초록 ▼

A method is provided for increasing the permeability of skin or mucosal tissue to a topically or transdermally administered pharmacologically or cosmeceutically active peptide, polypeptide or protein. The method involves use of a specified amount of a hydroxide-releasing agent, the amount optimized

A method is provided for increasing the permeability of skin or mucosal tissue to a topically or transdermally administered pharmacologically or cosmeceutically active peptide, polypeptide or protein. The method involves use of a specified amount of a hydroxide-releasing agent, the amount optimized to increase the flux of the peptide, polypeptide or protein through a body surface while minimizing the likelihood of skin damage, irritation or sensitization. Formulations and drug delivery devices employing hydroxide-releasing agents as permeation enhancers are provided as well.

대표청구항 ▼

A method is provided for increasing the permeability of skin or mucosal tissue to a topically or transdermally administered pharmacologically or cosmeceutically active peptide, polypeptide or protein. The method involves use of a specified amount of a hydroxide-releasing agent, the amount optimized

A method is provided for increasing the permeability of skin or mucosal tissue to a topically or transdermally administered pharmacologically or cosmeceutically active peptide, polypeptide or protein. The method involves use of a specified amount of a hydroxide-releasing agent, the amount optimized to increase the flux of the peptide, polypeptide or protein through a body surface while minimizing the likelihood of skin damage, irritation or sensitization. Formulations and drug delivery devices employing hydroxide-releasing agents as permeation enhancers are provided as well. on in mice, Cytokine, vol. 7, No. 2, 150-156pps, Feb. 1995. Sarraf, P. et al., Multiple Cytokines and acute inflammation raise mouse Leptin Levels: potential role in inflammatory anorexia, The Journal of Experimental Medicine, vol. 185, No. 1, 171-175 pps, Jan. 1997. Gloaguen, I. et al., Ciliary neurotrophic factor corrects obesity and diabetes associated with Leptin deficiency and resistance, Proc. Natl. Acad. Sci. USA, vol. 94, 6456-6461 pps, Jun. 1997. Poduslo, J. F. et al., Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF, Molecular Brain Research, vol. 36, 280-286 pps, Sep. 1996. ALS CNTF Treatment Study Group, A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis, Neurology, vol. 46, 1244-1249 pps, May 1996. Miller, R. G. et al., A Placebo-controlled Trial of Recombinant Human Ciliary Neurotrophic (rhCNTF) Factor in Amyotrophic Lateral Sclerosis, Ann Neurol, vol. 39, 256-260 pps, Feb. 1996. Halaas, J. L. et al., Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene, Science, vol. 269, 543-546 pps, Jul. 1995. Pelleymounter, M. A. et al., Effects of the obese Gene Product on Body Weight Regulation in ob/ob Mice, Science, vol. 269, 540-543 pps, Jul. 1995. Henderson, J. T. et al., Systemic Administration of ciliary Neurotrophic Factor Induces Cachexia in Rodents, J. Clin. Invest., vol. 93, 2632-2638 pps, Jun. 1994. Panayotatos, N. et al., Exchange of a Single Amino Acid Interconverts the Specific Activity and Gel Mobility of Human and Rat Ciliary Neurotrophic Factors, The Journal of Biological Chemistry, vol. 268, No. 25, 19000-19003 pps, Sep. 1993. Di Marco, Annalise et al., "Identification of ciliary neurotrophic factor (CNTF) residues essential for leukemia inhibitory factor receptor binding and generation of CNTF receptor antagonists.", Proc. Natl. Acad. Sci. USA, vol. 93, pp. 9247-9252 (1996). Saggio, Isabella et al., "CNTF variants with increased biological potency and receptor selectivity define a functional site of receptor interaction.", The Embo Journal, vol. 14, No. 13, pp. 3045-3054 (1995). Fantuzzi, Giamila et al., "Ciliary neurotrophic factor (CNTF) induces serum amyloid A, hypoglycemia and anorexia, and potentiates IL-1 induced corticosterone and IL-6 production in mice.", Cytokine, vol. 7, No. 2, pp. 150-156 (1995). Sarraf, Pasha et al., "Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia.", The Journal of Experimental Medicine, vol. 185, No. 1, pp. 171-175 (1997). Gloaguen, Isabelle et al., "Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance.", Proc. Natl. Acad. Sci. USA, vol. 94, pp. 6456-6461 (1997). t al.; US-6004566, 19991200, Friedman et al.; US-6019988, 20000200, Parab et al., 424/400; US-6019997, 20000200, Scholz et al.; US-6197331, 20010300, Lerner et al., 424/443