Dissolution of arterial plaque
Embodiments of methods of treating atherosclerosis are described. In some embodiments an emulsifier is provided to achieve levels in the systemic circulation that are effective to solubilize atherosclerotic plaque, resulting in plaque regression. In some embodiments, levels of greater than 50 μM are achieved; in some embodiments levels ranging from about 100 μM to about 600 μM are achieved; in some embodiments, levels ranging from about 100 μM to about 300 μM are achieved. Emulsifiers can include bile salts, saponins, and ionic, nonionic, and zwitterionic detergents, or salts, conjugates, hydrates, solvates, or polymorphs thereof. In some embodiments, a statin can be administered simultaneously or sequentially with an emulsifier.
1. A method of treating atherosclerosis in a patient in need thereof comprising:
administering to said patient a pharmaceutical formulation comprising a bile acid consisting of unconjugated ursodeoxycholic acid (UDCA), or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, in an amount effective to achieve a concentration of UDCA greater than about 50 μM in the patient's systemic circulation;
wherein said concentration of UDCA in the systemic circulation is sustained for a period of at least two hours; and
wherein said concentration of UDCA is effective to result in regression of an atherosclerotic plaque.
2. The method of claim 1 , wherein the formulation further comprises a saponin, a detergent, or a mixture thereof
3. The method of claim 1 , wherein said UDCA, or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, is administered in an amount to achieve a concentration of between about 50 μM and about 600 μM of UDCA in the patient's systemic circulation.
4. The method of claim 1 , wherein said UDCA, or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, is administered in an amount to achieve a concentration of between about 100 μM and about 300 μM of UDCA in the patient's systemic circulation.
5. The method of claim 1 , wherein said formulation further comprises a permeability enhancer.
6. The method of claim 5 , wherein the permeability enhancer comprises a non-ionic detergent, an ionic detergent, or a zwitterionic detergent.
7. The method of claim 1 , further comprising administering a statin to said patient.
8. The method of claim 1 , wherein the pharmaceutical formulation further comprises a statin.
9. A method of treating atherosclerosis in a patient in need thereof comprising:
administering to said patient a pharmaceutical formulation comprising ursodeoxycholic acid (UDCA), or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, in an amount effective to achieve a concentration of UDCA greater than about 50 μM in the patient's systemic circulation at five minutes after the onset of administration;
wherein said concentration of UDCA in the patient's systemic circulation is sustained at greater than about 50 μM for a period of at least two hours; and
wherein said concentration of UDCA is effective to result in regression of an atherosclerotic plaque.
10. The method of claim 9 , wherein said UDCA, or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, is administered in an amount to achieve a concentration of between about 50 μM and about 600 μM of UDCA in the patient's systemic circulation.
11. The method of claim 9 , wherein said UDCA, or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, is administered in an amount to achieve a concentration of between about 100 μM and about 300 μM of UDCA in the patient's systemic circulation.