Didroxyprogesterone was an oral progesterone developed by Solvay, Germany. Later, Abbott acquired Solvay. The drug has been on the market in more than 150 countries since it was launched in the 1960s. It can be used to treat diseases caused by endogenous progesterone deficiency, such as dysmenorrhea, endometriosis, secondary amenorrhea, irregular menstrual cycle, dysfunctional uterine bleeding, premenstrual syndrome, threatened abortion or habitual abortion caused by progesterone deficiency and infertility caused by corpus luteum deficiency.

pharmacological action：

       Didroxyprogesterone is an oral progesterone, which can make the endometrium enter the complete secretory phase, so as to prevent the risk of endometrial hyperplasia and carcinogenesis caused by estrogen. Didroxyprogesterone can be used in various diseases with insufficient endogenous progesterone.
Didroxyprogesterone has stronger progesterone activity than progesterone, especially for non menopausal women; In addition, it has a lot of advantages when it is used during pregnancy, because didroxyprogesterone itself has no androgen activity, no anti androgen activity, no estrogen activity, no anti estrogen activity, and then it has no anti glucocorticoid effect. During pregnancy, pregnant women will not have masculine effect, and it will not have masculine or feminine effect on the fetus; Its characteristics can also be used in assisted conception, because women want to be pregnant; In addition, it has good progesterone effect, so it is better for endometrium. In addition, it does not antagonize the benefits of estrogen on blood lipid, homocysteine and glucose metabolism; As progestin, it does not increase the risk of thrombosis nor increase the risk of breast cancer in menopausal women. It also has no negative effects on the central nervous system (CNS); It also does not affect the metabolism of glucocorticoids; Of course, it is not toxic to the liver.

Market prospect at home and abroad

       As a progesterone drug, this product is used for gynecological diseases with many indications and good market sales. According to statistics, from 2008 to 2010, the progesterone market of sample hospitals in 22 key cities in China continued to grow, with an average growth rate of 29.62% in three years, of which didroxyprogesterone ranked first with a market share of 7.42%.
        In 2017, the sales of daprotone (didroxyprogesterone tablets) in the domestic market reached more than 1.3 billion yuan. In addition, the sales of fenbutone (compound preparation of didroxyprogesterone + estradiol) reached more than 300 million yuan, with a cumulative sales of nearly 1.7 billion yuan (based on this calculation, the annual consumption of domestic API is 2-3 tons). At the same time, the international market has a great demand for APIs. The annual demand of countries such as India, Europe, Russia and Brazil is expected to be 3-5 tons, and the global demand for APIs will be more than 9 tons in 2019. The selling price of API is expected to be USD 15000-20000 / kg.
Because the synthetic process of didroxyprogesterone involves photochemical reaction, and other steps are also difficult, and the overall process is very difficult, there has been no generic drug on the market at home and abroad for more than 60 years. Although many domestic companies have applied for relevant patents and many companies have applied for the environmental impact assessment of the project, it is understood that they are actually difficult to industrialize.

Development content and progress：

API：

       At present, our company has completed the preparation process development of kilogram finished products. The structure of the target and the intermediates of key photochemical reactions are confirmed to be correct by NMR, high-resolution mass spectrometry and single crystal test.

Preparation：

       At present, Abbott's products on the market in China include Daphne (didroxyprogesterone tablets) and fenbutone (estradiol tablets / estradiol didroxyprogesterone tablets in composite packaging). Fenbutone actually includes estradiol tablets and estradiol + didroxyprogesterone compound preparations, including 1mg and 2mg specifications), Therefore, it is essentially necessary to develop three completely different formulations from the preparation of didroxyprogesterone, namely didroxyprogesterone tablets, estradiol tablets and estradiol + didroxyprogesterone compound preparation. Estradiol API can be purchased directly.
At present, the small-scale and pilot scale-up study of the preparation process has been completed, and three batches of validation batches are being prepared.