Non-protein clostridial toxin compositions

Abstract

A pharmaceutical composition describing a stable active ingredient of clostridium toxin. The composition may be a liquid or solid composition and includes surfactants and antioxidants. In some specific examples, the composition includes surfactants selected from poloxamer and polysorbate; antioxidants selected from methionine, N-acetycysteine, ethylenediaminetetraacetic acid, and combinations thereof; and optionally, tensioning agents and / or lyoprotectors selected from, for example, trehalose and sucrose.

Claims

1. A solid pharmaceutical composition free of protein excipients, the composition comprising: (i) Clostridium botulinum toxin active ingredient; (ii) poloxamer surfactant; and (iii) 0.1 to 0.3% by weight of methionine; wherein the solid pharmaceutical composition is suitable for subcutaneous or intramuscular injection after being reconstituted with an aqueous carrier; and wherein the solid pharmaceutical composition is stable at 40°C for at least 1 month; and wherein the solid pharmaceutical composition does not contain polysorbate.

2. The solid pharmaceutical composition of claim 1, wherein the active ingredient of Clostridium botulinum toxin is Clostridium botulinum toxin serotype A (BoNT / A).

3. The solid pharmaceutical composition of claim 1, wherein the poloxamer surfactant comprises poloxamer 188.

4. A solid pharmaceutical composition as claimed in claim 1, wherein the solid pharmaceutical composition further comprises a disaccharide.

5. The solid pharmaceutical composition of claim 4, wherein the disaccharide is selected from sucrose or trehalose.

6. The solid pharmaceutical composition of claim 4, wherein the disaccharide comprises trehalose.

7. The solid pharmaceutical composition of claim 1, wherein the aqueous carrier comprises a buffer solution.

8. The solid pharmaceutical composition of claim 7, wherein the buffer solution comprises histidine buffer.

9. The solid pharmaceutical composition of claim 1, wherein the Clostridium botulinum toxin active ingredient comprises a 150 kDa neurotoxin unrelated to the complex protein.

10. A solid pharmaceutical composition as claimed in claim 1, wherein the solid pharmaceutical composition further comprises a salt.

11. The solid pharmaceutical composition of claim 10, wherein the salt comprises NaCl.

12. The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin active ingredient; (ii) 0.5 to 8% by weight of poloxamer surfactant; and (iii) 0.1 to 0.3% by weight of methionine.

13. The solid pharmaceutical composition of claim 12, wherein the Clostridium botulinum toxin active ingredient is Clostridium botulinum toxin serotype A (BoNT / A).

14. The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin active ingredient; (ii) histidine buffer; (iii) 0.5 to 8% by weight of poloxamer surfactant; and (iv) 0.1 to 0.3% by weight of methionine.

15. The solid pharmaceutical composition of claim 14, wherein the Clostridium botulinum toxin active ingredient is Clostridium botulinum toxin serotype A (BoNT / A).

16. The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin active ingredient; (ii) histidine buffer; (iii) 0.5 to 8% by weight of poloxamer 188; and (iv) 0.1 to 0.3% by weight of methionine.

17. The solid pharmaceutical composition of claim 16, wherein the Clostridium botulinum toxin active ingredient is Clostridium botulinum toxin serotype A (BoNT / A).

18. The solid pharmaceutical composition of claim 5, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin active ingredient; (ii) histidine buffer; (iii) 0.5 to 8% by weight of poloxamer 188; (iv) 0.1 to 0.3% by weight of methionine; and (v) NaCl.

19. The solid pharmaceutical composition of claim 18, wherein the Clostridium botulinum toxin active ingredient is Clostridium botulinum toxin serotype A (BoNT / A).

20. The solid pharmaceutical composition of claim 8, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin active ingredient; (ii) histidine buffer; (iii) 0.5 to 8% by weight of poloxamer 188; (iv) 0.1 to 0.3% by weight of methionine; and (v) trehalose.

21. The solid pharmaceutical composition of claim 20, wherein the Clostridium botulinum toxin active ingredient is Clostridium botulinum toxin serotype A (BoNT / A).

22. The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin serotype A (BoNT / A); (ii) 20 mM histidine buffer; (iii) 4% by weight poloxamer 188; (iv) 0.2% by weight methionine; and (v) 8% by weight trehalose.

23. The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin serotype A (BoNT / A); (ii) 20 mM histidine buffer; (iii) 4% by weight poloxamer 188; (iv) 0.2% by weight methionine; and (v) 2% by weight trehalose.

24. The solid pharmaceutical composition of claim 1, wherein the solid pharmaceutical composition comprises: (i) Clostridium botulinum toxin serotype A (BoNT / A); (ii) 20 mM histidine buffer; (iii) 4% by weight poloxamer 188; (iv) 0.2% by weight methionine; and (v) 8% by weight trehalose.

25. A solid pharmaceutical composition as claimed in any of claims 1 to 24, wherein the solid pharmaceutical composition is in the form of freeze-dried or vacuum-dried form.