Dialkyl ether delivery agents

1. A pharmaceutical composition comprising:

(A) a biologically active agent; and

(B) at least one delivery agent compound having the formula

or a pharmaceutically acceptable salt thereof, wherein

A is a C 1 -C 6 alkylene group;

B is a C 1 -C 2 alkylene group;

R 1 , R 2 , R 3 , R 4 and R 5 are independently H, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkoxyl, un substituted or substituted haloalkoxyl, hydroxyl, —C(O)R 8 , —NO 2 , —NR 9 R 10 , —N + R 9 R 10 R 11 (R 12 ), carbonate, ureido, —CX 3 , or —CN, optionally interrupted by a O, N, S, or —C(O)— group, wherein A and R 1 may together form a cycloalkyl group, wherein

R 8 is independently H, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or —NH 2 ;

R 9 , R 10 , R 11 , and R 12 are independently H or C 1 -C 10 alkyl; and

X is a halogen, and

wherein said biologically active agent is selected from: amylin and amylin agonists; adrenocorticotropin; antigens; antimicrobials, antibiotics, anti-bacterials and anti-fungal agents; anti-migraine agents; BIBM-4096BS, sumatriptan succinate; antivirals, acyclovir, valacyclovir; atrial naturetic factor; argatroban; bisphosphonates, alendronate, clodronate, etidronate, ibandronate, incadronate, minodronate, neridronate, olpadronate, pamidronate, risedronate, tiludronate, zoledronate, EB1053, AND YH529; BIBN4096BS-(1-piperidinecarboxamide. n-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl)carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4(1,4-dih ydro-2-oxo-3(2HO-quinazolinyl)-. [R—(R*,S*)])—); calcitonin, salmon calcitonin, eel calcitonin, porcine calcitonin, human calcitonin; cholecystokinin (CCK) and CCK agonists, CCK-8; cromolyn sodium (sodium or disodium chromoglycate); CPHPC; cyclosporine; desferrioxamine (DFO); erythropoietin; exedin and exedin agonists, exendin-3, exendin-4; filgrastim; follicle stimulating hormone (recombinant and natural); gallium nitrate; glucagon; glucagon-like peptide 1 (GLP-1), glucagon, glucagon-like peptide 2 (GLP-2); glucocerebrosidase; gonadotropin releasing hormone; growth hormone releasing factor; growth hormone releasing hormones; growth hormone, human growth hormone (hGH), recombinant human growth hormone (rhGH), bovine growth hormone, porcine growth hormone; heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, synthetic heparin, fondiparinux; insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, optionally having counter ions selected from the group consisting of zinc, sodium, calcium and ammonium; insulin-like growth factor, IGF-1; interferons, α-interferon, β-interferon, omega interferon, γ interferon; interleukin-1; interleukin-2; interleukin-11; interleukin-21; leutinizing hormone and leutinizing hormone releasing hormone; leptin (OB protein); methyphenidate salt; monoclonal antibodies, retuxin, tnf-alpha soluble receptors; oxytocin; parathyroid hormone (PTH), PTH 1-34 and PTH 1-38; peptide YY (PYY), PYY agonists, PYY3-36; dipeptidyl peptidase IV (DPP-4) inhibitors; prostaglandins; protease inhibitors; somatostatin; thrombopoietin; vancomycin; vasopressin; vitamins; vaccines, anthrax vaccines, y. pestis vaccines, influenza vaccines, herpes vaccines; analogs, mimetics and polyethylene glycol-modified derivatives of any of the above compounds, and any combination thereof.

2. The composition of claim 1 , wherein said delivery agent compound is selected from:

and pharmaceutically acceptable salts thereof.

3. The pharmaceutical composition of claim 1 , wherein A is an unbranched and unsubstituted C 1 -C 6 alkylene group.

4. The pharmaceutical composition of claim 1 wherein B is an unbranched and unsubstituted C 1 -C 2 alkylene group.

5. The pharmaceutical composition of claim 1 wherein B is a methylene group.

6. The pharmaceutical composition of claim 1 wherein R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy or hydroxyl.

7. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 and R 5 is a methyl, chlorine, fluorine, methoxy, bromine, 1-methylethyl, butyl, ethyl, —OC 4 H 9 , or phenyl.

8. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R and R 5 is methyl.

9. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 and R 5 is chlorine.

10. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 and R 5 is fluorine.

11. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 and R 5 is methoxy.

12. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 and R 5 is bromine.

13. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 and R 5 is 1-methylethyl.

14. The pharmaceutical composition of claim 1 wherein at least one of R 1 , R 2 , R 3 , R 4 and R 5 is butyl.

15. A compound selected from:

and pharmaceutically acceptable salts thereof.

16. The pharmaceutical composition of claim 1 , wherein said biologically active agent comprises insulin, unfractionated heparin, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, parathyroid hormone, erythropoietin, daptomycin, human growth hormones, analogs, mimetics or polyethylene glycol-modified derivatives of these compounds, or any combination thereof.

17. 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 pharmaceutical composition of claim 1 .

18. A method for preparing a pharmaceutical composition of claim 1 , comprising mixing:

(A) at least one biologically active agent;

(B) at least one delivery agent compound of Formula I; and

(C) optionally, a dosing vehicle.