The present invention pro vides a significant improvement over the type of com positions disclosed in the aforementioned patent by reducing the amount of inhibited phenol required to produce the same ameliorative effect.

Some are a con sequence of a local effect (such as a laceration, or cut) while others may reflect underlying constitutional dis orders (such as the yellowing of skin that may occur in liver diseases).

The objectionable external appear ance caused by these disorders may be minimized or corrected in a non-surgical fashion by the application of a composition, such as that disclosed herein, which is not harmful to one's health and which produces two fundamental and simultaneous reactions, one in the epidermis and another in the dermis.

These responses, in turn, are manifest by a peeling of the outermost skin layer and the consequent removal of surface irregularities, blem ishes and discolorations, and by a strengthening of the underlying dermis which results from an increase in the numbers of connective tissue cells which surround and support the hair follicles, glands and vessels.

Moreover, this same response may cause the obliteration or collapse of certain poorly formed blood vessels in the dermis and result in the disappearance or fading of certain types of birth marks.

[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.

Al- though recent efforts in using chemical enhancers have fo- cused on substances categorized as generally recognized as safe (GRAS), early work included a wide range of materi- als.

Additives that en- hance skin delivery by altering solubility of the active ingredi- ent in the formulation (including supersaturation) or by opti- AQUESTIVE EXHIBIT 1024 page 0002

Penetration of Guinea Pig Skin by Acyclovir in Different Vehicles and Correlation with the Efficacy of Topical Therapy of Experimental Cutaneous Herpes Simplex Virus Infection.

Effect of Azone and Propylene Glycol on Penetration of Trifluorothymidine Through Skin and Efficacy of Different Topical Follnulations Against Cutaneous Herpes Simplex Virus Infections in Guinea Pigs.

Effect of Penetration Enhancers on the in vitro Transport of Ephedrine Through Rat Skin and Human Epidermis from Matrix Based Trans dermal Foi inulations .

Perceived Barriers to Diazepam Rectal Gel Administration in the School Perceived Barrier Number Privacy/setting Access/availability of nurse Legal/delegation issues Staff anxiety/fear Lack of training None Consent of ...

In some embodiments, the benzodiazepine drug is selected from the group consisting of: alprazolam, brotizolam, chlordiaz- epoxide, clobazam, clonazepam, clorazepam, demox- azepam, diazepam, flumazenil, flurazepam, halazepam, midazolam, nordazepam, medazepam, nitrazepam, oxazepam, lorazepam, prazepam, quazepam, triazolam, temazepam, loprazolam, any pharmaceutically-acceptable salts thereof, and any combinationsthereof.

In some embodiments, the benzodiazepine drug is selected from the group consisting of alprazolam, brotizolam, chlor- diazepoxide, clobazam, clonazepam, clorazepam, demox- azepam, diazepam, flumazenil, flurazepam, halazepam, midazolam, nordazepam, medazepam, nitrazepam, oxazepam, lorazepam, prazepam, quazepam, triazolam, temazepam, loprazolam, any pharmaceutically-acceptable salts thereof, and any combinationsthereof.

In some embodiments, the benzodiazepine drug is selected from the group consisting of alprazolam, brotizolam, chlor- diazepoxide, clobazam, clonazepam, clorazepam, demox- azepam, diazepam, flumazenil, flurazepam, halazepam, midazolam, nordazepam, medazepam, nitrazepam, oxazepam, lorazepam, prazepam, quazepam, triazolam, temazepam, loprazolam, or any pharmaceutically-acceptable salts thereof, and any combinationsthereof.

In some embodiments, the benzodiazepine drug is selected from the group consisting of alprazolam, brotizolam, chlor- diazepoxide, clobazam, clonazepam, clorazepam, demox- azepam, diazepam, flumazenil, flurazepam, halazepam, midazolam, nordazepam, medazepam, nitrazepam, oxazepam, lorazepam, prazepam, quazepam, triazolam, temazepam, loprazolam, any pharmaceutically-acceptable salts thereof, and any combinationsthereof.

In some embodiments, the benzodiazepine drug is selected from the group consisting of alprazolam, brotizolam, chlor- diazepoxide, clobazam, clonazepam, clorazepam, demox- azepam, diazepam, flumazenil, flurazepam, halazepam, midazolam, nordazepam, medazepam, nitrazepam, oxazepam, lorazepam, prazepam, quazepam, triazolam, temazepam, loprazolam, or any pharmaceutically-acceptable salts thereof, and any combinationsthereof.