Acetylspiramycin is an organic compound with chemical formula Cforty-fiveHseventy-sixNtwoOfifteen[3]It is mainly used to treat respiratory system infection, pyoderma, scarlatina, etc.
Chinese name
Acetylspiramycin
Foreign name
Acetylspiramycin
chemical formula
Cforty-fiveHseventy-sixNtwoOfifteen
molecular weight
eight hundred and eighty-five point zero eight nine
Chemical formula: Cforty-fiveHseventy-sixNtwoOfifteen
Molecular weight: 885.089
CAS No.: 24916-51-6
Physical and chemical properties
Density: 1.21 g/cmthree
Melting point: 130-133 º C
Boiling point: 916.7 º C
Flash point: 508.2 º C
Refractive index: 1.543
Appearance: white powder[2]
purpose
It is mainly used to treat respiratory system infection, pyoderma, scarlatina, etc.
Pharmacopoeia standard
Announce
edit
essential information
This product is a mixture mainly composed of four components: monacetyl spiramycin Il, monacetyl spiramycin Il, diacetyl spiramycin Il and diacetyl spiramycin Il.The potency per 1mg of dried product shall not be less than 1200 acetylspiramycin units.
character
This product is white to yellowish powder.
This product is dissolved in methanol, ethanol, acetone or ether, almost insoluble in water, and insoluble in petroleum ether.
identify
1. Test according to thin layer chromatography (general rule 0502).
Test solution
Take this product and add methanol to prepare a solution containing about 5mg per 1mL.
Standard solution
Take acetylspiramycin standard and add methanol to prepare a solution containing about 5mg per 1mL.
Chromatographic conditions
Use a thin layer plate (take 0.6g of silica gel G, add 2.5mL of 0.1mol/L sodium hydroxide solution, grind it into a paste, mix it well, coat it on a 20cm × 5cm glass plate, dry it in the air, activate it at 105 ℃ for 30 minutes), and use toluene methanol (9:1) as the developing agent.
Assay
Take 10 µ L each of the test solution and the standard solution, dab them on the same thin layer plate, develop them, dry them, and color them in iodine vapor.
Result determination
The position and color of the four main spots of the test solution should be the same as those of the standard solution.
2. In the chromatogram recorded under the item of acetylspiramycin component determination, the retention time of the four main component peaks of the test solution should be consistent with the retention time of the four main component peaks of acetylspiramycin standard solution.
One of the above two items can be selected.
inspect
Loss on drying
Take this product, dry it at 105 ℃ to constant weight, and the weight loss shall not exceed 3.0% (general rule 0803).
Determination of acetylspiramycin components
Determine according to the method of high performance liquid chromatography (general rule 0512).
Test solution: Take an appropriate amount of this product, weigh it accurately, add mobile phase to dissolve it and dilute it quantitatively to prepare a solution containing about 1mg per 1mL.
Standard solution: Take an appropriate amount of acetylspiramycin standard, weigh it precisely, add mobile phase to dissolve it and dilute it quantitatively to make a solution containing about 1mg per 1mL.
Chromatographic conditions: octadecyl silicon bonded silica gel is used as filler.The mobile phase is acetonitrile-0.1mol/L ammonium acetate solution (60: 40) (adjust the pH value to 7.2 ± 0.1 with acetic acid), the detection wavelength is 232 nm, and the injection volume is 10 µ L.
System applicability requirements: the chromatogram of standard solution shall be consistent with the standard chromatogram.
Determination method: Precisely measure the test solution and standard solution, inject them into the liquid chromatograph respectively, and record the chromatogram. The peak sequence of each component of acetylspiramycin in the chromatogram of the test solution is as follows: monacetyl spiramycin II, monacetyl spiramycin III, diacetyl spiramycin II and diacetyl spiramycin Ill.The content of single and diacetyl spiramycin (II+III) is calculated according to the corresponding peak area in the chromatogram of the test solution according to the following formula.
Content of single acetylspiramycin (II+IIl)% ＝
Content of diacetyl spiramycin (II+IIl)%=
Where,ASingle IIIs the peak area of single acetylspiramycin II.
ASingle IIIIs the peak area of single acetylspiramycin III.
