Abstract: A packaged kit for treating keratosis obturans includes a plurality of ear needles having different shaped absorbent applicators on distal ends of the needles, a vial of a single dose of an otologic formulation of mitomycin-C, and a diluent carrier syringe containing sterilized water. The component parts of the kit are used together to reconstitute the contents of the vial with the water in the diluent carrier syringe. A selected one of the plurality of ear needles is then communicated with the syringe. The syringe and needle are then used to inject the reconstituted drug into the absorbent pad at the end of the needle, and the absorbent pad containing the drug is used to apply the drug to the surface of the external ear canal.

Abstract: This disclosure relates to methods of inhibiting cell motility or cell migration, and of treating diseases involving cell migration or cell motility, using polyamine analogs, such as conformationally restricted polyamine analogs. The diseases to be treated include immune disorders, inflammatory conditions, infection, abnormal immune responses, undesired angiogenesis, tumor cell metastasis or invasion, atherosclerosis, vascular graft occlusion, transplant rejection, other complications of transplants, glomerulonephritis, arthritis, inflammatory responses subsequent to stroke or ischemia, and asthma.

Abstract: Described herein are various compounds for treatment of ocular neurodegenerative diseases, including but not limited to glaucoma and diabetic retinopathy. The compounds described herein can act to attenuate and/or block calcium release from external neuronal environments as well as intracellular stores.

Abstract: The present invention relates to tetracyclic indole derivatives of formula (I); wherein Ar, D1, D2, D3, D4, W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.

Abstract: The present invention relates to novel porphyrin derivates of formula (I), especially to porphyrins which carry substituted phenyl moieties in meso-position. The porphyrin derivates of the invention are useful as photosensitizers in photodynamic therapy (PDT), especially in photodynamic tumor therapy. Due to their excellent photophysical properties the compounds of formula I are extremely efficient in photodynamic treatment.

Abstract: A process is described for preparing chlorides of phthalocyanine derivatives comprising at least a quaternary ammonium group, products useful as photosensitising agents in photodynamic therapy.

Abstract: PhotoDynamic Therapy method is used to treat problems associated with pilosebaceous units including acne and other skin conditions. At least one liposomal-formulated, hydrophobic photosensitizer, such as a dihydro- or tetrahydro-porphyrin, is topically applied to acne affected regions, and is allowed to penetrate the hair follicle before being irradiated with a suitable wavelength of light energy overlapping the absorption spectrum of the selected photosensitizer. The photoactivated agent initiates a cytotoxic effect in the sebaceous gland, reducing excess oil production and destroying bacterial growth in the follicle thus subsiding inflammatory action. Scarring of the skin is minimized and the skin heals faster due to collagen cell stimulation.

Abstract: This invention provides a method of synthesizing enantioenriched merrilactone A and enantiopure merrilactone A, as well as an improved method of synthesizing racemic merrilactone.

Abstract: A method of making a bacteriochlorin is carried out by condensing a pair of compounds of Formula II to produce the bacteriochlorin, wherein R is an acetal or aldehyde group. The condensing may be carried out in an organic solvent, preferably in the presence of an acid. The bacteriochlorins are useful for a variety of purposes such as active agents in photodynamic therapy, luminescent compounds in flow cytometry, solar cells, light harvesting arrays, and molecular memory devices.

Abstract: Described herein are composites that inhibit or reduce adhesion between two or more tissues. Also described herein are methods of using the composites.

Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract: The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the enzyme Thimet oligopeptidase, or TOP. Also disclosed are methods of designing prodrugs by utilizing TOP-cleavable sequences within the conjugate and methods of treating patients with prodrugs of the invention.

Abstract: The present invention relates to tetracyclic thienopyrrole compounds of formula (I), wherein Ar, A, D1, D2, W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.

Abstract: A method for treating a cell proliferation disorder in a subject, comprising: (1) administering to the subject at least one activatable pharmaceutical agent that is capable of activation by a simultaneous two photon absorption event and of effecting a predetermined cellular change when activated; and (2) applying an initiation energy from an initiation energy source to the subject, wherein the initiation energy is capable of penetrating completely through the subject, and wherein the applied initiation energy activates the activatable agent by the simultaneous two photon absorption event in situ, thus causing the predetermined cellular change to occur, wherein the predetermined cellular change treats the cell proliferation related disorder, and a kit for performing the method, a computer implemented system for performing the method, a pharmaceutical composition useful in the method and a method for causing an autovaccine effect in a subject using the method.

Abstract: The present invention relates generally to targeted molecular agents (TMAs) directed to a particular organism or group of organisms and uses thereof. More particularly, the present invention provides TMAs having a targeting moiety which comprises a natural or induced auxotrophic requirement of the particular organism as a vehicle for directing an agent linked to the moiety to be delivered to the target organism. The TMAs of the present invention are useful for targeting molecules such as antimicrobial agents and diagnostic agents to selected organisms.

Abstract: The present invention discloses methods of using of compounds for the enhancement of the innate immune system of a patient. In particular, the active compounds of the present invention include at least one calcineurin inhibitor, mTOR inhibitor or non-immunosuppresive derivative, or a derivative, isomer, or pharmaceutically acceptable salt thereof; and optionally, at least one calciferol or LMW inhibitor, or a derivative, isomer, or pharmaceutically acceptable salt thereof. Pharmaceutical formulations comprising same are also disclosed.

Abstract: Highly flexible penetrating liposomal carrier systems are formulated with enhanced skin penetration properties. These specialized formulations of highly flexible penetrating liposomal delivery systems comprise one or more phospholipids, lysophosphatides and hydrophobic photosensitizer. This new formulations can squeeze liposomal particles through intercellular regions of stratum corneum as intact structures, and, in this way, deliver encapsulated photosensitizer to the epidermis, dermis, hypodermis and surroundings. The penetrating liposomal formulation provides therapeutically effective amounts of the hydrophobic photosensitizer through topical application with better skin penetration thus improving drug targeting and the efficacy of photodynamic therapy (PDT).

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TPO activity, particularly diseases or disorders that involve thrombocytopenia.

Abstract: Disclosed is a pharmaceutical composition for prophylaxis and treatment of pancreatitis comprising a 5-HT2A receptor antagonist as an effective component, wherein the binding activity (pKi) of the 5-HT2A receptor antagonist to a 5-HT2A receptor is higher at least by 1.0 than the binding activities to a 5-HT2B receptor and a 5-HT2C receptor. Preferably the binding activity (pKi) of the 5-HT2A receptor antagonist to the 5-HT2A receptor is at least 7.0, and more preferably at least 8.0. The present invention also provides a method of identifying a candidate substance for prophylactic and therapeutic agent for pancreatitis, comprising determining whether a test substance has a 5-HT2A receptor antagonistic activity.

Abstract: The present invention relates to photosensitizer compounds based on functionalized fullerenes useful in targeted photodynamic therapy (PDT), and methods of use thereof.

Abstract: The present invention relates to the treatment of cancer with compounds that inhibit the activity of endo-exonuclease. Endo-exonuclease has been shown to be necessary for the repair of damaged DNA. Compounds that inhibit the activity of endo-exonuclease have been shown to be particularly effective for treating cancer when used in combination with drugs that induce DNA breaks such as cisplatin and mitomycin C. These compounds have a synergistic effect when used in combination for inhibiting tumour growth. The invention includes pharmaceutical compositions for inhibiting tumour growth comprising a compound that inhibits endo-exonuclease activity. These pharmaceutical compositions preferably include compounds that induce DNA breaks. The invention includes methods of treating cancer with these pharmaceutical compositions and uses of these compositions to treat cancer. The preferred compounds that inhibit the activity of endo-exonuclease have low toxicity. One such compound is pentamidine.

Abstract: A conjugate of formula: V—(Y)a-Z-T??(I), T-X—B—(Y)a-Z-T???(II), V—(Y)a-Z-(Y?)a—V???(III), T-X—B—(Y)a-Z-(Y?)a—X?—B?-T???(IV), V—(Y)a-Z-(Y?)a—X—B-T??(V), V—(Y)a-Z-X—B-Z?-(Y?)a—(V?)b??(VI), or (W)a—(Y)b-[(Z)c-(Y?)d—(X—B)e—(Y?)f-(Z?)g]h-(Y??)i—(W?)j??(VII), in which W and W? are independently a DNA intercalator or terminal subunit, V and V? are independently a DNA intercalator, X and X? are independently a DNA alkylator, B and B? are the same or different and each is a heteroaromatic residue that is attached to the N-terminus of an alkylator subunit (X or X?), Y, Y?, Y? and Y?? are independently a linker, T and T? are independently terminal subunits, Z and Z? are independently a polyamide group that binds to the minor groove of DNA, a, b, c, d, f, g, i, and j are independently 0 to 5, and e and h are independently 1 to 5, a composition comprising a conjugate of any of formulae (I)-(VII) and a carrier, and a method for treating cancer in a mammal comprising administering an effective amount of

Abstract: The invention concerns the treatment of obesity, in particular abdominal visceral obesity. More specifically, the invention concerns the use of selective 15-lipoxygenase (LO) inhibitors for preparing medicines useful in the treatment of obesity, or at least abdominal visceral obesity, and/or its consequences.

