The formation of the peptide/lipid complex by joint lyophilization

 

The invention relates to the field of pharmaceutical industry and relates to lyophilized peptide/lipid product. The invention lies in the fact that they form a peptide/lipid vesicles and complexes through co-lyophilization of peptides, preferably those who are able to accept amphipatic alpha-helical conformation, and one or more lipids. Get lyophilized peptide/lipid complex. Dissolve as peptides and lipids, receiving only one solution, or two separate solution. The invention provides for obtaining a stable peptide/lipid vesicles complexes. 12 C. and 49 C.p. f-crystals, 1 tab., 8 Il.

Description text in facsimile form (see graphic part)

Claims

1. A method of obtaining a lyophilized peptide/lipid product, which includes lyophilization solubilizing solution containing the peptide or analogue of the peptide, which is able to take amphipatic conformation and lipid, and specified the lipid dissolved in the specified solution without the use of detergent and where the specified product can be rehydration with the formation of the peptide/lipid complex.

2. The method according to claim what is a lipid.

4. The method according to p. 1, where the specified analog peptide is similar Area-I, Area-II, Area-IV, AROS-I, AROS-II, AROS-III and APOE.

5. The method according to p. 1, where the specified lipid is a saturated lipid, unsaturated lipid or mixtures thereof.

6. The method according to p. 1, where the specified solution is prepared using an organic solvent.

7. The method according to p. 1, which further includes the selection of specified aliquot of a solution of the peptide/lipid in separate containers before lyophilization to obtain the dosage form containing a unit dose.

8. The method according to p. 1, which further includes sterilization of the specified product before, during or after lyophilization.

9. Pharmaceutical composition for the prevention and treatment of disorders associated with dyslipoproteinemia and atherosclerosis, septic shock, cardiovascular or infectious diseases, containing a unit dose comprising lyophilized peptide/lipid product obtained by PP.1-8.

10. The method according to p. 1, where the specified lipid is a natural lipid, a synthetic lipid or mixtures thereof.

11. The method according to p. 10, where the specified lipid is selected from the group consisting of ethers of phospholipids, phospholipids with short chains, cholesterol derivatives XB, phosphatidylglycerol, gangliosides and cerebrosides.

12. The method according to p. 10, where the specified lipid is selected from the group consisting of egg phosphatidylcholine, phosphatidylcholine from soy beans, dipalmitoylphosphatidylcholine, dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, 1-myristoyl-2-palmitoyloleoylphosphatidylcholine, 1-Palmitoyl-2-myristoyltransferase, 1-Palmitoyl-2-stearoylethanolamine, 1 stearoyl-2-palmitoyloleoylphosphatidylcholine, dioleoylphosphatidylcholine, dioleoylphosphatidylcholine, dilaurylracglycerol, diphosphatidylglycerol, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine acid, dipalmitoylphosphatidyl acid, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, sphingomyelin, dipalmitoylphosphatidyl, distearyldimonium, phosphatidic acid, galactocerebroside, dilaurylracglycerol, (1,3)-D-mannosyl(1,3)diglyceride, aminophenylacetate, 3-cholesteryl-6'-(glycosylation)hexylamine glycolipids and mixtures thereof.

13. The method according to p. 12, wherein said lipline the ratio of lipid : peptide or the molar ratio of lipid : analog peptide is from about 2:1 to about 200:1.

15. The method according to p. 14, in which the molar ratio of lipid: peptide or the molar ratio of lipid : analog peptide is from about 2:1 to about 50:1.

16. The method according to p. 15, in which the molar ratio of lipid : peptide or the molar ratio of lipid : analog peptide is from about 5:1 to about 50:1.

17. A method of obtaining a lyophilized peptide/lipid product, which can be rehydration with the formation of the peptide/lipid complex, the method includes

(i) solubilization of at least one amphipatic peptide or amphipatic analogue peptide in the first solvent to form a first solution,

(ii) solubilization of at least one lipid in the second solvent without the use of detergent with the formation of the second solution, and the specified second solution is mixed with a first solution,

(iii) the Union of the specified first solution with the specified second solution with the formation of the peptide/lipid solution and

(iv) the lyophilization of the specified peptide/lipid solution so as to form a lyophilized peptide/lipid product.

