(17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate
norethisterone enantate
CAS: 3836-23-5
Molecular Formula: C27H38O3
(17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate - Names and Identifiers
| Name | norethisterone enantate |
| Synonyms | Norigest Norethindrone Enanthate norethisterone enantate NORETHISTERONEOENANTHATE NORETHISTERONE ENANTHATE 17-ethynyl-3-oxoestr-4-en-17-yl heptanoate 17alpha-ethynyl-19-nortestosterone 17-heptanoate 17alpha-Ethynyl-19-nortestosterone 17-heptanoate (17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate (8xi,17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate [(9S,10R,13S,14S,17S)-17-ethynyl-13-methyl-3-oxo-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] heptanoate |
| CAS | 3836-23-5 |
| EINECS | 223-326-7 |
| InChI | InChI=1/C27H38O3/c1-4-6-7-8-9-25(29)30-27(5-2)17-15-24-23-12-10-19-18-20(28)11-13-21(19)22(23)14-16-26(24,27)3/h2,18,21-24H,4,6-17H2,1,3H3 |
(17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate - Physico-chemical Properties
| Molecular Formula | C27H38O3 |
| Molar Mass | 410.59 |
| Density | 1.0736 (rough estimate) |
| Melting Point | 69.5°C |
| Boling Point | 470.54°C (rough estimate) |
| Flash Point | 219°C |
| Solubility | Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly) |
| Vapor Presure | 9.93E-11mmHg at 25°C |
| Appearance | Solid |
| Color | Crystals from pet ether |
| Storage Condition | Refrigerator, Under inert atmosphere |
| Stability | Chloroform (Slightly), Dmso (Slightly), Methanol (Slightly) |
| Refractive Index | 1.4700 (estimate) |
| Use | Content determination |
(17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate - Risk and Safety
| Toxicity | TDLo vn-wmn: 4 mg/kg:EYE ADVPB4 8,103,72 |
(17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate - Compound Norethisterone Enanthate Injection
Authoritative Data Verified Data
This product is a sterilized oil solution of norethisterone heptanate and estradiol valerate. The contents of norethisterone heptanoate (C27H3803) and estradiol valerate (C23H303) shall be 90.0% to 110.0% of the indicated value.
prescription
50g
Estradiol valerate 5G
Appropriate amount of solvent
Made up to 1000ml
trait
This product is a clear oily liquid, almost colorless to yellowish.
identification
(1) Take 2 drops of this product, add 5 drops of ethyl acetate, shake, add 5 drops of water, shake, add 5 drops of sulfuric acid, that is, purplish red.
(2) Take 1 drop of this product, add 1ml of ethanol, shake well, add 3 drops of silver nitrate test solution to generate internal color precipitate; Add 1 drop of Methyl red indicator solution, and touch red.
(3) the retention time of the two t peaks of the test solution should be consistent with the retention time of the corresponding two main peaks of the control solution in the chromatographic cabinet of id record under the content measurement.
examination
should comply with the relevant provisions under the injection (General Principle 0102).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using octanosilane bonded silica as filler; Methanol water (85:15) as mobile phase; The detection wavelength was 222nm, the number of theoretical plates shall not be less than 1500 based on the calculation of the peak of norgestrel heptanate. The separation degree between the peak of norgestrel heptanate and the peak of estradiol valerate shall be consistent with the demand.
- Content for determination: the sample was accurately metered with a child pipette, and quantitatively diluted with methanol to prepare a melt containing 20ug of norethisterone heptanoate and 20 ml of estradiol valerate per 1 ml, which was used as a sample solution, 20u1 was injected into the liquid chromatograph accurately, and the chromatogram was recorded. The reference substance of norgestrel heptanate and estradiol valerate was dissolved in methanol and quantitatively diluted to prepare a solution containing 200ug of norgestrel heptanate and 20ug of estradiol valerate per lml, which was determined by the same method, according to the external standard method to calculate the peak area, that is.
category
long-acting contraceptives.
specification
lml: norethisterone heptanoate 50mg and estradiol valerate 5Mg
storage
light shielding, closed storage.
