A boron-containing drug with tumor targeting ability and its preparation method and application

Abstract

The present invention relates to a boron-containing drug with tumor targeting ability and its preparation method and application. The boron-containing drug includes a polypeptide and a hydrophobic molecule located at the nitrogen terminal of the polypeptide; the amino acid forming the polypeptide includes phosphorylated L-phenol amino acid, 4-boron-L-phenylalanine and L-phenylalanine. The preparation method adopts the classic solid-phase synthesis method, which is simple in operation and high in total yield, and the prepared boron-containing drug has specific, rapid and efficient accumulation ability in tumor cells, good biocompatibility, and no systemic toxicity , can better meet the therapeutic needs of boron neutron capture therapy.

Description

technical field [0001] The invention belongs to the field of chemical medicine, and in particular relates to a boron-containing drug and its preparation method and application, in particular to a boron-containing drug with tumor targeting ability, its preparation method and application. Background technique [0002] Boron neutron capture therapy (BNCT) is a treatment that destroys cancer cells through nuclear reactions inside tumor cells. By injecting boron-containing compounds, it is concentrated in tumor cells, while the distribution in other tissues is small. When irradiated with an epithermal neutron ray, the neutron and the boron entering the cancer cell can undergo a strong nuclear reaction, releasing a very lethal ray, thereby killing the cancer cell. [0003] As an important member of BNCT therapy, boron-containing drugs have not performed satisfactorily in clinical applications, because BNCT requires drugs to target tumors and accumulate sufficient boron-containing...

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Problems solved by technology

[0003] As an important member of BNCT therapy, boron-containing drugs have not performed satisfactorily in clinical applications, because BNCT requires drugs to target tumors and accumulate sufficient boron-containing drugs in tumor cells. The ratio of the concentration in normal tissue or blood should be greater than 3.0, entering the concentration of each gram of tumor 10 The average amount of B is required to be 20-35 μg, and corresponds to a tumor cell containing at least 10 9 indivual 10 B atoms, but existing technologies such as the two BNCT drugs currently approved by the FDA, BSH (mercapto polyhedral boron clathrate) and BPA (4-boron-L-phenylalanine), cannot reach this level, and various boron loadings Targeted drugs such as low molecular weight borides, boron-doped peptides, antibody fragments and various proteins, intact antibodies and antibody-based conjugates, and liposomes, etc., are also due to low drug loading, poor penetration, and systemic Problems such as strong toxicity are difficult to meet the treatment requirements of BNCT

[0004] CN106279231A discloses a boron-containing compound used in BNCT and its preparation method and application. The new boron-containing compound provided by the invention is obtained through condensation, ammonolysis and ring-forming reactions, and is easy to prepare, low in cost, and has good biological properties. Its performance is superior to BPA in the uptake, accumulation and retention of tumor cells, and it has good application prospects in BNCT. It is also expected to become a clinical potential positron emission tomography tumor imaging agent. The identification of diseases and the detection of metastatic lesions in the whole body have created favorable conditions, but the boron-containing compounds are still not ideal in terms of tumor cell targeting and accumulation

However, this preparation needs the help of an external magnetic field to target it to the tumor site, and there may be problems such as low drug loading and poor penetration.

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