UNSYMMETRICAL AROMATIC ETHER DIACIDS AND ABSORBABLE POLYMERS THEREFROM
First Claim
Patent Images
1. A compound of formula I or a pharmaceutically acceptable salt thereof:
-
[R′
—
(Y)p—
O]q—
Ar—
[O—
(X)r—
R′
]s
I Ar is the aromatic portion of a diphenol;
X and Y are independently selected from;
—
CH2COO—
;
—
CH(CH3)COO—
;
—
CH2CH2OCH2COO—
;
—
CH2CH2CH2CH2CH2COO—
;
—
(CH2)yCOO—
where y is independently selected from 2-4 and 6-24; and
, —
(CH2CH2O)zCH2COO—
where z is independently selected from 2-24;
provided that the groups represented by [R′
—
(Y)p—
O]q— and
—
[O—
(X)r—
R′
], are different from one another;
R′
is selected from H, benzyl, and C1-6 alkyl;
p is selected from 1, 2, 3, 4, 5, and 6;
q is selected from 1, 2, and 3. r is selected from 1, 2, 3, 4, 5, and 6; and
, s is selected from 1, 2, and 3.
1 Assignment
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Accused Products
Abstract
The present invention relates to compounds of formula I, which are unsymmetrical aromatic ether diacids, and polymers formed from the same.
[R′—(Y)p—O]q—Ar—[O—(X)r—R′]s I Polymers formed from the functionalized unsymmetrical aromatic ether diacids are expected to have controllable degradation profiles, enabling them to release an active component over a desired time range. The polymers are also expected to be useful in a variety of medical applications.
-
Citations
64 Claims
-
1. A compound of formula I or a pharmaceutically acceptable salt thereof:
-
[R′
—
(Y)p—
O]q—
Ar—
[O—
(X)r—
R′
]s
IAr is the aromatic portion of a diphenol;
X and Y are independently selected from;
—
CH2COO—
;
—
CH(CH3)COO—
;
—
CH2CH2OCH2COO—
;
—
CH2CH2CH2CH2CH2COO—
;
—
(CH2)yCOO—
where y is independently selected from 2-4 and 6-24; and
,—
(CH2CH2O)zCH2COO—
where z is independently selected from 2-24;
provided that the groups represented by [R′
—
(Y)p—
O]q— and
—
[O—
(X)r—
R′
], are different from one another;
R′
is selected from H, benzyl, and C1-6 alkyl;
p is selected from 1, 2, 3, 4, 5, and 6;
q is selected from 1, 2, and 3. r is selected from 1, 2, 3, 4, 5, and 6; and
,s is selected from 1, 2, and 3. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
z is independently selected from 2, 3, and 4;
p is selected from 1, 2, and 3;
q is selected from 1, 2, and 3;
r is selected from 1, 2, and 3; and
,s is selected from 1, 2, and 3.
-
-
3. A compound of claim 1, wherein
X and Y are independently selected from: -
—
CH2COO—
;
—
CH(CH3)COO—
;
—
CH2CH2OCH2COO—
; and
,—
CH2CH2CH2CH2CH2COO—
;
p is selected from 1 and 2;
q is selected from 1 and 2;
r is selected from 1 and 2; and
,s is selected from 1 and 2.
-
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4. A compound of claim 1, wherein Ar corresponds to the residue of a diphenol selected from:
- phenols, naphthols, indoles, acetophenones, benzophenones, flavonoids, chalcones, drugs containing diphenol groups, and natural products containing diphenol groups.
-
5. A compound of claim 4, wherein Ar corresponds to the residue of a natural product containing diphenol groups selected from:
- benzoic acids, cinnamic acids (e.g.,caffeic acid, ferulic acid, chlorogenic acid), capsaicin, coumarins, furanocoumarins, alkaloids, catechins, chromones, chalcones, flavonoids or bioflavonoids, isoflavones, curcumine, ellagic acid, resveratrol.
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6. A compound of claim 5, wherein Ar corresponds to the residue of an unsymmetrical aromatic ether diacid selected from:
- caffeic acid, chlorogenic acid, ferulic acid, 2,5-dihydroxybenzoic acid, capsaicin, isopimpinellin, daidzein, genistein, equol, glycitein, puerarin, curcumine, ellagic acid, and resveratrol.
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7. A compound of claim 4, wherein Ar corresponds to the residue of an unsymmetrical aromatic ether diacid selected from:
- resorcinol, catechol, 1,4-dihydroxy-phenyl, tri-hydroxy-phenyls, dihydroxy-naphthyl, tri-hydroxy-naphthyl, and tetra-hydroxy-napthyl, chromones, chalcones, flavonoids, dihydroxy-benzoic acid, indoles, acetophenones, benzophenones, catechins, hydroquinone, and polyphenols.
-
8. A compound of claim 2, wherein:
Ar is a substituted or unsubstituted aryl ring consisting of 1-6 phenyl rings.
