Sphingomyelin liposomes for the treatment of hyperactive bladder disorders

• US 20070122466A1
• Filed: 10/11/2006
• Published: 05/31/2007
• Est. Priority Date: 08/13/2001
• Status: Active Grant

• Current Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education), University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• Inventors: Huang, Leaf, Yoshimura, Naoki, Chuang, Yao-Chi, de Groat, William, Fraser, Matthew, Chancellor, Michael, Tyagi, Pradeep
• Granted Patent: US 8,110,217 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides pharmaceutical compositions and methods for the instillation of lipid vehicles comprised of liposomes containing sphingomyelin or sphingomyelin metabolites to prevent, manage, ameliorate and/or treat disorders involving neuropathic pain and aberrant muscle contractions, such as what occurs in bladder hyperactivity disorders such as interstitial cystitis (IC) in animals or humans in need thereof. Also provided is a liposome-based delivery of drugs, e.g., antibiotics, pain treatments and anticancer agents, to the bladder, genitourinary tract, gastrointestinal system, pulmonary system and other organs or body systems. In particular, liposome-based delivery of vanilloid compounds, such as resiniferatoxin, capsaicin, or tinyatoxin and toxins, such as botulinum toxin is provided for the treatment of bladder conditions, including pain, inflammation, incontinence and voiding dysftunction.

Claims

1. A pharmaceutical composition, comprising:

a) a non-cationic liposome; and

b) a physiologically acceptable carrier.

2. The pharmaceutical composition according to claim 1, wherein the liposome is comprised of at least one lipid.

6. The pharmaceutical composition according to any one of claims 2-5, wherein the at least one lipid is selected from the group consisting of phospholipids, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol or cardiolipin (CL);

glycolipids;

sphingophospholipids, such as sphingomyelin,;

sphingoglycolipids (also known as 1-ceramidyl glucosides), such as ceramide galactopyranoside, gangliosides and cerebrosides;

cholesterol;

1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); and

1,2-dioleoylphosphatidylcholine (DOPC).

7. The pharmaceutical composition according to claim 1, wherein the non-cationic liposome is comprised of a phospholipid.

8. The pharmaceutical composition according to claim 7, wherein the phospholipid is phosphatidylcholine.

9. The pharmaceutical composition according to claim 1, wherein the non-cationic liposome is comprised of a sphingoglycolipid.

10. The pharmaceutical composition according to claim 9, wherein the sphingoglycolipid is sphingomyelin.

15. The pharmaceutical composition according to any one of claims 1, 3, 4 or 5, wherein the pharmaceutical composition is administered to prevent, manage, ameliorate and/or treat hyperactivity bladder disorders in animals or humans afflicted with said hyperactivity bladder disorders.

16. The pharmaceutical composition according to claim 15, wherein the hyperactivity bladder disorder is interstitial cystitis.

17. A method of preventing, managing, ameliorating and/or treating hyperactivity bladder disorders in animals or humans in need thereof, comprising:

a) administering to said animal or human a therapeutically effective amount of the pharmaceutical composition as claimed in any one of claims 1, 3, 4 or 5.

18. The method according to claim 17, wherein the therapeutically effective amount of the pharmaceutical composition ranges from a dosage of about 0.1 mg to about 20 mg per kilogram body weight of the animal or human.

19. The method according to claim 17, wherein the therapeutically effective amount of the pharmaceutical composition ranges from a dosage of about 0.5 mg to about 10 mg per kilogram body weight of the animal or human.

20. The method according to claim 17, wherein the therapeutically effective amount of the pharmaceutical composition ranges from a dosage of about 1.0 mg to about 5.0 mg per kilogram body weight of the animal or human.

21. The method according to claim 17, wherein the route of administration is selected from the group consisting of intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intravesical, transdermal, intra-arterial, intrathecal, enteral, epidural, intranasal, inhalated, sublingual, oral, rectal, vaginal and intestinal.

22. The method according to claim 21, wherein the route of administration is by intravesical instillation.

3. A pharmaceutical composition, comprising:

a) a liposome, and

b) a physiologically acceptable carrier,

wherein the liposome is comprised of ceramide and at least one lipid.

11. The pharmaceutical composition according to any one of claims 3 or 4, wherein the ceramide or sphingosine is included in the lipid in a concentration ranging from about 0.1 mol % to about 10.0 mol %.

12. The pharmaceutical composition according to any one of claims 3 or 4, wherein the ceramide and sphingosine is included in the lipid in a concentration ranging from about 0.5 mol % to about 2.0 mol %.

13. The pharmaceutical composition according to any one of claims 3 or 4, wherein the ceramide or sphingosine is included in the lipid in a concentration of about 1 mol %.

4. A pharmaceutical composition, comprising:

a) a liposome, and

b) a physiologically acceptable carrier,

wherein the liposome is comprised of sphingosine and at least one lipid.

5. A pharmaceutical composition, comprising:

a) a liposome, and

b) a physiologically acceptable carrier,

wherein the liposome is comprised of sphingosine 1-phosphate and at least one lipid.

14. The pharmaceutical composition according to claim 5, wherein the sphingosine 1-phosphate is included in the synthetic lipid in a concentration ranging from about 2.0 mol % to about 5 mol %.