INJECTION VEHICLE FOR POLYMER-BASED FORMULATIONS

• US 20070098736A1
• Filed: 12/21/2006
• Published: 05/03/2007
• Est. Priority Date: 10/15/1999
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Okumu, Franklin, Cleland, Jeffrey, Lam, Xanthe
• Granted Patent: US 7,651,703 B2
• Time in Patent Office: Days
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• 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 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 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• 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: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/55 Fab or Fab'

Abstract

The invention provides injection vehicles suitable for administering particulate suspensions, such as polymer-based formulations, as well as associated pharmaceutical formulations, articles of manufacture, and kits. Other aspects of the invention included methods for producing and administering pharmaceutical formulations. The injection vehicles of the invention are superior to conventional injection vehicles in that they include a pseudoplastic composition that improves injectability, which facilitates delivery of the desired dose. The injection vehicles of the invention also allow the use of smaller-bore needles than are usually necessary to inject polymer-based formulations, reducing the pain associated with injection of such formulations.

Claims

1. An injection vehicle comprising hyaluronic acid or a derivative thereof at a concentration of about 0.01 to about 0.8 percent by volume.

2. The injection vehicle of claim 1, wherein the injection vehicle comprises hyaluronic acid.

3. The injection vehicle of claim 1, wherein the hyaluronic acid or derivative thereof is dissolved in physiological saline.

4. A pharmaceutical formulation comprising:

(a) an effective amount of a biologically active agent in particulate form or coated on, dispersed within, or accompanied by particles; and

(b) an injection vehicle comprising hyaluronic acid or a derivative thereof.

5. The pharmaceutical formulation of claim 4 wherein the biologically active agent dispersed within particles comprising a biocompatible polymeric matrix.

6. The pharmaceutical formulation of claim 5, wherein the injection vehicle comprises hyaluronic acid.

7. The pharmaceutical formulation of claim 6, wherein the concentration of hyaluronic acid is between about 0.01 and about 0.8 percent weight per volume.

8. The pharmaceutical formulation of claim 6, wherein the hyaluronic acid is dissolved in physiological saline.

9. The pharmaceutical formulation of claim 6, wherein the polymer matrix comprises a polymer selected from the group consisting of a biodegradable polymer, a non-biodegradable polymer, a mixture of biodegradable and non-biodegradable polymers, and a copolymer comprising biodegradable and non-biodegradable units.

10. The pharmaceutical formulation of claim 6, wherein the polymeric matrix comprises a polymer selected from the group consisting of blocked polymers, unblocked polymers, and mixtures thereof.

11. The pharmaceutical formulation of claim 6, wherein the polymeric matrix comprises a polymer selected from the group consisting of a poly(glycolide);

a poly(lactide-co-glycolide);

a poly(lactic acid);

a poly(glycolic acid);

a poly(lactic acid-co-glycolic acid);

a polyanhydride;

a polyorthoester;

a polyetherester;

a polycaprolactone;

a polyesteramide;

a block copolymer of polyethylene glycol and lactide or glycolide; and

a blend or copolymer thereof.

12. The pharmaceutical formulation of claim 11, wherein the polymer is a poly(lactide-co-glycolide) polymer.

13. The pharmaceutical formulation of claim 6, wherein the biologically active agent is a polypeptide.

14. The pharmaceutical formulation of claim 11, wherein the polypeptide is selected from the group consisting of a growth hormone, a hepatocyte growth factor (HGF), a vascular endothelial growth factor (VEGF), an anti-vascular endothelial growth factor Fab (anti-VEGF Fab), a glucagon-like peptide I (GLP-I), a nerve growth factor, and an insulin-like growth factor.

15. The pharmaceutical formulation of claim 6, wherein the concentration of the polymeric matrix comprising the biologically active agent is between at least about 1 mg/mL to about 500 mg/mL of formulation.

16. The pharmaceutical formulation of claim 15, wherein the concentration of the polymeric matrix comprising the biologically active agent is between at least about 1 mg/mL to about 300 mg/mL of formulation.

17. A pharmaceutical formulation comprising:

(a) particles comprising a biocompatible polymeric matrix comprising a poly(lactide-co-glycolide) polymer;

(b) an effective amount of a biologically active polypeptide dispersed within the polymeric matrix; and

(c) an injection vehicle comprising hyaluronic acid or a derivative thereof.

20. A method for administering a pharmaceutical formulation of claim 17 comprising injecting the pharmaceutical formulation through a 23-gauge or smaller needle.

18. A method for producing a pharmaceutical formulation comprising:

adding an effective amount of a biologically active agent in particulate form or coated on, dispersed within, or accompanied by particles

to an injection vehicle comprising hyaluronic acid or a derivative thereof.

19. The method of claim 18 wherein the injection vehicle comprises hyaluronic acid.