Abstract: The present invention provides novel compounds represented by formula I: or pharmaceutically acceptable salts thereof useful for treating flaviviridae viral infection.

Abstract: The present invention relates to a novel technology for forming fine particles with a size of 0.02˜3 microns from a solid that can be dissolved in a liquid solvent and is not decomposed by heat. The particle preparation technology according to the present invention may be applicable to the fields of food, cosmetics, biopolymer, polymer compositions, and pharmaceuticals.

Abstract: Provided are methods and kits for administering progestogen as a glucocorticoid sensitizer to restore corticosteroid sensitivity or reverse the glucocorticoid insensitivity or enhance glucocorticoid sensitivity, in order to treat one or more glucocorticoid insensitivity related diseases or conditions. For example, these include methods for reversing the glucocorticoid insensitivity in a subject having no history of menstrual cycle-related exacerbation or allergy to self-hormones, particularly progesterone, such as premenstrual or perimenstrual deterioration in the symptoms, e.g., premenstrual worsening of atopic dermatitis or premenstrual exacerbations of asthma, and exhibiting relatively or totally refractory responses to glucocorticoid therapy, e.g., glucocorticoid resistance. The methods and kits provide for the administration of a sex hormone to the subject who is corticosteroid dependent or corticoid resistant or unresponsive or intolerant to corticosteroids.

Abstract: The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of human diseases.

Abstract: Compositions and methods for treating or preventing unwanted immune responses are provided. The compositions relate to novel soluble CD83 (sCD83) polypeptides and nucleic acids encoding such polypeptides, improved (sCD83) formulations, and the use of such polypeptides and formulations in the treatment or prevention of allergy, autoimmune disease and transplant rejection. A sCD83 polypeptide is provided, comprising SEQ ID NO:7 or an amino acid sequence having at least 70% identity to SEQ ID NO:7; wherein one or more of amino acid residues 12, 20, 85 and 92 of SEQ ID NO:7 is an amino acid other than cysteine; and optionally, one or more of amino acid residues 1, 2, 3, 4 and 130 are absent.

Abstract: A pharmaceutical dosage form comprises a solid dispersion product of at least one active ingredient dispersed in a polymeric binder composition, the polymeric carrier composition comprising a) a vinylpyrrolidone homopolymer, wherein at least 95% by weight of the vinylpyrrolidone homopolymer has a molecular weight distribution within the range of from 1000 to 13 000; and b) a vinylpyrrolidone copolymer having a weight-average molecular weight of from 5000 to 1 500 000. The dosage form is preferably prepared by a melt extrusion process. The polymeric carrier composition exhibits a high drug dissolution power and allows a reduction of the viscosity of the melt without deteriorating the mechanical properties and storage stability of the dosage form.

Abstract: The disclosure generally describes methods of preventing or treating ophthalmic diseases or conditions in a mammalian subject, such as diabetic retinopathy, cataracts, retinitis pigmentosa, glaucoma, macular degeneration, choroidal neovascularization, retinal degeneration, and oxygen-induced retinopathy. The methods comprise administering an effective amount of an aromatic-cationic peptide to subjects in need thereof.

Abstract: The eye is effectively treated by providing it with formulations including uncoated cationically charged microparticles of reversed cubic phase or reversed hexagonal phase material. The treatment methods are effective; for a variety of diseases and conditions including dry eye. The structure, charge and components of the microparticles in dispersion, with or without an active ingredient, provide mucoadhesion, layering, protection and prolonged duration of ophthalmic action.

Abstract: A pH-sensitive solid pharmaceutical composition for oral formulation and preparation method thereof is provided. The solid pharmaceutical composition contains a pharmaceutical active ingredient, a nano-matrix carrier and a pH-sensitive polymer material.

Abstract: Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Abstract: The present invention provides polymer aggregates as delivery vehicles for therapeutics and diagnostics. The present invention additionally provides methods of synthesis and uses for such aggregates.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporin and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: Disclosed are non-immunosuppressive cyclophilin-binding cyclosporins, e.g., of formula (I, Ia or II) as defined herein, having useful properties in the prevention of Hepatitis C infections.

Abstract: This invention provides an emulsion, e.g., microemulsion, pre-concentrate comprising a difficultly soluble active agent and a carrier medium. The active agent may, e.g., be a cyclosporin or a macrolide.