18. The method according to p. 17, wherein said peptide is a protein.

the hydrated analogue of the peptide is similar Area-I, Area-II, Area-IV, AROS-I, AROS-II, AROS-III and APOE.

21. The method according to p. 17, where the specified lipid is a saturated lipid, unsaturated lipid or mixtures thereof.

22. The method according to p. 17, in which the first and second solvents are the same.

23. The method according to p. 17, which further includes the selection of specified aliquot of a solution of the peptide/lipid in separate containers before lyophilization to obtain the dosage form containing a unit dose.

24. The method according to p. 17, which further includes sterilization of the specified product before, during or after lyophilization.

25. Pharmaceutical composition for the prevention and treatment of disorders associated with dyslipoproteinemia and atherosclerosis, septic shock, cardiovascular or infectious diseases, containing a unit dose comprising a stable lyophilized peptide/lipid product obtained under item 17.

26. The method according to p. 17, where the specified lipid is a natural lipid, a synthetic lipid or mixtures thereof.

27. The method according to p. 26, where the specified lipid is selected from the group consisting of ethers of phospholipids, phospholipids with short chains, cholesterol, derivatives of cholesterol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidyl lipid is selected from the group consisting of egg phosphatidylcholine, phosphatidylcholine from soy beans, dipalmitoylphosphatidylcholine, dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, 1-myristoyl-2-palmitoyloleoylphosphatidylcholine, 1-Palmitoyl-2-myristoyltransferase, 1-Palmitoyl-2-stearoylethanolamine, 1 stearoyl-2-palmitoyloleoylphosphatidylcholine, dioleoylphosphatidylcholine, dioleoylphosphatidylcholine, dilaurylracglycerol, diphosphatidylglycerol, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine acid, dipalmitoylphosphatidyl acid, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, sphingomyelin, dipalmitoylphosphatidyl, distearyldimonium, phosphatidic acid, galactocerebroside, dilaurylracglycerol, (1,3)-D-mannosyl(1,3)diglyceride, aminophenylacetate, 3-cholesteryl-6'-(glycosylation)hexylamine glycolipids and mixtures thereof.

29. The method according to p. 28, wherein said lipid is a 3-cholesteryl-6'-(glycosylation)hexylamine glycolipid.

30. The method according to p. 17, in which melanoblastoma 200:1.

31. The method according to p. 30, in which the molar ratio of lipid : peptide or the molar ratio of lipid : analog peptide is from about 2:1 to about 50:1.

32. The method according to p. 31, in which the molar ratio of lipid : peptide or the molar ratio of lipid : analog peptide is from about 5:1 to about 50:1.

33. The peptide/lipid complex obtained by the method including

(i) the solubilization of one or more amphipatic peptide or amphipatic peptides and at least one lipid in a solvent system without the use of detergent with the formation of the peptide/lipid solution,

(ii) the lyophilization of the specified peptide/lipid solution with the formation of digidratirovannogo peptide/lipid product and

(iii) rehydration specified digidratirovannogo peptide/lipid product with the formation of the indicated peptide/lipid complex.

34. The peptide/lipid complex of p. 33, where the specified peptide is a protein, lipid binding.

35. The peptide/lipid complex of p. 33, where the specified peptide is similar Area.

36. The peptide/lipid complex of p. 33, where the specified lipid is a saturated lipid, unsaturated lipid or mixtures thereof.

37. Peptide/Liny complex p. 33, where in the specified process uses a solvent system consisting of a single solvent.

39. The peptide/lipid complex of p. 33, which is almost equal to the size of the high density lipoprotein.

40. The peptide/lipid complex of p. 33, where this complex is sterile.

41. The peptide/lipid complex of p. 33, where this complex is formulated as a sterile form containing a unit dose.

42. Pharmaceutical composition for the prevention and treatment of disorders associated with dyslipoproteinemia and atherosclerosis, septic shock, cardiovascular or infectious diseases, containing a unit dose comprising a stable lyophilized peptide/lipid product obtained by p. 33 or 41.

43. The peptide/lipid complex of p. 33, where the specified lipid is a natural lipid, a synthetic lipid or mixtures thereof.

