US20140274992A1 - Ceftolozane pharmaceutical compositions - Google Patents

Ceftolozane pharmaceutical compositions Download PDF

Info

Publication number
US20140274992A1
US20140274992A1 US14/213,997 US201414213997A US2014274992A1 US 20140274992 A1 US20140274992 A1 US 20140274992A1 US 201414213997 A US201414213997 A US 201414213997A US 2014274992 A1 US2014274992 A1 US 2014274992A1
Authority
US
United States
Prior art keywords
ceftolozane
pharmaceutical composition
arginine
active
sodium chloride
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US14/213,997
Other languages
English (en)
Inventor
Nicole Miller Damour
Jacqueline Marie Walsh
Joseph Terracciano
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cubist Pharmaceuticals LLC
Merck Sharp and Dohme LLC
Original Assignee
Calixa Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=50280243&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20140274992(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Calixa Therapeutics Inc filed Critical Calixa Therapeutics Inc
Priority to US14/213,997 priority Critical patent/US20140274992A1/en
Assigned to CUBIST PHARMACEUTICALS, INC. reassignment CUBIST PHARMACEUTICALS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MILLER DAMOUR, Nicole, TERRACCIANO, JOSEPH, WALSH, JACQUELINE MARIE
Publication of US20140274992A1 publication Critical patent/US20140274992A1/en
Assigned to CALIXA THERAPEUTICS, INC. reassignment CALIXA THERAPEUTICS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CUBIST PHARMACEUTICALS, INC.
Assigned to MERCK SHARP & DOHME CORP. reassignment MERCK SHARP & DOHME CORP. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CALIXA THERAPEUTICS, INC.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A61K31/431—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This disclosure relates to pharmaceutical compositions comprising ceftolozane.
  • Ceftolozane is a cephalosporin antibacterial agent.
  • the antibacterial activity of ceftolozane is believed to result from its interaction with penicillin binding proteins (PBPs) to inhibit the biosynthesis of the bacterial cell wall which acts to stop bacterial replication.
  • Ceftolozane is commonly combined (e.g., mixed) with a ⁇ -lactamase inhibitor (“BLI”), such as tazobactam.
  • BLI ⁇ -lactamase inhibitor
  • Tazobactam is a BLI against Class A and some Class C ⁇ -lactamases, with well-established in vitro and in vivo efficacy in combination with active ⁇ -lactam antibiotics.
  • Ceftolozane is commonly administered intravenously as a pharmaceutically acceptable salt, most commonly as ceftolozane sulfate (I):
  • Intravenous administration imposes a number of stringent requirements on a pharmaceutical composition.
  • the drug is typically provided as a lyophilized product that is reconstituted immediately prior to use.
  • patients receiving intravenous medication are at risk for developing phlebitis, which is an inflammation of the veins.
  • the reconstituted pharmaceutical composition should have a pH above 5.9 and preferably at least 6.3, and the osmolarity should be less than 600 mOsm/L (see for example, Stranz and Kastango, International Journal of Pharmaceutical Compounding 6:216 2002).
  • Achieving a suitable pharmaceutical composition is further complicated by the fact that decomposition products are formed from ceftolozane during lyophilization and thereafter during storage (see Examples 5-7).
  • Achieving a suitable pharmaceutical composition is further complicated by the fact that alkalizing agents used bring the pH of the reconstituted pharmaceutical composition into the correct pH range, also cause decomposition products during lyophilization and storage (see Examples 3 and 4).
  • ceftolozane sulfate pharmaceutical composition with greater stability that can be reconstituted in solutions having a pH and osmolarity suitable for intravenous administration.
  • Ceftolozane compositions can be stabilized by combination with a stabilizing-effective amount of an alkalizing agent selected from the group consisting of: sodium hydroxide, L-arginine and sodium bicarbonate.
  • the ceftolozane compositions can be obtained by lyophilizing a solution comprising a stabilizing-effective amount of the alkalizing agent (e.g., to provide a pH of about 5-7) prior to lyophilization.
  • the ceftolozane in the ceftolozane compositions can be ceftolozane sulfate.
  • ceftolzoane related substances e.g., decomposition products from ceftolozane during lyophilization and subsequent storage
  • L-arginine is used as an alkalizing agent
  • One embodiment of the invention is a pharmaceutical formulation for parenteral administration, comprising ceftolozane and between 500-700 mg of L-arginine per 1,000 mg of ceftolozane active reconstituted in 10 mL per 1000 mg ceftolozane active of a first liquid medium suitable for parenteral administration.
  • the pharmaceutical formulation is typically diluted 10:1 v/v with a second liquid medium.
  • the first and second liquid mediums are independently selected from sterile water, 0.9% Sodium Chloride Injection USP and 5% Dextrose Injection USP.
  • the second medium is commonly 0.9% Sodium Chloride Injection USP.
  • Another embodiment of the invention is a method of treating a bacterial infection in a mammal.
  • the method comprises intravenously administering to said mammal a therapeutically effective amount of the disclosed pharmaceutical formulation.
  • the disclosed pharmaceutical formulation is commonly administered over one hour three times daily.
  • FIG. 1 is a diagram of a lyophilization process.
  • FIG. 2 is a table (Table 1a) showing the effect of various alkalizing agents on the recovery of ceftolozane after lyophilization and storage.
  • FIGS. 3 is a table (Table 2) showing the effect of sodium bicarbonate and L-Arginine on total impurities lyophilization of pH profile.
  • FIG. 4 is a table (Table 3) showing the composition of various ceftolozane pharmaceutical compositions in which the sodium chloride concentration is varied.
  • FIG. 5 is a table (Table 4) showing data obtained by HPLC for the RT 63 impurity as detected in certain pharmaceutical compositions containing ceftolozane.
  • FIG. 6 is a table (Table 5) showing the composition of various additional ceftolozane pharmaceutical compositions.
  • FIG. 7 is a table (Table 6) showing the total purity of ceftolozane in the pharmaceutical compositions of FIG. 6 , as measured by HPLC peak area.
  • FIG. 8 is a graph showing the total purity of certain pharmaceutical compositions disclosed in FIG. 6 , as measured by HPLC peak area.
  • FIG. 9A is a table (Table 7) showing the amount of material from characteristic peak 1 in the pharmaceutical compositions of FIG. 6 , as measured by HPLC peak area according to the analytical method as described in Example 2.
  • FIG. 9B is a graph showing the amount of material from characteristic peak 1 in the pharmaceutical compositions of FIG. 6 , as measured by HPLC peak area according to the analytical method as described in Example 2.
  • FIG. 10A is a table (Table 8) showing the amount of material from characteristic peak 3 in the pharmaceutical compositions of FIG. 6 , as measured by HPLC peak area according to the analytical method as described in Example 2.
  • FIG. 10B is a graph showing the amount of material from characteristic peak 3 in the pharmaceutical compositions of FIG. 6 , as measured by HPLC peak area according to the analytical method as described in Example 2.
  • FIG. 11A is a table (Table 9) showing the amount of material from characteristic peak 7 in the pharmaceutical compositions of FIG. 6 , as measured by HPLC peak area according to the analytical method as described in Example 2.
  • FIG. 11B is a graph showing the amount of material from characteristic peak 7 in the pharmaceutical compositions of FIG. 6 , as measured by HPLC peak area according to the analytical method as described in Example 2.
  • FIG. 12 is a table (Table 10) showing the composition of various ceftolozane pharmaceutical compositions in which the sodium chloride concentration is varied.
  • FIG. 13 is a table (Table 11) showing the purity of Ceftolozane in CXA-201 Compositions with varying amounts of sodium from sodium chloride at time zero, 1 day, 3 days and 7 days at 60° C.
  • FIG. 14 is a table (Table 12) showing the HPLC area of Impurity of Peak 1 in CXA-201 Compositions with varying amounts of sodium from sodium chloride at time zero, 1 day, 3 days and 7 days at 60° C.
  • FIG. 15 is a table (Table 13) showing the HPLC area of the Impurity at RRT 0.43 and Impurity Peak 3 in CXA-201 Compositions with varying amounts of sodium from sodium chloride at time zero, 1 day, 3 days and 7 days at 60° C.
  • FIG. 16 is a table (Table 14) showing the HPLC area of Impurity of Peak 7 in CXA-201 Compositions with varying amounts of sodium from sodium chloride at time zero, 1 day, 3 days and 7 days at 60° C.
  • lyophilizing ceftolozane from solutions containing certain alkalizing agents such as L-arginine, sodium hydroxide and sodium bicarbonate results in lyophilized compositions having improved ceftolozane chemical stability over the course of time and/or in the presence of heat (e.g., see Examples 3 and 4).
  • L-arginine can be used as the alkalizing agent to prepare pharmaceutical formulations of ceftolozane for parenteral administration.
  • Lyophilizing a solution containing ceftolozane and an amount of L-arginine effective to adjust the pH of the solution within a desired range can result in lyophilized compositions with improved ceftolozane chemical stability, as disclosed herein (e.g., about 600 mg L-arginine per 1,000 mg of ceftolozane active in the solution).
  • ceftolozane chemical stability e.g., about 600 mg L-arginine per 1,000 mg of ceftolozane active in the solution.
  • L-arginine may stabilize the ceftolozane molecule during the lyophilization process, resulting in greater ceftolozane stability in the resulting lyophilized powder composition.
  • the lyophilized stabilized ceftolozane compositions can be reconstituted to form injectable formulations having pH values within acceptable limits for intravenous administration (e.g., 6.0 and 7.0).
  • ceftolozane can be stabilized by including a stabilizing-effective amount of L-arginine in a solution and then lyophilizing the composition.
  • the stabilizing-effective amount of L-arginine can be an amount effective to bring the pH of the solution to 5-7, and preferably 6-7.
  • the stabilizing-effective amount of L-arginine 500-700 mg of L-arginine per 1000 mg ceftolozane active are used, more specifically between 575 and 625 mg and preferably about 600 mg of L-arginine per 1,000 mg of ceftolozane active in the solution.
  • the addition of sodium chloride, preferably between 450-500 mg per 1000 mg ceftolozane active, to the solution prior to lyophilization can further stabilize ceftolozane in the resulting lyophilized product.
  • the resulting lyophilized composition can be readily reconstituted in sterile water, 0.9% Sodium Chloride Injection USP and/or 5% Dextrose Injection USP to result in a solution having a pH (e.g., between 6 and 7) and osmolarity (e.g., about 400-600 mOsm/mL, preferably about 400 mOsm/L) that is suitable for intravenous administration.
  • compositions comprise stabilized ceftolozane sulfate and about 500-700 mg of L-arginine (preferably, about 600 mg of L-arginine) per 1000 mg of ceftolozane active.
  • pharmaceutical compositions can comprise about 125-500 mg (preferably between 450-500 mg) sodium chloride per 1000 mg of ceftolozane active.
  • compositions comprising stabilizing effective amounts of L-arginine and/or sodium chloride provided improved ceftolozane stability over the course of time and/or in the presence of heat, and a reduction in the formation (or rate of formation) of ceftolozane-related impurities than comparative pharmaceutical compositions.
  • Ceftolozane was less stable in compositions having less than a stabilizing effective amount of sodium chloride or in the presence of certain comparative alkalizing agents (e.g., see Examples).
  • stabilized ceftolozane compositions include 450-500 mg sodium chloride per 1000 mg ceftolozane active, and more specifically between 480 and 500 mg.
  • ceftolozane stability can be improved in compositions comprising between about 450-500 mg sodium chloride and between about 500-700 mg L-Arginine per 1000 mg ceftolozane active in the composition, including compositions having between 480 and 500 mg of sodium chloride and 575-625 mg L-Arginine per 1000 mg ceftolozane active.
  • compositions can be solid powders that can be dissolved in a pharmaceutically acceptable carrier and subsequently parenterally administered to a patient.
  • suitable pharmaceutically acceptable carriers for intravenous administration of compositions comprising stabilized ceftolozane sulfate and L-arginine include (without limitation): Sodium Chloride Injection, USP 0.9% and 0.45%, as a sterile, nonpyrogenic, isotonic solution; water for injection; and/or 0.5% Dextrose Injection, USP solution as sterile and nonpyrogenic parenteral solution containing dextrose in water for injection prepared for intravenous administration (each 100 mL of 5% Dextrose Injection, USP, contains dextrose, hydrous 5 g in water for injection).
  • Ceftolozane is the cephalosporin (6R,7R)-3-[(5-amino-4- ⁇ ](2-aminoethyl)carbamoyl]amino]-1-methyl-1H-pyrazol-2-ium-2-yl)methyl]-7-( ⁇ (2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[(1-carboxy-l-methylethoxy)imino]acetyl ⁇ amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, and is also referred to as “CXA-101,” FR264205, or (6R,7R)-3-[5-Amino-4-[3-(2-aminoethyl)ureido]-1-methyl-1H-pyrazol-2-ium-2-ylmethyl]-7-[2-(5-amino-1,2,4-thiadia
  • Ceftolozane includes both ceftolozane free base and salts of ceftolozane, such as ceftolozane sulfate.
  • Ceftolozane sulfate is a pharmaceutically acceptable salt of ceftolozane that can be combined with sodium chloride and other components to obtain an antibiotic composition suitable for administration by injection or infusion.
  • the disclosed pharmaceutical compositions can include a ⁇ -lactamase inhibitor, such as tazobactam (CAS#: 89786-04-9), avibactam (CAS#1192500-31-4), Sulbactam (CAS#68373-14-8) and/or clavulanate (CAS#58001-44-8).
  • the beta lactamase inhibitor can be included in a crystalline or amorpous form, such as a lyophilized tazobactam or crystalline tazobactam (e.g., U.S. Pat. Nos. 8,476,425 and 5,763,603) to obtain the pharmaceutical composition.
  • Tazobactam is the most commonly used BLI in the disclosed pharmaceutical formulations. It is typically used as the free acid, sodium salt or arginine salt. Tazobactam free acid has the following structure:
  • the disclosed pharmaceutical formulations preferably have a 2:1 w/w ratio of ceftolozane active to tazobactam active.
  • a unit dosage form of the disclosed pharmaceutical formulation typically as 1000 mg of ceftolozane active, preferably from ceftolozane sulfate and 500 mg of tazobactam active, preferably from tazobactam free acid, sodium salt or arginine salt.
  • 1,000 mg of ceftolozane as ceftolozane active refers to an amount of ceftolozane sulfate effective to provide 1,000 mg of ceftolozane active.
  • the amount of sodium chloride per gram of ceftolozane activity in a pharmaceutical composition containing ceftolozane sulfate and sodium chloride can be calculated using the relevant molecular weights of ceftolozane, ceftolozane sulfate, sodium chloride and sodium.
  • 500 mg of tazobactam as tazobactam active refers to an amount of tazobatam sodium or tazbactam arginine effective to provide 500 mg of tazobactam active.
  • Citric acid is a common additive to the disclosed pharmaceutical formulations. 20-22 mg of citric acid per 1000 mg ceftolozane active can be added to a stabilized ceftolozane, preferably 21 mg of citric acid per 1000 mg ceftolozane active.
  • compositions comprising ceftolozane and sodium chloride can be obtained by lyophilization.
  • lyophilization is a process of freeze-drying in which water is sublimed from a frozen solution of one or more solutes. Specific methods of lyophilization are described in Remington's Pharmaceutical Sciences, Chapter 84, page 1565, Eighteenth Edition, A. R. Gennaro, (Mack Publishing Co., Easton, Pa., 1990).
  • a pharmaceutical composition comprising ceftolozane can be prepared by adding i) L-arginine; or ii) L-arginine and sodium chloride in a fixed ratio to ceftolozane in an aqueous solution prior to lyophilization.
  • the method can comprise the steps of: (1) adding i) L-arginine or ii) L-arginine and sodium chloride and optionally citric acid to ceftolozane followed by lyophilizing ceftolozane; and (2) combining the separately lyophilized ceftolozane with other components to obtain said pharmaceutical composition.
  • “Other components” include a BLI such tazobactam, preferably a lyophilized tazobactam.
  • the method comprises adding 500-700 L-arginine and 450-500 mg sodium chloride (and optionally 20-22 mg citric acid) per 1000 mg of ceftolozane (such as the ceftolozane sulfate) in an aqueous solution, then lyophilizing the solution to obtain a lyophilized material comprising i) L-arginine, or ii) L-arginine and sodium chloride (and optionally citric acid) and ceftolozane (such as ceftolozane sulfate) in a ratio effective to stabilize the ceftolozane.
  • ceftolozane such as the ceftolozane sulfate
  • the lyophilised product can then be combined with tazobactam, preferably a lyophilized tazobactam.
  • This lyophilized product can be combined or blended with tazobactam, typically a lyophilized tazobactam.
  • tazobactam typically a lyophilized tazobactam.
  • 550-650 mg L-arginine, 480-500 mg sodium chloride and optionally 20-22 mg citric acid per 1000 mg ceftolozane active are used.
  • the combined products are then transferred to a vial in unit dosage form, which contains 500 mg of tazobactam active and 1000 mg ceftolozane active.
  • a pharmaceutical formulation for parenteral administration can include: ceftolozane and between 500-700 mg of L-arginine per 1,000 mg of ceftolozane active reconstituted in 10 mL of a first liquid medium suitable for parenteral administration per 1000 mg ceftolozane active.
  • the pharmaceutical formulation can further comprise between 450-500 mg sodium chloride per 1,000 mg of ceftolozane active, and/or 500 mg of tazobactam active per 1,000 mg ceftolozane.
  • the pharmaceutical formulation can be obtained wherein the ceftolozane, sodium chloride and L-arginine are co-lyophilsed and the tazobactam is separately lyophilized and combined with the ceftolozane, L-arginine and sodium chloride.
  • the pharmaceutical formulation of can include between 575 and 625 mg of L-arginine per 1,000 mg of ceftolozane.
  • the ceftolozane in the pharmaceutical composition is preferably ceftolozane sulfate and the tazobactam is preferably tazobactam sodium.
  • the pharmaceutical formulation can further comprise between 20-22 mg of citric acid per 1000 mg ceftolozane.
  • the first liquid medium can be selected from sterile water, 0.9% Sodium Chloride Injection USP and/or 5% Dextrose Injection USP.
  • the pharmaceutical formulation is diluted 10:1 v/v with a second liquid medium selected from sterile water, 0.9% Sodium Chloride Injection USP and 5% Dextrose Injection USP.
