Colistin sulfate CAS 1264-72-8
Introduction：Basic information about Colistin sulfate CAS 1264-72-8, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Colistin sulfate Basic information
| Product Name: | Colistin sulfate |
| Synonyms: | belcomycin;Animal Feed Additives colistin sulfate Colistin Sulfate;Animal Feed Additives colistin sulfate CAS 1264-72-8 Colistin Sulfate;liusuanlianjunsu;N-[4-amino-1-[[1-[[4-amino-1-oxo-1-[[6,9,18-tris(2-aminoethyl)-3-(1-hydroxyethyl)-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino;COLISTINE SULFATE;COLISTIN SULPHATE PURE GRADE;Colistin sulphate premix 10% 40% |
| CAS: | 1264-72-8 |
| MF: | 2(C52H98N16O13).5(H2SO4) |
| MW: | 2801.27 |
| EINECS: | 215-034-3 |
| Product Categories: | Intermediates & Fine Chemicals;Pharmaceuticals;Veterinaries;Active Pharmaceutical Ingredients;SYNCURINE;antibiotic;Inhibitors;API;1264-72-8 |
| Mol File: | 1264-72-8.mol |
Colistin sulfate Chemical Properties
| Melting point | 200-220°C |
| storage temp. | Inert atmosphere,2-8°C |
| solubility | H2O: soluble50mg/mL |
| form | powder |
| color | White to off-white |
| PH | 4.0～6.0（10g/l, 25℃） |
| Water Solubility | Soluble in water |
| Merck | 14,2479 |
| Specific Activity | ≥19,000IU/mg |
| Major Application | USP Biologics pharmaceutical (small molecule) |
| InChIKey | VEXVWZFRWNZWJX-NBKAJXASSA-N |
| SMILES | C(NC(C(=O)NC(C(=O)NC(C(=O)NC1CCNC(=O)C(C(O)C)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O)CCN)C(O)C)CCN)(=O)CCCC(C)CC.S(O)(O)(=O)=O |
| CAS DataBase Reference | 1264-72-8(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 25 |
| Safety Statements | 45 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | 3 |
| RTECS | TR1500000 |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| HS Code | 29419000 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 3 Oral |
| Chemical Properties | White or almost white, hygroscopic powder. |
| Uses | antibacterial |
| Uses | neuromuscular blocker |
| Uses | Cyclic polypeptide antibiotic produced by Bacillus polymyxa. Complex mixture of at least 30 components, primarily colistins A and B.[a]D= -65?(c= 1, Water) LOD: 3% |
| Uses | Colistin sulfate A Polymyxin potent antibiotic and apoptosis inducer. This compound induces apoptosis through interaction with the cytoplasmic membrane. Colistin is a key microbiological component in Colistin Oxolinic Acid Blood Agar utilized in the cultivation of Aminobacter aminovorans, Bacillus species, Hyphomicrobium species and Methylobacterium species. It is also a critical component is VCN Inhibitor & VCNT Inhibitor growth media used in the isolation of Neisseria species. |
| Brand name | Coly-Mycin (Monarch). |
| Antimicrobial activity | All the polymyxins have a similar antibacterial spectrum,although there are slight quantitative differences in theiractivity in vitro. They are inactive against Gram-positiveorganisms, but nearly all enterobacteria, except Proteus spp.,Burkholderia cepacia and Ser. marcescens, are highly susceptible.The MIC of polymyxin B or colistin sulfate for Esch. coliand Klebsiella spp. is 0.01–1 mg/L; the corresponding concentrationfor Ps. aeruginosa is 0.03–4 mg/L. Bacteroides fragilis isresistant, but other Bacteroides spp. and fusobacteria are susceptible.Resistance of V. cholerae eltor to polymyxin B distinguishesit from the classic vibrio. The sulfomethyl derivatives are generally 4–8 times lessactive than the sulfates, but their activity is difficult to measureprecisely since on incubation they spontaneously decayto the parent compound, with a corresponding progressiveincrease in antibacterial activity. Binding of polymyxins to the bacterial cell membrane canincrease permeability to hydrophilic compounds, includingsulfonamides and trimethoprim, producing significant synergy.Synergy with ciprofloxacin is also described. Calciumions exert a strong pH-dependent competition for membranebinding sites, and the presence of calcium and magnesiumions in certain culture media adversely affects the bactericidalactivity, notably against Ps. aeruginosa. |
