What Is Bacitracin?

Bacitracin, molecular formula C66H103N17O16S, white or light yellow powder; odorless, bitter taste; hygroscopic; easy to be destroyed by oxidants, can be precipitated by a variety of heavy metal salts in solution. This product is soluble in water, soluble in ethanol, and insoluble in acetone, chloroform or ether. Clinically, the antibacterial spectrum is similar to penicillin, and it has bactericidal effect on Gram-positive bacteria and negative cocci, diplococcus pneumoniae, staphylococcus, gonococcus, meningococcus and spirochaete. ^[1]

Chinese name: Bacitracin ^[1]
English name: Bacitracin ^[1]
nickname: Epirubicin hydrochloride
Chemical formula: C66H103N17O16S
Molecular weight: 1422.69
CAS Registry Number: 1405-87-4
EINECS registration number: 215-786-2

Melting point: 221-225 ° C
Boiling point: 1750.1ºC
Water soluble: Easy to contain in water
Density: 1.43 g / cm3
Exterior: White to almost white powder
Flash point: 1012.2ºC
Molecular formula: C66H103N17O16S ^[1]

Introduction to bacitracin compounds

Basic information of bacitracin

Chinese name: bacteriocin

Chinese alias: epirubicin hydrochloride

English name: Bacitracin

English alias: BACIDRIN; baci-jel; usafcb-7; baciguent; ayfivin; Agfivin; Zutracin; Bacitracin; Baciguen; ALTRACIN; septa;

CAS number: 1405-87-4

MDL number: MFCD00062640

EINECS number: 215-786-2

RTECS number: CP0175000

PubChem number: 24891503

Molecular formula: C ₆₆ H ₁₀₃ N ₁₇ O ₁₆ S

Structural formula:

Molecular weight: 1422.69000

Exact mass: 1421.75000

PSA: 556.17000

LogP: 3.72410

Physicochemical properties of bacitracin

Appearance and properties: white to almost white powder

Density: 1.43 g / cm ³

Melting point: 221-225 ° C

Boiling point: 1750.1ºC at 760 mmHg

Flash point: 1012.2ºC

Refractive index: 1.655

Water solubility: soluble

Stability: Stable under normal temperatures and pressures.

Storage conditions: ventilated, dry at low temperature, stored separately from food materials in the warehouse

Vapor pressure: 0mmHg at 25 ° C

Bacitracin safety information

Customs Code: 2941909000

Dangerous Goods Transport Code: 2811

WGK Germany: 2

Danger category code: R20 / 21/22

Safety instructions: S22; S24 / 25; S45; S36

RTECS number: CP0175000

Dangerous goods mark: Xn ^[2]

Bacitracin toxicology data

Acute toxicity: LD50 of rat abdominal cavity: 300mg / kg; LD50 of mouse abdominal cavity: 190mg / kg; LD50 of mouse oral cavity:> 3750mg / kg; LD50 of subcutaneous mouse: 1300mg / kg; LD50 of mouse vein: 360mg / kg kg; guinea pig mouth LD50: 2gm / kg; quail mouth LD50:> 316mg / kg

Molecular structure data of bacitracin

1. Molar refractive index: 365

2. Molar volume (cm / mol): 994.4

3. Isometric Zhang Rong (90.2K): 2761.7

4. Surface tension (dyne / cm): 59.4

5. Dielectric Constant: None available

6. Polarizability (10cm): 144.7

7. Mass of single isotope: 11421.74894 Da

8. Nominal mass: 1421 Da

9. Average quality: 1422.6933 Da

Bacitracin calculated chemical data

1. Number of hydrogen-bonded donors: 16

2. Number of hydrogen bond acceptors: 21

3. Number of rotatable chemical bonds: 31

4. Number of tautomers: 1001

5. Topological molecular polar surface area (TPSA): 527

6. Number of heavy atoms: 101

7. Surface charge: 0

8. Complexity: 2950

9. Number of isotope atoms: 0

10. Determine the number of atomic stereocenters: 0

11. Uncertain number of atomic stereocenters: 16

12. Determine the number of chemical bond stereocenters: 0

13. Uncertain number of chemical bond stereocenters: 0

14. Number of covalent bond units: 2

Bacitracin synthesis method

The producing bacteria is Bacillus subtilis. The culture medium is defatted soybean flour (5%), sucrose (1.2%), ammonium sulfate (0.2%), calcium carbonate (0.2%), and the like. The culture of bacteria can be divided into two stages: the development of bacteria and the production of antibiotics. The optimal temperature for producing bacitracin is about 37 ° C, and the temperature during the bacterial development period needs to be slightly higher than 1-2 ° C, and the aeration volume per minute is 90% of the fermentation broth volume. The bacitracin produced was adsorbed on a carboxylic acid-type exchange resin at a pH of 4-5.7, and then eluted with a weak base (ammonia).