  • the pH of the pharmaceutical formulation can be between 5-7, preferably 6-7; and the osmolarity of the pharmaceutical formulation is between 450-550 mOsm/kg.
  • the pharmaceutical formulation can include 1000 mg ceftolozane active.
  • the pharmaceutical composition can be provided in a unit dosage form comprising the pharmaceutical composition in dry form stored in a container (e.g., bag, vial, or the like) until use.
  • a container e.g., bag, vial, or the like
  • the combined unit dose is reconstituted in 10 mL of a diluent (e.g., sterile water for injection, 0.9% Sodium Chloride Injection USP and/or 5% Dextrose Injection USP).
  • a diluent e.g., sterile water for injection, 0.9% Sodium Chloride Injection USP and/or 5% Dextrose Injection USP.
  • the reconstituted mixture is then diluted with 100 mL sterile water for injection, 0.9% Sodium Chloride Injection USP and/or 5% Dextrose Injection USP, after which it is ready for administration, such as by intravenous infusion.
  • a pharmaceutical composition can comprise ceftolozane obtained by a process comprising lyophilizing a solution including ceftolozane and an alkalizing agent selected from the group consisting of: sodium hydroxide, L-arginine and sodium bicarbonate in an amount effective to provide a pH of 5-7, preferably 6-7, to the solution prior to lyophilization to obtain a lyophilized ceftolozane pharmaceutical composition.
  • the lyophilized ceftolozane pharmaceutical composition can comprise at least about 93% of an initial amount of ceftolozane prior to lyophilization after 3 days at 70 degrees C.
  • the lyophilized ceftolozane pharmaceutical composition can contain 1,000 mg of ceftolozane active.
  • the alkalizing agent can be selected from the group consisting of: L-arginine and sodium bicarbonate.
  • the lyophilized ceftolozane can be obtained by a process comprising lyophilizing a solution comprising ceftolozane sulfate, 125 mg-500 mg sodium chloride and the alkalizing agent.
  • the lyophilized ceftolozane can be obtained by a process comprising lyophilizing a composition comprising about 1,000 mg of ceftolozane active per unit dose form in the pharmaceutical composition.
  • the lyophilized ceftolozane can be obtained by a process comprising lyophilizing a composition comprising about 500-700 mg of L-arginine per 1,000 mg of ceftolozane active.
  • the alkalizing agent can be L-arginine.
  • the lyophilized ceftolozane can be obtained by a process comprising lyophilizing a solution comprising ceftolozane sulfate, citric acid, about 600 mg L-arginine per 1,000 mg of ceftolozane active, and about 125-500 mg of sodium chloride per 1,000 mg of ceftolozane active.
  • a pharmaceutical composition can comprise ceftolozane and an alkalizing agent selected from the group consisting of: L-arginine and sodium bicarbonate, wherein the lyophilized ceftolozane pharmaceutical composition comprises at least about 93% of an initial amount of ceftolozane prior to lyophilization after 3 days at 70 degrees C. after lyophilization, as measured by high performance liquid chromatography using a Develosil column ODS-UG-5; 5 micrometers; 250 ⁇ 4.6 mm, a mobile phase of sodium perchlorate buffer solution (pH 2.5)/CH 3 CN 90:10 (v/v) at a 1.0 mL/min flow rate and oven temperature of 45° C.
  • the alkalizing agent can be L-arginine.
  • the lyophilized ceftolozane pharmaceutical composition can comprise ceftolozane sulfate, citric acid, L-arginine, and about 125-500 mg of sodium chloride per 1,000 mg of ceftolozane active.
  • the pharmaceutical composition can further comprise sodium chloride and citric acid.
  • the lyophilized ceftolozane composition can be obtained by a process comprising lyophilizing a solution consisting of water, ceftolozane sulfate, L-arginine, sodium chloride, and citric acid.
  • the pharmaceutical composition can be characterized by the following: the ceftolozane is present as ceftolozane sulfate; the alkalizing agent is L-arginine; and the lyophilized ceftolozane composition is obtained by a process comprising lyophilizing a solution comprising water, ceftolozane sulfate, L-arginine, sodium chloride, and citric acid; and the pharmaceutical composition further comprises tazobactam blended with the lyophilized ceftolozane.
  • the lyophilized ceftolozane composition can be obtained by a process comprising lyophilizing a solution comprising: 125-500 mg sodium chloride per 1,000 mg ceftolozane active; an amount of L-arginine to provide a pH of about 5-7, preferably 6-7, prior to lyophilization; about 21 mg citric acid per 1,000 mg ceftolozane active; about 487 mg sodium chloride per 1,000 mg ceftolozane active.
  • the pharmaceutical composition can comprise tazobactam sodium in an amount providing about 500 mg tazobactam active per 1,000 mg ceftolozane active.
  • a unit dosage form can include a pharmaceutical composition formulated for parenteral administration for the treatment of complicated intra-abdominal infections or complicated urinary tract infections.
  • This pharmaceutical composition can comprise 1,000 mg of ceftolozane active, about 600 mg L-arginine alkalizing agent, citric acid and about 487 mg of sodium chloride, wherein the lyophilized ceftolozane pharmaceutical composition comprises at least about 93% of an initial amount of ceftolozane prior to lyophilization after 3 days at 70 degrees C.
  • the unit dosage form can also comprise tazobactam sodium in an amount providing about 500 mg tazobactam active per 1,000 mg ceftolozane active.
  • the unit dosage form pharmaceutical composition can be obtained by: (a) lyophilizing a ceftolozane solution comprising: about 487 mg sodium chloride per 1,000 mg ceftolozane active; an amount of L-arginine to provide a pH of about 5-7, preferably 6-7, in the solution prior to lyophilization; about 21 mg citric acid per 1,000 mg ceftolozane active, to obtain a lyophilized ceftolozane composition; and (b) blending the lyophilized ceftolozane composition with tazobactam sodium in an amount providing about 500 mg of tazobactam acid equivalent per 1,000 mg ceftolozane active in the vial.
  • a method for the treatment of bacterial infections in a mammal comprising administering to said mammal a therapeutically effective amount of a pharmaceutical composition prepared according to the methods described herein.
  • a method for the treatment of bacterial infections in a mammal can comprise administering to said mammal a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane sulfate and sodium chloride.
  • Non-limiting examples of bacterial infections that can be treated by the methods of the invention include infections caused by: aerobic and facultative gram-positive microorganisms (e.g., Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus pneumonia, Streptococcus pyogenes, Viridans group streptococci ), aerobic and facultative gram-negative microorganisms (e.g., Acinetobacter baumanii, Escherichia coli, Haemophilus influenza, Klebsiella pneumonia, Pseudomonas aeruginosa, Citrobacter koseri, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Providencia stuartii
  • bacterial infection is associated with one or more of the following conditions: complicated intra-abdominal infections, complicated urinary tract infections (cUTIs) and pneumonia (e.g., community-acquired, or nosocomial pneumonia).
  • cUTIs complicated intra-abdominal infections
  • pneumonia e.g., community-acquired, or nosocomial pneumonia.
  • Community-acquired pneumonia can include infections caused by piperacillin-resistant, beta-lactamase producing strains of Haemophilus influenza.
  • Nosocomial pneumonia caused by piperacillin-resistant, beta-lactamase producing strains of Staphylococcus aureus and by Acinetobacter baumanii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
  • a method of treating a bacterial infection in a mammal can include intravenously administering to a mammal a therapeutically effective amount of the pharmaceutical formulation disclosed herein (e.g., the pharmaceutical formulation is administered over one hour three times daily).
  • the method of treating can further include reconstituting a unit dosage form of a pharmaceutical composition disclosed herein to obtain a reconstituted composition, combining the reconstituted composition with a pharmaceutically acceptable carrier and intravenously administering the unit dosage form of the pharmaceutical composition over a therapeutically effective period (e.g., 1 hour).
  • treating describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of a pharmaceutical composition of the present invention to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder.
  • the term “treat” can also include treatment of a cell in vitro or an animal model.
  • a “therapeutically effective amount” of a compound of the invention is meant a sufficient amount of the compound to treat the disorder (e.g., bacterial infection).
  • the specific therapeutically effective amount that is required for the treatment of any particular patient or organism will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound or composition employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts (see, for example, Goodman and Gilman's, “The Pharmacological Basis of Therapeutics”, Tenth Edition, A.
  • 450-500 mg sodium chloride per 1000 mg of ceftolozane refers to a ratio of sodium chloride to ceftolozane.
  • 450-500 to 1000 mg sodium chloride per 1000 mg of ceftolozane includes, for example, 225-250 mg sodium chloride per 500 mg of ceftolozane, as well as, for example, 112.5-125 mg sodium chloride per 250 mg ceftolozane.
  • 1,000 mg of ceftolozane as ceftolozane sulfate refers to an amount of ceftolozane sulfate effective to provide 1,000 mg of ceftolozane.
  • the amount of sodium per gram of ceftolozane activity in a pharmaceutical composition containing ceftolozane sulfate and sodium chloride can be calculated using the relevant molecular weights of ceftolozane, ceftolozane sulfate, sodium chloride and sodium.
  • the term “related substances” with respect to HPLC detection refers to all the ceftolozane related process impurities and degradation products other than ceftolozane separated and detected by HPLC according to Example 2.
  • the term “% related substances” refers to the % of the total HPLC peak area obtained by Example 2 attributed to all the ceftolozane related process impurities and degradation products other than ceftolozane.
  • ceftolozane recovery refers to the % of total HPLC peak area obtained and detected by the HPLC method of Example 2 attributed to the amount of ceftolozane.
  • CXA-101 bulk drug product manufacturing process There are four main steps in the manufacture of CXA-101 bulk drug product: dissolution, sterile filtration, bulk lyophilization, and packaging into Sterbags®. These four main steps are composed of a total of 20 minor steps.
  • the CXA-101 bulk drug product manufacturing process is presented below.
  • Solution pH is verified to be in the target range of 6.5 to 7.0.
  • Solution pH is verified to be in the target range of 6.0 to 7.0. If the pH is out of this range adjust with either L-Arginine or citric acid.
  • the solution is passed through the filter (pore size 0.45 ⁇ m) followed by double filters (pore size 0.22 ⁇ m) onto a shelf on the Criofarma lyophilizer.
  • the washing solution is passed from Step 12 through sterile filtration.
  • the washing solution is loaded onto a separate shelf in the lyophilizer (and later discarded).
  • the solution is lyophilized until dry.
  • the product shelf is cooled to 20° C. ⁇ 5° C.
  • the lyophilized bulk drug product powder is milled.
  • the milled powder is sieved.
  • the sieved powder is blended for 30 minutes.
  • a sterile tilter-set which consists of a 0.2 um polyvinylidene fluoride membrane filter (Durapore®, Millipore) and a 0.1 urn polyvinylidene fluoride membrane filter (Durapore®, Millipore) connected in tandem. Confirm the integrity of each filter before and after the filtration. Take approximately 100 mL of the filtrate in order to check bioburden.
  • a sterile filter-set which consists of a 0.2 um polyvinylidene fluoride membrane filter and a 0.1 urn polyvinylidene fluoride membrane filter connected in tandem, and introduce the final filtrate into an aseptic room. Confirm the integrity of each filter before and after the filtration.
  • Adjust the fill weight of the filtered compounded solution to 11.37 g (corresponds to 10 mL of the compounded solution), then start filling operation. Check the filled weight in sufficient frequency and confirm it is in target range (11.37 g ⁇ 1%, 11.26 to 11.43 g). When deviation from the control range (11.37 g ⁇ 2%, 11.14 to 11.59 g) is occurred, re-adjust the filling weight.
  • HPLC measurements are made using a Develosil column ODS-UG-5; 5 micrometers; 250'4.6 mm, a mobile phase of sodium perchlorate buffer solution (pH 2.5)/CH 3 CN 90:10 (v/v) at a 1.0 mL/min flow rate and oven temperature of 45° C. (Example 2).
  • Sodium Perchlorate Buffer Solution was made by dissolving 14.05 g of sodium perchlorate Monohydrate in 1000.0 mL of water followed by adjusting pH to 2.5 with diluted perchloric acid (1 in 20).
  • Sodium Acetate Buffer Solution pH 5.5 (Diluent) was made by dissolving 1.36 g of sodium acetate trihydrate in 1000.0 mL of water followed by adjusting to pH 5.5 with diluted acetic acid (1 in 10).
  • Sample solution dissolve 20.0 mg, exactly weighed, of Sample, in 20.0 mL of water (Prepare just before injection into HPLC system).
  • System Suitability Solution (1%): take 1.0 mL of the Sample Solution (use first sample if more are present) and transfer into a 100.0 mL volumetric flask, dilute with water to volume and mix.
  • a i area of CXA-101 peak in the sample chromatogram
  • ⁇ A i total peak areas of impurities in the sample chromatogram
  • Ceftolozane recovery was consistently at least 90% in the presence of sodium hydroxide, L-arginine, or sodium bicarbonate. Although sodium hydroxide performed well, as a strong base, it could promote base hydrolysis of the active more readily during scale up and be more difficult to dry during lyophilization than other alkalizing agents. Accordingly sodium hydroxide was not considered for further formulation development. Sodium bicarbonate and L-Arginine were further tested, as outlined in Example 4.
  • Table 1a provides examples of certain preferred ceftolozane compositions that provide for a rate of ceftolozane recovery (as measured by HPLC according to Example 2) that are characterized by:
  • Each sample contained 1000 mg of ceftolozane active, 40 mg citric acid monohydrate (equivalent of 36 mg citric acid anhydrous), and the same amount of L-arginine.
  • Stabilizing reagents in four samples are 480 mg sodium chloride, 300 mg of trehalose, 300 mg of sucrose, and 300 mg of PVP, respectively.
  • One sample was a control that contained no stabilizing reagent.
  • the samples were in lyophilized form and stored at 60° C. for 7 days. The purities of the samples were monitored by HPLC on day 0, day 1, day 3 and day 7.
  • the bicarbonate-adjusted sample showed a larger increase in related substances and a less stable pH profile. Accordingly, it was decided to maintain L-arginine as the alkalizing agent in the formulation.
  • ceftolozane in ceftolozane sulfate can be calculated based on the respective molecular molar weights of ceftolozane and ceftolozane sulfate (e.g., 1,147 mg ceftolozane sulfate contains about 1,000 mg of ceftolozane).
  • the Amount of Sodium Chloride can be Selected to Stabilize Ceftolozane in Pharmaceutical Compositions
  • a 7-day stability study of multiple ceftolozane pharmaceutical compositions was carried out at 60% RH in accordance with ICH guidelines. This stability study examined the effect of temperature and humidity on various ceftolozane pharmaceutical compositions bulk drug product stability when stored in the container closure configuration of Sterbag®.
  • CXA-101 Purity increases in Compositions having at Least about 125 mg NaCl/1,000 mg Ceftolozane Active
  • Example 6 A stability study was carried out at 30° C. and 60° C. as described in Example 6. Sodium chloride content in test samples is described in Table 5 ( FIG. 6 ). The samples were formulated with 481, 190, 125, 75, and 50 mg sodium chloride per 1 g of ceftolozane active.
  • FIG. 7 is Table 6 with data for total purity of ceftolozane measured by HPLC during the 7-day stability test using the HPLC method in Example 2, with the data plotted in the graph of FIG. 8 .
  • Example 6 A stability study was carried out at 30° C. and 60° C. as described in Example 6. Sodium chloride content in test samples is described in Table 5 ( FIG. 6 ). The samples were formulated with 481, 190, 125, 75, and 50 mg sodium chloride per 1 g of ceftolozane active.
  • FIGS. 9A , 10 A and 11 A Stability data for amounts of additional substances in the ceftolozane compositions from Table 5 ( FIG. 6 ) as measured by peaks 1, 3 and 7 by HPLC (according to Example 2) are summarized in Tables 7, 8 and 9 ( FIGS. 9A , 10 A and 11 A).
  • the 60° C. data are also plotted in FIGS. 9B , 10 B and 11 B to show trends of peak 1, RRT 0.43+peak 3, and peak 7 with respect to sodium chloride (NaCl), respectively.
  • Example 6 A stability study was carried out at 30° C. and 60° C. as described in Example 6.
  • the sodium chloride content in the CXA-201 compositions is described in Table 10, FIG. 12 .
  • the HPLC data at 30° C. and 60° C. are summarized in Tables 11-14, FIGS. 13-16 .
  • Preferred Antibiotic Composition Comprising Ceftolozane, L-Arginine and Tazobactam
  • Table 15 An example of the unit composition of ceftolozane/tazobactam drug product for injection is presented in Table 15 below.
  • the composition in Table 15 can be reconstituted in water for injection or 0.9% aqueous sodium chloride to form a pharmaceutical formulation for intravenous administration for treatment of infections.
  • the unit dosage form of Table 15 can be obtained by lyophilizing an aqueous solution comprising ceftolozane sulfate, citric acid, sodium chloride and L-arginine to obtain a lyophilized ceftolozane composition.
  • the aqueous solution preferably contains the components of Ceftolozane composition in the Table 15, including enough L-arginate (e.g., about 600 mg per 1,000 mg of ceftolozane active in the solution) to provide a pH of about 6-7 prior to lyophliziation.
  • the lyophilized ceftolozane composition can be combined with tazobactam (e.g., by blending a tazobactam composition comprising tazobactam sodium) in an amount providing a 2:1 weight ratio between the amount of ceftolozane active and the amount of tazobactam free acid equivalent.
  • the excipients in ceftolozane composition were chosen to ensure stability and processability of the ceftolozane drug substance into the drug product.
  • the specific excipients, their quantities and functions are provided in Table 16. All excipients are compendial and typical for sterile pharmaceutical dosage forms, requiring no additional treatment prior to use in the formulation.
  • the excipients are used in levels within the range established in other FDA approved products as described in the Inactive Ingredients Database (IID).

