Compositions and methods for stabilized polysaccharide formulations

• US 8,623,839 B2
• Filed: 06/30/2011
• Issued: 01/07/2014
• Est. Priority Date: 06/30/2011
• Status: Active Grant

• Current Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Original Assignee: Depuy Mitek LLC (Johnson & Johnson)
• Inventors: Su, Dongling, Hwang, Julia, Story, Brooks J.
• Primary Examiner(s): Jiang, Shaojia Anna
• Assistant Examiner(s): Krishnan, Ganapathy
• Application Number:
  US13/173,658
• Publication Number:
  US 20130005681A1
• Time in Patent Office: 922 Days
• Field of Search: 514/54
• US Class Current: 514/54
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/726 Glycosaminoglycans, i.e. mucopolysaccharides chondroitin sulfate, dermatan sulfate A61K31/737
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/505 Stabilizers
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Compositions and methods are provided for treating joint conditions, such as osteoarthritis and/or the pain associated therewith. The compositions and methods utilize a first component, namely hyaluronic acid (“HA”), in combination with at least one stabilizer. The composition can include a stabilizer that increases the stability and shelf-life of the HA. In another embodiment, the compositions and methods can also include an additional component, such as one or more glycosaminoglycans (“GAG”) or GAG precursors. Examples of GAGs or GAG precursors can include chondroitin sulfate (“CS”), dermatan sulfate, heparin, heparan sulfate, keratan sulfate, and glucosamine (“GlcN”).

Claims

1. A composition for treating a joint condition, comprising:

a formulation comprising high molecular weight hyaluronic acid (HA); and

at least one stabilizer, wherein the stabilizer increases stability of the formulation, wherein the at least one stabilizer comprises trehalose, and wherein the trehalose is present in a range of about 0.1% to 50% by weight of the composition.

2. The composition of claim 1, wherein the high molecular weight HA has a molecular weight in the range of about 1 MDa to 6 MDa.

3. The composition of claim 1, wherein the HA is present at a liquid concentration of at least about 1 mg/ml.

4. The composition of claim 1, wherein the HA is lyophilized.

5. The composition of claim 1, wherein the at least one stabilizer further comprises at least one of tocopherol, tocopherol derivatives, mannitol, and sucrose.

6. The composition of claim 1, wherein the formulation is stable at room temperature.

7. The composition of claim 1, further comprising at least one additional component.

8. The composition of claim 7, wherein the additional component is selected from the group consisting of a glycosaminoglycan (GAG) and a GAG precursor and is present within the composition at a ratio of HA to additional component in the range of about 1:

0.005 to 1;

100.

9. A kit, comprising:

a composition of high molecular weight hyaluronic acid (HA) and at least one stabilizer, wherein the at least one stabilizer comprises trehalose, and wherein the trehalose is present in a rang of about 0.1% to 50% by weight of the composition; and

a syringe comprising the composition of HA and stabilizer in a single chamber.

10. The kit of claim 9, wherein the HA has a molecular weight greater than 1 MDa.

11. The kit of claim 9, wherein the HA is present at a liquid concentration of at least about 1 mg/ml.

12. The kit of claim 9, wherein the HA is lyophilized.

13. The kit of claim 9, wherein the at least one stabilizer further comprises at least one of tocopherol, tocopherol derivatives, mannitol, and sucrose.

14. The kit of claim 9, wherein the composition further comprises at least one additional component selected from the group consisting of a glycosaminoglycan (GAG) and a GAG precursor.

15. The kit of claim 14, wherein the syringe further comprises a separate chamber that comprises the at least one additional component.

16. The kit of claim 14, wherein the at least one additional component is lyophilized.

17. A method for treating joints, comprising:

administering a formulation comprising high molecular weight hyaluronic acid and at least one stabilizer to a subject in need thereof, wherein the at least one stabilizer comprises trehalose, and wherein the trehalose is present in a range of about 0.1% to 50% by weight of the composition.

18. The method of claim 17, wherein the step of administering further comprises storing the formulation at room temperature prior to administration.

19. The method of claim 17, wherein the step of administering further comprises combining the formulation with at least one additional component prior to administration.