Patent EA-004058-B1 (EA)
Title: Artificial peptides having surface activity and the use thereof in the preparation of artificial surfactant
Inventor: CURSTEDT TORE
IPC: A61P11/06
Filed: 2000-02-09
Abstract: 1. SP-C analogues having general formula (I), according to one-letter amino acid code: FeGfIPZZPVHLKR (XaB) (XbB) n (XcB) mXdGALLMGL (I) wherein:X is an amino acid selected from the group consisting of I,L, Nle (norleucine); B is an amino acid selected from the group consisting of ornithine, K, W, F, Y, Z is S, and optionally is linked via ester or thioester bonds with acyl group containing 12-22 carbon atoms. a is an integer from 1 to 19; b is an integer from 1 to 19; c is an integer from 1 to 21; d is an integer from 0 to 20; e is 0 or 1; f is 0 or 1; n is 0 or 1; m is 0 or 1, with the following conditions: - n + m > 0; - f >= e; - (XaB) (XbB) n (XCB) mXd is a sequence having a maximum of 22 amino acids, preferably from 10 to 22 amino acids. 2. SP-C analogues according to claim 1, having formula (Ia): (Ia) FGIPSSPVHLKRX4BX4BX4BXGALLMGL. 3. SP-C analogues according to claim 1, having formula (Ib): (Ib) FGIPSSPVHLKRX5BX5BX4GALLMGL. 4. SP-C analogues according to claim1, having formula (Ic) (Ic) FGIPSSPVHLKRX4BX11GALLMGL. 5. SP-C analogues according to claim1, having formula (Id) (Id)FGIPSSPVHLKRX8BX7GALLMGL. 6. SP-C analogues according to claim 1, having formula (Ie) (Ie) FGIPSSPVHLKRX11BX4GALLMGL. 7. SP-C analogues according to claims 1-6, in which Ser residues are acylated preferably with palmitoyl groups. 8. SP-C analogues according to claims 1-7, in which B is Lysine or Phenylalanine and X is Leucine, Isoleucine or Norleucine. 9. SP-C analogues according to claim 8, selected from the group consisting of: SP-C (LKS) FGIPSSPVHLKRLLILKLLLLKILLLKLGALLMGL SP-C (LKS)1 FGIPSSPVHLKRLLILLKLLLLIKLLILGALLMGL SP-C (LKS)2 FGIPSSPVHLKRLLILKLLLLLILLLILGALLMGL SP-C (LKS)3 FGIPSSPVHLKRLLILLLLLKLILLLILGALLMGL SP-C (LKS)4 FGIPSSPVHLKRLLILLLLLLLIKLLILGALLMGL SP-C (LFS) FGIPSSPVHLKRLLILFLLLLFILLLFLGALLMGL. 10. A synthetic surfactant comprising at least one SP-C analogue of formula (I) in admixture with lipids and phospholipids. 11. A synthetic surfactant according to claim 9, in which the mixture lipids/phospholipids comprises DPPG(1,2-dipalmitoyl-sn-glicero-3-phospholine), PG(phosphatidylglicerine), PA(palmitine acid). 12. A synthetic surfactant according to claims 10-11, further comprising SP-B or an active derivative thereof or a polymyxin, preferably polymyxin B. 13. A synthetic surfactant according to claims 10-12, in form of solution, dispersion, suspension, dry powder. 14. Use of SP-C analogues of claims 1-7 for the preparation of a synthetic surfactant to be used in all cases of surfactant deficiencies. 15. Use of a polymyxin, preferably polymyxin B for the preparation of an artificial surfactant according to claims 10-13, for the treatment of all cases of surfactant deficiencies or dysfunction, related pulmonary diseases such as pneumonia, bronchitis, asthma, meconium aspiration syndrome and also other diseases such as serous otitis media (glue ear). 16. Use according to claims 14 and 15, in which the surfactant deficiency is respiratory distress syndrome.