.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,045,824

« Back to Dashboard

Details for Patent: 6,045,824

Title: Sustained-release liposomal anesthetic compositions
Abstract:The invention provides a method for obtaining local anesthetics encapsulated in liposomes, such as multivesicular liposomes, with high encapsulation efficiency and slow release in vivo. When the encapsulated anesthetic is administered as a single intracutaneous dose, the duration of anesthesia and half-life of the drug at the local injection site is increased as compared to injection of unencapsulated anesthetic. The maximum tolerated dose of the encapsulated anesthetic is also markedly increased in the liposomal formulation over injection of unencapsulated anesthetic. These results show that the liposomal formulation of local anesthetic is usefuil for sustained local infiltration and nerve block anesthesia.
Inventor(s): Kim; Sinil (Solano Beach, CA), Kim; Taehee (Los Angeles, CA), Murdandi; Sharad (Groton, CT)
Assignee: SkyePharma Inc. (San Diego, CA)
Filing Date:Sep 18, 1998
Application Number:09/156,214
Claims:1. A pharmaceutical composition comprising:

a) a multivesicular liposome comprising

at least one amphipathic lipid, and

at least one neutral lipid; and

b) an aqueous phase comprising

polyhydroxy carboxylate salts and di- or tri-protic mineral salts of amide anesthetics,

wherein the aqueous phase is encapsulated within the multivesicular liposome.

2. The pharmaceutical composition of claim 1, wherein the aqueous phase further comprises hydrochloric acid.

3. The pharmaceutical composition of claim 1, wherein the amphipathic lipid is provided in admixture with cholesterol, plant sterols, or combinations thereof.

4. The pharmaceutical composition of claim 1, wherein the di- or tri-protic mineral salts of the amide anesthetics are selected from the group consisting of sulfates, phosphates, and combinations thereof.

5. The pharmaceutical composition of claim 1, wherein the polyhydroxy carboxylate salts of the amide anesthetics are selected from the group consisting of glucuronate, gluconate, tartarate, and combinations thereof.

6. The pharmaceutical composition of claim 1, wherein the amphipathic lipid is selected from the group consisting of phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylglycerols, phosphatidylserines, phosphatidylinositols, phosphatidic acids, cardiolipins, diacyl dimethylammonium propanes, and stearylarnines.

7. The pharmaceutical composition of claim 1, wherein the neutral lipid is selected from the group consisting of triglycerides, diglycerides, ethylene glycol, esters and squalene.

8. The pharmaceutical composition of claim 1, wherein the amide anesthetic is a xylidide.

9. The pharmaceutical composition of claim 8, wherein the xylidide is selected from the group consisting of bupivacaine, mepivacaine, ropivacaine, lidocaine, pyrrocaine, prilocaine and stereoisomers thereof.

10. The pharmaceutical composition of claim 8, wherein the xylidide has the following structure: ##STR2## wherein R.sub.1 is a secondary or tertiary alkyl amine or a secondary or tertiary alkylene amine, R.sub.2 is hydrogen, alkyl or alkylene which further links to R.sub.1, R.sub.3 is an alkyl substituted phenyl substituent.

11. The pharmaceutical composition of claim 10, wherein R.sub.1 and R.sub.2 form a substituent selected from the group consisting of N-alkyl piperidine, and N-alkyl pyrrolidine.

12. The pharmaceutical composition of claim 10, wherein R.sub.3 is 2,6-dimethylphenyl substituent.

13. A process for preparing a multivesicular liposome-encapsulated anesthetic composition, the process comprising:

a) forming a "water-in-oil" emulsion from a first aqueous phase and a volatile organic phase, wherein the first aqueous phase comprises

polyhydroxy carboxylate salts and di- or tri-protic mineral salts of amide anesthetics,

and the volatile organic phase comprises

a volatile organic solvent,

at least one amphipathic lipid, and

at least one neutral lipid;

b) dispersing the "water-in-oil" emulsion into a second aqueous phase to form solvent spherules; and

c) removing the volatile organic solvent from the solvent spherules to form a multivesicular liposome-encapsulated amide anesthetic suspended in the second aqueous phase.

14. The process of claim 13, wherein the amide anesthetic is a xylidide.

15. The process of claim 14, wherein the xylidide is selected from the group consisting of bupivacaine, mepivacaine, ropivacaine, lidocaine, pyrrocaine, prilocaine and stereoisomers thereof.

16. A method of locally anesthetizing a subject, the method comprising subcutaneously, intracutaneously, or via a nerve block, injecting the pharmaceutical composition of claim 1 into a subject in need of anesthetization.

17. The method of claim 16, wherein the amide anesthetic is a xylidide.

18. The method of claim 17, wherein the xylidide is selected from the group consisting of bupivacaine, mepivacaine, ropivacaine, lidocaine, pyrrocaine, prilocaine and stereoisomers thereof.

19. A method of increasing drug loading in multivesicular liposomes by converting an amide anesthetic into a binary salt mixture wherein the two counterions are derived from a polyhydroxy carboxylic acid and a di- or tri-protic mineral acid.

20. The method of claim 19, wherein the polyhydroxy carboxylic acid is selected from the group consisting of sulfuric acid, phosphoric acid, and combinations thereof.

21. The method of claim 19, wherein the di- or tri-protic mineral acid is selected from the group consisting of sulfuric acid, phosphoric acid, and combinations thereof.

22. The method of claim 19, wherein the amide anesthetic is a xylidide, selected from the group consisting of bupivacaine, mepivacaine, ropivacaine, lidocaine, pyrrocaine, prilocaine and stereoisomers thereof.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc