What Is Glyburide?
Glibenclamide (INN), also known as hypoglycemic (USAN), is a sulfonylurea hypoglycemic agent. It is also commercially available as a mixture of metformin and metformin called Glucovance [1] . Glibenclamide inhibits liver glycogenolysis and glycogenogenesis by increasing portal vein insulin levels or directly acting on the liver, reducing liver production and glucose output; fast oral absorption, high protein binding rate, 95%, after oral administration The plasma concentration reached the peak in 2 to 5 hours, and the effect continued for 24 hours. T1 / 2 is 10 hours. Metabolized in the liver, about 50% each by the liver and kidneys.
Basic Information
- Chinese name
- Glibenclamide
- English name
- Glibenclamide
- nickname
- Excellent hypoglycemic; Daan therapy, etc.
- Chemical formula
- C23H28ClN3O5S
- Molecular weight
- 494.01
- CAS Registry Number
- 10238-21-8
Introduction to Glibenclamide
Glibenclamide Basic Information
- Chinese name: glibenclamide
- Chinese alias: Youjiangtang; Da'an therapy; Da'anning; Ethylsulfenyl urea; Yougelukang; Cyclopenzamide; N- (2- (4-((((Cyclohexylamino) carbonyl) amino)) Sulfonyl) phenyl) ethyl) -2-methoxy-5-chlorobenzamide
- English name: Glibenclamide
- English alias: glycenclamide; glycybride usp; Glibenclamide; Glyburide; 5-chloro-n- (2- (4-(((((cyclohexylamino) carbonyl) -amino) sulfonyl) phenyl) -ethyl) -2-methoxybenzamide; 5-chloro -N- (2- {4-[(cyclohexylcarbamoyl) sulfamoyl] phenyl} ethyl) -2-methoxybenzamide; 5-chloro-2-methoxy-N- [2- [4- (phenylcarbamoylsulfamoyl) phenyl] ethyl] benzamide; HB -419; maninil; adiab
- CAS number: 10238-21-8
- EINECS number: 233-570-6
- Molecular formula: C 23 H 28 ClN 3 O 5 S
- Molecular weight: 494.01
- Exact mass: 493.14400
- PSA: 121.98000
- LogP: 5.89520
Glibenclamide physicochemical properties
- Density: 1.376g / cm 3
- Dosage form: API
- Appearance: white crystalline powder.
- Melting point: 173-175 ° C
- Refractive index: 1.628
- Stability: stable under normal temperature and pressure
- Storage conditions: low temperature, ventilated and dry in the warehouse
- Content: 99%
- Solubility: Insoluble in water, slightly soluble in ethanol, acetone and chloroform.
Glibenclamide Safety Information
- Customs Code: 29350009090
- Danger category code: R20 / 21/22
- Safety instructions: S22-S36 / 37/39
- RTECS number: YS4725200
- Dangerous goods sign: Xn
Glibenclamide use
- Hypoglycemic. It is suitable for mild-to-moderate type II diabetes with unsatisfactory curative effect. The pancreatic islet cells of patients have certain function of secreting insulin, and there are no serious complications [1] .
Glibenclamide Drug Analysis
- Method name:
- Determination of GlibenclamideHigh performance liquid chromatography
- Application:
- This method uses high performance liquid chromatography to determine the content of glibenclamide.
- This method is applicable to glibenclamide.
- Method principle:
- This method uses high performance liquid chromatography to determine the content of glibenclamide.
- This method is applicable to glibenclamide.
- Reagent:
- Methanol
- 2. Ammonium dihydrogen phosphate solution: Take 1.725 g of ammonium dihydrogen phosphate, add 300 mL of water to dissolve, and adjust the pH value to 3.5 ± 0.05 with phosphoric acid.
- equipment:
- Instrument
- 1.1 HPLC
- 1.2 Column
- Octadecylsilane-bonded silica gel is used as a filler. The number of theoretical plates calculated based on the glibenclamide peak should not be less than 1000. The resolution of the glibenclamide peak and the internal standard substance peak should meet the requirements.
- 1.3 UV absorption detector
- Chromatographic conditions
- 2.1 Mobile phase: methanolic ammonium dihydrogen phosphate solution = 5 3
- 2.2 Detection wavelength: 274nm
- 2.3 Column temperature: room temperature
- Sample preparation:
- Weigh the test product
- Take 20mg of this product and weigh it accurately.
- 2. Preparation of internal standard solution
- Take 10 mg of butyl parahydroxybenzoate, put it into a 100 mL measuring flask, add 6 mL of methanol, sonicate to dissolve it, dilute to the mark with mobile phase, and shake to obtain.
