Compositions of activated botulinum toxin type B
The present invention relates to pharmaceutical compositions of activated botulinum toxin type B. In particular, the present invention relates to botulinum toxin type B pharmaceutical compositions wherein at least 75% of said botulinum toxin type B is activated—i.e., “nicked”. The invention also relates to a process of activating botulinum toxin type B wherein at least 75% of said botulinum toxin type B is nicked. The invention further relates to methods for the treatment of a variety of neuromuscular diseases, pain, inflammatory and cutaneous disorders comprising administering a pharmaceutical composition of activated botulinum toxin type B wherein at least 75% of said botulinum toxin type B is nicked.
1 . A pharmaceutical composition comprising:
(a) activated botulinum toxin type B; and
(b) at least one excipient;
wherein at least 75% of said botulinum toxin type B is nicked.
2 . The pharmaceutical composition of claim 1 , wherein greater than 75 percent of said botulinum toxin B is nicked.
3 . The pharmaceutical composition of claim 1 , wherein approximately about 75 percent to about 85 percent of said botulinum toxin type B is nicked.
4 . The pharmaceutical composition of claim 1 , wherein greater than 80 percent of said botulinum toxin B is nicked.
5 . The pharmaceutical composition of claim 1 , wherein greater than 85 percent of said botulinum toxin B is nicked.
6 . The pharmaceutical composition of claim 1 , wherein approximately about 85 percent to about 95 percent of said botulinum toxin type B is nicked.
7 . The pharmaceutical composition of claim 1 , wherein greater than 90 percent of said botulinum toxin B is nicked.
8 . The pharmaceutical composition of claim 1 , wherein approximately about 95 percent to about 100 percent of said botulinum toxin type B is nicked.
9 . The pharmaceutical composition of claim 1 , wherein greater than 95 percent of said botulinum toxin B is nicked.
10 . The pharmaceutical composition of claim 1 , wherein greater than 99 percent of said botulinum toxin B is nicked.
11 . The pharmaceutical composition of claim 1 , wherein said at least one excipient is selected from the group consisting of: buffers, carriers, stabilizers, preservatives, diluents, vehicles, bulking agents, albumins, gelatins, collagens, proteins, polysaccharides, metals, non-oxidizing amino acid derivatives, and sodium chloride.
12 . The pharmaceutical composition of claim 1 , wherein said at least one excipient is albumin.
13 . The pharmaceutical composition of claim 1 , wherein said at least one excipient is a buffer.
14 . The pharmaceutical composition of claim 13 , wherein said buffer is a succinate buffer.
15 . A process of activating botulinum toxin type B, comprising the stages of: cell growth, activation, purification, and dilution; wherein at least one protease is administered to a volume of said botulinum toxin type B, and wherein the levels of nicked botulinum toxin type B is increased to at least 75%.
16 . The process of claim 15 , wherein said at least one protease administered is selected from the group consisting of: trypsin, immobilized TPCK-trypsin, metalloproteases, endogenous proteases, bacterial proteases, and gastric proteases.
17 . The process of claim 16 , wherein said protease administered is trypsin.
18 . The process of claim 15 , wherein greater than 75 percent of said botulinum toxin B is nicked.
19 . The process of claim 15 , wherein approximately about 75 percent to about 85 percent of said botulinum toxin type B is nicked.
20 . The process of claim 15 , wherein greater than 80 percent of said botulinum toxin B is nicked.
21 . The process of claim 15 , wherein greater than 85 percent of said botulinum toxin B is nicked.
22 . The process of claim 15 , wherein approximately about 85 percent to about 95 percent of said botulinum toxin type B is nicked.
23 . The process of claim 15 , wherein greater than 90 percent of said botulinum toxin B is nicked.
24 . The process of claim 15 , wherein approximately about 95 percent to about 100 percent of said botulinum toxin type B is nicked.
25 . The process of claim 15 , wherein greater than 95 percent of said botulinum toxin B is nicked.
26 . The process of claim 15 , wherein greater than 99 percent of said botulinum toxin B is nicked.
27 . A method of treating a disorder, comprising administering to a patient in need thereof, a pharmaceutical composition comprising:
(a) activated botulinum toxin type B; and
(b) at least one excipient;
wherein at least 75% of said botulinum toxin type B is nicked.
28 . The method of claim 27 , wherein approximately about 75 percent to about 85 percent of said botulinum toxin type B in said pharmaceutical composition is nicked.
29 . The method of claim 27 , wherein approximately about 85 percent to about 95 percent of said botulinum toxin type B in said pharmaceutical composition is nicked.
30 . The method of claim 27 , wherein approximately about 95 percent to about 100 percent of said botulinum toxin type B in said pharmaceutical composition is nicked.
31 . The method of claim 27 , wherein said at least one excipient of said pharmaceutical composition is selected from the group consisting of: buffers, carriers, stabilizers, preservatives, diluents, vehicles, bulking agents, albumins, gelatins, collagens, proteins, polysaccharides, metals, non-oxidizing amino acid derivatives, and sodium chloride.
32 . The method of claim 31 , wherein said at least one excipient of said pharmaceutical composition is albumin.
33 . The method of claim 31 , wherein said at least one excipient of said pharmaceutical composition is a buffer.
34 . The method of claim 33 , wherein said buffer is a succinate buffer.
35 . The method of claim 27 , wherein said disorder is selected from the group consisting of: ophthalmologic disorders, neuromuscular diseases, otorhinolaryngological disorders, urogenital disorders, dermatological disorders, pain disorders, inflammatory disorders, secretory disorders, and cutaneous disorders or cosmetic treatment.