IP Library › Granted Patent US 6,960,355

Granted Patent B2

US 6,960,355 · App. 10/005,511 · Granted Nov 1, 2005

Compounds and compositions for delivering active agents

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Quick Facts

Patent No.: US 6,960,355
App. No.: 10/005,511
Granted: Nov 1, 2005
Kind: B2

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Abstract

Modified amino acid compounds useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Claims (233)

1. A pharmacological composition comprising:

(A) at least one biologically-active agent; and

(B) at least one carrier compound having the formula

2—HO—Ar—CONR 8 —R 7 —COOH

or a salt thereof, wherein

Ar is a phenyl or naphthyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H;

R 7 is selected form the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, phenyl, naphthyl, (C 1 to C 10 alkyl)phenyl, (C 1 to C 10 alkenyl)phenyl, (C 1 to C 10 alkyl)naphthyl, (C 1 to C 10 alkenyl)naphthyl, phenyl (C 1 to C 10 alkyl), phenyl (C 1 to C 10 alkenyl), naphthyl (C 1 to C 10 alkyl) and naphthyl (C 1 to C 10 alkenyl);

R 7 is optionally substituted with C 1 to C 4 alkyl, C 1 to C 4 alkenyl, C 1 to C 4 alkoxy, —OH, —SH and —CO 2 R 9 or any combination thereof;

R 7 is optionally interrupted by oxygen, nitrogen, sulfur or any combination thereof;

R 8 is selected from the group consisting of hydrogen, C 1 to C 4 alkyl, C 1 to C 4 alkenyl, hydroxy, and C 1 to C 4 alkoxy; and

R 8 is optionally substituted with C 1 to C 4 alkyl, C 1 to C 4 alkenyl, C 1 to C 4 alkoxy, —OH, —SH and —CO 2 R 9 or any combination thereof;

R 9 is hydrogen, C 1 to C 4 alkyl, or C 1 to C 4 alkenyl; with the proviso that the compounds are not substituted with an amino group in the position alpha to the acid group.

2. The composition of claim 1 wherein Ar is a phenyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H.

3. The composition of claim 1 , wherein Ar is a phenyl substituted with —Cl.

4. The composition of claim 1 , wherein Ar is a phenyl substituted with —F.

5. The composition of claim 3 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkenyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

6. The composition of claim 3 , wherein R 7 is C 4 -C 20 alkyl.

7. The composition of claim 6 , wherein R 7 is not substituted or interrupted.

8. The composition of claim 7 , wherein R 8 is hydrogen.

9. The composition of claim 1 , wherein the biologically active agent comprises at least one peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

10. The composition of claim 9 , wherein the biologically active agent is a peptide.

11. The composition of claim 9 , wherein the biologically active agent is a mucopolysaccharide.

12. The composition according to claim 1 , wherein the biologically active agent comprises human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine, parathyroid hormone, an antimicrobial, an antifungal agent or a combination thereof.

13. The composition according to claim 12 , wherein said biologically-active agent comprises human growth hormone, an interferon, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, cromolyn sodium, parathyroid hormone, an antimicrobial, an antigen or a combination thereof.

14. The composition according to claim 13 , wherein said biologically-active agent comprises human growth hormone.

15. The composition according to claim 13 , wherein said biologically-active agent comprises insulin.

16. The composition according to claim 13 , wherein said biologically-active agent comprises heparin.

17. The composition according to claim 13 , wherein said biologically-active agent comprises low molecular weight heparin.

18. The composition according to claim 13 , wherein said biologically-active agent comprises calcitonin.

19. The composition according to claim 13 , wherein said biologically-active agent comprises cromolyn sodium.

20. The composition according to claim 13 , wherein said biologically-active agent comprises parathyroid hormone.

21. A dosage unit form comprising

(A) a pharmacological composition according to claim 1 ; and

(B) (i) an excipient,

(ii) a diluent

(iii) a disintegrant

(iv) a lubricant,

(v) a plasticizer,

(vi) a colorant,

(vii) a dosing vehicle, or

(viii) any combination thereof.

22. The dosage unit form according to claim 21 , comprising a tablet, a capsule, or a liquid.

23. The dosage unit form according to claim 21 , wherein said dosing vehicle is selected form the group consisting of water, 1,2-propane diol, ethanol, and any combination thereof.