ADouble IIIs the peak area of diacetyl spiramycin II.
ADouble IIIIs the peak area of diacetyl spiramycin III.
The total content of the four components of acetylspiramycin is calculated according to the peak area of the external standard method according to the following formula.
Total content of four components of acetylspiramycin%=
Where,ATIs the total area of the four peaks of acetylspiramycin in the chromatogram of the test solution;
ASIs the total area of the four peaks of acetylspiramycin in the chromatogram of standard solution;
WTIs the weight of the test article;
WSIs the weight of the standard;
PIt is the total percentage content of the four components of the standard.
Limit: The content of single and diacetyl spiramycin (II+III) should not be less than 35%, and the total content of the four components of acetylspiramycin should not be less than 75%.
Assay
Accurately weigh an appropriate amount of the product, add ethanol to dissolve it (2mL of ethanol is added every 5mg), dilute it quantitatively with sterile water to make a solution containing about 1000 units per 1mL, and determine it according to the Antibiotic Microbiological Test Method (General Rule 1201).
category
Macrolide antibiotics.
Storage
Seal and store in a cool, dark and dry place.
preparation
1. Acetylspiramycin tablets.
2. Acetylspiramycin capsules.[4]
Determination method
Announce
edit
Chemical analysis method
overview
The amount of acetylspiramycin tablets is usually determined by microbiological method. The operation is tedious and time-consuming, and it is difficult to meet the needs of production. According to the literature, spiramycin has the maximum ultraviolet absorption at 232 mn of length.Therefore, the content of acetylspiramycin was determined by UV spectrophotometry, and the determination conditions were investigated.Compared with biological method, the results are satisfactory.This method is simple and rapid, and can be used as a reference for pharmaceutical factories to monitor the quality of spiramycin tablets and their intermediate products.
Acetylspiramycin reference substance, Hunan Yueyang Institute for Drug Control.
Acetylspiramycin tablet and intermediate Harbin No.3 Traditional Chinese Medicine Factory.
Methanol is analytically pure.
Phosphate buffer solution: prepared according to the appendix of Chinese Pharmacopoeia.
Selection of measurement conditions
Ultraviolet absorption spectrum of acetylspiramycin: weigh an appropriate amount of acetylspiramycin, dissolve it with methanol, and prepare a solution with a concentration of 10 μ g/mL with distilled water. With distilled water as a blank, automatically scan on the μ V-2101 ultraviolet spectrophotometer (with a wavelength of 200~300nm), and there is maximum absorption at the wavelength of 232nm.
Relationship between concentration and absorbance: accurately weigh an appropriate amount of acetylspirillum standard, dissolve it with methanol, prepare it with distilled water to the concentration of 5, 7, 10, 13, 15, 18, 20 μ g/mL, and determine the absorbance at 232 nm. It is found that there is a linear relationship between the absorbance and the absorbance in the range of 5-18 μ g/mL, and the linear equation is:A=0.001323+0.0305×c, correlation coefficientR=0.9993。
Relationship between blank storage and absorbance: accurately weigh three equal parts of acetylspiramycin standard, dissolve them with methanol, respectively use distilled water, 7.8 phosphate buffer, methanol to make 10 μ g/mL solution, and determine the absorbance.It can be seen that the blank solution has little effect on the degree of warming.In this experiment, distilled water was selected as the dilution blank group.
Determination of tablet content
Take 10 tablets of the product and weigh them precisely. After grinding, weigh accurately an appropriate amount (about 0.1g of spiramycin), dissolve and wash it in 100mL volumetric flask with 20mL methanol in batches, dilute it with distilled water to the scale, measure the absorbance at 232nm with distilled water as a blank, and calculate the content according to the standard curve.
Recovery experiment
Accurately weigh three portions of acetylspiramycin, add appropriate amount of dextrin, magnesium stearate and other auxiliary materials according to the prescription, and mix evenly. The average recovery rate measured according to the law is 98.98%, and the coefficient of variation is 0.27%.
Comparison between ultraviolet spectrophotometry and bioassay
Take spiramycin tablets of the same batch number and use two methods to determine them respectively.
discuss
1. The experimental results show that the maximum absorption of caprylspiramycin in various concentrations is about 232 nm, and the absorbance is linear with the concentration in the range of 5~18 μ g/mL.