| Acquired resistance | There is complete cross-resistance between the polymyxins,but stable acquired resistance in normally susceptiblespecies is very rare. Adaptive resistance, probably due tochanges in cell-wall permeability, is readily achieved by passageof a variety of enterobacteria in the presence of theagents in vitro. |
| General Description | In 1950, Koyama et al. isolated an antibiotic fromAerobacillus colistinus (B. polymyxa var. colistinus) thatwas given the name colistin (Coly-Mycin S). It was used inJapan and in some European countries for several years beforeit was made available for medicinal use in the UnitedStates. It is recommended especially for the treatment of refractory urinary tract infections caused by Gram-negativeorganisms such as Aerobacter, Bordetella, Escherichia,Klebsiella, Pseudomonas, Salmonella, and Shigella spp. Chemically, colistin is a polypeptide, reported by Suzukiet al. whose major component is colistin A. They proposedthe structure for colistin A differs from polymyxin B only by the substitution of D-leucine for D-phenylalanine as one of the amino acid fragments inthe cyclic portion of the structure. Wilkinson and Lowehave corroborated the structure and have shown that colistinA is identical with polymyxin E1. Two forms of colistin have been prepared, the sulfate andmethanesulfonate, and both forms are available for use in theUnited States. The sulfate is used to make an oral pediatricsuspension; the methanesulfonate is used to make an intramuscularinjection. In the dry state, the salts are stable, andtheir aqueous solutions are relatively stable at acid pH from 2to 6. Above pH 6, solutions of the salts are much less stable. |
| Hazard | A poison by ingestion. |
| Pharmaceutical Applications | Polymyxin B and colistin (polymyxin E); mixtures of sulfatesof polypeptides produced by strains of B. polymyxa andB. polymyxa var. colistinus. Colistimethate sodium (colistin sulfomethatesodium). Molecular weights: polymyxin B 1 1203;polymyxin B 2 1189; colistimethate sodium 1748. A group of basic polypeptide antibiotics with a side chain terminatedby characteristic fatty acids. Five polymyxins (A–E)were originally characterized and others have since beenadded. Polymyxin B and colistin (polymyxin E) sulfates havebeen commercially developed. By treatment with formalin and sodium bisulfite, five ofthe six diaminobutyric acid groups of the polymyxins can bemodified by sulfomethyl groups to form undefined mixturesof the mono-, di-, tri-, tetra- and penta-substituted derivatives.Sulfomethyl polymyxins differ considerably in their properties from the parent antibiotics: they are less activeantibacterially, less painful on injection, more rapidly excretedby the kidney and less toxic. Only colistimethate sodium isnow commercially available for systemic use, but polymyxinB and colistin sulfates are found as ingredients of several topicalformulations. |
| Biochem/physiol Actions | Mode of Action: Binds to lipids on the cell cytoplasmic membrane of Gram-negative bacteria and disrupts the cell wall integrity. Antimicrobial spectrum: Gram-negative bacteria. It is proposed that renal reabsorption of colistin may involve organic cation transporters and peptide transporters and that the process is sensitive to pH . |
| Pharmacokinetics | Oral absorption: Negligible Cmax (colistimethate sodium) 2 mega-units: 6–7 mg/L after 2–3 h (c. 16 mg colistin base) i.m. Plasma half-life (colistimethate sodium): c.4–6 h Plasma protein binding: Very low Absorption Polymyxins are not absorbed from the alimentary tract ormucosal surfaces, but can be absorbed from denuded areasor large burns. Distribution After parenteral administration of the sulfates, blood levels areusually low (1–4 mg/L 2 h after a 500 000 unit intramusculardose). Substantially higher plasma levels are obtained fromintramuscular injections of sulfomethyl polymyxins. Thereis some accumulation in patients receiving 120 mg every8 h. In patients treated