What Is Thiamphenicol?

Methanesulfomycin is a white to off-white crystalline powder or crystal. Melting point (° C) 178-180 (mixed rotation), 164-166 (right rotation). Its chemical formula is [R- (R *, R *)] N- [1- (hydroxymethyl) -2-hydroxy-2- [4- (methylsulfonyl) phenyl] ethyl] -2,2 -Dichloroacetamide, soluble in dimethylformamide, slightly soluble in absolute ethanol, slightly soluble in water. It is mainly used in the clinical treatment of respiratory, urinary, hepatobiliary, typhoid and other intestinal surgery, gynecological and pediatric infections, especially for moderate and mild infections.

Chinese name: Methanesulfomycin
Foreign name: thiamphenicol

CAS number: 15318-45-3
Molecular formula: C12H15Cl2NO5S

Brief Introduction of Methanesulfomycin Compounds

Methanesulfomycin Basic Information

Chinese name: methanesulfomycin

Chinese alias: Methylsulfone Chloramphenicol

English name: thiamphenicol

English alias: Neomyson; 2,2-Dichloro-N-[(1R, 2R) -1,3-dihydroxy-1- [4- (methylsulfonyl) phenyl] -2-propyl] acetamide; thiocymetin; D-Thiophenicol; ThiaMphenicol ; Dextrosulphenidol; Thiamphenicol; 8065c.b.; Win-5063-2; THIAMPHENICHOL; D-Thiocymetin; thiophenicol;

CAS number: 15318-45-3

MDL number: MFCD00467983

EINECS number: 239-355-3

RTECS number: AB6680000

BRN number: 2819542

PubChem number: 24899874

Molecular formula: C ₁₂ H ₁₅ Cl ₂ NO ₅ S

Structural formula:

Molecular weight: 356.22200

Exact mass: 355.00500

PSA: 112.08000

LogP: 1.87600 ^[1]

Physical and Chemical Properties of Methanesulfomycin

Appearance and properties: off-white solid

Density: 1.491g / cm ³

Melting point: 163-166ºC

Boiling point: 695.9ºC at 760mmHg

Flash point: 374.7ºC

Refractive index: 1.589

Stability: Stable at normal temperatures and pressures. ^[1]

Molecular Structure Data of Methylsulfomycin

V. Molecular property data:

1. Molar refractive index: 79.78

2. Molar volume (m / mol): 238.7

3. Isometric ratio (90.2K): 661.0

4. Surface tension (dyne / cm): 58.7

5. Polarizability (10cm): 31.62 ^[2]

Calculated Chemical Data for Methanesulfomycin

1. Hydrophobic parameter calculation reference value (XlogP): None

2.Number of hydrogen-bonded donors: 3

3.Number of hydrogen bond acceptors: 5

4.Number of rotatable chemical bonds: 6

5.Number of tautomers: 2

6. Topological molecular polar surface area 112

7.Number of heavy atoms: 21

8.Surface charge: 0

9.Complexity: 443

10.Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 2

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 0

14. Uncertain number of chemical bond stereocenters: 0 ^[2]

15.Number of covalent bond units: 1

Methromycin use

It is mainly used for the treatment of respiratory, urinary, hepatobiliary, typhoid and other intestinal surgery, gynecological and pediatric infections, especially for moderate to mild infections. ^[2]

Methromycin Pharmacopoeia Standard

Source (name) and content (potency) of methanesulfomycin

This product is [R- (R, R)] N- [1- (hydroxymethyl) -2-hydroxy-2- [4- (methylsulfonyl) phenyl] ethyl] -2,2-di Chloroacetamide. Calculated on dry basis, containing C12H15Cl2NO5S shall not be less than 98.0%.

Methromycin traits

This product is white crystalline powder; odorless.

This product is soluble in dimethylformamide, slightly soluble in anhydrous ethanol, slightly soluble in water.

Melting point

The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 163 to 167 ° C.

Specific rotation

Take this product, weigh it accurately, add dimethylformamide to dissolve and quantitatively dilute it to make a solution containing about 50mg per 1ml, and measure it according to law (Appendix VI E of the Pharmacopoeia Part II of the 2010 edition). The specific rotation is -21 ° to -24 °.

Absorption coefficient

Take this product, accurately weigh it, dissolve it with water (about 40 ° C heating aid) and quantitatively dilute it to make a solution containing about 0.2mg per 1ml, according to the ultraviolet-visible spectrophotometry (Appendix IVA of the second edition of the Pharmacopoeia of the 2010 edition), The absorbance was measured at the wavelengths of 266nm and 273nm, and the absorption coefficients were 25-28 and 21.5-23.5, respectively: Precisely measure the appropriate amount of the test solution mentioned above, and quantitatively dilute with water to make a solution containing about 10g per 1ml. The absorbance was measured at a wavelength of 224 nm, and the absorption coefficient () was 370 to 400.

