Phenoxy carboxylic acid compounds and compositions for delivering active agents
View Patent ↗Phenoxy carboxylic acid compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are provided as well.
1. A compound having the formula
and salts thereof, wherein
R 1 is H, —OH, halogen, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy, —C(O)R 8 , —NO 2 , —NR 9 R 10 , or —N + R 9 R 10 R 11 (R 12 ) − ;
R 2 is H, —OH, halogen, C 2 -C 4 alkenyl, C 2 -C 4 alkoxy, —C(O)R 8 , —NO 2 , —NR 9 R 10 , or —N + R 9 R 10 R 11 (R 12 );
R 3 is H, halogen, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy, —C(O)R 8 , —NO 2 , —NR 9 R 10 , or —N + R 9 R 10 R 11 (R 12 );
R 4 is H, —OH, halogen, C 2 -C 4 alkenyl, C 2 -C 4 alkoxy, —C(O)R 8 , —NO 2 , —NR 9 R 10 , or —N + R 9 R 10 R 11 (R 12 );
R 5 is —NO 2 , halogen, —NR 14 R 15 ,—N + R 14 R 15 R 16 (R 13 ) − , amide, C 1 -C 12 alkoxy, C 2 -C 12 alkenyl, carbamate, carbonate, ureido, or —C(O)R 18 ;
R 5 is optionally substituted with halogen, —OH, —SH, or —COOH;
R 5 is optionally interrupted by O, N, S, or —C(O)—;
R 6 is a C 4 -C 12 linear or branched alkyl, C 2 -C 12 linear or branched alkenyl, or aryl;
R 6 is optionally substituted with a C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy, —OH, —SH, halogen, —NH 2 , or —CO 2 R 8 ;
R 6 is optionally interrupted by O or N;
R 7 is a bond or aryl;
R 7 is optionally substituted with —OH, halogen, —C(O)CH 3 , —NR 10 R 11 , or —N + R 10 R 11 R 12 (R 13 ) − ;
R 8 is C 1 -C 4 alkyl, or C 2 -C 4 alkenyl;
R 9 , R 10 , R 11 , and R 12 are independently H or C 1 -C 10 alkyl;
R 13 is a halide, hydroxide, sulfate, tetrafluoroborate, or phosphate; and
R 14 , R 15 and R 16 are independently C 1 -C 10 alkyl, C 2 -C 12 alkenyl, —C(O)R 7 ;
R 17 is —OH, C 1 -C 10 alkyl, or C 2 -C 12 alkenyl; and
R 18 is C 1 -C 6 alkyl, —OH, —NR 14 R 15 , or N + R 14 R 15 R 16 (R 13 ).
2. A compound selected from the group consisting of
Cpd
#
R 1
R 2
R 3
R 4
1
H
H
H
H
2
H
H
H
H
9
H
H
H
H
10
H
H
H
H
11
H
H
H
H
12
H
H
H
H
18
H
H
H
H
19
H
H
H
H
20
H
H
H
H
22
H
H
Cl
H
23
H
H
Cl
H
24
H
H
H
H
25
H
H
H
H
26
H
H
H
H
27
H
H
H
H
28
H
H
H
H
29
H
H
H
H
30
H
H
H
H
31
H
H
H
H
32
H
H
H
H
33
H
H
H
H
34
H
H
H
H
35
H
H
H
H
36
H
H
H
H
37
H
H
H
H
38
H
H
H
OH
39
H
H
H
OCH 3
