US 20150297733A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0297733 A1 Oberegger et al. (43) Pub. Date: Oct. 22, 2015

(54) CONTROLLED RELEASE TOPICAL A647/22 (2006.01) FORMULATIONS AND A647/4 (2006.01) METHODS A6M 35/00 (2006.01) A647/26 (2006.01) (71) Applicant: TRIMEL BIOPHARMA SRL, A647/02 (2006.01) Durants, Christ Church (BB) A647/38 (2006.01) A647/32 (2006.01) (72) Inventors: Werner Oberegger, Waterdown (CA); A619/00 (2006.01) Paul José Pierre Marie Maes, Visé A647/10 (2006.01) (BE) (52) U.S. Cl. CPC ...... A61K 47/44 (2013.01); A61 K9/0014 (21) Appl. No.: 14/442,949 (2013.01); A61 K3I/568 (2013.01); A61 K 47/22 (2013.01); A6 IK 4 7/14 (2013.01); A6IK (22) PCT Filed: Nov. 14, 2013 47/0 3:38: A6 IK 47/26 38. A61 K 47/02 (2013.01); A61 K47/38 (2013.01); A61 K (86). PCT No.: PCT/B2O13AOO2913 47/32 (2013.01); A61M35/003 (2013.01) S371 (c)(1), (2) Date: May 14, 2015 (57) ABSTRACT O O The present invention relates to testosterone topical formula Related U.S. Application Data tions, especially high testosterone concentration formula (60) Provisional application No. 61/729,304, filed on Nov. tions, such as between about 6% to about 15% w/w or higher, 21, 2012, provisional application No. 61/726,564, for the controlled release of testosterone into the systemic filed on Nov. 14, 2012. circulation of males and females for providing constant effec tive testosterone blood levels, without inducing undesired Publication Classification testosterone spike in blood levels or testosterone transfer ence, following topical administration. The present invention (51) Int. Cl. also relates to methods and pre-filled multi-dose airless appli A6 IK 47/44 (2006.01) cator systems for pernasal administration of the nasal test A6 IK3I/568 (2006.01) osterone gels of the present invention

1. O Patent Application Publication Oct. 22, 2015 Sheet 1 of 29 US 2015/0297733 A1

FIG. 1 Patent Application Publication Oct. 22, 2015 Sheet 2 of 29 US 2015/0297733 A1

FG. 2 Patent Application Publication Oct. 22, 2015 Sheet 3 of 29 US 2015/0297733 A1

FG. 3 Patent Application Publication Oct. 22, 2015 Sheet 4 of 29 US 2015/0297733 A1

FG. 4 Patent Application Publication Oct. 22, 2015 Sheet 5 of 29 US 2015/0297733 A1

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Patent Application Publication Oct. 22, 2015 Sheet 11 of 29 US 2015/0297733 A1

Patent Application Publication Oct. 22, 2015 Sheet 12 of 29 US 2015/0297733 A1

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Time (hr) F.G. 14 Patent Application Publication Oct. 22, 2015 Sheet 14 of 29 US 2015/0297733 A1

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FIG. 16 Patent Application Publication Oct. 22, 2015 Sheet 15 of 29 US 2015/0297733 A1

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F.G. 18 Patent Application Publication Oct. 22, 2015 Sheet 16 of 29 US 2015/0297733 A1

Corpound Activity

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Compound Activity Control

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wrwa Preparation of Buik Ge. Mixing speed Add Active Mixture to

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