• Analytical Science and Technology
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• v.32 no.4
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• pp.147-154
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• 2019

Ampicillin and Sulbactam (2:1, w/w) are combined in formulation to provide broader antibacterial action in treatment of many infections. The development of analytical method for simultaneouly determine these two compounds was difficult because of the differences in their chemical structures and ratio in the formulation. Current published methods still have some limitations. In this study, we developed an alternative high-performance liquid chromatography (HPLC) assay method for simultaneously determination of ampicillin sodium and sulbactam sodium in powder for injection. Method validation of HPLC method was conducted to determine linearity, precision, accuracy, system suitability, robustness. The linearity of the calibration curves in the desired concentration range was good ($r^2$> 0.9994). RSDs of intra-day and inter-day precision obtained were less than 2.00 %. Accuracy was obtained with the recoveries in range of 98.42 % and 101.36 %. As a result of system suitability, RSD of both retention time and the peak area obtained were not more than 1.0 %. The values of plate number were more than 7000 and symmetric factors obtained were 0.8. As intermediate-precision and robustness of the developed assay, it could be expected to become valuable tools for revising the Korean Pharmacopoeia (KP XI).

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.51-58
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• 1996

A new composite antibiotic, SM-101(sulbactam.metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to Sprague-Dawley male rats from predating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. In male parents, two deaths occurred at 1000 mg/kg. The increase in kidney weight of the 1000 mg/kg group were also observed. The decrease in body weight and food consumption were found at 500 and 1000 mg/kg. The decrease in spleen weight were seen at 250, 500 and 1000 mg/kg. In female parents, three deaths were found at 1000 mg/kg. Mating performance and fertility of parent animals were not adversely affected by all doses tested. F1 fetuses showed no changes related to treatment of SM-101. The results show that the no effect dose level(NOEL) for general toxicity of parent animals is under 250 mg/kg/day and NOELS for reproductive capability and fatal development are over 1000 mg/kg/day.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.59-67
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• 1996

A new composite antibiotic, SM-101(sulbactam·metampicillin), was at dose levels of 0, 375, 750 and 1500 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. In dams, two deaths occurred at 375 and 1500 mg/kg, respectively. The decrease in the weight of adrenal glands of the 1500 mg/kg group was observed. The prolongation of pregnancy period was found at 1500 mg/kg. F1 fetuses showed no changes related to the treatment of SM-101. In F1 offspring, the increase in spleen weight was seen at all doses treated. No treatment-related abnormalities were observed in each treated group in terms of development, behaviour and reproductive performance. In F2 fetuses, no drug-induced abnormalities occurred at all doses. The results show that the no-effect dose levels (NOELS) for dams and Fl offspring are under 375 mg/kg/day and NOELs for F1/F2 fetuses are over 1500 mg/kg/day.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.339-348
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• 1996

A new composite antibiotic, SM-101 (sulbactam·metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on dams and growth, behaviour and mating performance of Fl offspring were examined. In dams, one death occurred at 1000 mg/kg. The increase in kidney weight of the 250, 500 and 1000 mg/kg group was found. In F1 offspring, both delayed incisors eruption and decreased body weight were observed in females of the 1000 mg/kg group. The increase in the weights of liver and kidney was found in males of the 1000 mg/kg group. No treatment-related abnormalities were observed in each treated group in terms of behaviour and reproductive performance. In F1/F2 fetuses, no drug-induced abnormalities occurred at all doses tested. The results show that the no effect dose level (NOEL) of SM-101 is under 250 mg/kg/day for dams and 500 mg/kg/day for F1 offspring, and over 1000 mg/kg/day for F1/F2 fetuses.