Abstract: The present invention relates to a composition and method for preventing and treating cancer and modulating cell proliferation using compositions extracted from pinoresinol-rich Olea europaea Caiazzana olives. The present invention provides contacting one or more cells with a pharmaceutical effective amount of a polyphenolic composition isolated from Olea europaea Caiazzana olives. The polyphenolic composition includes one or more polyphenolic compounds extracted from Olea europaea Caiazzana olives.

Abstract: A class of macrocyclic compounds of formula (I), wherein R7, A, Ar, B, D, F, M, Q1, Q2, W, X, Y and Z are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: Compounds are described that are active on PPARs, including pan-active compounds. Also described are methods for developing or identifying compounds having a desired selectivity profile.

Abstract: A novel drug for treating a vascular lesion in the skin or the subcutaneous soft tissue caused by light irradiation which is efficacious in treating a vascular lesion in the deep part of the skin or the subcutaneous soft tissue caused by light irradiation without destroying normal cells on the skin surface and yet requires only a short shading time after the treatment. This drug for treating a vascular lesion in the skin or the subcutaneous soft tissue caused by light irradiation contains, as the active ingredient, mono-L-aspartyl chlorin e6, mono-L-glutamyl chlorin e6 or a pharmacologically acceptable salt thereof.

Abstract: The present invention provides a method of inhibiting the leakage of a drug encapsulated in liposomes, which comprises satisfying at least two requirements selected from the group consisting of the following three requirements: using at least two lipid bilayers of the liposomes, controlling the average particle size of the liposomes to 120 nm or more, and using lipid having a phase transition temperature higher than in vivo temperature as lipid constituting the liposomes. Also, the present invention provides a liposome preparation which is stable in vivo and satisfies at least two requirements selected from the group consisting of the following three requirements: the number of lipid bilayers of the liposomes is at least two, the liposomes have an average particle size of 120 nm or more, and lipid constituting the liposomes has a phase transition temperature higher than in vivo temperature.

Abstract: This inventive subject matter relates to novel metal complex protein kinases inhibitors, methods for making such compounds, and methods for using such compounds for treating diseases and disorders mediated by kinase activity.

Abstract: A liposome formulation for stably incorporating high content of hydrophobic substance is disclosed. The liposome includes two phospholipids with different phase transition temperatures such as saturated and unsaturated phosphatidyl cholines, hydrophobic substances, cholesterol, cholesterol derivatives, antioxidant and hydrophilic polymer-modified lipids such as MPEG-DSPE.

Abstract: Antimicrobial molecular conjugates for the treatment and prevention of infectious diseases caused by pathogenic microorganisms in human and animals are provided. The key to these conjugates is a special spacer connecting at least one photosensitizer to a microorganism receptor (vector) which in turn binds selectively to the surface of a microorganism bringing about photo-destruction upon irradiation. Spacers having hydrophilic structure such as ethylene glycol units and amino carboxyl end capped ethylene glycol units must be used for linking the vector to the photosensitizer. In a preferred embodiment a spacer would have at least 3 ethylene glycol units and be end capped with a carboxyl group on one end and a amino group at the other end.

Abstract: The invention relates to coagulation of the blood. Disclosed are novel compounds of formula (I), a method for the production of these compounds, pharmaceutical compositions containing them, and methods of using them for the prevention and/or treatment of various diseases.

Abstract: Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds' overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer. One preferred class of the novel compounds has the structure of formula (IV) wherein: R1, R2, R3, R4, R5, R6, R7, R8, R5A, R6A, R7A, R8A, R22 and R23 are defined herein. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

Abstract: This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

Abstract: Compounds are described that are active on PPARs, including pan-active compounds. Also described are methods for developing or identifying compounds having a desired selectivity profile.

Abstract: The present invention describes the use of the magnetic magnesium isotope 25Mg2+ for the manufacture of a medicament for treating hypoxia. Furthermore, the present invention provides a medicament for treating hypoxia comprising the magnetic magnesium isotope 25Mg2+ and a porphylleren compound according to formula (I) wherein the residues A1, A2, A3, and A4 independently are a group containing 1 to 40 carbon atoms and at least one carboxylic group, the residues R, R? and R? independently are hydrogen or a group containing 1 to 80 carbon atoms, M is 2 H or an element capable of complexing with pyrrole nitrogen atom and L is a linking group and B is a fullerene residue.

Abstract: The present invention relates to the use of K-252a, a physiologically active substance produced by microorganisms, and of its salts or synthetic and/or chemically modified derivatives for the prevention or treatment of HMGB1 associated pathologies. More particularly, the present invention relates to the use of K-252a for the prevention or treatment of restenosis.

