Claims
- 1. A pharmaceutical composition comprising a drug-oligomer conjugate comprising a drug covalently coupled to an oligomeric moiety and a bile salt, in a pharmaceutically acceptable carrier.
- 2. The pharmaceutical composition of claim 1, wherein the bile salt is selected from the group consisting of taurocholate, taurodeoxycholate, cholate, deoxycholate and glycodeoxycholate.
- 3. The pharmaceutical composition of claim 2, wherein the bile salt is present in a concentration in the range of about 0.15% to about 10% bile salt.
- 4. The pharmaceutical composition of claim 2, wherein the bile salt is present in a concentration in the range of about 0.5% to about 5% bile salt.
- 5. The pharmaceutical composition of claim 1, wherein the pH of the composition is between 6.2 and 9.0.
- 6. The pharmaceutical composition of claim 1, further comprising a buffering component.
- 7. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a liquid pharmaceutical composition.
- 8. The pharmaceutical composition of claim 7, wherein the liquid pharmaceutical composition is suitable for oral administration.
- 9. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a solid dosage pharmaceutical composition.
- 10. The pharmaceutical composition of claim 1, wherein the composition is suitable for a route of administration selected from the group consisting of buccal, transdermal, peroral and nasal administration.
- 11. The pharmaceutical composition of claim 1, wherein the drug is a calcitonin polypeptide.
- 12. The pharmaceutical composition of claim 10, wherein the calcitonin polypeptide is salmon calcitonin.
- 13. The pharmaceutical composition of claim 12, wherein the drug-oligomer moiety comprises salmon calcitonin coupled to two oligomeric moieties, wherein one oligomeric moiety is coupled to the lysine at the 11 position of the salmon calcitonin and wherein one oligomeric moiety is coupled to the lysine at the 18 position of the salmon calcitonin.
- 14. The pharmaceutical composition of claim 13, wherein the oligomeric moiety coupled to the lysine at the 11 position comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)— and wherein the oligomeric moiety coupled to the lysine at the 18 position of the salmon calcitonin comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)—.
- 15. The pharmaceutical composition of claim 1, wherein the drug-oligomer conjugate is present as a substantially monodispersed mixture.
- 16. The pharmaceutical composition of claim 1, wherein the drug-oligomer conjugate is present as a monodispersed mixture.
- 17. The pharmaceutical composition of claim 1, wherein the drug-oligomer conjugate is amphiphilically balanced.
- 18. The pharmaceutical composition of claim 1, wherein the oligomeric moiety is hydrophilic.
- 19. The pharmaceutical composition of claim 18, wherein the oligomeric moiety is polyethylene glycol.
- 20. The pharmaceutical composition of claim 1, wherein the oligomeric moiety is lipophilic.
- 21. The pharmaceutical composition of claim 20, wherein the oligomeric moiety is alkane.
- 22. The pharmaceutical composition of claim 1, wherein the oligomeric moiety comprises a hydrophilic moiety and a lipophilic moiety.
- 23. A pharmaceutical composition comprising, in a pharmaceutically acceptable carrier:
a drug; a bile salt; and a fatty acid, wherein the fatty acid and the bile salt are present in a weight-to-weight ratio of between 1:5 and 5:1, and wherein the fatty acid is present in an amount wherein the solubility of the bile salt in the presence of the fatty acid is greater than the solubility of the bile salt in a corresponding composition lacking the fatty acid.
- 24. The pharmaceutical composition of claim 23, wherein the fatty acid and the bile salt are present in a weight to weight ratio of about 1:4, 1:3, 1:2 or 1:1.
- 25. The pharmaceutical composition of claim 23, wherein the fatty acid comprises one or more fatty acids in the range of C4 to C20.
- 26. The pharmaceutical composition of claim 23, wherein the fatty acid is selected from the group consisting of lauric acid, capric acid, oleic acid and mixtures thereof.
- 27. The pharmaceutical composition of claim 23, wherein the pH of the composition is between 6.2 and 9.0.
- 28. The pharmaceutical composition of claim 23, further comprising a buffering component.
- 29. The pharmaceutical composition of claim 23, wherein the pharmaceutical composition is a liquid pharmaceutical composition.
- 30. The pharmaceutical composition of claim 29, wherein the liquid pharmaceutical composition is suitable for oral administration.
- 31. The pharmaceutical composition of claim 23, wherein the composition is suitable for a route of administration selected from the group consisting of buccal, transdermal, peroral and nasal administration.