24. A method for preparing a pharmacological composition, said method comprising mixing:

(A) at least one biologically-active agent;

(B) at least one carrier compound having the formula

2OH—Ar—CONR 8 —R 7 —COOH

wherein

Ar is a phenyl or naphthyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H;

R 7 is optionally substituted with C 1 to C 4 alkyl, C 1 to C 4 alkenyl, C 1 to C 4 alkoxy, —OH, —SH and —CO 2 R 9 or any combination thereof;

R 7 is optionally interrupted by oxygen, nitrogen, sulfur or any combination thereof;

R 8 is selected from the group consisting of hydrogen, C 1 to C 4 alkyl, C 1 to C 4 alkenyl, hydroxy, and C 1 to C 4 alkoxy; and

R 9 is hydrogen, C 1 to C 4 alkyl, or C 1 to C 4 alkenyl;

with the proviso that the compounds are not substituted with an amino group in the position alpha to the acid group; and

25. A method for administering a biologically-active agent to an animal in need of said agent, said method comprising administering orally to said animal a composition as defined in claim 1 .

26. A method for administering a biologically-active agent to a mammal in need of said agent, said method comprising administering orally to said mammal a composition as defined in claim 1 .

27. The composition of claim 1 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl) and wherein R 8 is hydrogen.

28. The composition of claim 1 , wherein R 7 is C 4 -C 20 alkyl and wherein R 8 is hydrogen.

29. The composition of claim 1 , wherein R 7 is riot substituted or interrupted and wherein R 8 is hydrogen.

30. The composition of claim 1 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl) and wherein R 8 is C 1 -C 4 alkyl.

31. The composition of claim 1 , wherein R 7 is C 4 -C 20 alkyl and wherein R 8 is C 1 -C 4 alkyl.

32. The composition of claim 1 , wherein R 7 is not substituted or interrupted and wherein R 8 is C 1 -C 4 alkyl.

33. The composition of claim 1 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

34. The composition of claim 1 , wherein R 7 is C 4 -C 20 alkyl.

35. The composition of claim 1 , wherein R 7 is not substituted or interrupted.

36. The composition of claim 1 , wherein R 8 is hydrogen.

37. The composition of claim 1 , wherein R 8 is C 1 -C 4 alkyl.

38. The composition of claim 2 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl) and wherein R 8 is hydrogen.

39. The composition of claim 2 , wherein R 7 is C 4 -C 20 alkyl and wherein R 8 is hydrogen.

40. The composition of claim 2 , wherein R 7 is not substituted or interrupted and wherein R 8 is hydrogen.

41. The composition of claim 2 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl) and wherein R 8 is C 1 -C 4 alkyl.

42. The composition of claim 2 , wherein R 7 is C 4 -C 20 alkyl and wherein R 8 is C 1 -C 4 alkyl.

43. The composition of claim 2 , wherein R 7 is not substituted or interrupted and wherein R 8 is C 1 -C 4 alkyl.

44. The composition of claim 2 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

45. The composition of claim 2 , wherein R 7 is C 4 -C 20 alkyl.

46. The composition of claim 2 , wherein R 7 is not substituted or interrupted.

47. The composition of claim 2 , wherein R 8 is hydrogen.

48. The composition of claim 2 , wherein R 8 is C 1 -C 4 alkyl.

49. The composition of claim 2 , wherein the biologically active agent is a peptide.

50. The composition of claim 2 , wherein the biologically active agent is a mucopolysaccharide.

51. The composition of claim 3 , wherein R 7 is not substituted or interrupted and wherein R 8 is hydrogen.

52. The composition of claim 3 , wherein R 7 is not substituted or interrupted and wherein R 8 is C 1 -C 4 alkyl.

53. The composition of claim 3 , wherein R 7 is not substituted or interrupted.

54. The composition of claim 3 , wherein R 8 is hydrogen.

55. The composition of claim 3 , wherein R 8 is C 1 -C 4 alkyl.

56. The composition of claim 3 , wherein the biologically active agent is a peptide.

57. The composition of claim 3 , wherein the biologically active agent is a mucopolysaccharide.

58. The composition of claim 4 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl) and wherein R 8 is hydrogen.

59. The composition of claim 4 , wherein R 7 is C 4 -C 20 alkyl and wherein R 8 is hydrogen.

60. The composition of claim 4 , wherein R 7 is not substituted or interrupted and wherein R 8 is hydrogen.

61. The composition of claim 4 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl) and wherein R 8 is C 1 -C 4 alkyl.

