Oversaturated self-microemulsified progesterone composition and preparation method of same

Abstract

The invention provides an oversaturated self-microemulsified progesterone composition. The oversaturated self-microemulsified progesterone composition consists of progesterone, non-natural plant oil, emulsifier, assistant emulsifier, stabilizer and the like. A preparation method of the oversaturated self-microemulsified progesterone composition comprises the following steps of: uniformly mixing the non-natural plant oil and the assistant emulsifier; dissolving the progesterone in the mixed liquid after being subjected to ultrasonic treatment; and adding the emulsifier into the mixture, and adding to dissolve or suspend the stabilizer in the mixture to obtain the composition. In the invention, as the progesterone is solubilized in 10-90nm oil-in-water microemulsion, dissolubility and dissolution rate of the progesterone in gastrointestinal fluid are increased; the microemulsion which is formed after oral administration envelops the progesterone in the non-natural plant oil and a surfactant layer so as to prevent the progesterone from being degraded by acid and enzyme in a gastrointestinal tract; and the stabilizer can be used for inhibiting progesterone crystals from precipitation during the dilution of the microemulsion to form oversaturated progesterone solution, so that more progesterone can be absorbed. The oversaturated self-microemulsified progesterone composition has the characteristics of low viscosity, stability in quality, high bioavailability, low toxicity, less side effect, short preparation time, low energy consumption and the like.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a progesterone supersaturated self-microemulsion composition with high oral bioavailability and a preparation method thereof. Background technique [0002] Progesterone (English name progesterone, chemical name pregn-4-ene-3,20-dione) is a natural progesterone with a progesterone-like effect, and is widely used in the treatment of threatened abortion, habitual abortion, and post-artificial insemination. , infertility, premenstrual tension syndrome, anovulatory DUB, anovulatory amenorrhea, endometrial hyperplasia, endometrial adenocarcinoma, endometriosis and menopausal syndrome and other progesterone or luteal insufficiency disease or symptoms caused by it. In hormone replacement therapy (HRT), while estrogen is given, progesterone must be given continuously for a long time or at the end of menstruation at the same time, so as to avoid excessive proliferation of endometr...

AI Technical Summary

Problems solved by technology

However, synthetic progesterone has an androgen-like effect, and it is easy to cause fluid retention after application, which can lead to changes in high-density lipoprotein (HDL), interfere with glucose metabolism, and change the shape of arterial wall tissue, as well as headaches, emotional changes, and masculinization of the fetus , teratogenic and other side effects

So far, no synthetic progesterone can exert the same hormonal effect as natural progesterone, and artificial synthetic oral progesterone cannot completely replace progesterone

[0005] U.S. patent US4196188 has reported a micronized progesterone oral capsule, and domestic Zhejiang Aisheng Pharmaceutical Co., Ltd. has also launched a micronized progesterone capsule (micronized progesterone, specification 100mg / grain), and micronized progesterone can The small particle size of progesterone increases the absorption of progesterone after oral administration and improves the bioavailability, but the individual variation of micronized progesterone medication is relatively large, and the metabolism of progesterone in the body cannot be avoided. Poor absorption and metabolic problems, the application of progesterone to oral administration, has become a key issue in the application of progesterone

[0006] Chinese patent 200710049940.X discloses a submicron emulsion (fat emulsion) progesterone injection, the injection contains at least 45.5% water, the natural vegetable oil used is difficult to be emulsified, the emulsion formed has a larger particle size, and the submicron Milk is a thermodynamically unstable system, which is likely to cause instability of progesterone injection; and injection administration has many adverse reactions, is inconvenient to carry, and poor patient compliance; in addition, this method also requires high-pressure homogenization when preparing submicron emulsion progesterone injection. Machines and other external forces do work, and the preparation process is more complicated

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