(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 2017/152129 A2 8 September 2017 (08.09.2017) P O P C T (51) International Patent Classification: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61K 9/00 (2006.01) A61K 47/12 (2006.01) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, A61K 31/19 (2006.01) A61K 47/10 (2017.01) KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, A61K 31/505 (2006.01) A61K 45/06 (2006.01) MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (21) International Application Number: RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, PCT/US20 17/020795 TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (22) International Filing Date: ZA, ZM, ZW. 3 March 2017 (03.03.2017) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (26) Publication Language: English TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (30) Priority Data: TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 62/303,333 3 March 2016 (03.03.2016) US DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (71) Applicant: OCULAR TECHNOLOGIES SARL SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, [CH/CH]; Route de la Corniche 3B, 1066 Epalinges (CH). GW, KM, ML, MR, NE, SN, TD, TG). (72) Inventor; and Declarations under Rule 4.17 : (71) Applicant : WEISS, Sidney L. [US/US]; 6 Dawn Lane, — as to applicant's entitlement to applyfor and be granted a Randolph, New Jersey 07869 (US). patent (Rule 4.1 7(H)) (74) Agent: REITER, Stephen E.; Kilpatrick Townsend & — as to the applicant's entitlement to claim the priority of the Stockton LLP, 1100 Peachtree Street, Suite 2800, Atlanta, earlier application (Rule 4.1 7(in)) Georgia 30309 (US). Published: (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, — without international search report and to be republished AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, upon receipt of that report (Rule 48.2(g)) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, < o- (54) Title: TREATMENT OF GLAUCOMA AND/OR RETINAL DISEASES AND FORMULATIONS USEFUL THEREFORE (57) Abstract: Provided herein are formulations for topical administration, such as ophthalmic formulations, and methods of using such formulations. In some aspects and embodiments the formulations may include a polyoxyl lipid or fatty acid, and/or a polyalkoxylated alcohol and may include nanomicelles. Also included are methods of treating or preventing diseases or conditions, such as ocular diseases or conditions. TREATMENT OF GLAUCOMA AND/OR RETINAL DISEASES AND FORMULATIONS USEFUL THEREFORE FIELD [0001] The present disclosure relates to the field of formulations for topical administration, such as ophthalmic formulations, and methods of using such formulations. BACKGROUND [0002] The information provided herein and references cited are provided solely to assist the understanding of the reader, and does not constitute an admission that any of the references or information is prior art to the present invention. [0003] United States Patent Application Nos US2010/0310462 and US2009/0092665 disclose drug delivery systems for ophthalmic use that have nanomicelles that include vitamin E TPGS. [0004] PCT publication number WO/2014/032026 also describes drug delivery systems for ophthalmic use. [0005] Travoprost involves a formulation for glaucoma or ocular hypertension that includes HCO-40 and a prostaglandin analog as the active ingredient. See dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=338e7ff4-0d91-4208-a45d-bfa2be52334d on the world-wide web. The active ingredient is present at 0.004%. The formulation includes propylene glycol and does not include nanomicelles. HCO-40 is present in Travoprost at 0.5%. See ema.europa.eu/docs/en GB/document library/EPAR - Product Informatioii/human/000665/WC500038389.pdf on the world-wide web. SUMMARY [0006] The present disclosure relates to topical formulations such as formulations suitable for ophthalmic administration of an active ingredient (the term active ingredient is used herein interchangably with the term active agent). Exemplary active ingredients include iloprost, macitentan,and the like, optionally in the further presence of one or more receptor tyrosine kinase (RTK) inhibitors (especially RTK inhibitors for retinal disease(s)), prostaglandins (e.g., latanoprost, travoprost, bimatoprost, iloprost, and the like), prostacyclins, ET-1 inhibitors (e.g., bosentan, ambrisentan, macitentan, sitaxentan, and the like), steroids, and the like, as well as combinations of