The present invention relates to improved Nanobodies™ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.

The present invention is directed to compounds of Formula (I), which includes enantiomer and diasteromers thereof:

##STR00001##

The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

Compounds of the formula ##STR00001##
where the variables have the meaning defined in the specification have analgesic and/or immunostimulant effect in mammals.

Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH.sub.2—SO.sub.3H)COOH or Arg-Gly-NH—CH(CH.sub.2—SO.sub.3H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting integrins including but not necessarily limited to α.sub.5β.sub.1-Integrin, α.sub.vβ.sub.3-Integrin and α.sub.vβ.sub.5-Integrin, inhibiting cellular adhesion to RGD binding sites, preventing or treating viral or other microbial infections, inhibiting angiogenesis in tumors, retinal tissue or other tissues or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.

The present application provides novel tetrahydro-isohumulone (THIAA) derivatives and substantially enantiomerically pure compositions and pharmaceutical formulations thereof. The application further provides methods of using the disclosed compounds and compositions to activate PPARγ, inhibit inflammation, and treat conditions associated with inflammation and conditions responsive to PPARγ modulation such as diabetes.

The invention provides pyrrolo-pyrrole carbamate and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., solid tumor cancer, obesity, Down's syndrome, Alzheimer's disease, or pain, in a patient. The octahydropyrrolo pyrrole carbamates could be derived from hexafluoroisopropanol, N,N-disuccinimide and such. The activity of carbamates in MAGL, FAAH, and ABHD6 assays are also described.

Disclosed herein are topical formulations comprising about 0.001 to about 3 wt % detomidine or a salt thereof; and, a carrier that is suitable for topical administration to a subject's skin, wherein the carrier optionally comprises a water-miscible solubilizer that is present in an amount of up to 40% by weight of the formulation; wherein the formulation has a pH of 4.5 to 9, and, wherein the formulation provides prolonged, substantially non-systemic treatment for pain. Also provided are methods for providing prolonged, non-systemic treatment for pain in a subject in need thereof comprising topically administering to the subject the presently disclosed topical formulations.

Disclosed herein are topical formulations comprising about 0.001 to about 3 wt % detomidine or a salt thereof; and, a carrier that is suitable for topical administration to a subject's skin, wherein the carrier optionally comprises a water-miscible solubilizer that is present in an amount of up to 40% by weight of the formulation; wherein the formulation has a pH of 4.5 to 9, and, wherein the formulation provides prolonged, substantially non-systemic treatment for pain. Also provided are methods for providing prolonged, non-systemic treatment for pain in a subject in need thereof comprising topically administering to the subject the presently disclosed topical formulations.

Oral solid pharmaceutical compositions containing meloxicam co-crystals described herein allow for the use of meloxicam for the treatment of acute pain. In particular, the improved dissolution and bioavailability of the meloxicam co-crystal compositions provide more rapid uptake of meloxicam in vivo as evidenced by increase blood plasma concentrations in a decreased amount of time following administration. A correlation between improved plasma concentrations and in vivo analgesic action are provided for the first time.

Oral solid pharmaceutical compositions containing meloxicam co-crystals described herein allow for the use of meloxicam for the treatment of acute pain. In particular, the improved dissolution and bioavailability of the meloxicam co-crystal compositions provide more rapid uptake of meloxicam in vivo as evidenced by increase blood plasma concentrations in a decreased amount of time following administration. A correlation between improved plasma concentrations and in vivo analgesic action are provided for the first time.