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Targeted boron preparation and preparation method thereof

A targeting and preparation technology, applied in the field of biomedicine, can solve the problems of low enrichment and poor targeting, and achieve the effects of low cytotoxicity, high encapsulation rate and prolonging survival period.

Inactive Publication Date: 2017-02-15
THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The present invention aims at the shortcomings of low tumor tissue enrichment and poor targeting of boron atom carriers currently used in BNCT clinical trials, and provides a targeted boron preparation with high boron content

Method used

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  • Targeted boron preparation and preparation method thereof
  • Targeted boron preparation and preparation method thereof
  • Targeted boron preparation and preparation method thereof

Examples

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preparation example Construction

[0045] The invention also provides a preparation method of the targeting boron preparation.

[0046] A kind of preparation method of targeting boron preparation, by 3-(2-pyridine dimercapto) propionic acid N-hydroxysuccinimide ester and undecanoic acid maleimide-hydrazide-trifluoroacetic acid salt The amide-amine dendrimer and the epidermal growth factor antibody are connected to form a functionalized dendrimer, and then the polyhedral borane is loaded to obtain the targeted boron preparation.

[0047] N-hydroxysuccinimide 3-(2-pyridyldimercapto)propionate (SPDP), the molecular formula is C 12 h 12 N 2 o 4 S 2 , is a short-chain cross-linking agent, which connects the amino group on the PAMAM molecule through the hydroxysuccinimide ester active group (-NH 2 ). The molecular formula of undecanoic acid maleimide-hydrazide-trifluoroacetate (KMUH) is C 15 h 25 N 3 o 3 · CF 3 CO 2 H, is a long-chain cross-linking agent, which reacts with the sulfhydryl group (-SH) on th...

Embodiment 1

[0108] Example 1: Preparation of PAMAM-mAbEGFR / BSH

[0109] (1) Mix 0.1 mg of the epidermal growth factor receptor monoclonal antibody mAbEGFR with 2 mg of sodium periodate in 1 ml of 0.1 M acetate buffer at pH 4.5, use magnetic beads to keep stirring at room temperature for 2 h, and pass the reaction mixture through Sephadex Desalting the G25 chromatography column, removing excess sodium periodate, eluting with 50mM phosphate buffer at pH 7.5, and collecting the oxidized EGFR monoclonal antibody obtained;

[0110] (2) 0.58ml of 5% polyamidoamine dendrimer (PAMAM) solution (Sigma Company), which contains 29mg of PAMAM, is mixed with 3.12mg SPDP in 1ml of 0.1M phosphate buffered saline buffer solution at pH 7.5, and reacted at room temperature 2h, the reaction mixture was desalted by Sephadex G25 chromatography column to remove unreacted SPDP, and eluted with 50mM phosphate buffer solution with pH 7.5 to obtain the intermediate PAMAM-SPDP;

[0111](3) Dissolve 1.54mg of DTT in...

Embodiment 2

[0119] Embodiment 2: Preparation of PAMAM-mAbEGFR / BSH

[0120] (1) mAbEGFR 0.3mg and sodium periodate 6mg were mixed in 3ml of 0.1M acetate buffer solution with a pH of 4.5, stirred continuously at room temperature for 2 hours using magnetic beads, and the reaction mixture was desalted by Sephadex G25 chromatography column to remove Excess sodium periodate was eluted with 50 mM phosphate buffer at pH 7.5, and the resulting oxidized EGFR monoclonal antibody was collected;

[0121] (2) 1.74ml of polyamidoamine dendrimer PAMAM (Sigma company) solution, which contains 87mg of PAMAM, is mixed with 9.36mg of SPDP in 3ml of 0.1M phosphate buffer saline at pH7.5, reacted for 2h, reacted The mixture was desalted by Sephadex G25 chromatographic column to remove unreacted SPDP, and eluted with 50mM phosphate buffer at pH 7.5 to obtain the intermediate PAMAM-SPDP;

[0122] (3) 4.62 mg of DTT was dissolved in 3 ml of 0.1 M phosphate buffer solution with pH 7.5, and 0.3 g of DMSO was added...

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Abstract

The invention belongs to the biological medicine field, and discloses a targeted boron preparation and a preparation method and application. The target boron preparation comprises polyamidoamine-amine dendrimers, epidermal growth factor receptor antibody and polyhedral boranes, the polyamide amine dendrimers are connected with the epidermal growth factor receptor antibody, and are internally loaded with the polyhedral boranes. The targeted boron preparation is high in boron content, can meet the requirements of BNCT (boron neutron capture therapy) on the boron atom dose, is well targeted to tumor cells, has good stability and low cell toxicity, and can be efficiently uptaken by human glioma U87MG cells of high surface expression EGFR (epidermal growth factor receptor). The target boron preparation can effectively improve the content of boron in orthotopic transplantation tumor nude mice tumor tissues, can significantly prolong orthotopic transplantation tumor nude mice lifetime by neutron irradiation, and is suitable for boron neutron capture therapy for glioma. The preparation method of the targeted boron preparation has the advantages of simple operation, and the prepared targeted boron preparation has good stability.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to an epidermal growth factor antibody-coupled dendrimer targeted drug delivery system loaded with polyhedral borane and a preparation method thereof, which is suitable for boron neutron capture therapy for treating glioma. Background technique [0002] Glioma accounts for about 45% of primary intracranial tumors, and is the most common primary malignant intracranial tumor. It is characterized by infiltrative growth of the tumor, unclear tumor boundaries, difficult to completely resected by surgery, and easy to relapse after surgery. At present, surgery combined with postoperative radiotherapy and chemotherapy is considered to be the best treatment for glioma. Therefore, radiotherapy has become one of the important links in the comprehensive treatment of glioma. [0003] Boron neutron capture therapy (BNCT) is a therapeutic method that can selectively kill tumor cells that ha...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/10A61P35/00A61K101/00
Inventor 孙婷周幽心王中
Owner THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIV
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