Sirolimos sustained and controlled release preparation and preparation method thereof

Abstract

The invention provides a Sirolimus slow controlled release preparation and a preparation method thereof. By adopting the solubilizing methods including a solid dispersion technology or cyclodextrin inclusion technology or adding one or a plurality of surface active agents after micronizing drugs and the like, the solubility is dramatically improved and further the bioavailability is improved, therefore, a matrix type slow controlled release preparation is made by adding one or a plurality of framework materials and other accessories, or a diaphragm-controlled or osmotic pump type slow controlled release preparation is made by adopting slow controlled release materials for coating. The Sirolimus slow controlled release preparation has better solubility and dissolution rate, high bioavailability as well as slow controlled release effect, thus being capable of maintaining steady blood concentration, bringing down the concentration of peak, reducing the occurrence of adverse reaction and improving the safety of clinical medicines, in addition, the raw materials can be acquired easily, the preparation process is simple and feasible with high yield rate and low cost, and the large-scale industrial production can be realized and the economic benefit is marked.

Description

technical field [0001] The invention belongs to the field of medicines, and more specifically relates to a sirolimus sustained and controlled release preparation and a preparation method thereof. Background technique: [0002] Sirolimus, as the third generation of immunosuppressant, is a new and powerful immunosuppressant with less toxicity discovered so far, and it is becoming the basic drug for long-term immunosuppressive treatment of organ transplant patients. Clinically, it can be used for the anti-rejection effect of organ transplantation and the treatment of autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, psoriasis, etc. Its immunosuppressive effect is 100 times stronger than cyclosporine and 30 times stronger than tacrolimus. However, due to its narrow therapeutic window and high incidence of adverse reactions such as hypertriglyceridemia and hypercholesterolemia, its wide application in clinical practice is limited. [0003] Sirolimus is a kin...

AI Technical Summary

Problems solved by technology

[0008] ①Typical poorly soluble drug with low oral bioavailability

There are many problems in the clinical application of this preparation: 1) sirolimus is unstable in solution, sirolimus contains cis-trans isomers, and sirolimus exists with trans configuration in solid state, However, in the solution, sirolimus exists in two configurations of cis and trans, and the configuration ratio changes with different solvents and temperatures

2) The lecithin in the oral solution is in a solution state and is easily oxidized, which requires harsh production conditions

3) The human bioavailability is low, only 14%

4) It is difficult to take quantitatively. It is necessary to use a specific applicator to accurately draw the prescribed amount from the bottle, and then dilute it to take

5) The solution is not easy to transport and store. Sirolimus oral liquid should be stored at 2-8°C. After opening, it must be used up within 1 month, and it should not be stored at room temperature (over 25°C) for more than 30 days.

However, its preparation process is relatively complicated, and it cannot maintain a stable blood drug concentration, which can effectively reduce the incidence of adverse reactions such as hyperlipidemia caused by excessive blood drug concentration.

[0011] ② Narrow therapeutic window, high incidence of hyperlipidemia

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