What Is Danazol?

Danazol is a synthetic steroid heterocyclic compound, that is, the derivative of androgen 17a-acetylene testosterone, which is white or milky white crystal or crystalline powder. Soluble in chloroform, soluble in acetone, slightly soluble in ethanol, insoluble in water. It is clinically used for the treatment of endometriosis, and can also be used for the treatment of fibrocystic mastopathy, spontaneous thrombocytopenic purpura, hereditary angioedema, systemic lupus erythematosus, male and female breasts, and precocious puberty.

Danazol is a synthetic steroid heterocyclic compound, that is, the derivative of androgen 17a-acetylene testosterone, which is white or milky white crystal or crystalline powder. Soluble in chloroform, soluble in acetone, slightly soluble in ethanol, insoluble in water. It is clinically used for the treatment of endometriosis and can also be used for the treatment of fibrocystic mastopathy, spontaneous thrombocytopenic purpura, hereditary angioedema, systemic lupus erythematosus, male and female breasts, and adolescent precocity.
Chinese name
Danazol
Foreign name
Danazol
CAS number
17230-88-5
Molecular weight
337.45500

Danazol compounds

Danazol Basic Information

Chinese name: Danazol
Chinese alias: Anconazole; 17ALPHA-pregnost-2,4-diene-20-alkyn [2,3-D] isoazole-17BETA-ol;
English name: danazol
English alias: Danatol; Danazolum; Ladogal; Chronogyn; Danol; Cyclomen; Danzol; Danocrine; Winobanin;
CAS number: 17230-88-5
MDL number: MFCD00056838
EINECS number: 241-270-1
RTECS number: TU4157070
PubChem number: 24277708
Molecular formula: C 22 H 27 NO 2
Structural formula:
Molecular weight: 337.45500
Exact mass: 337.20400
PSA: 46.26000
LogP: 4.22100

Danazol physicochemical properties

Appearance and properties: white solid
Density: 1.21 g / cm 3
Melting point: 224.4-226.8ºC
Boiling point: 478.2ºC at 760 mmHg
Flash point: 243ºC
Refractive index: 1.604
Stability: Stable at normal temperatures and pressures.
Vapor pressure: 0mmHg at 25 ° C

Danazol Safety Information

Customs code: 2937290014
WGK Germany: 3
Danger category code: R20 / 21/22; R63
Safety instructions: S22-S36
Dangerous goods mark: Xn [1]

Danazol molecular structure data

1. Molar refractive index: 95.82
2. Molar volume (m / mol): 278.6
3. Isometric Zhang Rong (90.2K): 759.0
4. Surface tension (3.0 dyne / cm): 55.0
5. Polarizability (0.5 10cm): 37.98

Danazol Computational Chemical Data

1. Hydrophobic parameter calculation reference value (XlogP): 3.8
2.Number of hydrogen-bonded donors: 1
3.Number of hydrogen bond acceptors: 3
4.Number of rotatable chemical bonds: 1
5.Number of tautomers: none
6. Topological molecular polar surface area 46.3
7.Number of heavy atoms: 25
8.Surface charge: 0
9.Complexity: 677
10.Number of isotope atoms: 0
11. Determine the number of atomic stereocenters: 6
12. Uncertain number of atomic stereocenters: 0
13. Determine the number of chemical bond stereocenters: 0
14. Uncertain number of chemical bond stereocenters: 0
15.Number of covalent bond units: 1

Danazol uses

It is suitable for the treatment of endometriosis and spontaneous thrombocytopenia. [2]

Danazol Pharmacopoeia Standard

Danazol source (name), content (potency)

This product is 17-pregnost-2,4-diene-20-alkyn [2,3-d] isoxazole-17-ol. Calculated based on dry products, C22H27NO2 should be 97.0% to 103.0%.

Danazol traits

This product is white or off-white crystal or crystalline powder.
This product is easily soluble in chloroform, soluble in acetone, slightly soluble in ethanol, and insoluble in water.

Danazol specific rotation

Take this product, weigh it accurately, add chloroform to dissolve and quantitatively dilute it to make a solution containing about 10mg per 1ml, and measure it according to the law (Appendix VIE of Part Two of the 2010 Pharmacopoeia). The specific rotation is + 21 ° to + 27 ° .

