[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).

[streetAddress:_|3894 Courtney St [internal Address: Suite 180 | city, Bethlehem PROPERTY NUMBERSTotal: 1

WHEREAS, we, Garry Thomas Gwozdz of 329 South Main Street, Nazareth, Pennsylvania 18064, Andrew Loxley of 126 Market Street, #5, Philadelphia, Pennsylvania 19105 and Mark Mitchnick of 80 Three Mile Harbor Drive, East Hampton, New York 11937, hereinafter referred to as the assignors are the joint inventors of certain inventions or improvements for which we have made application for Letters Patent to the United States, identified as Serial No. 61/040,281, filed March 28, 2008, entitled Pharmaceutical Solutions and Method for Solubilizing Therapeutic Agents; and WHEREAS, Particle Sciences, Inc., hereinafter referred to as the assignee, of 3894 Courtney Street, Suite 180, Bethlehem, Pennsylvania 18017, a corporation of Delaware, is desirous of acquiring the entire right, title and interest in and to the said inventions or improvements and in and to the said application, and in, to and under any and all Letters Patent which may be granted on or aS a result thereof in any and.all countries: the for good and valuable consideration,

receipt of which is hereby acknowledged, we, the said assignors, have sold, assigned, transferred and set over, and by these presents do hereby sell, assign, transfer and set over to said assignee, the entire right, title and interest in and to said inventions or improvements and said application and any and all continuations, divisions and renewals of and substitutes for said application or any other application based in whole or in part thereon and in, to and under any and all Letters Patent which may be granted on or as a result thereof in the United States and any and all other countries, and any reissue or reissues or extension or extensions of said Letters Patent, and assign to and authorize said assignee, to file in our names applications for Letters Patent in all countries, the same to be held and enjoyed by said assignee, its successors, assigns, nominees or legal representatives, to the full end of the term or terms for which said Letters Patent respectively may be granted, reissued or extended, as fully and entirely as the same would have been held and enjoyed by us had this assignment, sale and transfer not been made.

to said said application and said Letters Patent improvements, legal assignee, its successors, assigns, nominees, or representatives, and each of us agrees to communicate to said assignee or to its nominee all known facts respecting said inventions or improvements, said application and said Letters Patent, to testify in any legal proceedings, to sign all lawful papers to execute all disclaimers and divisional, continuing, reissue and foreign applications, to make all rightful oaths, and generally to do everything possible to aid said assignee, its successors, assigns, nominees and legal representatives to obtain and enforce for its or their own benefit proper patent protection for said inventions or improvements in any and all countries.

Notatial Seal Maureen A. Cochran, Notary Public LowerSaucon Twp., Northampton County .

The holder is mounted ona laboratory stirring device, ang yt entire die, with thecompacted pelletstill in place, is immersed inte dissolution medium and rotated bythe stirring-device (see Dissoh a aa tion (711)).

USPy General Information | (1088) In Vitro and In Vivo Evaluation 2335 d theaefal roq ' pelle Ined 7 a ‘theYo of : die, % tched to, ©, and 3ed ing, Dissoly Dissolution testing should be conducted on equipmentthat con- fclinically successful formulations.

Other types Where a single set of specifications cannot be established to cover sinker devices that achieve minimal coverage of dosage form sur- multisource monographarticles, application ofa Case Three standard are commercially available.

Additional physicochemical information may be needed on poly- morphism, particle size distribution, solubility, dissolution rate, sta- bility, and other release-controlling variables ofthe active drug entity under conditions that may react to the extremes of the physiologic environment experienced by the dosage form.

USPy| gsP 26 o drug Pc The recognition and utilization of deconvolution techniques tion, special studies may be necessary to assess specific risk factors related to the dosage form (e.g., irritation and/or sensitization at the Jprelation 1 well as statistical moment calculations represented a major ady.

Hussain et al. 14 have recently evaluated a new aminopeptidase inhibitor, boroleucine, and its effect on the degradation rate of leucine enkephalin in the nasal cavity of rat using an in vitro perfusing method.