51
H
H
H
H
52
H
H
H
H
54
H
H
H
H
55
H
H
OCH 3
H
56
H
OCH 3
H
H
57
H
H
OH
H
58
H
H
CH 3
H
59
H
H
H
H
61
H
H
H
H
62
H
H
C(O)CH 3
H
63
H
H
C(O)CH 2 CH 3
H
64
H
C(O)CH 3
H
H
68
H
Cl
H
H
71
H
H
F
H
72
H
H
H
H
73
H
H
H
H
74
H
NO 2
H
H
75
H
H
H
H
76
H
H
H
H
77
H
H
H
H
79
H
H
H
H
80
H
H
OCH 3
H
81
H
H
OH
H
82
H
H
OH
H
83
H
H
OH
H
84
H
H
OH
H
85
H
H
OCH 3
H
86
H
H
OCH 3
H
87
H
H
H
H
88
H
H
H
H
89
H
H
Cl
H
90
H
H
H
H
91
H
OCH 3
H
H
92
H
H
H
H
93
H
CH 3
H
H
94
H
CH 3
H
H
Cpd
#
R 5
R 6
R 7
1
C(O)CH 3
CH 2
para-
Ph
2
OH
CH 2
para-
Ph
9
C(O)CH 3
(CH 2 ) 3
bond
10
C(O)CH 3
(CH 2 ) 4
bond
11
C(O)CH 3
(CH 2 ) 5
bond
12
C(O)CH 3
(CH 2 ) 7
bond
18
CH═CHCH 3
(CH 2 ) 7
bond
19
NH 2
(CH 2 ) 7
bond
20
NO 2
(CH 2 ) 7
bond
22
NH 2
(CH 2 ) 7
bond
23
NH 2
(CH 2 ) 4
bond
24
NHC(O)CH 3
(CH 2 ) 7
bond
25
CH═CHCO 2 H
(CH 2 ) 7
bond
26
C(O)CH 2 CH 3
(CH 2 ) 3
bond
27
C(O)CH 2 CH 3
(CH 2 ) 5
bond
28
C(O)CH 2 CH 3
(CH 2 ) 7
bond
29
C(O)CH 2 CH 3
(CH 2 ) 9
bond
30
C(O)NH 2
(CH 2 ) 7
bond
31
C(O)NHCH 3
(CH 2 ) 7
bond
32
COOH
(CH 2 ) 7
bond
33
C(O)NHCH 2 CH 3
(CH 2 ) 7
bond
34
C(O)NHCH(CH 3 ) 2
(CH 2 ) 7
bond
35
OCH 3
(CH 2 ) 7
bond
36
CH(OH)CH 3
(CH 2 ) 7
bond
37
C(CH 3 ) 2 OH
CH 2
para-
Ph
38
C(O)CH 3
(CH 2 ) 7
bond
39
C(O)CH 3
(CH 2 ) 7
bond
51
C(O)NHCH 3
(CH 2 ) 9
bond
52
C(O)NH 2
CH 2
para-
Ph
54
C(O)CH 3
(CH 2 ) 9
bond
55
C(O)CH 3
(CH 2 ) 7
bond
56
C(O)CH 3
(CH 2 ) 7
bond
57
C(O)CH 3
(CH 2 ) 7
bond
58
C(O)CH 3
(CH 2 ) 5
bond
59
C(O)H
CH 2
para-
Ph
61
C(O)H
(CH 2 ) 7
bond
62
H
(CH 2 ) 7
bond
63
H
(CH 2 ) 7
bond
64
H
(CH 2 ) 7
bond
68
H
(CH 2 ) 7
bond
71
F
(CH 2 ) 7
bond
72
OH
(CH 2 ) 10
bond
73
Cl
(CH 2 ) 7
bond
74
OH
(CH 2 ) 7
bond
75
F
(CH 2 ) 4
bond
76
CF 3
(CH 2 ) 4
bond
77
F
(CH 2 ) 7
bond
79
OH
CH 2 CH(OH)
para-
Ph
80
H
(CH 2 ) 6 —CH(CH 3 )
bond
81
H
(CH 2 ) 6 —CH(CH 3 )
bond
82
H
(CH 2 ) 6 —CH(CH 2 CH 2 CH 3 )
bond
83
H
(CH 2 ) 7 —(CH 3 )
bond
84
H
(CH 2 ) 7 (CH 2 CH 2 CH 3 )
bond
85
H
(CH 2 ) 7 (CH 3 )
bond
86
H
(CH 2 ) 7
bond
87
—C(O)NH—(CH 2 ) 7 —COOH
(CH 2 ) 7
bond
88
—C(O)NH—(CH 2 ) 9 —OH
CH 2
bond
89
—C(O)NH—(CH 2 ) 7 —COOH
(CH 2 ) 7
bond
90
—C(O)NH—(CH 2 ) 9 —COOH
(CH 2 ) 9
bond
91
—C(O)NH—(CH 2 ) 7 —COOH
(CH 2 ) 7
bond
92
—O(CH 2 ) 5 COOH
(CH 2 ) 5
bond
93
CH 3
(CH 2 ) 7
bond
94
CH 3
(CH 2 ) 5
bond
and salts thereof.