Danazol identification

(1) Take about 2mg of this product, add 5ml of ethanol to dissolve, add 2 drops of silver nitrate test solution, and a white precipitate is formed.
(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 ("Infrared Spectra of Drugs" 147).

Danazol check

chloride
Take 1.0g of this product, add 30ml of water, shake to make the dispersion uniform, filter, take 15ml of the filtrate, check according to law (Appendix A of the second edition of the Pharmacopoeia, 2010 edition), and compare it with a control solution made of 4.0ml of standard sodium chloride solution. Thicker (0.008%).
Sulfate
Take 1.0g of this product, add 30ml of water, shake to make the dispersion uniform, filter, take 15ml of the filtrate, check according to law (Appendix B of Pharmacopoeia Part II of the 2010 edition), compare with the control solution made of 4.0ml of standard potassium sulfate solution Thicker (0.08%).
relative substance
Take this product, add the mobile phase to dissolve and dilute it to make a solution containing about 2mg 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, as a control Solution. According to the chromatographic conditions under the content determination item, take 10 l of the reference solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full range; and then accurately measure the test solution and the reference solution. Each 10 l was injected into a liquid chromatograph, and the chromatogram was recorded to twice 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 must not be greater than 0.5 times (0.5%) the area of the main peak of the control solution; the sum of the area of each impurity peak must not be greater than the area of the main peak of the control solution (1.0%).
Loss on drying
Take this product and dry it under reduced pressure at 60 ° C to constant weight, and the weight loss shall not exceed 1.0% (Appendix L of Pharmacopoeia Part II of 2010 Edition).

Determination of Danazol

It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition).
Chromatographic conditions and system suitability tests
Octadecylsilane-bonded silica gel was used as the filler; acetonitrile-methanol-water (4: 4: 3) was used as the mobile phase; the detection wavelength was 270nm. The number of theoretical plates is not less than 2500 calculated based on the danazol peak.
Assay
Take this product, weigh it accurately, add mobile phase to dissolve and quantitatively dilute it to make a solution containing about 0.2mg per 1ml. Precisely measure 10l into the liquid chromatograph and record the chromatogram; Method determination. Calculate the peak area according to the external standard method. [3]

Danazol method

Method name: Danazol API-Danazol-High Performance Liquid Chromatography
Danazol
Scope of application: This method uses high performance liquid chromatography to determine the content of danazol in danazol drug substance.
This method is suitable for danazol drug substance.
Principle of the method: The test sample was dissolved in a mobile phase and quantitatively diluted, and then subjected to HPLC for chromatographic separation. The ultraviolet absorption detector was used to detect the peak area of danazol at a wavelength of 270 nm and calculate its content.
Reagent: 1. Methanol
Acetonitrile
Equipment: 1. Instrument
1.1 HPLC
1.2 Column
Octadecylsilane-bonded silica gel is used as a filler, and the number of theoretical plates calculated based on the danazol peak should not be less than 2500.
1.3 UV absorption detector
Chromatographic conditions
2.1 Mobile phase: acetonitrile methanol water = 4 4 3
2.2 Detection wavelength: 270nm
2.3 Column temperature: 40 ° C
Sample preparation: 1. Preparation of reference solution
Accurately weigh the appropriate amount of danazol reference substance, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 0.2mg per 1mL, which is the reference solution.
2. Preparation of test solution
Accurately weigh the appropriate amount of the test product, add mobile phase to dissolve and quantitatively dilute it to make a solution containing about 0.2mg per 1mL, which is 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, and inject them into a high-performance liquid chromatograph. Use a UV absorption detector to measure the peak area of danazol (C22H27NO2) at a wavelength of 270 nm and calculate its content. [4]

