What Factors Affect a Sufficient Mebendazole Dose?

Mebendazole is a broad-spectrum intestinal repellent. Both in vivo and in vitro tests have proven that it can directly inhibit the intake of glucose by nematodes, leading to the depletion of glycogen, making it unable to survive. It has a significant effect on killing larvae and inhibiting egg development. , But does not affect blood glucose levels in the body. It can be used to control intestinal parasitic diseases such as hookworms, roundworms, roundworms, whipworms, and feces.

Drug Name: Mebendazole
Foreign name: Mebendazole

Molecular formula: C16H13N3O3
CAS number: 31431-39-7

Brief introduction

Tolumidazole Alias Name: (5-benzoyl-1-benzimidazol-2-yl) methyl carbamate benzophenone guanidyl methylphenidazole tomidazole 5-benzimidazole-2-benzimidazole carboxylic acid Other aliases of methyl tolazole: (5-Benzoyl-1H-benzimidazol-2-yl) carbamicacidmethylester (5-Benzoyl-1h-benzimidazol-2-yl) -carbamicacidmethylester (5-Benzoyl-1h-benzimidazol-2-yl) -carbamicacimethylester 5-Benzoyl-2-benzimidazolecarbamicacimethylester Bantenol Besantin Lomper mbdz

EINECS number: 250-635-4
Properties: Odorless white to light yellow crystalline powder. Solubility: soluble in formaldehyde, formic acid, glacial acetic acid and bitter almond oil, insoluble in water ^[1]

Mebendazole

Mebendazole application

Method for preparing tolazole

Tolumidazole method one

4-Chloro-3-nitrobenzoic acid was chlorinated with thionyl chloride, condensed with benzene under the catalysis of aluminum trichloride, and then aminated and reduced to obtain 3,4-diaminobenzophenone. Cyclization to make tolazole.

Tolumidazole method two

It is also possible to add 3,4-diaminobenzophenone hydrochloride to the mixture obtained by the reaction of S-methylisothiourea sulfate, methyl chloroformate and sodium hydroxide, and then add sodium acetate at 85 ° C. The reaction was also carried out for 45 min, and tolazole was also prepared.

Tolumidazole method three

It is obtained by using o-dichlorobenzene and benzoyl chloride as raw materials through condensation, ammoniation and cyclization. O-dichlorobenzene, benzoyl chloride, and anhydrous aluminum trichloride were mixed, and the reaction was stirred at 130-135 ° C for 4 hours. After cooling slightly, it was poured into dilute hydrochloric acid, filtered and washed with water to neutrality to obtain a crude product of xylylene. The crude product was dissolved in hydrochloric acid and decolorized by adding activated carbon under reflux for 0.5 h. The decoloring solution is cooled to below 10 ° C. After filtration, it was dried to obtain 2,4-dichlorobenzophenone. Yield: 70%. The 2,4-dichlorobenzophenone, cuprous chloride, magnesium chloride, and ammonia water were reacted in an autoclave at 200-210 ° C and 5-6 MPa for 15 hours. After cooling to 40-50 ° C and filtering, the filter cake was dissolved in dilute hydrochloric acid and decolorized by adding activated carbon (80 ° C, 0.5h). The decoloring solution was cooled to 10 ° C, and crystals were precipitated. After filtration and drying, 3,4-diaminoxylone hydrochloride was obtained with a yield of 65%. The product is then combined with methyl cyanurate ring. ^[2]

Precautions for mebendazole

(1) In a few cases, slight dizziness, diarrhea, and abdominal discomfort may occur, and occasional roundworms may cause abdominal pain or vomiting (combined with a small dose of thiapyrimidine to avoid it), but none of them affect the treatment.

(2) Laxatives are not required except for those who are habitually constipated.

(3) Animal tests have shown that this product can cause teratogenesis, so pregnant women should not use it.

(4) Serious side effects often occur in the case of excessive doses, too long medication times, short intervals, or combined corticosteroids, which should be paid attention to.

Toxazole drug toxicology

Toluimazole is a derivative of benzimidazole. This class of drugs has a strong affinity for the -tubulin of the insect body, and can bind to it at very low concentrations, thereby inhibiting the polymerization of microtubules and causing the epidermis of the insect body. Or the disappearance of intestinal cells reduces digestion and absorption of nutrients such as glucose, leading to the death of the worm. The drug can also inhibit fumarate reductase in mitochondria, reduce glucose transport, and uncouple oxidative phosphorylation, thereby affecting the production of ATP. This medicine has effects on adults and eggs.