2. Due to the difference between the reference substance and its potency, the curves obtained from different reference substances are slightly different, so the standard curve should be made for each batch of production.
3. After several times of comparison, this method can be used in pharmaceutical factories to control the content of intermediates in the production of spiramycin tablets.
4. After the sample is dissolved in methanol, which diluent should be used? After many experiments, the results measured with 7.8 phosphate buffer solution are higher, and the results measured with methanol or distilled water are close. Considering the economy, distilled water is selected for this experiment.
microbiological assay
Method name
Acetylspiramycin API Determination of acetylspiramycin Microbiological assay of antibiotics
Scope of application
The method adopts antibiotic microbiological assay to determine the content of acetylspiramycin in acetylspiramycin raw material drug.
The method is suitable for acetylspiramycin raw material.
Methodology
After the test article is dissolved in ethanol, sterilized water is added to make a solution containing about 1000 units per 1mL, which is determined according to the antibiotic microbiological assay method.
reagent
1. Ethanol
2. Sterilized water
3. Bacillus subtilis suspension
4. Medium II
Instrument and equipment
Sample preparation
1. Bacillus subtilis suspension
Take the nutrient agar slant culture of Bacillus subtilis [CMCC (B) 63 501], inoculate it into the culture bottle containing the nutrient agar culture medium, cultivate it at 35~37 ℃ for 7 days, and use the Gram staining method to smear for microscopic inspection. It should have more than 85% of the spores.Wash the spores with sterilized water and heat them at 65 ℃ for 30 minutes for standby.
2. Medium II
Mixed frozen 6g, beef extract 1.5g, yeast extract 6g and water 1000mL. Adjust the pH to make it slightly higher than the final pH by 0.2~0.4. Add 15~20g agar, heat it, dissolve it, filter it, add 1g glucose to dissolve it, shake it up, adjust the pH value to make it 8.0~8.2 after sterilization, and sterilize it at 115 ℃ for 30 minutes.
3. Preparation of test solution
Accurately weigh an appropriate amount of the test article, add ethanol to dissolve it (2mL of ethanol is added every 5mg), and add sterile water to make a solution containing about 1000 units per 1mL, which is the test article solution.
Note: "Precision weighing" means that the weighing shall be accurate to one thousandth of the weighing weight."Precision measurement" means that the accuracy of volume measurement shall meet the accuracy requirements of the national standard for the volume pipette
Operation steps
Take the test solution for determination according to the antibiotic microbiological assay.
Drug description
Announce
edit
pharmacological action
Spiramycin is a macrolide antibiotic obtained from Streptomyces ambofaciens culture medium.Acetylspiramycin is the acetate of spiramycin, which shows strong antibacterial effect by deacetylation after oral administration.Acetylspiramycin is a strong bacteriostatic agent, which has bactericidal effect only at a very high concentration.Its antibacterial mechanism is the same as that of erythromycin. By combining with the 50S subunit of bacterial ribonucleoprotein body, it blocks the extension of peptide chain and affects the synthesis of bacterial protein to achieve antibacterial effect.The antibacterial activity of acetylspiramycin is similar to that of spiramycin, but its in vitro activity is weaker than that of spiramycin.The antibacterial spectrum of acetylspiramycin is similar to that of erythromycin, with less antibacterial activity than erythromycin, and lower oral bioavailability than erythromycin. However, many erythromycin resistant Staphylococcus aureus are sensitive to acetylspiramycin.In addition, acetylspiramycin has better post antibiotic effect than erythromycin.The bacteria showed partial cross resistance to acetylspiramycin and erythromycin.Acetylspiramycin has strong antibacterial activity against Staphylococcus aureus, hemolytic streptococcus, pneumococcus, diphtheria bacillus, anthrax bacillus and clostridium;In addition, acetylspiramycin also has a strong effect on Listeria, Branhamma catarrhalis, Neisseria gonorrhoeae, Campylobacter foetus, Influenza bacillus, Pertussis bacillus, Bacteroides, Aerocapsulatum, Propionibacterium acnes, Digestive coccus and Digestive Streptococcus, as well as Mycoplasma, Chlamydia, Treponema pallidum, Toxoplasma, Cryptosporidium, etc.[1]
Pharmacokinetics
Acetylspiramycin was slightly affected by gastric acid after oral administration, about 40% of which was absorbed.Acetylspiramycin 100mg and 200mg were taken orally, and the peak plasma concentration was 0.8mg/L and 1mg/L respectively at 2h.The drug is widely distributed after absorption.The concentration in urine, pus, bronchial secretions and lung tissue is higher than that in blood, and when the blood concentration drops to the lowest, there is still a higher drug concentration in the tissue.The concentration of the drug in the lung, liver and bile is higher (the concentration in bile can reach 7~10 times of the serum concentration).Acetylspiramycin can penetrate into macrophages, and also through the placental barrier and blood cerebrospinal fluid barrier. The concentration of acetylspiramycin in cerebrospinal fluid during meningitis is 65% of the blood concentration.After absorption, the drug is first metabolized to spiramycin in the liver.The half-life of acetylspiramycin is longer than that of erythromycin and spiramycin, and it can accumulate in the body after repeated administration.
