Composition and method for vancomycin oral liquid

• US 10,493,028 B2
• Filed: 10/24/2017
• Issued: 12/03/2019
• Est. Priority Date: 03/14/2014
• Status: Active Grant

• Current Assignee: Azurity Pharmaceuticals, Inc.
• Original Assignee: Cutispharma, Inc. (Azurity Pharmaceuticals, Inc.)
• Inventors: Muni, Indu, Mione, Peter, Gandhi, Anisa, LeChiara, Cristina
• Primary Examiner(s): Milligan, Adam C
• Assistant Examiner(s): Alawadi, Sarah
• Application Number:
  US15/791,717
• Publication Number:
  US 20180116955A1
• Time in Patent Office: 770 Days
• CPC Class Codes: A23L 2/52 Adding ingredients adding preservatives A23L2/44
• CPC Class Codes: A23L 2/56 Flavouring or bittering agents sweeteners A23L2/60
• CPC Class Codes: A23L 2/60 Sweeteners
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A61K 38/14 Peptides containing saccharide radicals; Derivatives thereof , e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

The invention relates to stable vancomycin hydrochloride powder for oral liquid formulations. Also provided herein are methods of using vancomycin oral liquid formulations for the treatment of certain diseases such as Clostridium difficile pseudomembranous colitis and Staphylococcal enterocolitis as well as kits and related products thereof.

Claims

1. A non-sterile stable liquid formulation formulated for oral administration, consisting of:

(a) 0.1-0.4% w/v anhydrous citric acid,

(b) water,

(c) 0.1-0.3% w/v sucralose,

(d) 0.01-0.1% w/v of a flavoring agent,

(e) 0.08-0.2% w/v sodium benzoate,

(f) 0.0001-0.0003% w/v of a dye, and

(g) vancomycin hydrochloride,

wherein the non-sterile stable liquid formulation is homogenous and stable for at least 30 days at ambient and refrigerated temperature conditions and has a pH of 2.5-4.5, and wherein the concentration of vancomycin in the solution is 25-50 mg/ml.

2. The liquid formulation of claim 1, wherein the non-sterile stable liquid formulation is stable for up to 3 months at accelerated conditions.

3. The liquid formulation of claim 1, wherein the non-sterile stable liquid formulation is stable for up to 24 months at ambient conditions.

4. The liquid formulation of claim 1, wherein the non-sterile stable liquid formulation has 0.12% w/v anhydrous citric acid.

5. The liquid formulation of claim 1, wherein the no-sterile stable liquid formulation has 0.2% w/v sucralose.

6. The liquid formulation of claim 1, wherein the flavoring agent is 0.05% w/v artificial grape flavor.

7. The liquid formulation of claim 1, wherein the non-sterile stable liquid formulation has 0.1% w/v sodium benzoate.

8. The liquid formulation of claim 1, wherein the dye consists of 0.0002% w/v D&

C Yellow No. 10 and 0.000038% w/v FD&

C Red No. 40.

9. The liquid formulation of claim 1, wherein the non-sterile stable liquid formulation is formulated for use in the treatment of C. difficile pseudomembranous colitis and Staphylococcal enterocolitis.

10. The liquid formulation of claim 1, wherein the non-sterile stable liquid formulation is formulated to inhibit the growth of bacteria, mold and yeast for at least 30 days at ambient and refrigerated temperature conditions.

11. The liquid formulation of claim 1, wherein the non-sterile stable liquid formulation is formulated to inhibit the growth of mold and yeast for greater than 30 days at room temperature conditions.

12. The liquid formulation of claim 1, wherein the anhydrous citric acid in the formulation is 0.12% w/v, the sucralose in the formulation is 0.2% w/v, the flavoring agent in the formulation is 0.05% w/v, the sodium benzoate in the formulation is 0.1% w/v, and the dye in the formulation is 0.0002% w/v.

13. The liquid formulation of claim 12, wherein the dye is 0.0002% w/v D&

C Yellow No. 10 and 0.000038% w/v FD&

C Red No. 40.

14. The liquid formulation of claim 12, wherein the non-sterile stable liquid formulation is formulated for use in the treatment of C. difficile pseudomembranous colitis and Staphylococcal enterocolitis.

15. The liquid formulation of claim 12, wherein the non-sterile stable liquid formulation is formulated to inhibit the growth of bacteria, mold and yeast for at least 30 days at ambient and refrigerated temperature conditions.

16. The liquid formulation of claim 12, wherein the non-sterile stable liquid formulation is formulated to inhibit the growth of mold and yeast for greater than 30 days at room temperature conditions.

17. The liquid formulation of claim 12, wherein the non-sterile stable liquid formulation is stable for up to 3 months at accelerated conditions.

18. The liquid formulation of claim 12, wherein the non-sterile stable liquid formulation is stable for up to 24 months at ambient conditions.