Methromycin identification

(1) Take an appropriate amount of this product and a reference product of methanesulfomycin, dissolve and dilute it in methanol to make a solution containing about 10 mg per 1 ml, and perform the test according to thin layer chromatography (Appendix VB of Part Two of the Pharmacopoeia, 2010 Edition). 5 l of each solution were spotted on the same silica gel GF254 thin layer plate, using ethyl acetate-methanol (97: 3) as a developing agent, developed, dried, and examined under an ultraviolet light (254 nm). 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 reference solution.

(2) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.

(3) The infrared absorption spectrum of this product should be the same as that of the control (Figure 594 of the "Infrared Spectra of Drugs").

(4) Take 5ml of 0.1% solution of this product, and add 2ml of 0.1mol / L silver nitrate solution, no precipitation will occur. Take 50 mg of this product, add 2 ml of potassium hydroxide test solution made of ethanol to dissolve, prevent ethanol from scattering, and heat in a water bath for 15 minutes. The solution shows a chloride identification reaction (Appendix III of Part Two of the 2010 Pharmacopoeia).

The above two items (1) and (2) are optional.

Methanesulfomycin test

Take 0.1g of this product, add 20ml of water to dissolve, add 0.1ml of bromothymol blue indicator liquid; if it is blue, add 0.10ml of hydrochloric acid titration solution (0.02mol / L), the strain should be yellow; if it is yellow, add hydrogen Sodium oxide titration solution (0.02mol / L) 0.10ml, the strain turned blue.

relative substance

Take this product, add the mobile phase to dissolve and dilute it to make a solution containing 1mg per 1ml as the test solution; take 1ml precisely, place it in a 100ml volumetric flask, dilute to the mark with the mobile phase, shake well, and use it as a control solution . According to the chromatographic conditions under the content determination item, take 10 l of the control solution and inject it into the liquid color, spectrometer, and adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full range; the precise amount is taken for the test solution and the control Each 10 l of the solution was injected into a liquid chromatograph, and the chromatogram was recorded to 3.5 times the peak retention time of the main component. If there are impurity peaks in the chromatogram of the test solution, the area of a single impurity peak should not be greater than the area of the main peak of the control solution (1.0%); the sum of the area of each impurity peak should not be greater than 2 times the area of the main peak of the control solution (2.0%). Any peak less than 0.05 times the area of the main peak of the control solution in the solution chromatogram is negligible.

chloride

Take 0.5g of this product, add 30ml of water, shake for 5 minutes, filter, take 15ml of filtrate, add 1.5ml of dilute nitric acid, and immediately add 1ml of 0.1mol / L silver nitrate solution, leave it in the dark for 2 minutes, check according to law (2010 Appendix A) of the second edition of the Pharmacopoeia of the Year Edition, compared with the control solution made of 5.0ml of standard sodium chloride solution, it must not be more concentrated (0.02%).

Loss on drying

Take this product and dry it at 105 ° C to constant weight, and the weight loss shall not exceed 1.0% (Appendix L of Pharmacopoeia Part II of 2010 Edition).

Residue on ignition

Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.

Heavy metal

Take the residue left under the burning residue and inspect it according to law (Appendix H of the 2010 edition of the Pharmacopoeia, the second method). The heavy metal must not exceed 10 parts per million.

Determination of Methanesulfomycin

It was determined by high performance liquid chromatography (Appendix D, Part Two of the Pharmacopoeia, 2010 Edition).

Chromatographic conditions and system suitability tests

Octadecylsilane-bonded silica gel was used as the filler; water-acetonitrile (4: 1) was used as the mobile phase; the detection wavelength was 225 nm. Take 25mg of this product, put it into a 25ml measuring flask, add 2ml of 1mol / L sodium hydroxide solution to dissolve, leave it at room temperature for 10 minutes, add 2ml of 1mol / L hydrochloric acid solution, dilute to the mark with mobile phase and shake well. Measure 5ml, put it into a 50ml measuring bottle, add 5mg of methromycin reference substance, dissolve with mobile phase and dilute to the mark, shake well, take 10l into the liquid chromatograph, record the chromatogram, alkaline degradation of methromycin The resolution of the product peak and the sulfomycin peak should meet the requirements.

