Abstract: Kappa opioid receptor antagonists are provided that yield significant improvements in functional binding assays to kappa opioid receptors, and the use of these antagonists in treatment of disease states that are ameliorated by binding of the kappa opioid receptor such as heroin or cocaine addictions.

Abstract: Medical devices comprising nanobeads encapsulating one or more bioactive agents and methods of use thereof are provided.

Abstract: The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate casein kinase (CK) activity and/or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such molecules.

Abstract: A pharmaceutical composition comprising tacrolimus (FK-506) dissolved and/or dispersed in a hydrophilic or water-miscible vehicle to form a solid dispersion or solid solution at ambient temperature have improved bioavailability.

Abstract: The invention relates to a new crystalline form of tiotropium bromide, processes for preparing it and its use for preparing a pharmaceutical composition for the treatment of respiratory complaints, particularly for the treatment of COPD (chronic obstructive pulmonary disease) and asthma.

Abstract: A modified release composition comprising tacrolimus releases less than 20% w/w of the active ingredient within 0.5 hours when subjected to an in vitro dissolution test using USP Paddle method and using 0.1 N HCl as dissolution medium and has increased bioavailability by effectively reducing or even avoiding the effects of CYP3A4 metabolism. The modified composition may be coated with an enteric coating; and/or may comprise a solid dispersion or a solid solution of tacrolimus in a hydrophilic or water-miscible vehicle and one or more modifying release agents; and/or may comprise a solid dispersion or a solid solution of tacrolimus in an amphiphilic or hydrophobic vehicle and optionally one or more modifying release agents.

Abstract: This invention provides a method of inducing a lacrimal acinar cell in a tissue to degrade a secretory vesicle and its content protein or proteins from the trans-Golgi network (TGN) by contacting the cells with an effective amount of an agent that induces autophagy. Also provided is a method for treating a mammal suffering from defective trans-Golgi network-secretory vesicle (TGN-SV) sorting by administering to the mammal an effective amount of an agent that induces autophagy in the tissue having the defective TGN-SV.

Abstract: The invention relates to the combined use of at least one monoterpene which can be applied systemically, in particular perorally, and at least one respiratory tract therapeutic agent which can be applied topically, in particular through inhalation, for the prophylactic and/or therapeutic treatment, in particular combination therapy and/or co-medication, of respiratory tract diseases, in particular bronchopulmonary diseases. Through the combined use of the systemic monoterpene with the topical, in particular inhaled respiratory tract therapeutic agent, the effect or efficiency of the topical or inhaled respiratory disease therapeutic agent can be increased significantly, in particular in a synergistic manner, on the one hand, and the required dosage thereof can be reduced significantly on the other hand, combined with the resulting advantages (e.g., avoidance or reduction of side effects).

Abstract: The invention relates to novel macrocyclic compounds of the formula in which all of the variables are as defined in the specification, in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.

Abstract: A modified release composition comprising tacrolimus releases less than 20% w/w of the active ingredient within 0.5 hours when subjected to an in vitro dissolution test using USP Paddle method and using 0.1 N HCl as dissolution medium and has increased bioavailability by effectively reducing or even avoiding the effects of CYP3A4 metabolism. The modified composition may be coated with an enteric coating; and/or may comprise a solid dispersion or a solid solution of tacrolimus in a hydrophilic or water-miscible vehicle and one or more modifying release agents; and/or may comprise a solid dispersion or a solid solution of tacrolimus in an amphiphilic or hydrophobic vehicle and optionally one or more modifying release agents.

Abstract: A modified release composition comprising tacrolimus releases less than 20% w/w of the active ingredient within 0.5 hours when subjected to an in vitro dissolution test using USP Paddle method and using 0.1 N HCl as dissolution medium and has increased bioavailability by effectively reducing or even avoiding the effects of CYP3A4 metabolism. The modified composition may be coated with an enteric coating; and/or may comprise a solid dispersion or a solid solution of tacrolimus in a hydrophilic or water-miscible vehicle and one or more modifying release agents; and/or may comprise a solid dispersion or a solid solution of tacrolimus in an amphiphilic or hydrophobic vehicle and optionally one or more modifying release agents.