- 3. Preparation of test solution
- The above test product was placed in a 50mL volumetric flask, 12mL of methanol was added, and the glibenclamide was dissolved by sonication. The mobile phase was diluted to the mark. 25mL of the solution and 5mL of the internal standard solution were accurately measured. The phases were diluted to the mark and shaken to obtain the test solution.
- 4. Preparation of reference solution
- Accurately weigh the appropriate amount of the glibenclamide reference substance and prepare it in the same way as the test product.
- Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weight taken. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards.
- Steps:
- Precisely measure 20 L of the test solution and the reference solution into the high-performance liquid chromatograph, and use an ultraviolet absorption detector to measure the absorption values of glibenclamide and internal standard butyl paraben at a wavelength of 274 nm. The standard method uses the peak area to calculate [2] .
Glibenclamide Pharmacopoeia Standard
Glibenclamide source (name), content (potency)
- This product is N- [2- [4-[[[(cyclohexylamino) carbonyl] amino] sulfonyl] phenyl] ethyl] -2-methoxy-5-chlorobenzamide. Calculated as dry product, including
- C 23 H 28 ClN 3 O 5 S shall not be less than 99.0%.
Glibenclamide traits
- This product is white crystalline powder; almost odorless and tasteless.
- This product is slightly soluble in chloroform, slightly soluble in methanol or ethanol, and insoluble in water or ether.
- Melting point
- The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 170-174 ° C.
Glibenclamide identification
- (1) 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.
- (2) Take this product, add ethanol to dissolve and dilute it to make a solution containing 0.1mg per 1ml. According to UV-Vis spectrophotometry (Appendix IVA of Pharmacopoeia Part II of 2010 edition), it has a maximum at 274nm and 300nm Absorption, with minimal absorption at wavelengths of 272nm and 278nm.
- (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (Figure 307 of "Infrared Spectra of Drugs").
- (4) Take about 0.1g of this product and 0.2g of potassium nitrate, mix, heat to carbonize, then ash, let cool, and add 10ml of water to dissolve the residue. After filtration, the filtrate shows chloride and sulfate (the second edition of the 2010 Pharmacopoeia) Appendix III).
Glibenclamide check
- chloride
- Take 1.0g of this product, add 50ml of water, boil, quickly cool, filter, add water to the filtrate to make 50ml, take 25ml, check according to law (Appendix A of Part Two of the 2010 Pharmacopoeia) and 7.0ml of standard sodium chloride solution The control solution must not be more concentrated (0.014%).
- Sulfate
- Take 25ml of the remaining filtrate under the above chloride and check it according to law (Appendix B of Part II of the Pharmacopoeia 2010), compared with the control solution made of 2.0ml of standard potassium sulfate solution.
- relative substance
- Take about 25mg of this product, accurately weigh it, put it in a 50ml measuring bottle, add 25ml of methanol, dissolve it with sonication, dilute to the mark with mobile phase, shake well, and use it as a test solution; 4- [2- (5 -Chloro-2-methoxybenzamide) -ethyl] -benzenesulfonamide (impurity I) reference and 4- [2- (5-chloro-2-methoxybenzamide) -ethyl] -Benzenesulfonylamino-ethyl formate (impurity ) 15mg each, accurately weighed, put in the same 50ml measuring bottle, add 10ml of methanol, sonicate to dissolve, dilute to the mark with mobile phase, shake well, and mix as Impurity reference product stock solution; precisely measure 1ml of the test solution and mixed impurity reference product stock solution respectively, put them in the same 100ml volumetric flask, dilute to the mark with mobile phase, shake well, and use it as the control solution. According to the chromatographic conditions under the content determination item, take 20 l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the impurity chromatographic peak is about 15% of the full range, and then accurately measure the test solution and the control solution. Each 20 l was injected into the liquid chromatograph, and the chromatogram was recorded to twice the peak retention time of the main component. The chromatograms of the test solution have any retention peaks corresponding to the impurity peaks of impurity I and impurity in the reference solution. The peak area calculated according to the external standard method shall not exceed 0.6%. The sum of the peak areas of other impurities shall not be greater than the control. 0.5 times (0.5%) of the main peak area of the solution.
- Loss on drying
- Take this product and dry it to constant weight at 105 ° C, and the weight loss shall not exceed 0.5% (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 Glibenclamide
- It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition).
- Chromatographic conditions and system suitability tests
- Use octadecylsilane bonded silica as a filler; use ammonium dihydrogen phosphate solution (take 1.725g of ammonium dihydrogen phosphate, add 300ml of water to dissolve, adjust the pH value to 3.5 ± 0.05 with phosphoric acid)-methanol (3: 5) is Mobile phase; detection wavelength is 300nm. Take 20 l of the reference solution under the relevant substance into the liquid chromatograph, record the chromatogram, and the peak order of each component is impurity I, impurity II, and glibenclamide. The number of theoretical plates calculated from the glibenclamide peak is not less than 5000, and the resolution of the impurity and impurity peaks should meet the requirements.