any two or more thereof. [0007] In certain aspects and embodiments, the formulations of the present disclosure may include a polyoxyl lipid or fatty acid, and or a polyalkoxylated alcohol and may include nanomicelles. [0008] In certain aspects and embodiments as described herein, the formulations as described herein may have certain surprising features and advantages that could not have been predicted prior to the present disclosure. For example, formulations of the instant disclosure may be able to support a dose of an active ingredient (e.g., a receptor tyrosine kinase (RTK) inhibitor, a prostaglandin, a prostacyclin, an ET-1 inhibitor, a steroid, and the like, as well as combinations of any two or more thereof) that is surprisingly higher than many prior art formulations. [0009] The dose of active ingredient used in the formulations described herein may be selected based on various criteria, including the amount that the formulation can support, the desired dose for various therapeutic applications, etc. In this regard, in some embodiments the active ingredient (such as for ophthalmic administration), may be at least about 0.05%, or at least about 0.08%, or at least about 0.09%, or at least about 0.1%, or at least about 0.15%; or at least about 0.2%: or at least about 0.3%: or at least about 0.4%; or at least about 0.5%; or at least about 0.6%; or at least about 0.7%; or at least about 0.8%; or at least about 0.9%; or at least about 1.0%; or at least about 1.5%; or at least about 2%; or at least about 3%; or at least about 4%; or at least about 5%; or between 0.05 and 5%; or between 0.05 and 0.5%; or between 0.05 and 0.2%, or between 0.08 and 0 .12%; or between 0.1 and 0.5%, or between 0.5 and 1%, or between 0.5 and 1.5%; or between 1 and 5%; or between 2 and 4%; or between 4 and 6% of the formulation. [0010] In some embodiments the formulation has nanomicelles with a relatively increased entrapment efficiency; in such embodiments the active ingredient (for ophthalmic administration) may be at least about 0.05%, or at least about 0.08%, or at least about 0.09%, or at least about 0.1%, or at least about 0.15%; or at least about 0.2%: or at least about 0.3%: or at least about 0.4%; or at least about 0.5%; or at least about 0.6%; or at least about 0.7%; or at least about 0.8%; or at least about 0.9%; or at least about 1.0%; or at least about 1.5%; or at least about 2%; or at least about 3%; or at least about 4%; or at least about 5%; or between 0.05 and 5%; or between 0.05 and 0.5%; or between 0.05 and 0.2%, or between 0.08 and 0.12%; or between 0.1 and 0.5%, or between 0.5 and 1%, or between 0.5 and 1.5%; or between 1 and 5%; or between 2 and 4%; or between 4 and 6% of the formulation and is present in nanomicelles of the formulation. [0011] In certain aspects and embodiments, the formulations of the disclosure are surprisingly effective in dissolving and/or delivering active ingredient, without a need for organic solvents (such as propylene glycol) that can be an irritant when included in ophthalmic formulations. [0012] In some embodiments, the formulations of the present disclosure are surprisingly stable at high temperatures, for example, temperatures above about 40 degrees C. [0013] In some aspects and embodiments the nanomicellular nature of some formulations described herein allow for improved ocular tissue distribution. [0014] In certain aspects and embodiments, formulations as described herein are particularly suitable for anterior eye delivery, or posterior eye delivery, or anterior and posterior eye delivery. Moreover, the formulations of certain aspects and embodiments of the disclosure may have the surprising advantage of being adaptable to facilitate delivery of active ingredient(s) having various sizes or properties; for example, in certain embodiments in formulations that include a polyoxyl castor oil, HCO-60 could be used for active ingredients having relatively small molecule sizes and HCO-80 and/or HCO-100 could be used for relatively larger sized active ingredients. [0015] Accordingly, in a first aspect provided is an ophthalmic formulation that includes (1) iloprost, macitentan,and the like, optionally in the further presence of one or more additional active ingredients (e.g., a receptor tyrosine kinase (RTK) inhibitor, a prostaglandin, a prostacyclin, an ET-1 inhibitor, a steroid, and the like, as well as combinations of any two or more thereof), (2) a polyoxyl lipid or fatty acid and (3) a polyalkoxylated alcohol.