Pain management with liposome-encapsulated analgesic drugs

Abstract

Liposome-encapsulated opioid analgesic agents delivered by the pulmonary route provide local, or systemic analgesia superior to that produced by the solution form of these agents administered by parentral (intravenous, intramuscular, or subcutaneous injection) or oral routes.

We claim:  
     
       1. A method of managing pain in a patient comprising administering to said patient a composition containing a liposome-encapsulated opioid analgesic agent through said patient's pulmonary system. 
     
     
       2. The method of  claim 1  in which the liposome-encapsulated opioid analgesic agent comprises multilamellar lipid vesicles. 
     
     
       3. The method of  claim 1  wherein the liposome-encapsulated opioid analgesic agent comprises unilamellar lipid vesicles. 
     
     
       4. The method of  claim 1  wherein the liposome-encapsulated opioid analgesic agent is multivesicular. 
     
     
       5. The method of  claim 1  wherein the liposome-encapsulated opioid analgesic agent comprises a multiphase liposomal system. 
     
     
       6. The method of  claim 1  wherein the liposome-encapsulated opioid analgesic agent is prepared using a phospholipid. 
     
     
       7. The method of  claim 6  wherein the phospholipid is selected from the groups consisting of phosphatidylcholines, lysophosphatidylcholines, phosphatidylserines, phosphatidylethanolamines, phosphatidylinositols and mixtures thereof. 
     
     
       8. The method of  claim 6  wherein said phospholipid is provided in admixtures with a modifying agent selected from the group consisting of cholesterol, stearyl amines, stearic acid, tocopherols, and mixtures thereof. 
     
     
       9. The method of  claim 8  wherein said opioid analgesic agent is selected from the group consisting of alfentanil, anileridine, codiene, diamorphine, fentanyl, hydrocodone, hydromorphone, meperidine (pethidine), morphine, oxycodone, oxymorphone, propoxyphene, sufentanil, pentazocine and nalbuphine. 
     
     
       10. The method of  claim 1  wherein the composition contains said opioid in an amount of between 0.005% to 10% by weight. 
     
     
       11. A method for providing systemic analgesia in a patient by administering a liposomal  both a free and liposome-encapsulated opioid analgesic agent by inhalation through said patient's pulmonary system, said analgesic agent being selected from the group consisting of fentanyl, alfentanil and sufentanil. 
     
     
       12. The method of  claim 1  wherein the opioid analgesic agent is fentanyl or a salt form thereof. 
     
     
       13. The method of  claim 12  wherein the opioid analgesic is fentanyl base. 
     
     
       14. The method of  claim 12  wherein the opioid analgesic is fentanyl citrate. 
     
     
       15. The method of  claim 1  wherein the opioid analgesic is alfentanil or a salt form thereof. 
     
     
       16. The method of  claim 15  wherein the opioid analgesic is alfentanil base. 
     
     
       17. The method of  claim 15  wherein the opioid analgesic is alfentanil HCl. 
     
     
       18. The method of  claim 1  wherein the opioid analgesic is sufentanil. 
     
     
       19. The method of  claim 2  wherein the free form selected opioid analgesic agent is in the range of  10 - 20 %  of opioid dose.   
     
     
       20. The method of  claim 2  wherein the selected analgesic agent is fentanyl citrate. 
     
     
       21. The method of  claim 1  wherein the opioid analgesic agent is selected from the group consisting of fentanyl, alfentanyl and sufentanil. 
     
     
       22. A method of managing pain in a patient comprising administering to said patient a composition containing both free and liposome- encapsulated fentanyl citrate through said patient's pulmonary system, wherein said liposome - encapsulated fentanyl citrate is prepared using a phosphatidylcholine in admixture with cholesterol, and wherein said liposome - encapsulated fentanyl citrate comprises a mixture of unilamellar vesicles and multilamellar vesicles.   
     
     
       23. The method of  claim 22 , wherein the composition comprises an amount of fentanyl citrate suitable to afford a plasma concentration in a range of between  0 . 2  ng/ml to about  1 . 2  ng/ml. 
     
     
       24. A method for providing systemic analgesia in a patient by administering both free and liposome- encapsulated fentanyl citrate by inhalation through said patient's pulmonary system, wherein said liposome - encapsulated fentanyl citrate is prepared using a phosphatidylcholine in admixture with cholesterol, and wherein said liposome - encapsulated fentanyl citrate comprises a mixture of unilamellar vesicles and multilamellar vesicles.   
     
     
       25. The method of  claim 24 , wherein the composition comprises an amount of fentanyl citrate suitable to afford a plasma concentration in a range of between about  0 . 2  ng/ml to about  1 . 2  ng/ml.