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CN-122005513-A - Anti-tumor and/or anti-iron death small molecule composition and application thereof

CN122005513ACN 122005513 ACN122005513 ACN 122005513ACN-122005513-A

Abstract

The invention belongs to the technical field of medicines, and particularly provides a small molecule composition which can be used for preventing or treating diseases such as tumors, especially for preventing or treating diseases such as tumors by combining with other anti-tumor medicines, and can also be used for inhibiting iron death of cells.

Inventors

  • Zhou Zhanmusi
  • XIE BAIBO

Assignees

  • 北京慧宝源生物技术股份有限公司

Dates

Publication Date
20260512
Application Date
20241112

Claims (10)

  1. 1. A small molecule composition comprising licochalcone a, licochalcone C, licochalcone D, licochalcone E, licarpa-licochalcone, isoliquiritigenin, formononetin, glycyrrhizin, licoflavone C, glabridol, licoisoflavone a, and licoisoflavone B.
  2. 2. The composition of claim 1, wherein the weight ratio of licochalcone a, licochalcone C, licochalcone D, licochalcone E, licochalcone, isoliquiritigenin, formononetin, glycyrrhizin, licoflavone C, glabridol, licoisoflavone a and licoisoflavone B is 6.2~6.8：0.62~0.68：0.4~0.44：0.83~0.92：0.1~0.13：0.12~0.18：0.4~0.5：0.18~0.25：0.1~0.13：0.15~0.2：0.16~0.21：0.1~0.15, preferably 6.4~6.6：0.64~0.66：0.41~0.43：0.87~0.89：0.11~0.13：0.14~0.16：0.44~0.46：0.2~0.22：0.11~0.13：0.17~0.19：0.18~0.2：0.12~0.14,, most preferably 6.5:0.65:0.42:0.88:0.12:0.15:0.45:0.21:0.12:0.18:0.19:0.13.
  3. 3. The composition of claim 1 for use in anticancer or oncological therapy, for use in anti-cellular iron death, or for use in anticancer or oncological drug sensitization.
  4. 4. An anti-cancer or tumor composition comprising the composition of claim 1 or 2 and an anti-cancer or tumor drug.
  5. 5. The composition of claim 4, wherein the anticancer or oncological agent is an EGFR-targeted anticancer or oncological agent (e.g. octenib) and/or a cytotoxic anticancer or oncological agent (preferably 5-fluorouracil or a platinum-like compound such as oxaliplatin or cisplatin).
  6. 6. The composition of claim 4, wherein the cancer or tumor is a drug resistant cancer or tumor, preferably a cancer or tumor resistant to EGFR-targeted anticancer or tumor drugs (e.g., octenib).
  7. 7. A formulation comprising the composition of any one of claims 1-6 and a pharmaceutically acceptable adjuvant.
  8. 8. Use of a composition according to any one of claims 1 to 6 for the manufacture of a medicament for anticancer or oncological use, for anti-iron cell death or for sensitization of anticancer or oncological drugs.
  9. 9. Use according to claim 8, wherein the cancer or tumour is a lung tumour, a liver tumour, a stomach tumour, a colon cancer and/or a pancreatic cancer, or the cancer or tumour is a drug resistant cancer or tumour, preferably a cancer or tumour resistant to EGFR-targeted anti-cancer or tumour drugs (e.g. octenib).
  10. 10. The use according to claim 8 in combination with an anticancer or oncological agent according to any one of claims 1 to 6.

Description

Anti-tumor and/or anti-iron death small molecule composition and application thereof Technical Field The invention belongs to the technical field of medicines, and particularly provides a small molecule composition which can be used for preventing or treating diseases such as tumors, especially for preventing or treating diseases such as tumors by combining with other anti-tumor medicines, and can also be used for inhibiting iron death of cells. Background Cancer threatens human life and health. Although a certain effect is achieved through more than half century of efforts, the effectiveness of various anticancer drugs is difficult to last and finally is disabled due to tumor drug resistance due to the extremely complex etiology and pathology of tumors, such as heterogeneity, clonality, adaptation variability and other factors of tumor cells. Iron death is an iron-dependent apoptosis caused by accumulation of lipid peroxidation products. When the activity of glutathione peroxidase 4 (GPX 4), a key regulator of iron death, is inhibited, the antioxidant capacity of cells is reduced, and Reactive Oxygen Species (ROS) are accumulated in a large amount, so that oxidative damage is initiated to cause iron death of cells. Cellular iron death occurs widely during organ tissue decay. Licorice is a common Chinese herbal medicine, and in a traditional Chinese medicine prescription, licorice is usually used as a decoction, and the licorice is mainly used as a water-soluble molecule from the basis of pharmaceutical substances. The liquorice contains a plurality of components, and the interaction among the components is more complex. The present inventors have long focused on modern research of traditional Chinese medicine, and have developed Z018A from licorice extract at an early stage, which is disclosed in chinese patent ZL201610169121.8 (incorporated herein by reference in its entirety). Z018A has three characteristic peaks (only 3 components are expected) on HPLC detection spectrum, and can be used for preventing or treating fatty liver injury and obesity, reducing blood lipid level, and reducing inflammatory factor level. On this basis, the inventors have developed a crystalline product of Z018A, which is disclosed in chinese patent ZL201910410704.9 (incorporated herein by reference in its entirety). It also has three characteristic peaks (only 3 components are expected) on HPLC detection spectrum, is an SIRT1 agonist, can obviously improve the in vivo expression level of SIRT1, and can be used for resisting aging. Thereafter, the study of Z018A was due to silence. However, the present inventors have not stopped, and have unexpectedly found, in one unsuccessful experiment in studying the extraction of Z018A, a licorice extract component Z018C, and have made modern improvements, to develop a clear-component, stable-quality small molecule pharmaceutical composition which can inhibit tumors (including resistant tumors) alone or in combination with existing antitumor agents, and which exhibits very significant synergistic effects, especially in combination with commonly used antitumor agents, and which also has a protective effect on cell iron death. Disclosure of Invention The technical problem to be solved by the invention is to provide a novel small molecule composition which can be used for preventing or treating diseases such as tumors, especially for preventing or treating diseases such as tumors by combining with other anti-tumor drugs, and can also be used for inhibiting iron death of cells. In addition, the invention also provides a pharmaceutical preparation containing the small molecule composition, application and the like. Specifically, in a first aspect, the present invention provides a small molecule composition comprising licochalcone a, licochalcone C, licochalcone D, licochalcone E, licochalcone spinosa, isoliquiritigenin, formononetin, glycyrrhizin, licoflavone C, glabridol, licoisoflavone a, and licoisoflavone B. In a specific embodiment of the present invention, the composition of the first aspect of the present invention is preferably composed of licochalcone a, licochalcone C, licochalcone D, licochalcone E, licarpa chalcone, isoliquiritigenin, formononetin, glycyrrhizin, licoflavone C, glabridin, licoflavone a and licoisoflavone B. The small molecule composition of the first aspect of the invention may be used for anticancer or oncological purposes, i.e. the small molecule composition provided by the invention may be an anticancer or oncological composition. The small molecule composition of the first aspect of the invention may also be used to combat iron cell death, i.e. the small molecule composition provided by the invention may also be an anti-iron death composition. The anti-iron death composition can be used for resisting organ damage and other symptoms. The small molecule composition of the first aspect of the invention may also be used for sensitization of an anti-cancer or tumor drug