- 32. The pharmaceutical composition of claim 29, wherein the liquid pharmaceutical composition is suitable for parenteral administration.
- 33. The pharmaceutical composition of claim 23, wherein the pharmaceutical composition is a solid dosage pharmaceutical composition.
- 34. The pharmaceutical composition of claim 23 wherein the drug is a calcitonin polypeptide.
- 35. The pharmaceutical composition of claim 34, wherein the calcitonin polypeptide is salmon calcitonin.
- 36. The pharmaceutical composition of claim 35, wherein the drug-oligomer moiety comprises salmon calcitonin coupled to two oligomeric moieties, wherein one oligomeric moiety is coupled to the lysine at the 11 position of the salmon calcitonin, and wherein one oligomeric moiety is coupled to the lysine at the 18 position of the salmon calcitonin.
- 37. The pharmaceutical composition of claim 36, wherein the oligomeric moiety coupled to the lysine at the 11 position comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)— and wherein the oligomeric moiety coupled to the lysine at the 18 position of the salmon calcitonin comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)—.
- 38. The pharmaceutical composition of claim 23, wherein the bile salt is present in a range of about 0.5% to about 20% weight/volume and the fatty acid is present in a range of about 0.2% to about 10% weight/volume.
- 39. The pharmaceutical composition of claim 23, wherein the bile salt is cholate and the fatty acid is laurate.
- 40. The pharmaceutical composition of claim 23, wherein the bile salt is cholate and the cholate is present in the amount of about 1.5% weight/volume and the fatty acid is laurate and the laurate is present in the amount of 2% weight/volume.
- 41. The pharmaceutical composition of claim 24, wherein the fatty acid is caprate and laurate and the bile salt and fatty acid is present in the proportions of three parts bile salt, one part caprate and one part laurate.
- 42. A method of treating a bone disorder in a subject in need of such treatment, said method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 1.
- 43. The method of claim 42, wherein the method comprises orally administering the pharmaceutical composition to the subject.
- 44. The method of claim 42, wherein the method comprises administering the pharmaceutical composition to the subject by an administration route selected from the group consisting of buccal, transdermal, peroral and nasal administration.
- 45. The method of claim 42, wherein the drug is a calcitonin polypeptide.
- 46. The method of claim 45, wherein the calcitonin polypeptide is salmon calcitonin.
- 47. The method of claim 46, wherein the drug-oligomer moiety comprises salmon calcitonin coupled to two oligomeric moieties, wherein one oligomeric moiety is coupled to the lysine at the 11 position of the salmon calcitonin, and wherein one oligomeric moiety is coupled to the lysine at the 18 position of the salmon calcitonin.
- 48. The method of claim 47, wherein the oligomeric moiety coupled to the lysine at the 11 position comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)— and wherein the oligomeric moiety coupled to the lysine at the 18 position of the salmon calcitonin comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)—.
- 49. The method of claim 42, wherein the drug-oligomer conjugate is present as a substantially monodispersed mixture.
- 50. The method of claim 42, wherein the drug-oligomer conjugate is present as a monodispersed mixture.
- 51. The method of claim 42, wherein the drug-oligomer conjugate is amphiphilically balanced.
- 52. The method of claim 42, wherein the oligomeric moiety comprises a hydrophilic moiety and a lipophilic moiety.
- 53. The method of claim 42, wherein the oligomeric moiety is hydrophilic.
- 54. The method of claim 53, wherein the oligomeric moiety is polyethylene glycol.
- 55. The method of claim 42, wherein the oligomeric moiety is lipophilic.
- 56. The method of claim 55, wherein the oligomeric moiety is alkane.
- 57. A method of treating a bone disorder in a subject in need of such treatment, said method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 23.
- 58. The method of claim 57, wherein the method comprises orally administering the pharmaceutical composition to the subject.
- 59. The method of claim 57, wherein the method comprises administering the pharmaceutical composition to the subject by an administration route selected from the group consisting of buccal, transdermal, peroral and nasal administration.
- 60. The method of claim 57, wherein the drug is a calcitonin polypeptide.
- 61. The method of claim 60, wherein the calcitonin polypeptide is salmon calcitonin.
- 62. The method of claim 61, wherein the drug-oligomer moiety comprises salmon calcitonin coupled to two oligomeric moieties, wherein one oligomeric moiety is coupled to the lysine at the 11 position of the salmon calcitonin, and wherein one oligomeric moiety is coupled to the lysine at the 18 position of the salmon calcitonin.
