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WO 2017/180788 Al 19 October 2017 (19.10.2017) P O P C T

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WO 2017/180788 Al 19 October 2017 (19.10.2017) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/180788 Al 19 October 2017 (19.10.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every Λ 61Κ 8/02 (2006.01) A61K 45/00 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 8/18 (2006.01) A61P 17/18 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 8/19 (2006.01) A61Q 19/00 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, A61K 33/00 (2006.01) C07K 14/78 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61K 38/00 (2006.01) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, (21) International Application Number: MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, PCT/US20 17/027275 NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (22) International Filing Date: RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, 12 April 2017 (12.04.2017) TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/321,626 12 April 2016 (12.04.2016) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: ILLUSTRIS PHARMACEUTICALS, INC. DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, [US/US]; 4030 Fabian Way, Unit B, Palo Alto, California LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 94303 (US). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (72) Inventor: WAUGH, Jacob; 14 Point Loma Drive, Corona del Mar, California 92625 (US). Published: (74) Agent: WADSWORTH, Curtis C ; Pepper Hamilton — with international search report (Art. 21(3)) LLP, 500 Grant Street, Suite 5000, Pittsburgh, Pennsylvania 15219-2507 (US). 00 00 o 00 o (54) Title: COMPOSITIONS FOR TOPICAL APPLICATION OF COMPOUNDS (57) Abstract: Compositions for transdermal delivery of an active agent and methods for using such compositions are described herein. COMPOSITIONS FOR TOPICAL APPLICATION OF COMPOUNDS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 62/321,626, entitled "Compositions for Topical Application of Compounds," filed April 12, 2016, incorporated herein by reference in its entirety. BACKGROUND [0002] A topical route of drug administration is desirable because the risks and inconvenience of parenteral treatment can be avoided; the variable absorption and metabolism associated with oral treatment can be circumvented; drug administration can be continuous, thereby permitting the use of pharmacologically active agents with short biological half-lives; the gastrointestinal irritation associated with many compounds can be avoided; and cutaneous manifestations of diseases can be treated more effectively than by systemic approaches. Most transdermal and transmucosal delivery systems achieve penetration by using a penetration-enhancing vehicle. Such compounds or mixtures of compounds are known in the art as "penetration enhancers" or "skin enhancers." Many of the penetration enhancers in the literature enhance transdermal absorption, yet they also possess certain drawbacks in that some are regarded as toxic; some irritate the skin; some have a thinning effect on the skin on prolonged use; and most are incapable of delivering high molecular weight pharmaceuticals and cosmetic agents. Clearly, there remains a need for safe and effective transdermal delivery compositions and systems that can administer a wide- range of pharmaceuticals and cosmetic agents to and through the skin, mucosa, hair, nails, teeth, and various other surfaces. BRIEF SUMMARY [0003] Various embodiments of the invention include compositions containing one or more active agents and about 0.1 wt. % to about 5.0 wt. % of a extracellular matrix component or a fragment thereof having average molecular weight of about 2,000 daltons to about 60,000 daltons. In some embodiments, the decoy molecule may be selected from the group consisting of hyaluronic acid, collagen, fibronectin, elastin, lectin, and combinations thereof, and in certain embodiments, the collagen may be selected from the group consisting of collagen type I, collagen type II, collagen type III, collagen type IV, collagen type V, fibrillary collagen, non-fibrillary collagen, and combinations thereof. [0004] In particular embodiments, the compositions may include about 1 mg to about 1000 mg of the extracellular matrix component or a fragment thereof. In some embodiments, the compositions may include about 0.1 wt. % to about 25 wt. % active agent, and in some embodiments, the compositions may include about 1 g to about 1000 mg active agent. In various embodiments, the active agent may be selected from the group consisting of analgesic agents, antibacterial agents, antifungal agents, anesthetics, steroids, retinol, gabapentin, pregabalin, minocycline, salicylate, acetyl