Compounds and compositions for delivering active agents

• US 6,642,411 B1
• Filed: 04/19/2001
• Issued: 11/04/2003
• Est. Priority Date: 07/27/1998
• 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: Leone-Bay, Andrea, OʼToole, Doris
• Primary Examiner(s): Killos, Paul J.
• Application Number:
  US09/744,862
• Time in Patent Office: 929 Days
• Field of Search: 562/455, 562/457, 514/563
• US Class Current: 562/455
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• 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: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided Methods of administration and preparation are provided as well.

Claims

1. A salt of the compound having the formula

wherein the salt is not a sodium salt.

27. 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) at least one active agent; and

(B) a carrier comprising a compound having the formula

 

or salt thereof.

3. A composition as defined in claim 2, wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.

4. A composition as defined in claim 3, wherein said biologically active agent comprises at least one peptide, mucopolysaccharide, carbohydrate, or lipid.

5. A composition as defined in claim 3, wherein said biologically active agent is selected from the group consisting of growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormone, porcine growth hormones, growth hormone-releasing hormones, interferons, α

-interferon, β

-interferon, γ

-interferon, interleukin-1, interleukin-II;

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, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, anti-fungal agents, analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and

any combination thereof.

6. A composition as defined in claim 3, wherein said biologically active agent is selected from the group consisting of human growth hormones (hGH), bovine growth hormone, growth hormone-releasing hormones, interferons, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, very low molecular weight heparin, calcitonin, erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), antimicrobials, anti-fungal agents, and any combination thereof.

7. A composition as defined in claim 3, wherein said biologically active agent comprises an interferon, interleukin-II, insulin, heparin, low molecular weight heparin, very low molecular weight heparin, calcitonin, parathyroid hormone (PTH), erythropoietin (EPO), human growth hormone (hGH), oxytocin, vasopressin, vancomycin, desferrioxamine (DFO), parathyroid hormone, and combinations thereof.

8. A composition as defined in claim 3, wherein said biologically active agent comprises unfractionated heparin, ultra low molecular weight heparin, and combinations thereof.

9. A composition as defined in claim 3, wherein said biologically active agent comprises insulin.

10. A composition as defined in claim 3, wherein said biologically active agent comprises parathyroid hormone.

11. A composition as defined in claim 3, wherein said biologically active agent comprises human growth hormone.

12. A composition as defined in claim 3, wherein said biologically active agent comprises erythropoietin.

13. A composition as defined in claim 2, wherein said carrier comprises a poly(amino acid) or a polypeptide.

14. A dosage unit form comprising:

(A) a composition as defined in claim 2; and

(B)

(a) an excipient

(b) a diluent,

(c) a disintegrant,

(d) a lubricant,

(e) a plasticizer,

(f) a colorant,

(g) a dosing vehicle, or

(h) any combination thereof.

15. A dosage unit form as defined in claim 13, wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.

16. A dosage unit form as defined in claim 14, wherein said biologically active agent comprises at least one peptide, mucopolysaccharide, carbohydrate, or lipid.

17. A dosage unit form as defined in claim 14, wherein said biologically active agent is selected from the group consisting of growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormone, porcine growth hormones, growth hormone-releasing hormones, interferons, α

-interferon, β

-interferon, γ

-interferon, interleukin-1, interleukin-II, 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, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, anti-fungal agents, analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds, and any combination thereof.

18. A dosage unit form as defined in claim 14, wherein said biologically active agent is selected from the group consisting of human growth hormones (hGH), bovine growth hormone, growth hormone-releasing hormones, interferons, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, very low molecular weight heparin, calcitonin, erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), antimicrobials, anti-fungal agents, and any combination thereof.

19. A dosage unit form as defined in claim 14, wherein said biologically active agent comprises an interferon, interleukin-II, insulin, heparin, low molecular weight heparin, very low molecular weight heparin, calcitonin, parathyroid hormone (PTH), erythropoietin (EPO), human growth hormone (hGH), oxytocin, vasopressin, vancomycin, desferrioxamine (DFO), parathyroid hormone, and combinations thereof.

20. A dosage unit form as defined in claim 14, wherein said biologically active agent comprises unfractionated heparin, ultra low molecular weight heparin, and combinations thereof.

21. A dosage unit form as defined in claim 14, wherein said biologically active agent comprises insulin.

22. A dosage unit form as defined in claim 14, wherein said biologically active agent comprises parathyroid hormone.

23. A dosage unit form as defined in claim 14, wherein said biologically active agent comprises human growth hormone.

24. A dosage unit form as defined in claim 14, wherein said biologically active agent comprises erythropoietin.

25. A dosage unit form as defined in claim 13, comprising a tablet, a powder, a capsule, or a liquid.

26. A method for administering a biologically-active agent to an animal in need of said agent, said method comprising administering orally to said animal a composition as defined in claim 3.