Fermented from Bacillus licheni formus. Soybean flour, starch, corn extract, molasses and inorganic salts were used as the medium, inoculated 5% -10%, and fermented for 30-40h. After 7-8 hours of fermentation, the pH was reduced from 7.3-7.5 to 6.06; the initial temperature of the fermentation was controlled at about 30 ° C, and the temperature was increased to 37 ° C after 2-3 hours. After the fermentation was completed, the pH was adjusted to 5.5 with concentrated hydrochloric acid, and then 50 kg of zinc oxide was added to the 20M fermentation broth and mixed for 30 minutes. Then vacuum, evaporation and concentration to increase the dry matter content from 4.5% -5% to 17% -20%, and then spray-dried to obtain the product.

Use of bacitracin

This product is mainly added to feed as an animal growth promoter. As zinc, cadmium, and mercury salts are present, the activity of the product is enhanced, so zinc and manganese salts of the product are often used as feed additives. Growth promoters are non-nutritive additives that can stimulate the growth of livestock and poultry, increase the rate of weight gain and feed utilization, and improve the health of livestock and poultry. This product has a strong antibacterial effect on most Gram-positive bacteria, similar to penicillin, and also effective against penicillin-resistant Staphylococcus aureus. As a medicine, it is mainly used to treat various infections caused by drug-resistant Staphylococcus aureus, such as sepsis, pneumonia, and endocarditis.

Bacitracin storage method

Keep the container sealed and stored in a cool, dry place, and ensure that there is good ventilation or exhaust in the workplace ^[3]

Bacteriocin standard

Bacitracin source content

This product is calculated on a dry basis, and the potency per 1mg should not be less than 55 bacitracin units.

Bacitracin traits

This product is a white to light yellow powder; odorless, bitter taste; hygroscopic; easy to be destroyed by oxidants, and can be precipitated by a variety of heavy metal salts in solution.

This product is soluble in water, soluble in ethanol, and insoluble in acetone, chloroform or ether.

Bacitracin identification

Take an appropriate amount of this product and the standard bacitracin, and use 1% ethylenediamine tetraacetic acid disodium acetate solution to make a solution containing about 6.0mg per 1ml, as the test solution and standard solution, according to thin layer chromatography ( 2010 Pharmacopoeia Part II Appendix VB) Test, take 5l of each of the above two solutions respectively on the same silica gel GF254 thin-layer plate (activated at 105 ° C for 1 to 2 hours before use), and naturally dry it with n-butanol-ice Acetic acid-water-pyridine-ethanol (60: 15: 10: 6: 5) as a developing agent, develop, dry, spray with a 1% ninhydrin butanol-pyridine (99; 1) solution, and heat at 105 ° C About 5 minutes until brown-red spots appear. The position and color of the main spots displayed by the test solution should be the same as the position and color of the main spots of the standard solution.

Bacitracin test

Take this product, add water to make a solution containing 1000 units per 1ml, and measure it according to law (Appendix VIH of the second edition of the Pharmacopoeia, 2010 edition). The pH value should be 5.5 to 7.5.

Loss on drying

Take this product, use phosphorus pentoxide as a desiccant, and dry it under reduced pressure at 60 ° C for 3 hours. The weight loss should not exceed 5.0% (Appendix L of the second part of the Pharmacopoeia of the 2010 edition).

Determination of bacitracin content

Accurately weigh an appropriate amount of this product, and make a solution containing about 100 units per 1ml with sterilized water, and measure it according to the antibiotic microbiological test method (Appendix A tube dish method or turbidity method of the 2010 Pharmacopoeia Part II).

Bacitracin category

Antibacterials.

Bacitracin storage

Sealed and stored in a dry place.