Abstract: The present invention provides methods of screening for compositions useful for treating, ameliorating, or preventing fibrosis and/or fibrosis-associated conditions by measuring changes in the level(s) of IL-21 and/or IL-21 receptor (IL-21R) (e.g., the level of expression of IL-21 and/or IL-21R protein and/or mRNA, the level of activity of IL-21 and/or IL-21R, the level of interaction of IL-21 with IL-21R). The invention further provides antagonists of IL-21 or IL-21R for the treatment of fibrosis and/or fibrosis-associated conditions. Further provided herein are methods of diagnosing, prognosing, and monitoring the progress (e.g., the course of treatment) of fibrosis and/or fibrosis-associated conditions by measuring the level of IL-21 and/or IL-21R (i.e., the level of activity of IL-21 and/or IL-21R, the level of expression of IL-21 and/or IL-21R (e.g., the level of IL-21 and/or IL-21R gene products), and/or the level of interaction of IL-21 with IL-21R).

Abstract: The invention relates to the use of PDE5 inhibitors for treating and/or preventing hypopigmentary disorders.

Abstract: The present disclosure relates to formulations containing cyclosporin analogs that are structurally similar to cyclosporin A, in particular isomeric mixtures of cyclosporin analogs that are structurally similar to cyclosporin A. The formulations form stable microemulsion preconcentrates and may provide superior drug bioavailability and/or may reduce one or more adverse effects associated with the administration of cyclosporin. Also disclosed are methods for using and preparing the formulations.

Abstract: A method of forming an ocular delivery device includes exposing a solid, shaped cellulose polymer to a solution including an active pharmaceutical ingredient (API) and a solvent capable of solubilizing the API, wherein the polymer absorbs at least a portion of the solution, including the API and solvent. The method may further include removing at least a portion of the absorbed solvent from the polymer by allowing the absorbed solvent to evaporate from the polymer or by drying the polymer. A variety of cellulose polymers may be used, including hydroxypropyl cellulose. A variety of APIs may be used, including Cyclosporine, Tobramycin and Vancomycin. Ocular delivery devices prepared by the methods may be used to treat a variety of eye disorders.

Abstract: The present invention relates to a method for processing microbiologically produced, non-polar, cyclic oligopeptides comprising the step of a) extracting the entire fermentation broth incident to the microbiological production process using a liquid extractant that contains ether and is immiscible with water, wherein the amount of extractant is sufficient to form a two-phase system together with the total fermentation broth, and novel solvates of cyclosporin A and methyl-t-butyl ether.

Abstract: The present invention relates to the treatment of protozoal diseases by administering cytotoxic and/or cytostatic compounds, in particular those used in anticancer therapy, to patients. In particular, the invention relates to the use of anticancer agents that can penetrate into the CNS for treatment of late stage African sleeping sickness or cerebral malaria.

Abstract: This invention provides for biocompatible and biodegradable syringeable liquid, implantable solid, and injectable gel pharmaceutical formulations useful for the treatment of systemic and local disease states.

Abstract: Cosmetic compositions comprising therapeutic agents for the treatment of various eye conditions and methods of use are described. In particular, the invention provides cosmetic compositions comprising ophthalmic therapeutic agents in combination with a muscle fasciculating agent for application to the outer surface of the upper eyelid, perimeter of the eyelid and/or eyelashes thereby causing transfer of the therapeutic agents into the vascular network within the eyelid for delivery into all parts of the eye, including the posterior segments of the eye, the eyelid glands, conjuctiva and periocular tissue.

Abstract: The invention provides a method for manipulating or formulating a solid substance which melts under pressure of a gas without degrading at a temperature lower than the melting point of the substance at atmospheric pressure including: applying to the substance a liquefied gas or dense gas to melt the substance without degrading the substance; then contacting the molten substance with a carrier fluid, which is at substantially the same pressure as the liquefied gas or dense gas, to form a solution or mixture of at least a part of the molten substance and the carrier fluid; and passing the solution or mixture into a vessel of lower pressure than the pressure of the liquefied gas or dense gas and carrier fluid to form particles of the substance; and particles formed by the method.

Abstract: The invention comprises a method of treatment using an oral capsule dose of rapamycin formulated with PEG-lipids. Two types of PEG-lipids are used in the formulation. A solubilizing agent dissolves the rapamycin, and solidifying agent is used to convert the solution of rapamycin/solubilizing agent to a more solid form.

Abstract: Methods of inhibiting cytochrome P450 enzymes are provided that can be used for improving the treatment of diseases by preventing degradation of drugs or other molecules by cytochrome P450. Pharmaceutical compositions are provided that can act as boosters to improve the pharmacokinetics, enhance the bioavailability, and enhance the therapeutic effect of drugs that undergo in vivo degradation by cytochrome P450 enzymes.