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Dermatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
US14/213,997 2013-03-15 2014-03-14 Ceftolozane pharmaceutical compositions Abandoned US20140274992A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US14/213,997 US20140274992A1 (en) 2013-03-15 2014-03-14 Ceftolozane pharmaceutical compositions

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201361792092P 2013-03-15 2013-03-15
US201361793007P 2013-03-15 2013-03-15
US201361882936P 2013-09-26 2013-09-26
US201361893436P 2013-10-21 2013-10-21
US14/213,997 US20140274992A1 (en) 2013-03-15 2014-03-14 Ceftolozane pharmaceutical compositions

Publications (1)

Publication Number Publication Date
US20140274992A1 true US20140274992A1 (en) 2014-09-18

Family

ID=50280243

Family Applications (7)

Application Number Title Priority Date Filing Date
US14/213,997 Abandoned US20140274992A1 (en) 2013-03-15 2014-03-14 Ceftolozane pharmaceutical compositions
US14/214,324 Abandoned US20140274995A1 (en) 2013-03-15 2014-03-14 Parenteral ceftolozane antibiotic compositions
US14/212,625 Abandoned US20140274989A1 (en) 2013-03-15 2014-03-14 Manufacturing beta-lactam combination products
US14/214,260 Abandoned US20140274994A1 (en) 2013-03-15 2014-03-14 Stabilizing ceftolozane
US14/251,381 Abandoned US20140309205A1 (en) 2013-03-15 2014-04-11 Ceftolozane antibiotic compositions
US14/251,372 Active US9044485B2 (en) 2013-03-15 2014-04-11 Ceftolozane antibiotic compositions
US15/086,479 Abandoned US20160279140A1 (en) 2013-03-15 2016-03-31 Ceftolozane antibiotic compositions

Family Applications After (6)

Application Number Title Priority Date Filing Date
US14/214,324 Abandoned US20140274995A1 (en) 2013-03-15 2014-03-14 Parenteral ceftolozane antibiotic compositions
US14/212,625 Abandoned US20140274989A1 (en) 2013-03-15 2014-03-14 Manufacturing beta-lactam combination products
US14/214,260 Abandoned US20140274994A1 (en) 2013-03-15 2014-03-14 Stabilizing ceftolozane
US14/251,381 Abandoned US20140309205A1 (en) 2013-03-15 2014-04-11 Ceftolozane antibiotic compositions
US14/251,372 Active US9044485B2 (en) 2013-03-15 2014-04-11 Ceftolozane antibiotic compositions
US15/086,479 Abandoned US20160279140A1 (en) 2013-03-15 2016-03-31 Ceftolozane antibiotic compositions

Country Status (17)

Country Link
US (7) US20140274992A1 (es)
EP (3) EP3100732A1 (es)
JP (3) JP6543611B2 (es)
KR (2) KR102329764B1 (es)
CN (2) CN105392485B (es)
AU (1) AU2014227660B2 (es)
BR (1) BR112015023523B8 (es)
CA (1) CA2906151A1 (es)
CL (1) CL2015002755A1 (es)
EA (1) EA029090B1 (es)
IL (1) IL241581B (es)
MX (2) MX2015012833A (es)
NZ (1) NZ700372A (es)
PE (1) PE20160048A1 (es)
TN (1) TN2015000411A1 (es)
UA (1) UA121298C2 (es)
WO (1) WO2014144295A1 (es)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8968753B2 (en) 2013-03-15 2015-03-03 Calixa Therapeutics, Inc. Ceftolozane-tazobactam pharmaceutical compositions
US9044485B2 (en) 2013-03-15 2015-06-02 Calixa Therapeutics, Inc. Ceftolozane antibiotic compositions
US9724353B2 (en) 2011-09-09 2017-08-08 Merck Sharp & Dohme Corp. Methods for treating intrapulmonary infections
US9872906B2 (en) 2013-03-15 2018-01-23 Merck Sharp & Dohme Corp. Ceftolozane antibiotic compositions
US10376496B2 (en) 2013-09-09 2019-08-13 Merck, Sharp & Dohme Corp. Treating infections with ceftolozane/tazobactam in subjects having impaired renal function

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2684150C (en) 2007-05-14 2016-10-04 Research Foundation Of State University Of New York Decenoic acid dispersion inducers in the treatment of biofilms
US8906898B1 (en) * 2013-09-27 2014-12-09 Calixa Therapeutics, Inc. Solid forms of ceftolozane
CN104721190B (zh) * 2015-03-26 2017-01-11 新乡医学院 头孢替唑钠注射液及其制备方法
CA2983256A1 (en) * 2016-03-31 2017-10-05 Wockhardt Limited Antibacterial compositions
CN107835686A (zh) * 2016-03-31 2018-03-23 沃克哈特有限公司 抗菌组合物
US11541105B2 (en) 2018-06-01 2023-01-03 The Research Foundation For The State University Of New York Compositions and methods for disrupting biofilm formation and maintenance
WO2023039947A1 (zh) * 2021-09-18 2023-03-23 湘北威尔曼制药股份有限公司 一种含有头孢哌酮钠和他唑巴坦钠的药物组合物及其应用
WO2023149411A1 (ja) * 2022-02-01 2023-08-10 いなば食品株式会社 動物用の医薬又は食品組成物

