Method and composition for regulating serum calcium levels of mammals

• US 4,692,433 A
• Filed: 08/01/1985
• Issued: 09/08/1987
• Est. Priority Date: 10/12/1983
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Hostetler, Karl Y., Deftos, Leonard J.
• Primary Examiner(s): Brown, Johnnie R.
• Assistant Examiner(s): Stone, Jacqueline M.
• Application Number:
  US06/761,751
• Time in Patent Office: 768 Days
• Field of Search: 514/808, 514/12, 424/38
• US Class Current: 424/450
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 9/127 Liposomes

Abstract

Method for regulating serum calcium levels in mammals by orally administering a composition which includes a polypeptide hormone such as parathyroid hormone (PTH) or calcitonin. The polypeptide hormone is protected from destruction in the digestive tract by encapsulation in liposomes. The liposome preferably includes a cationic amphiphilic agent so that the surface of the liposome has a net positive charge. Agents for enhancing the action of the liposome encapsulated hormones are also disclosed.

Claims

1. A method for regulating blood calcium levels in a mammal which comprises:

orally administering to said mammal a blood calcium-regulating effective amount of a composition consisting essentially of an aqueous solution of a polypeptide hormone selected from the group consisting of parathyroid hormone and calcitonin, said polypeptide hormone being encapsulated in a liposome.

2. A method according to claim 1 wherein said polypeptide hormone is parathyroid hormone.

3. A method according to claim 2 wherein said polypeptide hormone is the hPTH 1-34 fragment of parathyroid hormone.

4. A method according to claim 1 wherein said polypeptide hormone is calcitonin.

5. A method according to claim 1 wherein said liposome contains from about 1 to 20 molar percentage of an alkylamine having the general formula C_n H_2n+1 NH₂, where n is 12 to 20.

6. A method according to claim 5 wherein said alkylamine is stearylamine.

7. A method according to claim 1 including the additional step of administering salicylate, salicylamide, acetylsalicylate or methylsalicylate to said mammal to improve the blood calcium-regulating action of said polypeptide hormone encapsulated in said liposome.

8. A method according to claim 1 wherein said liposome is made from phospholipids selected from the group consisting of phosphatidylcholine, dimyristoylphosphatidylcholine and dipalmitoylphosphatidylcholine.

15. A method according to claim 1 including the additional step of administering aprotinin to said mammal to improve the blood calcium-regulating action of said polypeptide hormone encapsulated in said liposome.

16. A method according to claim 4 wherein said polypeptide hormone is salmon calcitonin.

9. A composition for use in oral administration in mammals to regulate blood calcium levels, said composition consisting essentially of a polypeptide hormone selected from the group consisting of parathyroid hormone and calcitonin, said polypeptide hormone being encapsulated in a liposome, said liposome containing from about 1 to 20 molar percentage of an alkylamine having the general formula C_n H_2n+1 NH₂,where n is 12 to 20.

10. A composition according to claim 9 wherein said polypeptide hormone is parathyroid hormone.

11. A composition according to claim 9 wherein said polypeptide hormone is calcitonin.

12. A composition according to claim 9 wherein said polypeptide hormone is the hPTH 1-34 amino acid fragment of parathyroid hormone.

13. A composition according to claim 9 wherein said alkylamine is stearylamine.

14. A composition according to claim 9 wherein said liposome is made from phospholipids selected from the group consisting of phosphatidylcholine, dimyristoylyphosphatidylcholine and dipalmitoylphosphatidylcholine.

17. A composition according to claim 11 wherein said polypeptide hormone is salmon calcitonin.

18. A composition for oral administration in mammals to regulate blood calcium levels, said composition comprising:

a polypeptide hormone selected from the group consisting of parathyroid hormone and calcitonin, said polypeptide hormone being encapsulated in a liposome, said liposome containing from about 1 to 20 molar percentage of an alkylamine having a general formula C_n H_2n+1 NH₂, where n is 12 to 20; and

a pharmaceutically acceptable aqueous buffer solution have a pH of between about 4.0 and 8.0.

19. A composition for oral administration according to claim 18 wherein cysteine is added to said buffer solution as a preservative.

20. A composition for oral administration according to claim 18 wherein aprotinin, salicylate, salicylamide, acetylsalicylate or methylsalicylate is added to said buffer solution in an amount sufficient to improve the calcium-regulating action of said polypeptide hormone encapsulated in said liposome.

21. A composition for oral administration according to claim 18 wherein said polypeptide hormone is calcitonin.

22. A composition for oral administration according to claim 18 wherein said alkylamine is stearylamine.