Assay

Take about 0.1g of this product, accurately weigh it, place it in a 100ml measuring bottle, add the mobile phase to dissolve and dilute it to the mark, and shake well. Take a precise amount of 5ml, place it in a 50ml measuring bottle, dilute to the mark with the mobile phase, and shake well. Precisely measure 10 l into the liquid chromatograph and record the chromatogram; another appropriate amount of the sulfomycin reference substance was measured in the same way. Calculate the peak area according to the external standard method. ^[3]

Methromycin drug analysis

Method name: Methromycin Enteric-Coated Tablets-Methromycin-High Performance Liquid Chromatography

Scope of application: This method uses high-performance liquid chromatography to determine the content of methanemycin in methanesulfomycin enteric-coated tablets.

This method is suitable for enteric-coated tablets.

Principle of the method: research the test product, dissolve it in mobile phase and dilute it quantitatively, enter the high performance liquid chromatography for chromatographic separation, and use UV absorption detector to detect the peak area of methanesulfomycin at a wavelength of 225nm and calculate its content .

Reagent: acetonitrile

Equipment: 1. Instrument

1 HPLC

2 Column

Octadecylsilane bonded silica is a filler.

3 UV absorption detector

Chromatographic conditions

1 Mobile phase: water acetonitrile = 4 1

2 Detection wavelength: 225nm

3 Column temperature: room temperature

Sample preparation: 1. Preparation of reference solution

Precisely weigh 0.1g of methanesulfomycin reference substance, place it in a 100mL volumetric flask, add the mobile phase to dissolve and dilute to the mark, shake well, and accurately measure 5mL, place it in a 50mL volumetric flask, add the mobile phase to the scale, and shake well Is the reference solution.

Preparation of test solution

Take 10 test samples, accurately weigh, grind carefully, accurately weigh an appropriate amount (approximately 0.1 g of methylsulfomycin), place it in a 100mL volumetric flask, add an appropriate amount of mobile phase, and shake to dissolve the methylsulfomycin and use Dilute the mobile phase to the scale, shake well, and filter. Measure 5 mL of the filtrate and place it in a 50-mL volumetric flask. Add the mobile phase to the scale and shake well to obtain the test solution.

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards.

Operation steps: Precisely draw 10 mL of each of the reference solution and the test solution, inject them into a high-performance liquid chromatograph, and use an ultraviolet absorption detector to measure the peak area of methanesulfomycin (C12H15Cl2NO5S) at a wavelength of 225 nm, and calculate its content. ^[4]

Methromycin pharmacological action

This product is a methylsulfone derivative of chloramphenicol. It is a synthetic broad-spectrum antibacterial drug. Its antibacterial spectrum and antibacterial effect are basically similar to chloramphenicol. It mainly diffuses into bacterial cells and reversibly binds to the 50S of bacterial ribosomes. On the subunit, the growth of the peptide chain is blocked (possibly inhibiting the effect of transpeptidase), the formation of the peptide chain is inhibited, and the synthesis of the protein is prevented, thereby playing an antibacterial effect. Its antibacterial activity is not as good as chloramphenicol except for Streptococcus pyogenes, Pneumococcus, Pertussis, and Shigella dysenteriae; it has a strong effect on Gram-positive bacteria such as pneumococcus and hemolytic streptococcus; , Salmonella or Escherichia coli, pneumoniae, etc. are slightly worse than chloramphenicol. It also has certain effects on anaerobic bacteria, Borrelia, Rickettsia, Amoeba. This product does not easily penetrate the bacterial cell wall, which makes the antibacterial effect in vitro slightly weaker than chloramphenicol. In contrast, this product is not inactivated in combination with glucuronic acid in the liver, and the content of free active methoxamycin in the blood is higher, so it has stronger antibacterial activity, and the resistance of bacteria to methoxamycin is slower. And has complete cross-resistance to chloramphenicol. Methanesulfomycin still has a strong immunosuppressive effect (about 6 times stronger than chloramphenicol), which can inhibit immunoglobulin synthesis and antibody production. ^[5]

Methromycin pharmacokinetics

This product is well absorbed after oral or injection administration. The absorption is rapid and complete. The peak plasma drug concentration is reached within 2 hours after oral administration and within 1 hour after intramuscular injection. The peak blood dose of normal people after oral, intramuscular and intravenous injection of 0.5 g Concentrations were above 4.7-9 g / ml, and then slowly decreased. Plasma drug concentration and maintenance time were higher and longer than chloramphenicol. After every 6 to 8 hours of administration, it can be quickly and widely distributed to various tissues throughout the body. Among them, the kidney, spleen, liver, and lung are more abundant, and the content in the kidney and liver is approximately about the same dose as chloramphenicol. It is 3 to 4 times higher and can reach a certain concentration in the brain tissue. Due to the presence of enterohepatic circulation, the concentration in the bile is also high. It is easy to enter the cerebrospinal fluid through the blood-cerebrospinal fluid barrier, and it can also be infiltrated into milk and purulent and mucus in small amounts. Sexual sputum. Plasma half-life is 1.5h, and it has less binding to plasma proteins. This product does not combine with glucuronic acid in the liver. It is excreted from the bile as the original drug, and part of it is secreted by the renal tubules. 70% to 90% of the excreted dose is excreted in urine in 24 hours. Adults can take 0.5g orally. Up to 400 g / ml, urine output is significantly reduced when renal function declines, and the body may have a tendency to accumulate. ^[5]