44. The peptide/lipid complex of p. 43, where the specified lipid is selected from the group consisting of ethers of phospholipids, phospholipids with short chains, cholesterol, derivatives of cholesterol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingolipids, phosphatidylglycerol, gangliosides and cerebr is phosphatidylcholine, phosphatidylcholine from soy beans, dipalmitoylphosphatidylcholine, dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, 1-myristoyl-2-palmitoyloleoylphosphatidylcholine, 1-Palmitoyl-2-myristoyltransferase, 1-Palmitoyl-2-stearoylethanolamine, 1 stearoyl-2-palmitoyloleoylphosphatidylcholine, dioleoylphosphatidylcholine, dioleoylphosphatidylcholine, dilaurylracglycerol, diphosphatidylglycerol, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine acid, dipalmitoylphosphatidyl acid, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, sphingomyelin, dipalmitoylphosphatidyl, distearyldimonium, phosphatidic acid, galactocerebroside, dilaurylracglycerol, (1,3)-D-mannosyl(1,3)diglyceride, amino-phenylglycine, 3-cholesteryl-6'-(glycosylation)hexylamine glycolipids and mixtures thereof.

46. The peptide/lipid complex of the method according to p. 45, where the specified lipid is a 3-cholesteryl-6'-(glycosylation)hexylamine glycolipid.

47. Freeze-dried composition obtained spacesystem solvents without the use of detergent with the formation of the peptide/lipid solution,

(ii) the lyophilization specified solubilizing peptide/lipid solution with the formation of this freeze-dried composition.

48. Liofilizirovannaya composition on p. 47, which is sterile.

49. Liofilizirovannaya composition on p. 47, where the peptide is a peptide that binds the lipid or similar Area-I, Area-II, Area-IV, AROS-I, AROS-II, AROS-III and APOE.

50. Freeze-dried composition according to p. 47, where the specified amphipatic peptide or amphipatic similar peptide is able to adopt a conformation-spiral.

51. Liofilizirovannaya composition on p. 47, which is used in the method, the solvent system includes a single solvent.

52. Pharmaceutical composition for the prevention and treatment of disorders associated with dyslipoproteinemia and atherosclerosis, septic shock, cardiovascular or infectious diseases, containing a unit dose comprising a stable lyophilized peptide/lipid product obtained by p. 47.

53. A method of obtaining a lyophilized peptide/lipid compositions, the method includes (i) solubilization of at least one amphipatic peptide or amphipatic analogue peptide in the first dissolve the Le without the use of detergent with the formation of the second solution, moreover, the specified second solution is mixed with a first solution,

(iii) the Union of the specified first solution with the specified second solution with the formation of the peptide/lipid solution and

(iv) the lyophilization of the specified peptide/lipid solution with formation of a dehydrated peptide/lipid composition.

54. The method according to p. 53, in which the molar ratio of lipid : peptide or the molar ratio of lipid : analog peptide is from about 2:1 to about 200:1.

55. The method according to p. 54, in which the molar ratio of lipid : peptide or the molar ratio of lipid : analog peptide is from about 2:1 to about 50:1.

56. Pharmaceutical composition for the prevention and treatment of disorders associated with dyslipoproteinemia and atherosclerosis, septic shock, cardiovascular or infectious diseases, containing a unit dose comprising a stable lyophilized peptide/lipid product obtained by p. 53.

57. A method of obtaining a peptide/lipid complex, the method includes

(i) solubilization of at least one amphipatic peptide or amphipatic analogue peptide in the first solvent to form the first rastovaniem second solution, moreover, the specified second solution is mixed with a first solution,

(iii) the Union of the specified first solution with the specified second solution with the formation of the peptide/lipid solution,

(iv) the lyophilization of the specified peptide/lipid solution with obtaining digidrirovanny peptide/lipid compositions and

v) the hydration of the dried peptide/lipid composition of obtaining the peptide/lipid complex.

58. The method according to p. 57, in which the molar ratio of lipid : peptide or the molar ratio of lipid : analog peptide is from about 2:1 to about 200:1.

59. Pharmaceutical composition for the prevention and treatment of disorders associated with dyslipoproteinemia and atherosclerosis, septic stock, cardiovascular or infectious diseases, containing a unit dose comprising a stable lyophilized peptide/lipid product obtained by p. 57.

60. The method according to p. 17, 53 or 57, where the first solvent is selected from the group consisting of water, methanol, 1-butanol and mixtures thereof.

61. The method according to p. 17, 53 or 57, where the specified second solvent is selected from the group consisting of xylene, benzene, methanol, chloroform and mixtures thereof.

 

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