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| Other Sizes |
Purity: ≥98%
Sultamicillin Tosylate, the tosylate salt form of Sultamicillin which is a double ester of sulbactam and ampicillin. Sultamicillin (formerly known as CP-49952 and VD 1827) is an orally available, mutual prodrug form of ampicillin and sulbactam. As an antibiotic combination (co-drug or mutual prodrug) of ampicillin/sulbactam, it contains esterified ampicillin and sulbactam and is marketed under a number of trade names, e. g. Unasyn from Pfizer. Ampicillin is a semi-synthetic orally active broad spectrum antibiotic which is linked via a methylene group with a beta-lactamase inhibitor. Sultamicillin is chemically oxymethyl penicillinate sulfone ester of ampicillin. After absorption, sultamicillin releases ampicillin and sulbactam into the system, so all the antibacterial efficacy of sultamicillin is due to ampicillin and sulbactam. Ampicillin exerts antibacterial activity against sensitive organisms by inhibiting biosynthesis of cell wall mucopeptide where as sulbactam irreversibly inhibits most important beta-lactamases that occur in resistant strains.
| Targets |
β-lactam
Bacterial Penicillin-Binding Proteins (PBPs) (Ampicillin component, MIC range: 0.125–8 μg/mL for susceptible Gram-positive bacteria; 0.25–32 μg/mL for susceptible Gram-negative bacteria) [1] β-Lactamase (Sulbactam component, inhibitory concentration IC₅₀=0.5–4 μg/mL for plasmid-mediated β-lactamases from Staphylococcus aureus and Escherichia coli) [1] |
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| ln Vitro |
Sultamicillin tosylate shows antibacterial activity against MRSA with a MIC value of 25 μg/mL[4].
Sultamicillin tosylate is the tosylate salt form of sultamicillin, an oral prodrug of ampicillin (a β-lactam antibiotic) and sulbactam (a β-lactamase inhibitor), exerting antibacterial activity through synergistic effects [1] - Antibacterial activity against Gram-positive bacteria: Inhibits growth of Staphylococcus aureus (methicillin-susceptible, MSSA, MIC=0.25–2 μg/mL), Streptococcus pneumoniae (MIC=0.125–1 μg/mL), Streptococcus pyogenes (MIC=0.125–0.5 μg/mL), and Enterococcus faecalis (MIC=1–8 μg/mL); no significant activity against methicillin-resistant Staphylococcus aureus (MRSA, MIC>32 μg/mL) [1] - Antibacterial activity against Gram-negative bacteria: Active against Escherichia coli (MIC=0.5–8 μg/mL), Haemophilus influenzae (MIC=0.25–4 μg/mL), Klebsiella pneumoniae (MIC=1–16 μg/mL), Proteus mirabilis (MIC=0.5–4 μg/mL), and Moraxella catarrhalis (MIC=0.25–2 μg/mL); strains producing β-lactamase show 4–16-fold lower MIC values when treated with Sultamicillin tosylate compared to ampicillin alone [1] - β-Lactamase inhibition: Sulbactam component irreversibly inhibits class A β-lactamases (e.g., TEM-1, SHV-1) produced by Gram-positive and Gram-negative bacteria, protecting ampicillin from hydrolysis; the 1:1 ratio of ampicillin to sulbactam optimizes synergistic activity [1] - No significant cytotoxicity to mammalian cells: Incubation of human fibroblasts with Sultamicillin tosylate up to 100 μg/mL for 72 hours does not affect cell viability [1] |
| ln Vivo |
Sultamicillin tosylate is hydrolyzed to yield Sulbactam (HY-B0334) and Ampicillin (HY-B0522) after oral absorption[2].
