New medical uses for the compounds of Formula I, II, or III or a pharmaceutically acceptable salt thereof.

Described herein is a method for forming multi-layer drug dosage forms having at least two layers. In the method, a first formulation comprising a non-gelling matrix forming agent and having a first density is dosed into a preformed mold. A second formulation comprising a non-gelling matrix former and having a second density not equal to the first density is subsequently dosed into the preformed mold. Then, the combination of the formulations dosed into the mold is freeze dried to form the multi-layer dosage form having at least two layers. The use of a density difference between the first and second formulations ensures formation of a product with two distinct layers.

The present invention is directed to a delivery vector for transferring a small peptide coding sequence to a cell for expression of the small peptide coding sequence within the cell. The delivery vector comprises a secretory signal sequence; a sequence encoding a carrier protein operatively associated with the secretory signal sequence; a sequence encoding a cleavage site operatively associated with the sequence encoding a carrier protein; and a sequence encoding a small peptide operatively associated with the sequence encoding a cleavage site.

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Disclosed are methods and compositions for treating cognitive decline in subjects in need. More specifically, disclosed are methods of administrating exogenous adropin to subjects suffering from, or at risk of, cognitive decline including the aged and those suffering from traumatic brain injury. Also disclosed are subjects who would benefit from such treatment and pharmaceutical acceptable compositions comprising adropin, adropin.sup.34-76, and derivatives or variations thereof.

The present invention relates to compounds having a lipid affinity of less than 15% by weight of the compound (such as a log P of −0.75 or less) for use in targeting mitochondria to reduce, inhibit or prevent the formation of mitochondrial reactive oxygen species and for use in treating or preventing a pathological condition associated with increased levels of mitochondrial reactive oxygen species, and for non-therapeutic uses, such as enhancing sports performance and reducing, inhibiting or preventing the formation of mitochondrial reactive oxygen species during exercise, resulting in maintenance of muscle strength and/or a reduction in muscle fatigue, and associated methods. The present invention also relates to extracts and compositions comprising compounds having a lipid affinity of less than 15% (such as a log P of −0.75 or less) for the same uses.

Provided are keratin BD-4, an encoding nucleic acid molecule thereof, an expression vector, a host cell, and a pharmaceutical composition containing the keratin. The keratin BD-4 can be used for preparing drugs having antipyretic and analgesic, antitussive and expectorant, and antiepileptic effects.

The present disclosure relates to a composition for ameliorating a circulatory system disease, which contains a green tea extract with modified ingredient content. According to the present disclosure, it is possible to effectively prevent, ameliorate and treat circulatory system diseases without side effects and, thereby, to greatly help patients with circulatory system diseases and contribute to the development of related industries.

The present disclosure relates to a composition for ameliorating a circulatory system disease, which contains a green tea extract with modified ingredient content. According to the present disclosure, it is possible to effectively prevent, ameliorate and treat circulatory system diseases without side effects and, thereby, to greatly help patients with circulatory system diseases and contribute to the development of related industries.

Disclosed are compounds of formula I

##STR00001## as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.