Preparation and clinic application of hydroxycamptothecin derivative and preparation thereof

Abstract

A product of the invention is a variety of hydroxycamptothecin derivative referred to as bipiperidine hydroxycamptothecin {chemical name: (+)-(4S)-4-ethyl-4-hydroxy-9 [ (4-piperidyl piperidine) carbonyl]-1H-pyrano [ 3 ', 4 ', 6 ', 7 '] butoprizine [1, 2-b] quinoline-3, 14-( 4H, 12H ) dione and (0-10) hydrate thereof}. The derivative is a broad-spectrum antineoplastic drug, and has curative effects on primary liver cancer, gastric cancer, head and neck adenoid epithelial cancer, leukemia, colon cancer, bladder cancer and other malignant tumors. The ipiperidine hydroxycamptothecin, salts thereof and (0-10) hydrate of the salts are prodrugs for hydroxycamptothecin and converted into closed hydroxycamptothecin in vivo, so as to overcome defects of open loop, poor effect and instability of a hydroxycamptothecin preparation (injection, lyophilized injection and oral preparation); and the derivative has good water solubility and is suitable for preparation of various types of preparations. The bipiperidine hydroxycamptothecin can be added with different salts to be prepared into different water-soluble compounds and hydrates thereof, is beneficial to preparation of various preparations, and has stable quality and curative effect obvious better than that of hydroxycamptothecin and preparation thereof. The bipiperidine hydroxycamptothecin, salts thereof, (0-10) hydrate of the salts and preparations thereof are in forms of tablet, capsule, particulate agent, oral liquid, injection, infusion solutions and lyophilized injection.

Description

1. Technical field [0001] The invention belongs to the preparation and clinical application of a class of hydroxycamptothecin derivatives (abbreviated as hydroxycamptothecin) and its preparations. 2. Background technology [0002] Hydroxycamptothecin is a cutting-edge drug of the camptothecin class. Its anti-tumor effect is higher than that of camptothecin, and its toxicity is lower than that of camptothecin. However, its water solubility and ester solubility are poor, and it is difficult to make suitable preparations. It must be ring-opened. Otherwise, it is not absorbed when it is made into an oral preparation, and it is unstable when it is made into an injection (opening ring), and the ring-opening effect is relatively poor. Therefore, making hydroxycamptothecin into a prodrug not only solves the shortcomings of hydroxycamptothecin instability and poor ring-opening curative effect, but also absorbs well and is easy to be made into different preparations, which will comple...

AI Technical Summary

Problems solved by technology

[0002] Hydroxycamptothecin is a cutting-edge drug of the camptothecin class. Its anti-tumor effect is higher than that of camptothecin, and its toxicity is lower than that of camptothecin. However, its water solubility and ester solubility are poor, and it is difficult to make suitable preparations. It must be ring-opened. Otherwise, it will not be absorbed when it is made into an oral preparation, and it will be unstable if it is made into an injection (opening ring), and the ring-opening effect is poor.

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