Compounds and compositions for delivering active agents

• US 6,646,162 B2
• Filed: 08/24/2001
• Issued: 11/11/2003
• Est. Priority Date: 02/26/1999
• Status: Expired due to Fees

• Current Assignee: NOVO Nordisk North America Operations A/S
• Original Assignee: Emisphere Technologies, Inc. (Novo Nordisk A/S)
• Inventors: Tang, Pingwah, Gschneidner, David, Leone-Bay, Andrea
• Primary Examiner(s): Killos, Paul J.
• Application Number:
  US09/939,511
• Publication Number:
  US 20020040061A1
• Time in Patent Office: 809 Days
• Field of Search: 564/167, 548/543, 548/346.1, 544/222
• US Class Current: 564/167
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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 2601/14 The ring being saturated
• CPC Class Codes: C07D 207/27 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain

Abstract

Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Claims

1. A compound selected from

and salts thereof.

28. 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.

2. A composition comprising:

(A) an active agent; and

(B) at least one compound selected from

and salts 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, hormone, 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 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, cromolyn 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 5, wherein the biologically active agent comprises insulin, heparin, calcitonin, parathyroid hormone, erythropoietin, growth hormones or combinations thereof.

7. The composition of claim 5, wherein the biologically active agent comprises recombinant human growth hormone.

8. The composition of claim 5, wherein the biologically active agent comprises parathyroid hormone.

9. The composition of claim 5, wherein the biologically active agent comprises insulin.

10. The composition of claim 5, wherein the biologically active agent comprises heparin.

11. The composition of claim 5, wherein the biologically active agent comprises calcitonin.

12. The composition of claim 5, wherein the biologically active agent comprises interferon.

13. The composition of claim 5, wherein the biologically active agent comprises cromolyn.

14. 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.

15. The dosage unit form of claim 14, wherein the active agent is selected from the group consisting of a biologically active agent, a chemically active agent, and a combination thereof.

16. The dosage unit form of claim 15, wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

17. 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, cromolyn 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.

18. The dosage unit form of claim 15, wherein the biologically active agent comprises insulin, heparin, calcitonin, parathyroid hormone, erythropoietin, human growth hormones or combinations thereof.

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

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

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

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

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

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

25. 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.

26. 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.

27. 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.