USE OF LIPID CONJUGATES IN CYSTIC FIBROSIS AND APPLICATIONS THEREOF
This invention provides for the use of compounds represented by the structure of the general formula (A): wherein L is a lipid or a phospholipid, Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol, Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, X is a physiologically acceptable monomer, dimer, oligomer, or polymer, wherein X is a glycosaminoglycan; and n is a number from 1 to 1000, wherein any bond between L, Z, Y and X is either an amide or an esteric bond in treating a subject suffering from cystic fibrosis, reducing or delaying the mortality of a subject suffering from cystic fibrosis or ameliorating symptoms associated with cystic fibrosis.
1 . A method for treating a subject suffering from cystic fibrosis, reducing or delaying the mortality of a subject suffering from cystic fibrosis, or ameliorating symptoms associated with cystic fibrosis, the method comprising the step of administering a therapeutically effective amount of a compound represented by the structure of the general formula (A):
wherein
L is a phospholipid;
Z is ethanolamine;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a glycosaminoglycan; and
n is a number from 1 to 1000;
wherein any bond between L, Z, Y and X is either an amide or an esteric bond to a subject suffering from symptoms of cystic fibrosis.
2 . A method for treating a subject suffering from cystic fibrosis, reducing or delaying the mortality of a subject suffering from cystic fibrosis or ameliorating symptoms associated with cystic fibrosis, the method comprising the step of administering therapeutically effective amount of a compound represented by the structure of the general formula (I):
wherein
R 1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
R 2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a glycosaminoglycan; and
n is a number from 1 to 1,000;
wherein if Y is nothing the phosphatidylethanolamine is directly linked to X via an amide bond and if Y is a spacer, said spacer is directly linked to X via an amide or an esteric bond and to said phosphatidylethanolamine via an amide bond to a subject suffering from symptoms of cystic fibrosis.
3 . The method of claim 1 , wherein said compound is represented by the structure of the general formula (VIII):
wherein
R 1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
R 2 is either hydrogen or a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
Z is ethanolamine;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a glycosaminoglycan; and
n is a number from 1 to 1000;
wherein any bond between the phospholipid, Z, Y and X is either an amide or an esteric bond.
4 . The method of claim 1 , wherein said compound is represented by the structure of the general formula (IX):
wherein
R 1 is either hydrogen or a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
R 2 is either hydrogen or a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
Z is ethanolamine;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a glycosaminoglycan; and
n is a number from 1 to 1000;
wherein any bond between the phospholipid, Z, Y and X is either an amide or an esteric bond.
5 . The method of claim 1 , wherein said compound is represented by the structure of the general formula (X):
wherein
R 1 is either hydrogen or a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
R 2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
Z is ethanolamine;
Y is either nothing or a spacer group ranging in length from 2 to 30 atoms;
X is a glycosaminoglycan; and
n is a number from 1 to 1000;
wherein any bond between the ceramide phosphoryl, Z, Y and X is either an amide or an esteric bond.
6 . The method according to anyone of claims 1 - 5 , wherein said glycosaminoglycan is hyaluronic acid, heparin, heparin sulfate, chondroitin sulfate, keratin, keratin sulfate or dermatan sulfate.
7 . The method according to anyone of claims 1 - 5 , wherein L is palmitoyl phosphatidylethanolamine or myristoyl phosphatidylethanolamine.
8 . The method according to anyone of claims 1 - 5 , wherein said n is a number between 2 to 100.