salicylic acid, cyclosporine, tacrolimus (FK506), hydrocortisone, lidocaine, bimatoprost, botulinum toxin, tadalafil, an antibody, an antibody fragment, and the like or combinations thereof. [0005] The compositions of embodiments may be formulated as a liquid, cream, ointment, gel, or aerosol. In some embodiments, the compositions my further include one or more pharmaceutical additives selected from the group consisting of diluents, fillers, disintegrants, binders, lubricants, surfactants, hydrophobic vehicles, water soluble vehicles, emulsifiers, buffers, humectants, moisturizers, solubilizers, preservatives, colorants, plastizers, carriers, excipients, or combinations thereof. In some embodiments, the compositions may further include one or more cosmetic additives selected from the group consisting of vitamins, cosmetic peptides, oil control agents, other skin care agents, and hydrating compositions. In some embodiments, the composition may further include a compound that absorbs or reflects UV photons. [0006] In particular embodiments, the compositions may include about 0.25 wt. % to about 2.0 wt. % of the decoy molecule wherein the active agent is selected from the group consisting of salicylate, lidocaine, sunblock, retinol, bimatoprost, steroids, and combinations thereof. In certain embodiments, the compositions may include about 1.0 wt. % to about 5.0 wt. % of the decoy molecule wherein the active agent is selected from the group consisting of antibiotics, antifungal agents, biologies, antibodies, macromolecule active agents, peptide- based therapeutics, and combinations thereof. [0007] Further embodiments include methods for delivering an active agent including the steps of applying to a surface tissue of a subject a composition comprising one or more active agents and about 0.25 wt. % to about 10 wt. % of a extracellular matrix component or a fragment thereof having average molecular weight of about 2,000 daltons to about 60,000 daltons. In particular embodiments, the decoy molecule may be selected from the group consisting of hyaluronic acid, collagen, fibronectin, elastin, lectin, and fragments and combinations thereof. [0008] In particular embodiments, the compositions of such methods may include about 1 mg to about 1000 mg of the extracellular matrix component or a fragment thereof. In some embodiments, the compositions of such methods may include about 0.1 wt. % to about 25 wt. % active agent, and in some embodiments, the compositions of such methods may include about 1 mg to about 1000 mg active agent. In various embodiments, the active agent may be selected from the group consisting of analgesic agents, antibacterial agents, antifungal agents, anesthetics, steroids, retinol, gabapentin, pregabalin, minocycline, salicylate, acetyl salicylic acid, cyclosporine, tacrolimus (FK506), hydrocortisone, lidocaine, bimatoprost, botulinum toxin, tadalafil, an antibody, an antibody fragment, and the like or combinations thereof. BRIEF DESCRIPTION OF THE DRAWINGS [0009] For a fuller understanding of the nature and advantages of the present invention, reference should be made to the following detailed description taken in connection with the accompanying drawings, in which: [0010] FIGS. 1A-1B are graphs showing the percent of peptide flux relative to flux of peptide from the composition of peptide alone, for peptide compositions comprising a decoy molecule of hyaluronic acid with a molecular weight of 10,000 Da, 20,000 Da, 40,000 Da, 60,000 Da, or 100,000 Da, where flux was measured in skin with stratum corneum intact (FIG. 1A) and in skin with stratum corneum stripped (FIG. IB) and each composition was measured in duplicate (solid line, dashed line). [0011] FIG. 2 is a bar graph showing the percent increase of salicylate flux from compositions of salicylate and a decoy molecule of hyaluronic acid with molecular weights designated as small (5,000 Da to 10,000 Da), small to mid (10,000 Da to 20,000 Da), low to mid (20,000 Da to 30,000 Da), and mid (30,000 Da to 40,000 Da) over a composition with no decoy molecule. [0012] FIG. 3 is a bar graph showing the percent increase of hydrocortisone flux from compositions of hydrocortisone and a decoy molecule of hyaluronic acid with molecular weights designated as very small (5,000 Da to 10,000 Da), small (10,000 Da to 20,000 Da), mid (30,000 Da to 40,000 Da), and large (40,000 Da to 60,000 Da) over a composition with no decoy molecule. [0013] FIG. 4 is a bar graph showing the percent of lidocaine in porcine skin from topically applied compositions of lidocaine and an elastin decoy molecule with a molecular weight designated as very very small (2,000 Da to 5,000 Da), very small (5,000 Da to 10,000 Da), and small (10,000 Da to 20,000 Da) and no decoy molecule.
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