What Is Dapsone?
Dapsone, this product is white or off-white crystalline or crystalline powder, odorless and slightly bitter. Dapsone is used in combination with other anti-leprosy drugs for the treatment of various types of leprosy caused by Mycobacterium leprae. Dapsone can also be used for the treatment of other skin diseases [1] .
- Drug Name
- Dapsone
- Alias
- Diaminodiphenylsulfone
- Foreign name
- dapsone
- Main indications
- Antibacterial effect
- Dapsone, this product is white or off-white crystalline or crystalline powder, odorless and slightly bitter. Dapsone is used in combination with other anti-leprosy drugs for the treatment of various types of leprosy caused by Mycobacterium leprae. Dapsone can also be used for the treatment of other skin diseases [1] .
Dapsone Basic Information
- Chinese name: aminophenylsulfone
- Chinese alias: 4,4'-sulfonyldiphenylamine; 4,4'-diaminophenylsulfone; 4-aminophenylsulfone; bis (4-aminophenyl) sulfone; 4-aminophenylsulfone;
- English name: dapsone
- English alias: 4,4'-Diaminodiphenylsulfone; Benzenamine, 4,4'-sulfonylbis-; 4- (4-aminophenyl) sulfonylaniline;
- CAS number: 80-08-0
- Molecular formula: C 12 H 12 N 2 O 2 S
- Molecular weight: 248.30100
- Exact mass: 248.06200
- PSA: 94.56000
- LogP: 3.92700
- Physical and chemical properties
- Appearance and properties: white crystalline powder
- Density: 1.361 g / cm 3
- Melting point: 175-177 ° C (lit.)
- Boiling point: 511.7ºC at 760 mmHg
- Flash point: 263.2ºC
- Stability: stable, flammable, incompatible with strong oxidants
- Storage conditions: storeroom is ventilated, low-temperature and dry, and stored separately from food materials
- Security Information
- Symbol: GHS07
- Signal Word: Warning
- Hazard statement: H302
- Packing level: III
- Hazard category: 6.1 (b)
- Customs Code: 29309070
- Dangerous Goods Transport Code: 3249
- WGK Germany: 1
- Danger category code: R22
- Safety instructions: S22
- RTECS number: BY8925000
- Dangerous goods mark: Xn [2]
- production method
- Add 4,4'-dichlorodiphenylsulfone, ketone powder, ketene chloride and ammonia water to the autoclave, heat with stirring, and react at 170-202 ° C and 3MPa for 14 hours, then lower the temperature to 60 ° C and filter , Water washing and drying to obtain the crude product 4,4'-diaminodiphenyl sulfone. The crude product is refined according to the use of the product. For example, the crude product can be dissolved in 10% hydrochloric acid, decolorized with activated carbon, filtered, cooled to below 10 ° C, adjusted to a pH of 2 to 2.5 with sodium carbonate solution, centrifuged, washed with water to neutrality, and dried to obtain Finished product. The yield is over 78%.
- (1) Using p-nitrochlorobenzene and p-aminobenzenesulfonic acid as raw materials (2) Using p-nitrochlorobenzene as raw material (3) Using p-chlorobenzenesulfonyl chloride and chlorobenzene as raw materials
- use
- Amine curing agent [2] .
Dapsone pharmacopoeia standard
Source (name) and content (potency) of dapsone
- This product is 4,4'-sulfonylbisaniline. Calculated on dry basis, containing C12H12N2O2S shall not be less than 99.0%.
Dapsone
- This product is white or almost white crystalline or crystalline powder; odorless, slightly bitter.
- This product is easily soluble in acetone, soluble in methanol, slightly soluble in ethanol, almost insoluble in water; soluble in dilute hydrochloric acid.
- Melting point
- The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 176 to 181 ° C.
Dapsone identification
- (1) Take this product, add methanol to make a solution containing 5 g per 1 ml, and measure according to the ultraviolet-visible spectrophotometry (Appendix IVA of Pharmacopoeia Part II of 2010 Edition). It has the maximum absorption at the wavelengths of 261nm and 296nm. Its absorbance is 0.35 to 0.38 and 0.59 to 0.62, respectively.
- (2) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Medicine" 412).
- (3) Identification of the first aromatic amines (Appendix III of Part Two of the 2010 Pharmacopoeia).