Abstract: An injectable polymer-lipid blend is provided as a localized drug delivery system for a pharmaceutically active agent. The blend may be prepared from a chitosan-based material, fatty acid and phospholipid. The chitosan-based material may be a water soluble chitosan derivative. The fatty acid may be a fatty acid or a fatty aldehyde, such as laurinaldehyde, having an acyl chain length of C8-C16. The rheological properties of the blend relates to the ratio of the components and to the acyl chain length of the fatty acid. The injectable system is well suited for the delayed release of pharmaceutically active agents in the treatment of cancer and other diseases requiring localized drug delivery.

Abstract: Embodiments of the present invention are related to novel therapeutic drugs, drug combinations, and associated methods for treating or preventing pulmonary disease, including pulmonary hypertension, pulmonary fibrosis, asthma and COPD, and heart failure, together with other pulmonary and cardiovascular diseases and their complications. More particularly, aspects of the present invention are related to the use of cicletanine and ruboxistaurin as monotherapies or in combination with other agents for treatment of disease. Cicletanine may be used as pure (+) or (?) enantiomers or as a racemic or non-racemic mixture of those enantiomers.

Abstract: Compounds of the structure: are provided. Also provided are methods of using these compounds as progesterone receptor modulators. Also described are methods of producing these compounds from a Verticillium species.

Abstract: The present invention relates to DP IV-inhibitors of formula (1) for the treatment and/or prophylaxis of diseases of mammals including cancer and tumors, metastasis and tumor colonization; and metabolic diseases.

Abstract: This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

Abstract: The present invention is directed to low toxicity boronated compounds and methods for their use in the treatment, visualization, and diagnosis of tumors. More specifically, the present invention is directed to low toxicity glycosylated carborane-containing 5,10,15,20-tetraphenylporphyrin compounds and methods for their use particularly in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) for the treatment of tumors of the brain, and head and neck. The invention is also directed to using these glycosylated carborane-containing tetraphenylporphyrin compounds in methods of tumor imaging and/or diagnosis such as MRI, SPECT, or PET.

Abstract: Novel derivatives of metallotexaphyrins are prepared by modifying the apical ligands associated with the central metal component of a metallotexaphyrin.

Abstract: Highly flexible penetrating liposomal carrier systems are formulated with enhanced skin penetration properties. These specialized formulations of highly flexible penetrating liposomal delivery systems comprise one or more phospholipids, lysophosphatides and hydrophobic photosensitizer. This new formulations can squeeze liposomal particles through intercellular regions of stratum corneum as intact structures, and, in this way, deliver encapsulated photosensitizer to the epidermis, dermis, hypodermis and surroundings. The penetrating liposomal formulation provides therapeutically effective amounts of the hydrophobic photosensitizer through topical application with better skin penetration thus improving drug targeting and the efficacy of photodynamic therapy (PDT).

Abstract: A photodynamic composition and a method for in vivo photonic treatments that is minimally invasive, versatile and precise are described. The invention allows for photonic treatments with only minimal insertions into the area of treatment, often a single one. The invention may be used with a standard insertion component making the system inexpensive and easy for doctors to use. The invention has applications in several areas of treatment. In vivo treatment of aesthetic skin blemishes such as varicose veins can be performed with minimal external effects. A predetermined amount of a photodynamic composition, as a foam, is injected into the vein or structure of concern. The composition is a sclerosis foam including a photosensitizer. By external compression, where applicable, the photodynamic composition is forced to remain in the vein or structure. After a predetermined time, radiation of appropriate wavelength from a light source is delivered directly to the vascular structure.

Abstract: Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions.

Abstract: This invention provides a new generalized method for screening, identifying, selecting and designing symmetry-based compounds useful for blocking pores or prepores formed by pathogenic agents including bacteria, viruses, fungi, parasites, and other proteins capable of forming pores on cellular membranes as a step in the pathogenic mechanism of the agent. Also provided are pharmaceutical compositions, filtering devices, and treatment methods useful for preventing, delaying, or otherwise altering the pathogenesis of the pore-forming pathogenic agents.

Abstract: The present invention relates to a method for preserving the vision of a patient suffering from diabetic retinopathy which comprises administering to said patient an effective amount of ruboxistaurin or a pharmaceutical salt thereof wherein said administration is in conjunction with focal or grid laser photocoagulation therapy.

Abstract: The use of diaryl acid derivatives of formula (I) or pharmaceutically acceptable salts, N-oxides, hydrates or solvates thereof, wherein the variables shown are defined in the disclosure, and their pharmaceutical compositions as PPAR ligand receptor binders. The PPAR ligand receptor binders of this invention are useful as agonists or antagonists of the PPAR receptor.