Phenoxy carboxylic acid compounds and compositions for delivering active agents

1. A compound having the formula

or a salt thereof, wherein

R 1 , R 2 , R 3 , and R 4 are H;

R 5 is —OH;

R 6 is a C 4 -C 12 alkylene; and

R 7 is a bond.

2. A compound selected from the group consisting of

Cpd #

R 1

R 2

R 3

R 4

R 5

R 6

R 7

5

H

H

H

H

OH

(CH 2 ) 5

bond

6

H

H

H

H

OH

(CH 2 ) 6

bond

7

H

H

H

H

OH

(CH 2 ) 7

bond

8

H

H

H

H

OH

(CH 2 ) 9

bond

43

H

OH

H

H

H

(CH 2 ) 7

bond

44

H

OH

H

H

H

(CH 2 ) 9

bond

45

H

OH

H

H

H

(CH 2 ) 5

bond

46

H

OH

H

H

H

(CH 2 ) 3

bond

47

H

H

OH

H

H

(CH 2 ) 7

bond

48

H

H

OH

H

H

(CH 2 ) 9

bond

and salts thereof.

3. A compound having the formula

or a salt thereof, wherein

R 1 , R 2 , R 3 , and R 5 are H;

R 4 is OH;

R 6 is a C 2 -C 12 alkylene; and

R 7 is a bond.

4. A compound having the formula

or a salt thereof, wherein

R 1 , R 2 , R 4 , and R 5 are H;

R 3 is OH;

R 6 is a C 6 -C 9 alkylene; and

R 7 is a bond.

5. A compound having the formula

and salts thereof, wherein

R 1 , R 2 , R 3 , and R 4 are H;

R 5 is OH;

R 6 is a C 1 alkylene; and

R 7 is a bond.

6. A compound having the formula

or a salt thereof, wherein

R 1 , R 2 , R 4 , and R 5 are H;

R 3 is OH;

R 6 is a C 11 -C 12 alkylene; and

R 7 is a bond.

7. The compound of claim 2 , wherein the compound is selected from:

Cpd #

R 1

R 2

R 3

R 4

R 5

R 6

R 7

43

H

OH

H

H

H

(CH 2 ) 7

bond

44

H

OH

H

H

H

(CH 2 ) 9

bond

45

H

OH

H

H

H

(CH 2 ) 5

bond

46

H

OH

H

H

H

(CH 2 ) 3

bond

47

H

H

OH

H

H

(CH 2 ) 7

bond

and salts thereof.

8. The compound of claim 7 , wherein the compound is selected from:

Cpd #

R 1

R 2

R 3

R 4

R 5

R 6

R 7

47

H

H

OH

H

H

(CH 2 ) 7

bond

and salts thereof.

9. A composition comprising:

(A) at least one biologically active agent; and

(B) at least one compound of claim 1 .

10. A composition comprising:

(A) at least one biologically active agent; and

(B) at least one compound of claim 2 .

11. The composition of claim 10 , wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, polar organic molecules, or lipid.

12. The composition of claim 10 , 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, 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, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine, parathyroid hormone, fragments of parathyroid hormone, antimicrobials, daptomycin, anti-fungal agents, vitamins; and any combination thereof.

13. The composition of claim 12 , wherein the 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, or any combination thereof.

14. The composition of claim 13 , wherein the biologically active agent comprises calcitonin.

15. The composition of claim 13 , wherein the compound has the formula

Cpd #

R 1

R 2

R 3

R 4

R 5

R 6

R 7

43

H

OH

H

H

H

(CH 2 ) 7

bond.

16. A dosage unit form comprising:

(A) the composition of claim 10 ; 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.

17. The dosage unit form of claim 16 , wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, polar organic molecules, 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, 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, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, daptomycin, anti-fungal agents, vitamins, and any combination thereof.

19. The dosage unit form of claim 18 , wherein the 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, human growth hormones, or any combination thereof.

20. The dosage unit form of claim 19 , wherein the biologically active agent comprises calcitonin.

21. The dosage unit form of claim 16 , wherein the dosage unit form comprises a tablet, a capsule, a powder, or a liquid.

22. A method of increasing the bioavailability of a biologically active agent comprising orally administering to an animal in need thereof the composition of claim 10 .

23. A method for preparing a composition comprising mixing:

(A) at least one biologically active agent;

(B) at least one compound as claimed in claim 2 ; and

(C) optionally, a dosing vehicle.