Patent EA-003959-B1 (EA)
Title: Antiparasitic formulations
Inventor: LUKAS TIMOTHY MICHAEL
IPC: A61P33/00
Filed: 1999-10-20
Abstract: 1. An antiparasitic formulation including: (a) 0.1-50% w/v an avermectin 13-monosaccharide 5-oxime of formula (1): wherein the dotted line in position 22-23 is optional bond, which is present and R<1> in that case is absent, or bond is absent and R<1> is H, OH, oxo or oximino, optionally substituted with C1-8 alkyl, R<2> is C1-8, C2-8 alkenyl, or C3-8 cycloalkyl or 3-6-membered heterocyclic ring, containing sulphur or oxygen atom, wherein said ring is saturated or partially or entirely saturated and optionally substituted with one or more C1-4 alkyl or halogen, R<3> is H or OH, R<4> is H or a group hydrolysable in vivo to compound, where R<4> is H R<5> is OH, optionally substituted with group hydrolysable in vivo to compound, R<5> is OH R<6> is H or C1-4alkyl, or R<6> is H and R<5> is amino, optionally substituted with at least one group, selected from C1-8 alkyl and C1-8 alkanoil, having activity against endo- and/or ecto-parasites; (b) 1-50% v/v a di(C2-4 glycol) mono(C1-4 alkyl) ether; (c) an optional antioxidant; and (d) an optional skin acceptable volatile solvent up to 100 v/v. 2. A formulation according to claim 1 wherein the amount of the di(C2-4 glycol) mono(C2-4alkyl) ether is in the range of about 1-20% v/v. 3. A formulation according to any preceding claim wherein the avermectin 13-monosaccharide 5 oxime has activity against both endo- and ectoparasites. 4. A formulation according to any preceding claim wherein the avermectin 13-monosaccharide 5-oxime is 5oximino-22,23-dihydro-25-cyclohexylavermectin B1 monosaccharide (selamectin). 5. A formulation according to any preceding claim wherein the di (C2-4 glycol) mono(C1-4 alkyl) ether is diethylene glycol monomethyl ether (DEGMME) or dipropylene glycol monomethyl ether (DPGMME). 6. A formulation according to claim 5 wherein, the glycol monomethyl ether is DPGMME. 7. A formulation according to any preceding claim wherein the skin-acceptable solvent is present and is ethanol at isopropanol. 8. A formulation according to any preceding claim wherein the skin-acceptable solvent is present and is isopropanol. 9. A formulation according to any preceding claim wherein the w/y to v/v ratio of active compound to di(C2-4 glycol) mono(C2-4alkyl) ether, wherein di(C2-4 glycol) mono(C2-4alkyl) ether is glycol monomethyl ether in the range (0.5 to 2) to 1. 10. A formulation according to any preceding claim wherein the w/y to v/v ratio of active compound to di(C2-4 glycol) mono(C2-4alkyl) ether, wherein di(C2-4 glycol) mono(C2-4alkyl) ether is glycol monomethyl ether in the range (0.7 to 1.4) to 1. 11. A formulation according to any preceding claim wherein the w/y to v/v ratio of active compound to di(C2-4 glycol) mono(C2-4alkyl) ether, wherein di(C2-4 glycol) mono(C2-4alkyl) ether is glycol monomethyl ether in the range (0.9 to 1.1) to 1. 12. A formulation according to any preceding claim wherein the w/y to v/v ratio of active compound to di(C2-4 glycol) mono(C2-4alkyl) ether, wherein di(C2-4 glycol) mono(C2-4alkyl) ether is glycol monomethyl ether is 1:1. 13. A formulation according to any preceding claim wherein the level of avermectin 13-monosaccharide 5 oxime in the total formulation is in the range 1% to 16%. 14. A formulation according to any preceding claim wherein the level of avermectin 13-monosaccharide 5 oxime in the total formulation is in the range 4% to 12%. 15. A formulation according to any preceding claim where the level of avermectin 13-monosaccharide 5 oxime in the total formulation is in the range 6% to 12%. 16. A formulation according to any preceding claim wherein the antioxidant is present, and is selected from propylgallate, BHA (2-t-butyl-4-methoxyphenol), and BHT (2,6-di-t-butyl-4-methylphenol). 17. A formulation according to any preceding claim wherein the antioxidant is present and is BHT. 18. A formulation according to claim 1 wherein the formulation consists of: (a) 5-oximino-22,23-dihydro-25-cyclohexylavermectin B1 monosaccharide (selamectin, at a level of 1% to 16% w/v); (b) DEGMME or DPGMME at 1 to 16% v/v, and at a w/v to v/v ratio of active compound to DEGMME/DPGMME of about 1:1; (c) optionally BHT at less than 0.1% w/v; and (d) isopropanol up to 100% v/v. 19. A formulation according to claim 18 which consists of: (a) 5-oximino-22,23-dihydro-25-cyclohexylavermectin B1 monosaccharide (selamectin), at a level of 6% to 12% w/v; (b) DEGMME or DPGMME 6 to 12% v/v, and at a w/v to v/v ratio of active compound to DEGMME/DPGMME of about 1:1; (c) optionally BHT (at less than 0.1% w/v), and, (d) isopropanol up to 100% v/v; 20. A formulation according to any one of claims 1 to 19 for use in medicine. 21. The use of a formulation according to any one of claims 1 to 19 in the manufacture of a medicament for the treatment of a condition caused by an endo- or ectoparasite.