What Is Mifepristone?

Mifepristone, in addition to anti-pregnant pregnancy, catamenopause and pregnancy, intrauterine induction of fetal death, is also used for gynecological operations, such as the placement and removal of intrauterine devices, endometrial specimens, and abnormal cervical development Laser separation and cervical dilation and curettage.

Drug type: Essential medicines
Drug name: Mifepristone

English name: Mifepristone
Chinese alias: Antiprogesterone
English alias: RU-38486; Lunarette; RU-486

Introduction to mifepristone compounds

Mifepristone Basic Information

Chinese name

Chinese alias: 11- [4- (N, N-dimethylamino)] phenyl-17-hydroxy-17- (1-propynyl) -estrone-4,9-dien-3-one; 11- (4-Dimethylamino) phenyl-17-hydroxy-17- (1-propynyl) estra-4,9-dien-3-one; (1L, 17) -11- [4- (dimethylamino) phenyl ] -17-Hydroxy-17- (1-propynyl) estrone-4,9-dien-3-one; bead-containing;

English name: mifepristone

English alias: Mifepristone

CAS number: 84371-65-3

Molecular formula: C ₂₉ H ₃₅ NO ₂

Molecular weight: 429.59400

Exact mass: 429.26700

PSA: 40.54000

LogP: 5.40650

Physical and chemical properties of mifepristone

Appearance and properties: light yellow solid

Density: 1.18 g / cm ³

Melting point: 195-198 ° C

Boiling point: 628.6ºC at 760 mmHg

Flash point: 334ºC

Refractive index: 1.623

Stability: stable under normal temperature and pressure

Storage conditions: 2-8ºC

Mifepristone Safety Information

Symbol: GHS08

Signal Word: Danger

Hazard statement: H360

Cautionary statement: P201; P308 + P313

WGK Germany: 3

Danger category code: R60

Safety instructions: S53-S22-S36 / 37 / 39-S45

RTECS number: KG2955000

Dangerous goods mark: T ^[1]

Mifepristone production method

Method 1: Using the ketal compound (I) at position 3 of 4,9 estadiene-3,17-dione as a raw material, and reacting with propyne magnesium bromide Grignard reagent, introducing propynyl at position 17 to obtain Compound (II). Then, the 5-position ethylenic bond is selectively epoxidized to obtain compound (III). Then, it is reacted with p-dimethylaminobenzene magnesium bromide in tetrahydrofuran containing a copper bromide-methyl sulfide complex, and p-dimethylaminophenyl is introduced at the 11 position to obtain compound (IV). Finally, it was hydrolyzed with hydrochloric acid and dehydrated in methanol to obtain mifepristone. Yield was 21.5%.

Method 2: Also use 4,9-estradiene-3,17-dione as the raw material to protect the carbonyl group at the 3-position; then epoxidize, then introduce the propynyl group at the 17-position, and introduce the pair at the 11-position Dimethylaminophenyl, finally hydrolyzed to give mifepristone. Compared with scheme 1, only the order of epoxidation and introduction of propynyl group is different, and the reaction steps are the same. The total yield is 35% -40% ^[1] .

Mifepristone use

A new type of antiprogestin with anti-glucocorticoid activity, but no progesterone, estrogen, androgen and anti-estrogen activity. Affinity to progesterone receptor is 5 times stronger than progesterone. It is used to prevent early pregnancy, induce menstruation and stop pregnancy, and induce intrauterine induction of labor. It is used as a new antiprogestin in anti-early pregnancy drugs and has anti-glucocorticoid activity. Mifepristone has anti-fertilized egg implantation, induces menstruation, and promotes cervical maturity. Its mechanism of promoting menstruation and pregnancy is mainly through the competition of progesterone receptors on the endometrium (decidua) to block the effect of progesterone. Affinity to progesterone receptor is 5 times stronger than progesterone. It is used to prevent early pregnancy, induce menstruation and abortion, and induce intrauterine induction of fetal death ^[1] .

Mifepristone Pharmacopoeia Standard

[Identification] (1) Take this product, add ethanol to dissolve and dilute it to make a solution containing about 10 g per lml, and measure according to ultraviolet-visible spectrophotometry (Appendix IV A). There are 304 nm and 260 nm wavelengths. Maximum absorption. (2) The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 1141).