Methanesulfomycin indications

It is used for infections of respiratory system, hepatobiliary system, urinary system and digestive system caused by influenza bacilli, Escherichia coli and salmonella. It also has a certain effect on typhoid, paratyphoid and brucellosis; it is also used for gonorrhea and gonorrhea. ^[5]

Methylsulfomycin Usage and Dosage

Adults: (1) Oral administration: 1.5 to 3.0 g per day, divided into 3 to 4 times. (2) Gas-soluble inhalation: 5% to 10% sulfomycin solution is available for gas-soluble inhalation. (3) Intrathoracic, intraperitoneal and intravesical administration: 0.5 1g each time.
Oral administration for children: 25-50 mg / kg daily, divided into 4 doses.
For typhoid fever: 3g orally every day on day 1 to 3, 1.5g a day on day 4 to 6, and 1g a day thereafter;
For gonorrhea: a single dose of 2.5g.
Intramuscular injection, intravenous injection: the same dose as oral. ^[5]

Metomycin Contraindications

During pregnancy, especially during the last trimester or childbirth.
Newborns, premature babies. ^[5]

Methromycin adverse reactions

This drug has fewer adverse reactions than chloramphenicol.

Myelosuppression: Reversible myelosuppression is the most serious adverse reaction of this drug. This response is related to the dosage and course of treatment. It is common in patients whose blood concentration exceeds 25 g / ml. Clinical manifestations are anemia, and can be associated with leukocytes and thrombocytopenia.
Aplastic anemia: Aplastic anemia is rare after medication. Its clinical manifestations include bleeding tendency due to thrombocytopenia, concurrent stasis, ecchymosis, and nosebleeds, as well as signs of infection caused by granulocytopenia, such as high fever, sore throat, and jaundice.
Gray infant syndrome: There have been no reports of "gray infant syndrome" caused by the use of this drug in preterm infants and newborns, and only cases of transient skin and pale appearance have been reported.
Hepatotoxicity: People with existing liver disease may cause jaundice, liver fat infiltration, and even acute severe hepatitis after administration.
Allergic reactions: Allergic reactions such as rash, solar dermatitis, angioedema, and drug fever are rare after taking the drug, and the general symptoms are mild, and they can quickly improve after stopping the drug.
Nervous system: Peripheral neuritis and optic neuritis can occur after long-term medication, manifesting as neurological symptoms such as hearing loss, insomnia, hallucinations, delirium, etc., which are mostly reversible. Optic nerve atrophy and blindness have also been reported after long-term use.
Gastrointestinal reactions: Gastrointestinal symptoms such as loss of appetite, nausea, vomiting, epigastric discomfort, and diarrhea are more common after administration, and their incidence is about 10% or less.
Double infection: After long-term use, the normal flora in the body can be reduced, causing a double infection.
Others: (1) Some patients with congenital glucose-6-phosphate dehydrogenase deficiency may develop hemolytic anemia after administration; (2) Long-term oral administration may inhibit the intestinal flora and hinder vitamin K synthesis and induce Bleeding tendency. ^[5]

Methylsulfomycin precautions

Use with caution: (1) those with liver dysfunction; (2) those with impaired renal function; (3) those who are old and weak.
During the treatment process, the blood routine should be checked regularly. Long-term treatment patients still need to check the reticulocyte count and timely find the adverse reactions of the blood system.
If there is a tendency to decrease the white blood cell count, the drug should be stopped immediately.
Renal insufficiency is reduced in the excretion of methamycin, and the body may have a tendency to accumulate and should be reduced.
When the copper sulfate method was used to determine urine glucose, it could be false positive.
During the medication, the whole blood image should be checked regularly; long-term treatment patients still need to check the reticulocyte count; if necessary, bone marrow examination is performed in order to find the blood system adverse reactions in time. ^[5]

Methromycin for pregnant and lactating women:

It should be avoided as much as possible during pregnancy, especially during late pregnancy or during childbirth. Breastfeeding women should suspend breastfeeding when applied.

