Eutectic of Piperacillin sodium and Sulbactam sodium, preparation method thereof, pharmaceutical composition containing eutectic and application of pharmaceutical composition
A technology of piperacillin sodium and sulbactam sodium, which is applied in the field of co-crystallization of compound drugs, can solve the problems of short validity period and poor stability, and achieve the effects of constant antibacterial activity, low hygroscopicity, easy filtration and drying
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Embodiment 1
[0067] Add 40g (0.074mol) of piperacillin sodium (calculated as salt) and 20g (0.078mol) of sulbactam sodium (calculated as salt) to a mixed solution of 40mL acetone+32mL DMF+12mL water (mixed solution 1) , then add 280mL of acetone (high-purity ketone 1), filter out the insoluble matter, let it stand at 5°C for 24 hours, filter out the generated crystals, and then mix with 72mL of acetone + 6.8mL of DMF + 2.4mL of water Solution (mixed solution 2) and 120mL acetone (high-purity ketone 2) wash the crystals filtered out after the above-mentioned standing to obtain white crystals, namely piperacillin sodium and sulbactam sodium cocrystal A, its X-ray powder diffraction Spectrum such as Figure 1-a (see Table 1 for the corresponding data, see the attached Figure 1-b ), its DSC spectrum is as image 3 As shown, its IR spectrum is the same as Figure 4 shown.
[0068] Table 1: X-ray powder diffraction data of cocrystal A
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Embodiment 2
[0072] Add 400g (0.74mol) of piperacillin sodium (calculated as salt) and 179g (0.70mol) of sulbactam sodium (calculated as salt) to a mixed solution of 400mL acetone+300mL DMF+120mL water (mixed solution 1) , and then add 2800mL acetone (high-purity ketone 1), filter out the insoluble matter, let it stand at 5°C for 24 hours, filter out the generated crystals, and then successively use the mixed solution of 700mL acetone+60mL DMF+20mL water ( Mixed solution 2), and 1200mL acetone (high-purity ketone 2) wash the above-mentioned crystals filtered out after standing to obtain white crystals, namely piperacillin sodium and sulbactam sodium cocrystal A, its X-ray powder diffraction spectrum , DSC spectrum and IR spectrum are similar to Figures 1, 3 and 4 respectively, which can show that the cocrystal A is prepared.
Embodiment 3
[0074] Add 420g (0.78mol) of piperacillin sodium (calculated as salt) and 200g (0.78mol) of sulbactam sodium (calculated as salt) to a mixed solution of 500mL acetone+350mL DMF+120mL water (mixed solution 1) , and then add 3000mL acetone (high-purity ketone 1), after filtering out the insoluble matter, let it stand at 5°C for 24 hours, filter out the generated crystals, and then successively use the mixed solution of 800mL acetone+60mLDMF+20mL water (high Purity ketone 2), and 1400mL acetone (high-purity ketone 2) wash the crystals filtered out after the above-mentioned standing to obtain white crystals, namely piperacillin sodium and sulbactam sodium cocrystal A, its X-ray powder diffraction spectrum , DSC spectrum and IR spectrum are similar to Figures 1, 3 and 4 respectively, which can show that the cocrystal A is prepared.
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