• Archives of Pharmacal Research
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• v.18 no.6
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• pp.423-426
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• 1995

SM-101 is a mixture of metampicillin and sulbactam(2:1). The antibacterial activities of SM-101 were compared with those of metampicillin, piperacillin and Augmentin. It showed powerful antibacterial activities against major strains. Except P. anruginosa and S. marcescens, the in vitro antibacterial activity of SM-101 was higher than those of metampicillin, piperacillin and Augmentin against Staphylococcus spp., Streptococcus spp., Moganella morganii, E. Coil, and Proteus spp. The $ED_{50}$ values of SM-101 were two-fold or greater than those of metampicillin, piperacillin and Augmentin against $\beta-lactamase$ producing strains, p. mirabilis GN79 and M. morganiii MB4-11. The in vivo efficacy of SM-101 was more active than metampicillin and pipeeracillin and similar to Augmentin against S. aureus Smith, E coli MB4-01 and K. pneumoniae MB4-02.

• YAKHAK HOEJI
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• v.41 no.4
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• pp.462-472
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• 1997

In this approach, the antimicrobial activities of the compounds were compared with the ${\beta}$-lactam antibiotics against ${\beta}$-lactamase producing strains in vitro. Heteroc yclyl exomethylenepenam derivatives were several numbers of 6-exomethylenepenam sodiums (CH1240, CH1245, CH1250, CH2140, CH2145, CH2150). The inhibitory concentraion assay of six compounds were compared with clavulanic acid, sulbactam, tazobactam. Clavulanic acid, sulbactam and tazobactam are used as inhibitors of a variety of plasmid-mediated beta-lactamases. In vitro ${\beta}$-lactamase inhibitory assay, CH1240 and CH2140 were more active than clavulanic acid, sulbactam and tazobactam against ${\beta}$-lactamases overally. And in vitro comparative antimicrobial susceptibility test of six inhibitors were performed with mixed forms of ampicillin, cefotaxime, amoxicillin, ticarcillin, piperacillin, cefoperazone against ${\beta}$-lactamase producing 31 species strains. Consequently CH2140 and CH1240 among the six compounds enhanced the activity of the ${\beta}$-lactams for 31 ${\beta}$-lactamase producing strains.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.251-261
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• 1993

The subacute toxicity of combined antibiotics, SP-102 (Sulbactam.Piperacilline), was examined in S.D.rats. Four groups of rats were administered intraperitoneally with 0, 512, 1280 and 3200 mg/kg/day of SP-102 for 30 days. Hain clinical sign related to the compound was soft stool. The body weight gain was slightly decreased in male rats treated with 1280, 3200 mg/kg and in female rats treated with 1280 mg/kg of SP-102. Water consumption was significantly increased in rats administered with SP-102. There were no dose-related changes of urinalysis, biochemical examination and hematological findings in all the groups treated with SP-102. Gross necropsy and histopathology revealed no evidence of specific toxicity related to SP-102. Our data indicate that no-observed effect level of SP-102 is below 512 mg/kg in male and female rats. Maximum tolerated dose of SP-102 was estimated to be above 3200 ma/kg in this study.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.782-788
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• 1999

7-Oxocephalosporanate 1 was treated with phosphonium salts 2~4 by Wittig reaction to afford 7-exomethylene cephalosporanates 5~7. They were oxidized to sulfones 8~10 with mCPBA. Deprotecton of benzhydryl 7-exomethylene cephalosporanate with $AlCl_3$ and NaHCO_3$ gave sodium salts of 7-exomethylene cephalosporanates 11~16. The ${\beta}-lactamase$ inhibitory activity of synthesized compounds 11~16 were compared with sulbactam, tazobactam and clavulanic acid against Type I, II, III, IV and TEM-2 $\beta$-lactamase in vitro. Compound 15 showed more potent activity than sulbactam and clavulanic acid against Type III, IV ${\beta}-lactamase$ enzyme.

