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Lactobionic acid-novel indocyanine green conjugate as well as preparation method and application thereof

A new indocyanine green and lactobionic acid technology, applied in the field of biomedicine, can solve the problems of poor repeatability, poor tumor photothermal, photodynamic therapy fluorescence imaging of tumors, and complicated drug loading steps, and achieve the effect of simple structure

Pending Publication Date: 2022-06-03
CHANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, free new indocyanine green lacks tumor targeting, which leads to poor effects of tumor photothermal, photodynamic therapy and tumor fluorescence imaging, and will cause toxic side effects caused by non-specific uptake of new indocyanine green.
[0003] Improving the tumor targeting of new indocyanine green through nano-drug delivery system is a current research hotspot. A variety of organic polymer nanomaterials and inorganic nanomaterials have been studied for active or passive targeted delivery of new indocyanine green. , which improves the tumor targeting of new indocyanine green to a certain extent, but there are still disadvantages such as low drug loading, complicated drug loading steps, poor reproducibility, and potential side effects related to the carrier.

Method used

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  • Lactobionic acid-novel indocyanine green conjugate as well as preparation method and application thereof
  • Lactobionic acid-novel indocyanine green conjugate as well as preparation method and application thereof
  • Lactobionic acid-novel indocyanine green conjugate as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Preparation of 1,6-Hexanediamined Neoindocyanine Green

[0044] 20 mL of anhydrous methanol was added to a 50 mL round-bottomed flask, followed by magnetic stirring, neo-indocyanine green (85 mg, 0.1 mmol) and 1,6-hexanediamine (116 mg, 1.0 mmol) were added and stirred at room temperature to dissolve, and heated to 50 Reflux for 3 hours at ℃, then cooled to room temperature, added to a dialysis bag (molecular weight cut-off 800Da), dialyzed in ultrapure water for three days, freeze-dried to obtain 87 mg of blue powdery solid with a yield of 94%.

[0045] The synthesized 1,6-hexanediamined neoindocyanine green was characterized by 1,6-hexanediamined neoindocyanine green by H NMR spectroscopy and high performance liquid chromatography. like figure 1 As shown, compared with the free neo-indocyanine green, the characteristic peak of the methylene group in the 1,6-hexanediamine group appears in the H NMR spectrum of the 1,6-hexanediamined neo-indocyanine green ( ...

Embodiment 2

[0046] Example 2: Preparation of compounds of formula (I)

[0047] Add 10 mL of N,N-dimethylformamide to a 50 mL round-bottomed flask, add magnetic stirring, add lactobionic acid (115 mg, 0.32 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbon Diimine hydrochloride (153 mg, 0.8 mmol), 4-dimethylaminopyridine (20 mg, 0.16 mmol) and 1,6-hexanediamined neoindocyanine green (74 mg, 0.08 mmol) were stirred and dissolved at room temperature, Heated to 50°C for 24 hours, then cooled to room temperature, added to a dialysis bag (molecular weight cut-off 800Da), dialyzed in ultrapure water for three days, freeze-dried, and the freeze-dried product was separated and purified by column chromatography to obtain a blue color Powdered solid 89 mg (purity 93%), yield 88%.

[0048]The synthesized compound of formula (I) was characterized by H NMR spectroscopy, infrared spectroscopy and high performance liquid chromatography. like figure 1 As shown, compared with 1,6-hexanediamined neoindocyani...

Embodiment 3

[0049] Example 3: Preparation of cystamined neoindocyanine green

[0050] 20 mL of anhydrous methanol was added to a 50 mL round-bottomed flask, followed by magnetic stirring, and neo indocyanine green (85 mg, 0.1 mmol), cystamine dihydrochloride (450 mg, 2.0 mmol) and triethylamine (606 mg, 6.0 mmol) were added. mmol) at room temperature, stirring and dissolving, heating to 50°C for reflux for 3 hours, then cooling to room temperature, adding to a dialysis bag (molecular weight cut-off 800Da), dialyzing in ultrapure water for three days, and freeze-drying to obtain 84 mg of blue powdery solid. rate 87%.

[0051] The synthesized cystamined neoindocyanine green was characterized by 1H NMR and HPLC. like figure 2 As shown, compared with free neo indocyanine green, the characteristic peaks (a, b) of the methylene group in the cystamine group appeared in the H NMR spectrum of cystaminated neo indocyanine green, indicating that the cystaminated neo indocyanine green Successful ...

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a lactobionic acid-novel indocyanine green conjugate as well as a preparation method and application thereof. Firstly, new indocyanine green and three different diamines are used as raw materials to synthesize aminated new indocyanine green through nucleophilic substitution reaction, and then the aminated new indocyanine green and lactobionic acid are condensed to obtain three lactobionic acid-new indocyanine green conjugates. The conjugate provided by the invention can be used for liver cancer targeted delivery of the new indocyanine green, and the obtained conjugate can be specifically recognized by an asialoglycoprotein receptor highly expressed on the surface of a liver cancer cell, and is taken by the liver cancer cell through a receptor-mediated pathway, so that the liver cancer cell intake of the new indocyanine green is remarkably improved; the obtained conjugate has an in-vitro photodynamic effect superior to or equivalent to that of free new indocyanine green, has a liver cancer cell photodynamic killing effect superior to that of the free new indocyanine green, and has application prospects in liver cancer photodynamic therapy and liver cancer diagnosis.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and particularly relates to three lactobionic acid-new indocyanine green conjugates and their preparation methods and applications. Background technique [0002] New indocyanine green is a near-infrared fluorescent dye with potential applications in tumor photothermal, photodynamic therapy and tumor fluorescence imaging. However, free neo-indocyanine green lacks tumor targeting, resulting in poor tumor photothermal, photodynamic therapy and tumor fluorescence imaging, and can cause toxic side effects caused by non-specific uptake of neo-indocyanine green. [0003] Improving tumor targeting of new indocyanine green by nano-drug delivery system is a hot research topic at present, and a variety of organic polymer nanomaterials and inorganic nanomaterials have been studied for active or passive targeted delivery of new indocyanine green , to a certain extent, the tumor targeting of new indocyani...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H15/04C07H1/00A61K47/54A61K41/00A61P35/00
CPCC07H15/04C07H1/00A61K41/0057A61K47/549A61P35/00
Inventor 胡航徐德锋袁晓音陶亚宇肖文杜坤达
Owner CHANGZHOU UNIV
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