Composition and method for vancomycin oral liquid

• US 10,959,948 B2
• Filed: 07/28/2020
• Issued: 03/30/2021
• Est. Priority Date: 03/14/2014
• Status: Active Grant

• Current Assignee: Azurity Pharmaceuticals, Inc.
• Original Assignee: Azurity Pharmaceuticals, Inc.
• Inventors: Muni, Indu, Mione, Peter, Gandhi, Anisa, LeChiara, Cristina
• Primary Examiner(s): Alawadi, Sarah
• Application Number:
  US16/941,400
• Publication Number:
  US 20200360283A1
• Time in Patent Office: 245 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) a buffering agent, wherein the buffering agent is selected from the group consisting of citric acid, sodium citrate, sodium tartarate, sodium acetate, sodium carbonate, sodium polyphosphate, potassium polyphosphate, sodium pyrophosphate, potassium pyrophosphate, disodium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, sodium acetate, potassium metaphosphate, magnesium oxide, magnesium carbonate, magnesium silicate, calcium acetate, calcium glycerophosphate, calcium chloride, calcium hydroxide, calcium lactate, calcium carbonate, calcium bicarbonate, and calcium salts,

(b) water,

(c) a sweetener,

(d) sodium benzoate,

(e) vancomycin hydrochloride, and

(f) flavoring agent,

wherein the non-sterile stable liquid formulation is homogenous and stable for at least 1 week at ambient and refrigerated temperature and has a pH of 2.5-4.5.

2. The liquid formulation of claim 1, wherein the sodium benzoate is 0.02-0.08% w/v.

3. The liquid formulation of claim 1, wherein the buffer is citric acid 0.12% w/v.

4. The liquid formulation of claim 1, wherein the sweetener is 0.1-0.3% w/v.

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

(a) a buffering agent, wherein the buffering agent is selected from the group consisting of citric acid, sodium citrate, sodium tartarate, sodium acetate, sodium carbonate, sodium polyphosphate, potassium polyphosphate, sodium pyrophosphate, potassium pyrophosphate, disodium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, sodium acetate, potassium metaphosphate, magnesium oxide, magnesium carbonate, magnesium silicate, calcium acetate, calcium glycerophosphate, calcium chloride, calcium hydroxide, calcium lactate, calcium carbonate, calcium bicarbonate, and calcium salts,

(b) water,

(c) a sweetener,

(d) a preservative, wherein the preservative is selected from the group consisting of sodium benzoate, parabens, benzoic acid, potassium sorbate, benzyl alcohol or salts thereof,

(e) vancomycin hydrochloride, and

(f) flavoring agent,

wherein the non-sterile stable liquid formulation is homogenous and stable for at least 1 week at ambient and refrigerated temperature and has a pH of 2.5-4.5.

6. The liquid formulation of claim 5, wherein the buffer is citric acid 0.12% w/v.

7. A method of treating Clostridium difficile pseudomembranous colitis or Staphylococcal enterocolitis in a subject comprising administering a vancomycin oral liquid composition to the subject in a therapeutically effective amount, wherein the vancomycin oral liquid composition consists of:

(a) a buffering agent, wherein the buffering agent is selected from the group consisting of citric acid, sodium citrate, sodium tartarate, sodium acetate, sodium carbonate, sodium polyphosphate, potassium polyphosphate, sodium pyrophosphate, potassium pyrophosphate, disodium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, sodium acetate, potassium metaphosphate, magnesium oxide, magnesium carbonate, magnesium silicate, calcium acetate, calcium glycerophosphate, calcium chloride, calcium hydroxide, calcium lactate, calcium carbonate, calcium bicarbonate, and calcium salts,

(b) water,

(c) a sweetener,

(d) a preservative, wherein the preservative is selected from the group consisting of sodium benzoate, parabens, benzoic acid, potassium sorbate, benzyl alcohol, or salts thereof,

(e) vancomycin hydrochloride, and

(f) flavoring agent,

wherein the vancomycin oral liquid composition is homogenous and stable for at least 1 week at ambient and refrigerated temperature and has a pH of 2.5-4.5.

8. The method of claim 7, wherein the buffering agent is citric acid.

9. The method of claim 7, wherein the sweetener is 0.1-0.3% w/v.

10. The method of claim 7, wherein the flavoring agent is a berry flavor.

11. The method of claim 7, wherein the preservative is sodium benzoate.