Use of lipid conjugates in the treatment of disease
View Patent ↗This invention provides a method of preventing asthma, allergic rhinitis, or chronic obstructive pulmonary disease in a subject comprising the step of administering to a subject a compound comprising a lipid or phospholipid moiety bond to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof. This invention also provides a method of treating allergic rhinitis or chronic obstructive pulmonary disease in a subject comprising the step of administering to a subject a compound comprising a lipid or phospholipid moiety bond to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof.
1. A method of decreasing the number or frequency of relapse episodes or reducing the incidence of disease-related symptoms of asthma in a subject, comprising the step of administering to a subject 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 2 to 200; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
2. The method according to claim 1 , wherein said glycosaminoglycan is hyaluronic acid.
3. The method according to claim 1 , wherein said glycosaminoglycan is heparin.
4. A method of treating a subject suffering from allergic rhinitis, comprising the step of administering to 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
5. The method according to claim 4 , wherein said glycosaminoglycan is hyaluronic acid.
6. The method according to claim 4 , wherein said glycosaminoglycan is heparin.
7. A method of decreasing the number or frequency of relapse episodes or reducing the incidence of disease-related symptoms of allergic rhinitis in a subject, comprising the step of administering to a subject a compound of 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
8. The method according to claim 7 , wherein said glycosaminoglycan is hyaluronic acid.
9. The method according to claim 7 , wherein said glycosaminoglycan is heparin.
10. A method of treating a subject suffering from chronic obstructive pulmonary disease, comprising the step of administering to a subject a compound of 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
11. The method according to claim 10 , wherein said glycosaminoglycan is hyaluronic acid.
12. The method according to claim 10 , wherein said glycosaminoglycan is heparin.
13. A method of decreasing the number or frequency or reducing the incidence of disease-related symptoms of chronic obstructive pulmonary disease in a subject, comprising the step of administering to a subject 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
14. The method according to claim 13 , wherein said glycosaminoglycan is hyaluronic acid.
15. The method according to claim 13 , wherein said glycosaminoglycan is heparin.
16. The method according to claim 1 , wherein said glycosaminoglycan is chondroitin sulfate.
17. The method according to claim 16 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
18. The method according to claim 1 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
19. The method according to claim 4 , wherein said glycosaminoglycan is chondroitin sulfate.
20. The method according to claim 19 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
21. The method according to claim 4 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
22. The method according to claim 7 , wherein said glycosaminoglycan is chondroitin sulfate.
23. The method according to claim 22 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
24. The method according to claim 7 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
25. The method according to claim 10 , wherein said glycosaminoglycan is chondroitin sulfate.
26. The method according to claim 25 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
27. The method according to claim 10 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
28. The method according to claim 13 , wherein said glycosaminoglycan is chondroitin sulfate.
29. The method according to claim 28 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
30. The method according to claim 13 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
31. A method of delaying the onset of symptoms of asthma in a subject, comprising the step of administering to a subject 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
32. The method according to claim 31 , wherein said glycosaminoglycan is hyaluronic acid.
33. The method according to claim 31 , wherein said glycosaminoglycan is heparin.
34. A method of delaying the onset of symptoms of allergic rhinitis in a subject, comprising the step of administering to a subject 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
35. The method according to claim 34 , wherein said glycosaminoglycan is hyaluronic acid.
36. The method according to claim 34 , wherein said glycosaminoglycan is heparin.
37. A method of delaying the onset of symptoms of chronic obstructive pulmonary disease in a subject, comprising the step of administering to a subject 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
38. The method according to claim 37 , wherein said glycosaminoglycan is hyaluronic acid.
39. The method according to claim 37 , wherein said glycosaminoglycan is heparin.
40. The method according to claim 31 , wherein said glycosaminoglycan is chondroitin sulfate.
41. The method according to claim 40 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
42. The method according to claim 31 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
43. The method according to claim 34 , wherein said glycosaminoglycan is chondroitin sulfate.
44. The method according to claim 43 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
45. The method according to claim 34 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
46. The method according to claim 37 , wherein said glycosaminoglycan is chondroitin sulfate.
47. The method according to claim 46 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
48. The method according to claim 37 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.
49. A method of treating a subject suffering from asthma, comprising the step of administering to a subject a compound of 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; and
X is a glycosaminoglycan; and
n is a number 2 to 200;
wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof and said spacer is linked to a hydroxyl or carboxylic acid of said glycosaminoglycan; and wherein if Y is nothing the phosphatidylethanolamine is directly linked to glycosaminoglycane via a carboxylic group.
50. The method according to claim 49 , wherein said glycosaminoglycan is hyaluronic acid.
51. The method according to claim 49 , wherein said glycosaminoglycan is heparin.
52. The method according to claim 49 , wherein said glycosaminoglycan is chondroitin sulfate.
53. The method according to claim 46 , wherein said chondroitin sulfate is chondroitin-6-sulfate or chondroitin-4-sulfate.
54. The method according to claim 49 , wherein said phosphatidylethanolamine is dimyrisotyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine.