Abstract: Controlled release oral dosage forms are provided for the continuous, sustained administration of a pharmacologically active agent to the upper gastrointestinal tract of a patient in whom the fed mode as been induced. The majority of the agent is delivered, on an extended release basis, to the stomach, duodenum and upper regions of the small intestine, with drug delivery in the lower gastrointestinal tract and colon substantially restricted. The dosage form comprises a matrix of a biocompatible, hydrophilic, erodible polymer with an active agent incorporated therein, wherein the polymer is one that both swells in the presence of water and gradually erodes over a time period of hours, with swelling and erosion commencing upon contact with gastric fluid, and drug release rate primarily controlled by erosion rate.

Abstract: Drugs are formulated as oral dosage forms for controlled release in which the release rate limiting portion is a shell surrounding the drug-containing core. The shell releases drug from the core by permitting diffusion of the drug from the core. The shell also promotes gastric retention of the dosage form by swelling upon imbibition of gastric fluid to a size that is retained in the stomach during the postprandial or fed mode.

Abstract: A method of treatment for epilepsy and other disease states is described, which comprises the delivery of gabapentin in a gastric retained dosage form.

Abstract: Liposomes containing PEG-substituted neutral lipopolymers provide similar circulation times to liposomes incorporating conventional, negatively charged PEG-substituted phospholipids. Use of the uncharged lipopolymers can also present advantages in terms of interactions with cell surfaces and reduced leakage of charged substances, particularly cationic drugs, from the liposomes. The lipopolymers are of the formula: wherein each of R1 and R2 is an alkyl or alkenyl chain having between about 8 to about 24 carbon atoms, n is about 10 to about 300, Z is selected from the group consisting of hydroxy, alkoxy, benzyloxy, carboxylic ester, sulfonic ester, alkyl or aryl carbonate, amino, and alkylamino, and the linkage L is selected from the group consisting of (i) —X—(C═O)—Y—CH2—, (ii) —X—(C═O)—, and (iii) —X—CH2—, wherein X and Y are independently selected from oxygen, NH, and a direct linkage.

Abstract: A dosage form is disclosed comprising a semipermeable walled container that houses a capsule, which capsule comprises a drug formulation, a piston, and an osmotic composition. The dosage form delivers the drug formulation through a passageway at a controlled rate over a sustained-release period of time up to 24 hours.

Abstract: A composition for administration of a therapeutically effective dose of a topoisomerase inhibitor I or topoisomerase I/II inhibitor is described. The composition includes liposomes having an outer surface and an inner surface defining an aqueous liposome compartment, and being composed of a vesicle-forming lipid and of a vesicle-forming lipid derivatized with a hydrophilic polymer to form a coating of hydrophilic polymer chains on both the inner and outer surfaces of the liposomes. Entrapped in the liposomes is the topoisomerase inhibitor at a concentration of at least about 0.10 &mgr;mole drug per &mgr;mole lipid.

Abstract: Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.

Abstract: A composition for administration of a therapeutically effective dose of a topoisomerase inhibitor I or topoisomerase I/II inhibitor is described. The composition includes liposomes having an outer surface and an inner surface defining an aqueous liposome compartment, and being composed of a vesicle-forming lipid and of a vesicle-forming lipid derivatized with a hydrophilic polymer to form a coating of hydrophilic polymer chains on both the inner and outer surfaces of the liposomes. Entrapped in the liposomes is the topoisomerase inhibitor at a concentration of at least about 0.10 &mgr;mole drug per &mgr;mole lipid.

Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.

Abstract: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Abstract: Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

Abstract: An opiate analgesic composition and a non-opiate analgesic composition are disclosed for delivering an analgesic in either embodiment to a patient in need of relief from pain. The analgesics are present optionally with a nonionic surfactant and with an osmotic composition comprising a carbonate or bicarbonate for delivering the opiate analgesic and non-opiate analgesic from a dosage form.

Abstract: An inverter for reversing the orientation of a pharmaceutical dosage form at a discontinuity in a path of travel is described. The inverter receives dosage forms from an input path and delivers rectified dosage forms to an output path. In addition, a dosage form rectifier comprising an inverter is described. The dosage form rectifier receives randomly oriented dosage forms and delivers uniformly oriented dosage forms without recycling any of the dosage forms. In a repeating cycle for each dosage form supplied to the rectifier, the orientation of the dosage form is determined and dosage forms having a desired orientation are maintained in the desired orientation and delivered from the dosage form rectifier while dosage forms having an inverted orientation have their orientation rectified at the inverter before being delivered from the dosage form rectifier.

Abstract: A dosage form is disclosed for administering a leukatriene-receptor antagonist to a patient over time.

Abstract: A dosage form comprising a composition comprising a drug surrounded by a first coat and a second coat with an exit for administering the drug to a patient; and a method of using the dosage form are disclosed for an indicated therapy.

Abstract: The present invention relates to a method for manufacturing a silver halide photographic emulsion comprising a nucleation step, a growing step and a washing step, wherein a reduction sensitization is performed between said growing step and said washing step in the presence of a sulfuring agent and a stabilizer. According to a preferred embodiment a fine grain silver halide emulsion is added either between the addition of stabilizer and the addition of sulfuring agent or between the addition of sulfuring agent and the start of reduction sensitization or both.

Abstract: A purified glycoprotein complex of over 1200 kD apparent native molecular weight having a sedimentation value of approximately 25S and having the ability to selectively bind human Mac-2 or interfere with PHA activation of lymphocytes, DNA sequences that encode the protein, and expression systems for expressing it, thus providing for reagents that are useful for treating or diagnosing diseases, including cancer, infectious disease, and diseases of the immune system, and for monitoring the concentration of the glycoprotein in human milk.

Abstract: The present invention relates to a keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.

Abstract: The isolation, identification and production by recombinant methods of bone calcification factor, a 22 KD polypeptide, are disclosed. The peptide has calcification-inducing activity when implanted with matrix Gla protein into mammals.