Novel Cationic Prodrug of Ubiquinol-10 Enhances Intestinal Absorption via Efficient Formation of Nanosized Mixed-Micelles with Bile Acid Anions.

The aim of this study was to develop a prodrug of ubiquinol-10 (UqH-10), the active form of ubiquinone-10 (Uq-10), for oral delivery. Bioavailability of UqH-10 is hampered by its high susceptibility to oxidation and water-insolubility. We prepared three novel -dimethylglycine ester derivatives of UqH-10, including a 1-monoester (UqH-1-DMG), 4-monoester (UqH-4-DMG), and 1,4-bis-ester (UqH-DMG), and assessed their physicochemical properties in vitro and in vivo.

Preparation and in vivo evaluation of a water-soluble prodrug for 2R-gamma-tocotrienol and as a two-step prodrug for 2,7,8-trimethyl-2S-(beta-carboxyethyl)-6-hydroxychroman (S-gamma-CEHC) in rat.

2R-gamma-Tocotrienol (gamma-T3) is currently receiving attention because it has beneficial effects not observed with alpha-tocopherol. To achieve the effective delivery of gamma-T3, we synthesized three kinds of ester derivatives of gamma-T3 and evaluated their use as hydrophilic prodrugs for gamma-T3 in vitro and in vivo. 2R-gamma-Tocotrienyl N,N-dimethylamino-acetate hydrochloride (compound 3) was a solid compound, with high solubility and stability in water, and was converted to gamma-T3 by esterases in rat and human liver.

Vitamin E isoforms alpha-tocotrienol and gamma-tocopherol prevent cerebral infarction in mice.

Alpha-tocopherol and its derivatives have been shown to be effective in reducing cerebral ischemia-induced brain damage. However, the effects of other vitamin E isoforms have not been characterized. In the present study, we investigated the effects of six different isoforms of vitamin E on the ischemic brain damage in the mice middle cerebral artery (MCA) occlusion model.

Novel d-gamma-tocopherol derivative as a prodrug for d-gamma-tocopherol and a two-step prodrug for S-gamma-CEHC.

d-gamma-Tocopherol (gamma-Toc) and its major metabolite, 2, 7, 8-trimethyl-2S-(beta-carboxyethyl)-6-hydroxychroman (S-gamma-CEHC), are currently receiving attention concerning their unique pharmacological activities. In order to achieve the efficient delivery of gamma-Toc and S-gamma-CEHC in vivo, we synthesized d-gamma-tocopheryl N,N-dimethylglycinate hydrochloride (gamma-TDMG) as a water-soluble prodrug of gamma-Toc and a two-step prodrug of S-gamma-CEHC. gamma-TDMG is a solid (mp 161-163 degrees C) and is quite soluble in water over 50 mM.