Surfactant protein C esters
View Patent ↗Novel surfactant protein C esters suitable for preparing pharmaceutical compositions for the treatment of infant respiratory distress syndrome and adult respiratory distress syndrome are described.
1. A surfactant protein C (SP-C) having the amino acid sequence SEQ ID NO: 3 of the formula I
0 1 2 3 4 5 6 7 8 9 10 (I)
(A) Gly Ile Pro B B Pro Val His Leu Lys
11 12 13 14 15 16 17 18 19 20
Arg Leu Leu Ile Val Val Val Val Val Val
21 22 23 24 25 26 27 28 29 30
Leu Ile Val Val Val Ile Val Gly Ala Leu
31 32 33 34
Leu C Gly Leu
in which A is absent or Phe, B is Phe or Trp and C is Ile, Leu or Ser,
wherein the amino acid at the carboxy terminus of the surfactant protein is esterified with an alcohol having 1–4 carbon atoms, and
wherein the esterified surfactant protein C is isolated and purified,
or a pharmacologically acceptable salt thereof.
2. The surfactant protein C as claimed in claim 1 , wherein A is absent or Phe, B is Phe and C is Ile.
3. The surfactant protein C as claimed in claim 1 , wherein A is absent, B is Phe and C is Ile.
4. The surfactant protein C as claimed in claim 1 , wherein the alcohol is methanol or 2-propanol.
5. A pharmaceutical composition comprising a surfactant protein C ester as claimed in claim 1 , and/or a pharmacologically acceptable salt thereof, and a pharmaceutically acceptable auxiliary.
6. The pharmaceutical composition as claimed in claim 5 , which comprises at least one further surfactant protein from the group SP-A, unesterified SP-C and SP-B.
7. The pharmaceutical composition as claimed in claim 6 , which comprises recombinant SP-C (rSP-C) wherein the recombinant SP-C has an amino acid sequence SEQ ID NO: 3 of the formula I
0 1 2 3 4 5 6 7 8 9 10
(A) Gly Ile Pro B B Pro Val His Leu Lys
11 12 13 14 15 16 17 18 19 20
Arg Leu Leu Ile Val Val Val Val Val Val (I)
21 22 23 24 25 26 27 28 29 30
Leu Ile Val Val Val Ile Val Gly Ala Leu
31 32 33 34
Leu C Gly Leu
in which A is absent, B is Phe, and C is Ile, or a pharmacologically acceptable salt thereof.
8. The pharmaceutical composition as claimed in claim 5 , which comprises phospholipids, fatty acids and electrolytes.
9. The pharmaceutical composition as claimed in claim 8 , which comprises, based on the dry weight of the composition, from 80% to 95% by weight of phospholipids, from 0.2% to 5% by weight of surfactant protein, from 2% to 15% by weight of fatty acids and from 0% to 5% by weight of electrolytes.
10. A method of treating Acute Lung Injury (ALI) in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a surfactant protein C(SP-C) having the amino acid sequence SEQ ID NO: 3 of the formula I
0 1 2 3 4 5 6 7 8 9 10
(A) Gly Ile Pro B B Pro Val His Leu Lys
11 12 13 14 15 16 17 18 19 20
Arg Leu Leu Ile Val Val Val Val Val Val (I)
21 22 23 24 25 26 27 28 29 30
Leu Ile Val Val Val Ile Val Gly Ala Leu
31 32 33 34
Leu C Gly Leu
in which A is absent or Phe, B is Phe or Trp and C is Ile, Leu or Ser,
wherein the amino acid at the carboxy terminus of the surfactant protein is esterified with an alcohol having 1–4 carbon atoms, and
wherein the esterified surfactant protein C is isolated and purified,
or a pharmacologically acceptable salt thereof.
11. The method according to claim 10 , wherein A is absent or Phe, B is Phe and C is Ile.
12. The method according to claim 10 , wherein A is absent, B is Phe and C is Ile.
13. The method according to claim 10 , wherein the alcohol is methanol or 2-propanol.