[0009] The present invention also provides a method of treating diabetes including administering to a subject in need thereof via the oral, ocular, nasal, nasolacrimal, inhalation or pulmonary, or oral cavity (sublingual or Buccal cell), a blood glucose reducing amount of a therapeutic composition, for example, an incretin mimetic agent or a functional equiva lent thereof, and an absorption increasing amount of a suitable nontoxic, nonionic alkyl glycoside having a hydro phobic alkyl group joined by a linkage to a hydrophilic saccharide, thereby increasing the absorption of incretin mimetic agent or insulin and loWering the level of blood glucose and treating diabetes in the subject.

The linkage betWeen the hydrophobic alkyl group and the hydro philic saccharide can include, among other possibilities, a glycosidic, thioglycosidic (Horton), amide (Carbohydrates as Organic RaW Materials, F. W. Lichtenthaler ed., VCH Publishers, NeW York, 1991), ureide (Austrian Pat. 386,414 (1988); Chem.

A phar maceutically acceptable carrier can also be selected from substances such as distilled Water, benZyl alcohol, lactose, starches, talc, magnesium stearate, polyvinylpyrrolidone, alginic acid, colloidal silica, titanium dioxide, and ?avoring agents.

Other compounds include, for example, nicotine, interferon (e.g., alpha, beta, gamma), PYY, GLP-1, synthetic exendin-4 (Exenatide), parathyroid hormone, and human groWth hor mone or other loW molecular Weight peptides and proteins.

The sustained release format can be an ocular insert, erodible microparticulates, sWelling mucoadhesive particulates, pH sensitive micropar ticulates, nanoparticles/latex systems, ion-exchange resins and other polymeric gels and implants (Ocusert, AlZa Corp., California; Joshi, A., S. Ping and K. J. Himmelstein, patent application WO 91/19481).

The term "heteroaryl", as used herein, unless otherwise indicated, includes an organic radical derived from an aromatic heterocyclic compound by removal of one hydrogen, such as pyridyl, furyl, pyroy!, thienyl, isothiazoly!, imidazolyl, benzimidazolyl, tetrazolyl, pyrazinyl, pyrimidyl, quinolyl, isoquinoly:, benzofuryl, isobenzofury!, benzothieny!, pyrazolyl, indoiyl, isoindolyl, purinyl, carbazolyl, isoxazolyl, thiazoly!, oxazolyl, benzthiazoly!

The presentinvention also relates to a pharmaceutical composition for (a) the treatment of a condition selected from the group consisting ofarthritis, osteoporosis, cancer, synergy with cytotoxic anticancer agents, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, in combination with standard NSAID'S and analgesics and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic AQUESTIVE EXHIBIT 1004=page 1056 AQUESTIVE EXHIBIT 1004 page 1056

Solid compositions of a similar type may also be employedasfillers in gelatin capsules; preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene glycols.

intravenous use) a sterile injectable solution of the active ingredient Salutions of a therapeutic compoundof the present invention in either sesame or peanutoil orin aqueous propylene glycol may be employed.

)propionicacid A solution of (2S)-2-hydroxy-3-(4-methoxybenzenesulfonyl)propionic acid benzyl ester (1.0 grams, 2.8 mmole) in methanol (70 mL) wastreated with 10% palladium on activated carbon (100 mg) and hydrogenated at 3 atmospheres pressure for 3 hours in a Parr shaker.

Its use, however, is limited by its short duration of action and occasional reports of cardiovascu¬ lar and/or respiratory complications.2 Recent literature suggests that loraze¬ pam, a new longer-acting benzodiaze- pine, is both effective and safe in the management of status epilepticus in adults and older children.35 To our knowledge, comparative data docu¬ menting the safety and efficacy in neo¬ nates are unavailable to date.

Electroencephalographic monitor¬ ing before lorazepam administration in patients 3, 5, and 6 demonstrated burst suppression patterns and elec¬ trographic seizures in the form of rhythmic theta and delta activity or multifocal sharp waves.

In all patients, serum electrolyte, cal¬ cium, glucose, albumin, globulin, cho¬ lesterol, and triglycéride levels, and hepatic and renal functions remained improved following unchanged or lorazepam administration.

The former has caused hyperosmolality in infants receiving 10 mL of a multi¬ vitamin preparation containing 30% propylene glycol.9 The largest dose of lorazepam used in this study, 0.20 mg, required 0.1 mL of the solution, con¬ taining 0.018 mL of the solubilizer, approximately 1/500 the volume in the above-mentioned report.

Other than in vitro data, there is no documenta¬ tion that benzoate enhances this risk in the human newborn.12 Furthermore, the dose of benzyl alcohol was so small in our study (0.5 mg/kg) that the effect of bilirubin displacement was consid¬ ered insignificant.