# US 2017/0281644 A1 · Formulations of testosterone and methods of treatment therewith > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2017/0281644 A1 - Document ID: US20170281644A1 - Status: Published application - Kind: A1 - Application number: 15/507,246 - Filed: 2015-08-28 - Published: 2017-10-05 - Earliest claimed: 2014-08-28 - Assignees: Board of Regents, The University of Texas System; Medcara Pharmaceuticals, LLC - Applicants: Board of Regents, the University of Texas System; Medcara Pharmaceuticals, LLC - Inventors: Robert A. JOSEPHS; Craig HERMAN - Web page: https://patentgrep.com/patent/US20170281644A1 ## CPC - A61K 31/5685: having an oxo group in position 17, e.g. androsterone - A61K 9/0043: {Nose} - A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} - A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)} - A61K 31/568: substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone - A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) - A61P 25/00: Drugs for disorders of the nervous system - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present disclosure relates to novel pharmaceutical composition for the administration of testosterone or testosterone derivatives. The present disclosure also provides methods of treatment of diseases and disorders associated with fear and anxiety, a decrease in libido, or hypogonadism. ## Claims ### Claim 1 A pharmaceutical composition comprising the following components dissolved in an aqueous solution: (A) a compound of the formula: wherein: R1 is hydrogen, acyl(C≦12), or substituted acyl(C≦12); (B) a first additive substantially comprised of a compound of the formula: wherein: R2, R3, and R4 are each independently selected from alkyl(C≦12), alkenyl(C≦12), alkynyl(C≦12), or a substituted version of any of these groups; and (C) a second additive substantially comprised of a compound of the formula: wherein: x, y, z, a, b, and c are each independently a number selected from 0-40 provided that at least one of x, y, z, a, b, or c is not 0; and m and n are each independently selected from 0, 1, or 2. ### Claim 2 (depends on 1) The composition of claim 1, wherein R1 is acyl(C≦12). ### Claim 3 (depends on 2) The composition of claim 2, wherein R1 is ### Claim 4 (depends on 1, 2, 3) The composition according to any one of claims 1-3, wherein R2 is alkyl(C≦12) or substituted alkyl(C≦12). ### Claim 5 (depends on 4) The composition of claim 4, wherein R2 is alkyl(C6-12). ### Claim 6 (depends on 4, 5) The composition of either claim 4 or claim 5, wherein R2 is octyl or decyl. ### Claim 7 (depends on 1, 2, 3, 4, 5, 6) The composition according to any one of claims 1-6, wherein R3 is alkyl(C≦12) or substituted alkyl(C≦12). ### Claim 8 (depends on 7) The composition of claim 7, wherein R3 is alkyl(C6-12). ### Claim 9 (depends on 7, 8) The composition of either claim 7 or claim 8, wherein R3 is octyl or decyl. ### Claim 10 (depends on 1, 2, 3, 4, 5, 6) The composition according to any one of claims 1-6, wherein R4 is alkyl(C≦12) or substituted alkyl(C≦12). ### Claim 11 (depends on 10) The composition of claim 10, wherein R4 is alkyl(C6-12). ### Claim 12 (depends on 10, 11) The composition of either claim 10 or claim 11, wherein R4 is octyl or decyl. ### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) The composition according to any one of claims 1-12, wherein one of R2, R3, and R4 is decyl and the other two of R2, R3, and R4 are octyl. ### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The composition according to any one of claims 1-13, wherein the composition comprises between 0.1% to about 5% by weight of component (A). ### Claim 15 (depends on 14) The composition of claim 14, wherein the composition comprises between about 1% to about 3% by weight of component (A). ### Claim 16 (depends on 14, 15) The composition of either claim 14 or claim 15, wherein the composition comprises about 1.2% by weight of component (A). ### Claim 17 (depends on 14, 15) The composition of either claim 14 or claim 15, wherein the composition comprises about 2.2% by weight of component (A). ### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The composition according to any one of claims 1-16, wherein the composition comprises between about 1% to about 10% by weight of component (B). ### Claim 19 (depends on 18) The composition of claim 18, wherein the composition comprises between about 3% to about 7% by weight of component (B). ### Claim 20 (depends on 18, 19) The composition of either claim 18 or claim 19, wherein the composition comprises from about 4.5% to about 5.5% by weight of component (B). ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The composition according to any one of claims 1-16, wherein the composition comprises between about 10% to about 20% by weight of component (B). ### Claim 22 (depends on 21) The composition of claim 21, wherein the composition comprises between about 12% to about 16% by weight of component (B). ### Claim 23 (depends on 21, 22) The composition of either claim 21 or claim 22, wherein the composition comprises from about 14% to about 15% by weight of component (B). ### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The composition according to any one of claims 1-20, wherein the composition comprise about 15% to about 40% by weight of component (C). ### Claim 25 (depends on 24) The composition of claim 24, wherein the composition comprises about 15% to about 30% by weight of component (C). ### Claim 26 (depends on 24, 25) The composition of either claim 24 or claim 25, wherein the composition comprises from about 22% to about 