Family Cites Families (252)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL37879A (en) 1970-10-27 1974-12-31 Ciba Geigy Ag 3-unsubstituted cephalosporin derivatives,process for their manufacture and compositions containing them
US4299829A (en) 1976-03-12 1981-11-10 Fujisawa Pharmaceutical Co., Ltd. 2-Lower alkyl-7-substituted-2 or 3-cephem 4-carboxylic acid compounds
PH17188A (en) 1977-03-14 1984-06-14 Fujisawa Pharmaceutical Co New cephem and cepham compounds and their pharmaceutical compositions and method of use
US4464369A (en) 1977-03-14 1984-08-07 Fujisawa Pharmaceutical Co., Ltd. 7-Acylamino-3-cephem-4-carboxylic acid derivatives and pharmaceutical compositions
US4496562A (en) 1977-03-14 1985-01-29 Fujisawa Pharmaceutical Co., Ltd. 7-Substituted-3-cephem-4-carboxylic acid esters
US4409217A (en) 1977-03-14 1983-10-11 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
JPS543087A (en) 1977-06-03 1979-01-11 Fujisawa Pharmaceut Co Ltd Preparation of cephalosporin compound
GB1604738A (en) 1977-07-28 1981-12-16 Yamanouchi Pharma Co Ltd 1,3-dithietane-2-carboxylic acid derivatives and the preparation thereof
JPS609719B2 (ja) 1977-08-06 1985-03-12 武田薬品工業株式会社 セフアロスポリン誘導体およびその製造法
US4370326A (en) 1977-09-13 1983-01-25 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds and composition
IT1192287B (it) 1977-11-14 1988-03-31 Fujisawa Pharmaceutical Co Derivati di acido cefalosporanico ad azione farmaceutica e relativo procedimento di preparazione
US4363807A (en) 1978-04-06 1982-12-14 Fujisawa Pharmaceutical Company, Limited Cepham compounds
SE7804231L (sv) 1978-04-14 1979-10-15 Haessle Ab Magsyrasekretionsmedel
AR229883A1 (es) 1978-05-26 1983-12-30 Glaxo Group Ltd Procedimiento para la preparacion de antibiotico(6r,7r)-7-((z)-2-(2-aminotiazol-4-il)-2-(2-carboxiprop-2-oxiimino)-acetamido)-3-(1-piridinometil)-cef-3-em-4-carboxilato
US4264597A (en) 1978-06-06 1981-04-28 Masashi Hashimoto Cephalosporin analogues and processes for the preparation thereof
US4268509A (en) 1978-07-10 1981-05-19 Fujisawa Pharmaceutical Co., Ltd. New cephem compounds and processes for preparation thereof
US4284631A (en) 1978-07-31 1981-08-18 Fujisawa Pharmaceutical Co., Ltd. 7-Substituted cephem compounds and pharmaceutical antibacterial compositions containing them
US4305937A (en) 1978-08-17 1981-12-15 Fujisawa Pharmaceutical Co., Ltd. 2-Lower alkyl-7-substituted-2 or 3-cephem-4-carboxylic acid compounds and antibacterial pharmaceutical compositions containing them
US4703046A (en) 1978-09-08 1987-10-27 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds and processes for preparation thereof
EP0048504B1 (en) 1978-09-12 1988-08-17 Fujisawa Pharmaceutical Co., Ltd. Intermediate compounds for preparing cephem compounds; processes for their preparation and processes for preparing cephem compounds
US4327093A (en) 1978-10-24 1982-04-27 Fujisawa Pharmaceutical Co., Ltd. 3,7-Disubstituted-2 or 3-cephem-4-carboxylic acid compounds
DE2945248A1 (de) 1978-11-13 1980-05-22 Fujisawa Pharmaceutical Co Cephem-verbindungen, verfahren zu ihrer herstellung und sie enthaltende antibakterielle pharmazeutische mittel
AU536842B2 (en) 1978-12-29 1984-05-24 Fujisawa Pharmaceutical Co., Ltd. Cephalosporin antibiotics
US4332798A (en) 1978-12-29 1982-06-01 Fujisawa Pharmaceutical Co., Ltd. 7-Amino-thia-diazole oxyimino derivatives of cephem and cephem compounds
US4390534A (en) 1978-12-29 1983-06-28 Fujisawa Pharmaceutical Co., Ltd. Cephem and cepham compounds
US4291031A (en) 1979-02-19 1981-09-22 Fujisawa Pharmaceutical Co., Ltd. 3-Phosphonocephalosporanic acid derivatives, and pharmaceutical composition comprising the same
US4339449A (en) 1979-03-27 1982-07-13 Fujisawa Pharmaceutical Company, Limited Analogous compounds of cephalosporins, and pharmaceutical composition comprising the same
FR2462439A1 (fr) 1979-07-26 1981-02-13 Roussel Uclaf Nouveau procede de preparation de produits derives de l'acide 7-/(2-aryl) 2-hydroxyimino acetamido/cephalosporanique
EP0088454B1 (en) 1979-09-03 1986-03-05 Fujisawa Pharmaceutical Co., Ltd. New starting compounds for preparing cephem compounds and processes for their preparation
US4381299A (en) 1980-03-07 1983-04-26 Fujisawa Pharmaceutical Co., Ltd. 7-Amino-thiadiazole oxyimino derivatives of cephem and cepham compounds
US4332800A (en) 1979-10-12 1982-06-01 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4338313A (en) 1979-10-12 1982-07-06 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4409214A (en) 1979-11-19 1983-10-11 Fujisawa Pharmaceutical, Co., Ltd. 7-Acylamino-3-vinylcephalosporanic acid derivatives and processes for the preparation thereof
US4409215A (en) 1979-11-19 1983-10-11 Fujisawa Pharmaceutical Co., Ltd. 7-Acylamino-3-substituted cephalosporanic acid derivatives and processes for the preparation thereof
US4420477A (en) 1979-11-30 1983-12-13 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4443443A (en) 1979-12-17 1984-04-17 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4405617A (en) 1980-02-11 1983-09-20 Fujisawa Pharmaceutical Co., Ltd. 3-(Propynyltetrazol)thiomethyl-3-cephems
JPS56125392A (en) 1980-03-06 1981-10-01 Fujisawa Pharmaceut Co Ltd Cepham and cephem compound and preparation thereof
US4470980A (en) 1980-03-07 1984-09-11 Interx Research Corp. Method of increasing oral absorption of β-lactam antibiotics
JPS5711909A (en) 1980-06-23 1982-01-21 Shionogi & Co Ltd Stable freeze-dried preparation of beta-lactam
DE3173613D1 (en) 1980-07-04 1986-03-13 Fujisawa Pharmaceutical Co 7-oxo-cephalosporins and 6-oxo-penicillins, their analogues and process for their preparation
US4443444A (en) 1980-08-11 1984-04-17 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
EP0156118A1 (en) 1980-08-29 1985-10-02 Fujisawa Pharmaceutical Co., Ltd. New starting compounds for the preparation of cephem compounds and processes for preparation thereof
US4416879A (en) 1980-09-08 1983-11-22 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
GR78245B (es) 1980-09-12 1984-09-26 Ciba Geigy Ag
US4367228A (en) 1980-10-29 1983-01-04 Fujisawa Pharmaceutical Co., Ltd. Cephem compound and composition
US4431642A (en) 1980-12-01 1984-02-14 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
ES507942A0 (es) 1980-12-15 1983-02-01 Fujisawa Pharmaceutical Co Un procedimiento para preparar derivados del acido 7-acilaminocefalosporanico .
US4427677A (en) 1980-12-31 1984-01-24 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
DE3177090D1 (en) 1980-12-31 1989-09-28 Fujisawa Pharmaceutical Co 7-acylaminocephalosporanic acid derivatives and processes for the preparation thereof
GR76342B (es) 1981-02-02 1984-08-06 Fujisawa Pharmaceutical Co
US4336253A (en) 1981-03-11 1982-06-22 Eli Lilly And Company Cephalosporin antibiotics
JPS6011917B2 (ja) 1981-04-09 1985-03-28 山之内製薬株式会社 新規なセファロスポリン化合物
DE3118732A1 (de) 1981-05-12 1982-12-02 Hoechst Ag, 6000 Frankfurt Cephalosporinderivate und verfahren zu ihrer herstellung
JPS57193489A (en) 1981-05-21 1982-11-27 Fujisawa Pharmaceut Co Ltd Syn-isomer of 7-substituted-3-cephem-4-carboxylic acid ester and its preparation
GR75487B (es) 1981-06-22 1984-07-23 Fujisawa Pharmaceutical Co
IE53429B1 (en) 1981-08-03 1988-11-09 Fujisawa Pharmaceutical Co New cephem compounds and processes for preparation thereof
US4436912A (en) 1981-09-08 1984-03-13 Eli Lilly And Company 7-[2-(2-Aminooxazol-4-yl)-2-(oximino)acetamido cephalosporin antibiotics and intermediates therefor
US4577014A (en) 1981-09-08 1986-03-18 Eli Lilly And Company Thieno and furopyridinium-substituted cephalosporins
US4430499A (en) 1981-09-08 1984-02-07 Eli Lilly And Company 7-[2-(2-Aminooxazol-4-yl)-2-(oximino)acetamido]cephalosporin antibiotics
JPS5859991A (ja) 1981-09-14 1983-04-09 Fujisawa Pharmaceut Co Ltd 新規セフェム化合物
US4521413A (en) 1981-09-14 1985-06-04 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4402955A (en) 1981-10-02 1983-09-06 Eli Lilly And Company Dioximino cephalosporin antibiotics
US4450270A (en) 1981-10-02 1984-05-22 Eli Lilly And Company Dioximino cephalosporin antibiotics
US4501739A (en) 1982-01-19 1985-02-26 Eli Lilly And Company Thieno and furopyridinium-substituted cephalosporins
DE3207840A1 (de) 1982-03-04 1983-09-15 Hoechst Ag, 6230 Frankfurt "cephalosporinderivate und verfahren zu ihrer herstellung"
JPS58154547A (ja) 1982-03-09 1983-09-14 Nippon Shinyaku Co Ltd アズレン誘導体の安定化法
US4640915A (en) 1982-03-29 1987-02-03 Fujisawa Pharmaceutical Co., Ltd. 1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid derivatives
AU541028B2 (en) 1982-06-21 1984-12-13 Taiho Pharmaceutical Co., Ltd. 6-unsubstituted penicillin derivatives
JPS58225091A (ja) 1982-06-21 1983-12-27 Taiho Yakuhin Kogyo Kk ペニシリン誘導体及びその製造法
US4563449A (en) 1982-07-19 1986-01-07 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4546101A (en) 1982-09-10 1985-10-08 Fujisawa Pharmaceutical Co., Ltd. New cephem compounds useful for treating infectious diseases in human being and animals and processes for preparation thereof
GB8323034D0 (en) 1983-08-26 1983-09-28 Fujisawo Pharmaceutical Co Ltd 7-substituted-3-vinyl-3-cephem compounds
US4609730A (en) 1982-11-22 1986-09-02 Fujisawa Pharmaceutical Co., Ltd. 7-[substituted imino-2-(2-aminothiazol-4-yl)-acetamido]-3(2,2-dihalovinyl or ethynyl)-3-cephem-4-carboxylic acid (syn isomers), having antimicrobial activities
GR79043B (es) 1982-12-06 1984-10-02 Fujisawa Pharmaceutical Co
US4608373A (en) 1982-12-13 1986-08-26 Yamanouchi Pharmaceutical Co., Ltd. Cephem compounds
US4487768A (en) 1982-12-22 1984-12-11 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4463003A (en) 1982-12-22 1984-07-31 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