Abstract: Methods of inhibiting cytochrome P450 enzymes are provided that can be used for improving the treatment of diseases by preventing degradation of drugs or other molecules by cytochrome P450. Pharmaceutical compositions are provided that can act as boosters to improve the pharmacokinetics, enhance the bioavailability, and enhance the therapeutic effect of drugs that undergo in vivo degradation by cytochrome P450 enzymes.

Abstract: The present invention relates to new imidazole modulators of M3 muscarinic acetylcholine receptor activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention is directed to cyclosporine compositions and methods for stimulating the growth of nails and cuticles in a mammal, including humans. The compositions may be administered topically to the nail bed, nail matrix and cuticle in an amount effective to increase nail growth and thicken, strengthen and smooth the nail. The composition is also effective in strengthening and growing nails, including fingernails and toenails.

Abstract: The subject invention concerns methods and materials for assessing a patient's likelihood of responsiveness to an immunosuppressive therapy. The subject invention is contemplated for use with patients having an autoimmune disorder. In an exemplified embodiment, the methods of the invention are used for assessing and/or treating a patient with MDS. In one embodiment, a method of the invention comprises analyzing T cells of a patient for dysregulation of CD4+ and/or CD8+ T cell subsets, and determining the patient's likelihood of responsiveness to IST based on the level of dysregulation of the patient's CD4+ and/or CD8+ T cell subsets. In one embodiment, an increased likelihood of patient responsiveness to IST is associated with an increased percentage of CD4+ and/or CD8+ effector memory T cells and/or terminal effector memory T cells, for a patient. The subject invention also concerns methods for treating a patient with an autoimmune disorder, such as MDS.

Abstract: A polyethylene glycol (PEG) aerogel particles having an average particle diameter not substantially above about 2?, a volumetric porosity of greater than about 50%, and pore sizes capable of retaining drug molecules. A method for preparing such polyethylene glycol (PEG) aerogel particles includes initiating a catalyzed reaction using a catalyst of PEG forming ingredients to form PEG particles; partially drying the formed PEG particles under conditions to control pore size; and subjecting the partially dried formed PEG particles to CO2 supercritical extraction for form the PEG aerogel particles. Drug molecules include chemotherapeutic agents. The surface of the PEG aerogel particles are reactable with a variety of agents, for example, to selectively target tumors, protects irreversible damage to labile proteins, and protects degradation of sensitive drugs with subsequent loss of biological efficacy.

Abstract: The invention teaches a method for testing a prospective or known immunomodulatory drug for T-cell activation, comprising the step of contacting in-vitro a peripheral blood mononuclear cell (PBMC) culture with a predetermined amount of the prospective or known immunomodulatory drug and observing the PBMC culture for T-cell activation using a readout system, upon contact with the prospective or known immunomodulatory drug, wherein the cell density of a PBMC preculture is adjusted such that cell-cell contact of the PBMC is enabled and wherein the PBMC preculture is cultured for at least 12 h.

Abstract: Provided herein are methods for the administration of drugs using liposomes. In particular, provided herein is the use of liposomes as diluents for lyophilized or liquid drugs to deliver the drug safely, reduce the toxicity of the drug or the excipients used to solubilize or stabilize the drug.

Abstract: Provided herein are methods for preparing liposomes comprising docetaxel and uses thereof. In certain embodiments, liposomes are prepared without using heat, organic solvents, proteins, and/or inorganic salts in the process. In certain embodiments, the liposomal preparations are used in the treatment of diseases or disorders.

Abstract: Provided herein are methods for preparing liposomes and uses thereof. In certain embodiments, liposomes are prepared without using heat, organic solvents, proteins, and/or inorganic salts in the process. In certain embodiments, the liposomal preparation contains one or more active agents. In certain embodiments, the liposomal preparations are used in the treatment of diseases or disorders.

Abstract: A method of parenterally administering a composition, the method including parenterally administering to a person a composition including at least one omega-3 fatty acid and at least one drug, wherein the at least one omega-3 fatty acid source and the at least one drug are administered simultaneously.

Abstract: Certain diacylglycerol-polyethyleneglycol (DAG-PEG) lipids are especially useful for forming thermodynamically stable liposomes. Such liposomes are useful for a variety of purposes, including the delivery of therapeutic agents.

Abstract: The present invention is directed to a composition comprising a nanoparticulate cyclosporine having improved bioavailability. The nanoparticulate cyclosporine particles of the composition have an effective average particle size of less than about 2000 nm in diameter and are useful in the prevention and treatment of organ transplant rejection and autoimmune diseases such as psoriasis, rheumatoid arthritis, and other related diseases. The invention also relates to a controlled release composition comprising a cyclosporine or a nanoparticulate cyclosporine that in operation delivers the drug in a pulsed or bimodal manner for the prevention and treatment of organ transplant rejection and autoimmune diseases such as psoriasis, rheumatoid arthritis, and other related diseases.