62. The composition of claim 4 , wherein R 7 is C 4 -C 20 alkyl and wherein R 8 is C 1 -C 4 alkyl.

63. The composition of claim 4 , wherein R 7 is not substituted or interrupted and wherein R 8 is C 1 -C 4 alkyl.

64. The composition of claim 4 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

65. The composition of claim 4 , wherein R 7 is C 4 -C 20 alkyl.

66. The composition of claim 4 , wherein R 7 is not substituted or interrupted.

67. The composition of claim 4 , wherein R 8 is hydrogen.

68. The composition of claim 4 , wherein R 8 is C 1 -C 4 alkyl.

69. The composition of claim 4 , wherein the biologically active agent is a peptide.

70. The composition of claim 4 , wherein the biologically active agent is a mucopolysaccharide.

71. The composition of claim 5 , wherein R 7 is not substituted or interrupted.

72. The composition of claim 5 , wherein R 7 is not substituted or interrupted and wherein R 8 is C 1 -C 4 alkyl.

73. The composition of claim 5 , wherein R 7 is not substituted or interrupted and wherein R 8 is hydrogen.

74. The composition of claim 5 , wherein R 8 is hydrogen.

75. The composition of claim 5 , wherein R 8 is C 1 -C 4 alkyl.

76. The composition of claim 5 , wherein the biologically active agent is a peptide.

77. The composition of claim 5 , wherein the biologically active agent is a mucopolysaccharide.

78. The composition of claim 6 , wherein R 8 is hydrogen.

79. The composition of claim 6 , wherein R 8 is C 1 -C 4 alkyl.

80. The composition of claim 6 , wherein the biologically active agent is a peptide.

81. The composition of claim 6 , wherein the biologically active agent is a mucopolysaccharide.

82. The composition of claim 7 , wherein R 8 is C 1 -C 4 alkyl.

83. The composition of claim 7 , wherein the biologically active agent is a peptide.

84. The composition of claim 7 , wherein the biologically active agent is a mucopolysaccharide.

85. The composition of claim 8 , wherein the biologically active agent is a peptide.

86. The composition of claim 8 , wherein the biologically active agent is a mucopolysaccharide.

87. The composition according to claim 13 , wherein said biologically-active agent comprises interferon.

88. The composition according to claim 13 , wherein said biologically-active agent comprises erythropoietin.

89. The composition according to claim 13 , wherein said biologically-active agent comprises an antigen.

90. The composition according to claim 13 , wherein said biologically-active agent comprises an antimicrobial.

91. The dosage unit form according to claim 21 , wherein Ar is a phenyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H.

92. The dosage unit form according to claim 21 , wherein Ar is a phenyl substituted with —Cl.

93. The dosage unit form according to claim 21 , wherein R 8 is hydrogen.

94. The dosage unit form according to claim 21 , wherein R 8 is C 1 -C 4 alkyl.

95. The dosage unit form according to claim 21 , wherein said biologically active agent comprises at least one peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

96. The dosage unit form according to claim 21 , wherein said biologically active agent is a peptide.

97. The dosage unit form according to claim 21 , wherein said biologically active agent is a mucopolysaccharide.

98. The dosage unit form according to claim 21 , wherein said biologically active agent comprises human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine, parathyroid hormone, an antimicrobial, an antifungal agent or a combination thereof.

99. The dosage unit form according to claim 21 , wherein Ar is a phenyl substituted with —F.

100. The dosage unit form according to claim 21 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

101. The dosage unit form according to claim 21 , wherein R 7 is (C 4 -C 20 alkyl.

102. The dosage unit form according to claim 21 , wherein R 7 is not substituted or interrupted.

103. The dosage unit form according to claim 21 , comprising a tablet.

104. The dosage unit form according to claim 21 , comprising a capsule.

105. The method according to claim 24 , wherein the biologically active agent comprises at least one peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

106. The method according to claim 24 , wherein the biologically active agent is a peptide.

107. The method according to claim 24 , wherein the biologically active agent is a mucopolysaccharide.

108. The method according to claim 24 , wherein the biologically active agent comprises human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine, parathyroid hormone, an antimicrobial, an antifungal agent or a combination thereof.

109. The method according to claim 24 , wherein said biologically-active agent comprises human growth hormone, an interferon, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, cromolyn sodium, parathyroid hormone, an antimicrobial or a combination thereof.

