Claims for Patent: 6,960,346

Summary for Patent: 6,960,346

Title:	Vehicles for delivery of biologically active substances
Abstract:	A formulation containing one or more biologically active substances dissolved, dispersed, emulsified, or suspended within a vehicle of one or more citric acid esters and/or citric acid ethers. Methods for making and using are disclosed, as are kits for administration of the pharmaceutical formulation.
Inventor(s):	Shukla; Atul J. (Cordova, TN), Johnson; James R. (Germantown, TN), Sun; Yichun (Germantown, TN), Cooper; Robert (Starkville, MS), Boring; Gregg (Starkville, MS), Scruggs; Dan (Starkville, MS)
Assignee:	University of Tennessee Research Foundation (Knoxville, TN)
Application Number:	10/143,144
Patent Claims:	1. A composition comprising a biologically active substance (BAS) and a multiplicity of different citric acid esters (CAE) and/or citric acid ethers, wherein the amount of the CAE or the ether in the composition is sufficient to dissolve, disperse, emulsify, or suspend the entire amount of the BAS in the composition, and wherein the concentration of CAEs and citric acid ethers in the composition is higher than the concentration of any other constituent in the composition. 2. The composition of claim 1 which is a pharmaceutical composition packaged for parenteral administration into the body of a patient, for oral administration to a patient, or for topical administration to a body surface of a patient. 3. The composition of claim 2 wherein the administration is intravascular, intrathecal, intramuscular, subcutaneous, or intracavitary. 4. The composition of claim 2 wherein the topical administration is to the skin, to a mucosal surface, to the surface of the eye, to the nasal passages, or to the external ear. 5. The composition of claim 1 which is a liquid. 6. The composition of claim 1 which is a semi-solid, a gel, a paste, or a solid. 7. The composition of claim 1 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 3% w/w. 8. The composition of claim 7 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 10% w/w. 9. The composition of claim 8 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 25% w/w. 10. The composition of claim 9 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 50% w/w. 11. The composition of claim 1 wherein the CAE is hydrophobic. 12. The composition of claim 1 wherein one or more of the CAEs is hydrophobic. 13. The composition of claim 1 wherein one or more of the CAEs is hydrophilic. 14. The composition of claim 1 wherein at least one of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 15. The composition of claim 1 wherein each of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 16. A composition comprising a biologically active substance (BAS) and a citric acid ester (CAE) or a citric acid ether, wherein the amount of the CAE or the ether in the composition is sufficient to dissolve, disperse, emulsify, or suspend the entire amount of the BAS in the composition, wherein the composition comprises a multiplicity of different BASs. 17. The composition of claim 16 wherein the composition comprises a multiplicity of different CAEs and/or citric acid ethers. 18. A composition comprising a biologically active substance (BAS), a citric acid ester (CAE) or a citric acid ether, wherein the amount of the CAE or the ether in the composition is sufficient to dissolve, disperse, emulsify, or suspend the entire amount of the BAS, and a wax that is solid at room temperature. 19. A kit for treatment or prevention of a medical condition by administration of a pharmaceutical composition containing a biologically active substance (BAS) dissolved, dispersed, emulsified, or suspended in a citric acid ester and/or citric acid ether vehicle, the kit comprising a packaging, a biologically active substance within a container within the packaging, a citric acid ester (CAE) and/or a citric acid ether within a container within the packaging, and instructions within or on the packaging for applying the BAS and the CAE and/or citric acid ether into the body or onto a body part of a patient, wherein the amounts of the BAS and CAE and/or citric acid ether within the packaging are such that the CAE and/or citric acid ether is sufficient to completely dissolve, disperse, emulsify, or suspend the BAS. 20. The kit of claim 19 wherein the BAS and the CAE and/or citric acid ether are housed within a single container within the packaging. 21. The kit of claim 19 wherein the BAS and the CAE and/or citric acid ether are housed in separate containers within the packaging. 22. The kit of claim 19 wherein the concentration of CAE and citric acid ether in the composition is greater than 3% w/w. 23. The kit of claim 22 wherein the concentration of CAE and citric acid ether in the composition is greater than 10% w/w. 24. The kit of claim 23 wherein the concentration of CAE and citric acid ether in the composition is greater than 25% w/w. 25. The kit of claim 19 wherein the concentration of CAE and citric acid ether in the composition is higher than that of any other components of the composition. 26. The kit of claim 19 wherein the CAE is hydrophobic. 27. The kit of claim 19 wherein the CAE is hydrophilic. 28. The kit of claim 19 wherein the CAE or ether is a multiplicity of CAEs and/or citric acid ethers. 29. The kit of claim 28 wherein at least one of the CAEs is hydrophobic. 30. The kit of claim 19 wherein the CAE is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 31. The kit of claim 28 wherein at least one of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 32. The kit of claim 31 wherein each of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 33. The kit of claim 19 wherein the instructions are for internal administration into the body of a patient. 