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Targeting protein-polyethylene glycol-anticancer medicament junctional complex

A polyethylene glycol, anticancer drug technology, applied in antitumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of large toxic and side effects, poor solubility, low selectivity, etc., to prolong the half-life in vivo and increase the intake. , the effect of improving solubility

Inactive Publication Date: 2011-08-10
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The invention utilizes the excellent performance of PEG as a drug carrier and the active targeting function of targeting proteins to overcome the problems of poor solubility, low selectivity, and large toxic and side effects in the clinical application of anti-tumor drugs, and invents an active and passive tumor Targeting protein-polyethylene glycol-anticancer drug linker for targeted function

Method used

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  • Targeting protein-polyethylene glycol-anticancer medicament junctional complex

Examples

Experimental program
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Embodiment 1

[0028] Example 1Tf-PEG2K-SN38

[0029] (1) HO-PEG2K-NH 2 Synthesis

[0030] Weigh 2g of PEG (2K) into a 250ml round bottom flask and dissolve in 25ml of dichloromethane. Then add 0.4g silver oxide, 0.3g potassium iodide, and finally add 0.2g p-toluenesulfonyl chloride, stir magnetically at room temperature for 2-3h, filter with diatomaceous earth, wash with dichloromethane, and remove the solvent by rotary evaporation to obtain HO-PEG-OTs (1) About 2g of crude product. Thin-layer chromatography analysis, developer: dichloromethane-methanol-concentrated ammonia water (5:0.5:0.1), iodine vapor color development, the Rf of HO-PEG-OTs is 0.33. Dissolve the crude product (I) in 50ml of concentrated ammonia water (25%-28%), add 0.7g of ammonium chloride, stir magnetically for three days at room temperature, extract with dichloromethane, collect the organic layer, and remove the solvent by rotary evaporation to obtain HO- The crude product of PEG-NH2 is about 1.8g. The crude HO-...

Embodiment 2

[0041] Example 2Tf-PEG4K-SN38

[0042] (1) HO-PEG4K-NH 2 Synthesis

[0043] Weigh 2g of PEG (4K) into a 250ml round bottom flask and dissolve in 25ml of dichloromethane. Then add 0.23g of silver oxide, 0.17g of potassium iodide, and finally 0.11g of p-toluenesulfonyl chloride (TsCl), and stir magnetically at room temperature for 2-3h. The reaction solution was filtered with celite, washed with excess dichloromethane, and the solvent was removed by rotary evaporation to obtain about 2 g of crude HO-PEG-OTs (I).

[0044] Dissolve the crude product (I) in 50ml of concentrated ammonia water (25%-28%), add 0.345g of ammonium chloride, stir magnetically for three days at room temperature, extract with dichloromethane, collect the organic layer, and rotary evaporate to obtain the crude product of HO-PEG-NH2 About 1.8g, separated and purified by silica gel column chromatography to obtain white HO-PEG4K-NH 2 Pure product (II) 0.694g, yield 38.1%. TLC analysis is the same as that o...

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Abstract

The invention discloses a water-soluble targeting protein-polyethylene glycol-anticancer medicament junctional complex with targeting function and a preparation method thereof. The targeting protein-polyethylene glycol-anticancer medicament junctional complex provided by the invention is characterized by ensuring that the dissolvability of an anticancer medicament is improved, the in-vivo half-life period of the medicament is prolonged, and the anticancer medicament is selectively targeted so as to be released to tumor cells by virtue of the tumor passive targeting function of the macromolecular junctional complex and the tumor active targeting function of targeting protein specifically combined with the tumor cells. The preparation method of the junctional complex is characterized in that polyethylene glycol is utilized as a raw material to synthesize a heterobifunctional polyethylene glycol derivative, wherein one end of the heterobifunctional polyethylene glycol derivative is carboxyl, and the other end of the heterobifunctional polyethylene glycol derivative is maleimido; and the carboxyl end of the derivative is in covalent connection with the anticancer medicament, the maleimido end of the derivative is in covalent connection with the targeting protein, thus the targeting protein-polyethylene glycol-anticancer medicament junctional complex is obtained.

Description

technical field [0001] The invention relates to a water-soluble targeting protein-polyethylene glycol-anticancer drug linker with targeting function and a preparation method thereof. Background technique [0002] Cancer is known as the "killer" of human beings. It is a major challenge for human beings to develop and develop anticancer drugs with high efficiency and low toxicity. At present, chemotherapy is still one of the main ways to treat cancer clinically. However, many commonly used chemotherapy drugs such as paclitaxel and camptothecin analogues are difficult to develop due to their extremely low water solubility and low bioavailability; coupled with poor selectivity , high cytotoxicity, fast metabolism in vivo and other shortcomings greatly limit the clinical application of these drugs. In order to overcome the above defects, finding new and effective chemotherapeutic drugs for the treatment of tumors is still a focus of researchers. The PEGylation of anticancer dru...

Claims

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Application Information

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IPC IPC(8): A61P35/00A61K47/48A61K47/60A61K47/64
Inventor 栾立标张云坤
Owner CHINA PHARM UNIV
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