer containing a copolymer or homopolymer having a weight-average molecular weight of 7,000 to 30,000, wherein the composition ratio of lactic acid/glycolic acid in the copolymer or homopolymer is 80/10 to 100/0, and then subjecting said water-in oil emulsion to microencapsulation.

Abstract: A cosmetic composition is provided comprising:A) a cosmetically acceptable carrier; andB) 0.05 to 3.0% by weight, based on the weight of the total composition, of a .beta.-1,3-glucan having a mean molecular weight of 10.sup.5 to 25.10.sup.6.

Abstract: Methods of treatment and prevention of estrogen-related diseases, and of fertility control, include low dose (e.g. less than 50 nanomolar serum concentration) administration of certain anabolic steroids, progestins and other substantially non-masculinizing androgenic compounds. Sustained release formulations substantially free of organic solvent, and sustained release formulations for maintaining low serum levels of androgen are disclosed.

Abstract: A process for the manufacture of a slow-release excipient consisting mainly of cross-linked amylose in the form of solid particles, for use in the preparation of tablets or pellets. A starch containing a high amount of amylose (high amylose starch) is first subjected to a gelatinization. The gelatinized high amylose starch is then cross-linked with 1 to 5 g of a cross-linking agent per 100 g of dry-based gelatinized high amylose starch in an alkali medium, thereby forming a reaction medium containing a reaction product consisting of a cross-linked high amylose starch slurry. The obtained reaction medium is neutralized, thereby forming by-products mainly consisting of salts, which are removed from the reaction medium. The recovered cross-linked high amylose starch slurry is then subjected to a thermal treatment at a temperature of at least 60.degree. C. and the thermally treated product is dried to obtain the requested slow release excipient.

Abstract: This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a "glue" to cause more than one biological substance to adhere together, or as carriers for biologically active species. Several methods for forming these membranes are provided. Each of these methods utilizes a polymerization system containing water-soluble macromers, species which are at once polymers and macromolecules capable of further polymerization. The macromers are polymerized using a photoinitiator (such as a dye), optionally a cocatalyst, optionally an accelerator, and radiation in the form of visible or long wavelength UV light. The reaction occurs either by suspension polymerization or by interfacial polymerization.

Abstract: Liquisolid systems are acceptably flowing and compressible powdered forms of liquid medications. According to the concept of liquisolid systems, liquid lipophilic drugs, or water-insoluble solid drugs dissolved in suitable non-volatile solvents, may be converted into free-flowing and readily compressible powders by a simple admixture with selected powder excipients referred to as the carrier and coating materials. Various grades of microcrystalline or amorphous cellulose may be used as carriers, whereas very fine particle size silica powders may be used as coating materials. Based on the theory that the carrier and coating materials can retain only certain amounts of liquid and at the same time maintain acceptable flow and compression properties, a new formulation-mathematical model is provided to calculate the optimum quantities of carrier and coating materials required to yield acceptably flowing and compressible liquid/powder admixtures.

Abstract: This invention provides a deodorant composition in a dispensing container which is pressurized with an aerosol propellant. The primary ingredients of a typical product are particulate sodium bicarbonate, ethanol, volatile silicone oil and a suspending agent such as hydrophobic hectorite clay. An invention aerosol deodorant product has a stable particulate sodium bicarbonate suspension phase, and exhibits excellent fluid evacuation properties with a relatively high content of ethanol and low content of aerosol propellant.

Abstract: The invention relates to a method of sensitizing cancer cells for a killer cell mediated lysis which involves administering to a patient an effective amount of antiestrogen and killer cells either jointly or sequentially, wherein the killer cells are selected from the group of NK cells, LAK cells and CTL cells and the antiestrogen is selected from the group of triphenylethylene class antiestrogens, such as tamoxifen or toremifene or their pharmaceutically acceptable salt.

Abstract: Controlled release beads containing a core around which is a drug-containing layer e.g. a layer containing furosemid and a process for their preparation and their use in a pharmaceutical preparation. The controlled release beads have excellent mechanical and release characteristics.