Abstract: The invention relates to various PCSK9 RNAi constructs with gene silencing activities, and uses thereof. The construct has a double-stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. The sense strand may be modified such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC In addition, the antisense strand may also be modified by 2?-O-methyl groups at the 2nd 5?-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoid the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.

Abstract: A combination of a muscarinic cholinergic receptor agonist, a non-anticholinergic antiemetic agent and a non-selective, peripheral anticholinergic agent for the treatment of hypocholinergic disorders of the central nervous system.

Abstract: The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing. The RNAi constructs may be, for instance, miRNA constructs that are miRNA modulators.

Abstract: Embodiments of the invention relate to a method for the treatment of mIAS or prevention of symptoms associated with mIAS in a patient in need thereof comprising administering to a patient in need thereof an amount of a composition comprising extracts of the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica. Optionally the ratio of Sambucus nigra, Echinacea purpurea and Centella asiatica is about 7:1:2. Further embodiments relate to use of extracts of the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica for the manufacture of a medicament for the treatment of mIAS or prevention of symptoms associated with mIAS in a patient in need thereof.

Abstract: Large scale (bulk) compositions comprising high-purity stannsoporfin are disclosed, as well as methods of synthesizing such compositions.

Abstract: Provided are an aptamer having an inhibitory activity against NGF; a complex containing an aptamer having a binding activity or inhibitory activity against NGF and a functional substance (e.g., affinity substances, labeling substances, enzymes, drug delivery vehicles, drugs and the like); a medicament, a diagnostic agent, a labeling agent and the like containing an aptamer having a binding activity or inhibitory activity against NGF, or a complex containing the aptamer and the functional substance; and the like.

Abstract: The present invention provides a process for preparing the nanoparticles. The process comprises first forming a water-in-oil emulsion from chitosan lactate, amoxicillin, dioctyl sodium sulfosuccinate, glutaraldehyde or bis[sulfosuccinimidyl] suberate, and oil, and sonicating the mixture of to form nanoparticles comprising chitosan crosslinked by dioctyl sodium sulfosuccinate and glutaraldehyde or by dioctyl sodium sulfosuccinate and bis[sulfosuccinimidyl] suberate, wherein the nanoparticles have an average diameter of 100-600 nm and have amoxicillin entrapped by the crosslinked chitosan. The present invention is also directed to nanoparticles comprising crosslinked chitosan and amoxicillin, wherein amoxicillin is entrapped by the crosslinked chitosan. The nanoparticles have an average diameter of 100-600 nm, and the entrapped amoxicillin is at least 5% (w/w) of the total weight nanoparticles.

Abstract: Broad spectrum beta-lactamase inhibitors. Certain inhibitors also exhibit potent antibiotic activity in addition to beta-lactamase inhibition. Compounds of the invention are designed such that on cleavage of the beta-lactam ring reactive moieties are generated which can inactivate beta-lactamase. Also provided are methods of making beta-lactamase inhibitors and beta-lactam antibiotics exhibiting such inhibition. Additionally provided are pharmaceutical compositions for treatment or prevention of bacterial infections and methods of treatment of such infections.

Abstract: Pharmaceutical formulations and methods for the topical or transdermal delivery of 1-isobutyl-1H-imidazo[4,5-c]-quinolin-4-amine or 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine, i.e., imiquimod, to treat actinic keratosis with short durations of therapy, than currently prescribed for the commercially available Aldara® 5% imiquimod cream, as now approved by the U.S. Food & Drug Administration (“FDA”), are disclosed and described. More specifically, lower dosage strength imiquimod formulations to deliver an efficacious dose of imiquimod for treating actinic keratosis with an acceptable safety profile and dosing regimens that are short and more convenient for patient use than the dosing regimen currently approved by the U.S. Food & Drug Administration (“FDA”) for Aldara® 5% imiquimod cream to treat actinic keratosis are also disclosed and described.

Abstract: Pharmaceutical formulations and methods for the topical or transdermal delivery of 1isobutyl-1H-imidazo[4,5-c]-quinolin-4-amine or 1-(2-methylpropyl)-1H-imidazo[4,5 c]quinolin-4-amine, i.e., imiquimod, to treat genital/perianal warts with shorter durations of therapy than currently prescribed for the commercially available for Aldara® 5% imiquimod cream, as now approved by the U.S. Food & Drug Administration (“FDA”), are disclosed and described. More specifically, lower dosage strength imiquimod formulations to deliver an efficacious dose of imiquimod for treating genital/perianal warts with an acceptable safety profile and dosing regimens that are shorter and more convenient for patient use than the dosing regimen currently approved by the U.S. Food & Drug Administration (“FDA”) for Aldara® 5% imiquimod cream to treat genital/perianal warts are also disclosed and described.

Abstract: The present disclosure relates to RNAi constructs with improved cellular uptake characteristics and methods of use of these compounds for silencing expression of long coding RNAs (IncRNAs).

Abstract: Transdermal therapeutic system and method of using the same for safely treating hypocholinergic disorders of the central nervous system such as Alzheimer type dementia. The transdermal therapeutic system comprises oxybutynin in combination with a cholinergic receptor agonist (CRA) such as xanomeline.

Abstract: The invention pertains to the use of therapeutic approaches to treat various skin disorders and conditions. In particular, the invention pertains to the treatment of cutaneous cancers and cutaneous metastasis of solid tumors, as well as to the removal of tattoos, using a hapten. The invention provides various topical formulations comprising a hapten for treatment of these skin disorders and conditions.

Abstract: Disclosed herein are powder mixing apparatuses and methods that utilize the deagglomerizing and mixing effects of an air flow that impacts a flowing powder. The resulting powder can have smaller particle sizes and/or exhibit a more homogenous mixture than the premixed powder.

Abstract: The present invention relates to a pharmaceutical composition comprising propiverine, trospium or glycopyrrolate; and a non-anticholinergic antiemetic agent. It is also related to a pharmaceutical composition comprising a high dose of solifenacin or a pharmaceutically acceptable salts thereof; and a non-anticholinergic antiemetic agent. Pharmaceutical compositions containing high dose of nsPAChA for use for increasing the AChEI blood concentrations and for combating neurodegeneration are also described. The invention also relates to a method for inducing neuroprotection and combating neurodegeneration in a patient suffering from Alzheimer type dementia as well as to a method for increasing the blood levels of an acetyl choline esterase inhibitor (AChEI) in a human subject treated with an AChEI dose.

Abstract: The invention relates to various PCSK9 RNAi constructs with gene silencing activities, and uses thereof. The construct has a double-stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. The sense strand may be modified such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC In addition, the antisense strand may also be modified by 2?-O-methyl groups at the 2nd 5?-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoid the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.

Abstract: The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal and fibrotic applications.

Abstract: A combination of a muscarinic receptor antagonist consisting of a M2-receptor antagonist and of a non-selective, peripheral anticholinergic agent, and optionally an anticholinesterase inhibitor, and use of the same for treatment of hypocholinergic type disorders such as Alzheimer type dementia, schizophrenia, schizophrenia associated dementia, and schizoaffective disorders.

Abstract: There is described a pharmaceutical combination comprising oxybutynin or a pharmaceutically acceptable addition salt thereof, in a transdermal therapeutic system, and an acetylcholinesterase inhibitor, useful for safely treating hypocholinergic disorders of the central nervous system such as Alzheimer type dementia. In this combination, the acetylcholinesterase inhibitor (AChEI) is present at a dose that is higher than the maximal recommended dose, per unit form. In particular, the transdermal therapeutic system comprising oxybutynin is in combination with rivastigmine in a transdermal formulation or oral form.