Boron-containing preparation with nuclear targeting as well as preparation method and application thereof

A targeting, cell nucleus technology, applied in the field of biomedicine, can solve the problem of poor cell nucleus targeting ability, and achieve the effect of good biocompatibility, improved therapeutic effect, and large BNCT curative effect.

Active Publication Date: 2019-09-27
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Traditional boron capture agents have poor ability to target the nucleus, and the development of boron capture agents with nuclear targe

Method used

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  • Boron-containing preparation with nuclear targeting as well as preparation method and application thereof
  • Boron-containing preparation with nuclear targeting as well as preparation method and application thereof
  • Boron-containing preparation with nuclear targeting as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Embodiment 1 boron-containing doxorubicin preparation (DOXCB)

[0085] (A-1) Dissolve doxorubicin (i.e. doxorubicin hydrochloride) in anhydrous dimethyl sulfoxide, add triethylamine under nitrogen protection condition, stir for 2h, add 1-bromomethyl-o-carborane , magnetic sub-stirring at room temperature for 48h, then add excess ether, so that the precipitation is complete; the molar ratio of doxorubicin, triethylamine and 1-bromomethyl-o-carborane is 1:2:1;

[0086] (A-2) Collect the precipitate into a dialysis bag with a molecular weight cut-off of 500, use dimethyl sulfoxide as the dialysate for 24 hours, then use distilled water as the dialysate for 48 hours, and freeze-dry under reduced pressure to obtain a red powder, which is the Doxorubicin Borate (DOXCB).

[0087] The boron content of DOXCB in this embodiment was 5.15wt% after being digested with concentrated nitric acid by means of inductively coupled plasma mass spectrometry (ICP-MS).

[0088] Both DOX and ...

Embodiment 2

[0090] Example 2 Nano boron capture preparation (HA / PAMAM-CB)

[0091] (B-1) Add the 2nd generation dendritic polyamide, 1-bromomethyl-o-carborane and triethylamine into dimethyl sulfoxide in a molar ratio of 1:1:12, and after magnetic stirring at room temperature for 48 hours, add Excess ether until the precipitation is complete;

[0092] (B-2) Collect the precipitate into a dialysis bag with a molecular weight cut-off of 1000, use distilled water as the dialysate for 72 hours, then use a 200W power probe to sonicate for 3 minutes, pass through a 0.22 μm filter membrane, and freeze-dry the filtrate to obtain a dendritic high Molecular boron capture agent PAMAM-CB;

[0093] (B-3) Dissolve the dendrimer boron capture agent in water, add an equal mass of hyaluronic acid, let it stand for 0.5h, then ultrasonicate for 0.5h in a water bath, then ultrasonicate with a 200W power probe for 2min to obtain a clear aqueous solution, and obtain a clear HA / PAMAM - CB aqueous solution.

...

Embodiment 3

[0098] Embodiment 3 Dendrimer boron capture agent (PAMAM-BPABOC)

[0099] (C-1) Dissolve di-tert-butyl dicarbonate and 4-boron-L-phenylalanine in a molar ratio of 1:1 in a mixed solvent of tetrahydrofuran and distilled water with a volume ratio of 1:1, stir for 24 hours, and rotavap Remove tetrahydrofuran to obtain an aqueous solution containing the product, add 0.1M aqueous sodium bicarbonate solution to adjust the pH to 9, extract with ethyl acetate, and remove ethyl acetate by rotary evaporation to obtain product I;

[0100] (C-2) Dissolve the product I in distilled water, adjust the pH to 5 with 1M aqueous hydrochloric acid, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinyl imine, after stirring for 4h, add 1M sodium hydroxide aqueous solution to adjust the pH to 8, add 2 generations of dendritic polyamide, and continue stirring for 48h; the product I, 1-(3-dimethylaminopropyl)-3- The molar ratio of ethyl carbodiimide, N-hydroxysuccinimide and 2nd ge...

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Abstract

The invention discloses a boron-containing preparation with nuclear targeting as well as a preparation method and the application thereof. The boron-containing preparation comprises 1-bromomethyl dicarbadodecaborane and nuclear targeted drug containing active amino, or comprises 1-bromomethyl dicarbadodecaborane, generation 2 dendritic polyamide and hyaluronic acid, or comprises 4-boron-L-phenylalanine, di-tert-butyl dicarbonate and generation 2 dendritic polyamide, or comprises dicarbadodecaborane and dendritic polyethyleneimine. The boron-containing preparation can be further positioned to tumor cell nucleus in a targeted manner while showing good tumor cell intake, and belongs to a novel boron capturing agent with nuclear targeting.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a boron-containing preparation with cell nucleus targeting and a preparation method and application thereof. Background technique [0002] Tumors, especially malignant tumors, are major diseases that seriously threaten human health, and they have brought heavy burdens to patients, families and society. In recent years, the incidence of cancer has been on the rise. The International Cancer Center of the World Health Organization predicts that by 2020, the number of new cancer patients worldwide will reach 15 million each year. At present, the main treatment methods for tumors include surgery, radiotherapy, chemotherapy, immunotherapy, etc., but a considerable number of tumor patients (such as high-grade tumors, recurrent tumors, and metastatic tumors) have not benefited from them. The significance of exploring new means of tumor treatment profound. [0003] Boron neutron cap...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/704A61K9/19A61K9/08A61K47/34A61P35/00
CPCA61K41/0095A61P35/00A61K47/34A61K47/36A61K31/704A61K47/24A61K2300/00
Inventor 魏启春陈捷键杨琪瑶林梦婷王田田张振涛钟新程卢一莹韩旻高建青
Owner ZHEJIANG UNIV
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