Dapsone inspection
- relative substance
- Take this product, add methanol to dissolve and dilute it to make a solution containing about 10mg per 1ml, as a test solution; take an appropriate amount, and dilute with methanol to make a solution containing about 20g and 100l per 1ml, as a control. Solutions (1) and (2). According to the thin-layer chromatography (2010 Appendix B Pharmacopoeia Part II) test, draw 10 l of each of the three solutions, point them on the same silica gel G thin-layer plate, and use toluene-acetone (2: 1) as the developing agent to expand. Air dry, spray with a 0.1mol / L hydrochloric acid solution containing 0.5% sodium nitrite, and then spray with a 0.1% naphthylethylenediamine dihydrochloride solution for several minutes. If the test solution shows obvious impurity spots, it must not be deeper than the main spot of the control solution (1); if 1 or 2 points are exceeded, it should not be deeper than the main spot of the control solution (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).
- 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 dapsone content
- Take about 0.25g of this product, accurately weigh, add 30ml of water and 20ml of hydrochloric acid solution (1 2), according to the permanent stop titration method (Appendix A of the second edition of the Pharmacopoeia, 2010 edition), and use sodium nitrite titration solution (0.1mol / L) Titration. Each 1ml of sodium nitrite titration solution (0.1mol / L) is equivalent to 12.42mg of C 12 H 12 N 2 O 2 S [3] .
Dapsone category
- Anti-leprosy drugs.
Dapsone storage
- Keep sealed.
Dapsone preparation
- Dapsone tablets
Dapsone drug analysis
- Method name: Determination of dapsone-permanent titration
- Application: This method uses titration to determine the content of dapsone.
- This method is applicable to dapsone.
- Principle of the method: After adding water and hydrochloric acid solution to the test product, titrate with the sodium nitrite titration solution (0.1mol / L) according to the permanent stop titration method. Record the amount of sodium nitrite titration solution and calculate it.
- Reagent: 1. Water (new boiling to room temperature)
- 2. Sodium nitrite titration solution (0.1mol / L)
- 3. Hydrochloric acid solution (1 2)
- equipment:
- Sample preparation: 1. Sodium nitrite titration solution (0.1mol / L)
- Preparation: Take 5.6mL of clear sodium hydroxide saturated solution, add freshly boiled cold water to 1000mL.
- Calibration: Take about 0.6g of standard potassium hydrogen phthalate which is dried to constant weight at 105 ° C, weigh it accurately, add 50mL of freshly boiled cold water, shake it to dissolve it as much as possible; add 2 drops of phenolphthalein indicator solution, use When this solution is titrated, when the end point is reached, potassium hydrogen phthalate should be completely dissolved and titrated until the solution becomes pink. Each 1mL of sodium hydroxide 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.
- Storage: Put it in a polyethylene plastic bottle and keep it in a sealed container. There are 2 holes in the plug. One glass tube is inserted into the hole. One tube is connected to the soda lime tube. One tube is used to suck out the liquid.
- Dilute the above sodium nitrite titration solution (0.1 mol / L) twice to obtain a sodium nitrite titration solution with a concentration of 0.05 mol / L.
- Operation steps: Accurately weigh 0.25g of the test sample, add 30mL of water and 20mL of hydrochloric acid solution (1 2), and titrate with the sodium nitrite titration solution (0.1mol / L) according to the permanent stop titration method. The volume number (mL), each 1mL of sodium nitrite titration solution (0.1mol / L) is equivalent to 12.42mg of dapsone (C12H12N2O2S), that is, [4] .
- Note 1: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weight. Precision requirements.
Dapsone drug description
Pharmacological effects of dapsone
- This product is a sulfone bacteriostatic agent, which has a strong bacteriostatic effect on leprosy, and shows a bactericidal effect at high doses. Its mechanism of action is similar to that of sulfa drugs. It acts on dihydrofolate synthase in bacteria and interferes with folic acid synthesis. Both have similar antibacterial spectrum and can be antagonized by aminobenzoic acid. This product can also be used as a dihydrofolate reductase inhibitor. In addition, this product still has immunosuppressive effects, which may be related to the effect of suppressing herpes-like dermatitis. If used alone for a long time, Leprosy is prone to develop resistance to this product [1] .