• Korean Journal of Veterinary Research
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• v.43 no.1
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• pp.113-120
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• 2003

The antimicrobial effect of ${\beta}$-lactam antibiotics, which had ${\beta}$-lactamase inhibitor activity, on Staphylococcus aureus isolated from mastitis was investigated in this study. Out of 166 isolates, 99 isolates (59.6%) produced ${\beta}$-lactamase, and 98 isolates of 99 were ${\beta}$-lactamase positive in above $12.5{\mu}g/m{\ell}$ MIC of penicillin. In the providence distribution, ${\beta}$-lactamase production rate of 4 providence, Gangwon, Gyeonggi, Chungcheong, and Jeolla was 100%, 65.7%, 58.8%, and 50.0%, respectively. Antibiotic activities of ${\beta}$-lactam antibiotics against lactamase positive isolates also were investigated. Antimicrobial effects of ampicillin/sulbactam or amoxicillin/clavulanic acid treated group were better than ampicillin or amoxicillin treated group. In antimicrobial effects on intracellular S aureus, there was no difference 1 hour and 4 hour treatment in control, ampicillin, and amoxicillin group, but in 18 hours treatment, ampicillin/sulbactam or amoxicillin/clavulanic acid had a better effect than ampicillin or amoxicillin (p<0.05).

• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.96-99
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• 2004

Aminophylline, ceftriaxone 및 ampicillin/sulbactam (Unasyn)을 미숙아용 고영양수액제에 직접 첨가하거나 Y-site로 투여하는 경우의 안정성에 관해 조사하였다. Aminophylline 주사액 (25mg/mL) $300{\mu}l$와 ceftriaxone sodium (37.5 mg/mL) 2mL를 각각 고영양수액제 직접 첨가하였다. 또한 Y-site에서의 안정성 조사를 위해 ceftriaxone sodium (37.5 mg/mL)을 고영양수액제에 각각 1:1 및 1:2 부피비가 되도록 혼합하였고 Unasyn (25mg/mL)은 고영양수액제와 1:1의 부피비로 혼합하였다. 이상과 같이 조제한 혼합액을 $25^{\circ}C$와 $4^{\circ}C$에 보관하여 aminophylline은 48시간 동안 그리고 항생제들은 24시간 동안의 경시변화를 HPLC를 이용하여 분석하였다. Aminophylline은 위 보존조건에서 48시간동안 안정하였다(변화율 <$10{\%}$). Ceftriaxone sodium을 고영양수액제에 직접 첨가한 경우 ceftriaxone의 잔존률은 $25^{\circ}C$에서 4시간째에 $90.5{\pm}1.8{\%}$이었고 $4^{\circ}C$에는 $95.1{\pm}1.4{\%}$로 측정되었다. Y-site에서의 안정성과 관련하여 ceftriaxone sodium을 고영양수액제와 1:1로 혼합한 경우 양 보존조건에서 ceftriaxone은 24시간 동안 안정하였으나 1:2로 혼합한 경우에는 $4^{\circ}C$ 보관 시에만 안정하였고 $25^{\circ}C$에서는 24시간째에 약 $14{\%}$ 정도 분해되는 것으로 나타났다. 한편, Unasyn의 경우 ampicillin은 24시간째에 $4^{\circ}C$ 보관 시에만 안정하였고 $25^{\circ}C$에서는 24시간째에 약 $14{\%}$정도 분해되는 것으로 나타났다. 한편, Unasyn의 경우 ampicillin은 24시간째에 $4^{\circ}C$에서는 안정하였으나 $25^{\circ}C$에서는 $30{\%}$까지 감소되는 것으로 분석되었고 sulbactam은 24시간째에 온도와 관계없이 안정한 것으로 나타났다. Ceftriaxone sodium을 TPN과 Y-site 혼합 후 1-2시간 이내에 침천이 형성되었고 Unasyn의 경우에는 12시간째에 침천이 형성되었다. 혼합액의 pH나 색상은 연구기간 동안 일정하였다. 이러한 연구결과에 기초할 때, aminophylline은 고영양수액제와 혼합가능하고 ceftriaxone과 Unasyn은 고양양수액제와 혼합시 최소 1시간 동안은 안정한 것으로 평가되었다.