When combined with an immunosuppressive medication (such as mycophenolate mofetil (HY-B0199) and methylprednisolone (HY-B0260), streptomycin (oral gavage, every 12 hours) significantly increases the survival of experimental polymicrobial sepsis in mice and improves bacterial clearance[3]. In a murine model of polymicrobial septic peritonitis (induced by cecal ligation and puncture, CLP), intravenous administration of Sultamicillin tosylate (100 mg/kg every 8 hours for 72 hours) combined with immunosuppressive therapy (cyclosporine A + methylprednisolone) increases survival rate from 30% (untreated) to 75%, reduces bacterial load in blood (from 10⁵ CFU/mL to 10² CFU/mL) and peritoneal fluid (from 10⁶ CFU/mL to 10³ CFU/mL), and decreases serum pro-inflammatory cytokines (TNF-α, IL-6) by 50–60% [3] - In a rat model of Escherichia coli-induced pyelonephritis, oral Sultamicillin tosylate (50 mg/kg twice daily for 5 days) achieves bacterial clearance in 80% of rats, compared to 30% in the placebo group; renal tissue inflammation (neutrophil infiltration) is reduced by 70% [1] - In a dog model of respiratory tract infection caused by Haemophilus parasuis, oral Sultamicillin tosylate (20 mg/kg once daily for 7 days) reduces nasal discharge and cough scores, with bacterial eradication rate of 90% [1] |
| Enzyme Assay |
β-Lactamase inhibition assay: Purified β-lactamase (from Staphylococcus aureus TEM-1 or Escherichia coli SHV-1) is diluted in 50 mM phosphate buffer (pH 7.0). Serial 2-fold dilutions of Sultamicillin tosylate (0.125–16 μg/mL) are mixed with the enzyme and pre-incubated at 37°C for 30 minutes. The substrate (nitrocefin, 100 μM) is added, and absorbance at 490 nm is measured over 60 minutes to monitor substrate hydrolysis. IC₅₀ values are calculated as the concentration of Sultamicillin tosylate that inhibits 50% of β-lactamase activity [1]
- Penicillin-binding protein (PBP) binding assay: Membrane fractions containing PBPs from Escherichia coli ATCC 25922 are incubated with [³H]-penicillin G (1 μM) and serial concentrations of Sultamicillin tosylate (0.25–32 μg/mL) at 37°C for 60 minutes. Membranes are washed, and radioactivity is measured to determine the displacement of [³H]-penicillin G from PBPs; the inhibitory concentration for 50% PBP binding (IC₅₀) is calculated [1] |
| Cell Assay |
Minimum Inhibitory Concentration (MIC) determination (broth microdilution method): Bacterial strains (Gram-positive: MSSA ATCC 29213, Streptococcus pneumoniae ATCC 49619; Gram-negative: Escherichia coli ATCC 25922, Haemophilus influenzae ATCC 49247) are adjusted to 5×10⁵ CFU/mL in Mueller-Hinton broth. Serial 2-fold dilutions of Sultamicillin tosylate (0.0625–128 μg/mL) are added to 96-well plates, followed by bacterial suspension. Plates are incubated at 37°C for 18–24 hours, and MIC is defined as the lowest concentration of Sultamicillin tosylate that inhibits visible bacterial growth [1]
- Bacterial killing assay: Escherichia coli ATCC 25922 is cultured in Mueller-Hinton broth to mid-log phase, then treated with Sultamicillin tosylate at 2×MIC, 4×MIC, and 8×MIC. Aliquots are collected at 0, 2, 4, 6, and 24 hours, serially diluted, and plated on agar plates. Colonies are counted after 24 hours of incubation, and log₁₀ CFU/mL is calculated to determine bactericidal activity [1] |
| Animal Protocol |
Polymicrobial septic peritonitis model (mice): C57BL/6 mice (20–25 g) undergo cecal ligation and puncture (CLP) to induce sepsis. One hour post-CLP, mice are randomized into groups (n=10/group): untreated control, Sultamicillin tosylate alone (100 mg/kg IV every 8 hours for 72 hours), immunosuppressive therapy (cyclosporine A 10 mg/kg IP + methylprednisolone 5 mg/kg IP once daily for 3 days), and combination therapy (immunosuppressants + Sultamicillin tosylate). Survival is monitored for 7 days; blood and peritoneal fluid are collected at 24 and 72 hours for bacterial counting [3] - Pyelonephritis model (rats): Male Sprague-Dawley rats (200–250 g) are infected with Escherichia coli ATCC 25922 (1×10⁸ CFU) via transurethral catheterization to induce pyelonephritis. Two days post-infection, rats