Abstract: Solid, water-insoluble lipospheres including a solid hydrophobic core, having a layer of a phospholipid embedded on the surface of the core, that contain an antigen are disclosed for use in immunizing an animal. The antigen (or "immunogen"), alone or in combination with a carrier, can form the core, be attached to or within the phospholipid, or both. Lipospheres containing antigens are prepared by two general procedures, either melt preparation or solvent preparation. The resulting lipospheres have several advantages over other delivery systems, including emulsions, vesicles and liposomes, including stability, low cost of reagents, ease of manufacture, high dispersibility in an aqueous medium, a release rate for the entrapped substance that is controlled by the phospholipid coating and the carrier.

Abstract: Fatty acid terminated polyanhydrides suitable for use as controlled release matrices in biodegradable sustained release drug delivery systems and methods for making thereof are described. The polymers are more soluble in organic solvents, and have a lower melting point than the corresponding non-fatty acid terminated polyanhydrides. The fatty acid terminated polyanhydrides are also more hydrophobic than the corresponding polyanhydrides that are not terminated with a fatty acid, and combine the properties of thermodynamic and hydrolytic stability, and easy storage. The polymers can be produced with a controlled and low molecular weight. The polyanhydrides are useful in a number of applications, including as a matrix in biodegradable drug delivery systems.

Abstract: A polyanhydride suitable for use as a matrix material in controlled delivery devices polymerized from monomers of the general formula: ##STR1## wherein R, R', and R" are the same or a different aliphatic chain of C.sub.1 to C.sub.20 or hydrogen; m, n, and p are integers from 0 and 20; y is 0 or 1; and, if y is 0, one of R or R' is not H.

Abstract: Branched polyanhydrides that have superior properties for use in the controlled delivery of substances, prepared by the polymerization of a dicarboxylic acid monomer and a branching agent. The branching agent is a polycarboxylic acid monomer such as 1,3,5-benzenetricarboxylic acid ("BTC"), or an oligomerized fatty acid trimer. Alternatively, the branching agent is a polycarboxylic acid polymer such as poly(acrylic acid) ("PAA"). These branched polymers have significantly higher molecular weights and lower specific viscosity than linear polymers prepared under similar conditions. A major advantage of branched polyanhydrides is that the degradation and release kinetics can be substantially altered without significantly changing the physical properties of the polymer relative to the corresponding linear polymer. By manipulating both the diacid and the branching agent, a wide variety of biodegradable controlled delivery devices for diverse applications can be prepared.

Abstract: A local anesthetic microsuspension system is disclosed that includes lipospheres, that are solid, water-insoluble microparticles that have a layer of a phospholipid embedded on their surface. The core of the liposphere is a solid anesthetic such as lidocaine or marcaine, or an anesthetic dispersed in an inert solid vehicle, such as a wax. Anesthetic lipospheres provide a controlled delivery of local anesthetics to achieve extended, effective relief from pain by slowly releasing the anesthetic from the solid hydrophobic core. This is highly preferred over the situation in which an aqueous solution of local anesthetic must be frequently administered because it is quickly systemically absorbed.

Abstract: A microsuspension system containing insect repellent is disclosed that includes lipospheres, that are solid, water-insoluble microparticles that have a layer of a phospholipid embedded on their surface. The core of the liposphere is a solid insect repellent, or an insect repellent dispersed in an solid vehicle, such as a wax. Insect repellents include compounds that repel insects, are insecticidal, or regulate or inhibit insect growth on humans and other animals and plants. Insect repellent lipospheres provide controlled release of insect repellents while minimizing absorption through the skin.

Abstract: A microsuspension system and method for its preparation is disclosed. The microsuspension contain lipospheres, which are solid, water-insoluble microparticles that have a layer of a phospholipid embedded on their surface. The core of the liposphere is a solid substance to be delivered, or a substance to be delivered that is dispersed in an inert solid vehicle, such as a wax.

Abstract: PKC modulating compounds of the formula ##STR1## Also disclosed are pharmaceutical compositions including these compounds which inhibit PKC activity, methods of using these compounds to inhibit PKC activity in mammals, and intermediates useful in preparing the PKC modulating compounds.

Abstract: Fatty acid terminated polyanhydrides suitable for use as controlled release matrices in biodegradable sustained release drug delivery systems and methods for making thereof are described. The polymers are more soluble in organic solvents, and have a lower melting point than the corresponding non-fatty acid terminated polyanhydrides. The fatty acid terminated polyanhydrides are also more hydrophobic than the corresponding polyanhydrides that are not terminated with a fatty acid, and combine the properties of thermodynamic and hydrolytic stability, and easy storage. The polymers can be produced with a controlled and low molecular weight. The polyanhydrides are useful in a number of applications, including as a matrix in biodegradable drug delivery systems.

Abstract: Branched polyanhydrides that have superior properties for use in the controlled delivery of substances, prepared by the polymerization of a dicarboxylic acid monomer and a branching agent. The branching agent is a polycarboxylic acid monomer such as 1,3,5-benzenetricarboxylic acid ("BTC"), or an oligomerized fatty acid trimer. Alternatively, the branching agent is a polycarboxylic acid polymer such as poly(acrylic acid) ("PAA"). These branched polymers have significantly higher molecular weights and lower specific viscosity than linear polymers prepared under similar conditions. A major advantage of branched polyanhydrides is that the degradation and release kinetics can be substantially altered without significantly changing the physical properties of the polymer relative to the corresponding linear polymer. By manipulating both the diacid and the branching agent, a wide variety of biodegradable controlled delivery devices for diverse applications can be prepared.

