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-12221443-B2
Publication Date
2025-02-11
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 invention relates to a crystalline form II of a compound represented by Formula (VII-1), characterized by a specific powder X-ray diffraction pattern having characteristic peaks at defined lattice spacing (d) values. It further encompasses crystalline forms I, III, and IV of the same compound, each identified by their own powder X-ray diffraction peak sets, and linked in the description to crystalline form VII-CR and Formula (VII).
The disclosed compounds are described as β-lactamase inhibitor compounds, including Formula (VII-1) and examples such as VII-1 and VII-1-CR. Powder X-ray diffraction and DSC are used to distinguish crystalline forms via peak differences, and the crystalline form II of Formula (VII-1) is positioned for pharmaceutical use in the context of crystalline form polymorphs and crystalline form VII-CR.
The invention includes pharmaceutical compositions and combination therapy in which the crystalline form, including crystalline form II and mixtures of crystalline forms, is used together with β-lactam antimicrobial agents. β-lactam antibiotics explicitly described include penicillin, cephem, carbapenem, and aztreonam types, and the description includes oral and parenteral administration routes and formulation forms such as tablets, capsules, granules, powders, suspensions, and IV solution concepts.
Claims Coverage
The independent claims present three inventive features across the input items: a PXRD-defined crystalline form II, a pharmaceutical composition comprising a mixture of crystalline forms I and one of II, III, or IV, and a similar composition further combined with a selected β-lactam antibiotic. The claim coverage centers on crystalline identity of Formula (VII-1) via specified PXRD characteristic peaks and on compositions containing crystalline form mixtures.
Pxrd-defined crystalline form II of formula (VII-1)
A crystalline form II of a compound represented by Formula (VII-1) having characteristic peaks appearing at lattice spacing (d) of 9.46, 5.62, 5.23, 5.10, 5.00, 4.91, 4.67, 4.45, 4.29, 3.96, 3.78, 3.71, 3.52, 3.24, 3.18, 3.10, 3.02, 2.88, 2.81, 2.77, 2.67, 2.50 and 2.45 Å in the powder X-ray diffraction pattern.
Pharmaceutical composition with mixture of crystalline forms I and II, III, or 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 I and any one crystalline form selected from crystalline form II, crystalline form III, or crystalline form IV, each defined by its own characteristic powder X-ray diffraction peak set.
Pharmaceutical composition with mixture of crystalline forms and selected β-lactam antibiotic
A pharmaceutical composition comprising a mixture of at least two crystalline forms of a compound represented by Formula (VII-1) together with a β-lactam antibiotic selected from the group consisting of ampicillin, amoxicillin, piperacillin, ticarcillin, flomoxef, cefotaxime, ceftriaxone, ceftazidime, cefepime, ceftaroline, ceftolozane, imipenem, meropenem, biapenem, doripenem, ertapenem and aztreonam, optionally a pharmaceutically acceptable carrier, wherein the at least two crystalline forms comprise crystalline form I and any one crystalline form selected from crystalline form II, crystalline form III, or crystalline form IV.
Overall, the independent claims protect PXRD-defined crystalline form II of Formula (VII-1) and pharmaceutical compositions comprising mixtures of crystalline form I with crystalline forms II, III, or IV. The broad composition coverage is further narrowed by requiring a selected β-lactam antibiotic from a listed group.
Stated Advantages
Reports stable polymorph identity with crystal transformation not observed under solid-state storage and suspension tests.
The disclosure addresses the difficulty of isolating stable crystalline API from amorphous or lyophilized product.
The disclosure addresses difficult purification and crystallization steps.
Reports high-purity crystallizable product and high yield under described production conditions [procedural detail omitted for safety].
Reports water content and related substances stability over storage conditions including 40°C/75% RH and also 60°C.
Documented Applications
Pharmaceutical composition for parenteral administration in combination therapy with a beta-lactam antibiotic, including treating bacterial infection in a subject [procedural detail omitted for safety].
Combination with selected beta-lactam antibiotics from a specified group, including ampicillin, amoxicillin, piperacillin, ticarcillin, flomoxef, cefotaxime, ceftriaxone, ceftazidime, cefepime, ceftaroline, ceftolozane, imipenem, meropenem, biapenem, doripenem, ertapenem, and aztreonam [procedural detail omitted for safety].
Pharmaceutical use.
Pharmaceutical compositions and combination therapy with β-lactam antimicrobial agents.
Oral and parenteral administration routes, including tablets, capsules, granules, powders, suspensions, and IV solution concepts.
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