110. The method according to claim 24 , wherein said biologically-active agent comprises human growth hormone.

111. The method according to claim 24 , wherein said biologically-active agent comprises insulin.

112. The method according to claim 24 , wherein said biologically-active agent comprises heparin.

113. The method according to claim 24 , wherein said biologically-active agent comprises low molecular weight heparin.

114. The method according to claim 24 , wherein said biologically-active agent comprises calcitonin.

115. The method according to claim 24 , wherein said biologically-active agent comprises cromolyn sodium.

116. The method according to claim 24 , wherein said biologically-active agent comprises parathyroid hormone.

117. The method according to claim 24 , wherein said biologically-active agent comprises interferon.

118. The method according to claim 24 , wherein said biologically-active agent comprises erythropoietin.

119. The method according to claim 24 , wherein said biologically-active agent comprises an antigen.

120. The method according to claim 24 , wherein said biologically-active agent comprises an antimicrobial.

121. The method according to claim 24 , wherein Ar is a phenyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H.

122. The method according to claim 24 , wherein Ar is a phenyl substituted with —Cl.

123. The method according to claim 24 , wherein Ar is a phenyl substituted with —F.

124. The method according to claim 24 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

125. The method according to claim 24 , wherein R 7 is C 4 -C 20 alkyl.

126. The method according to claim 24 , wherein R 7 is not substituted or interrupted.

127. The method according to claim 24 , wherein R 8 is hydrogen.

128. The method according to claim 24 , wherein R 8 is C 1 -C 4 alkyl.

129. The method according to claim 25 , wherein the biologically active agent comprises at least one peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

130. The method according to claim 25 , wherein the biologically active agent is a peptide.

131. The method according to claim 25 , wherein the biologically active agent is a mucopolysaccharide.

132. The method according to claim 25 , wherein the biologically active agent comprises human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin in, cromolyn sodium, vancomycin, desferrioxamine, parathyroid hormone, an antimicrobial, an antifungal agent or a combination thereof.

133. The method according to claim 25 , wherein said biologically-active agent comprises human growth hormone, an interferon, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, cromolyn sodium, parathyroid hormone, an antimicrobial or a combination thereof.

134. The method according to claim 25 , wherein said biologically-active agent comprises human growth hormone.

135. The method according to claim 25 , wherein said biologically-active agent comprises insulin.

136. The method according to claim 25 , wherein said biologically-active agent comprises heparin.

137. The method according to claim 25 , wherein said biologically-active agent comprises low molecular weight heparin.

138. The method according to claim 25 , wherein said biologically-active agent comprises calcitonin.

139. The method according to claim 25 , wherein said biologically-active agent comprises cromolyn sodium.

140. The method according to claim 25 , wherein said biologically-active agent comprises parathyroid hormone.

141. The method according to claim 25 , wherein said biologically-active agent comprises interferon.

142. The method according to claim 25 , wherein said biologically-active agent comprises erythropoietin.

143. The method according to claim 25 , wherein said biologically-active agent comprises an antigen.

144. The method according to claim 25 , wherein said biologically-active agent comprises an antimicrobial.

145. The method according to claim 25 , wherein Ar is a phenyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H.

146. The method according to claim 25 , wherein Ar is a phenyl substituted with —Cl.

147. The method according to claim 25 , wherein Ar is a phenyl substituted with —F.

148. The method according to claim 25 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

149. The method according to claim 25 , wherein R 7 is C 4 -C 20 alkyl.

150. The method according to claim 25 , wherein R 7 is not substituted or interrupted.

151. The method according to claim 25 , wherein R 8 is hydrogen.

152. The method according to claim 25 , wherein R 8 is C 1 -C 4 alkyl.

153. The method according to claim 26 , wherein the biologically active agent comprises at least one peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

154. The method according to claim 26 , wherein the biologically active agent is a peptide.

155. The method according to claim 26 , wherein the biologically active agent is a mucopolysaccharide.

156. The method according to claim 26 , wherein the biologically active agent comprises human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine, parathyroid hormone, an antimicrobial, an antifungal agent or a combination thereof.

157. The method according to claim 26 , wherein said biologically-active agent comprises human growth hormone, an interferon, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, cromolyn sodium, parathyroid hormone, an antimicrobial or a combination thereof.