3. A pharmaceutical composition comprising:
(A) a biologically active agent; and
(B) at least one compound having the formula
and salts thereof, wherein
R 1 , R 2 , R 3 , and R 4 are independently H, —OH, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy, —C(O)R 8 , —NO 2 , —NR 9 R 10 , or —N + R 9 R 10 R 11 (R 12 ) − ;
R 5 is —OH, —NO 2 , halogen, —NR 14 R 15 , —N + R 14 R 15 R 16 (R 13 ) − , amide, C 1 -C 12 alkoxy, C 2 -C 12 alkenyl, carbamate, carbonate, ureido, or —C(O)R 18 ;
R 5 is optionally substituted with halogen, —OH, —SH, or —COOH;
R 5 is optionally interrupted by O, N, S, or —C(O)—;
R 6 is a C 1 -C 12 linear or branched alkyl, C 2 -C 12 linear or branched alkenyl, or aryl;
R 6 is optionally substituted with a C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy, —OH, —SH, halogen, —NH 2 , or —CO 2 R 8 ;
R 6 is optionally interrupted by O or N;
R 7 is a bond or aryl;
R 7 is optionally substituted with —OH, halogen, —C(O)CH 3 , —NR 10 R 11 , or —N + R 10 R 11 R 12 (R 13 ) − ;
R 8 is H, C 1 -C 4 alkyl, or C 2 -C 4 alkenyl;
R 9 , R 10 , R 11 , and R 12 independently H or C 1 -C 10 alkyl;
R 13 is a halide, hydroxide, sulfate, tetrafluoroborate, or phosphate; and
R 14 , R 15 and R 16 are independently H, C 1 -C 10 alkyl, C 2 -C 12 alkenyl, —C(O)R 7 ;
R 17 is —OH, C 1 -C 10 alkyl, or C 2 -C 12 alkenyl; and
R 18 is C 1 -C 6 alkyl, —OH, —NR 14 R 15 , or N + R 14 R 15 R 16 (R 13 );
with the proviso that
when R 1 , R 2 , R 3 , and R 4 are H, R 5 is —OH, R 7 is a bond then R 6 is not a C 1 -C 3 alkyl;
when at least one of R 1 , R 2 , R 3 , and R 4 is not H, R 5 is —OH, R 7 is a bond, then R 6 is not a C 1 -C 4 alkyl; and
when R 1 , R 2 , and R 3 are H, R 4 is —OCH 3 , R 5 is —C(O)CH 3 , and R 6 is a bond then R 7 is not a C 3 alkyl.
4. A pharmaceutical composition comprising:
(A) a biologically active agent; and
(C) at least one compound having the formula
Cpd
#
R 1
R 2
R 3
R 4
1
H
H
H
H
2
H
H
H
H
3
H
H
H
H
4
H
H
H
H
5
H
H
H
H
6
H
H
H
H
7
H
H
H
H
8
H
H
H
H
9
H
H
H
H
10
H
H
H
H
11
H
H
H
H
12
H
H
H
H
13
H
H
H
H
14
H
H
H
H
15
H
H
H
H
16
H
H
H
H
17
H
H
H
H
18
H
H
H
H
19
H
H
H
H
20
H
H
H
H
21
H
H
H
H
22
H
H
Cl
H
23
H
H
Cl
H
24
H
H
H
H
25
H
H
H
H
26
H
H
H
H
27
H
H
H
H
28
H
H
H
H
29
H
H
H
H
30
H
H
H
H
31
H
H
H
H
32
H
H
H
H
33
H
H
H
H
34
H
H
H
H
35
H
H
H
H
36
H
H
H
H
37
H
H
H
H
38
H
H
H
OH
39
H
H
H
OCH 3
43
H
OH
H
H
44
H
OH
H
H
45
H
OH
H
H
46
H
OH
H
H
47
H
H
OH
H
48
H
H
OH
H
49
H
H
OH
H
50
H
H
OH
H
51
H
H
H
H
52
H
H
H
H
54
H
H
H
H
55
H
H
OCH 3
H
56
H
OCH 3
H
H
57
H
H
OH
H
58
H
H
CH 3
H
59
H
H
H
H
60
H
H
H
H
61
H
H
H
H
62
H
H
C(O)CH 3
H
63
H
H
C(O)CH 2 CH 3
H
64
H
C(O)CH 3
H
H
65
H
H
H
H
66
H
H
H
H
67
H
H
OH
H
68
H
Cl
H
H
69
H
OCH 3
H
H
71
H
H
F