Danazol pharmacological action

Danazol is a derivative of 17-acetylene testosterone. It is a synthetic androgen, has weak androgenic activity, and has both anabolic and antiestrogenic effects. But there is no progestin and estrogen activity. Danazol is a gonadotropin inhibitor that reduces the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH). Danazol acts on the estrogen receptor of endometrial cells, inhibits the efficacy of estrogen, causes the endometrium to atrophy, leads to anovulation and amenorrhea, which can last for 6 to 8 months, thereby achieving endometrial treatment The purpose of ectopic disease, and can make the nodules of fibrocystic mastopathy disappear and reduce pain. When used to treat hereditary angioedema, it can increase the level of serum C1 esterase inhibitors, leading to an increase in the C4 serum concentration of the complement system. In addition, because danazol has an assimilation effect, it can also increase body weight and increase platelet numbers. Increase estradiol and progesterone clearance in the body. [5]

Danazol Pharmacokinetics

Danazol is absorbed from the stomach and intestines after oral administration. If each administration is 100mg, twice a day, the peak blood concentration will be 0.2 0.8g / ml; if every administration is 200mg, twice a day, even for 14 days, the blood concentration will reach 0.25 2g / ml. After taking plasma concentration is 3 to 4 times higher than fasting. The half-life is 4.5h. Danazol is metabolized in the liver to acetylacetyltestosterone. Mainly distributed in the adrenal glands, and concentrated in the liver and kidneys. Metabolites are mainly excreted from urine, and a small part is excreted from feces. Excreted by the kidney, no significant accumulation in the body. [5]

Danazol indication

1. Mainly used for endometriosis which is intolerable or ineffective for other drug treatments.
2. It can still be used to treat breast cystic hyperplasia (fibrocystic mastopathy), male breast development, breast pain, dysmenorrhea, etc.
3. Can also be used for idiopathic thrombocytopenic purple scar, hereditary angioedema, systemic lupus erythematosus, precocious puberty, infertility and hemophilia and hemophilia B (Christmas disease). [5]

Danazol contraindications

1. Severe heart, liver and kidney dysfunction.
2. Unexplained genital bleeding.
3. Lactating women.
4. Epilepsy and severe hypertension patients are disabled. [5]

Danazol dosage forms and specifications

Capsule: 100mg, 200mg.
Suppositories: 500mg / capsule [5]

Danazol dosage

1. Danazol is suitable for patients with mild and moderate dysmenorrhea, obvious or infertile endometriosis. Can also be used as a conservative medication before surgery. 400 to 800 mg per day orally 2 to 3 times. If 400 mg per day does not make the symptoms alleviate quickly, menstruation stops and signs improve, it can be gradually increased to 600 mg to 800 mg per day. It usually starts on the first day of menstruation and lasts for 6 months. In recent years, it has been reported that danazol can be administered transvaginally to avoid the first-pass effect of oral administration and metabolize by the liver. The dosage is small, the effect is good, and the adverse reactions are few.
2. Fibroid mastitis: 100 to 400 mg per day, divided into two or three times orally for three to six months.
3. Male breast development: 200 to 600 mg per day, divided into two or three times orally.
4. Precocious puberty: 200 to 400 mg per day, divided into two or three times orally.
5. Thrombocytopenic purpura: 400 to 800 mg per day, divided into two or three times orally.
6. Hemophilia: 600 mg daily, orally 2 to 3 times a day for 14 days.
7. Hereditary angioedema: 600 mg per day, 3 times a day orally, and gradually reduced to 100 to 200 mg per day after 6 to 12 weeks, until the onset of symptoms is constantly controlled.
8. Lupus erythematosus: 400 to 600 mg per day.
9. Fibrocystic breast disease: 50 to 200 mg each time, twice a day. If the symptoms recur within one year after stopping the drug, you can re-administer.
10. Male breast development: 200 to 600 mg per day. [5]

Danazol adverse reactions

1. The female clitoris enlarges and the male testis shrinks. When liver function is impaired, both men and women can develop yellow sclera and skin.
2. The following reactions should be noted if they continue to occur: (1) women with vaginal burning, dryness, itching, bleeding, or fungal vaginitis due to low estrogen efficacy; (2) skin redness, mood, or mental state Changes, nervousness or sweating. (3) Sometimes muscle spasm pain may occur, which is a symptom of muscle poisoning.
3. Breast nodules still exist or expand during treatment, and the possibility of cancer must be considered.
4. For adolescent precocious puberty, danazol has a stimulating effect of increasing bone growth, so it is limited to use when other drugs are not effective.
5. It can cause alanine aminotransferase to rise, and it can return to normal after 3 to 7 weeks of withdrawal. [5]

