Formulations comprising antisense nucleotides to connexins
A therapeutic and/or cosmetic formulation comprising at least one anti-sense polynucleotide to a connexin protein together with a pharmaceutically acceptable carrier or vehicle is useful in site specific down regulation of connexin protein expression, particularly in reduction of neuronal cells death, wound healing, reduction of inflammation, decrease of scar formation and skin rejuvenation and thickening.
1. A pharmaceutical composition comprising a connexin 26 antisense polynucleotide and a nonionic polyoxyethylene-polyoxypropylene copolymer, wherein said connexin 26 antisense polynucleotide is an oligonucleotide provided in an amount sufficient for treatment of a wound.
2. A pharmaceutical composition according to claim 1 , which is formulated for topical administration.
3. A pharmaceutical composition according to claim 1 , which is formulated for sustained release administration.
4. A pharmaceutical composition according to claim 1 , formulated with a connexin antisense polynucleotide in an amount sufficient to downregulate the expression of a connexin protein in a mammal.
5. A pharmaceutical composition according to claim 1 , formulated with a connexin antisense polynucleotide in an amount sufficient to decrease cell death in a tissue of a mammal.
6. A pharmaceutical composition according to claim 1 , formulated with a connexin antisense polynucleotide in an amount sufficient to decrease inflammation in a tissue of a mammal.
7. A pharmaceutical composition according to claim 1 , formulated with a connexin antisense polynucleotide in an amount sufficient for treatment of a wound in a tissue of a mammal.
8. A pharmaceutical composition of claim 1 , wherein said connexin antisense polynucleotide is about 12 to about 40 nucleotides in length.
9. A pharmaceutical composition of claim 1 , wherein said connexin antisense polynucleotide is about 20 nucleotides in length.
10. A pharmaceutical composition of claim 1 , wherein said connexin antisense polynucleotide is about 30 nucleotides in length.
11. A pharmaceutical composition of claim 1 , wherein said connexin antisense polynucleotide is about 40 nucleotides in length.
12. A pharmaceutical composition of claim 8 , wherein said connexin antisense polynucleotide comprises SEQ ID NO: 4.
13. A pharmaceutical composition of claim 1 , formulated as a cream, ointment, gel, emulsion, or paint.
14. A pharmaceutical composition of claim 13 , formulated as a gel.
15. A pharmaceutical composition of claim 14 , formulated as a gel for topical administration.
16. A pharmaceutical composition of claim 1 , wherein the polynucleotide is formulated for parenteral, intramuscular, intracerebral, intravenous, subcutaneous or transdermal administration.
17. A pharmaceutical composition comprising a connexin 26 antisense polynucleotide in an amount effective for treatment of a wound in a mammal and a nonionic polyoxyethylene-polyoxypropylene copolymer, wherein said connexin 26 antisense polynucleotide is an oligonucleotide.
18. A pharmaceutical composition according to claim 1 or 17 , wherein said nonionic polyoxyethylene-polyoxypropylene copolymer is in the form of a gel.
19. A pharmaceutical composition according to claim 1 or 17 , wherein said nonionic polyoxyethylene-polyoxypropylene copolymer is Pluronic F-127.
20. A pharmaceutical composition according to claim 17 , which is formulated for sustained release of the antisense polynucleotide.
21. A pharmaceutical composition according to claim 1 or 17 , which further includes a surfactant or transdermal penetration agent.
22. A pharmaceutical composition according to claim 1 or 17 , wherein said composition is formulated with an isotonic saline solution.
23. A pharmaceutical composition according to claim 1 or 17 , wherein said composition is formulated with phosphate buffered saline.
24. A pharmaceutical composition according to claim 18 , wherein the composition is formulated for topical administration.
25. A pharmaceutical composition according to claim 19 , wherein the composition is formulated for topical administration.
26. A pharmaceutical composition according to claim 20 , wherein the composition is formulated for topical administration.
27. A pharmaceutical composition according to claim 21 , wherein the composition is formulated for topical administration.
28. A pharmaceutical composition according to claim 1 or 17 , wherein said nonionic polyoxyethylene-polyoxypropylene copolymer is poloxamer 407.
29. A pharmaceutical composition according to any of claims 1 , 2 , 4 - 28 , wherein said polynucleotide is an unmodified phosphodiester oligomer.
30. A pharmaceutical composition according to any of claims 1 , 2 , 4 - 28 , wherein said antisense polynucleotide is chemically modified.