Preparation method of fatty acyl-RGD (Arg Gly Asp) induced docetaxel target liposome and antitumor activity thereof

A targeted and amphiphilic technology, applied in the field of biomedicine, can solve the problem that ordinary nano drug delivery systems do not have targeting

Inactive Publication Date: 2011-11-23
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Ordinary nano-drug delivery system is not targeted

Method used

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  • Preparation method of fatty acyl-RGD (Arg Gly Asp) induced docetaxel target liposome and antitumor activity thereof
  • Preparation method of fatty acyl-RGD (Arg Gly Asp) induced docetaxel target liposome and antitumor activity thereof
  • Preparation method of fatty acyl-RGD (Arg Gly Asp) induced docetaxel target liposome and antitumor activity thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1B

[0032] Embodiment 1Boc-Arg (NO 2 Preparation of )-Gly-OBzl

[0033] Will Boc-Arg(NO 2 )-OH 1.675g (5.25mmol) was dissolved in an appropriate amount of anhydrous DMF, and N-hydroxybenzotriazole (HOBt) 0.675g (5mmol) was added in an ice bath to completely dissolve. After 10 minutes 1.337 g (5.75 mmol) of dicyclohexylcarbodiimide (DCC) were added. Obtain reaction liquid (I), stand-by. Suspend 1.685g (5.0mmol) Tos·Gly-OBzl in an appropriate amount of anhydrous THF under ice-cooling, and then add a few drops of N-methylmorpholine (NMM) to adjust the pH to 8-9. Stir for 35 minutes to obtain the reaction solution (II), which is ready for use. The reaction solution (I) was added to the reaction solution (II) under ice-cooling, firstly stirred under ice-cooling for 1 h, then stirred at room temperature for 12 h, TLC (chloroform / methanol, 10:1) showed that Tos·Gly-OBzl disappeared. Dicyclohexylurea (DCU) was filtered off, and the filtrate was blown off of DMF. The residue was diss...

Embodiment 2

[0034] Example 2HCl H-Arg (NO 2 Preparation of )-Gly-OBzl

[0035] 2.33g (5mmol) Boc-Arg (NO 2 )-Gly-OBzl was dissolved in an appropriate amount of 4mol / l hydrogen chloride-ethyl acetate solution, stirred at room temperature for 2 hours, TLC (chloroform / methanol) showed that the raw material point disappeared, concentrated under reduced pressure to remove ethyl acetate, the residue was repeatedly added a small amount of ether for Concentrate under reduced pressure to remove hydrogen chloride gas. Finally, a small amount of diethyl ether was added to triturate the residue to obtain 1.91 g (95%) of crude product as a colorless solid, which was directly used in the next reaction. ESI-MS(m / z)367.1[M+H] + , 733.1[2M+H] + .

Embodiment 3

[0037] 1)C 7 h 15 CO-Arg (NO 2 Preparation of )-Gly-OBzl

[0038] According to Boc-Arg (NO 2 ) The preparation method of Gly-OBzl, 0.855g (5.95mmol) C 7 h 15 COOH and 2.17g (5.4mmol) HCl·H-Arg (NO 2 )-Gly-OBzl yielded 2.44 g (92.1%) of crude product as a yellow solid. Purification by silica gel column afforded 2.12 g (80%) of the title compound as a white solid. ESI-MS(m / z)515.3[M+Na] + , 1007.5[2M+Na] + ;Mp.146.9~147.5℃; (c1, MeOH:CHCl 3 =1:1)

[0039] 2)C 7 h 15 CO-Arg (NO 2 )-Gly-OH preparation

[0040] 2.46g (5mmol) C 7 h 15 CO-Arg (NO 2 )-Gly-OBzl was dissolved in 10ml methanol. Under ice-cooling, the resulting solution was adjusted to pH 12 with NaOH (2N) aqueous solution and stirred for 2 h, TLC (chloroform / methanol, 10:1) showed C 7 h 15 CO-Arg (NO 2 )-Gly-OBzl disappears. The reaction mixture was saturated with KHSO 4 The pH of the aqueous solution was adjusted to 7, and concentrated under reduced pressure to remove methanol. The residue was ...

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Abstract

The invention discloses a preparation method of a fatty acyl-RGD (Arg Gly Asp) induced docetaxel target liposome and antitumor activity thereof. Alkyl fatty acids with different carbon numbers are conjugated with the amino ends of RGD peptides, and hydrophobic modification is performed to synthesize amphiphilic conjugates of different alkyl fatty acid chains and RGD peptides, namely CnH2n+1CO-Arg-Gly-Asp, wherein n represents the carbon number of different long-chain fatty acids and is 7, 9,11,13 or 15. In addition, the invention also contains liposome preparations containing the conjugates and docetaxel, and the preparations are used to resist tumor.

Description

technical field [0001] The present invention relates to the preparation of integrin targeting carrier materials, in particular to a method for constructing a targeted drug delivery system for fat-soluble drugs, and also relates to the application of drug carriers in the preparation of targeted drug delivery preparations, belonging to the field of biomedicine. Background technique [0002] The growth and metastasis of many malignant tumors are related to abnormal expression of integrins or changes in molecular structure. Integrins are a large family of transmembrane proteins, consisting of α and β subunits to form heterodimers. At present, it has been found that there are about 18 kinds of α, about 8 kinds of β, and at least 24 kinds of integrin forms of heterodimers. The progression of integrins in tumors may be dual: 1) In the early stage of tumorigenesis, the reduction of integrin expression can weaken the adhesion between tumor cells and basement membrane or ECM componen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/09C07K1/06C07K1/02A61K31/337A61K47/48A61K47/24A61K9/127A61P35/00
CPCY02P20/55
Inventor 崔国辉崔纯莹任昭
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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