DE3247613A1 (de) 1982-12-23 1984-07-05 Hoechst Ag, 6230 Frankfurt Cephalosporinderivate und verfahren zu ihrer herstellung
US4562073A (en) 1982-12-24 1985-12-31 Taiho Pharmaceutical Company Limited Penicillin derivatives
US4499088A (en) 1983-01-04 1985-02-12 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
DE3316798A1 (de) 1983-05-07 1984-11-08 Hoechst Ag, 6230 Frankfurt Verfahren zur herstellung von cephemverbindungen
FR2550200B1 (fr) 1983-08-01 1988-04-08 Fujisawa Pharmaceutical Co Procede de preparation de composes de cephem a activite antimicrobienne et nouveaux produits ainsi obtenus
JPS6045514A (ja) 1983-08-22 1985-03-12 Shionogi & Co Ltd 安定な抗菌性凍結乾燥製剤
EP0137442A3 (de) 1983-10-08 1986-01-15 Hoechst Aktiengesellschaft Cephalosporinderivate und Verfahren zu ihrer Herstellung
DE3409431A1 (de) 1983-10-08 1985-04-18 Hoechst Ag, 6230 Frankfurt Cephalosporinderivate und verfahren zu ihrer herstellung
US4690921A (en) 1983-10-11 1987-09-01 Yamanouchi Pharmaceutical Co., Ltd. Cephalosporin compounds and salts thereof
EP0138552A3 (en) 1983-10-17 1986-03-19 Eli Lilly And Company Improvements on or relating to 3-bicyclicpyridinium-methyl cephalosporins
US4748172A (en) 1983-10-17 1988-05-31 Eli Lilly And Company 3-bicyclicpyridinium-methyl cephalosporins
US4692443A (en) 1983-10-17 1987-09-08 Eli Lilly And Company 3-bicyclicpyridinium-methyl cephalosporins
GB8329030D0 (en) 1983-10-31 1983-11-30 Fujisawa Pharmaceutical Co Cephem compounds
GB8401093D0 (en) 1984-01-16 1984-02-15 Fujisawa Pharmaceutical Co Cephem compounds
JPS60169486A (ja) 1984-02-10 1985-09-02 Yamanouchi Pharmaceut Co Ltd ７−アミノ−３−置換メチル−３−セフエム−４−カルボン酸およびその低級アルキルシリル誘導体の製造法
GB8406231D0 (en) 1984-03-09 1984-04-11 Fujisawa Pharmaceutical Co Cephem compounds
JPS60214792A (ja) 1984-04-06 1985-10-28 Taiho Yakuhin Kogyo Kk ペナム酸エステル誘導体
US4705851A (en) 1984-09-28 1987-11-10 Fujisawa Pharmaceutical Co., Ltd. Process for the preparation of 3-phosphoniummethyl-3-cephem compounds
US4761410A (en) 1985-01-14 1988-08-02 Fujisawa Pharmaceutical Co., Ltd. Cephem Compounds
CA1277977C (en) 1985-01-21 1990-12-18 Shigeo Shimizu Beta-lactam antibiotics
GB8504072D0 (en) 1985-02-18 1985-03-20 Fujisawa Pharmaceutical Co Cephem compounds
JPS62103092A (ja) 1985-07-18 1987-05-13 Sagami Chem Res Center β−ラクタム誘導体
JPS6230789A (ja) 1985-08-01 1987-02-09 Yamanouchi Pharmaceut Co Ltd ７−ホルミルアミノセフアロスポリン化合物およびその製造法
CN86107947A (zh) 1985-11-22 1987-05-27 藤沢药品工业株式会社 新的头孢烯化合物及其制备方法
US5194432A (en) 1985-11-22 1993-03-16 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4808617A (en) 1985-12-18 1989-02-28 Bristol-Myers Company Lyophilized or precipitated cephalosporin zwitterion and salt combination
JPS62158290A (ja) 1985-12-28 1987-07-14 Banyu Pharmaceut Co Ltd 新規セフアロスポリン誘導体
DE3789466T2 (de) 1986-03-17 1994-07-28 Fujisawa Pharmaceutical Co 3,7-Disubstituierte-3-Cephemverbindungen und Verfahren zu ihrer Herstellung.
JP2690009B2 (ja) 1986-07-10 1997-12-10 エーザイ 株式会社 セフアロスポリン注射剤
US4833134A (en) 1986-08-19 1989-05-23 Takeda Chemical Industries, Ltd. Cephem compounds
JPS6351389A (ja) 1986-08-22 1988-03-04 Teijin Ltd セフアロスポリン誘導体、その製造法及び抗菌活性組成物
JPS6351388A (ja) 1986-08-22 1988-03-04 Teijin Ltd セフアロスポリン誘導体、その製造法及び抗菌活性組成物
US5162520A (en) 1986-09-22 1992-11-10 Fujisawa Pharmaceutical Co., Ltd. Intermediates for cephem compounds
CA1293719C (en) 1986-09-22 1991-12-31 Takao Takaya Cephem compounds and processes for preparation thereof
US4882434A (en) 1986-10-29 1989-11-21 Takeda Chemical Industries, Ltd. Gamma-lactonecarboxylic acid derivatives and their use as antibacterial agents or intermediates
KR880006244A (ko) 1986-11-24 1988-07-22 후지사와 도모 기찌 로 3-피롤리디닐티오-1-아자바이스클로[3.2.0]햅트2-엔-2-카르복실산 화합물 및 이의 제조방법
DE3784147T2 (de) 1986-11-24 1993-06-03 Fujisawa Pharmaceutical Co 3-pyrrolidinylthio-1-azabicyclo(3.2.0)hept-2-en-2-carbonsaeure-derivate.
AU1630988A (en) 1987-05-30 1988-12-01 Kyoto Pharmaceutical Industries, Ltd. Cephalosporin compound and pharmaceutical composition thereof
IE61679B1 (en) 1987-08-10 1994-11-16 Fujisawa Pharmaceutical Co Water-soluble antibiotic composition and water-soluble salts of new cephem compounds
EP0303172A3 (de) 1987-08-14 1991-05-15 F. Hoffmann-La Roche Ag Oxyimino-Cephalosporine
US5073550A (en) 1987-08-14 1991-12-17 Hoffmann-La Roche Inc. Cephalosphorins with sulfur-containing oxyimino side chain
US5138066A (en) 1987-08-14 1992-08-11 Hoffmann-La Roche, Inc. Intermediates for cephalosporins with sulfur-containing oxyimino side chain
ZA885709B (en) 1987-08-19 1989-04-26 Fujisawa Pharmaceutical Co Novel crystalline 7-(2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido)-3-vinyl-3-cephem-4-carboxylic acid(syn isomer)
US5210080A (en) 1987-09-07 1993-05-11 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US5663163A (en) 1987-09-07 1997-09-02 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds and processes for preparation thereof
IE63094B1 (en) 1987-09-14 1995-03-22 Fujisawa Pharmaceutical Co Cephem compound and a process for preparation thereof
DK637888A (da) 1987-11-24 1989-05-25 Hoffmann La Roche Carboxylsyreestere
GB8804058D0 (en) 1988-02-22 1988-03-23 Fujisawa Pharmaceutical Co 3-alkenyl-1-azabicyclo(3 2 0)hept-2-ene-2-carboxylic acid compounds
JP2648750B2 (ja) 1988-03-02 1997-09-03 大塚化学株式会社 β−ラクタム誘導体の製造方法
US5173485A (en) 1988-03-09 1992-12-22 Fujisawa Pharmaceutical Company, Ltd. Cephem compounds
US5336768A (en) 1988-05-24 1994-08-09 Hoffmann-La Roche Inc. Antibacterial cephalosporin compounds
CS273349B2 (en) 1988-03-31 1991-03-12 Hoffmann La Roche Method of cephalosporin's new derivatives production
KR900006811B1 (ko) 1988-05-11 1990-09-21 주식회사 럭 키 신규 세팔로스포린 유도체 및 그의 제조방법
US4963544A (en) 1988-05-23 1990-10-16 Fujisawa Pharmaceutical Company, Ltd. 3-pyrrolidinylthio-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid compounds
US5244890A (en) 1988-06-06 1993-09-14 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
EP0366189A3 (en) 1988-10-24 1992-01-02 Norwich Eaton Pharmaceuticals, Inc. Novel antimicrobial lactam-quinolones
JP2785195B2 (ja) 1989-01-11 1998-08-13 ソニー株式会社 ディスク装置の光学式エンコーダ
GB8905301D0 (en) 1989-03-08 1989-04-19 Fujisawa Pharmaceutical Co New cephem compound and a process for preparation thereof
JPH0347187A (ja) 1989-04-12 1991-02-28 Yamanouchi Pharmaceut Co Ltd 新規なセファロスポリン誘導体
US5102877A (en) 1989-04-28 1992-04-07 Fujisawa Pharmaceutical Co., Ltd. 1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds
NO903360L (no) 1989-08-11 1991-02-12 Ici Pharma Antibiotiske forbindelser.
ES2059947T3 (es) * 1989-09-30 1994-11-16 Eisai Co Ltd Preparados inyectables que contienen cefalosporina y utilizacion de los mismos.
GB8923844D0 (en) 1989-10-23 1989-12-13 Fujisawa Pharmaceutical Co Carbapenem compounds
US5215982A (en) 1989-11-10 1993-06-01 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
US4982596A (en) 1990-01-26 1991-01-08 Buell Industries, Inc. Die for manufacturing a fastener blank
KR910015587A (ko) 1990-02-27 1991-09-30 후지사와 토모키치로 세펨 화합물
US5095012A (en) 1990-08-23 1992-03-10 Bristol-Myers Squibb Company Antibiotic c-7 catechol-substituted cephalosporin compounds, compositions, and method of use thereof
US5234920A (en) 1990-08-23 1993-08-10 Bristol-Myers Squibb Company Antibiotic C-7 catechol-substituted cephalosporin compounds, compositions, and method of use thereof
US5286721A (en) 1990-10-15 1994-02-15 Fujisawa Pharmaceutical Co., Ltd. 1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds
US5281589A (en) 1991-06-15 1994-01-25 Cheil Foods & Chemicals, Inc. 3-fused pyridiniummethyl cephalosporins
US5523400A (en) 1993-04-16 1996-06-04 Hoffmann-La Roche Inc. Cephalosporin antibiotics
KR100194994B1 (ko) 1993-06-05 1999-06-15 손경식 새로운 세펨 화합물
AU679800B2 (en) 1993-11-06 1997-07-10 Taiho Pharmaceutical Co., Ltd. Crystalline penicillin derivative, and its production and use
EP0664117A1 (de) 1994-01-25 1995-07-26 F. Hoffmann-La Roche Ag Liposomenlösungen
TW293010B (en) 1994-04-20 1996-12-11 Hui-Po Wang Method for preparing cephalosporin derivatives
US5661144A (en) 1994-08-16 1997-08-26 Meiji Seika Kabushiki Kaisha Cephem derivatives with 3-substituted bis heterocycles
DE4440141A1 (de) 1994-11-10 1996-05-15 Hoechst Ag Neue kristalline Cephem-Säureadditionssalze und Verfahren zu ihrer Herstellung
JPH09110877A (ja) 1995-10-17 1997-04-28 Katayama Seiyakushiyo:Kk セフェム化合物、その製造法及びそれを含有する抗菌剤
ATE341554T1 (de) 1996-04-04 2006-10-15 Shionogi & Co Cephemverbindungen und medikamente die diese verbindungen enthalten
AUPN955596A0 (en) 1996-04-30 1996-05-23 Fujisawa Pharmaceutical Co., Ltd. New compound
EP0970065A4 (en) 1997-11-29 2001-03-07 William L Truett ANTIBIOTICS AND THEIR PREPARATION PROCESS
US6288234B1 (en) 1998-06-08 2001-09-11 Advanced Medicine, Inc. Multibinding inhibitors of microsomal triglyceride transferase protein
WO2000004915A1 (en) 1998-07-23 2000-02-03 Intrabiotics Pharmaceuticals, Inc. Compositions and methods for the treatment or prevention of pulmonary infections
TW526202B (en) 1998-11-27 2003-04-01 Shionogi & Amp Co Broad spectrum cephem having benzo[4,5-b]pyridium methyl group of antibiotic activity
US6207661B1 (en) 1999-02-22 2001-03-27 Baxter International Inc. Premixed formulation of piperacillin sodium and tazobactam sodium injection
TWI233805B (en) 1999-07-01 2005-06-11 Fujisawa Pharmaceutical Co Stabilized pharmaceutical composition in lyophilized form as antifungal agent
NZ517663A (en) 1999-08-16 2006-02-24 Revaax Pharmaceuticals Llc Neurotherapeutic clavulanate composition and method
DK1277471T3 (da) 2000-04-24 2008-08-11 Daiichi Sankyo Co Ltd Stabilt væskepræparat omfattende sitafloxacin
JP3743823B2 (ja) 2000-08-11 2006-02-08 大塚化学ホールディングス株式会社 ペニシリン結晶及びその製造法
JP3743822B2 (ja) 2000-08-11 2006-02-08 大塚化学ホールディングス株式会社 ペニシリン結晶及びその製造法