Abstract: A modified release composition comprising tacrolimus releases less than 20% w/w of the active ingredient within 0.5 hours when subjected to an in vitro dissolution test using USP Paddle method and using 0.1 N HCl as dissolution medium and has increased bioavailability by effectively reducing or even avoiding the effects of CYP3A4 metabolism. The modified composition may be coated with an enteric coating; and/or may comprise a solid dispersion or a solid solution of tacrolimus in a hydrophilic or water-miscible vehicle and one or more modifying release agents; and/or may comprise a solid dispersion or a solid solution of tacrolimus in an amphiphilic or hydrophobic vehicle and optionally one or more modifying release agents.

Abstract: A stent is provided with a drug-eluting layer disposed on at least a portion of its surface, wherein the drug-eluting layer comprises an endosome-disrupting agent and a pharmaceutical agent. In an embodiment, the endosome-disrupting agent, when taken up through endocytosis into living cells, causes lysis of endosomes containing the endosome-disrupting agent. The pharmaceutical agent can accompany the endosome-disrupting agent into the living cells.

Abstract: Compositions and methods for the prevention and/or treatment of airway and/or respiratory disorders are provided. The compositions comprise arformoterol (the (R,R)-formoterol isomer) and tiotropium.

Abstract: Provided herein are coating designs for the tailored release of two therapeutic agents from polymer coatings and methods of making and using the same.

Abstract: The present invention relates to implantable medical devices, in particular stents, comprising pro-healing poly(ester-amide)s.

Abstract: Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-?B activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R5, R6, R7, and R8; J1, J2, and J3 are at each occurrence the same or different and are independently -A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3alkylene, substituted

Abstract: The invention provides a patch preparation containing (a) a support and (b) an adhesive layer containing a drug on the surface of the support, wherein a crystal of the drug is formed in the adhesive layer immediately after application of a physical stimulation to the adhesive layer, while a crystal of the drug is formed during preservation after the physical stimulation. The patch preparation which does not require an increase in the area and thickness of an adhesive layer, achieves a sufficiently high skin permeation amount of the drug, shows good adhesiveness to skin, and permits a long-term adhesion to skin. The invention also provides a method of producing the patch preparation.

Abstract: The present invention relates to biocompatible oligomer-polymer compositions for the in situ formation of implants, wherein the implants release a bioactive agent, a metabolite, or a prodrug thereof, at a controlled rate. The sustained release delivery system includes a flowable composition containing a bioactive agent, a metabolite, or a prodrug thereof, and an implant containing a bioactive agent, a metabolite, or a prodrug thereof. The flowable composition may be injected into tissue whereupon it coagulates to become the solid or gel, monolithic implant. The flowable composition includes a biodegradable, thermoplastic polymer, a biocompatible end-capped oligomeric liquid, and a bioactive agent, a metabolite, or a prodrug thereof.

Abstract: The present invention provides an absorbable coating for an implantable device and the methods of making and using the same.

Abstract: A polyketide synthase complex composed of polyketide synthase with 15 total modules, a non-ribosomal peptide synthetase with 1 module, and a cytochrome P450 hydroxylase is described. Also provided are novel Streptomyces species and methods of modified Streptomyces species. Further described are novel compounds, 36-ketomeridamycin, C9-deoxomeridamycin, and C9-deoxoprolylmeridamcyin and uses thereof.

Abstract: Provided is a rapamycin analog composition including a crystalline form of a rapamycin analog. The crystal can be a hydrate. dehydrate, solvate, or desolvate.

Abstract: Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Abstract: A pharmaceutical combination comprising an accelerated lymphocyte homing agent in free form or in pharmaceutically acceptable salt form, and one or more compounds selected from the group consisting of an antibody to the IL-2 receptor, an immunosuppressive macrocyclic lactone and a soluble human complement inhibitor is used to treat or prevent insulin-producing cell graft rejection.

Abstract: The present invention relates to compounds for the inhibition of poly(ADP-ribose) polymerase (PARP). In some embodiments, the compounds have the Formula: wherein the constituent variables are as defined herein. The invention further provides methods for the use of the compounds disclosed herein.

Abstract: This invention relates to an implantable medical device for and method of treating a vascular disease where the device is preferably a stent comprising a drug reservoir layer comprising poly(vinylidene fluoride-co-hexafluoropropylene) and zotarolimus.