H
72
H
H
H
H
73
H
H
H
H
74
H
NO 2
H
H
75
H
H
H
H
76
H
H
H
H
77
H
H
H
H
78
H
H
H
H
79
H
H
H
H
80
H
H
OCH 3
H
81
H
H
OH
H
82
H
H
OH
H
83
H
H
OH
H
84
H
H
OH
H
85
H
H
OCH 3
H
86
H
H
OCH 3
H
87
H
H
H
H
88
H
H
H
H
89
H
H
Cl
H
90
H
H
H
H
91
H
OCH 3
H
H
92
H
H
H
H
93
H
CH 3
H
H
94
H
CH 3
H
H
95
H
H
NO 2
H
96
H
H
NH 2
H
97
H
CH 3
H
H
Cpd
#
R 5
R 6
R 7
1
C(O)CH 3
CH 2
para-
Ph
2
OH
CH 2
para-
Ph
3
OH
CH 2
bond
4
OH
(CH 2 ) 3
bond
5
OH
(CH 2 ) 5
bond
6
OH
(CH 2 ) 6
bond
7
OH
(CH 2 ) 7
bond
8
OH
(CH 2 ) 9
bond
9
C(O)CH 3
(CH 2 ) 3
bond
10
C(O)CH 3
(CH 2 ) 4
bond
11
C(O)CH 3
(CH 2 ) 5
bond
12
C(O)CH 3
(CH 2 ) 7
bond
13
H
CH 2
bond
14
H
(CH 2 ) 3
bond
15
H
(CH 2 ) 5
bond
16
H
(CH 2 ) 9
bond
17
H
(CH 2 ) 10
bond
18
CH═CHCH 3
(CH 2 ) 7
bond
19
NH 2
(CH 2 ) 7
bond
20
NO 2
(CH 2 ) 7
bond
21
NH 2
(CH 2 ) 4
bond
22
NH 2
(CH 2 ) 7
bond
23
NH 2
(CH 2 ) 4
bond
24
NHC(O)CH 3
(CH 2 ) 7
bond
25
CH═CHCO 2 H
(CH 2 ) 7
bond
26
C(O)CH 2 CH 3
(CH 2 ) 3
bond
27
C(O)CH 2 CH 3
(CH 2 ) 5
bond
28
C(O)CH 2 CH 3
(CH 2 ) 7
bond
29
C(O)CH 2 CH 3
(CH 2 ) 9
bond
30
C(O)NH 2
(CH 2 ) 7
bond
31
C(O)NHCH 3
(CH 2 ) 7
bond
32
COOH
(CH 2 ) 7
bond
33
C(O)NHCH 2 CH 3
(CH 2 ) 7
bond
34
C(O)NHCH(CH 3 ) 2
(CH 2 ) 7
bond
35
OCH 3
(CH 2 ) 7
bond
36
CH(OH)CH 3
(CH 2 ) 7
bond
37
C(CH 3 ) 2 OH
CH 2
para-
Ph
38
C(O)CH 3
(CH 2 ) 7
bond
39
C(O)CH 3
(CH 2 ) 7
bond
43
H
(CH 2 ) 7
bond
44
H
(CH 2 ) 9
bond
45
H
(CH 2 ) 5
bond
46
H
(CH 2 ) 3
bond
47
H
(CH 2 ) 7
bond
48
H
(CH 2 ) 9
bond
49
H
(CH 2 ) 5
bond
50
H
(CH 2 ) 3
bond
51
C(O)NHCH 3
(CH 2 ) 9
bond
52
C(O)NH 2
CH 2
para-
Ph
54
C(O)CH 3
(CH 2 ) 9
bond
55
C(O)CH 3
(CH 2 ) 7
bond
56
C(O)CH 3
(CH 2 ) 7
bond
57
C(O)CH 3
(CH 2 ) 7
bond
58
C(O)CH 3
(CH 2 ) 5
bond
59
C(O)H
CH 2
para-
Ph
60
C(O)H
(CH 2 ) 5
bond
61
C(O)H
(CH 2 ) 7
bond
62
H
(CH 2 ) 7
bond
63
H
(CH 2 ) 7
bond
64
H
(CH 2 ) 7
bond
65
H
(CH 2 ) 7
bond
66
H
CH 2
para-
Ph
67
H
CH 2
para-
Ph
68
H
(CH 2 ) 7
bond
69
H
(CH 2 ) 7
bond
71
F
(CH 2 ) 7
bond
72
OH
(CH 2 ) 10
bond
73
Cl
(CH 2 ) 7
bond
74
OH
(CH 2 ) 7
bond
75
F
(CH 2 ) 4
bond
76
CF 3
(CH 2 ) 4
bond
77
F
(CH 2 ) 7
bond
78
Cl
CH 2
para-
Ph
79
OH
CH 2 CH(OH)
para-
Ph
80
H
(CH 2 ) 6 —CH(CH 3 )
bond
81
H
(CH 2 ) 6 —CH(CH 3 )
bond
82
H
(CH 2 ) 6 —CH(CH 2 CH 2 CH 3 )
bond
83
H
(CH 2 ) 7 —(CH 3 )
bond
84
H
(CH 2 ) 7 (CH 2 CH 2 CH 3 )
bond
85
H
(CH 2 ) 7 (CH 3 )
bond
86
H
(CH 2 ) 7
bond
87
—C(O)NH—(CH 2 ) 7 —COOH
(CH 2 ) 7
bond
88
—C(O)NH—(CH 2 ) 9 —OH
CH 2
bond
89
—C(O)NH—(CH 2 ) 7 —COOH
(CH 2 ) 7
bond
90
—C(O)NH—(CH 2 ) 9 —COOH
(CH 2 ) 9
bond
91
—C(O)NH—(CH 2 ) 7 —COOH
(CH 2 ) 7
bond
92
—O(CH 2 ) 5 COOH
(CH 2 ) 5
bond
93
CH 3
(CH 2 ) 7
bond
94
CH 3
(CH 2 ) 5
bond
95
H
para-Ph
bond
96
H
para-Ph
bond
97
CH 3
(CH 2 ) 3 —(C(CH 3 ) 2 )
Bond
and salts thereof.