US6599893B2 (en) 2000-08-29 2003-07-29 Essential Therapeutics, Inc. Cephalosporin antibiotics and prodrugs thereof
JP3306473B1 (ja) 2001-05-01 2002-07-24 大塚化学株式会社 β−ラクタム化合物の無水結晶及びその製造法
ES2254671T3 (es) 2001-05-01 2006-06-16 Astellas Pharma Inc. Compuestos de cefem.
JP2002338578A (ja) 2001-05-14 2002-11-27 Otsuka Chem Co Ltd β−ラクタム化合物の水和物結晶
WO2002102378A1 (en) 2001-06-18 2002-12-27 Revaax Pharmaceuticals, Llc Therapeutic treatment for sexual dysfunction
TWI335332B (en) 2001-10-12 2011-01-01 Theravance Inc Cross-linked vancomycin-cephalosporin antibiotics
US7378408B2 (en) * 2001-11-30 2008-05-27 Pfizer Inc. Methods of treatment and formulations of cephalosporin
WO2003066053A1 (en) 2002-02-07 2003-08-14 Rutgers, The State University Antibiotic polymers
TW200305422A (en) 2002-03-18 2003-11-01 Shionogi & Co Broad spectrum cefem compounds
EP1507796B1 (en) 2002-05-24 2012-05-02 Theravance, Inc. Cross-linked glycopeptide-cephalosporin antibiotics
ES2274978T3 (es) 2002-06-07 2007-06-01 Orchid Chemicals And Pharmaceuticals Limited Procedimiento para la reparacion de derivados de penam a partir de derivados de cefam.
AU2003260803A1 (en) 2002-08-30 2004-03-19 Orchid Chemicals And Pharmaceuticals Ltd. Sustained release pharmaceutical composition
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
ES2290498T7 (es) 2002-10-30 2015-07-10 Astellas Pharma Inc. Compuestos de cefem
AU2002952355A0 (en) * 2002-10-30 2002-11-14 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
AU2003274518A1 (en) 2002-11-01 2004-05-25 Orchid Chemicals And Pharmaceuticals Ltd A process for the preparation of benzyl 2-oxo-4- (heteroaryl) dithio-alpha-isoprenyl-1- azetidineazetate derivatives
ATE540129T1 (de) 2002-11-22 2012-01-15 Univ Johns Hopkins Target zur therapie kognitiver behinderungen
DE10304403A1 (de) 2003-01-28 2004-08-05 Röhm GmbH & Co. KG Verfahren zur Herstellung einer oralen Arzneiform mit unmittelbarem Zerfall und Wirkstofffreisetzung
JP2004269401A (ja) * 2003-03-07 2004-09-30 Sawai Pharmaceutical Co Ltd 凍結乾燥製剤
DE602004010862T2 (de) 2003-04-14 2009-01-02 Wyeth Holdings Corp. Zusammensetzungen enthaltend Piperacillin und Tazobactam zur Injektion
AU2003230899A1 (en) 2003-04-14 2004-11-26 Wyeth Holdings Corporation Compositions containing piperacillin and tazobactam useful for injection
AU2003902380A0 (en) 2003-05-16 2003-06-05 Fujisawa Pharmaceutical Co., Ltd. Cephem compounds
ES2335013T3 (es) 2003-05-23 2010-03-18 Theravance, Inc. Antibioticos de glucopeptido-cefalosporina reticulados.
ATE388153T1 (de) 2003-07-11 2008-03-15 Theravance Inc Quervernetzte glycopeptid-cephalosporin- antibiotika
US8173840B2 (en) 2003-07-29 2012-05-08 Signature R&D Holdings, Llc Compounds with high therapeutic index
US7589233B2 (en) 2003-07-29 2009-09-15 Signature R&D Holdings, Llc L-Threonine derivatives of high therapeutic index
US7273935B2 (en) 2003-08-21 2007-09-25 Orchid Chemicals & Pharmaceuticals, Ltd. Process for the preparation of 3-methylcepham derivatives
US7192943B2 (en) 2003-09-18 2007-03-20 Astellas Pharma Inc. Cephem compounds
FR2860235A1 (fr) 2003-09-29 2005-04-01 Yang Ji Chemical Company Ltd Utilisation d'un compose de formule (i) inhibiteur de l'aromatase a des fins therapeutiques et composes de formule (i) en tant que tels
TW200523264A (en) 2003-10-09 2005-07-16 Otsuka Chemical Co Ltd CMPB crystal and method for producing the same
TW200519119A (en) 2003-10-10 2005-06-16 Otsuka Chemical Co Ltd PENAM crystal and process for producing the same
JP4535366B2 (ja) 2003-12-03 2010-09-01 塩野義製薬株式会社 セフェム剤の製造方法
WO2005074925A1 (en) 2004-01-30 2005-08-18 Wyeth Compositions substantially free of galactomannan containing piperacillin and tazobactam
KR20060135796A (ko) 2004-03-05 2006-12-29 시오노기세이야쿠가부시키가이샤 3-피리디늄 메틸세펨 화합물
US7417143B2 (en) 2004-04-07 2008-08-26 Orchid Chemicals & Pharmaceuticals Limited Process for the preparation of Tazobactam in pure form
BRPI0516583A (pt) 2004-10-14 2008-09-16 Wyeth Corp composição farmacêutica e método de tratamento de uma infecção bacteriana
US20060099253A1 (en) 2004-10-20 2006-05-11 Wyeth Antibiotic product formulation
US20060173177A1 (en) 2005-01-28 2006-08-03 Gego Csaba L Process for preparation of penam derivatives
CN101080221A (zh) * 2005-02-14 2007-11-28 维纳斯药业有限公司 抗药性细菌感染疾病的肠胃外综合治疗
WO2006088305A1 (en) 2005-02-15 2006-08-24 Chong Kun Dang Pharmaceutical Corp. Gastric-retentive controlled release mono-matrix tablet
EP1919449A2 (en) 2005-06-07 2008-05-14 Foamix Ltd. Antibiotic kit and composition and uses thereof
ITMI20051630A1 (it) 2005-09-02 2007-03-03 Acs Dobfar Spa Formulazione farmaceutica sterile iniettabile contenente almeno due principi attivi
JP2009510077A (ja) * 2005-09-29 2009-03-12 ネクター セラピューティックス 抗生物質製剤、単位用量、キットおよび方法
EP1787641A1 (de) 2005-11-22 2007-05-23 Helm AG Tazobactam-Piperacillin-Lyophilisat
PL1959933T3 (pl) 2005-12-05 2011-04-29 Sandoz Ag Sposób wytwarzania liofilizowanej soli sodowej piperacyliny w kombinacji z solą sodową tazobaktamu o ulepszonej trwałości po odtworzeniu
WO2007086014A1 (en) 2006-01-25 2007-08-02 Jegannathan Srinivas Formulation comprising cefpirome, tazobactam and linezolid
WO2007086011A1 (en) * 2006-01-25 2007-08-02 Jegannathan Srinivas Formulation comprising cefepime, tazobactam and linezolid
WO2007086013A1 (en) 2006-01-25 2007-08-02 Jegannathan Srinivas Formulation comprising of ceftazidime, tazobactam and linezolid
WO2008075207A2 (en) 2006-04-04 2008-06-26 Foamix Ltd. Anti-infection augmentation foamable compositions and kit and uses thereof
WO2007129176A2 (en) 2006-04-28 2007-11-15 Wockhardt Ltd Improvements in therapy for treating resistant bacterial infections
US20070286818A1 (en) 2006-06-07 2007-12-13 Wyeth Treating cystic fibrosis with antibiotics via an aerosol drug
US20070286817A1 (en) 2006-06-07 2007-12-13 Wyeth Treating cystic fibrosis with antibiotics via a swirler delivery
WO2007145866A1 (en) 2006-06-07 2007-12-21 Wyeth Treating cystic fibrosis with antibiotics via a swirler delivery
PE20080329A1 (es) 2006-06-07 2008-04-09 Wyeth Corp Tratamiento de fibrosis cistica con antibioticos por via de una droga en aerosol
DK2046802T3 (da) 2006-07-12 2013-09-16 Allecra Therapeutics Gmbh 2-substituerede methylpenamderivater
CN101129381B (zh) 2006-08-25 2012-02-01 天津和美生物技术有限公司 含β-内酰胺类抗生素和离子螯合剂的抗生素复方
CN101129383B (zh) 2006-08-25 2014-04-02 天津和美生物技术有限公司 含氨基糖苷类抗生素的抗生素复方
CN101129382B (zh) 2006-08-25 2013-12-25 天津和美生物技术有限公司 含β-内酰胺类抗生素和缓冲组分的抗生素复方
AU2007293068C1 (en) 2006-09-07 2013-09-19 Boehringer Ingelheim Animal Health USA Inc. Soft chewable, tablet, and long-acting injectable veterinary antibiotic formulations
US20080103121A1 (en) * 2006-10-30 2008-05-01 Gole Dilip J Cephalosporin derivative formulation
FI119678B (fi) 2006-11-28 2009-02-13 Ipsat Therapies Oy Beta-laktamaasin käyttö
JP5324463B2 (ja) 2006-12-10 2013-10-23 チョンシー ユー β−ラクタム抗生物質の経皮送達システム
DE102007009242A1 (de) 2007-02-22 2008-09-18 Evonik Röhm Gmbh Pellets mit magensaftresistenter Wirkstoff-Matix
CA2677670C (en) 2007-03-20 2010-08-03 Centre De Recherche Sur Les Biotechnologies Marines Compositions comprising polyunsaturated fatty acid monoglycerides or derivatives thereof and uses thereof
ITMI20070568A1 (it) 2007-03-22 2008-09-23 Acs Dobfar Spa Comosizione farmaceutica sterile iniettabile avente piperacillina sodica e tazobactam sodico come principi attivi
US20090098088A1 (en) 2007-10-10 2009-04-16 The Procter & Gamble Company Methods And Kits For The Treatment Of Diverticular Conditions
WO2009105782A1 (en) 2008-02-21 2009-08-27 Sequoia Pharmaceuticals, Inc. Hiv protease inhibitor and cytochrome p450 inhibitor combinations
KR20100137439A (ko) * 2008-03-04 2010-12-30 엘란 파마 인터내셔널 리미티드 항감염제의 안정성 액체 포뮬레이션 및 항감염제의 조정된 용량투여 요법
ITPI20080025A1 (it) 2008-03-31 2009-10-01 Italmed S R L Composizione ad uso odontoiatrico per il trattamento delle perimplantiti
RU2010143460A (ru) 2008-05-01 2012-06-10 Дзе Проктер Энд Гэмбл Компани (US) Способы и наборы для терапии восстановительных состояний кишечника
CN101265263B (zh) * 2008-05-12 2010-06-02 海南百那医药发展有限公司 哌拉西林钠他唑巴坦钠复方注射剂的生产方法
JP2011520866A (ja) * 2008-05-14 2011-07-21 オーキッド ケミカルズ アンド ファーマシューティカルズ リミテッド セフォゾプランの改良した製造方法
WO2010014285A1 (en) 2008-07-30 2010-02-04 Estabrook Pharmaceuticals, Inc. Compositions including clavulanic acid and related methods of use
RU2016115906A (ru) 2009-06-10 2018-11-28 Текфилдз Байокем Ко., Лтд. Композиции или пролекарства противомикробных и родственных противомикробным соединений, обладающие высокой проникающей способностью
AU2010281439A1 (en) 2009-07-28 2012-03-15 Anacor Pharmaceuticals, Inc. Trisubstituted boron-containing molecules
EP2536408A1 (en) 2010-02-16 2012-12-26 Wockhardt Research Centre Efflux pump inhibitors
EP2544528A1 (en) 2010-03-09 2013-01-16 Merck Sharp & Dohme Corp. FtsZ INHIBITORS AS POTENTIATORS OF BETA-LACTAM ANTIBIOTICS AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS
JP2013523830A (ja) 2010-04-06 2013-06-17 プリサイエンス ラブス， エルエルシー ３−ブロモピルバートおよび他のａｔｐ産生の選択的阻害剤を用いる処置の方法
BR112013032770A2 (pt) * 2011-07-26 2017-02-07 Wockhardt Ltd composições farmacêuticas compreendendo antibiótico beta-lactama, sulbactama e inibidor de beta-lactamase
US20130065874A1 (en) 2011-09-09 2013-03-14 Cubist Pharmaceuticals, Inc. Methods for treating intrapulmonary infections
RU2671485C2 (ru) * 2012-09-27 2018-11-01 Мерк Шарп И Доум Корп. Антибиотические композиции тазобактама аргинина
US8476425B1 (en) 2012-09-27 2013-07-02 Cubist Pharmaceuticals, Inc. Tazobactam arginine compositions
US20140274997A1 (en) 2013-03-15 2014-09-18 Cubist Pharmaceuticals, Inc. Cephalosporin pharmaceutical compositions
CA2906151A1 (en) 2013-03-15 2014-09-18 Merck Sharp & Dohme Corp. Ceftolozane antibiotic compositions