Last Update：2022-01-01 13:43:30
(17beta)-17-ethynyl-3-oxoestr-4-en-17-yl heptanoate - Reference Information
| overview | contraceptives generally refer to oral contraceptives, including oral contraceptives for women and oral contraceptives for men. The principle of contraception is to inhibit ovulation, change the cervical mucus, so that the sperm is not easy to penetrate; or make the uterine glands reduce the production of liver sugar, so that the blastocyst is not easy to survive; or change the movement of the uterus and fallopian tubes, hindering the delivery of fertilized eggs, So that the sperm and eggs cannot be combined to form a fertilized egg, and ultimately achieve the purpose of contraception. Contraceptives are divided into three categories according to chemical institutions. The first category is progesterone derivatives, such as medroxyprogesterone, false progesterone, chloroprogesterone, etc.; the second category is estrogen derivatives, such as ethinylestradiol, ethinylestradiol cyclopentyl ether, ethylestradiol valerate, etc.; the third category is testosterone derivatives, which are derivatives after testosterone is methyl at the 19th position and have a strong progesterone effect, such as norethisterone, 18 methyl norethisterone, diacetinol, norethisterone enanthate, etc. norethisterone heptanoate (norethisteroneenanthate, referred to as hornethisterone, NET-OEN) is a long-acting contraceptive that is being widely used at home and abroad. It is injected into women and has a long-acting contraceptive effect. The memorandum of the Human Reproduction Department of the World Health Organization on the recent research of injectable contraceptives believes that "hornethindrone has become an important contraceptive to choose from due to its unique advantages of high efficiency, long-acting and reversible fertility suppression". More than 15 years of clinical trials have proved that there are no obvious adverse reactions. Since 1970, clinical pharmacology studies have been carried out on single and compound oxinone contraceptive injections. By the end of 1974, there were 7604 cases and 51410 cycles of users. The contraceptive effective rate was 98.6% ~ 99.96%. Among them, compound oxinone containing 50mg of oxinone and 5mg of estradiol valerate (E.V.) is an estrogen and progesterone contraceptive, and is a sterilized oil solution of oxinone enanthate and estradiol valerate, after injection, the drug can be released gradually and the long-term contraceptive effect is mainly by inhibiting the secretion of pituitary gonadotropin and inhibiting ovulation to achieve contraceptive effect. Intramuscular injection once a month, the contraceptive effect is almost 100%, and the menstrual cycle is good. |
| pharmacological action | a long-acting progesterone. Its main function is to inhibit the secretion of pituitary gonadotropin and inhibit ovulation, and at the same time affect the development of the endometrium, change the cervical mucus and hinder the penetration of sperm. After intramuscular injection, the injection is stored in local tissues and gradually released slowly to play a long-term effect. Using this product alone has no side effects of estrogen and does not affect milk secretion, but the incidence of irregular bleeding and amenorrhea is high. Intramuscular injection of 200mg on the 5th day of menstruation, once every two cycles or 60 days. |
| synthetic route | route 1: norethisterone (2) is used as raw material, esterified with heptanic anhydride in the presence of pyridine or p-toluenesulfonic acid to obtain a mixture of 3,17-position diheptanoate and 17-position heptanoate, hydrolyze the diester to obtain norethisterone heptanoate, the yield is 66%, the specific reaction process is as follows: route 2: using excess heptanic anhydride and appropriate amount of acetone as solvent, catalyzed by p-toluenesulfonic acid, then adding appropriate amount of water for hydrolysis, adding aluminum oxide to adsorb the finished product, and then using petroleum ether reflux extraction and elution. the specific reaction process is as follows: |
| Pharmacokinetics | Absorption and distribution: Compound norethisterone enanthate is stored in the injected local tissue after intramuscular injection, and is gradually released to exert a long-term effect. After a single intramuscular injection of 4-6 days, the active product norethisterone can reach the blood drug peak, and its apparent elimination half-life is 4-7 days. After one year of continuous administration, norethisterone heptanoate has no accumulation in the body. Metabolism and excretion: mainly through liver metabolism and kidney excretion. |