5. The pharmaceutical composition of claim 4 , wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, small polar organic molecule, or lipid.
6. The pharmaceutical composition of claim 4 , 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; analogs, fragments, mimetics and polyethylene glycol-modified derivatives of these compounds, and any combination thereof.
7. The pharmaceutical composition of claim 6 , 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, analogs, fragments, mimetics or polyethylene glycol-modified derivatives of these compounds; or any combination thereof.
8. The pharmaceutical composition of claim 7 , wherein the biologically active agent comprises calcitonin.
9. A dosage unit form comprising:
(A) a pharmaceutical composition of claim 4 ; 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.
10. The dosage unit form of claim 9 , wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, small polar organic molecule, carbohydrate, or lipid.
11. The dosage unit form of claim 9 , 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, analogs, fragments, mimetics and polyethylene glycol-modified derivatives of these compounds, and any combination thereof.
12. The dosage unit form of claim 11 , 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, analogs, fragments, mimetics or polyethylene glycol (PEG)-modified derivatives of these compounds; or any combination thereof.
13. The dosage unit form of claim 12 , wherein the active agent comprises calcitonin.
14. The dosage unit form of claim 9 , wherein the dosage unit form comprises a tablet, a capsule, a powder, or a liquid.
15. A method for administering a biologically active agent to an animal in need of the agent, the method comprising administering orally to the animal a pharmaceutical composition of claim 4 .
16. A method for preparing a pharmaceutical 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.
17. A pharmaceutical composition comprising:
(A) 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
47
H
H
OH
H
H
(CH 2 ) 7
bond
48
H
H
OH
H
H
(CH 2 ) 9
bond
and salts thereof; and
(B) a biologically active agent comprising at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, small polar organic molecule, or lipid.
18. The pharmaceutical composition of claim 17 , wherein the biologically active agent is selected from the group consisting of:
growth hormones, human growth hormones, recombinant human growth hormones, bovine growth hormones, porcine growth hormones, growth hormone-releasing hormones, interferons, cc interferon, β-interferon, γ-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor, 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, bisphosphonates, alendronate, tiludronate, etidronate, clodronate, pamidronate, olpadronate, incadronate, parathyroid hormone, fragments of parathyroid hormone, antimicrobials, daptomycin, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol-modified derivatives of these compounds, and any combination thereof.
19. The pharmaceutical composition 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, daptomycin, human growth hormones, analogs, fragments, mimetics or polyethylene glycol-modified derivatives of these compounds; or any combination thereof.
20. The pharmaceutical composition of claim 3 , wherein R 6 is a C 4 -C 12 linear or branched alkyl, C 2 -C 12 linear or branched alkenyl, or aryl, wherein R 6 is optionally substituted with a C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy, —OH, —SH, halogen, —NH 2 , or —CO 2 R 8 ; and R 6 is optionally interrupted by O or N.
21. A pharmaceutical composition comprising:
(A) a biologically active agent; and
(B) a compound of claim 1 .
22. The pharmaceutical composition of claim 21 , wherein the biologically active agent is selected from:
growth hormones, human growth hormones, recombinant human growth hormones, 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-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, bisphosphonates, alendronate, tiludronate, etidronate, clodronate, pamidronate, olpadronate, incadronate, parathyroid hormone, fragments of parathyroid hormone, antimicrobials, daptomycin, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol-modified derivatives of these compounds, and any combination thereof.
23. The pharmaceutical composition of claim 22 , 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, analogs, fragments, mimetics or polyethylene glycol-modified derivatives of these compounds; or any combination thereof.