Stable progesterone water-soluble injection and preparation method thereof

Abstract

The invention relates to a progesterone water-soluble injection and a preparation method thereof. The progesterone water-soluble injection comprises progesterone, a cyclodextrin derivative solubilizer, an inclusion accelerator and injection water. Sodium citrate and citric acid are taken as the inclusion accelerator, and a complex is formed with cyclodextrin by using the polyhydric structural features of sodium citrate and citric acid, so that the inclusion constant of the complex is improved, the problem that the using amount is excessive when the progesterone water-soluble injection is prepared by using a cyclodextrin derivative as the solubilizer is solved effectively, the using amount is reduced to less than 10%, and the renal toxicity, hemolytic activity and carcinogenicity risk of the cyclodextrin derivative are reduced obviously through such using amount, so that the safety is improved. The pain reaction is relatively lower when the progesterone water-soluble injection is used for injection, the injection is low in irritation, unlikely to be allergic and high in adaptability for long-time use of a patient, and relative to clinically frequently-used progesterone oil-soluble injection in the present stage, the injection has the advantages of dosage form.

Description

[0001] A progesterone aqueous solution type injection and a preparation method thereof. technical field [0002] The invention belongs to the field of pharmaceutical preparations, and relates to a progesterone aqueous solution type injection and a preparation method thereof. Background technique [0003] Progesterone is a natural progestin, insoluble in water, soluble in organic solvents such as ethanol. Progesterone is a commonly used sex hormone drug, which can regulate hormone balance. Progesterone has the general effect of progesterone. It is widely used in clinical practice. Sexual and recurrent abortion, treatment of premenstrual tension syndrome, and estrogen cycle use to counteract the effect of estrogen alone on the endometrium. [0004] Progesterone is a fat-soluble substance that is insoluble in water. Progesterone is rapidly destroyed in the gastrointestinal tract and liver when taken orally. Currently, in addition to oral administration, there are mainly two ro...

AI Technical Summary

Problems solved by technology

At present, the common progesterone aqueous solution injections on the market are oil solution injections. This type of injections has a greater pain response, greater irritation, and is prone to allergies. It is very inconvenient for long-term users and brings inconvenience to clinical use

In the Chinese patent CN101152186A, the progesterone drug is prepared into a submicron emulsion and then prepared into a progesterone aqueous solution type injection. This method improves the pain and sensitivity of the progesterone aqueous solution type injection of the traditional oil solution to a certain extent, and also has Less irritation and long-term use tolerance, but the pain of oil solution injection is still stronger than that of aqueous solution injection, and there are more types of excipients used in the preparation process, and water phase and oil phase preparation are also added in the preparation process. Homogenization, cooling and dilution, etc., the process is more complicated

But so far we don’t have a deep understanding of its safety. It has been reported in the literature that this excipient has certain nephrotoxicity, hemolysis and carcinogenicity, and there may be more serious side effects that are still unknown to us.