Methromycin for children:

Due to immature liver enzyme system and poor renal excretion function in newborns, the excretion of the drug from the kidney is slower than that in adults. Therefore, the application of this product in newborns may lead to high blood concentrations and toxic reactions (grey infant syndrome). Newborns should avoid it. ^[6]

Methromycin Interaction

The drug is used together with hydantoin antiepileptic drugs to inhibit the activity of liver cell microsomal enzymes, leading to a decrease in the metabolism of such drugs, or to replace the serum protein binding site of such drugs, so that hydantoin can act Enhancement or increased toxicity.
Used together with hypoglycemic agents (such as tolbutamide), it can replace the serum protein binding site of hypoglycemic drugs and enhance the hypoglycemic effect.
Combined with certain myelosuppressive drugs (colchicine, hydroxybutazone, batazone and penicillamine, etc.) can increase the bone marrow suppressive effect of these drugs.
When used in combination with the induction anesthetic alfentanil, due to its inhibitory effect on liver enzymes, it can reduce the clearance of alfentanil and prolong the effect of anesthetic.
The same use with vitamin B6 can antagonize the effect of vitamin B6 and increase its renal excretion rate, leading to the occurrence of anemia or peripheral neuritis.
Used with iron, folic acid, and vitamin B12, it can antagonize the hematopoiesis of these drugs.
The same use with -lactam antibiotics can antagonize the antibacterial effect of -lactam drugs.
Use with estrogen-containing contraceptives can reduce the effectiveness of the contraceptives and may increase extramenstrual bleeding.
It has an antagonistic effect when used with lincomycin and erythromycin drugs, because such antibiotics can replace or prevent the combination of methosomycin and the 50S subunit of bacterial ribosomes.
When used in combination with phenobarbital, phenytoin, and rifampin, these drugs can induce liver enzymes and reduce the blood concentration of methosulfin.
Probenecid can slow the excretion of this product and increase the blood concentration. ^[5]

Methanesulfomycin Expert Reviews

Methanesulfomycin has higher antibacterial activity in vivo, but its effects on Salmonella, Escherichia coli, and Pneumococcus are slightly worse than that of amomycin, and it is completely cross-resistant to chloramphenicol. This product is more suitable for respiratory infections, urinary tract infections and biliary system infections. In a multi-center clinical trial organized by 15 hospitals in Shanghai, a total of 344 patients were selected, including 176 cases of respiratory, urinary, biliary, and digestive infections, 121 cases of bronchial infections, and 47 cases of skin infections. The results were effective. They are 88%, 86%, and 53%, respectively. Among them, the effect is the best for treating pustular psoriasis, and the condition is quickly controlled once the drug is used. It is reported abroad that this product is successfully used in Japan and Europe for the treatment of gonococcal urethritis, and a single oral dose of 2.5g has the same effect as spectinomycin and cefuroxime. From 1960 to 1974, more than 6 million cases have been treated with this product in France alone. More than 90% of the 15796 cases published in the hospital, including gonorrhea, hepatobiliary, urinary tract, intestinal, respiratory, gynecological, and otolaryngology infections, and pertussis and salmonella infections, were "good". It has also been used for pustular psoriasis, 1 to 1.5 g per day, divided into doses, the course of treatment is 10 days to 4 weeks, 5 cases were treated, 4 cases were cured, and 1 case was markedly effective. High fever subsided quickly after treatment, pustules were controlled, joint pain was significantly reduced, rashes subsided or erythema faded. ^[5]

Methromycin poisoning

Methanesulfomycin (methylsulfone chloramphenicol, thiomycin) has an antibacterial spectrum similar to chloramphenicol, but its antibacterial effect is less than that of chloramphenicol. Oral absorption is complete, and plasma half-life is 1.5h. Adults usually take 1 to 2 g / d in 3 to 4 doses. The adverse reactions in the application of this drug are less than those of chloramphenicol, mainly gastrointestinal reactions, and the toxicity to the hematopoietic system is also small, which can cause peripheral neuritis, and no gray infant syndrome has been reported. People with renal insufficiency may develop alopecia areata, which should be reduced. For clinical manifestations and treatment points, see related content of chloramphenicol:

Clinical manifestations of methanesulfomycin

1. Nausea, vomiting, lack of appetite, glossitis, and stomatitis may occur when taken orally. This medicine may cause jaundice, liver fat infiltration, and even acute severe hepatitis.

2. Hematopoietic system toxicity:

(1) The dose-related is reversible myelosuppression, and clinical anemia, leukocytes, and thrombocytopenia occur.

(2) Severe and irreversible aplastic anemia is irrelevant to the dose, and a few develop into granulocytic leukemia. The majority of patients with aplastic anemia develop after oral chloramphenicol, and the incubation period can be as long as several weeks to several months, with bleeding tendency, infection and anemia. Some patients with congenital glucose-6-phosphate dehydrogenase deficiency can develop hemolytic anemia.

