Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula:

##STR00001##

wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds, methods and intermediates useful for making the compounds, and methods of using the compounds and compositions.

The present invention relates to compounds of formula (I) or the tautomers or pharmacologically acceptable acid addition salts thereof, characterized by a topological polar surface area value (TPSA) of at least 145, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z.sup.− have one of the meanings as defined in the specification, to the use of compounds of formula (I) as medicaments, to pharmaceutical compositions comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I). The compounds are ENaC inhibitors useful for the treatment of respiratory diseases and allergic diseases of the airways.

##STR00001##

The present invention relates to compounds of formula (I), or the tautomers or pharmacologically acceptable acid addition salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z have one of the meanings as defined in the specification, to the use of compounds of formula (I) as a medicament, to pharmaceutical composition comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I).

##STR00001##

Disclosed herein are polymorphic and amorphous forms of anhydrate, hydrate, and solvates of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide and methods of using such compositions for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging. Further disclosed are methods of making such polymorphic and amorphous forms.

A silybin injection contains silybin, sulfobutyl ether-β-cyclodextrin, an organic solvent for injection and may further contain a co-solvent, a lyophilization proppant, a pH regulator, water for injection and the like.

Bifunctional compounds that increase uric acid excretion and reduce uric acid production, and monofunctional compounds that either increase uric acid excretion or reduce uric acid production. Methods of using these compounds for reducing uric acid levels in blood or serum, for treating disorders or uric acid metabolism, and for maintaining normal uric acid levels in blood or serum are provided. Pharmaceutical compositions comprising the bifunctional and monofunctional compounds are also provided.

The present invention relates to compounds of formula (I), or the tautomers or pharmacologically acceptable acid addition salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, X, and Z have one of the meanings as defined in the specification, to the use of compounds of formula (I) as a medicament, to pharmaceutical composition comprising at least one compound of formula (I), as well as to medicament combinations containing one or more compounds of formula (I).

##STR00001##

The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.

Disclosed are a pharmaceutical composition, cosmetic product, and food or drink product each comprising a porous ceramic obtained by combustion synthesis of a starting material comprising (1) titanium and (2) at least one member selected from the group consisting of carbon, boron, nitrogen, and silicon; a pharmaceutical composition and cosmetic product each comprising a radical- and nanobubble-containing liquid; and a blood treatment device comprising a blood flow channel for extracorporeal circulation of a patient's blood, the blood flow channel being provided with the porous ceramic above, and the porous ceramic and the blood are brought into contact with each other.