Pharmaceutical compositions and methods for peptide treatment
Compositions and methods for treating a patient with a pharmaceutically active peptide that combines a pharmaceutically active peptide, a permeation enhancer, and a carrier, are disclosed.
1. A pharmaceutical composition in the form of an emulsified nasal spray comprising: a macrocyclic permeation enhancer, a liquid carrier comprising water, an emulsifying agent, and a therapeutically effective amount of a pharmaceutically active agent other than insulin selected from the group consisting of peptides, peptidomimetics, and proteins; wherein said pharmaceutical composition is free of a hydrocolloid emulsifier; and wherein said macrocyclic permeation enhancer is a Hsieh enhancer emulsified in the liquid carrier; said Hsieh enhancer having the following structure:
wherein X is oxygen, sulfur or an imino group of the structure
and wherein Y is oxygen, sulfur or an imino group of the structure
═N—R.
with the proviso that when Y is the imino group, S is an imino group, and when Y is sulfur, X is sulfur or an imino group, A is a group having the structure
wherein X and Y are defined above, m and n are integers having a value from 1 to 20 and the sum of m+n is not greater than 25, p is an integer having a value of 0 or 1, q is an integer having a value of 0 or 1, r is an integer having a value of 0 or 1, and each of R, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is independently hydrogen or an alkyl group having from 1 to 6 carbon atoms which may be straight chained or branched provided that only one of R 1 to R 6 can be an alkyl group, with the proviso that when p, q and r have a value of 0 and Y is oxygen, mtn is at least 11, and with the further proviso that when X is an imino group, q is equal to 1, Y is oxygen, and p and r are 0, then m+n is at least 11.
2. The pharmaceutical composition of claim 1 , wherein said Hsieh enhancer is cyclopentadecalactone or cyclohexadecanone.
3. The pharmaceutical composition of claim 1 , further comprising a crystallization inhibitor.
4. The pharmaceutical composition of claim 1 , further comprising an enzyme inhibitor.
5. The pharmaceutical composition of claim 4 , wherein said enzyme inhibitor is selected from the group consisting of leupeptin and aprotinin.
6. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is formulated in a manner suitable to be administered for use in treating chronic conditions.
7. A method for treating a patient with a peptide, a peptidomimetic, or a protein, said method comprising administering to a patient in need of peptide treatment, peptidomimetic treatment, or protein treatment, a pharmaceutical composition in the form of an emulsified nasal spray comprising: a macrocyclic permeation enhancer, a liquid carrier comprising water, an emulsifying agent, and a therapeutically effective amount of a pharmaceutically active agent other than insulin selected from the group consisting of peptides, peptidomimetics, and proteins; wherein said pharmaceutical composition is free of a hydrocolloid emulsifier; and wherein said macrocyclic permeation enhancer is a Hsieh enhancer emulsified in the liquid carrier; said Hsieh enhancer having the following structure:
wherein X is oxygen, sulfur or an imino group of the structure
and wherein Y is oxygen, sulfur or an imino group of the structure
═N—R
with the proviso that when Y is the imino group, X is an imino group, and when Y is sulfur, X is sulfur or an imino group, A is a group having the structure
wherein X and Y are defined above, m and n are integers having a value from 1 to 20 and the sum of m+n is not greater than 25, p is an integer having a value of 0 or 1, q is an integer having a value of 0 or 1, r is an integer having a value of 0 or 1, and each of R, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is independently hydrogen or an alkyl group having from 1 to 6 carbon atoms which may be straight chained or branched provided that only one of R 1 to R 6 can be an alkyl group, with the proviso that when p, q and r have a value of 0 and Y is oxygen, m+n is at least 11, and with the further proviso that when X is an imino group, q is equal to 1, Y is oxygen, and p and r are 0, then m+n is at least 11.
8. The method of claim 7 , wherein said Hsieh enhancer is cyclopentadecalactone or cyclohexadecanone.
9. The method of claim 7 , wherein said pharmaceutical composition further comprises a crystallization inhibitor.
10. The method of claim 7 , wherein said pharmaceutical composition further comprises an enzyme inhibitor.
11. The method of claim 10 , wherein said enzyme inhibitor is selected from the group consisting of leupeptin and aprotinin.
12. The method of claim 7 , wherein said pharmaceutical composition is formulated in a manner suitable to be administered for use in treating chronic conditions.
13. The pharmaceutical composition of claim 1 , wherein said emulsifying agent is selected from the group consisting of: surfactants that are free of carbon-carbon double bonds and mixtures or such surfactants.
14. The pharmaceutical composition of claim 13 , wherein said surfactant(s) is/are non-ionic.
15. The method of claim 7 , wherein said emulsifying agent is selected from the group consisting of: surfactants that are free of carbon-carbon double bonds and mixtures of such surfactants.
16. The method of claim 15 , wherein said surfactant(s) is/are non-ionic.