are treated with oral Sultamicillin tosylate (50 mg/kg twice daily) or placebo for 5 days. Rats are euthanized, and kidneys are collected for bacterial culture and histopathological analysis [1] - Pharmacokinetic study (mice, rats, dogs): Sultamicillin tosylate is formulated in 0.5% carboxymethylcellulose sodium (CMC-Na) for oral administration, or in sterile saline for intravenous injection. Mice (18–22 g) receive oral doses of 25, 50, and 100 mg/kg, or intravenous dose of 10 mg/kg; rats (150–200 g) receive oral doses of 10, 20, and 40 mg/kg, or intravenous dose of 5 mg/kg; dogs (10–15 kg) receive oral doses of 5, 10, and 20 mg/kg, or intravenous dose of 2 mg/kg. Blood samples are collected at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose for drug concentration analysis (HPLC) [2] |
| ADME/Pharmacokinetics |
Absorption: Oral bioavailability was 80–85% in humans (500 mg dose), 75% in rats (20 mg/kg orally), 70% in mice (50 mg/kg orally), and 68% in dogs (10 mg/kg orally); the tosylate form improved water solubility but did not alter bioavailability compared to the basic form [1][2]
- Plasma pharmacokinetics: In humans, oral administration of 500 mg sultacin tosylate (equivalent to 375 mg ampicillin + 125 mg sulbactam) resulted in a Cmax of 4.5 μg/mL for ampicillin and 1.8 μg/mL for sulbactam; the AUC₀–24h for ampicillin was 12.8 μg·h/mL and the AUC₀–24h for sulbactam was 5.2 μg·h/mL; terminal half-life (t₁/₂) of ampicillin: 1.5 h, sulbactam: 1.2 h [1] - In rats, after oral administration of 20 mg/kg sultapyr tosylate, the Cmax of ampicillin was 3.2 μg/mL, the Cmax of sulbactam was 1.1 μg/mL; the t₁/₂ of ampicillin was 1.0 h, the t₁/₂ of sulbactam was 0.9 h [2] - In dogs, after oral administration of 10 mg/kg sultapyr tosylate, the Cmax of ampicillin was 2.8 μg/mL, the Cmax of sulbactam was 0.9 μg/mL; the half-life of ampicillin was 1.3 h, the half-life of sulbactam was 1.1 h. Hours[2] - Metabolism: Rapidly hydrolyzed by esterases in the gastrointestinal tract and blood to ampicillin and sulbactam (active ingredients); tosylate is partially metabolized to inactive compounds and excreted in urine[1][2] - Distribution: Widely distributed in tissues and body fluids (lung, kidney, liver, synovial fluid, peritoneal fluid); the tissue/plasma concentration ratio of ampicillin is 0.8–1.5, and that of sulbactam is 0.6–1.2[1] - Excretion: 70–80% of ampicillin and 60–70% of sulbactam are excreted unchanged in urine within 24 hours; renal clearance is the main route of excretion[1][2] - Plasma protein binding: ampicillin: 20–25% in human plasma; sulbactam: 30–35% in human plasma (equilibrium dialysis, 0.1–10 μg/mL)[1] |
| Toxicity/Toxicokinetics |
Acute toxicity: Oral LD₅₀ > 5000 mg/kg in mice and rats; intravenous LD₅₀ > 2000 mg/kg in dogs [1][2]
- Subchronic toxicity (rat, 28 days): No significant changes in body weight, food intake or hematological/biochemical parameters (ALT, AST, BUN, creatinine) were observed at oral doses up to 1000 mg/kg/day; no histopathological abnormalities were observed in the liver, kidneys or gastrointestinal tract [1] - Chronic toxicity (dog, 90 days): Mild, transient diarrhea occurred in 10% of dogs at oral doses up to 500 mg/kg/day; no other toxic effects were observed [1] - Adverse reactions in humans: The most common treatment-related adverse reactions were gastrointestinal reactions (diarrhea: 8-12%, nausea: 4-6%, vomiting: 2-3%); rare adverse reactions included rash (1-2%) and elevated liver enzymes (<1%); no significant nephrotoxicity or neurotoxicity was reported [1] - Drug interactions: No significant inhibition or induction of CYP450 enzymes was observed; co-administration with probenecid increased plasma concentrations of ampicillin and sulbactam by reducing renal excretion [1] |
| References |
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| Additional Infomation |
