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CN-121987646-A - Application of amygdalin in preparing medicine for preventing and/or treating non-small cell lung cancer

CN121987646ACN 121987646 ACN121987646 ACN 121987646ACN-121987646-A

Abstract

The invention discloses application of amygdalin in preparation of a medicine for preventing and/or treating non-small cell lung cancer, belongs to the technical field of biological medicine, and discovers that natural compound amygdalin can effectively inhibit growth of EGFR mutant lung cancer by promoting lysosome degradation of EGFR protein and inhibiting downstream signal paths of EGFR protein for the first time, and has remarkable treatment potential on C797S mutation-mediated tyrosine kinase inhibitor resistance. In vivo studies have further shown that amygdalin in combination with octreotide can produce a synergistic effect enhancing antitumor efficacy. It is notable that amygdalin has no obvious cytotoxicity under the effective concentration, and has good safety. The result shows that the amygdalin is hopeful to become a novel EGFR targeted degradation agent and provides a novel treatment strategy for non-small cell lung cancer patients with tyrosine kinase inhibitor drug resistance.

Inventors

  • ZENG QI
  • WANG WEN
  • LI NINI

Assignees

  • 中山大学附属第五医院

Dates

Publication Date
20260508
Application Date
20260303

Claims (10)

  1. 1. The application of amygdalin or its pharmaceutically acceptable salt and hydrate in preparing medicine for preventing and/or treating non-small cell lung cancer is provided.
  2. 2. Application of amygdalin or its pharmaceutically acceptable salt and hydrate in combination with EGFR-TKI in preparing medicine for preventing and/or treating non-small cell lung cancer is provided.
  3. 3. The use according to claim 1 or 2, wherein the non-small cell lung cancer is a non-small cell lung cancer having an epidermal growth factor receptor mutation.
  4. 4. The use according to claim 1 or 2, wherein the non-small cell lung cancer is EGFR-TKI resistant non-small cell lung cancer.
  5. 5. The use according to claim 1 or 2, wherein the non-small cell lung cancer is EGFR C797S mutation mediated drug resistant non-small cell lung cancer.
  6. 6. The use according to claim 2, wherein the EGFR-TKI comprises at least one of octenib, ametinib, vomertinib, bei Futi b, afatinib, dacatinib, gefitinib, erlotinib, and eftinib, preferably is octenib.
  7. 7. Use of a composition comprising amygdalin in the manufacture of a reversal drug for reversing the acquired resistance of octenib in non-small cell lung cancer, preferably the composition comprising amygdalin further comprises an EGFR-TKI, more preferably the composition comprising amygdalin is a composition comprising amygdalin and octenib.
  8. 8. A pharmaceutical composition for treating non-small cell lung cancer, which is characterized in that the active ingredients comprise amygdalin or pharmaceutically acceptable salts, hydrates and octenib thereof.
  9. 9. The pharmaceutical composition of claim 8, wherein the drug further comprises a pharmaceutical excipient comprising at least one of a filler, a binder, a disintegrant, a lubricant, a flavoring agent, or a preservative.
  10. 10. The pharmaceutical composition of claim 8, wherein the dosage form of the drug comprises an oral formulation, an injection formulation.

Description

Application of amygdalin in preparing medicine for preventing and/or treating non-small cell lung cancer Technical Field The invention relates to the technical field of biological medicines, in particular to application of amygdalin in preparing medicines for preventing and/or treating non-small cell lung cancer. Background Lung cancer is a malignant tumor with high morbidity and mortality worldwide. About 80-85% of the compositions are Non-small cell lung cancer (NSCLC). In recent years, inhibitors of epidermal growth factor receptor tyrosine kinase (EPIDERMAL GROWTH FACTOR RECEPTORTyrosine kinase inhibitor, EGFR-TKI) is the drug of choice for patients with advanced EGFR mutant non-small cell lung cancer. However, a large number of patients develop acquired resistance due to the T790M mutation within 10 to 14 months after receiving EGFR-TKI treatment. Unfortunately, with the development of the third generation EGFR-TKI (particularly Ornitinib), the problem of reduced EGFR-TKI sensitivity caused by T790M resistance mutation is solved. Patients receiving octenib treatment typically develop resistance about 10 months after administration, with the most common being the C797S mutation at exon 20, which is 10% -26% in the case of second-line octenib resistance and 7% in the case of first-line octenib resistance. Fourth-generation EGFR inhibitors can specifically target the Lys745 site with catalytic activity, selectively change the spatial conformation of mutant EGFR and prevent it from binding to ligands, but most of these drugs are still in early stages of clinical trials. Thus, there is currently no standard treatment regimen recommended for such drug resistant patients. Disclosure of Invention Amygdalin is a naturally occurring cyanogenic glycoside compound which is widely found in a variety of plants, especially apricot, almond and peach seeds, with the highest levels and with the tendency to form hydrates. The toxicity is derived from benzaldehyde and hydrogen cyanide which are generated by decomposition after oral administration, and the toxicity of intravenous administration is obviously lower than that of oral administration. The oral tolerance dose of human body to amygdalin is 0.6-1 g/day, and the intravenous tolerance dose can reach 10 g/day. Amygdalin has been used for centuries in asia, europe, etc. for the treatment of cough, asthma, nausea and vomiting, leprosy, vitiligo, etc. Recent researches show that amygdalin can play a remarkable anti-tumor role on cervical cancer, renal cancer and liver cancer cells by affecting the cell cycle process, inducing apoptosis, regulating immune function and intestinal flora and other modes. The invention discovers for the first time that the natural compound amygdalin can effectively inhibit the growth of EGFR mutant lung cancer by promoting the lysosome degradation of EGFR protein and inhibiting the downstream signal path of EGFR protein, and has remarkable treatment potential on C797S mutation-mediated tyrosine kinase inhibitor resistance. In view of the above, the invention aims to provide an application of amygdalin in reversing EGFR-TKI resistance. In a first aspect, the invention provides an application of amygdalin or pharmaceutically acceptable salt and hydrate thereof in preparing a medicament for preventing and/or treating non-small cell lung cancer. Further, the amygdalin or the pharmaceutically acceptable salt and hydrate thereof and the EGFR-TKI are applied to the preparation of medicaments for preventing and/or treating non-small cell lung cancer. Further, the non-small cell lung cancer is a non-small cell lung cancer having an Epidermal Growth Factor Receptor (EGFR) mutation. Further, the non-small cell lung cancer is a non-small cell lung cancer that is resistant to EGFR-TKI. Namely, the non-small cell lung cancer is EGFR-TKI drug resistant non-small cell lung cancer. Further, the non-small cell lung cancer is EGFR C797S mutation-mediated drug resistant non-small cell lung cancer (NSCLC). Further, the EGFR-TKI comprises at least one of the following components of the formula of octreotide, amotinib, vomertinib, bei Futi, afatinib, dacatinib, gefitinib, erlotinib and Ecritinib, and is preferably the formula of octreotide. In a second aspect of the invention there is provided the use of amygdalin, in particular a composition comprising amygdalin, more preferably a composition comprising amygdalin and octenib, in the manufacture of a reversal drug for reversing the acquired resistance of octenib in non-small cell lung cancer. In vivo and in vitro studies of non-small cell lung cancer, the invention discovers that 1, amygdalin can effectively inhibit the expression level of EGFR protein under the condition of no obvious cytotoxicity, 2, the combination of the octenib and the amygdalin has obvious anti-tumor effect, and 3, the combination scheme has obvious inhibition effect on C797S mutant strain. In a third aspect of the present invention, there i