| indications | a long-acting contraceptive. The main function of this product is to inhibit ovulation. After intramuscular injection, most of it is stored in muscle tissue and gradually released to play a long-term role. |
| specification | compound noenoxone enanthate: 1ml contains 50mg norethisterone enanthate and 5mg estradiol valerate |
| usage and dosage | single acetylenoate needle is injected intramuscularly on the 5th day after menstruation and once every two weeks thereafter. compound norone enanthate is used to inject two branches intramuscularly on the 5th day after menstruation, and then one branch is injected on the 10th day of menstrual cycle. each branch can be used for one cycle. |
| adverse reactions | some patients have headache, abdominal distension and weight gain after use. Common adverse reactions are breakthrough bleeding, drip bleeding, shortened cycle and prolonged menstruation, which will gradually improve with the increase of the number of drugs, while the incidence of amenorrhea will gradually increase. |
| precautions | 1. the liquid medicine should be extracted clean and completely injected and injected into deep intramuscular injection on time. 2. When using this product, it needs to be heated in hot water, and it will be used after the fluidity is restored. |
| taboo | patients with acute and chronic hepatitis, nephritis, hypertension and breast lumps should not be used. |
| medication for pregnant and lactating women | this product has no effect on lactation of lactating women |
| Introduction to related drugs | Testosterone propionate: Testosterone propionate is an androgen drug, which is the propionate of testosterone. The effect is the same as testosterone and methyltestosterone, but the intramuscular injection lasts longer. It can promote the development and maturity of male organs and accessory. High doses have anti-estrogen effects, inhibit endometrial growth and ovarian and pituitary function. It also promotes protein synthesis and bone formation. The ratio of androgen to protein assimilation was 1:1. Clinically used for the treatment of primary or secondary male sexual dysfunction; male puberty growth retardation; palliative treatment of advanced breast cancer in postmenopausal women. This product is 98% bound to plasma proteins, and most of it is metabolized in the body and liver into less active androsterone and inactive 5-androsterone, which are combined with glucuronic acid or sulfuric acid and excreted in urine. Pain, induration, infection and urticaria may occur at the injection site; large doses can cause feminization, male testicular atrophy, sperm reduction; edema, jaundice, abnormal liver function and rash. Patients with allergic reactions should stop the drug immediately. Liver and renal insufficiency, pregnant women and prostate cancer patients are prohibited. |
| main reference | [1] Peng Ming et al. Study on the correlation between benzaldehyde content in compound norethisterone heptanoate injection and acid value and peroxide value of tea oil. Chinese pharmacy. 2013,24(13):1171-1173 [2] Peng Ming et al. Determination of related substances in compound norethisterone enanthate injection by high performance liquid chromatography. Chinese Journal of Pharmacy. 2012,47(23):1947-1951. [3] family planning institute, Zhejiang health experimental hospital. clinical pharmacology study of long-acting contraceptive injections with different doses of norethisterone enanthate. Chinese Journal of Clinical Pharmacology. 1985,2:16-23. [4] Shi Cheng. Research on the synthesis process of norethindrone. Zhejiang University. 2010 [5] Editor-in-Chief Zhao Kejian. Handbook of new pocket drugs. Beijing: China Medical Science and Technology Press. 2004. Page 226. [6] Wang Guoqiang et al. Preparation of oxindrone. Chinese Journal of Pharmaceutical Industry. 2008,39(1):9. [7] Cen Meizhi. Improvement of synthesis process of oxinone. Pharmaceutical industry. 1988,19(1):33-34. [8] compound norethisterone enanthate injection. [9] Zhang Junwu editor-in-chief. A new practical medical dictionary. Beijing: Beijing Medical University China Union Medical University Press. [10] Instructions for Testosterone Propionate Injection. |
Last Update：2024-04-09 20:02:46
