What Is Gliclazide?
Gliclazide, trade name Damicon. It is white crystal or crystalline powder; odorless and tasteless. It is soluble in chloroform, slightly soluble in methanol, slightly soluble in ethanol, and insoluble in water. Density: 1.35 g / cm3 Melting point: 163-169 ° C (lit.) It is a sulfonylurea oral antidiabetic agent.
- Chinese name
- Glezit
- Foreign name
- gliclazide
- CAS number
- 21187-98-4
- Molecular formula
- C15H21N3O3S
- Gliclazide, trade name Damicon. It is white crystal or crystalline powder; odorless and tasteless. It is soluble in chloroform, slightly soluble in methanol, slightly soluble in ethanol, and insoluble in water. Density: 1.35 g / cm3 Melting point: 163-169 ° C (lit.) It is a sulfonylurea oral antidiabetic agent.
Introduction to Glecitide compounds
Gleizit Basic Information
- Chinese name:
- Chinese alias: 1- (3-azabicyclo [3,3,0] octyl) -3-p-toluenesulfonylurea; mesylbicyclourea; Glecitide; Damicon; Glicknassa Mesosulfuride; Gleclide; Voglibose Impurity
- English name: gliclazide
- English alias: 1- [3-Azabicyclo [3.3.0] oct-3-yl] -3-p-toluenesulfonylurea; NORDIALEX; se1702; Glinormax; DIAMICRON;
- CAS number: 21187-98-4
- Molecular formula: C15H21N3O3S
- Structural formula:
- Molecular weight: 323.41100
- Exact mass: 323.13000
- PSA: 86.89000
- LogP: 3.43030 [1]
Glipizide physical and chemical properties
- Appearance and properties: white powder
- Density: 1.35 g / cm3
- Melting point: 163-169 ° C (lit.)
- Refractive index: 1.623
- Stability: Stable at normal temperatures and pressures. Heat.
- Storage conditions: Keep tightly closed. [1]
Glezit safety information
- Customs Code: 29350009090
- WGK Germany: 2
- Danger category code: R21
- Safety instructions: S25; S26; S36 / 37; S53
- RTECS number: YT4500000
- Dangerous goods mark: Xn; Xi [1]
Gliclazide pharmacopoeia standards
Glitazide source (name), content (potency)
- This product is 1- (3-azabicyclo [3.3.0] octyl) -3-p-toluenesulfonylurea. Calculated on dry basis, containing C15H21N3O3S shall not be less than 98.5%. [2]
Gleevec properties
- This product is white crystal or crystalline powder; odorless and tasteless.
- This product is soluble in chloroform, slightly soluble in methanol, slightly soluble in ethanol, and insoluble in water. [2]
Glitsit melting point
- The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 162 to 166 ° C. [2]
Glezide identification
- (1) Take this product, add ethanol to dissolve and dilute it to make a solution containing about 10g per 1ml. According to ultraviolet-visible spectrophotometry (Appendix IVA of Pharmacopoeia Part II of the 2010 edition), it has a maximum absorption at a wavelength of 228nm.
- (2) The infrared absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 629). [2]
Glezit inspection
- 1 related substances
- Take about 50mg of this product, weigh it accurately, place it in a 50ml measuring bottle, add about 20ml of acetonitrile to dissolve, dilute with water to the mark, shake well, as a test solution; take 5ml of precise quantity, put it in a 100ml measuring bottle, use 40 % Acetonitrile solution was diluted to the mark, shake well, as the control solution (1); precisely measure 2ml of the control solution (1), put it in a 50ml measuring bottle, diluted to the mark with 40% acetonitrile solution, shake well, and use it as the control solution (2 ); Also accurately weigh about 10 mg of 1- (3-azabicyclo [3.3.0] octyl) -3-o-toluenesulfonylurea (impurity I) reference substance, put it in a 100 ml measuring bottle, add about 40 ml of acetonitrile to make Dissolve, dilute with water to the mark, shake well, as the reference solution (1); precisely measure 1ml of the reference solution (1), put in a 100ml measuring bottle, dilute to the mark with 40% acetonitrile solution, shake well, and use as the reference Solution (2). Take 2ml of the control solution (1) and 3ml of the reference solution (1), put them in the same 20ml volumetric flask, and dilute to the mark with 40% acetonitrile solution, and shake it as the system suitability test solution. According to high performance liquid chromatography (2010 edition Pharmacopoeia Part II Appendix VD) test. Use octylsilane-bonded silica gel as filler, water-acetonitrile-triethylamine-trifluoroacetic acid (60: 40: 0.1: 0.1) as mobile phase, and detection wavelength is 235nm. Take 20l of the system suitability test solution and inject it into the liquid chromatograph. Record the chromatogram. The theoretical plate number is calculated to be not less than 3000 according to the Glitzit peak. The resolution of the Glitzit peak and the impurity I peak should be greater than 1.8. Take 20l of the reference solution (2) into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 15% of the full range, and then accurately measure the test solution, the control solution (2) and the reference substance Each 20 l of solution (2) was injected into the liquid chromatograph, and the chromatogram was recorded to twice the peak retention time of the main component. The chromatogram of the test solution (excluding the peak with a relative retention time less than 0.2). If there is an impurity peak corresponding to the main peak of the reference solution (2), its peak area must not be greater than the main peak area (0.1%) of the reference solution (2). ; The peak area of other single impurities should not be larger than 0.5 times (0.1%) of the main peak area of the control solution (2); the sum of the peak areas of other impurities should not be larger than the main peak area (0.2%) of the control solution (2). All solutions should be prepared fresh. [2]
- 2 Loss on drying
- Take this product and dry it at 105 to constant weight, and the weight loss shall not exceed 1.0% (Appendix L of Part Two of the Pharmacopoeia of 2010 Edition). [2]
- 3 burning residue
- 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%. [2]
- 4 heavy metals
- 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. [2]
Glitazide determination
- Take about 0.2g of this product, accurately weigh it, add 50ml of glacial acetic acid to dissolve it, then use potentiometric titration (Appendix A of Pharmacopoeia Part II of 2010 Edition), titrate with perchloric acid titration solution (0.1mol / L), The results were corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 32.34mg of C15H21N3O3S. [2]
Gliclazide pharmacokinetics
- Promote insulin secretion by pancreatic islet B cells, a 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 glycogenolysis and glycogenogenesis, liver formation And decreased glucose output; it may also increase insulin sensitivity and sugar utilization in extrapancreatic tissues (probably mainly through post-receptor effects).