-
9. A compound of claim 8, wherein:
Ar is a substituted or unsubstituted aryl ring consisting of 1-3 phenyl rings.
-
10. A compound of claim 9, wherein:
-
each Ar ring is independently substituted with 1, 2, or 3 R groups R is independently selected from H, ═
O, O-glycosides, —
(CH2)0-2—
ORa, —
(CH2)0-2—
C6H5, —
(CH2)0-2—
CHO, Cl, F, Br, I, —
(CH2)0-2—
OC(O)—
Ra, —
(CH2)0-2—
CO2—
Ra, —
(C(CH3))0-2—
CO2—
Ra, —
(CH2)0-2—
CO2—
(CH2)1-2—
CO2—
Ra, —
(C(CH3))0-2—
CO2—
(CH2)1-2—
CO2—
Ra, —
(CH2)0-2—
CO—
Ra, —
O(CH2)0-2C6H5, —
O(CH2)1-2—
CO2—
Ra, —
O(C(CH3))1-2—
CO2—
Ra, —
O(CH2)1-2—
CO—
Ra, —
CO2(CH2)1-2—
CO2—
Ra, —
CO2(C(CH3))1-2—
CO2—
Ra, —
(CH2)0-2—
NO2, —
(CH2)0-2—
NRaRa, —
(CH2)0-2—
NRaCORa, —
(CH2)0-2—
NRaC(O)(CH2)1-2ORa, —
C6H5, —
C6H5ORa, and —
C6H5—
CH═
CHCO2Ra; and
,Ra is independently selected from H and C1-6 alkyl.
-
-
11. A compound of claim 1, wherein:
-
Ar is selected from;
each Ar is substituted with 1-2 R;
R is independently selected from H, ═
O, —
(CH2)0-2—
ORa, —
(CH2)0-2—
C6H5, —
(CH2)0-2—
CHO, Cl, F, Br, I, —
(CH2)0-2—
OC(O)—
Ra, —
(CH2)0-2—
CO2—
Ra, —
(C(CH3))0-2—
CO2—
Ra, —
(CH2)0-2—
CO2—
(CH2)1-2—
CO2—
Ra, —
(C(CH3))0-2—
CO2—
(CH2)1-2—
CO2—
Ra, —
(CH2)0-2—
CO—
Ra, —
O(CH2)0-2—
C6H5, —
O(CH2)1-2—
CO2—
Ra, —
O(C(CH3))1-2—
CO2—
Ra, —
O(CH2)1-2—
CO—
Ra, —
CO2(CH2)1-2—
CO2—
Ra, —
CO2(C(CH3))1-2—
CO2—
Ra, —
(CH2)0-2—
NO2, —
(CH2)0-2—
NRaRa, —
(CH2)0-2—
NRaCORa, —
(CH2)0-2—
—
NRaC(O)(CH2)1-2ORa, —
C6H5, —
C6H5ORa, and —
C6H5—
CH═
CHCO2Ra; and
,Ra is independently selected from H and C1-4 alkyl.
-
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12. A compound of claim 1, wherein the compound is selected from:
-
13. A composition, comprising:
- at least two different compounds of claim 1.
-
14. A solvent for a drug, comprising:
- at least one compound of claim 1.
-
15. A nutritional composition, comprising at least one compound of claim 1.
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16. The nutritional composition of claim 15, wherein the diphenolic residue in the compound of formula I was derived from a compound that is a nutritional supplement or a food intermediary.
-
17. A cosmetic composition, comprising at least one compound of claim 1 and a cosmetic ingredient.
-
18. A pharmaceutical composition, comprising at least one compound of claim 1 and a pharmaceutically acceptable excipient.
-
19. The composition of claim 18, wherein the composition is suitable for administration via a route selected from oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, and vaginal.
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20. The composition of claim 18, wherein the diphenolic residue in the compound of formula I was derived from a cancer preventing diphenol
-
21. The composition of claim 20, further comprising:
- an anti-cancer agent.
-
22. The composition of claim 18, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with antimicrobial properties.
-
23. The composition of claim 22, further comprising:
- an antimicrobial agent.
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24. The composition of claim 18, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with anti-inflammatory properties.
-
25. The composition of claim 24, further comprising:
- anti-inflammatory agent.
-
26. The composition of claim 18, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with pain-reducing properties.
-
27. The composition of claim 26, further comprising:
- a pain reducing agent.
-
28. The composition of claim 18, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with antioxidant properties.
-
29. The composition of claim 28, further comprising:
- an antioxidant agent.