26% by weight of component (C). ### Claim 27 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26) The composition according to any one of claims 1-26, wherein the composition comprises from about 50% to about 90% by weight of water. ### Claim 28 (depends on 27) The composition of claim 27, wherein the composition comprises from about 60% to about 80% by weight of water. ### Claim 29 (depends on 27, 28) The composition of either claim 27 or claim 28, wherein the composition comprises from about 68% to about 72% by weight of water. ### Claim 30 (depends on 27) The composition of claim 27, wherein the composition comprises from about 50% to about 70% by weight of water. ### Claim 31 (depends on 30) The composition of claim 30, wherein the composition comprises from about 55% to about 60% by weight of water. ### Claim 32 A pharmaceutical composition comprising a testosterone ester(C≦12), water, and a first additive. ### Claim 33 (depends on 32) The composition of claim 32, wherein the testosterone ester(C≦12) is testosterone propionate. ### Claim 34 (depends on 32, 33) The composition of either claim 32 or claim 33, wherein the water is distilled water. ### Claim 35 (depends on 32, 33, 34) The composition according to any one of claims 32-34, wherein the first additive is a reaction mixture from the reaction of castor oil with ethylene oxide. ### Claim 36 (depends on 35) The composition of claim 35, wherein the reaction comprises a molar ratio of ethylene oxide to castor oil of about 35:1. ### Claim 37 (depends on 35) The composition of claim 35, wherein the first additive is a Cremophor® composition. ### Claim 38 (depends on 37) The composition of claim 37, wherein the first additive is Cremophor® 35. ### Claim 39 (depends on 32, 33, 34, 35, 36, 37, 38) The composition according to any one of claim 32-38, wherein the composition further comprises a second additive. ### Claim 40 (depends on 39) The composition of claim 39, wherein the second additive is a caprylic/capric triglyceride. ### Claim 41 (depends on 40) The composition of claim 40, wherein the second additive is a dicaprylic acid and monocarpic triglyceride. ### Claim 42 (depends on 39) The composition of claim 39, wherein the second additive is a Neobee® medium chain triglyceride composition. ### Claim 43 (depends on 42) The composition of claim 42, wherein the second additive is Neobee® M-5. ### Claim 44 (depends on 39, 40, 41, 42, 43) The composition according to any one of claims 39-43, wherein the second additive comprises from about 1% to about 10% by weight of the composition. ### Claim 45 (depends on 44) The composition of claim 44, wherein the second additive comprises from about 4.5% to about 5.5% by weight of the composition. ### Claim 46 (depends on 39, 40, 41, 42, 43) The composition according to any one of claims 39-43, wherein the second additive comprises from about 10% to about 20% by weight of the composition. ### Claim 47 (depends on 46) The composition of claim 46, wherein the second additive comprises from about 14% to about 16% by weight of the composition. ### Claim 48 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43) The composition according to any one of claims 32-43, wherein the testosterone ester(C≦12) comprises from about 0.1% to about 5% by weight of the composition. ### Claim 49 (depends on 48) The composition of claim 48, wherein the testosterone ester(C≦12) is about 1.2% by weight of the composition. ### Claim 50 (depends on 48) The composition of claim 48, wherein the testosterone ester(C≦12) is about 2.2% by weight of the composition. ### Claim 51 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50) The composition according to any one of claims 32-50, wherein the water comprises from about 65% to about 75% by weight of the composition. ### Claim 52 (depends on 51) The composition of claim 51, wherein the water is from about 68% to about 72% by weight of the composition. ### Claim 53 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50) The composition according to any one of claims 32-50, wherein the water comprises from about 55% to about 65% by weight of the composition. ### Claim 54 (depends on 53) The composition of claim 53, wherein the water comprises from about 57% to about 60% by weight of the composition. ### Claim 55 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52) The composition according to any one of claims 32-52, wherein the first additive comprises from about 15% to about 26% by weight of the composition. ### Claim 56 (depends on 55) The composition of claim 55, wherein the first additive is from about 22% to about 26% by weight of the composition. ### Claim 57 A pharmaceutical composition comprising about 1.2% by weight testosterone propionate, about 69.8% by weight distilled water, about 5.0% by weight Neobee® M-5, and about 24% by weight Cremophor® EL. ### Claim 58 A pharmaceutical composition comprising about 2.2% by weight testosterone propionate, about 58.7% by weight distilled water, about 14.3% by weight Neobee® M-5, and about 24.8% by weight Cremophor® EL. ### Claim 59 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57) The composition according to any one of claims 1-57, wherein the composition is formulated for administration nasally. ### Claim 60 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57) The composition according to any one of claims 1-57, wherein the composition further comprises a preservative. ### Claim 61 (depends on 60) The composition of claim 60, wherein the composition comprises from about 0.01% by weight to about 5% by weight of the preservative. ### Claim 