Abstract: A polyanhydride suitable for use as a matrix material in controlled delivery devices polymerized from monomers of the general formula: ##STR1## wherein R, R', and R" are the same or a different aliphatic chain of C.sub.1 to C.sub.20 or hydrogen; m, n, and p are integers from 0 and 20; y is 0 or 1; and, if y is 0, one of R or R' is not H.

Abstract: Disclosed are oligonucleotide compounds that inhibit interleukin receptor expression when administered to a human subject. Also disclosed are pharmaceutical compositions and methods for inhibiting human interleukin receptor expression.

Abstract: A controlled release device for the administration of biologically active growth hormone proteins or peptide fragments, and method of preparation thereof, wherein biologically active growth hormone is stabilized and release rate modulated by incorporation of a stabilizing compound. The controlled release devices are prepared by mixing a stabilizer, such as sucrose, with a biologically active growth hormone, such as bovine somatotropic hormone, in solution, lyophilizing, then incorporating the dried powder into a surface erodible, biocompatible polymeric matrix, such as a poly(anhydride) or poly(orthoester) matrix.

Abstract: The present invention relates to a method of treating an inflammatory condition, and to compounds and composition suitable for use in such a method, which compounds have the Formula: ##STR1## wherein: X is methylene, ethylene, ethyleneoxy, or oxygen;Q is ##STR2## where C' is a residue of a lipophilic amino acid, and Y is --CO.sub.2 H, --CH.sub.2 OH, --CONR.sub.1 R.sub.2, or --CO.sub.2 R.sub.1 where R.sub.1 and R.sub.2 hydrogen, alkyl, or aryl;R.sub.3 and R.sub.4 are, independently, hydrogen, alkyl or aryl; andA and B are, independently, hydrogen, fused phenyl, alkyl, aryl, alkaryl, aralkyl, alkoxy, alkoxyalkyl, halogen, or nitro;or pharmaceutically acceptable salts thereof.

Abstract: The present invention relates to a method of producing corticotropin-releasing factor (CRF) antagonist activity and thus provides a method of treating a wide range of stress-related disorders, including affective illnesses, such as depression and anxiety, as well as irritable bowel syndrome, anorexia nervosa, cardiovascular abnormalities and stress-induced immune suppression. The invention also relates to compounds (4-substituted thio-5-oxo-3-pyrazolines) and to pharmaceutical compositions suitable for use in such a method.

Abstract: The invention pertains to a method and pharmaceutical compositions for treating, preventing or reducing neurodegeneration associated with chronic central nervous system or hypoxic, ischemic and hypoglycemic injury to the central nervous system and for the treatment of anxiety through the use of 2-amino-.omega.-phosphonoalkanoic acids having a cycloalkyl group bridging adjacent carbons on the alkyl chain, their pharmaceutically acceptable salts and derivatives as neuroprotectants and anxiolytics.

Abstract: Biodegradable polyanhydrides or polyester compositions based on amino acids. The compositions may be used as carriers for drugs or the like or as the drug source itself. The polymers are prepared from amino acids which are modified to include an additional carboxylic acid group.

Abstract: Aromatic anhydride copolymers containing at least two aromatic diacid units, which are soluble in chloroform or dichloromethane to concentrations between approximately 0.5 to 50% weight/volume, melt at temperatures below 180.degree. C., and have low crystallinity are disclosed. The copolymers may contain between 0 and approximately 30% aliphatic diacid units. All copolymers are insoluble in carbon tetrachloride, i.e., less than 0.1% polymer by weight/volume solvent). The desired properties are the result of adding between 10 and 90% of a second aromatic diacid, to the copolymer composition which introduces irregularity in the polymer chains that dramatically alter the polymer properties, decreasing the crystallinity and melting point and increasing the solubility in the common solvents, dichloromethane or chloroform. An additional decrease in Tg and MP, with an increase in flexibility, is obtained by adding small amount of aliphatic diacid, up to about 30%.

Abstract: A pharmaceutical composition comprises an anti-epileptic drug that does not inhibit, enhance or otherwise modify dextromethorphan binding to the central nervous system dextromethorphan receptor and an effective amount of dextromethorphan to potentiate the anticonvulsant activity of the drug. Other related compounds similar to dextromethorphan which inhibit or enhance dextromethorphan binding to the dextromethorphan site in the brain are also suitable as potentiating agents for the anticonvulsants. A method of treating epilepsy and other convulsions include the steps of introducing to the patient an effective amount of the compound comprising an anti-epileptic drug and potentiating amount of dextromethorphan or one of the related compounds.

Abstract: A potent, selective opioid receptor agonist or antagonist exhibiting properties useful for a longacting analgesic or opiate abuse treatment agent or appetite suppressant having the general formula: ##STR1## wherein R is methyl, cyclopropylmethyl or allyl, and R.sub.1 is an unsubstituted or substituted aryl, aralkyl, heteroaryl, heteroaralkyl or a cycloalkyl group with or without a heteroatom like S,O,N; and the pharmaceutically acceptable salts thereof.