[Inspection] Take this product, dissolve and dilute it with methanol to make a solution containing about 0.5 mg per lml, and use it as the test solution. Take 2ml for precise measurement, place it in a 100ml measuring flask, and dilute to the mark with methanol. Shake well as control solution. Tested according to high performance liquid chromatography (Appendix VD), using octadecylsilicone bonded silica as a filler, methanol-water-triethylamine (75: 25: 0.05) as the mobile phase, and the detection wavelength is 304 nm . The number of theoretical plates is not less than 2000 calculated from the mifepristone peak. Take 10 l of the control solution and inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 10% of the full scale. Then accurately measure 10 l each of the test solution and the control solution, and inject them into the liquid chromatograph respectively, and record the chromatogram to twice the retention time of the main component peak. If there is an impurity peak in the chromatogram of the test solution, the area of a single impurity peak must not be greater than 0.5 times (1.0%) the area of the main peak of the control solution, and the sum of the area of each impurity peak must not be greater than the area of the main peak of the control solution (2.0%). Loss on drying: Take this product and dry to constant weight at 105 . Lose weight should not exceed 0.5% (Appendix L).

[Content determination] Take about 0.3 g of this product, accurately weigh, add 20 ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and titrate with perchloric acid titration solution (0.1 mol / L) until the solution becomes blue Green, and the results of the titration are corrected with a blank test. 1 ml of chloric acid titration solution (0.1 mol / L) is equivalent to 42.96mg of C29H35NO2

[Category] Anti-early pregnancy drugs.

[Storage] shading and sealed.

Mifepristone Drug Description

Mifepristone Pharmacology

It is a strong anti-progestin and can bind to progesterone receptors and glucocorticoid receptors. It has 5 times more affinity for progesterone receptors in the endometrium than progesterone. It has an induction effect on all stages of pregnancy in pregnant animals. Non-surgical anti-early pregnancy drugs. There was no significant effect on cortisol levels at effective doses. Because the drug can not cause sufficient uterine activity, it is high in incomplete abortion when used alone for anti-early pregnancy, but it can increase the sensitivity of the uterus to prostaglandins. Therefore, the addition of small doses of prostaglandins can reduce the adverse effects of prostaglandins. , And can significantly improve the complete abortion rate (over 95%). This product has the function of softening and dilating the cervix at the same time. Oral tmax is 1 ~ 3 hours, bioavailability is 70%, plasma protein binding rate is 98%, and t1 / 2 elimination is about 18 hours. Vaginal bleeding usually begins 30 hours after oral administration and lasts for 1 to 16 days.

Mifepristone indication

In addition to anti-pregnant pregnancy, catamenopause, and intrauterine induction of fetal death, it is also used for gynecological operations, such as placement and removal of IUDs, endometrial specimens, laser separation of cervical canal abnormalities, and cervical dilatation. And curettage.

Mifepristone dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Mifepristone adverse reactions

Nausea, vomiting, dizziness, and abdominal pain can be seen. Pain caused by uterine spasm can be treated with analgesics.

Mifepristone contraindications

People with heart, liver, kidney disease and adrenal insufficiency, who have been receiving corticosteroid therapy for a long time, ectopic pregnancy, bleeding disorders, patients who do not comply with treatment, do not understand the role of treatment, porphyria, intrauterine device IUD, allergies, etc. Are disabled.

Mifepristone precautions

(1) This product should not be used in early pregnancy with severe reactions, nausea and frequent vomiting to avoid worsening the reaction. (2) For men diagnosed with early pregnancy, menopause should not exceed 49 days. The shorter the pregnancy, the better the effect. (3) When using this product and prostaglandin sequential medication to fight early pregnancy, a small number of women have incomplete abortion, which can cause a lot of bleeding, so it must be used under the supervision of a doctor and processed in a timely manner. (4) After taking the drug, a small amount of vaginal bleeding usually occurs, and a small number of women have abortions before taking prostaglandin drugs; about 80% of pregnant women discharge villous fetal sacs within 6 hours after using prostaglandins, and about 10% during pregnancy Women excrete the fetal sac within one week after taking the medicine. (5) Patients should be consulted 8 to 15 days after administration to determine the effect of abortion. Ultrasound may be performed if necessary, or blood chorionic gonadotropin (HCG) may be determined. If the diagnosis is abortion failure or incomplete abortion, negative pressure suction hysterectomy should be performed. Terminate pregnancy or clear the uterine cavity. (6) All doctors or patients undergoing abortion surgery should be carefully considered before use, because this product may have some special risks, such as sepsis. (7) Because this product must be administered sequentially with prostaglandins, there are contraindications for prostaglandins, such as glaucoma, asthma, and allergies, mifepristone should not be used. Avoid use in pregnant women over 35 years old, smoking women.

Mifepristone drug interactions

Cannot be used in combination with rifampicin, carbamazepine, griseofulvin, barbiturates, phenytoin, non-steroidal anti-inflammatory drugs, aspirin, and adrenal corticosteroids.