Since nasal biopharmaceutical research is currently directed on absorption and bioavailability, we shall describe in more detail the most recently introduced enhancer systems, namely micro- spheres, STDHF and glycyrrhetinic acid derivatives.

23 Pontiroli, A.E., Alberetto, M., Calderara, A., Pajetta, E. and Pozza, G. (1989) Nasal absorption of glucagon and human calcitonin to healthy subjects: a comparison of powders and spray solutions and of different enhancing agents, Eur.

27 Pontiroli, A.E., Alberetto, M., Pajetta, E., Calderara, A. and Gozza, E. (1987) Human insulin plus sodium glycocholate in a nasal spray formulation: improved bioavailability and effectiveness in normal subjects, Diabetes Metab.

28 Aungst, B.J., Rogers, N.J. and Shefter, E. (1988) Comparison of nasal, rectal, buccal, sublingual and intramuscular insulin efficacy and the effects of a bile salt absorption promotor, J. Pharmacol.

[0003] Ethanol constitutes a good solubilizing agent for perfuming ingredients, and additionally has the advantage of being inexpensive and of alloWing the formulation of trans parent compositions.

[0005] A ?rst route consists in replacing ethanol With aqueous compositions containing hydrophilic solubilizing agents such as polyethoxylated hydrogenated castor oils.

Moreover, the presence of Water in a large quantity is capable of causing degradation of the perfuming ingredients over time and therefore of adversely affecting the olfactory characteristics of the product.

[0006] Another solution further consisted in providing perfume compositions in Which the ethanol is at least partially replaced by one or more volatile silicones Which are lineariof the polydimethylsiloxane type4or cyclic.

[0007] HoWever, the applicant has noW discovered, sur prisingly, that by choosing a particular combination of silicone compounds not described in the prior art, it Was possible to obtain a perfume composition Whose rate of evaporation is close to that of ethanol and possessing a ?ash point greater than or equal to 00 C., preferably greater than or equal to 10° C. [0008] The subject of the present invention is therefore a perfume composition comprising a mixture of fragrant mate rials in a physiologically acceptable carrier comprising a mixture of polydimethylsiloxanes, characterized in that the said mixture of polydimethylsiloxanes consists of hexam ethyldisiloxane and octamethyltrisiloxane in a hexamethyl disiloxane to octamethyltrisiloxane Weight ratio ranging from 30:70 to 70:30.

Many important contributions can be found in literature on the subject, focusing on different aspects of interest to researchers, such as the Proctor edited book (1), the edited and directly contributed books of Chien (2,3), and the reviews of Mum (4), Wilson (5), Edman (6), Merkus (7), Gizurarson (8), Duchene (9), Harris (10), Buri (11), and Alpar (12), A Nasal Drug Delivery Focus Group, organized in an American Association of Pharmaceutical Scientists section (13), has also been constituted as well as an Open Forum for free exchange and information in all R and D areas ranging from the formulation to the marketing of nasal preparations.

An instructive behavioral employment of the nose for drug absorption, usually in order to have hallucinations or more general mental effects, is the religious rite of the Amazo- nian population of Yanomamo to assume epeiza , that, is a Powdered mixture of different plant parts like Mimosa aca- cioides , Piptadenia peregrina, and others not identified (14).

The histological toxicity refers to the alteration of mucosa, including membrane protein removal, cell loss, ex- cessive mucus discharge, ciliotoxicity, and disturbance of the normal enzymatic balance (22,23).

However, from a technological point of view, the liquid preparations present problems linked to formula stability, low drug concentration at the absorption site, and short residence time in nasal cavity.

Thereafter, the primed lymphocytes migrate from the original MALT (e.g., the nasal associated lymphoid tissue) to the regional lymph nodes; here they get into further differentiation and then reach, by means of the systemic circulation, all the other mucosal surfaces, where both humoral and cellular immunity is provided.