Use of rapamycin in preparation of intraocularly embedded drug

Abstract

The invention relates to the application of rapamycin (RAPA ) and medicament capable of self-degrading in preparing eye implantation slow release medicament, the medicament can keep certain reinforcement and shape after complete release, and can be naturally degraded under internal physiological conditions, thus can be absorbed and discharged externally through metabolizing, and no secondary surgery is needed to be taken out. The invention can be applied to the repulsion reaction in cornea transplantation for treating ophthalmology diseases.

Description

technical field [0001] The present invention relates to an ophthalmic pharmaceutical preparation, especially the application of a rapamycin (mycin, sirolimus, RAPA) and a self-biodegradable pharmaceutical carrier in the preparation of a slow-release drug for intraocular implantation. The long-acting rapamycin sustained-release drug for implantation enables rapamycin to play a unique therapeutic role in some chronic immune-related eye diseases. Background technique [0002] Corneal transplantation is the only way to restore sight for blind people with corneal disease. Postoperative immune rejection is the main reason for the failure of surgery, and corneal neovascularization is the main high-risk factor. At present, glucocorticoids are the main means of clinical application to prevent and treat tissue rejection after corneal transplantation, etc., but long-term use of glucocorticoids will not only lead to a variety of complications, such as high blood pressure, diabetes, and ...

AI Technical Summary

Problems solved by technology

Furthermore, the absorption of rapamycin after oral administration is affected by the acidity and alkalinity in the body, and different foods can affect the absorption of rapamycin

(2) Rapamycin is a fat-soluble drug, which can only be dissolved in oily solvents, such as castor oil, soybean oil, etc., and its solubility is limited, and it is prone to precipitation

The rapamycin solution is unstable at room temperature and it is difficult to develop an ideal follow-up preparation, so it is difficult to achieve a high drug concentration in the eye drops

(3) Rapamycin has a large molecular weight and is difficult to pass through the corneal barrier

The suspension used in our experiment is to dissolve rapamycin in soybean oil for injection to make 1% rapamycin eye drops. After the suspension is dropped into the eyes, the drug concentration in the eyes is almost "zero "In addition, eye drops are affected by the dilution of tear fluid and are prone to fluctuations.

(4) The therapeutic window of rapamycin is narrow, and the current drug delivery method is difficult to achieve the drug concentration of the therapeutic window required for the treatment of ophthalmic diseases in the eye

However, because the problem of the drug carrier has not been well resolved, so far, there has not been a sustained-release agent for intraocular implantation with long-term stable drug release function.

There is also a cyclosporine release system that uses collagen or liposome as a carrier. Their sustained release time is relatively short, and there is also a carrier that has a certain impact on vision (such as collagen), or the carrier is very expensive. (such as liposomes), and the carrier will be affected by tears and the drug will be lost, thereby further shortening the shortcoming of the drug effect

The curative effect of the intraocular drug delivery system of the prior art is still unsatisfactory