Danazol precautions

1. Because danazol can cause a certain degree of fluid retention, those with epilepsy, migraine or heart and kidney dysfunction should be used with caution and must be closely monitored.
2. The effects of drugs on pregnancy: Generally, pregnancy will not occur during treatment. Once pregnancy is found, the drug should be stopped immediately. Danazol may have an estrogen effect on a fetus in theory, but it is rarely found clinically.
3. Danazol can affect the results of glucose tolerance test and thyroid function test, and can also reduce serum total T4 and increase serum T3.
4. When using danazol, pay attention to whether there is damage to the heart, liver, kidney function and reproductive organs. For men, pay attention to testicle size. When men take the medicine, they must follow up the semen volume and viscosity, and perform sperm counting and sperm motility testing. It is recommended to check every 3 to 4 months, especially for young patients.
5. For unexplained male breast development, danazol treatment can be considered before surgery.
6. For puberty precocious puberty, danazol can stop menstruation and degenerate breast development. Because it has the stimulating effect of increasing bone growth, it has no obvious advantages over other therapeutic precocious puberty drugs, so it is limited to severe patients who are ineffective for other drugs. use.
7. If there is no regular menstruation after 60 to 90 days of discontinuation, diagnosis and treatment should be performed. Those who need contraception during medication should use non-steroidal contraception instead of oral contraceptives.
8. Females should stop danazol treatment if they show symptoms of virilization. [5]

Danazol medication for pregnant and lactating women:

Pregnant women should not use this medicine, and those who are pregnant in the medication should terminate pregnancy. In theory, this product may have an androgenic effect on female fetuses, which cannot be taken by lactating women.

Danazol for children:

This experiment was not performed and there are no reliable references.

Danazol for the elderly:

General elderly patients with low physiological function should be taken in reduced amounts (such as 100 ~ 200mg a day). [6]

Danazol 's interaction with other drugs

1. Danazol combined with warfarin can enhance anticoagulant effect and prone to bleeding.
2. When danazol is combined with insulin, it is easy to develop drug resistance.
3. Generally do not become pregnant during treatment, once pregnancy is found, the drug should be stopped immediately. Danazol may have an estrogen effect on a fetus in theory, but it is rarely found clinically.
4. Taking danazol can affect the results of thyroid function tests, which can reduce total serum T4 and increase serum T3.
5. For men, follow up with semen volume and viscosity, count sperm and test sperm motility. It is recommended to check every 3 to 4 months, especially for young patients.
6. For puberty precocious puberty, it can stop the menstrual period and degenerate breast development. Because it has the stimulating effect of increasing bone growth, it has no obvious advantages over other therapeutic precocious puberty drugs, and is limited to severe patients who are ineffective for other drugs.
7. If there is no regular menstruation after stopping the drug for 60 to 90 days, diagnosis and treatment should be performed. Those who need contraception during medication should use non-steroidal contraception instead of oral contraceptives.
8. Females should stop danazol treatment if they show symptoms of virilization.
9. Combined with cyclosporine can increase the adverse reactions of cyclosporine.
10. Combined with adrenal corticosteroids can aggravate edema.
11. Combining with ampicillin, carbamazepine, phenobarbital, sodium phenytoin, phumidone, and rifampin can reduce the efficacy of danazol. [5]

Danazol expert review

Danadazazole binds to the androgen receptor of target cells, enabling the synthesis of mRNA and corresponding proteins, which is the basis of danazol's androgen action. However, some androgen-like effects are due to the effect of an increase in free testosterone concentration in plasma on danazol metabolites. For idiopathic thrombocytopenic purpura, refractory autoimmune hemolytic anemia. Danazol is a synthetic androgen, has weak androgenic activity, and has both assimilation and anti-estrogen effects. Danazol acts on the estrogen receptor site of endometrial cells and inhibits the efficacy of estrogen. Endometrial atrophy, resulting in anovulation and amenorrhea, which can last for 6 to 8 months, so as to achieve the purpose of treating endometriosis. Danazol is more toxic to the liver and should be checked for liver function. [5]

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