Crystalline forms of diazabicyclooctane derivative and production process thereof
Inventors
Abe, Takao • Furuuchi, Takeshi • Sakamaki, Yoshiaki • MITSUHASHI, Nakako • SAITO, Yumiko
Assignees
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Publication Number
US-11414417-B2
Publication Date
2022-08-16
Expiration Date
Abstract
A crystalline form I of a compound represented by Formula (VII-1): having characteristic peaks appearing at lattice spacing (d) of 7.34, 5.66, 5.53, 5.30, 5.02, 4.66, 4.37, 4.28, 4.06, 3.68, 3.62, 3.47, 3.36, 3.30, 3.16, 3.11, 3.03, 2.99 and 2.50 Å in the powder X-ray diffraction pattern.
Core Innovation
The disclosure provides crystalline forms of a compound represented by Formula (VII-1), including crystalline form I, crystalline form II, crystalline form III, and crystalline form IV, and defines crystalline solids by powder X-ray diffraction patterns using specified lattice spacing (d) values. The crystalline forms III and IV are characterized for solid-form identification and differentiation.
The document describes production and isolation of defined crystalline solids, including crystallization workflows with pH buffering, desalting, temperature adjustment, seeding, and precipitation using poor solvents or alcohol. It also describes deprotection, pH adjustment, sulfation, and precipitation to reach crystalline form IV and related crystalline forms.
The compound of Formula (VII-1) is presented for concomitant use with b2-lactam antimicrobial agents, and combination use is described with b2-lactam antibiotics selected from ampicillin, amoxicillin, piperacillin, ticarcillin, flomoxef, cefotaxime, ceftriaxone, ceftazidime, cefepime, ceftaroline, ceftolozane, imipenem, meropenem, biapenem, doripenem, ertapenem, aztreonam, and penicillin, cephem/cephalosporins, carbapenems, and aztreonam. Pharmaceutical composition aspects include mixtures of at least two crystalline forms of Formula (VII-1) and optional pharmaceutically acceptable carriers.
Claims Coverage
The claim coverage is centered on four inventive features: PXRD-defined crystalline form III, PXRD-defined crystalline form IV, pharmaceutical compositions comprising a mixture of crystalline form III and crystalline form IV, and a composition that further includes a selected b2-lactam antibiotic. The independent claims collectively define crystalline-form signatures and composition-level combinations involving form III and form IV.
Powder X-ray diffraction-defined crystalline form III
A crystalline form III of a compound represented by Formula (VII-1) having characteristic peaks appearing at lattice spacing (d) of 8.32, 6.10, 5.98, 5.51, 5.16, 5.07, 4.85, 4.70, 4.61, 4.35, 4.20, 4.06, 4.00, 3.95, 3.77, 3.73, 3.65, 3.42, 3.39, 3.36, 3.26, 3.23, 3.13, 3.09, 2.99, 2.81 and 2.52 c5 in the powder X-ray diffraction pattern.
Powder X-ray diffraction-defined crystalline form IV
A crystalline form IV of a compound represented by Formula (VII-1) having characteristic peaks appearing at lattice spacing (d) of 7.88, 6.41, 5.20, 4.67, 4.50, 4.02, 3.81, 3.75, 3.70, 3.62, 3.38, 3.23, 3.20, and 2.74 c5 in the powder X-ray diffraction pattern.
Pharmaceutical composition comprising a mixture of crystalline form III and crystalline form IV
A pharmaceutical composition comprising a mixture of at least two crystalline forms of a compound represented by Formula (VII-1), optionally a pharmaceutically acceptable carrier, wherein the at least two crystalline forms comprise crystalline form III and crystalline form IV.
Pharmaceutical composition comprising a mixture of crystalline form III and crystalline form IV with a b2-lactam antibiotic
A pharmaceutical composition comprising a mixture of at least two crystalline forms of a compound represented by Formula (VII-1), a b2-lactam antibiotic selected from ampicillin, amoxicillin, piperacillin, ticarcillin, flomoxef, cefotaxime, ceftriaxone, ceftazidime, cefepime, ceftaroline, ceftolozane, imipenem, meropenem, biapenem, doripenem, ertapenem and aztreonam, and optionally a pharmaceutically acceptable carrier, wherein the at least two crystalline forms comprise crystalline form III and crystalline form IV.
The claims are defined primarily by powder X-ray diffraction signatures that distinguish crystalline form III and crystalline form IV of Formula (VII-1). The composition claims then cover mixtures of these crystalline forms, with optional pharmaceutically acceptable carriers and, in one independent claim, a specified group of b2-lactam antibiotics.
Stated Advantages
Improved control of decomposition.
Higher purity/yield and reproducibility.
Prevention of crystallographic polymorph transformation under stress.
Stability of water content and related substances over time under specified conditions in packaging.
Documented Applications
Treating bacterial infection by administering crystalline form III of the compound represented by Formula (VII-1) in combination with a b2-lactam antibiotic selected from a specified group.
Treating bacterial infection by administering crystalline form IV of the compound represented by Formula (VII-1) in combination with a b2-lactam antibiotic selected from a specified group.
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