- Assay
- Take about 10mg of this product, accurately weigh it, place it in a 50ml measuring bottle, add 12ml of methanol, sonicate to dissolve the glibenclamide, dilute to the mark with mobile phase, shake well, and accurately measure 20l into the liquid chromatograph and record Chromatogram; another reference for glibenclamide was determined by the same method. Calculate the peak area according to the external standard method.
Glibenclamide category
- Hypoglycemic drugs.
Glibenclamide storage
- Keep tightly closed.
Glibenclamide
- Glibenclamide tablets [3]
Glibenclamide drug description
Glibenclamide pharmacological action
- The product releases insulin by stimulating islet cells, and its intensity of action is 200 times that of mesotrione, so the dose used is significantly reduced. Same as tolbutamide but with strong hypoglycemic effect. Promote insulin secretion by pancreatic islet B cells, the prerequisite is that pancreatic islet B cells also have a certain function of synthesizing and secreting insulin; by increasing portal vein insulin levels or directly acting on the liver, inhibit liver glycogen breakdown and glycogenogenesis, Decreased liver production and glucose output; It may also increase the sensitivity of extrapancreatic tissue to insulin and sugar utilization (possibly mainly through post-receptor effects), so the overall effect is to reduce fasting blood glucose and postprandial blood glucose. This product is mainly metabolized by the liver, and is excreted from urine in 50% within 24 hours. The effect can last for 15-24 hours.
Glibenclamide pharmacokinetics
- Oral absorption is rapid and complete. The peak time of plasma drug concentration is 2-6 hours, and absorption is not affected by food. However, in recent years, it has been reported that a small dose of glibenclamide is effective before breakfast. The peak time of plasma drug concentration is higher than that of meal. 1h in advance. The duration of action is more than 16 hours, the plasma protein binding rate is about 99%, the apparent distribution volume is 0.3 L / kg, and the plasma half-life is 6 to 12 hours. Glibenclamide is completely metabolized in the liver into two hydroxyl derivatives and another unclear metabolite, of which 4-trans-hydroxyglibenclamide has 15% activity. In 48 hours, 40% of the administered dose can be recovered in feces, and then excretion slows down, and excretion can reach 95% after 5 days. [4]
Glibenclamide caution
- Physical weakness, high fever, nausea and vomiting, hyperthyroidism, the elderly. 2. Blood glucose, urine glucose, urine ketone body, urine protein, liver and kidney function should be measured regularly during the medication, and ophthalmological examinations should be performed. 1. Animal tests and clinical observations prove that sulfonylurea hypoglycemic drugs can cause stillbirth and fetal malformations, and pregnant women should not take them. 2. This class of drugs can be excreted from breast milk, so nursing mothers should not take them to prevent hypoglycemia in infants. Elderly patients and those with renal insufficiency have reduced metabolism and excretion capacity of this class of drugs. This product has a relatively strong hypoglycemic effect. This product is not suitable. Other sulfonylurea hypoglycemic drugs with shorter action time can be used.
Glibenclamide indications
- It is suitable for mild and moderate non-insulin-dependent diabetes with unsatisfactory curative effect. The pancreatic islet B cells of patients have a certain function of secreting insulin, and there are no serious complications. For non-insulin-dependent (adult, obese) diabetic patients. Because it has a long clearance rate and is most prone to hypoglycemia, it should be used with caution in clinical applications, and it can be used in patients who have no obvious effect on blood glucose lowering drugs.
Glibenclamide dosage
- 2.5 mg orally, once before breakfast or before breakfast and lunch, 1.25 mg for mild patients, one day
- Glibenclamide
- This product is 250 to 500 times stronger than tolbutamide. Easy to produce hypoglycemia, so for mild, moderate and elderly non-insulin dependent diabetic patients, tolbutamide or the product should be started from a small dose;
- Switch to other oral hypoglycemic drugs or insulin for the use of this product or combined with insulin, see tolbutamide. Oral, 2.5 ~ 10mg each time, take after breakfast. If the daily dose exceeds 10mg, it should be taken twice in the morning and evening; or 5mg daily, 2.5mg each in the morning and before meals.
Glibenclamide notes
- 1. A small number of patients have symptoms of gastrointestinal discomfort, fever, skin allergies, and hypoglycemia, which should be reduced or discontinued.