158. The method according to claim 26 , wherein said biologically-active agent comprises human growth hormone.

159. The method according to claim 26 , wherein said biologically-active agent comprises insulin.

160. The method according to claim 26 , wherein said biologically-active agent comprises heparin.

161. The method according to claim 26 , wherein said biologically-active agent comprises low molecular weight heparin.

162. The method according to claim 26 , wherein said biologically-active agent comprises calcitonin.

163. The method according to claim 26 , wherein said biologically-active agent comprises cromolyn sodium.

164. The method according to claim 26 , wherein said biologically-active agent comprises parathyroid hormone.

165. The method according to claim 26 , wherein said biologically-active agent comprises interferon.

166. The method according to claim 26 , wherein said biologically-active agent comprises erythropoietin.

167. The method according to claim 26 , wherein said biologically-active agent comprises an antigen.

168. The method according to claim 26 , wherein said biologically-active agent comprises an antimicrobial.

169. The method according to claim 26 , wherein Ar is a phenyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H.

170. The method according to claim 26 , wherein Ar is a phenyl substituted with —Cl.

171. The method according to claim 26 , wherein Ar is a phenyl substituted with —F.

172. The method according to claim 26 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

173. The method according to claim 26 , wherein R 7 is C 4 -C 20 alkyl.

174. The method according to claim 26 , wherein R 7 is not substituted or interrupted.

175. The method according to claim 26 , wherein R 8 is hydrogen.

176. The method according to claim 26 , wherein R 8 is C 1 -C 4 alkyl.

177. A method for administering a biologically-active agent to a human in need of said agent, said method comprising administering orally to said human a composition as defined in claim 1 .

178. The method according to claim 177 , wherein the biologically active agent comprises at least one peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

179. The method according to claim 177 , wherein the biologically active agent is a peptide.

180. The method according to claim 177 , wherein the biologically active agent is a mucopolysaccharide.

181. The method according to claim 177 , wherein the biologically active agent comprises human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-1, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine, parathyroid hormone, an antimicrobial, an antifungal agent or a combination thereof.

182. The method according to claim 177 , wherein said biologically-active agent comprises human growth hormone, an interferon, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, cromolyn sodium, parathyroid hormone, an antimicrobial or a combination thereof.

183. The method according to claim 177 , wherein said biologically-active agent comprises human growth hormone.

184. The method according to claim 177 , wherein said biologically-active agent comprises insulin.

185. The method according to claim 177 , wherein said biologically-active agent comprises heparin.

186. The method according to claim 177 , wherein said biologically-active agent comprises low molecular weight heparin.

187. The method according to claim 177 , wherein said biologically-active agent comprises calcitonin.

188. The method according to claim 177 , wherein said biologically-active agent comprises cromolyn sodium.

189. The method according to claim 177 , wherein said biologically-active agent comprises parathyroid hormone.

190. The method according to claim 177 , wherein said biologically-active agent comprises interferon.

191. The method according to claim 177 , wherein said biologically-active agent comprises erythropoietin.

192. The method according to claim 177 , wherein said biologically-active agent comprises an antigen.

193. The method according to claim 177 , wherein said biologically-active agent comprises an antimicrobial.

194. The method according to claim 177 wherein Ar is a phenyl substituted with at least one of C 1 -C 5 alkyl, C 2 -C 4 alkenyl, —F, —Cl, —OH, —SO 2 , —COOH or —SO 3 H.

195. The method according to claim 177 , wherein Ar is a phenyl substituted with —Cl.

196. The method according to claim 177 , wherein Ar is a phenyl substituted with —F.

197. The method according to claim 177 , wherein R 7 is selected from the group consisting of C 4 to C 20 alkyl, C 4 to C 20 alkenyl, (C 1 -C 10 alkyl)phenyl, and phenyl (C 1 to C 10 alkyl).

198. The method according to claim 177 , wherein R 7 is C 4 -C 20 alkyl.

199. The method according to claim 177 , wherein R 7 is not substituted or interrupted.

200. The method according to claim 177 , wherein R 8 is hydrogen.

201. The method according to claim 177 , wherein R 8 is C 1 -C 4 alkyl.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 22, 2021

From: EMISPHERE TECHNOLOGIES, INC.

To: NOVO NORDISK NORTH AMERICA OPERATIONS A/S

Reel/Frame 056750/0169 →

SECURITY AGREEMENT Recorded Oct 3, 2005

From: EMISPHERE TECHNOLOGIES, INC.

To: MHR INSTITUTIONAL PARTNERS IIA LP

Reel/Frame 016617/0145 →