Compounds and compositions for delivering active agents

• US 6,663,887 B2
• Filed: 02/21/2002
• Issued: 12/16/2003
• Est. Priority Date: 04/22/1993
• Status: Expired due to Fees

• Current Assignee: NOVO Nordisk North America Operations A/S (Novo Nordisk A/S)
• Original Assignee: Emisphere Technologies, Inc. (Novo Nordisk A/S)
• Inventors: Ho, Koc-Kan, DeMorin, Frenel, Paton, Duncan R., Leone-Bay, Andrea
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Joynes, Robert M.
• Application Number:
  US10/090,012
• Publication Number:
  US 20020120009A1
• Time in Patent Office: 663 Days
• Field of Search: 424/451, 424/455, 424/491, 424/400, 514/563
• US Class Current: 424/451
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 38/25 Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: C07C 229/42 with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
• CPC Class Codes: C07C 233/48 having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a saturated carbon skeleton containing rings
• CPC Class Codes: C07C 233/55 having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
• CPC Class Codes: C07C 233/63 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 233/82 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
• CPC Class Codes: C07C 233/87 of a carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 235/26 the carbon skeleton being saturated and containing rings
• CPC Class Codes: C07C 235/38 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/64 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/78 the carbon skeleton containing rings
• CPC Class Codes: C07C 235/84 : with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/22 : having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated peptides C07K
• CPC Class Codes: C07C 2601/02 : with a three-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 2601/18 : with a ring being at least seven-membered
• CPC Class Codes: C07C 279/14 : being further substituted by carboxyl groups
• CPC Class Codes: C07K 1/1077 : by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
• CPC Class Codes: C07K 5/06043 : Leu-amino acid

Abstract

Modified amino acid compounds useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Claims

1. A composition comprising:

(a) a compound having the formula

 

or a salt thereof; and

(b) an active agent that is a peptide.

2. A composition as defined in claim 1, wherein the active agent is a pharmacological agent or a therapeutic agent.

3. A composition as defined in claim 1, wherein the active agent is a monoclonal antibody.

4. A composition comprising:

(a) a compound having the formula

 

or a salt thereof; and

(b) an active agent that is a polysaccharide.

5. A composition as defined in claim 4, wherein the active agent is a pharmacological agent or a therapeutic agent.

6. A composition comprising:

(a) a compound having the formula

 

or a salt thereof; and

(b) an active agent that is a mucopolysaccharide.

7. A composition as defined in claim 6, wherein the active agent is a pharmacological agent or a therapeutic agent.

8. A composition comprising:

(a) a compound having the formula

 

or a salt thereof; and

(b) an active agent that is a carbohydrate.

9. A composition as defined in claim 8, wherein the active agent is a pharmacological agent or a therapeutic agent.

10. A composition comprising:

(a) a compound having the formula

 

or a salt thereof; and

(b) an active agent that is a lipid.

11. A composition as defined in claim 10, wherein the active agent is a pharmacological agent or a therapeutic agent.

12. A composition comprising:

(a) a compound having the formula

 

or a salt thereof; and

(b) an active agent selected from the group consisting of a hormone, an anti-microbial agent and an anti-fungal agent.

13. A composition as defined in claim 12, wherein the active agent is selected from the group consisting of interleukin-I, insulin, and growth hormone-releasing hormone.

14. A composition as defined in claim 13, wherein the active agent is interleukin-I.

15. A composition as defined in claim 13, wherein the active agent is insulin.

16. A composition as defined in claim 13, wherein the active agent is growth hormone-releasing hormone.

17. A composition comprising:

(a) a compound having the formula

 

or a salt thereof; and

(b) cromolyn sodium.

18. A dosage unit form comprising

(a) a compound having the formula

 

or a salt thereof;

(b) a biologically active agent; and

(c) (i) an excipient,

(ii) a diluent,

(iii) a disintegrant,

(iv) a lubricant,

(v) a plasticizer,

(vi) a colorant,

(vii) a dosing vehicle, or

(viii) any combination thereof.

19. A dosage unit form as defined in claim 18, wherein the biologically active agent is a peptide.

20. A dosage unit form as defined in claim 18, wherein the biologically active agent is a polysaccharide.

21. A dosage unit form as defined in claim 18, wherein the biologically active agent is a mucopolysaccharide.

22. A dosage unit form as defined in claim 18, wherein the biologically active agent is a carbohydrate.

23. A dosage unit form as defined in claim 18, where the biologically active agent is a lipid.

24. A dosage unit form as defined in claim 18, wherein the biologically active agent is an anti-microbial agent.

25. A dosage unit form as defined in claim 18, wherein the biologically active agent is a monoclonal antibody.

26. A dosage unit form as defined in claim 18, wherein the biologically active agent is a hormone.

27. A dosage unit form as defined in claim 18, wherein the biologically active agent is an anti-fungal agent.

28. A dosage unit form as defined in claim 18, wherein the biologically active agent is selected from the group consisting of interleukin-I, insulin, and growth hormone-releasing hormone.

29. A dosage unit form as defined in claim 28, wherein the biologically active agent is interleukin-I.

30. A dosage unit form as defined in claim 28, wherein the biologically active agent is insulin.

31. A dosage unit form as defined in claim 28, wherein the biologically active agent is a growth hormone-releasing hormone.

32. A dosage unit form as defined in claim 18, comprised of a tablet, a capsule, or a liquid.

35. A method of administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal a dosage unit form as defined in claim 18.

37. A method of administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal a dosage unit form as defined in claim 19.

38. A method of administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal a dosage unit form as defined in claim 20.

39. A method of administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal a dosage unit form as defined in claim 21.

40. A method of administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal a dosage unit form as defined in claim 22.

41. A method of administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal a dosage unit form as defined in claim 23.

42. A method of administering interleukin-I to an animal in need of interleukin-I, the method comprising administering orally to the animal a dosage unit form as defined in claim 29.

43. A method of administering insulin to an animal in need of insulin, the method comprising administering orally to the animal a dosage unit form as defined in claim 30.

44. A method of administering growth hormone-releasing hormone to an animal in need of growth hormone-releasing hormone, the method comprising administering orally to the animal a dosage unit form as defined in claim 31.

33. A dosage unit form comprising

(a) a compound having the formula

 

or a salt thereof; and

(b) cromolyn sodium.

34. A dosage unit form as defined in claim 33, comprised of a tablet, a capsule or a liquid.

36. A method of administering cromolyn sodium to an animal in need thereof, the method comprising administering orally to the animal a dosage unit form as defined in claim 33.