- Therefore, the overall effect is to reduce fasting and postprandial blood glucose. Absorption is fast, and the blood concentration reaches 2 to 6 hours after oral administration, and reaches a peak value for 24 hours. T1 / 2 is 10-12 hours, and is mainly inactivated by liver metabolism, and 98% can be excreted on the second day. This product is rapidly absorbed orally. The peak time of the blood concentration is 2 to 4 hours, the plasma protein binding rate is 85% to 87%, the effect maintenance time is 24 hours, and the serum half-life is 10 to 12 hours. Most of this product is metabolized by the liver into inactive metabolites in the body. Within one day after administration, 59% is excreted with urine, a small amount is excreted with feces, and 95% is excreted through the kidneys within 5 days. [3-4]
Gliclazide pharmacological action
- Glipizide is a second-generation oral sulfonylurea hypoglycemic agent with a strong effect. Its mechanism is similar to that of tolbutamide, that is, it selectively acts on islet cells, promotes insulin secretion, and increases insulin after glucose intake. freed. Its effect is more than 10 times stronger than tolbutamide. In recent years, studies have also found that Glecid has an extrapancreatic effect, which enhances the effect of surrounding tissues on insulin. It may be the result of the enhanced biological effect after the insulin receptor, and at the same time, liver glucose production and output are also resisted, which makes Gleazec unique extra-pancreatic receptors or post-receptor effects. Another view is that sulfonylureas can increase the number of insulin receptors in target tissues and increase the sensitivity of peripheral target tissues to insulin. Glipizide has been proven in animal experiments and clinical use to reduce platelet aggregation and adhesion, prevent vitamins from depositing on the walls of microvessels, and prevent and treat diabetic microangiopathy. Some animal experiments have shown that long-term use of Glipizide can significantly reduce liver cholesterol and reduce triacylglycerol and fatty acids. Histological examination shows that it can resist the damage of arteries, especially coronary arteries caused by high cholesterol foods, and is beneficial for reducing cardiovascular complications of diabetes. [3-4]
- In addition, this product can inhibit the release of arachidonic acid from phospholipids in platelets, thereby reducing the synthesis of thromboxane (TXA3), inhibiting a variety of coagulation factors (such as , , ), and increasing fibrinolysis Enzyme activator levels promote fibrinolysis. Animal experiments have also found that this product can reduce plasma cholesterol, triglyceride and fatty acid levels.
Glezide indications
- It is suitable for mild and moderate non-insulin-dependent diabetes with unsatisfactory curative effect by using a single diet. Patients with islet B cells have a certain insulin secretion function.
- beta cells
Glezide adverse reactions and treatment
- Occasionally mild nausea, vomiting, epigastric pain, constipation, diarrhea, erythema, urticaria, thrombocytopenia, granulocytopenia, anemia, etc., mostly
- Glezit
Glipizide drug interactions
- Combination with thiazide diuretics, adrenocortical hormones and estrogen preparations may reduce the hypoglycemic effect of this product. With chloramphenicol, dicoumarin,
- Ethanol
- With non-steroidal anti-inflammatory drugs (especially salicylate), sulfonamide antibacterials, coumarin anticoagulants, monoamine oxidase inhibitors, -receptor blockers, benzodiazepines, tetracyclines, When chloramphenicol, dicyclohexylpiperidine, clobetin, ethanol and other drugs are combined, the dosage should be reduced. [3-4]
Glitazide dosage
- Take 80mg orally, once before breakfast or before breakfast and before lunch, also 40mg, 3 times a day, three meals before meals, daily if necessary after 7 days
- Ethanol
- After oral administration, 160 mg per day, generally starting at 80 to 160 mg per day, can be increased to 240 to 320 mg per day, divided into 2 to 3 times, depending on the condition. For those who switch to insulin, if the original dose is large (about 20-30 IU), the insulin will be halved on the first day, and this product will be added, and then gradually reduced according to the condition. Blood glucose and urine glucose should be regularly reviewed during the medication period in order to adjust the treatment plan. [3]
Glezide function and use
- It is the second-generation oral sulfonylurea hypoglycemic agent, which reaches the high bee 2-6 hours after oral administration, and about 10-12 hours at t1 / 2, which is mainly excreted by the kidneys. It has a hypoglycemic effect on adult diabetic patients, can reduce platelet adhesion, reduce plasma specific viscosity, reduce ADP-induced platelet aggregation, and improve nail wrinkle microcirculation.
- Platelets
Gleizit notes
- 1. Banned in pregnant women
- 2. Blood tests should be checked frequently while taking this medicine
- Glezit
- 3. Caution for those with poor renal function
- 4. Juvenile diabetes, ketodiabetes, diabetic coma, etc., require insulin injection, and cannot be used alone. [3]