3. Nervous system damage: Peripheral neuritis, optic neuritis, and visual impairment can progress to optic atrophy, which can cause toxic psychosis: severe insomnia, hallucinations, suspicion, mania, depression, etc.

4. Allergic reactions are rare, and there may be various rashes, solar dermatitis, and angioedema. Topical application can cause contact dermatitis. Occasional anaphylactic shock has been reported.

5. Grey infant syndrome can occur when preterm infants or newborns are given large doses of chloramphenicol (more than 25mg / kg daily): bloating, vomiting, progressive paleness, cyanosis, microcirculation disorders, temperature rise, breathing irregular. Similar performance can also occur when the dosage is 100 mg / kg in adults or older children.

Essentials of Methanesulfomycin Treatment

1. Those who take large doses orally should induce vomiting, gastric lavage, catharsis, and fluid replacement to promote their excretion.

2. When chloramphenicol is used in excess, there is no specific antidote, and dialysis therapy cannot clear the drug, and symptomatic and supportive treatment is the main.

3. Give oxygen to newborns when circulatory failure occurs, and actively treat circulatory failure.

4. When dose-related bone marrow suppression occurs, the drug should be discontinued immediately and treated accordingly, which is generally reversible.

5. Peripheral neuritis, bleeding tends to stop early, and treatment with vitamin B6 and multivitamins is often reversible. After the drug is discontinued when toxic psychiatric symptoms occur, no special treatment is required, and the symptoms usually disappear within 2 to 7 days.

6. Discontinue treatment promptly when allergic reactions occur, and give anti-allergic treatment. Those with severe jaundice should be treated with glucocorticoids. ^[7]

Moxacin Research

1.Develop new drugs with multiple modes of action and stable effects on existing drug-resistant bacteria

Methanesulfomycin Respiratory infections (RTIs) are a major cause worldwide. Therefore, the common RTIs pathogens, which were once sensitive to the antibiotics used, have become increasingly resistant to the antibiotics commonly used in the prescription. This phenomenon has caused great concern. In order to limit the proliferation of drug-resistant strains, the key is to solve the problem of drug resistance. To this end, the following measures are mainly taken:

Develop new drugs with multiple modes of action or stable effects on existing drug-resistant bacteria

Re-evaluation of known antibiotics to screen for drugs sensitive to RTIs pathogens

2.Methromycin hydrochloride glycine has a broad antibacterial spectrum

Methromycin is a chloramphenicol broad-spectrum antibiotic. Its antibacterial spectrum is basically similar to that of chloramphenicol. It belongs to a broad-spectrum antibiotic. It has a stronger bactericidal effect on influenza bacilli, meningococci and gonococci at low concentrations. Many Enterobacteriaceae bacteria, such as Escherichia coli, Pluviden, Aeromonas, Klebsiella, Enterobacter cloacae, typhoid and Salmonella, Serratia, etc. are all sensitive to this; Gram Negative bacteria such as diphtheria, listeria, anthracnose, pneumococcus, and streptococcus are most sensitive. Various anaerobic bacteria and bacilli include Bacillus fragilis, Treponema pallidum, Leptospira, Mycoplasma, Chlamydia, Ricketts The body is also sensitive to the product.

3.Methromycin hydrochloride and glycine ester have no cross-resistance with other antibiotics commonly used in clinical practice

Methanesulfomycin can affect and inhibit the physiological metabolic process of pathogenic bacteria. By binding to the 50s subunit of the bacterial core ribosomes, it can inhibit the extension of peptide acyltransferase and peptide chains, and can specifically prevent mRNA from binding to ribosomes. It breaks the bacterial protein synthesis and has a broad antibacterial spectrum. It has strong killing power against chlamydia, mycoplasma, and gonococcus. It can reach the highest concentration in blood quickly after oral administration for 2 hours, and immediately penetrates into the lesion and exerts highly effective antibacterial effect.

These antibiotics have no cross-resistance (except chloramphenicol) with other commonly used antibiotics in the clinic. The only antibiotics that can be used clinically are chloramphenicol and methamphenicol. Because chloramphenicol has liver, The multiple toxicity of bone marrow and blood has been replaced by other antibacterial drugs in clinical application, and typhoid and paratyphoid are reserved for clinical use. Most of the clinically isolated pathogenic viruses are susceptible to chloramphenicol antibiotics. In the chemical structure of methoxamycin, the nitrosyl group in chloramphenicol has been replaced by methylsulfone groups, and 63% of its metabolites are excreted by the prototype. It is less toxic than chloramphenicol, has a lower incidence of bone marrow suppression, and is reversible. The product does not easily penetrate the bacterial cell wall, making the antibacterial effect in vitro slightly weaker than that of chloramphenicol. On the other hand, it is not inactivated by binding to glucofuranoic acid in the liver, and the content of free active methosomycin in blood is higher, so it has stronger antibacterial activity.

