Nano realgar compound medicine and preparation method and application thereof

A nano-realgar and drug technology, which is applied in the direction of drug combinations, pharmaceutical formulas, and non-effective ingredients of polymer compounds, can solve problems such as interference with CML cell signal transduction pathways, difficulty in eradicating malignant progenitor cells, and drug resistance in patients, achieving increased Cumulative amount, simple and controllable preparation process, and the effect of prolonging the residence time

Active Publication Date: 2022-08-09
HUNAN PROVINCIAL TUMOR HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Imatinib (Imatinib, IMA) is the first artificially synthesized molecular targeted drug targeting the mechanism of CML. IMA inhibits the combination of ATP and substrate protein with the catalytic center region of bcr-abl fusion protein by competitively inhibiting the bcr-abl fusion protein. The activation of -abl fusion protein inhibits its PTK activity, interferes with the signal transduction pathway on which CML cell survival depends, and induces CML cell apoptosis. However, in patients with chronic phase, IMA is also difficult to eradicate malignant progenitor cells, and most Patients develop drug resistance and are prone to relapse

Method used

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  • Nano realgar compound medicine and preparation method and application thereof
  • Nano realgar compound medicine and preparation method and application thereof
  • Nano realgar compound medicine and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] A nano-realgar compound medicine includes realgar and bovine serum albumin.

[0047] The nano-realgar compound medicine of the present embodiment is prepared by the following method:

[0048] Will As 4 S 4 Dissolved in ethylenediamine at a concentration of 20 mg / mL, ultrasonicated for 15 min, centrifuged at 15000 rpm for 5 min, and the supernatant was taken. 2mLAs 4 S 4 The supernatant was dispersed in 8mL of water, 3ml of 20mg / ml BSA solution was added, stirred for 5min, 7mL of 4MHCl was added, stirred for 30min, and dialyzed in water for 8h with a dialysis bag with MWCO=3500Da to obtain the nano-realgar compound drug: As 4 S 4 @BSANPs.

Embodiment 2

[0050] A nano-realgar compound medicine, including realgar, bovine serum albumin, folic acid.

[0051] The nano-realgar compound medicine of the present embodiment is prepared by the following method:

[0052] (1) According to the molar ratio of FA, EDC and NHS: 1:2:1, dissolve in DMSO and stir for 30min in the dark to obtain FA with a concentration of 25mg / ml. According to the ratio of FA and BSA molar ratio of 1:50 The FA solution was slowly added dropwise to the BSA carbonate buffer solution, and after stirring at room temperature for 24 h, dialyzed in PBS (10 mm, PH=7.4) with a dialysis bag with MWCO=3500Da for 2 d, and dialyzed in water for 1 d. After collecting and lyophilizing, BSA was obtained. -FA.

[0053] (2) Put As 4 S 4 Dissolved in ethylenediamine at a concentration of 20 mg / mL, ultrasonicated for 15 min, centrifuged at 15000 rpm for 5 min, and the supernatant was taken. At the same time, lyophilized 60 mg BSA-FA was dissolved in 3 ml ultrapure water, and the...

Embodiment 3

[0055] A nano-realgar compound medicine, including realgar, imatinib, bovine serum albumin, folic acid.

[0056] The nano-realgar compound medicine of the present embodiment is prepared by the following preparation method:

[0057] (1) According to the molar ratio of FA, EDC and NHS: 1:2:1, dissolve in DMSO and stir for 30min in the dark to obtain FA with a concentration of 25mg / ml. According to the ratio of FA and BSA molar ratio of 1:50 The FA solution was slowly added dropwise to the BSA carbonate buffer solution, and after stirring at room temperature for 24 h, dialyzed in PBS (10 mm, PH=7.4) with a dialysis bag with MWCO=3500Da for 2 d, and dialyzed in water for 1 d. After collecting and lyophilizing, BSA was obtained. -FA.

[0058] (2) Dissolve 1ml of 5mg / ml IMA in methanol, dissolve 60mg of freeze-dried BSA-FA with 3ml of ultrapure water, then slowly add the dissolved IMA dropwise to the BSA-FA solution and stir for 3h to obtain IMA@BSA- FA solution.

[0059] (3) Put...

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Abstract

The invention provides a nano-realgar compound medicine and a preparation method and application thereof. The nano-realgar compound medicine mainly comprises As 4 S 4 , BSA, IMA and FA. Its preparation method is as 4 S 4 ‑Ethylenediamine molecular cluster solution is the precursor, and the acid-base reaction is used to make As 4 S 4 Nucleate growth under the stabilization of BSA to form nanoparticles. At the same time, IMA was loaded into the hydrophobic domain of BSA by utilizing the hydrophobic force. The nanocomposite drug can be further modified with targeting ligands to increase the targeting and therapeutic index of tumor cells. The nano-realgar composite drug of the present invention can down-regulate the BCR-ABL protein level, induce apoptosis of chronic myeloid leukemia cells from the mitochondrial pathway, and deliver the two drugs to the treatment site in a specific ratio, so as to maximize the curative effect and reduce potential toxic and side effects.

Description

technical field [0001] The invention relates to the field of nano-biology technology, in particular to a nano-realgar compound medicine and a preparation method and application thereof. Background technique [0002] Chronic myeloid leukemia (CML) is a malignant clonal proliferative hematopoietic disease originating from multipotent hematopoietic stem cells in the bone marrow, accounting for 15-20% of all leukemias. Genetic studies have shown that more than 95% of CML patients have Philadelphia chromosome (ph), and its pathogenesis is formed by the mutual translocation of the proto-oncogene abl located on chromosome 9 and bcr (break cluster region) on chromosome 22 t(9;22)(q34;q11), according to the bcr gene breaking site, can form three bcr-abl fusion proteins: p210, p230, p190. The bcr-abl fusion protein is an abnormal receptor-type tyrosine kinase (PTK), which can significantly increase the phosphorylation level of specific substrate protein molecules downstream of the si...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K47/42A61K47/22A61K33/36A61K31/506A61P35/02
CPCA61K9/5169A61K9/5123A61K33/36A61K31/506A61P35/02A61K2300/00Y02A50/30
Inventor 上官丹罡廖德华周治波
Owner HUNAN PROVINCIAL TUMOR HOSPITAL
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