Injection agent for protecting ischemic myocardium and preparation method of injection

Abstract

The invention relates to an injection agent for protecting ischemic myocardium and a preparation method of the injection. Injection emulsion is prepared from the following raw materials in parts by mass: 1 to 5 parts of N-SAHA (Suberoylanilide Hydroxamic Acid), 0.2 to 12.5 parts of emulsifying agent, 2 to 100 parts of oil for injection, 0.02 to 5 parts of solubilizer, 0.03 to 0.4 part of oleic acid, 0.4 to 12.5 parts of glycerinum and the balance of water for injection. The injection emulsion can be effectively used for increasing local drug concentration of the N-SAHA in lipophilic organs such as angiocarpy and / or tissues before cardiac interventional operation, increasing the bioavailability of the N-SAHA, reducing general side effects of the N-SAHA, realizing effective protection on myocardium under an ischemic or reperfusion injury state and reducing or avoiding the occurrence of myocardial infarction; meanwhile, a new optional dosage form is provided for application of the N-SAHAin treating cancer by the injection emulsion.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an injection for protecting ischemic myocardium and a preparation method thereof, in particular to an emulsion for injection containing N-suberoylanilide hydroxamic acid for protecting ischemic myocardium and its preparation method. Background technique [0002] Histone deacetylase inhibitors (histone deacetylase inhibitors, HDACI) are a class of compounds that interfere with the function of histone deacetylases. research reports. [0003] It is known that N-suberoylanilide hydroxamic acid (SAHA, see formula I below for chemical structure) as a histone deacetylase (HDAC) inhibitor can induce cell differentiation and block cell cycle , Induce cell regulation and play a therapeutic role. In vitro studies have shown that N-suberoylanilide hydroxamic acid at nanomolar concentrations (IC 50 <86nmol / L) can inhibit HDAC 1, HDAC 2 and HDAC 3 (type I) and HDAC 6 (type II) e...

AI Technical Summary

Problems solved by technology

[0007] However, currently marketed N-suberoylanilide hydroxamic acid preparations are limited to antitumor oral dosage forms

Due to the poor water solubility of N-suberoylanilide hydroxamic acid, and the obvious first-pass metabolic elimination of N-suberoylanilide hydroxamic acid after oral administration, its oral bioavailability is very low, and it cannot be used in cardiovascular and other related diseases. Form effective therapeutic concentrations in adipose tissue

In addition, N-suberoylanilide hydroxamic acid can only play a therapeutic role as a prototype, and its metabolites are inactive, so chemical derivatization cannot be used to improve its oral bioavailability

In addition, oral N-suberoylanilide hydroxamic acid can cause systemic side effects if taken before cardiac interventional procedures

[0008] The problems mentioned above in the prior art have greatly limited the clinical application of N-suberoylanilide hydroxamic acid, especially its in ischemia / reperfusion During cardioprotection, because effective local drug concentrations cannot be achieved in cardiac tissue prior to cardiac intervention

Therefore, there is an urgent need to develop a new pharmaceutical dosage form of N-suberoylanilide hydroxamic acid to solve the excessive local drug concentration in the heart tissue of N-suberoylanilide hydroxamic acid in the process of ischemic myocardial protection. low problem

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