.

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

Claims for Patent: 7,229,630

« Back to Dashboard

Claims for Patent: 7,229,630

Title:Stabilized formulations of alpha adrenergic receptor antagonists and the uses thereof
Abstract:The present invention provides compositions and stable liquid formulations comprising alpha adrenergic receptor antagonists and use thereof for increasing blood flow. In one embodiment, the stable liquid formulations of this invention are useful for reversing the effects of an anesthetic agent, preferably a long-lasting local anesthetic agent administered in conjunction with an alpha adrenergic receptor agonist.
Inventor(s): Chen; Andrew X. (San Diego, CA), Knowles; Julius (Del Mar, CA), Weber; Eckard (San Diego, CA)
Assignee: Novalar Pharmaceuticals, Inc. (DE)
Application Number:10/465,810
Patent Claims: 1. A stable liquid formulation consisting essentially of a low dose of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent, and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 and 6.0.

2. A stable liquid formulation consisting essentially of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 and about 6.0, and wherein said stable liquid formulation is present in a dental cartridge or a pre-filled sterile syringe.

3. The stable liquid formulation according to claim 1 or 2, wherein said alpha adrenergic receptor antagonist is selected from phentolamine, phentolamine hydrochloride, phentolamine mesylate, tolazoline, yohimbine, rauwolscine, doxazosine, labetalol, prazosine, tetrazosine or trimazosine or a pharmaceutically acceptable salt of any of the above.

4. The stable liquid formulation of claim 3, wherein said alpha adrenergic receptor antagonist is phentolamine mesylate.

5. The stable liquid formulation according to claim 1 or 2, wherein said alpha adrenergic receptor antagonist is present at a concentration of between about 0.01 mg/ml and about 10 mg/ml.

6. The stable liquid formulation according to claim 5, wherein said alpha adrenergic receptor antagonist is present at a concentration of between about 0.1 mg/ml and about 0.25 mg/ml.

7. The stable liquid formulation of claim 6, wherein said alpha adrenergic receptor antagonist is phentolamine mesylate.

8. The stable liquid formulation according to claim 1 or 2, wherein said aqueous solvent is water.

9. The stable liquid formulation according to claim 1 or 2, wherein said metal chelator is EDTA present at a concentration of between about 0.5 and about 1.0 mg/ml.

10. The stable liquid formulation of claim 9, wherein said alpha adrenergic receptor antagonist is phentolamine mesylate.

11. The stable liquid formulation according to claim 1 or 2, wherein the pH of said formulation is between about 3.5 and about 4.5.

12. The stable liquid formulation according to claim 1 or 2, wherein said pH is achieved with a 10 to 50 mM acetate buffer, or with methanesulfonic acid.

13. The stable liquid formulation of claim 12, wherein said alpha adrenergic receptor antagonist is phentolamine mesylate.

14. A stable liquid formulation consisting essentially of a low dose of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent, a tonicity modifier, and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 and 6.0.

15. A stable liquid formulation consisting essentially of a low dose of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent, an antioxidant in an amount sufficient to prevent oxidization of said alpha adrenergic receptor antagonist, and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 and 6.0.

16. A stable liquid formulation consisting essentially of a low dose of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent, a complexing agent, and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 and 6.0.

17. A stable liquid formulation comprising 0.235 mg/ml phentolamine mesylate, 0.5 mg/ml EDTA, 5% d-mannitol, and 16.6 mM acetate buffer, wherein said formulation has a pH of 3.8 to 4.2.