indication
It is applicable to tonsillitis, bronchitis, pneumonia, pharyngitis, otitis media, skin and soft tissue infections, mastitis, cholecystitis, scarlatina, dental and ophthalmic infections caused by staphylococcus, streptococcus pyogenes, streptococcus pneumoniae, meningococcus, gonococcus, diphtheria, mycoplasma, treponema pallidum and other sensitive bacteria.Clinically, it is mainly used for infections caused by Staphylococcus aureus, Streptococcus, Pneumonia, Escherichia coli, and Neisseria gonorrhoeae, such as pneumonia, bronchitis, lung abscess, scarlet fever, osteomyelitis, urethritis, mastitis, stylosoma, and dacryocystitis.[1]
contraindication
Allergies to acetylspiramycin and other macrolides
matters needing attention
1. Cross allergy: people who are allergic to one kind of macrolide may also be allergic to other macrolide drugs.
3. Influence of drugs on test value or diagnosis: A few patients may have increased serum alkaline phosphatase, bilirubin, alanine aminotransferase and aspartate aminotransferase after taking drugs.
Usage and dosage
1. Adults: 0.8-1.2g per day, three to four times, and 1.6-2g per day for severe cases.
2. Children: 20~30mg/kg per day, divided into 2~4 times.
Drugs for pregnant and lactating women
This product can penetrate into the placenta, so it should be used in pregnant women after fully weighing the advantages and disadvantages.There is no data to show whether acetylspiramycin is excreted through milk, but since many macrolide drugs can be excreted through milk, lactating women should use this product with caution, and if necessary, breast feeding should be suspended.
Adverse reactions
1. Gastrointestinal reactions were lighter than erythromycin, mainly including nausea, vomiting, dry mouth and anorexia.It often occurs in large doses of medication, and the symptoms disappear after drug withdrawal.
2. Occasionally, there are skin rash, drug rash and other allergic reactions.
3. Occasionally, dizziness, headache, lethargy and fatigue symptoms occur.
4. Occasionally, abnormal liver function (temporarily elevated aminotransferase) was reported.[1]
Drug interactions
1. When used together with metronidazole, it has synergistic antibacterial effect on Bacteroides fragilis in vitro.
2. When used with trimethoprim, it has synergistic antibacterial effect on Haemophilus influenzae.
3. Combined with cytochrome P450 metabolic drugs, the concentration of carbamazepine, terfenadine, cyclohexbarbital and phenytoin sodium in serum can be increased.
4. When combined with levodopa/carbido/carbidopa, the area under the time concentration curve (AUC) of levodopa can be reduced.
poisoning
Acetylspiramycin is made by acetylation of spiramycin. Its antibacterial spectrum is similar to that of erythromycin. It is transformed into spiramycin in vivo to play an antibacterial effect.Oral absorption was improved and the properties were stable.It can be taken after meals, with low adverse reactions of digestive tract.The common dosage for adults is 0.2g, 4/d.Adverse reactions may be treated symptomatically.