4.Methromycin hydrochloride glycine has good pharmacokinetic properties

Methylsulfomycin hydrochloride glycine ester is rapidly hydrolyzed in vivo to release methanesulfomycin and exert antibacterial activity. Methylsulfomycin was absorbed quickly and completely after oral or injection administration. The peak blood concentration was reached within 2 hours after oral administration and within 1 hour after intramuscular injection. The peak plasma concentrations of normal people after oral administration, intramuscular injection, and intravenous injection of 500 were above 4.7 and 9 & micro; g / ml, respectively, and then slowly decreased. The half-life of intramuscular injection was 1.5 hours, and the intravenous injection was about 35 minutes. There is no obvious accumulation in the body when administered every 6-8 hours. Serum protein binding rate is 10% -20%, which can be quickly distributed to all tissues of the body after systemic administration. It is more abundant in kidney, spleen, liver, lung, etc., and the content in kidney and liver is higher than that in the same dose. Chloramphenicol is about 3-4 times higher and can reach a certain concentration in brain tissue. This product can also be excreted from the bile in its original form. Due to the existence of hepato-intestinal circulation, the concentration in bile is high. Methromycin is excreted in the original form by the kidney, filtered by the glomerulus, and partly secreted by the renal tubules. 70% to 90% of the amount of urinary excretion administered in 24 hours, 0.5 g orally for adults, and the urine concentration can reach 400 & micro; g / ml after 12 hours. Urinary excretion is significantly reduced when renal function declines.

Clinical Needs for Methanesulfomycin

Methylsulfomycin is higher in blood than other gonococcal MIC values in various organs, and is not metabolized in human tissues.

Methromycin Pseudomonas aeruginosa Bad, excreted by the kidneys in the original form, so it has a high effect on gonorrhea without comorbidities, and its cure rate is 95.56%. Methanesulfomycin not only has a strong bactericidal effect on Neisseria gonorrhoeae, but also has a good effect on anaerobic bacteria. Non-gonococcal urethritis (NGU) in STD in China is increasing year by year, and many of NGU are caused by anaerobic bacteria and trichomoniasis. Gonorrhea patients often merge with NGU while gonococci are infected. Methanesulfomycin has some NGU Also effective, especially bacterial vaginitis. The successful development of methamphenicol hydrochloride and glycine ester will add another new and effective drug for the prevention and treatment of sexually transmitted diseases.

Methanesulfomycin is slightly soluble in water. Methanesulfomycin used in the market are all oral dosage forms. Methanesulfomycin hydrochloride glycine ester has good water solubility, which can meet the needs of injections. Fill this gap.

Due to its extensive antibacterial spectrum and pharmacokinetic properties, methanesulfomycin can be used for a variety of etiologies and infections at different sites.

The latest research shows that methanesulfomycin has a good therapeutic effect on a variety of pathogens that are difficult to treat, have multiple drug resistance, and are susceptible to the population, including S. pneumoniae and S. aureus that are resistant to penicillin. SA strains, most isolates that are resistant to methicillin, atypical pathogens such as Mycoplasma pneumoniae and Chlamydia, etc.3. Therefore, methanesulfomycin is indeed one of the few precious drugs with extensive antibacterial activity. To this end, we have re-developed it and developed the parenteral drug methoxamycin glycine ester (TAPA-P) hydrochloride.

Methanesulfomycin Glycine Ester (TAP-G) is an injection of Methanesulfomycin. After taking it, it can be quickly hydrolyzed by tissue esterase in the body to release methylsulfomycin, and its antibacterial activity is produced by methylsulfomycin.

Methylsulfomycin Application

Methanesulfomycin and its tablets and capsules are listed in the Chinese Pharmacopoeia. The current two editions of the 2000 edition of the Chinese Pharmacopoeia contain its raw materials, tablets, injections, and capsules. Methanesulfomycin hydrochloride glycinate is a prodrug of methanesulfomycin, which hydrolyzes into methanesulfomycin in the body and functions. Methromycin hydrochloride glycine ester and its lyophilized preparation are listed in the Japanese Pharmacopoeia's Pharmaceutical Ingredient Specifications (1985) 7 and Italian Pharmacopoeia 8. And it is marketed abroad (Japan, Italy, etc.). For this reason, we declare and register according to the third category, item 1 of the chemical drug registration classification.