Memidazole Drug Analysis

2005 Tolumidazole 2005 Chinese Pharmacopoeia

Method name: Mebendazole drug substanceDetermination of tolmidazolepotentiometric titration

Scope of application: This method uses a titration method to determine the content of tomidazole in the tomidazole raw material drug.

This method is applicable to the tomidazole drug substance.

Principle of the method: After the test product is dissolved in formic acid, glacial acetic acid and acetic anhydride are added, and the titration is performed with perchloric acid titration solution according to the potentiometric titration method. The titration result is corrected with a blank test. content.

Reagent:

Glacial acetic acid

Formic acid

Acetic anhydride

4. Perchloric acid titration solution (0.1mol / L)

5. Crystal violet indicator liquid

6. Reference potassium phthalate

equipment:

Sample preparation: 1. Perchloric acid titration solution (0.1mol / L)

Preparation: Take 750mL of anhydrous glacial acetic acid (calculated with water content, add 5.22mL of acetic anhydride per 1g of water), add 8.5mL of perchloric acid (70 ~ 72%), shake well, let cool, add an appropriate amount of anhydrous glacial acetic acid 1000mL, shake well and leave for 24 hours. If the test sample is easily acetylated, the water content of the solution must be determined by the moisture measurement method, and then the water content of the solution is adjusted to 0.01% ~ 0.2% with water and acetic anhydride.

Calibration: Take about 0.16g of standard potassium hydrogen phthalate dried to constant weight at 105 , accurately weigh, add 20mL of anhydrous glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and slowly titrate with this solution to Blue, and the titration results are corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 20.42mg of potassium hydrogen phthalate. Calculate the concentration of this solution based on the consumption of this solution and the amount of potassium hydrogen phthalate taken.

Crystal violet indicator liquid

Take 0.5 g of crystal violet and add 100 mL of glacial acetic acid to dissolve.

Operation steps: Precisely weigh about 0.25g of the test sample, add 8mL of formic acid to dissolve, then add 40mL of glacial acetic acid and 5mL of acetic anhydride. Titrate with perchloric acid titration solution (0.1mol / L) according to the potentiometric titration method. The results were corrected with a blank test. 1mL perchloric acid titration solution (0.1mol / L) is equivalent to 29.58mg of C16H13N3O3.

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. ^[3]

2010 Tolumidazole 2010 Chinese Pharmacopoeia

Inspection: Take 50mg of this product, put it into a 10ml measuring bottle, add 2ml of formic acid to dissolve, dilute to the mark with acetone, shake well, and use it as the test solution; take an appropriate amount of the precise amount, add acetone and dilute each into 1ml respectively Contains 0.025mg and 0.0125mg solutions. According to the thin layer chromatography (Appendix VB) test, draw 10 & micro; l of the above three solutions, respectively point on the same silica gel GF254 thin layer plate, with chloroform-methanol-formic acid (90: 5: 5) as the developing agent , Unfold, dry, and inspect under UV light (254nm). The control solution (2) should show a noticeable spot, and the test solution, such as a spot of impurities, should have a darker color (0.5%) than the main shift point of the control solution (1). ^[4]

Application and development of tolumazole

Understand the development, market situation and clinical application of tomidazole. Search for search engines and medical websites in foreign countries. Results Synthesis of mebendazole was launched in 1971, and it was put into clinical practice in the same year. The sales volume ranked 3 to 6 in the antiparasitic drug market, which is suitable for expelling intestinal parasitic infections. It has the characteristics of broad spectrum, high efficiency and low toxicity. It is cheap and has a large population demand. It is also the drug of choice to drive intestinal parasites. ^[5]

But there is also a problem that cannot be ignored:

In recent years, China's aquaculture industry has developed rapidly, both in output value, yield and quality have been greatly improved, but due to the expansion of intensive farming models, the water environment is too eutrophic and disturbed by factors such as misuse and abuse of drugs; artificial breeding The incidence of aquatic animals is increasing year by year, and new diseases occur every year. It is also increasingly difficult to use medication. ^[6]