Sulfacillin tosylate is the tosylate form of sulfacillin, an oral fixed-dose combination prodrug composed of ampicillin (a semi-synthetic penicillin) and sulbactam (a β-lactamase inhibitor); the tosylate portion enhances water solubility, facilitates formulation development, and does not alter pharmacological activity [1] - Its antibacterial mechanism: ampicillin binds to bacterial PBPs, inhibiting peptidoglycan synthesis (essential for bacterial cell wall formation), leading to bacterial cell lysis; sulbactam irreversibly binds to β-lactamase, thereby preventing the hydrolysis of ampicillin by resistant bacteria [1] - Approved indications include respiratory tract infections (pneumonia, bronchitis), urinary tract infections (cystitis, pyelonephritis), skin and soft tissue infections, and intra-abdominal infections caused by susceptible Gram-positive and Gram-negative bacteria [1] - Clinical efficacy: In a phase III clinical trial, sulbactam tosylate (500 mg twice daily for 7-14 days) achieved a clinical cure rate of 85-90% for community-acquired pneumonia and 80-85% for uncomplicated urinary tract infections [1]. - This product is available in oral tablets and suspensions. The recommended adult dose is 500 mg twice daily (or 375 mg three times daily), depending on the severity of the infection. [1] - It is ineffective against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, or anaerobic bacteria (e.g., Bacteroides fragilis) due to low affinity for penicillin-binding protein (PBP) or the presence of resistance mechanisms. [1]
|
| Molecular Formula |
C32H38N4O12S3
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|---|---|
| Molecular Weight |
766.86
|
| Exact Mass |
766.164
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| Elemental Analysis |
C, 47.87; H, 5.27; N, 6.98; O, 27.90; S, 11.98
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| CAS # |
83105-70-8
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| Related CAS # |
76203-99-1 (HCl);76497-13-7 (free);83105-70-8;
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| PubChem CID |
444021
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| Appearance |
White to off-white solid powder
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| Boiling Point |
907.7ºC at 760 mmHg
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| Flash Point |
502.8ºC
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| LogP |
3.781
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
10
|
| Heavy Atom Count |
51
|
| Complexity |
1450
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| Defined Atom Stereocenter Count |
6
|
| SMILES |
S1([C@]2([H])C([H])([H])C(N2[C@@]([H])(C(=O)OC([H])([H])OC([C@@]2([H])C(C([H])([H])[H])(C([H])([H])[H])S[C@]3([H])[C@@]([H])(C(N32)=O)N([H])C([C@@]([H])(C2C([H])=C([H])C([H])=C([H])C=2[H])N([H])[H])=O)=O)C1(C([H])([H])[H])C([H])([H])[H])=O)(=O)=O.S(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(=O)(=O)O[H]
|
| InChi Key |
KNVDAMRBJYZXRW-ZAKZIJIGSA-N
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| InChi Code |
InChI=1S/C25H30N4O9S2.C7H8O3S/c1-24(2)17(29-20(32)16(21(29)39-24)27-19(31)15(26)12-8-6-5-7-9-12)22(33)37-11-38-23(34)18-25(3,4)40(35,36)14-10-13(30)28(14)18;1-6-2-4-7(5-3-6)11(8,9)10/h5-9,14-18,21H,10-11,26H2,1-4H3,(H,27,31);2-5H,1H3,(H,8,9,10)/t14-,15-,16-,17+,18+,21-;/m1./s1
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| Chemical Name |
[(2S,5R)-3,3-dimethyl-4,4,7-trioxo-4lambda6-thia-1-azabicyclo[3.2.0]heptane-2-carbonyl]oxymethyl (2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;4-methylbenzenesulfonic acid
|
| Synonyms |
Sultamicillin tosilate; Sultamicillin tosylate hydrate; Sultamicillin; CP-49,952; CP 49,952; CP49,952; CP-49952; CP 49952; CP49952. VD 1827; Bacimex; p-Toluenesulfonate Sbtpc; Unacid PD oral; acim orale.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100~125 mg/mL ( 130.4~163.00 mM )
Ethanol : ~100 mg/mL Water : ~9 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (2.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (2.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.08 mg/mL (2.71 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3040 mL | 6.5201 mL | 13.0402 mL | |
| 5 mM | 0.2608 mL | 1.3040 mL | 2.6080 mL | |
| 10 mM | 0.1304 mL | 0.6520 mL | 1.3040 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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