Methods and Compositions for Treating Skin Conditions Associated With Vascular Hyper-reactivity
The present invention provides a methods and compositions for treating a patient having a skin condition characterized by vascular hyper-reactivity, such as chronic or episodic flushing or blushing, and/or rosacea. The method comprises applying a topical composition to affected areas of the patient's skin. The topical composition comprises an effective amount of a botulinum neurotoxin for decreasing vasodilation in cutaneous microvasculature, and a carrier for effectively transporting the botulinum toxin to the cutaneous microvasculature. The invention thereby provides a safe, effective, comfortable, and/or convenient manner of treating vascular hyper-reactivity in skin.
1 - 48 . (canceled)
49 . A method for treating a patient having a skin condition characterized by cutaneous vascular hyper-reactivity, comprising:
administering a composition to the affected area(s) of the patient's skin, the composition comprising an effective amount of a botulinum neurotoxin and a positively charged carrier non covalently associated with the botulinum toxin, wherein the administration of the composition for decreases vasodilation in the cutaneous microvasculature, and a carrier for transporting the botulinum toxin to the cutaneous microvasculature.
50 . The method of claim 49 , wherein the condition is flushing or blushing.
51 . The method of claim 49 , wherein the patient has rosacea.
52 . The method of claim 51 , wherein the rosacea is one or more of erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and/or ocular rosacea.
53 . The method of claim 51 , wherein the patient has one or more symptoms of rosacea selected from erythema, flushing, blushing, telangiectasias, papules, pustules, rhinophyma, burning sensations, and itching sensations.
54 . The method of claim 51 , wherein the patient has rosacea, but does not have rhinophyma.
55 . The method of claim 49 , wherein the botulinum neurotoxin is a purified botulinum neurotoxin having a 100 kDa heavy chain and a 50 kDa light chain.
57 . The method of claim 49 , wherein the botulinum neurotoxin is from a Clostridium botulinum type A-producing strain.
58 . The method of claim 57 , wherein the type A-producing strain is type A1, is type A2, or type A3.
59 . The method of claim 49 , wherein the botulinum neurotoxin is type B or type C.
60 . The method of any one of claims 1 to 14 , wherein the carrier is peptide.
61 . The method of claim 60 , wherein the carrier further comprises at least one protein transport domain.
62 . The method of claim 61 , wherein the protein transport domain is an HIV-TAT basic region or reverse HIV-TAT basic region amino acid sequence.
63 . The method of claim 61 , wherein the protein transport domain is the reverse HIV-TAT amino acid sequence of SEQ ID NO: 1.
64 . The method of 61, wherein the carrier comprises an HIV-TAT basic sequence (SEQ ID NO:2) or reverse HIV-TAT basic sequence (SEQ ID NO:1) at the N- or C-terminus, or both the N-terminus and the C-terminus.
65 . The method of claim 64 , wherein the carrier comprises an N-terminal portion that is an HIV-TAT or reverse HIV-TAT basic sequence, a C-terminal portion that is an HIV-TAT or reverse HIV-TAT basic sequence, and one or more cationic residues between the N- terminal portion and the C-terminal portion.