Claims for Patent: 11,207,332

Summary for Patent: 11,207,332

Title:	Enzymatic process for obtaining 17 .alpha.-monoesters of cortexolone and/or its 9,11-dehydroderivatives
Abstract:	The present invention refers to a new enzymatic process for obtaining 17.alpha.-monoesters of cortexolone and/or its 9,11-dehydroderivatives starting from the corresponding 17.alpha.,21-diesters which comprises an enzymatic alcoholysis reaction. Furthermore, the present invention refers to new crystalline forms of cortexolone-17.alpha.-propionate and 9,11-dehydro-cortexolone 17.alpha.-butanoate.
Inventor(s):	Ajani; Mauro (Lainate, IT), Moro; Luigi (Cairate, IT)
Assignee:	Cassiopea S.P.A. (Lainate, IT)
Application Number:	16/686,738
Patent Claims:	1. A composition comprising: a) crystalline form III of cortexolone-17.alpha.-propionate characterized by a DRX spectrum as represented in FIG. 7, 10, or 13, or a DRX spectrum with at least peaks at about: 6.2, 12.6, 14.1, 14.3, 16.0, 22.4, and 23.7 degrees 2theta, or a DSC spectrum as represented in FIG. 8, 11, or 14, or an IR spectrum as shown in FIG. 9, 12, or 15; and b) crystalline form IV of cortexolone-17.alpha.-propionate characterized by a DRX spectrum as represented in FIG. 28, or a DRX spectrum with at least peaks at about: 4.8, 12.9, 14.4, 15.8, 16, 19.3, and 19.5 degrees 2theta. 2. The composition of claim 1, further comprising at least one physiologically acceptable excipient. 3. The composition of claim 2, wherein the at least one physiologically acceptable excipient is propylene glycol, cetylic alcohol, glyceryl monostearate, liquid paraffin, or a combination of any of the foregoing. 4. The composition of claim 2, further comprising mixed tocopherols, polysorbate 80, or a combination thereof. 5. The composition of claim 2, wherein the composition is in the form of a tablet, capsule, powder, pellet, suspension, emulsion, cream, gel, ointment, lotion, or paste. 6. The composition of claim 2, wherein the composition is in the form of a solid, semi-solid, or a paste. 7. The composition of claim 5, wherein the composition is in the form of a cream. 8. The composition of claim 7, wherein the composition further comprises solubilized cortexolone-17.alpha.-propionate. 9. The composition of claim 8, wherein the solubilized cortexolone-17.alpha.-propionate is present in the composition in a concentration of from 0.1 to 2% by weight of the composition. 10. The composition of claim 8, wherein the solubilized cortexolone-17.alpha.-propionate, crystalline form III of cortexolone-17.alpha.-propionate, and crystalline form IV of cortexolone-17.alpha.-propionate together comprise 0.1 to 2% by weight of the composition or comprise 0.2 to 1% by weight of the composition. 11. A method of treating a pathology affecting the skin and/or the cutaneous appendages, wherein the pathology affecting the skin and/or the cutaneous appendages is acne, androgenetic alopecia, hirsutism, or seborrheic dermatitis, the method comprising administering to a subject in need thereof an effective amount of a composition comprising a) crystalline form III of cortexolone-17.alpha.-propionate characterized by a DRX spectrum as represented in FIG. 7, 10, or 13, or a DRX spectrum with at least peaks at about: 6.2, 12.6, 14.1, 14.3, 16.0, 22.4, and 23.7 degrees 2theta, or a DSC spectrum as represented in FIG. 8, 11, or 14, or an IR spectrum as shown in FIG. 9, 12, or 15; and; b) crystalline form IV of cortexolone-17.alpha.-propionate characterized by a DRX spectrum as represented in FIG. 28, or a DRX spectrum with at least peaks at about: 4.8, 12.9, 14.4, 15.8, 16, 19.3, and 19.5 degrees 2theta. 12. The method of claim 11, wherein the administering comprises topically applying the composition. 13. The method of claim 12, wherein the pathology affecting the skin and/or the cutaneous appendages is acne. 14. The method of claim 12, wherein the pathology affecting the skin and/or the cutaneous appendages is androgenetic alopecia. 15. The method of claim 12, wherein the pathology affecting the skin and/or the cutaneous appendages is hirsutism. 16. The method of claim 12, wherein the pathology affecting the skin and/or the cutaneous appendages is seborrheic dermatitis. 17. A method of treating a pathology affecting the skin and/or the cutaneous appendages, wherein the pathology affecting the skin and/or the cutaneous appendages is acne, androgenetic alopecia, hirsutism, or seborrheic dermatitis, the method comprising administering to a subject in need thereof an effective amount of a composition comprising: a) water; b) at least one physiologically acceptable excipient; c) crystalline form III of cortexolone-17.alpha.-propionate characterized by a DRX spectrum as represented in FIG. 7, 10, or 13, or a DRX spectrum with at least peaks at about: 6.2, 12.6, 14.1, 14.3, 16.0, 22.4, and 23.7 degrees 2theta, or a DSC spectrum as represented in FIG. 8, 11, or 14, or an IR spectrum as shown in FIG. 9, 12, or 15; and d) crystalline form IV of cortexolone-17.alpha.-propionate characterized by a DRX spectrum as represented in FIG. 28, or a DRX spectrum with at least peaks at about: 4.8, 12.9, 14.4, 15.8, 16, 19.3, and 19.5 degrees 2theta. 18. The method of claim 17, wherein the administering comprises topically applying the composition. 19. The method of claim 18, wherein the pathology affecting the skin and/or the cutaneous appendages is acne. 20. The method of claim 18, wherein the at least one physiologically acceptable excipient is propylene glycol, cetylic alcohol, glyceryl monostearate, liquid paraffin, or a combination of any of the foregoing.