- 2. Use with caution in patients with liver dysfunction.
- 3. Severely decompensated acidosis, diabetic coma, renal insufficiency, diabetic ketosis, and young people, children and pregnant women should not be used.
- 4. This medicine has a mild diuretic effect.
- 5. Insulin dependent diabetes with acute complications, pregnancy and liver and kidney dysfunction are contraindicated.
Glibenclamide adverse reactions
- Occasionally abdominal or stomach discomfort, fever, skin allergies, hypoglycemia, should be reduced or discontinued. There are gastrointestinal discomfort, fever, skin irritation, changes in blood vision, etc. Improper use of doses can cause severe hypoglycemic reactions, especially if overdose, there is a risk of death and should be corrected in time. Glibenclamide can cause thrombocytopenic purple scar and allergic vasculitis. The product is hepatotoxic and is dose-dependent. Less common adverse reactions are jaundice-free or cytolytic hepatitis, cholestasis-type jaundice, and the symptoms are easily confused with viral hepatitis.
Glibenclamide side effects
- Glibenclamide, also known as hypoglycemic, is a western medicine with obvious hypoglycemic effect, but because of the obvious side effects, many patients are not suitable to take this oral hypoglycemic agent. It is especially dangerous to take glibenclamide without knowing it. Taking glibenclamide in large amounts for a long time will eventually cause hypoglycemia and kidney disease in patients, and even cause death. In addition, inducing patients to take medications without the need to control their diet can also lead to patient death.
- According to the current level of medical development, diabetes cannot be cured, and there is no so-called specific medicine. The correct treatment method is that the patient must strictly control the diet and use the medicine scientifically under the guidance of a doctor.
Glibenclamide Drug Interactions
- This product should not be used with salicylic acids, sulfa drugs, propranolol, monoamine oxidase inhibitors, penicillin, probenecid, butemethan, indomethacin, dicoumarin anticoagulants, methotrexate Equal use, combined use will enhance the effect of lowering blood sugar, causing hypoglycemic response. Chloramphenicol, coumarins, doxycycline, muscle relaxant fenyramidol, butepine, probenecid, and sulfamethoxazole can inhibit the metabolism and excretion of sulfonylureas and prolong the decline. The role of blood sugar.
- Salicylic acids, sulfonamides and sulfonylureas compete for plasma protein binding, -adrenaline, monoamine oxygen
- beta cells
- When taken with alcohol, it can cause abdominal cramps, nausea, vomiting, headaches, facial flushing, and hypoglycemia. Combination with beta-blockers can increase the risk of hypoglycemia, and can mask the symptoms of hypoglycemia, such as faster pulse rate and increased blood pressure; selective beta-blockers such as atenolol in small amounts (Atenolol) and metoprolol are less likely to cause this.
- Chloramphenicol, guanethidine, insulin, monoamine oxidase inhibitors, butepine, oxybuteone, probenecid, salicylate, and sulfonamides can be used at the same time to enhance blood sugar lowering effect. Adrenal corticosteroids, epinephrine, phenytoin, thiazide diuretics, and thyroxine can increase blood sugar levels. When used with this class of drugs, the amount of this class of drugs may need to be increased. When coumarin anticoagulants are used together with this class of drugs, the plasma concentrations of each other initially increase, but the plasma concentrations of each other decrease thereafter, so the dosage of both needs to be adjusted.
Glibenclamide poisoning
- Glibenclamide (hypoglycemic, daan therapy) is the second-generation oral sulfonylurea hypoglycemic agent with the longest action and the strongest hypoglycemic effect, which is 100 times that of D-860. Oral absorption, the duration of effect is about 16-24 hours. This product is prone to hypoglycemic reactions, and may have local and systemic allergic reactions, so it should be started from a small dose. The general dose is 2.5-10mg, taken once after breakfast. Adverse reactions and treatment points are the same as those of metsulfenil [5] .
Glibenclamide Expert Reviews
- Glibenclamide has been clinically tested in a total of 3149 cases, with an effective rate of 85%, a primary early failure rate of 15%, and application in 2767 patients for 12 to 36 months, and a secondary failure rate of 9%. There is no certain effect on the prevention and treatment of complications of microangiopathy. Glibenclamide has a strong effect. In patients with certain islet function, it has a significant hypoglycemic effect and can reduce fasting and postprandial blood glucose. However, due to its high incidence of hypoglycemia, it is currently generally not used as a drug of choice in clinical practice. However, glibenclamide is cheap and has strong drug action. Many patients are still using it, especially in rural and low-diabetes patients. Pay attention to the dosage of the drug and monitor blood glucose during application to avoid the occurrence of hypoglycemic adverse reactions [4 ] .