Slow-released injection containing nolatrexed dihydrochloride and synergist thereof

Abstract

The invention relates to a slow-release injection containing nolatrexed and a synergistic agent of the nolatrexed, which consists of a slow-release microballoon sphere and a solution medium, wherein, the slow-release microballoon sphere comprises active anti-cancer ingredients and slow-release accessories; and the solution medium is a special solution medium containing a suspending agent. The active anti-cancer ingredients are antimetabolites, such as pemetrexed, rumitrexed, raltitrexed, nolatrexed, carmofur, dexrazoxane, tegafur, zalcitabine, emtricitabine, ibatabine, ancitabine, decitabine, flurocitabine, enocitabine, imidazoletabine, capecitabine, gemcitabine, fludarabine or cladribine, and the like, and synergistic agents of the antimetabolites selected from topoisomerase inhibitors and / or tetrazine compounds; the slow-release accessories are selected from one of polifeprosan, di-fatty acid and decanedioic acid copolymer, polylactic acid copolymer and EVAC or the combination thereof; the viscosity of the suspending agent is 100cp to 3000cp (at the temperature of 20 DEG C to 30 DEG C) and the suspending agent is selected from carboxymethylcellulose sodium and the like. The slow-release microballoon sphere can also be prepared into a slow-release implant used for being injected or put in tumors or the surrounding of the tumors so as to enhance the effects of radiotherapy and chemotherapy.

Description

(1) Technical field [0001] The invention relates to a slow-release injection containing an anti-metabolite drug and / or a synergist thereof and a preparation method thereof, belonging to the technical field of medicines. (2) Background technology [0002] As a commonly used chemotherapeutic drug, antimetabolites have been widely used in the treatment of various malignant tumors. However, its unexpected toxicity and drug resistance greatly limit the application of this class of drugs. The blood vessels, connective tissue, matrix protein, fibrin, and collagen in the tumor stroma not only provide scaffolds and essential nutrients for the growth of tumor cells, but also affect the concentration of chemotherapy drugs around the tumor and in the tumor tissue. Infiltration and diffusion (see Netti et al. "The influence of the status of the extracellular matrix on the drug delivery in solid tumors" "Cancer Research" 60 pp. 2497-503 (2000) (Netti PA, Cancer Res.2000, 60 (9 ): 2497-5...

AI Technical Summary

Problems solved by technology

Not only that, the excessive expansive hyperplasia of solid tumors, the interstitial pressure, tissue elastic pressure, fluid pressure and interstitial viscosity are all higher than those of the surrounding normal tissue. Therefore, it is difficult for conventional chemotherapy to form an effective drug concentration in the tumor. See Kong Qingzhong et al. "Intratumoral placement of cisplatin plus systemic carmustine in the treatment of rat brain tumors" "Journal of Surgical Oncology" 69 pages 76-82 (1998) (Kong Q et al., J SurgOncol.1998 Oct; 69 (2): 76-82), simply increasing the dosage is limited by systemic reactions

Local application of drugs may solve the problem of drug concentration to some extent. However, surgical operations such as drug implantation are more complicated and traumatic. In addition to easily leading to various complications such as bleeding, infection, and decreased immunity, it may also cause or Accelerate tumor spread and metastasis

In addition, the preparation and expensive costs before and after the operation often affect its effective implementation.

[0003] The DNA repair function in tumor cells is significantly increased after chemotherapy, which often leads to the enhancement of tumor cell resistance to anticancer drugs, resulting in treatment failure