Cyclodextrin-based polymers for therapeutics delivery
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C03B-037/16
A61K-009/48
A61K-047/40
출원번호
US-0277780
(2011-10-20)
등록번호
US-8314230
(2012-11-20)
발명자
/ 주소
Cheng, Jianjun
Davis, Mark E.
Khin, Kay T.
출원인 / 주소
Cerulean Pharma Inc.
대리인 / 주소
Lando & Anastasi LLP
인용정보
피인용 횟수 :
1인용 특허 :
107
초록▼
The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers improve drug stability and solubility, and red
The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers improve drug stability and solubility, and reduce toxicity of the small molecule therapeutic when used in vivo. Furthermore, by selecting from a variety of linker groups and targeting ligands the polymers present methods for controlled delivery of the therapeutic agents. The invention also relates to methods of treating subjects with the therapeutic compositions described herein. The invention further relates to methods for conducting pharmaceutical business comprising manufacturing, licensing, or distributing kits containing or relating to the polymeric compounds described herein.
대표청구항▼
1. A modified cyclodextrin ring, wherein exactly two hydroxyl moieties are substituted with an amino acid selected from cysteine, tryptophan, glutamic acid, aspartic acid, lysine, and arginine. 2. The modified cyclodextrin ring of claim 1, wherein the two hydroxyl moieties are substituted with a nit
1. A modified cyclodextrin ring, wherein exactly two hydroxyl moieties are substituted with an amino acid selected from cysteine, tryptophan, glutamic acid, aspartic acid, lysine, and arginine. 2. The modified cyclodextrin ring of claim 1, wherein the two hydroxyl moieties are substituted with a nitrogen or sulfur atom of the amino acid. 3. The modified cyclodextrin ring of claim 1, wherein the amino acid is cysteine. 4. The modified cyclodextrin ring of claim 1, wherein the amino acid is a boc protected glutamic acid. 5. The modified cyclodextrin ring of claim 1, wherein the amino acid is included in an oligopeptide comprising 2 to 50 amino acid residues. 6. The modified cyclodextrin ring of claim 5, wherein the oligopeptide comprises 2 to 30 amino acid residues. 7. The modified cyclodextrin ring of claim 6, wherein the oligopeptide comprises 2 to 15 amino acid residues. 8. The modified cyclodextrin ring of claim 1, wherein the cyclodextrin is a β-cyclodextrin. 9. A compound of the formula: wherein is a cyclodextrin, wherein each AA independently comprises an amino acid selected from cysteine, tryptophan, glutamic acid, aspartic acid, lysine, and arginine. 10. The compound of claim 9, wherein the amino acid is linked to the cyclodextrin via a nitrogen or a sulfur atom of the amino acid. 11. The compound of claim 9, wherein the amino acid is cysteine. 12. The compound of claim 9, wherein the amino acid is included in an oligopeptide comprising 2 to 50 amino acid residues. 13. The compound of claim 9, wherein is a β-cyclodextrin. 14. The compound of claim 13, wherein is linked in an A, D configuration. 15. The compound of claim 9, wherein the compound is: 16. A compound of the formula: is a cyclodextrin, wherein each AA independently comprises an amino acid. 17. The compound of claim 16, wherein the amino acid is linked to the cyclodextrin via a nitrogen or a sulfur atom of the amino acid. 18. The compound of claim 16, wherein the amino acid is an alpha-amino acid. 19. The compound of claim 16, wherein the amino acid is selected from cysteine, tryptophan, glutamic acid, aspartic acid, lysine, arginine, and histidine. 20. The compound of claim 19, wherein the amino acid is cysteine. 21. The compound of claim 16, wherein the amino acid is included in an oligopeptide comprising 2 to 50 amino acid residues. 22. The compound of claim 16, wherein is a β-cyclodextrin. 23. A compound of the formula: is a cyclodextrin, wherein each AA independently comprises an alpha-amino acid. 24. The compound of claim 23, wherein the alpha-amino acid is linked to the cyclodextrin via a nitrogen or a sulfur atom of the amino acid. 25. The compound of claim 23, wherein the alpha-amino acid is selected from cysteine, tryptophan, glutamic acid, aspartic acid, lysine, arginine, and histidine. 26. The compound of claim 25, wherein the alpha-amino acid is cysteine. 27. The compound of claim 23, wherein the alpha-amino acid is included in an oligopeptide comprising 2 to 50 amino acid residues. 