Bacitracin preparation

(1) bacitracin ointment (2) bacitracin ointment (3) compound neomycin ointment ^[4]

Bacteriocin effect

Bacitracin is a polypeptide antibiotic with many components. It is a slow bactericide, which can specifically inhibit the dephosphorylation of the bacterial cell wall synthesis stage, affect the transport of phospholipids and deliver mucin to the cell wall scaffold, and inhibit the bacterial cell wall. It synthesizes and damages cell membranes, causing ions and amino acids to flow out and killing bacteria. Bacitracin has strong antibacterial activity against Staphylococcus aureus, drug-resistant Staphylococcus aureus, hemolytic streptococcus, Streptococcus pyogenes, pneumococcus, Neisseria, Haemophilus influenzae, and certain Gram-negative cocci, some Actinomyces, Treponema pallidum, and Amoeba have some activity, but are resistant to almost all Gram-negative bacilli. Systemic application can produce severe nephrotoxicity, local application is less irritating, rare allergic reactions, enzyme resistance, bacteria are slow to develop resistance to them, acquired resistant strains are extremely rare, and the potency is not affected by pus, sputum Fluid, blood, exudate, and necrotic tissue, it has been used as a local anti-infective agent so far. ^[5]

Bacitracin pharmacokinetics

Oral absorption is not obvious, there is no obvious absorption in local application, but it can be absorbed in a small amount when it is infused into a body cavity in large doses or used in large-scale surgical wounds. The intramuscular injection is rapid absorption, the plasma drug concentration peak time is 2h, it is widely distributed in the body, it is not easy to penetrate the blood-cerebrospinal fluid barrier, and the content is small when non-meningitis. Bacitracin is slowly excreted by glomerular filtration, and 10% to 40% of the excreted dose is excreted in the urine in the first 24 hours. There is no obvious absorption in local application, but a large amount of perfusion in the infected body cavity or surgical wound may have a slight absorption. ^[5]

Bacitracin indications

For local skin and soft tissue infections, skin wound infections, large-scale surgery or burns, eye and conjunctival infections, facial and oral infections, bladder irrigation, or pus injection. ^[5]

Bacitracin contraindications

1. Banned from allergic to bacitracin.

2. Renal insufficiency is disabled. ^[5]

Dosage of bacitracin

1. Disperse the drug powder topically, apply 0.05% ointment, 4 to 5 times a day, or inject the body cavity or flush the bladder with 0.05% to 0.1% solution, and apply 0.05% eye ointment 2 to 3 times a day.

2. Intramuscular injection: 900U / kg per day for children weighing less than 2.5kg and 1000U / kg per day for children weighing more than 2.5kg.

3. Intrathecal injection: 5000 ~ 10000U each time, dissolved in 0.9% sodium chloride solution to make 1000U / ml injection, once a day.

4. Oral: used for pseudomembranous enteritis caused by Clostridium difficile, 25000U each time, 4 times a day for 7 to 10 consecutive days. ^[5]

Bacitracin adverse reactions

1. Common skin mild skin allergies, rashes, itching, redness, irritation and sensation are usually mild, and severe systemic allergies are rare. Large doses of perfusion are slightly absorbed, which may cause nephrotoxicity.

2. Intramuscular injection can be painful and can cause hematuria, proteinuria, and local induration.

3. Oral nausea, vomiting, diarrhea, abdominal pain and other common reactions. ^[5]

Bacitracin considerations

1. Pregnant women and lactating women should be used with caution.

2. Intramuscular injection of renal tubular and glomerular necrosis has been reported, and renal function should be monitored. ^[5]

Interaction between bacitracin and other drugs

Combined with neomycin and polymyxin can expand the antibacterial spectrum. ^[5]

Bacitracin poisoning

The bacitracin has a bactericidal effect on gram-negative bacteria. Due to the severe renal toxicity of this drug, it is not used systemically, but only topically. Absorption is not obvious after oral administration of this drug; local application, such as a large amount of medication infused into the abdominal cavity, may be absorbed in trace amounts, which may cause renal toxicity. Local application may cause allergic reactions: local skin itching, rash, redness, or other irritation, and occasional reports of severe systemic allergic reactions caused by local application. Symptomatic treatment. ^[6]

Bacitracin expert review

Systemic application can produce severe nephrotoxicity, local application has little irritation, rare allergic reactions, and is resistant to enzymes. Bacteria develop resistance to it slowly, and acquired resistant strains are extremely rare. The potency is not affected by pus, sputum, blood, exudate and necrotic tissue, so it has been used as a topical anti-infective agent so far. ^[5]