62 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61) The composition according to any one of claims 1-61, wherein the composition is sterilized. ### Claim 63 (depends on 62) The composition of claim 62, wherein the composition is sterilized by filtration. ### Claim 64 (depends on 63) The composition of claim 63, wherein the composition is sterilized by filtration with a Tuffryn® filter. ### Claim 65 (depends on 64) The composition of claim 64, wherein the Tuffryn® filter is a 0.22 micron Tuffryn® filter. ### Claim 66 A method of treating a disease or disorder in a patient in need thereof comprising nasally administering to the patient a therapeutically effective amount of testosterone. ### Claim 67 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66) The method of claim 66, wherein the testosterone is comprised in a composition according to any one of claims 1-65. ### Claim 68 (depends on 66, 67) The method of either claim 66 or claim 67, wherein the disease or disorder is a disease or disorder associated with fear and anxiety. ### Claim 69 (depends on 68) The method of claim 68, wherein the disease or disorder is a disorder of the fear processing system. ### Claim 70 (depends on 66, 67, 68, 69) The method according to any one of claims 66-69, wherein the disease or disorder is anxiety disorder, major depressive disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder, social phobia, non-social phobia, social anxiety disorder, or obsessive compulsive disorder. ### Claim 71 (depends on 70) The method of claim 70, wherein the disease or disorder is post-traumatic stress disorder. ### Claim 72 (depends on 70) The method of claim 70, wherein the disease or disorder is major depressive disorder. ### Claim 73 (depends on 70) The method of claim 70, wherein the disease or disorder is an anxiety disorder. ### Claim 74 (depends on 70) The method of claim 70, wherein the disease or disorder is a generalized anxiety disorder. ### Claim 75 (depends on 70) The method of claim 70, wherein the disease or disorder is a panic disorder. ### Claim 76 (depends on 70) The method of claim 70, wherein the disease or disorder is a social phobia. ### Claim 77 (depends on 70) The method of claim 70, wherein the disease or disorder is a non-social phobia. ### Claim 78 (depends on 70) The method of claim 70, wherein the disease or disorder is a social anxiety disorder. ### Claim 79 (depends on 70) The method of claim 70, wherein the disease or disorder is an obsessive compulsive disorder. ### Claim 80 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79) The method according to any one of claims 66-79, wherein the method comprises administering a second therapeutic agent. ### Claim 81 (depends on 80) The method of claim 80, wherein the second therapeutic agent is a second pharmaceutical agent, psychotherapy, or cognitive behavioral therapy. ### Claim 82 (depends on 81) The method of claim 81, wherein the second pharmaceutical agent is cortisol. ### Claim 83 (depends on 80, 81) The method of either claim 80 or claim 81, wherein the method leads to the reduction of one or more symptoms of an anxiety or fear related disease or disorder. ### Claim 84 (depends on 66, 67) The method of either claim 66 or claim 67, wherein the disease or disorder is associated with a deficiency in testosterone. ### Claim 85 (depends on 84) The method of claim 84, wherein the deficiency in testosterone leads to decreased libido. ### Claim 86 (depends on 85) The method of claim 85, wherein the decreased libido is self reported. ### Claim 87 (depends on 85) The method of claim 85, wherein the decreased libido results in the patient having comparatively low or no libido. ### Claim 88 (depends on 85, 86, 87) The method according to any one of claims 85-87, wherein the decreased libido is in a male or female patient. ### Claim 89 (depends on 88) The method of claim 88, wherein the patient is female. ### Claim 90 (depends on 88) The method of claim 88, wherein the patient is male. ### Claim 91 (depends on 66) The method of claim 66, wherein the disease or disorder is associated with hypogonadism. ### Claim 92 (depends on 66) The method of claim 66, wherein the patient has erectile dysfunction. ### Claim 93 (depends on 91, 92) The method of claim 91 or claim 92, wherein the patient is a male. ### Claim 94 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92) The method according to any one of claims 66-92, wherein the patient is human. ### Claim 95 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94) The method according to any one of claims 66-94, wherein the therapeutically effective amount is administered in a single dose per day. ### Claim 96 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94) The method according to any one of claims 66-94, wherein the therapeutically effective amount is administered in two or more doses per day. ### Claim 97 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94) The method according to any one of claim 66-94, wherein the therapeutically effective amount is administered as needed. ### Claim 98 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96) The method according to any one of claims 66-96, wherein the patient is treated at least a second time. ### Claim 99 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98) The method according to any one of claims 66-98, wherein the patient is treated over a period of 1 week to 6 months. ### Claim 100 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98) The method according to any one of claims 66-98, wherein the patient is treated for a period of 6 months to 5 years.