Use and preparation method of berberine compounds

Inventors

LIANG, Xinmiao • Wang, Chaoran • Zhang, Xiuli • Zhang, Yan • Wang, Zhiwei • Civelli, Olivier • Ke, Yanxiong • Wang, Lien

Assignees

Dalian Institute of Chemical Physics of CAS • University of California Irvine

Abstract

A method of treating nervous system diseases associated with dopamine receptors comprising administering a patent in need a compound having a structure of general formula (I) or a pharmaceutical acceptable salt, hydrate, or solvate thereof in a pharmaceutically effective amount, and a method of making the compound having the structure of general formula (I) or a pharmaceutical acceptable salt, hydrate, or solvate thereof. The compound of formula (I) has multiple pharmacological functions such as the functions of activating opioid receptors and blocking dopamine D2 receptors, and has good physicochemical properties and oral bioavailability. General animal experiments show that such a compound has significant and long-lasting analgesic and calming effects and can be used to treat pain and other mental illnesses.

Core Innovation

The invention provides a method for treating nervous system diseases associated with dopamine receptors by administering a compound having the structure of general formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof in a pharmaceutically effective amount. These compounds, based on quaternary ammonium type berberine derivatives, show multiple pharmacological activities, including activation of opioid receptors and blockade of dopamine D2 receptors, and are characterized by good physicochemical properties and oral bioavailability.

The invention seeks to address the ongoing problem of pain treatment where current analgesic drugs, especially opioid analgesics, pose risks such as addiction, drug resistance, and various adverse reactions, while non-narcotic analgesics have limited efficacy. The goal is to provide analgesic agents with significant activity but without addiction or other serious side effects associated with current options.

Through the systematic screening of Corydalis yanhusuo's compounds, the inventors discovered that specific quaternary ammonium berberines possess dopamine D2 receptor blocking activity and, in certain cases, opioid receptor activity. The invention details methods of synthesizing these compounds, including protection and selective modification of hydroxyl groups, leading to derivatives effective against pain and potentially other nervous system diseases like depression linked to dopamine receptor activity.

Claims Coverage

There is one principal independent claim that covers the main inventive features relating to the use of specific berberine compounds for treating pain.

The independent claim broadly covers the pharmaceutical use of defined berberine compounds for pain treatment, including their specific structural features and forms.

Stated Advantages

Documented Applications