Dapsone pharmacokinetics
- This product is absorbed quickly and completely after oral administration. The protein binding rate is 50% to 90%. After absorption, it is widely distributed in body tissues and fluids. The concentration of liver and kidney is high, and the concentration of damaged skin is 10 times higher than that of normal skin. This product is metabolized in the liver by N-acetyltransferase. Patients can be divided into dapsone slow acetylation type and fast acetylation type. The peak blood concentration of the former is also higher after taking the drug, which is prone to adverse reactions, especially adverse reactions in the blood system, but the clinical efficacy has not increased. Fast-acetylated patients may need to adjust the dose. This product can be measured in the blood a few minutes after oral administration. The peak time is 2-6 hours, sometimes 4-8 hours. This product has hepatobiliary circulation.
- Dapsone tablets
Dapsone indication
- This product is used in combination with other leprosy drugs for the treatment of various types of leprosy and herpes-like dermatitis caused by Mycobacterium leprae. Treatment of polychondritis, annular granuloma, certain skin lesions of systemic lupus erythematosus, actinomycosis mycoplasmosis, party acne, psoriasis, shingles. It can be used in combination with trimethoprim to treat pneumocystis for the prevention of vivax malaria.
Dapsone usage dosage
- 1. Leprosy is inhibited orally, in combination with one or more other anti-leprosy drugs. Adults 50 100mg once a day; or 0.9 1.4mg / kg once a day according to body weight, the highest dose is 200mg daily. It can be taken orally from 12.5 to 25 mg daily, and then gradually increased to 100 mg daily. For children, the weight is 0.9 1.4mg / kg once a day. Due to the accumulation of this product, the drug is discontinued for 1 day every 6 days and 2 weeks for every 10 weeks.
- 2. For oral treatment of herpes-like dermatitis, adults start with 50 mg daily. If the symptoms are not completely suppressed, the daily dose can be increased to 300 mg. The maximum adult dose is 500 mg daily. After the condition is controlled, the minimum effective maintenance dose is reduced. Children begin to weigh 2mg / kg once a day, once a day. If the symptoms are not completely suppressed, the dose can be gradually increased, and the minimum effective amount is reduced after the condition is controlled.
- Dapsone
- Medication for pregnant and lactating women
- This product can reach an effective concentration in milk and has a preventive effect on newborns. However, sulfone drugs may cause hemolytic anemia in neonates with G-6-PD deficiency. Pregnant women and lactating women should fully weigh the pros and cons before taking the drug before deciding whether to use it. If there are indications for application, they should be applied under close observation.
- Medication for children
- Children's dosage is reduced, and generally has no significant effect on children's growth and development.
- Medication for elderly patients
- The liver and kidney function of elderly patients is reduced, and the dosage should be reduced.
Dapsone administration instructions
- 1. Monophenylsulfone treatment of leprosy is prone to bacterial resistance, so it should be applied on an equal basis with other drugs such as clofazimine and rifampicin.
- 2. The treatment of leprosy-negative, undefined and tuberculous leprosy needs to be taken in combination with other anti-leprosy drugs for six months. For other types of leprosy that are positive for bacteria, a combination of drugs is required for 2 years.
- 3. When treating herpes-like dermatitis, a gluten-free diet should be taken. After 6 months, the dose of dapsone can be reduced by 50%, or even discontinued.
Dapsone adverse reactions
- 1. In the early stage of treatment with this product, some patients may have mild discomfort, such as nausea, epigastric discomfort, anorexia, headache, dizziness, insomnia, weakness, etc., but they will soon disappear on their own.
- 2. Anemia, which can be caused by hemolysis, iron deficiency, or malnutrition, is generally seen in the early stages of treatment and can be corrected on its own. There may also be blood system reactions such as agranulocytosis and leukopenia.
- 3 Drug eruption is severe in the form of exfoliative dermatitis. If there is fever, enlarged lymph nodes, liver and kidney damage, and increased monocytes, it is called "dapsone syndrome."
- 4 Acute poisoning, taking a large dose of this product at one time can convert hemoglobin to methemoglobin, causing damage to tissues such as hypoxia, cyanosis, toxic hepatitis, nephritis, and neuropsychiatry, which can cause death if not treated in time.
Dapsone contraindications
- Those who are allergic to this product and sulfa drugs, severe liver damage and mental disorders are prohibited.
Dapsone matters needing attention
- 1. This product should be used with caution in the following cases: severe anemia, G-6-PD deficiency, degenerative hemoglobin reductase deficiency, liver and kidney dysfunction, gastric and duodenal ulcers, and those with a history of mental illness.
