Furthermore, due to the nature of seizures and muscle spasms, it can be extremely difficult for either a patient or a care-giver to administer the benzodiazepine drug orally and care-givers may be reluctant to place their hands in patients’ mouths.

[011] - Some embodiments described herein provide a method oftreating a patient with a disorder which may be treatable with a benzodiazepine drug, comprising: administering to one or more nasal mucosal membranes of a patient a pharmaceutical solution for nasal administration consisting of a benzodiazepine drug, one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, in an amount from about 30% to about 95% (w/w); one or more alcohols or glycols, or any combinations thereof, in an amount from about 10% to about 70% (w/w); and an alkyl glycoside.

[054] In some embodiments, the composition contains a benzodiazepine drug that at least partially in a paniculate form suspended in a carrier system containing a natural or synthetic tocopherol or tocotrienol and one or more alcohols or glycols.

[055] In some embodiments, the composition contains a benzodiazepine drug that at least partially in a particulate form suspended in a carrier system containing a natural or synthetic tocopherol or tocotrienol, one or more alcohols or glycols, and an alkyl glycoside.

In some embodiments, benzodiazepine comprises a member of the group consisting of alprazolam, diazepam, flurazepam, loracham, medazepam, mexazolam, midazolam, temazepam and pharmaceutically acceptable salts and combinations thereof.

A synthetic analogue of calcitonin, a hypocalcemic pep tide has been shown to be elfectively absorbed percutane ously in the rat by applying it in transdermal dosage form as a gel containing a combination of bile salts and the alkyl glycosides octylglucoside or octylthioglucoside (Ogiso, T. et al., Chem.

We had previously shown that systemic delivery of insu lin via the ocular and nasal-lacrimal route in amounts sufticient to lower blood sugar in experimentally diabetic rats was made possible by including 1% saponin in the eye drops with the insulin (Pillion, D. J. et al., Invest.

The major limiting factors which have prevented the practical development of this route for general use is the low e?iciency of absorption across the nasal mucosa and the local and systemic toxicity of the penetration-enhancing agents used (Moses et al., Gordon et al., Salzmann et al and Chadwick, U.S. et al., Gut, 17:10-17 (1976)).

Dodecylmaltoside and other alkyl glycosides can readily be obtained in pure form and have well de?ned, simple AQUESTIVE EXHIBIT 1020 page 0002 structures (Neugebauer, J.. “A Guide to the Properties and Uses of Detergents in Biology and Biochemistry,” Calbio chem Corporation (1988)).

rats were anesthetized with sodium pentobar bital rather than xylaZine/ketamine; this modi?cation of the procedure resulted in basal blood glucose levels in the normoglycemic range and made it possible to readily moni tor the hyperglycemic action of any glucagon absorbed from the eye.

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Exemplary hydrophobic or lipophilic therapeutic agents which can be solubilized in accordance with the present invention include, but are in no way limited to, steroids such as Dexamethasone, l7-beta—Estradiol; benzodiazepenes such as Diazepam, alpraxolam, bromazepam, chlordiazepoxidem, clonazepam, estazolam, flunitrazepam, flurazepam, lorazepam, lormetazepam, mexazolam, nitrazepam, oxazepam, temazepam, and triazolam; Rapamycin and analogues; Taxol (paclitaxel)

of following any the invention can be administered by nonlimiting exemplary routes, intraabdominal, intraarterial, intraarticular, intracapsular, intracervical, intracranial, intraductal, intradural, intralesional, intralocular, intramural, intranasal, intraocular, intraparietal, intraperitoneal, intralumbar, intraoperative, intrapleural,

Pharmaceutical solutions of the instant invention are particularly useful in formulations to be administered to mucosal membranes, i.e. the nasal mucosa or lungs of a subject by any suitable means.

Formulations suitable for transdermal administration can also be delivered by iontophoresis for example, Pharmaceutical Research 3 (6):3l8 (1986)) and typically take the form of an optionally (see, buffered aqueous solution.

Journal of Controlled Release, 2 0 1992 Elsevier Science Publishers B.V. All rights reserved 01%3659/92/$05.00 165 COREL 00753 Microspheres as a nasal delivery system for peptide drugs P. EdmanaTb, E. Bjiirka>b and L. RydCnb “Kabi Pharmacia Therapeutics, Uppsala, Sweden bCrppsala University, Department of Pharma~~t~cs, BMC, Uppsa~a, Sweden (Received 7 July 199 1; accepted in revised form 9 March 1992 ) Microspheres of starch and dextran, cross-linked with epichlorohydrine, function as an enhancer system for the absorption of insulin in rats.

A conceivable hypothesis with regard to the mech- anism of action of DSM can be that the epithelial mucosa is dehydrated, with a reversible “shrinkage” of the cells, thus giving a physical separation of the intercellular junctions.

Variations of pH [ 61, ionic strength f 71, and inhibition of proteolytic enzymes in the nose [ 8 ] are some ex- amples of parameters which can be varied in or- der to promote the nasal absorption of peptides.

This finding indicates that the mode of action of DSM on the epitheiial cell barrier, giving in- creased permeability of hydrophiIic compounds, is a temporary widening of the tight junctions, AQUESTIVE EXHIBIT 1032 page 0006

K. Morimoto, H. Yamaguchi, Y. Iwakura, K. Morisaka, Y. Ohashi and Y. Nakai, Effects of viscous hyaluronate- sodium solution on the nasal absorption of vasopressin and an analogue, Pharm. Res.