Compounds and compositions for delivering active agents

• US 6,693,208 B2
• Filed: 07/15/2002
• Issued: 02/17/2004
• Est. Priority Date: 12/16/1999
• Status: Expired due to Term

• Current Assignee: NOVO Nordisk North America Operations A/S
• Original Assignee: Emisphere Technologies, Inc. (Novo Nordisk A/S)
• Inventors: Leone-Bay, Andrea, Wang, Eric, Gscheidner, David, Freeman, John J., Shields, Lynn, OʼToole, Doris C.
• Primary Examiner(s): Carr, Deborah D.
• Application Number:
  US10/168,275
• Publication Number:
  US 20030216589A1
• Time in Patent Office: 582 Days
• Field of Search: 554/36, 554/6, 554/62, 554/63, 554/65, 554/67, 564/152, 564/155, 564/161, 564/170, 564/171, 564/174, 424/451, 424/452, 424/464, 424/465, 424/489, 514/613, 514/616, 514/617, 514/621, 514/866, 514/889
• US Class Current: 554/1
• CPC Class Codes: C07C 235/60 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• 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 235/84 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 237/42 having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated

Abstract

Amino acid derivative as carrier compounds and compositions which are useful in the delivery of active agents are provided. The active agents can be a peptide, mucopolysaccharide, carbohydrate, or lipid. Methods of administration, including oral administration, and preparation are provided as well.

Claims

1. A compound selected from the group consisting of compounds:

and salts thereof.

2. A composition comprising:

(A) an active agent; and

(B) the compound of claim 1, and mixtures thereof.

3. The composition of claim 2, wherein the active agent is selected from the group consisting of a biologically active agent, a chemically active agent, and a combination thereof.

4. The composition of claim 3, wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormome, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

5. The composition of claim 3, wherein the biologically active agent is selected from the group consisting of:

growth hormones, human growth hormones recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone releasing hormones, growth hormone releasing factor, interferons, α

-interferon, β

-interferon, γ

-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor (IGF), IGF-1, heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human calcitonin;

erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoeitin, filgrastim. postaglandins, cyclosporin, vasopressin, cromolym sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, anti-fungal agents, vitamins;

analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and

any combination thereof.

6. The composition of claim 3, wherein the biologically active agent comprises insulin, heparin, calcitonin, parathyroid hormone, erythropoietin, growth hormones or combinations thereof.

7. The composition of claim 3, wherein the biologically active agent comprises recombinant human growth hormones.

8. The composition of claim 3, wherein the biologically active agent comprises parathyroid hormone.

9. The composition of claim 3, wherein the biologically active agent comprises insulin.

10. The composition of claim 3, wherein the biologically active agent comprises heparin.

11. The composition of claim 3, wherein the biologically active agent comprises calcitonin.

12. The composition of claim 3, wherein the biologically active agent comprises interferon.

13. A composition comprising:

(A) an active agent; and

(B) a poly(amino acid) comprising a compound having a formula selected from the group consisting of the compounds of claim 1, salts thereof and mixtures thereof.

14. The composition of claim 13 wherein the poly (amino acid) is a polypeptide.

15. A dosage unit form comprising:

(A) the composition of claim 2; and

(B) (a) an excipient

(b) a dilutent

(c) a disintegrant,

(d) a lubricant,

(e) a plasticizer,

(f) a colorant,

(g) a dosing vehicle, or

(h) any combination thereof.

16. The dosage unit form of claim 15, wherein the active agent is selected from the group consisting of a biologically active agent, a chemically active agent, and a combination thereof.

17. The dosage unit form of claim 16, wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

18. The dosage unit form of claim 16, wherein the biologically active agent is selected from the group consisting of:

growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone releasing hormones, growth hormone releasing factor, interferons, α

-interferon, β

-interferon, γ

-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor, insulin-like growth factor-1, heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human calcitonin;

erythropoietin, atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoeitin, filgrastim, postaglandins, cyclosporin, vasopressin, cromolym sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine, parathyroid hormone, fragments of PTH, antimicrobials, anti-fungal agents, vitamins;

analogs, fragments, mimetics and polyethylene glycol-modified derivatives of these compounds; and

any combination thereof.

19. The dosage unit form of claim 16, wherein the biologically active agent comprises insulin, heparin, calcitonin, parathyroid hormone, erythropoietin, human growth hormones or combinations thereof.

20. The dosage unit form of claim 15, wherein the active agent comprises recombinant human growth hormone.

21. The dosage unit form of claim 15, wherein the active agent comprises parathyroid hormone.

22. The dosage unit form of claim 15, wherein the active agent comprises insulin.

23. The dosage unit form of claim 15, wherein the active agent comprises heparin.

24. The dosage unit form of claim 15, wherein the active agent comprises calcitonin.

25. The dosage unit form of claim 15, wherein the active agent comprises interferon.

26. The dosage unit form of claim 15, wherein the dosage unit form comprises a dosing vehicle comprising a tablet, a capsule, a powder, or a liquid.

27. The dosage unit form of claim 15, wherein the dosing vehicle is liquid selected from the group consisting or water, 1,2-propane diol, ethanol, and any combination.

28. A method for administering a biologically-active agent to an animal in need of the agent, the method comprising administering orally to the animal the composition of claim 3.

29. A method for preparing a composition comprising mixing:

(A) at least one active agent;

(B) the compound of claim 1; and

(C) optionally, a dosing vehicle.