Abstract: A composition comprising microspheres of a polymer matrix, having two different pharmaceutical actives having complementary, usually synergistic, activity in killing cells. The compositions have particular utility for treating tumours. Useful combinations are doxorubicin with rapamycin, irinotecan with ibuprofen, ibuprofen with doxorubicin and irinotecan with doxorubicin. The polymer matrix is preferably a crosslinked polyvinyl alcohol. The drugs may be included in the same microsphere, or microspheres each with an individual pharmaceutical agent may be mixed together. The microspheres are preferably used in chemoembolisation of tumours.

Abstract: A prodrug compound of a rapamycin analog and methods for inhibiting, treating, and preventing mammalian diseases.

Abstract: The invention provides compounds having the formula: wherein R1 is halogen. The invention also provides compositions comprising the compounds, and methods of treating diseases or disorders that comprise administering one or more of the compounds to a subject in need thereof. The disclosed compounds have CCR1 antagonist activity.

Abstract: An inhalation kit comprising: (a) an inhaler displaying a flow resistance of about 0.01 to 0.1 ?{square root over (kPa)} min/L; and (b) an inhalable powder comprising tiotropium in admixture with a physiologically acceptable excipient with an average particle size of between 10 to 500 ?m, and a method of administering an inhalable powder containing tiotropium in admixture with a physiologically acceptable excipient with an average particle size of between 10 ?m to 500 ?m, the method comprising actuating an inhaler a flow resistance of about 0.01 to 0.1 ?{square root over (kPa)} min/L containing the inhalable powder.

Abstract: The invention relates to pharmaceutical compositions comprising an ascomycin in dissolved form and a pharmaceutically acceptable cellulose derivative for prevention or reduction of crystal growth.

Abstract: Methods and compositions containing huperzine for direct delivery to central nervous system (CNS) tissue are used to alleviate pain and for the prevention and/or treatment of seizures and epilepsy. The invention is also directed to methods and compositions for using huperzine for the prevention and/or treatment of neuropathic pain and orthostatic hypotension.

Abstract: The invention features methods, compositions, and kits useful for the treatment of muscular dystrophy, e.g., Duchenne muscular dystrophy, in a patient.

Abstract: The present invention relates to a micelle composition comprising a hydrophobic compound and an amphiphilic block copolymer, wherein the amphiphilic block copolymer consists of a hydrophobic block A and a hydrophilic block B, the hydrophobic block A comprises at least one hydrophobic polymeric unit X and the hydrophilic block B comprises at least one hydrophilic polymeric unit Y whereby the X and Y blocks alternate. The present invention further relates to a process for the preparation of the micelle composition wherein the process comprises the steps of: a) dissolving the hydrophobic compound and the amphiphilic block copolymer in an organic solvent to form a solution, b) adding said organic solution into an aqueous medium, c) optionally repeating aforementioned steps.

Abstract: The present invention provides methods and compositions for selective modulation of certain protein kinases, and especially mTor complexes. The methods and compositions are particularly useful in inhibiting mTor selectively for therapeutic applications.

Abstract: An encoding/decoding apparatus and method using a low-density parity-check code (LDPC code) is disclosed. Basic column group information, serving as a set of information regarding positions of rows with weight 1, is extracted from a reference column in each column group of a predetermined parity-check matrix. Column group information transforms the positions of rows with weight 1 into positions whose lengths are within a required parity length. A parity-check matrix is generated according to the generated column group information. Data is encoded or decoded based on the generated parity-check matrix.

Abstract: The invention is generally directed to a drug-release composition that contains drug-linker-drug compound that is combined with another therapeutic agent that can be an antirestenotic agent. The therapeutic agent can be partially bound to the drug-linker-drug compound, miscible with the drug-linker-drug compound, combined with the drug-linker-drug compound at various ratios, and tuned to control the release of drugs to a tissue in need thereof.

Abstract: The present disclosure is directed in part to a biocompatible nanoparticle composition comprising a plurality of non-colloidal long circulating nanoparticles, each comprising a ?-hydroxy polyester-co-polyether and a therapeutic agent, wherein such disclosed compositions provide a therapeutic effect for at least 12 hours.

Abstract: The present invention relates to the topical and oral delivery of a composition comprising one or more active agents for treating a disease or symptoms in a subject. In some embodiments, the present invention comprises a composition comprising at least one active compound, e.g., finasteride or minoxidil, and one or more lipids. In some embodiments, the present invention relates to composition and method of preparation for treating androgenic alopecia (AGA), prevention of hair loss and female hirsutism. In some embodiment, the present invention comprises finasteride and at least one lipid component for the treatment of benign prostatic hyperplasia. In some embodiment, the present invention comprises tacrolimus or amphotericin B and at least one lipid component for the treatment of skin or eye related diseases.

Abstract: Disclosed are a method for preparing a powder containing a nanoparticulated sparingly soluble drug, a powder prepared thereby, and a pharmaceutical composition containing the same. The disclosed method includes: providing a uniformly dispersed solution of a sparingly soluble drug which is formed into nanoparticles in the presence of a surface stabilizer; mixing the uniformly dispersed solution with a water-soluble dispersant solution; and drying the mixed solution to obtain the powder. When the powder containing the nanoparticulated sparingly soluble drug obtained by the disclosed method is redispersed in an aqueous solution, the sparingly soluble drug retains a particle size in the nano scale while the solubility and the dissolution rate of the drug are increased, thereby providing enhanced bioavailability. Consequently, the present disclosure can be useful in the development of preparations of a sparingly soluble drug for oral or parenteral administration.

Abstract: The present invention provides tacrolimus containing ointment having low dermal irritation and excellent stability. It was found that an ointment comprising triacetin as a solubilizer for tacrolimus may sufficiently solubilize tacrolimus, has low dermal irritation and excellent stability. Preferably, the ointment of the present invention is an o/o type (oil-in-oil type) ointment in which tacrolimus-solubilized triacetin droplets are dispersed in an ointment base, preferably a mixture of beeswax and petrolatum.

Abstract: A process is described for loading hydrophilic polymer particles with a water-insoluble solvent-soluble drug. The particles are preferably embolic agents. The method provides particles having little or no drug at the surface and in a surface layer, whereby the burst effect is minimised. The drug is precipitated in the core of the particle, leading to extended release. The drug is, for instance, paclitaxel, rapamycin, dexamethasone or ibuprofen.

Abstract: The present invention relates to 39-desmethoxyrapamycin derivatives and their uses thereof. The present invention provides for the use of these compounds in the treatment of cancer and/or B-cell malignancies, the induction or maintenance of immunosuppression, the treatment of transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation, vascular disease and fibrotic diseases, the stimulation of neuronal regeneration or the treatment of fungal infections.

Abstract: The use of sesquiterpenes and, in particular sesquiterpene lactone endoperoxides, such as artemisinin and analogs thereof, for the treatment of hepatitis C virus infections. Artemisinin, analogs of artemsisnin and some crude Artemisia extracts were tested in vitro against DNA-viruses, retro-viruses and Flavivirida, (an important family of human and animal RNA pathogens). These compounds were also screened for anti-tumor activity. Strong activity of artemisinin was noticed against the bovine viral diarrhea virus (BVDV). As pestiviruses, such as BVDV, share many similarities with hepatitis C virus (HCV), we can conclude that endoperoxides in general and artemisinin more specifically have efficacy as treatments for hepatitis C viral infections.

Abstract: Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula I, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Abstract: Disclosed is a method for preventing the development of head and neck squamous cell carcinoma (HNSCC) in a mammal who is at risk for developing such carcinoma comprising administering an effective amount of a mammalian target of rapamycin (mTOR) inhibitor to the mammal. An example of such inhibitor is rapamycin.

Abstract: The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.

Abstract: The invention relates to a stable pharmaceutical composition comprising comprising a solid dispersion of tacrolimus in a vehicle further comprising a stabilizing agent capable of providing a pH below 7 in the composition, as measured after re-dispersion in water, and preventing or reducing the formation upon storage of major degradation products of tacrolimus, in particular the 8-epitacrolimus.

Abstract: Provided is a tricyclic compound having a PPAR ? agonist activity, which is represented by the general formula (I) wherein Z represents a single bond or the like, Y represents a hydrogen atom, lower alkyl optionally having substituent(s) or the like, X represents a hydrogen atom or the like, A represents aryl or the like, B and C are the same or different and each represents an aromatic carbocycle or the like, R4-R9 are the same or different and each represents hydrogen or the like, V represents a single bond or the like, R10 and R11 are the same or different and each represents hydrogen or the like, or a pharmaceutically acceptable salt thereof or the like:

Abstract: A method of forming a coating on a medical device having a controlled morphology is described. A medical device having a controlled morphology is described.