Application of a drug in the preparation of drugs for treating brain metastases and related diseases

A technology for brain metastases and drugs, applied in the field of medicine, can solve problems such as large side effects, inability to apply brain metastases treatment, and inability to obtain therapeutic effects.

Active Publication Date: 2021-08-20
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Under normal circumstances, after the discovery of brain metastases, conventional surgery, radiotherapy, chemotherapy and other methods often cannot obtain good therapeutic effects, and the side effects are large, the prognosis is not ideal, and there is a great risk
[0005] Brain metastases are not the same as primary brain tumors. For example, if a patient’s brain metastases are formed by lung cancer brain metastases, then the patient’s brain metastases are lung cancer cells. If a patient’s brain metastases are breast cancer If brain metastases are formed, then the patient's brain metastases cells are breast cancer cells, so the drugs for the treatment of primary brain tumors cannot be applied to the treatment of brain metastases
Due to the existence of the blood-brain barrier, most drugs for the treatment of lung cancer and breast cancer cannot pass through the blood-brain barrier and enter the brain to exert their due efficacy. Therefore, how to treat brain metastases has become an urgent problem to be solved.

Method used

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  • Application of a drug in the preparation of drugs for treating brain metastases and related diseases
  • Application of a drug in the preparation of drugs for treating brain metastases and related diseases
  • Application of a drug in the preparation of drugs for treating brain metastases and related diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] This embodiment provides a drug for inhibiting brain metastases, which is a TRPV4 agonist. The TRPV4 agonist can promote the influx of calcium ions in the TRPV4 signaling channel, thereby promoting the induction of autophagy in brain tumor cells and achieving a stronger anti-brain tumor effect. The dosage of TRPV4 agonist is: the concentration is 0.01 μM-30 μM, such as 0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM, 15 μM, 20 μM, 25 μM, 30 μM, etc.

Embodiment 2

[0048] On the basis of Example 1, the TRPV4 agonist is cannabidiol, and the concentration of the cannabidiol is 0.01 μM-30 μM, such as 0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM, 15μM, 20μM, 25μM, 30μM, etc. Cannabidiol promotes the influx of calcium ions through the TRPV4 signaling channel, thereby promoting the induction of mitophagy in tumor cells, and finally achieving a strong anti-tumor effect.

[0049] Among them, TRPV4 (transient receptor potential channel 4) is a transient calcium ion channel. After the action of cannabidiol on TRPV4, it will cause calcium ion influx, and calcium ion influx is the main cause of activating endoplasmic reticulum stress. In the case of TRPV4 antagonists, the above-mentioned effects of cannabidiol can be reversed, so TRPV4 can be used as a potential target of cannabidiol in brain tumors.

[0050] Cannabidiol can also significantly induce the morphological changes of mitochondria, and the number of mitochondria decreases signific...

Embodiment 3

[0053] This embodiment provides a drug for inhibiting brain metastases, which includes a TRPV4 agonist and a tumor suppressor with anti-tumor activity. The concentration ratio of the TRPV4 agonist and the tumor suppressor is (that is, the case where the two concentration units are the same in the same solution): (10-30): (10-500). The mechanism of action of the TRPV4 agonist is combined with the inhibitory mechanism of the tumor inhibitor, and the combination of the two achieves the anti-tumor effect of increasing efficiency and reducing toxic and side effects.

[0054] In this embodiment, any one or more TRPV4 agonists can be used in combination with any one or more tumor suppressors.

[0055] Preferably, the tumor suppressor comprises temozolomide. The temozolomide may be used in combination with at least one TRPV4 agonist.

[0056] Preferably, the TRPV4 agonist includes cannabidiol. The TRPV4 agonist cannabidiol can be used in combination with at least one tumor suppress...

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PUM

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Abstract

The present application provides an application of a drug in the preparation of a drug for the treatment of brain metastases-related diseases, wherein the drug includes at least one TRPV4 agonist capable of promoting calcium ion influx of TRPV4 signaling channels, the brain metastases and Related diseases include brain metastases, diseases arising during the formation of brain metastases, complications and sequelae caused by brain metastases, and diseases related to brain metastases. Applying the above-mentioned medicine to the preparation of medicines for treating diseases related to brain metastases can play a significant anti-tumor effect through a clear mechanism of action, with good therapeutic effects and good application prospects.

Description

technical field [0001] The application relates to the technical field of medicine, in particular to the application of a medicine in the preparation of medicines for treating brain metastases and related diseases. Background technique [0002] Brain tumors refer to new organisms growing in the cranial cavity, also known as intracranial tumors and brain cancers, which can originate from the brain, meninges, nerves, blood vessels, and brain appendages, or form by metastasizing from other tissues or organs of the body into the brain , most of which can produce headache, intracranial hypertension and focal symptoms, including primary brain tumors and brain metastases. [0003] Brain metastases are secondary malignant tumors, the most common adult intracranial tumors, mainly from lung and breast cancers; in addition, digestive tract, liver, pancreas, uterus, ovary, thyroid, adrenal gland, prostate, Kidney, bone and other malignant tumors and sarcoma can be transferred to the bra...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K31/05A61K31/4188A61K31/045A61P35/04A61P1/08A61P39/00
CPCA61K45/06A61K31/05A61K31/4188A61K31/045A61P35/04A61P1/08A61P39/00A61K2300/00
Inventor 闫超黄腾飞徐天琦
Owner NANJING UNIV
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