Lipopeptide compositions and related methods

• US 9,138,456 B2
• Filed: 12/04/2013
• Issued: 09/22/2015
• Est. Priority Date: 11/23/2009
• Status: Active Grant

• Current Assignee: Cubist Pharmaceuticals, LLC (Merck & Co., Inc.)
• Original Assignee: Cubist Pharmaceuticals, LLC (Merck & Co., Inc.)
• Inventors: O'Connor, Sandra, Sun, Sophie, Naik, Gaauri
• Primary Examiner(s): Ha, Julie
• Assistant Examiner(s): KOMATSU, LI N
• Application Number:
  US14/096,346
• Publication Number:
  US 20140364380A1
• Time in Patent Office: 657 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• 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 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• 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 9/08 Solutions composition of solutions 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: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 11/02 cyclic, e.g. valinomycins ; Derivatives thereof

Abstract

The present disclosure provides novel powder daptomycin formulations which have improved chemical stability and faster reconstitution times when in the solid state. Some examples of the compositions comprise daptomycin and sucrose.

Claims

1. A solid pharmaceutical daptomycin composition, wherein said composition is prepared by lyophilizing an aqueous daptomycin solution comprising daptomycin and sucrose.

2. The solid pharmaceutical daptomycin composition of claim 1, wherein the molar ratio of daptomycin to sucrose is about 1:

1.12 to about 1;

8.98.

3. The solid pharmaceutical daptomycin composition of claim 1, wherein the aqueous daptomycin solution further comprises a buffering agent.

4. The solid pharmaceutical daptomycin composition of claim 3, wherein the buffering agent is selected from the group consisting of phosphate, citrate, maleate, carbonate, or a combination thereof.

5. The solid pharmaceutical daptomycin composition of claim 3, wherein the buffering agent is selected from the group consisting of sodium phosphate dibasic, sodium citrate, sodium bicarbonate, histidine monohydrochloride, tris(hydroxymethyl)aminomethane, maleate, or a combination thereof.

6. The solid pharmaceutical daptomycin composition of claim 3, wherein the buffering agent is sodium phosphate dibasic.

7. The solid pharmaceutical daptomycin composition of claim 1, wherein the aqueous daptomycin solution has a pH of about 4.5 to about 8.0.

8. The solid pharmaceutical daptomycin composition of claim 7, wherein the aqueous daptomycin solution has a pH of about 6.5 to about 7.5.

9. The solid pharmaceutical daptomycin composition of claim 8, wherein the aqueous daptomycin solution has a pH of about 7.0.

10. A pharmaceutical product comprising the solid pharmaceutical daptomycin composition of claim 1 and a pharmaceutically acceptable diluent.

11. The pharmaceutical product according to claim 10, wherein the pharmaceutically acceptable diluent is selected from sterile water for injection, sterile sodium chloride for injection, or bacteriostatic water for injection.

12. A solid pharmaceutical daptomycin composition, wherein the solid pharmaceutical daptomycin composition is prepared by a process comprising:

a. forming an aqueous solution comprising daptomycin, wherein the aqueous solution has a pH of about 4.5 to about 5.0;

b. adding a buffering agent to the aqueous solution of daptomycin;

c. dissolving sucrose in the aqueous solution of daptomycin to form a buffered daptomycin sucrose formulation;

d. adjusting the pH of the buffered daptomycin sucrose formulation to about 6.5 to about 7.5; and

e. converting the buffered daptomycin sugar formulation to the solid pharmaceutical daptomycin composition.

13. The solid pharmaceutical daptomycin composition of claim 12, wherein the buffering agent is selected from the group consisting of phosphate, citrate, maleate, carbonate, or a combination thereof.

14. The solid pharmaceutical daptomycin composition of claim 12, wherein the buffering agent is selected from the group consisting of sodium phosphate dibasic, sodium citrate, sodium bicarbonate, histidine monohydrochloride, tris(hydroxymethyl)aminomethane, maleate, or a combination thereof.

15. A solid pharmaceutical daptomycin composition, wherein the solid pharmaceutical daptomycin composition is prepared by a process comprising:

a. dissolving sucrose in an aqueous solution comprising daptomycin to form a daptomycin sucrose formulation;

b. adjusting the pH of the daptomycin sucrose formulation to about 6.5 to about 7.5; and

c. converting the daptomycin sugar formulation to the solid pharmaceutical daptomycin composition.