18. A stable liquid formulation selected from: TABLE-US-00012 a. Phentolamine Mesylate 0.222 mg EDTA Na.sub.2 0.5 mg D-Mannitol 50 mg Sodium Acetate 1.36 mg Acetic Acid q.s. to pH 3.8 to 4.2 WFI q.s. to 1.0 mL; b. Phentolamine Mesylate 0.222 mg EDTA Na.sub.2 1.0 mg D-Mannitol 50 mg Sodium Acetate 1.36 mg Acetic Acid q.s. to pH 3.8 to 4.2 WFI q.s. to 1.0 mL; c. Phentolamine Mesylate 0.222 mg EDTA Na.sub.2 0.5 mg D-Mannitol 50 mg WFI q.s. to 1.0 mL; d. Phentolamine Mesylate 0.222 mg EDTA Na.sub.2 1.0 mg D-Mannitol 50 mg WFI q.s. to 1.0 mL; e. Phentolamine Mesylate 0.222 mg EDTA Na.sub.2 0.5 mg D-Mannitol 50 mg Methanesulfonic Acid q.s. to pH 3.5 to 4.5 WFI q.s. to 1.0 mL; f. Phentolamine Mesylate 0.222 mg EDTA Na.sub.2 1.0 mg D-Mannitol 50 mg Methanesulfonic Acid q.s. to pH 3.5 to 4.5 WFI q.s. to 1.0 mL; g. Phentolamine Mesylate 0.222 mg EDTA Na.sub.2 0.5 mg D-Mannitol 50 mg PPG 259.5 mg WFI q.s. to 1.0 mL; h. Phentolamine Mesylate 0.1 mg EDTA Na.sub.2 0.5 mg D-Mannitol 50 mg Sodium Acetate 1.36 mg Acetic Acid q.s. to pH 3.5 WFI q.s. to 1.0 mL; i. Phentolamine Mesylate 0.1 mg EDTA Na.sub.2 0.5 mg D-Mannitol 50 mg Sodium Acetate 1.36 mg Acetic Acid q.s. to pH 4.0 WFI q.s. to 1.0 mL; j. Phentolamine Mesylate 0.1 mg EDTA Na.sub.2 0.5 mg D-Mannitol 44 mg Sodium Acetate 1.36 mg Acetic Acid q.s. to pH 3.5 WFI q.s. to 1.0 mL; k. Phentolamine Mesylate 0.1 mg EDTA Na.sub.2 0.5 mg Sodium Acetate 6.80 mg Acetic Acid q.s. to pH 3.5 WFI q.s. to 1.0 mL; or l. Phentolamine Mesylate 0.235 mg EDTA Na.sub.2 0.5 mg D-Mannitol 50 mg Sodium Acetate 1.36 mg Acetic Acid q.s. to pH 3.8 to 4.2 WFI q.s. to 1.0 mL.

19. A stable liquid formulation consisting essentially of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent, a tonicity modifier, and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 to about 6.0, and wherein said stable liquid formulation is present in a dental cartridge or a pre-filled sterile syringe.

20. A stable liquid formulation consisting essentially of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent, an antioxidant in an amount sufficient to prevent oxidization of said alpha adrenergic receptor antagonist, and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 to about 6.0, and wherein said stable liquid formulation is present in a dental cartridge or a pre-filled sterile syringe.

21. A stable liquid formulation consisting essentially of an alpha adrenergic receptor antagonist, a buffer for maintaining pH, an aqueous solvent, a complexing agent, and a metal chelator selected from diammonium ethylenediamine triacetate, hydroxyethyl-ethylenediamine triacetic acid, diethylenetriamine pentaacetic acid, nitriloacetic acid, citric acid, or EDTA, wherein said formulation has a pH of from about 2.0 to about 6.0, and wherein said stable liquid formulation is present in a dental cartridge or a pre-filled sterile syringe.

22. The stable liquid formulation according to claim 14 or 19, wherein said tonicity modifier is selected from NaCl, d-mannitol or dextrose.

23. The stable liquid formulation according to claim 22, wherein said tonicity modifier is d-mannitol present at a concentration of between about 4 and about 5% (w/v).

24. The stable liquid formulation of claim 23, wherein said alpha adrenergic receptor antagonist is phentolamine mesylate.

25. The stable liquid formulation according to claim 15 or 20, wherein said antioxidant is selected from ascorbic acid, sodium metabisulfite, butylated hydroxyanisole, and butylated hydroxytoluene.

26. The stable liquid formulation of claim 25, wherein said alpha adrenergic receptor antagonist is phentolamine mesylate.

27. The stable liquid formulation according to claim 16 or 21, wherein said complexing agent is selected from .alpha.-cyclodextrin or niacinamide.

28. The stable liquid formulation of claim 27, wherein said alpha adrenergic receptor antagonist is phentolamine mesylate.

29. A container comprising a single dosage form of a stable liquid formulation according to any one of claims 1, 2, 14, 15, 16, 17, 18, 19, 20, or 21.

30. The container according to claim 29, selected from an ampule, a dental cartridge or a pre-filled sterile syringe.

31. The container according to claim 30, wherein said stable liquid formulation is present in a volume of between about 1.6 and 1.8 mL.

32. A kit comprising a carrier having in close confinement therein two or more containers, wherein a first container contains an anesthetic agent and optionally an alpha adrenergic receptor agonist and a second container contains the stable liquid formulation according to any one of claims 1, 2, 14, 15, 16, 17, 18, 19, 20, or 21.

33. The kit according to claim 32, wherein said second container comprises a single dosage form of said stable liquid formulation.
« 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