28. The compound of claim 23, wherein is a β-cyclodextrin. 29. A compound of the formula: wherein each AA independently comprises an alpha-amino acid. 30. The compound of claim 29, wherein the alpha-amino acid is linked to the cyclodextrin via a nitrogen or a sulfur atom of the alpha-amino acid. 31. The compound of claim 29, wherein the alpha-amino acid is selected from cysteine, tryptophan, glutamic acid, aspartic acid, lysine, arginine, and histidine. 32. The compound of claim 31, wherein the alpha-amino acid is cysteine. 33. The compound of claim 29, wherein the alpha-amino acid is included in an oligopeptide comprising 2 to 50 amino acid residues. 34. The compound of claim 29, wherein the compound is: 35. A salt of the modified cyclodextrin ring of claim 1. 36. A salt of the compound of claim 9. 37. A salt of the compound of claim 16. 38. A salt of the compound of claim 23. 39. A salt of the compound of claim 29. 40. A composition comprising the modified cyclodextrin ring of claim 1 and a solvent. 41. A composition comprising the compound of claim 9 and a solvent. 42. A composition comprising the compound of claim 16 and a solvent. 43. A composition comprising the compound of claim 23 and a solvent. 44. A composition comprising the compound of claim 29 and a solvent. 45. A composition comprising the compound of claim 34 and a solvent. 46. The composition of claim 40, further comprising an activated monomer. 47. The composition of claim 41, further comprising an activated monomer. 48. The composition of claim 42, further comprising an activated monomer. 49. The composition of claim 43, further comprising an activated monomer. 50. The composition of claim 44, further comprising an activated monomer. 51. The composition of claim 45, wherein the activated monomer comprises an activated monomer. 52. The composition of claim 46, wherein the activated monomer comprises an activated ester. 53. The composition of claim 47, wherein the activated monomer comprises an activated ester. 54. The composition of claim 48, wherein the activated monomer comprises an activated ester. 55. The composition of claim 49, wherein the activated monomer comprises an activated ester. 56. The composition of claim 50, wherein the activated monomer comprises an activated ester. 57. The composition of claim 51, wherein the activated monomer comprises an activated ester. 58. The modified cyclodextrin ring of claim 3, wherein the cysteine is attached at the A and D positions of the cyclodextrin and wherein the two hydroxyl moieties are substituted with the sulfur atom of the cysteine. 59. The modified cyclodextrin ring of claim 3, wherein the cyclodextrin is beta-cyclodextrin and wherein the two hydroxyl moieties are substituted with the sulfur atom of the cysteine. 60. The modified cyclodextrin ring of claim 31, wherein the two hydroxyl moieties are substituted with the sulfur atom of the cysteine. 61. The compound of claim 12, wherein the oligopeptide comprises 2 to 30 amino acid residues. 62. The compound of claim 61, wherein the oligopeptide comprises 2 to 15 amino acid residues. 63. The compound of claim 21, wherein the oligopeptide comprises 2 to 30 amino acid residues. 64. The compound of claim 60, wherein the oligopeptide comprises 2 to 15 amino acid residues. 65. The compound of claim 27, wherein the oligopeptide comprises 2 to 30 amino acid residues. 66. The compound of claim 62, wherein the oligopeptide comprises 2 to 15 amino acid residues. 67. The compound of claim 33, wherein the oligopeptide comprises 2 to 30 amino acid residues. 68. The compound of claim 64, wherein the oligopeptide comprises 2 to 15 amino acid residues. 69. The compound of claim 1, wherein the amino acid is glutamic acid. 70. The compound of claim 9, wherein the amino acid is glutamic acid. 71. The compound of claim 16, wherein the amino acid is glutamic acid. 72. The compound of claim 23, wherein the alpha-amino acid is glutamic acid. 73. The compound of claim 29, wherein the alpha-amino acid is glutamic acid. 74. The compound of claim 9, wherein the amino acid is a boc protected glutamic acid. 75. The compound of claim 16, wherein the amino acid is a boc protected glutamic acid. 76. The compound of claim 23, wherein the alpha-amino acid is a boc protected glutamic acid. 77. The compound of claim 29, wherein the alpha-amino acid is a boc protected glutamic acid.
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