Ceftolozane antibiotic compositions

Patent metadata

Field	Value
Publication number	US-2020009251-A1
Application number	US-201916574825-A
Country	US
Kind code	A1
Filing date	Sep 18, 2019
Priority date	Mar 15, 2013
Publication date	Jan 9, 2020
Grant date	—

Abstract

This disclosure provides pharmaceutical compositions comprising ceftolozane, pharmaceutical compositions comprising ceftolozane and tazobactam, methods of preparing those compositions, and related methods and uses of these compositions.

First claim

1 - 26 . (canceled)

27 . A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need therof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% of a compound of formula (III)

relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.

28 . The method of claim 27 , wherein the infection is a hospital acquired bacterial pneumonia infection.

29 . The method of claim 27 , wherein the infection is a ventilator-associated bacterial pneumonia infection.

30 . The method of claim 27 , wherein the composition contains less than 0.1% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.

31 . The method of claim 27 , wherein the composition contains less than 0.03% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.

32 . The method of claim 27 , wherein the composition the amount of ceftolozane active is 2,000 mg and the amount of tazobactam active is 1,000 mg.

33 . The method of claim 27 , wherein the composition is provided in a unit dosage form.

34 . The method of claim 32 , wherein the composition is provided in a unit dosage form.

35 . The method of claim 27 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by parenteral administration.

36 . The method of claim 27 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.

37 . The method of claim 28 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.

38 . The method of claim 29 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.

39 . The method of claim 32 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.

40 . A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need therof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% of the compound of formula (III)

relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, and less than 1.5% of a compound of formula (IV)

relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 3 months at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.

41 . The method of claim 40 , wherein the infection is a hospital acquired bacterial pneumonia infection.

42 . The method of claim 40 , wherein the infection is a ventilator-associated bacterial pneumonia infection.

43 . The method of claim 40 , wherein the composition contains less than 0.05% of the compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 3 months at a temperature of 25° C. and at a relative humidity of 60%.

44 . The method of claim 40 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.

45 . A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need therof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% relative to ceftolozane sulfate of the compound having a mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%, wherein the ceftolozane sulfate and tazobactam sodium provide ceftolozane active and tazobactam active in a ratio of 2:1 by weight.

46 . The method of claim 45 , wherein the infection is a hospital acquired bacterial pneumonia infection.

47 . The method of claim 45 , wherein the infection is a ventilator-associated bacterial pneumonia infection.

48 . The method of claim 45 , wherein the composition contains less than 0.1% relative to ceftolozane sulfate of the compound with the mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.

49 . The method of claim 45 , wherein the composition contains less than 0.03% relative to ceftolozane sulfate of the compound with the mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored as a solid for 1 month at a temperature of 25° C. and at a relative humidity of 60%.

50 . The method of claim 45 , wherein the composition the amount of ceftolozane active is 2,000 mg and the amount of tazobactam active is 1,000 mg.

51 . The method of claim 45 , wherein the composition is provided in a unit dosage form.

52 . The method of claim 50 , wherein the composition is provided in a unit dosage form.

53 . The method of claim 45 , wherein the pharmaceutical composition is dissolved in a pharmaceutically acceptable carrier and administered by intravenous infusion.

54 . A method for treating an infection which is a nosocomial pneumonia infection in a human patient in need therof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium, said composition comprising less than 0.15% relative to ceftolozane sulfate of a compound having a mass spectra depicted in FIG. 14 , as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, and less

Assignees

• Merck Sharp & Dohme

Inventors

• Terracciano Joseph
• Damour Nicole Miller
• Jiang Chun
• Fogliato Giovanni
• Donadelli Giuseppe Alessandron
• Resemini Dario

Classifications

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title

• A61K31/546

  containing further heterocyclic rings, e.g. cephalothin · CPC title

• A61K47/02 Primary

  Inorganic compounds · CPC title

• A61K9/19

  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 title