- 63. The method of claim 62, wherein the oligomeric moiety coupled to the lysine at the 11 position comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)— and wherein the oligomeric moiety coupled to the lysine at the 18 position of the salmon calcitonin comprises the structure CH3O(C2H4O)7—(CH2)7—C(O)—.
- 64. The method of claim 57, wherein the drug-oligomer conjugate is present as a substantially monodispersed mixture.
- 65. The method of claim 57, wherein the drug-oligomer conjugate is present as a monodispersed mixture.
- 66. The method of claim 57, wherein the drug-oligomer conjugate is amphiphilically balanced.
- 67. The method of claim 57, wherein the oligomeric moiety comprises a hydrophilic moiety and a lipophilic moiety.
- 68. The method of claim 57, wherein the oligomeric moiety is hydrophilic.
- 69. The method of claim 68, wherein the oligomeric moiety is polyethylene glycol.
- 70. The method of claim 57, wherein the oligomeric moiety is lipophilic.
- 71. The method of claim 70, wherein the oligomeric moiety is alkane.
- 72. The method of claim 57, wherein the bile salt component is present in a range of about 0.5% to about 20% weight/volume and the fatty acid component is present in a range of about 0.2% to about 10% weight/volume.
- 73. The method of claim 57, wherein the bile salt is cholate and the fatty acid is laurate.
- 74. The method of claim 57, wherein the bile salt is cholate and the cholate is present in the amount of about 1.5% weight/volume and the fatty acid is laurate and the laurate is present in the amount of 2% weight/volume.
- 75. A method of delivering a drug oligomer conjugate across the gut wall in a subject by simultaneously contacting the gut wall with a bile salt and the drug oligomer conjugate, comprising administering to the subject the pharmaceutical composition of claim 1.
- 76. A method of delivering a drug across the gut wall in a subject by simultaneously contacting the gut wall with a bile salt and the drug, comprising administering the subject a pharmaceutical composition comprising, in a pharmaceutically acceptable carrier, a drug and a bile salt.
- 77. A method of delivering a drug oligomer conjugate across the gut wall in a subject by simultaneously contacting the gut wall with a bile salt, a fatty acid and the drug oligomer conjugate, comprising administering to the subject a pharmaceutical composition comprising, in a pharmaceutically acceptable carrier,
a drug covalently coupled to an oligomeric moiety; a bile salt; and a fatty acid, wherein the fatty acid and the bile salt are present in a weight-to-weight ratio of between 1:5 and 5:1, and wherein the fatty acid is present in an amount wherein the solubility of the bile salt in the presence of the fatty acid is greater than the solubility of the bile salt in a corresponding composition lacking the fatty acid.
- 78. A method of delivering a drug across the gut wall in a subject by simultaneously contacting the gut wall with a bile salt, a fatty acid and the drug, comprising administering to the subject a pharmaceutical composition comprising, in a pharmaceutically acceptable carrier,
a drug; a bile salt; and a fatty acid, wherein the fatty acid and the bile salt are present in a weight-to-weight ratio of between 1:5 and 5:1, and wherein the fatty acid is present in an amount wherein the solubility of the bile salt in the presence of the fatty acid is greater than the solubility of the bile salt in a corresponding composition lacking the fatty acid.
- 79. The method of claim 77, wherein the fatty acids are laurate and caprate and fatty acids and bile salts are present in the pharmaceutical composition in the ratio of three parts bile salt, one part laurate and one part caprate.
- 80. The method of claim 78, wherein the fatty acids are laurate and caprate and fatty acids and bile salts are present in the pharmaceutical composition in the ratio of three parts bile salt, one part laurate and one part caprate.
RELATED APPLICATION
[0001] This application is a continuation-in-part application of U.S. application Ser. No. 10/235,281, filed Sep. 5, 2002, which status is pending and U.S. application Ser. No. 10/235,284, filed Sep. 5, 2002, which status is pending and which claim the benefit of U.S. Provisional Application No. 60/318,193, filed Sep. 7, 2001 and U.S. Provisional Application No. 60/377,865, filed May 3, 2002, the disclosures of each of which are incorporated herein by reference in their entireties.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60318193 |
Sep 2001 |
US |
|
60377865 |
May 2002 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
10235281 |
Sep 2002 |
US |
Child |
10382069 |
Mar 2003 |
US |
Parent |
10235284 |
Sep 2002 |
US |
Child |
10382069 |
Mar 2003 |
US |