intravenously with a priming dose of1.5–2.5 mg/kg followed by continuous infusion of 4.8–6.0 mg/hfor 20–30 h, steady state levels were around 5–10 mg/L.The volume of distribution is unknown, but polymyxinsdiffuse poorly into tissue fluids and penetration to cerebrospinalfluid is poor. As a result of binding to mammalian cellmembranes (sulfomethates less so), they persist in the tissues,where they accumulate on repeated dosage, although they disappearfrom the serum. Polymyxin crosses the placenta, butthe levels achieved are low. A small amount appears in thebreast milk. Metabolism and excretion The sulfates are excreted almost entirely by the kidney, butafter a considerable lag, with very little of the dose appearingin the first 12 h. The sulfomethyl derivatives are muchmore rapidly excreted, accounting for their shorter half-lives.Around 80% of a parenteral dose of colistimethate sodiumis eventually found in the urine, with concentrations reachingaround 100–300 mg/L at 2 h. The fate of the remainderis unknown, but no metabolic products have been describedand none is excreted in the bile. Polymyxins accumulate inrenal failure and are not removed by peritoneal dialysis. |
| Clinical Use | Colistimethate sodium Infections due to Ps. aeruginosa and other Gram-negative rods resistant toless toxic agents Cystic fibrosis (inhalation therapy for pseudomonas infection) Polymyxin B and colistin sulfate Component of preparations for local application Superficial infections with Ps. aeruginosa and to prevent the colonizationof burns Selective decontamination of the gut and as a paste for control ofupper respiratory tract colonization in patients on prolonged mechanicalventilation (in combination with other agents) |
| Side effects | Pain and tissue injury can occur at the site of injection of thesulfates, but this is less of a problem with the sulfomethylderivatives. Neurological symptoms such as paresthesia withtypical numbness and tingling around the mouth, dizzinessand weakness are relatively common, and neuromuscularblockade, sometimes severe enough to impede respiration,occurs. Evidence of nephrotoxicity is observed in about 20%of patients, leading to acute tubular necrosis in about 2%.Damage is more likely in patients with pre-existing renal disease.The appearance of any evidence of deterioration of renalfunction or of neuromuscular blockade calls for immediatecessation of treatment. All the toxic manifestations appear tobe reversible, but complete recovery may be slow. Although less toxic than the sulfate, untoward effectshave been observed in up to one-quarter of those treated with colistimethate sodium. Nephrotoxicity is common, withan increase in urea and creatinine over the first few days oftreatment. Acute tubular necrosis is heralded by the appearanceof proteinuria, hematuria and casts, sometimes withoutprior evidence of functional impairment. Renal damage usuallycontinues to progress for up to 2 weeks after withdrawalof therapy. Renal damage is likely to increase with the doseand with the simultaneous administration of other potentiallynephrotoxic agents.Manifestations of central and peripheral neurotoxicityoccur particularly in patients with impaired renal function.Neuromuscular blockade is seen principally in patients alsoreceiving anesthetics or other agents that impair neuromusculartransmission. Complete flaccid paralysis with respiratoryarrest and subsequent complete recovery has been seen in apatient with myasthenia gravis. Allergy is occasionally seen, andnebulized colistin has caused bronchial hyperreactivity withtightness in the chest in adults with cystic fibrosis. Applicationof colistin or polymyxin B ear drops can lead to ototoxicity. |
| Safety Profile | A poison by ingestion,intraperitoneal, subcutaneous, andintravenous routes. When heated todecomposition it emits toxic vapors of NOxand SOx. |
Colistin sulfate Preparation Products And Raw materials
| Preparation Products | Polymyxin B, N-sulfomethyl deriv., sodium salt-->COLISTIN |