Methylsulfomycin Prospect Forecast

Methromycin hydrochloride glycine ester is mainly used clinically for respiratory infections, typhoid fever, urinary tract, biliary tract, and intestinal infections. It can also be used for pulmonary secondary bacterial infections such as chronic bronchitis.

Methromycin hydrochloride glycine ester can quickly hydrolyze in vivo to release methromycin and exert antibacterial activity.

Methylsulfomycin protein binding site . In the treatment of secondary bacterial infections of the lung such as bronchitis and bronchitis, methosomycin glycine ester hydrochloride can be administered by inhalation and intra-respiratory injection. Methosomycin can be administered orally or intramuscularly or intravenously. The oral dose is 250 to 500 mg6 every 6 or 8 hours.

1 Bronchitis 6: 250 mg of sulfomycin glycinate three times a day for 3 to 4 weeks, 20 patients with a daily output of 60 g or more of sputum were successfully treated, and 5 of 21 patients with a higher daily sputum output were successful. . About one-third of the patients first improved and then relapsed. Intratracheal injection of 500 mg of methosomycin 1 to 3 times a day: Intra-pharyngeal injection, 10 of 15 patients were successful but relapsed many times later. Injection of 11 of the 14 patients by cyclomembrane perichondrium was successful but relapsed repeatedly afterwards. (3) Injected through a fine polyethylene tube inserted into the ciliary cartilage and left it in place for two months. Eight of the ten patients succeeded but six later relapsed.

2 Gonorrhea 6: Most of the 580 gonococcal infections were eliminated after a single dose of 2.5 g of oral sulforamycin per day for 5 consecutive days. Of these, 11 did not respond after taking sulforamycin and were found to be resistant to sulfone. Neisseria gonorrhoeae.

3 Immunosuppressive 6: A single dose of oral sulfothromycin 2g per day for 16 days, 4 of the 6 patients with infectious lupus and glomerulonephritis subsided, and the duration lasted from 9 months to 3 years.

4 Biliary tract infection 6: After intramuscular injection of 1 g of methothromycin glycine ester, 500 mg per hour, the concentrations in plasma, urine and bile are very high, so methomycin can be used for prevention and treatment after biliary tract surgery.

5 Methanesulfomycin for 45 cases of gonorrhea without comorbidities: 45 cases of gonorrhea without comorbidities, 35 males and 10 females took 250 mg three times daily for 4 days after taking sulfomycin 5-8 days to return to the clinic for smears and culture. Observe the clinical manifestations, time for symptom resolution, and whether there are adverse reactions. The efficacy was judged according to the standards set by the Department of Disease Control of the Ministry of Health. Forty-five patients recovered from 43 patients and 2 patients did not heal. The cure rate was 95.56%. Among 43 cured patients, the clinical symptoms basically subsided within 2 days, and healed within 3 days after taking the medicine. The two patients who failed treatment were females. After 3 days of taking the medicine, the vulva itching and leucorrhea were significantly reduced, but the culture was still positive at the time of review. Adverse reactions: All patients did not experience nausea, vomiting, upset stomach, dizziness and other adverse reactions.

6 Methromycin for gonorrhea, non-gonococcal urethritis, and mixed infections observation 2: use of 1.5 g of methromycin for the first time, and then 1.5 g again for 3 days, 28 cases of gonorrhea, non-gonococcal urethritis (NGU) 70 cases and 22 cases of mixed infection, the total cure rate reached 89.17%, the drug's negative conversion rate to N. gonorrhoeae was 84.00%, the negative conversion rate of Chlamydia 97.06%, the negative conversion rate of Mycoplasma 82.05%.

Methromycin hydrochloride glycine ester clinically shows its high efficacy and safety characteristics, and can treat a variety of pathogen infections for clinical selection. The sulfomycin hydrochloride glycine ester for injection is exclusive in China, and the market prospect is very optimistic.

Methanesulfomycin manufacturers

Tianzifu International Pharmaceutical (Jiangsu) Company, Shanghai Tianping Pharmaceutical Co., Ltd., Hunan Xiangyao Pharmaceutical Co., Ltd., Jiangsu Chenpai Pharmaceutical Co., Ltd., Hangzhou Minsheng Pharmaceutical Group Co., Ltd., Yangzhou Zhongbao Pharmaceutical Co., Ltd., Yangzhou Xingdou Medicine Industry Co., Ltd., Shanghai No. 6 Pharmaceutical Factory, Nanjing No. 3 Pharmaceutical Factory, Wuxi Aixion Pharmaceutical Co., Ltd., Suzhou Pharmaceutical Group Co., Ltd., Suzhou Pharmaceutical Group Co., Ltd., Tianjin Zhongjin Pharmaceutical Co., Ltd.