-
30. A polymer, comprising:
- an unsymmetrical aromatic ether diacid of formula I;
;
[R′
—
(Y)p—
O]q—
Ar—
[O—
(X)r—
R′
]s
IAr is the aromatic portion of a diphenol;
X and Y are independently selected from;
—
CH2COO—
;
—
CH(CH3)COO—
;
—
CH2CH2OCH2COO—
;
—
CH2CH2CH2CH2CH2COO—
;
—
(CH2)yCOO—
where y is independently selected from 2-4 and 6-24; and
,—
(CH2CH2O)zCH2COO—
where z is independently selected from 2-24;
provided that the groups represented by [R′
—
(Y)p—
O]q— and
—
[O—
(X)r—
R′
]s are different from one another;
R′
is selected from H, benzyl, and C1-6 alkyl;
p is selected from 1, 2, 3, 4, 5, and 6;
q is selected from 1, 2, and 3. r is selected from 1, 2, 3, 4, 5, and 6; and
,s is selected from 1, 2, and 3. - View Dependent Claims (31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64)
p is selected from 1 and 2;
q is selected from 1 and 2;
r is selected from 1 and 2; and
,s is selected from 1 and 2.
- an unsymmetrical aromatic ether diacid of formula I;
-
32. A polymer of claim 30, wherein
y is independently selected from 2, 3, and 4; -
z is independently selected from 2, 3, and 4;
p is selected from 1, 2, and 3;
q is selected from 1, 2, and 3;
r is selected from 1, 2, and 3; and
,s is selected from 1, 2, and 3.
-
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33. A polymer of claim 30, wherein the unsymmetrical aromatic ether diacid is selected from:
-
34. A polymer of claim 30, wherein the unsymmetrical aromatic ether diacid is reacted with a compound selected from a dicarboxylic acid, a dialcohol, an amino-alcohol, and a diamine to form a polymer selected from a polyester, polyesteramide, polyamide, and polyanhydride.
-
35. A polymer of claim 30, wherein the polymer, further comprises:
- a second unsymmetrical aromatic ether diacid.
-
36. A polymer of claim 30, wherein the polymer is further polymerized with a lactone monomer.
-
37. A polymer of claim 36, wherein the lactone monomer is selected from glycolide, lactide, ε
- -caprolactone, trimethylene carbonate, and p-dioxanone.
-
38. An implantable medical device, comprising:
- a polymer of claim 30.
-
39. The implantable medical device of claim 38, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε
- -caprolactone, trimethylene carbonate, and p-dioxanone.
-
40. The implantable medical device of claim 38, wherein the device is a stent.
-
41. The implantable medical device of claim 40, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε
- -caprolactone, trimethylene carbonate, and p-dioxanone.
-
42. The implantable medical device of claim 38, wherein the device is a scaffold for tissue engineer, comprising:
- a porous structure for the attachment and proliferation of cells.
-
43. The implantable medical device of claim 42, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε
- -caprolactone, trimethylene carbonate, and p-dioxanone.
-
44. A coating for a stent, comprising:
- a polymer of claim 30.
-
45. The stent coating of claim 44, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε
- -caprolactone, trimethylene carbonate, and p-dioxanone.
-
46. A drug delivery system, comprising:
- a polymer of claim 30 physically admixed with a biologically or pharmacologically active agent.
-
47. The drug delivery system of claim 46, wherein the biologically or pharmacologically active agent is physically embedded or dispersed into the polymer and the polymer is in the form of a polymeric matrix.
-
48. The drug delivery system of claim 46, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε
- -caprolactone, trimethylene carbonate, and p-dioxanone.
-
49. A polymer blend, comprising:
- two different polymers of claim 30.
-
50. A nutritional composition, comprising at least one polymer of claim 30.
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51. The nutritional composition of claim 50, wherein the diphenolic residue in the polymer was derived from a compound that is a nutritional supplement or a food intermediary.
-
52. A cosmetic composition, comprising at least one polymer of claim 30 and a cosmetic ingredient.
-
53. A pharmaceutical composition, comprising at least one polymer of claim 30 and a pharmaceutically acceptable excipient.
-
54. The composition of claim 53, wherein the composition is suitable for administration via a route selected from oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, and vaginal.
-
55. The composition of claim 53, wherein the diphenolic residue in the polymer was derived from a cancer preventing diphenol
-
56. The composition of claim 55, further comprising:
- an anti-cancer agent.
-
57. The composition of claim 53, wherein the diphenolic residue in the polymer was derived from a diphenol with antimicrobial properties.
-
58. The composition of claim 57, further comprising:
- an antimicrobial agent.
-
59. The composition of claim 53, wherein the diphenolic residue in the polymer was derived from a diphenol with anti-inflammatory properties.
-
60. The composition of claim 59, further comprising:
- anti-inflammatory agent.
-
61. The composition of claim 53, wherein the diphenolic residue in the polymer was derived from a diphenol with pain-reducing properties.
-
62. The composition of claim 61, further comprising:
- a pain reducing agent.
-
63. The composition of claim 53, wherein the diphenolic residue in the polymer was derived from a diphenol with antioxidant properties.
-
64. The composition of claim 63, further comprising:
- an antioxidant agent.
Specification