FORMULATIONS OF INTRAARTICULAR PHARMACEUTICAL AGENTS AND METHODS FOR PREPARING AND USING THE SAME

• US 20170209587A1
• Filed: 07/20/2015
• Published: 07/27/2017
• Est. Priority Date: 07/21/2014
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: TARRAND, Jeffrey J., ANDERSSON, Borje S.
• Granted Patent: US 10,646,574 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 31/75 of ethene
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis

Abstract

Provided herein are compositions and methods for preparing intraarticular formulations comprising biocompatible pharmaceutical agents and use thereof in the treatment of diseases, such as degenerative bone diseases, including osteoarthritis of the knee, hip, or other joints, and similar chronic or acute destructive arthropathies resulting from autoimmune disorders or infectious disease.

Claims

1. A method for lubricating a joint of a mammal comprising administered into a cavity of the joint an effective amount of a composition comprising at least 0.6% polyethylene glycol (PEG), wherein the composition is a liquid at the temperature of the joint and the oncotic pressure of the composition is not greater than the serum oncotic pressure of the mammal.

2. The method of claim 1, wherein the composition comprises at least 1.5% PEG.

3. The method of claim 1, wherein administering comprises injecting the composition into an intra-articular cavity of the joint.

4. The method of claim 1, wherein the composition further comprises polyvinyl pyrrolidone (PVP) or polyvinyl alcohol (PVA).

5. The method of claim 1, wherein the composition further comprises hydroxyethyl cellulose (HEC), methylcellulose, hydroxypropyl cellulose (HPC), or a combination thereof.

6. The method of claim 1, wherein the composition further comprises chondroitin, dextran, polyglucosame (chitosan), agarose, xanthan gum, alginate, carrageenan, guar gum, locust bean gum, or a combination thereof.

7. The method of claim 1, wherein the composition further comprises DMSO, mineral oil, paraffin jelly, silicone oil, or a combination thereof.

8. The method of claim 1, wherein the composition further comprises ethanol, steryl alcohol, phosphatidylcholine, oleic acid, oleyl alcohol, hydroxyl stearate, cetyl alcohol, myristyl lactate, isopropyl myristate, or a combination thereof.

9. The method of claim 1, wherein the composition comprises PEG-tyramine.

10. The method of claim 1, wherein the composition comprises up to about 6% PEG 600K-10M.

11. The method of claim 1, wherein the composition comprises up to about 2% PEG 1-2M.

12. The method of claim 1, wherein the composition comprises up to about 12% PEG 100-600K.

13. The method of claim 1, wherein the composition comprises up to about 2% PEG 100-600K.

14. The method of claim 1, wherein the composition comprises up to about 12% HEC.

15. The method of claim 1, wherein the composition comprises up to about 12% PVP.

16. The method of claim 1, wherein at least a portion of the PEG is conjugated to an antimicrobial agent, antifungal agent, and/or antiviral agent.

17. The method of claim 1, wherein at least a portion of the PEG is comprised in a block polymer.

18. The method of claim 1, wherein the composition has a pH from about 7.5 to about 7.8.

19. The method of claim 1, wherein the composition is hydrophobic.

20. The method of claim 1, wherein the composition is hydrophilic.

21. The method of claim 1, wherein administering comprises warming the composition to the temperature of the joint prior to administration.

22. The method of claim 1, wherein the mammal has joint dysfunction.

23. The method of claim 22, wherein the joint dysfunction is caused by a degenerative bone disease, osteoarthritis, rheumatoid arthritis, an infectious disease, an immune disease, an autoimmune disease, or sepsis.

24. A method for lubricating a joint of a mammal comprising administered an effective amount of a composition comprising at least 10% polyethylene glycol 400 (PEG 400).

25. The method of claim 24, wherein administering comprises intravenous injection, slow bolus infusion, subcutaneous injection, intraperitoneal injection, or oral administration.

26. An intraarticular formulation comprising an effective concentration of polyethylene glycol (PEG) of at least 600,000.

27. The intraarticular formulation of claim 26, further comprising hydroxyethyl cellulose (HEC).

28. The intraarticular formulation of claim 26, further defined as comprising 1.4% PEG 600K.

29. The intraarticular formulation of claim 26, further defined as comprising 4.5% PEG 600K.

30. The intraarticular formulation of claim 26, further defined as comprising 6% PEG 600K.

31. The intraarticular formulation of claim 26, further defined as comprising 9% PEG 600K.

32. The intraarticular formulation of claim 26, further defined as comprising 0.9% PEG 3.6M.

33. The intraarticular formulation of claim 26, further defined as comprising 0.9% PEG 4M.

34. The intraarticular formulation of claim 26, comprising an effective concentration of polyethylene glycol (PEG) of at least 1,000,000.

35. The intraarticular formulation of claim 34, comprising an effective concentration of polyethylene glycol (PEG) of at least 5,000,000.

41. A method for lubricating a joint of a mammal comprising administered into a cavity of the joint an effective amount of a composition according to any one of claims 26-40, wherein the composition is a liquid at the temperature of the joint and the oncotic pressure of the composition is not greater than the serum oncotic pressure of the mammal.

36. An intraarticular formulation comprising a high molecular weight polyethylene glycol (PEG) and hydroxyethyl cellulose (HEC).

37. The intraarticular formulation of claim 36, further comprising PEG-tyramine and/or HEC-tyramine.

38. The intraarticular formulation of claim 36, further comprising polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and/or carboxymethyl cellulose (CMC).

39. The intraarticular formulation of claim 36, further defined as comprising PEG 2M, HEC 1.3M, PEG 600K, carboxymethyl cellulose (CMC) 1.7M, and/or PVP 360K.

40. The intraarticular formulation of claim 36, further defined as comprising PEG-tyramine 2M, HEC 1.3M, PEG 600K, CMC 1.7M, and/or PVP 360K.

42. A method for lubricating a joint of a mammal comprising administered into a cavity of the joint an effective amount of a composition comprising petroleum jelly or silicon oil, and phosphatidylcholine, wherein the composition is a liquid at the temperature of the joint and the oncotic pressure of the composition is not greater than the serum oncotic pressure of the mammal.

43. A method for lubricating a joint of a mammal comprising administered into a cavity of the joint an effective amount of a composition comprising hydroxyethyl cellulose, wherein the composition is a liquid at the temperature of the joint and the oncotic pressure of the composition is not greater than the serum oncotic pressure of the mammal.

44. A method for lubricating a joint of a mammal comprising administered into a cavity of the joint an effective amount of a composition comprising hydroxyethyl cellulose and polyethylene glycol, wherein the composition is a liquid at the temperature of the joint and the oncotic pressure of the composition is not greater than the serum oncotic pressure of the mammal.

45. A method for lubricating a joint of a mammal comprising administered into a cavity of the joint an effective amount of a composition comprising hydroxyethyl cellulose, polyethylene glycol, carboxymethyl cellulose, and polyvinylpyrrolidone, wherein the composition is a liquid at the temperature of the joint and the oncotic pressure of the composition is not greater than the serum oncotic pressure of the mammal.

46. A method for lubricating a joint of a mammal comprising administered into a cavity of the joint an effective amount of a composition comprising hydroxyethyl cellulose, polyethylene glycol, and polyvinyl alcohol, wherein the composition is a liquid at the temperature of the joint and the oncotic pressure of the composition is not greater than the serum oncotic pressure of the mammal.