Abstract: The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts, solvates or esters of said compound, or of said prodrug, said compound having the general structure shown in Formula 1: or a pharmaceutically acceptable salt, solvate or ester thereof, wherein the various moieties are defined herein. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non-limiting example(s) include, psoriasis), autoimmune diseases (non-limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non-limiting example(s) include, allograft rejection, xenograft rejection), infectious diseases (e.

Abstract: Methods for rapidly obtaining a nanoscale apolipoprotein bound phospholipid bilayer (NABB) associated with at least one membrane protein are provided. Also disclosed are methods for rapidly obtaining a NABB not associated with membrane proteins. Immunogenic compositions comprising NABBs with native conformational epitopes are also provided along with their methods of use.

Abstract: Methods of treating humans or animals having dysfunctional oral mucosal tissue are disclosed which include topically administering cyclosporine A, salts thereof and/or mixtures thereof in an oral cavity of the human or animal.

Abstract: A nanoemulsion and corresponding methods of making and using systems of single or blended high HLB value surfactant(s) for the emulsification of single or blended oils and vitamin E components in an aqueous phase are provided. The resulting nanoemulsions and methods of administering the nanoemulsions, including a corresponding kit, provide delivery of the nanoemulsions to a patient.

Abstract: Use of topically applied cyclosporine to enhance corneal sensitivity restoration rate in an eye of an individual after ocular surgery such as laser-assisted in situ keratomileusis (LASIK) in which nerves are severed.

Abstract: Lipid-polymer compounds are used to solubilize cyclosporin. Diacylglycerol-polyethyleneglycols (DAG-PEGs) are especially useful in this regard. A preferred embodiment of the invention is an aqueous solution of cyclosporin suitable for opthalmic use.

Abstract: Several diterpene glycosides (e.g., rubusoside, rebaudioside, steviol monoside and stevioside) were discovered to enhance the solubility of a number of pharmaceutically and medicinally important compounds, including but not limited to, paclitaxel, camptothecin, curcumin, tanshinone HA, capsaicin, cyclosporine, erythromycin, nystatin, itraconazole, and celecoxib. The use of the diterpene glycoside rubusoside increased solubility in all tested compounds. The diterpene glycosides are a naturally occurring class of water solubility-enhancing compounds that are non-toxic and that will be useful as new complexing agents or excipients in the pharmaceutical, agricultural (e.g., solubilizing pesticides), cosmetic and food industries. Aqueous solutions by using rubusoside to increase the solubility of otherwise insoluble drugs will have several new routes of administration. In addition, aqueous solutions of therapeutic compounds with rubusoside were shown to retain the known pharmacological activity of the compounds.

Abstract: Pharmaceutical compositions, which enable high absorption when administered orally, and which comprise a cyclosporin or cyclosporin derivative dissolved in a solvent-surfactant system further comprising a hydrophilic surfactant and a lipophilic surfactant, with minimal quantities of solvents.

Abstract: The invention relates to compounds of formula (I) wherein X, R1, R2, R3, R8, R9 have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of ZAP-70 for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

Abstract: The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of genes in rejection-associated gene clusters. The disclosed gene clusters include genes that are substantially co-expressed with cytotoxic lymphocyte pro-apoptotic genes, cytoprotective genes and several other cytokine and immune cell genes.

Abstract: The present invention describes soft gelatin capsules that encapsulate a water-insoluble active ingredient and an excipient composed of a crystallization inhibitor that stabilizes the water-insoluble inhibitor. The crystallization inhibitor being at least one mononacylglycerol compound whose acyl group is a fatty acid residue of 6-18 carbon atoms. The capsule contents are more resistant to turbidity, forming a coarse emulsion, and crystallization of the active ingredient compared with compositions absent the crystallization inhibitor.

Abstract: Oil-in-water emulsion including a non-steroidal anti-inflammatory drug and a quaternary ammonium halide useful for the prevention and treatment of inflammation in the eye, and process for manufacturing thereof.

Abstract: The invention relates to methods of preventing, treating, ameliorating and otherwise inhibiting organ or transplant rejection in a patient by administering B Lymphocyte Stimulator antagonists. In addition, therapeutic treatment regimens are provided to promote transplant tolerance in a patient following the administration of B Lymphocyte Stimulatorantagonists.