34. The kit of claim 33 wherein the administration is parenteral. 35. The kit of claim 19 wherein the instructions are for topical administration onto a body part of a patient. 36. The kit of claim 35 wherein the administration is to the skin, to a mucosal surface, to a serosal surface, to the surface of the eye, to the nose, to the ear, oral, intravaginal, or rectal. 37. The composition of claim 16 which is a pharmaceutical composition packaged for parenteral administration into the body of a patient, for oral administration to a patient, or for topical administration to a body surface of a patient. 38. The composition of claim 37 wherein the administration is intravascular, intrathecal, intramuscular, subcutaneous, or intracavitary. 39. The composition of claim 37 wherein the topical administration is to the skin, to a mucosal surface, to the surface of the eye, to the nasal passages, or to the external ear. 40. The composition of claim 16 which is a liquid. 41. The composition of claim 16 which is a semi-solid, a gel, a paste, or a solid. 42. The composition of claim 16 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 3% w/w. 43. The composition of claim 42 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 10% w/w. 44. The composition of claim 43 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 25% w/w. 45. The composition of claim 44 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 50% w/w. 46. The composition of claim 16 wherein the CAE is hydrophobic. 47. The composition of claim 16 wherein the composition comprises a multiplicity of different CAEs and/or citric acid ethers. 48. The composition of claim 47 wherein one or more of the CAEs is hydrophobic. 49. The composition of claim 47 wherein one or more of the CAEs is hydrophilic. 50. The composition of claim 16 wherein at least one of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 51. The composition of claim 16 wherein each of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 52. The composition of claim 18 wherein the concentration of CAEs and citric acid ethers in the composition is higher than the concentration of any other constituent in the composition. 53. The composition of claim 18 which is a pharmaceutical composition packaged for parenteral administration into the body of a patient, for oral administration to a patient, or for topical administration to a body surface of a patient. 54. The composition of claim 53 wherein the administration by intravascular, intrathecal, intramuscular, subcutaneous, or intracavitary parenteral administration. 55. The composition of claim 53 wherein the topical administration is to the skin, to a mucosal surface, to the surface of the eye, to the nasal passages, or to the external ear. 56. The composition of claim 18 which is a liquid. 57. The composition of claim 18 which is a semi-solid, a gel, a paste, or a solid. 58. The composition of claim 18 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 3% w/w. 59. The composition of claim 58 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 10% w/w. 60. The composition of claim 59 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 25% w/w. 61. The composition of claim 60 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 50% w/w. 62. The composition of claim 18 wherein the CAE is hydrophobic. 63. The composition of claim 18 wherein one or more of the CAEs is hydrophobic. 64. The composition of claim 18 wherein one or more of the CAEs is hydrophilic. 65. The composition of claim 18 wherein at least one of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 66. A composition comprising a biologically active substance (BAS) and a multiplicity of different citric acid esters (CAE) and/or citric acid ethers, wherein the amount of the CAE or the ether in the composition is sufficient to dissolve, disperse, emulsify, or suspend the entire amount of the BAS in the composition wherein each of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate. 67. The composition of claim 66, wherein the concentration of CAEs and citric acid ethers in the composition is higher than the concentration of any other constituent in the composition. 68. The composition of claim 66 which is a pharmaceutical composition packaged for parenteral administration into the body of a patient, for oral administration to a patient, or for topical administration to a body surface of a patient. 69. The composition of claim 68 wherein the administration is by intravascular, intrathecal, intramuscular, subcutaneous, or intracavitary parenteral administration. 70. The composition of claim 68 wherein the topical administration is to the skin, to a mucosal surface, to the surface of the eye, to the nasal passages, or to the external ear. 71. The composition of claim 66 which is a liquid. 72. The composition of claim 66 which is a semi-solid, a gel, a paste, or a solid. 73. The composition of claim 66 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 3% w/w. 74. The composition of claim 73 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 10% w/w. 75. The composition of claim 74 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 25% w/w. 76. The composition of claim 75 wherein the concentration of the CAE and the citric acid ether in the composition is greater than 50% w/w. 77. The composition of claim 66 wherein the CAE is hydrophobic. 78. The composition of claim 66 wherein one or more of the CAEs is hydrophobic. 79. The composition of claim 66 wherein one or more of the CAEs is hydrophilic. 80. The composition of claim 66 wherein at least one of the CAEs is selected from the group consisting of triethyl citrate, acetyl triethyl citrate, tri-n-butyl citrate, acetyl tri-n-butyl citrate, acetyl tri-n-hexyl citrate, and butyryl tri-n-hexyl citrate.