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9724353B2 (en) 2011-09-09 2017-08-08 Merck Sharp & Dohme Corp. Methods for treating intrapulmonary infections
US10028963B2 (en) 2011-09-09 2018-07-24 Merck Sharp & Dohme Corp. Methods for treating intrapulmonary infections
US8968753B2 (en) 2013-03-15 2015-03-03 Calixa Therapeutics, Inc. Ceftolozane-tazobactam pharmaceutical compositions
US9044485B2 (en) 2013-03-15 2015-06-02 Calixa Therapeutics, Inc. Ceftolozane antibiotic compositions
US9320740B2 (en) 2013-03-15 2016-04-26 Merck Sharp & Dohme Corp. Ceftolozane-tazobactam pharmaceutical compositions
US9872906B2 (en) 2013-03-15 2018-01-23 Merck Sharp & Dohme Corp. Ceftolozane antibiotic compositions
US9925196B2 (en) 2013-03-15 2018-03-27 Merck Sharp & Dohme Corp. Ceftolozane-tazobactam pharmaceutical compositions
US10420841B2 (en) 2013-03-15 2019-09-24 Merck, Sharp & Dohme Corp. Ceftolozane antibiotic compositions
US11278622B2 (en) 2013-03-15 2022-03-22 Merck Sharp & Dohme Corp. Ceftolozane antibiotic compositions
US10376496B2 (en) 2013-09-09 2019-08-13 Merck, Sharp & Dohme Corp. Treating infections with ceftolozane/tazobactam in subjects having impaired renal function
US10933053B2 (en) 2013-09-09 2021-03-02 Merck Sharp & Dohme Corp. Treating infections with ceftolozane/tazobactam in subjects having impaired renal function