- 2. Cross-allergy: Cross-allergy exists between sulfone drugs. In addition, patients who are allergic to sulfonamides, furosemides, thiazines, sulfonylureas, and carbonic anhydrase inhibitors may also be allergic to this product.
- 3 Follow-up inspection: (1) blood count, once a week before medication and in the first month of treatment, once a month thereafter, for 6 consecutive months, and once every six months thereafter. (2) Determination of glucose-6-phosphate dehydrogenase (G-6-PD). If it is G-6-PD deficiency, this product should be used with caution. (3) Liver function tests (such as urinary bilirubin and aspartate aminotransferase assays) should be performed when patients experience anorexia, nausea, or vomiting during treatment, and should be discontinued if there is liver damage. (4) Determination of renal function. Patients with impaired renal function should regularly measure renal function during treatment and adjust the dose accordingly.
- 4 The number of primary and secondary dapsone-resistant leprosy strains is increasing, and this product should not be used alone to treat leprosy. It should be used with rifampicin, clofazimine, ethionamide, promethionamine, oxygen Combination of flufloxacin, minocycline, clarithromycin, etc.
- 5. Patients with skin lesion-negative bacteria have a treatment course of 6 months, and those with positive skin lesions have been treated for at least 2 years or until the bacteria turn negative. Treatment of indefinite and tuberculous leprosy requires 3 years, type 2 leprosy takes 2 to 10 years, and tumor leprosy requires lifelong medication.
- 6. The blood concentration of this product in fast-acetylated patients may be very low, and the dose needs to be adjusted. Patients with slow acetylation may have higher plasma concentrations of this product, and dose adjustments are also required.
- 7. Patients with impaired renal function need to reduce the amount of medication. If the creatinine clearance is less than 4ml / min, the blood concentration needs to be measured. Patients with anuria should discontinue this product.
- 8. If new or toxic skin irritation occurs during medication, this product should be discontinued immediately. However, there is no need to stop the drug when a leprosy reaction occurs.
- 9. If severe "reversible" irritation (type I) or neuritis occurs during treatment, a large dose of adrenaline should be used in combination.
- 10 Glucose-6-phosphate dehydrogenase deficiency patients need to reduce the amount of this product.
- 11. When treating rash-like dermatitis, a gluten-free diet should be taken for 6 consecutive months to reduce the dose of dapsone by 50% or discontinue this product.
Dapsone drug interactions
- Combined with probenecid, it can reduce the secretion of sulfones in the renal tubules, make the blood concentration of sulfone drugs high and long-lasting, and easily cause toxic reactions. Therefore, the dose of sulfones needs to be adjusted at the same time or later when applying probenecid. 2. Rifampicin can stimulate the activity of liver microsomal enzymes and reduce the blood concentration of this product by 1-7-1 / 10. Therefore, the dose of the latter should be adjusted while taking rifampicin or in the future application of dapsone. 3 This product should not be combined with myelosuppressive drugs, because it can aggravate the degree of leukocytes and thrombocytopenia, the toxicity to bone marrow must be closely observed when combined. 4 This product can aggravate the hemolytic reaction when combined with other hemolytic drugs. 5. When combined with trimethoprim, the blood concentrations of both can be increased. The mechanism may be: (1) Inhibition of dapsone metabolism in the liver. (2) The two compete for excretion in the kidney, and the increased blood concentration of this product can aggravate its adverse reactions. 6. When combined with didanosine, it can reduce the absorption of this product, because oral dosinosine needs to take a buffer to neutralize gastric acid, and this product needs to increase absorption in an acidic environment, so if the two must be used together Should be at least 2 hours apart. [1]
Dapsone overdose
- Overdose of this product mainly causes methemoglobinemia, hemolysis, liver and kidney function damage and mental disorders. Excessive treatment: (1) gastric lavage, 30 g of activated carbon, and laxatives once every 6 hours, at least for 24 to 48 hours. (2) In an emergency, patients with normal and degenerative hemoglobin reductase deficiency are given a slow intravenous injection of methylene blue 1-2 mg / kg. If the degenerative hemoglobin is severely accumulated, the injection can be repeated. (3) In non-emergency situations, use methylene blue 3 to 5 mg / kg orally every 4 to 6 hours, but patients with G-6-PD deficiency cannot use it. Activated carbon can also be used, even after using this product for several hours. [1]