Also Published As

Publication number Publication date
JP6870029B2 (ja) 2021-05-12
US20160279140A1 (en) 2016-09-29
AU2014227660A1 (en) 2014-10-09
CN110279698B (zh) 2022-10-28
TN2015000411A1 (en) 2017-01-03
MX2015012833A (es) 2016-06-10
MX2020004205A (es) 2021-11-16
UA121298C2 (uk) 2020-05-12
US20140274994A1 (en) 2014-09-18
BR112015023523B8 (pt) 2023-03-07
WO2014144295A1 (en) 2014-09-18
CA2906151A1 (en) 2014-09-18
KR20210031758A (ko) 2021-03-22
WO2014144295A8 (en) 2015-04-23
BR112015023523B1 (pt) 2021-09-14
IL241581B (en) 2020-11-30
EA201591712A1 (ru) 2016-04-29
WO2014144295A4 (en) 2014-11-13
KR20150135363A (ko) 2015-12-02
US20140303136A1 (en) 2014-10-09
US9044485B2 (en) 2015-06-02
NZ700372A (en) 2016-01-29
US20140309205A1 (en) 2014-10-16
AU2014227660B2 (en) 2014-11-06
CN105392485B (zh) 2019-08-02
CN105392485A (zh) 2016-03-09
US20140274995A1 (en) 2014-09-18
JP7177314B2 (ja) 2022-11-24
CL2015002755A1 (es) 2016-12-23
JP2019151668A (ja) 2019-09-12
US20140274989A1 (en) 2014-09-18
BR112015023523A2 (pt) 2020-03-10
JP2021102652A (ja) 2021-07-15
KR102226197B1 (ko) 2021-03-11
EP2893929A1 (en) 2015-07-15
NZ711823A (en) 2021-05-28
AU2014227660A8 (en) 2014-10-23
EA029090B1 (ru) 2018-02-28
EP3100732A1 (en) 2016-12-07
PE20160048A1 (es) 2016-02-12
EP2777705A1 (en) 2014-09-17
JP2016517436A (ja) 2016-06-16
KR102329764B1 (ko) 2021-11-23
CN110279698A (zh) 2019-09-27
JP6543611B2 (ja) 2019-07-10

Similar Documents

Publication Publication Date Title
US20140274992A1 (en) Ceftolozane pharmaceutical compositions
US9925196B2 (en) Ceftolozane-tazobactam pharmaceutical compositions
US11278622B2 (en) Ceftolozane antibiotic compositions
AU2015200599B2 (en) Ceftolozane Antibiotic Compositions
NZ711823B2 (en) Ceftolozane antibiotic compositions

Legal Events

Date Code Title Description
AS Assignment

Owner name: CUBIST PHARMACEUTICALS, INC., MASSACHUSETTS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TERRACCIANO, JOSEPH;MILLER DAMOUR, NICOLE;WALSH, JACQUELINE MARIE;REEL/FRAME:033024/0819

Effective date: 20140603

AS Assignment

Owner name: CALIXA THERAPEUTICS, INC., MASSACHUSETTS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CUBIST PHARMACEUTICALS, INC.;REEL/FRAME:033972/0841

Effective date: 20140603

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: MERCK SHARP & DOHME CORP., NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CALIXA THERAPEUTICS, INC.;REEL/FRAME:037198/0658

Effective date: 20150610