Liver and heart dual targeting mitochondrial fatty acid oxidation activators
By constructing a dual-state isomeric acyl cluster core, a quantum self-regulating coenzyme bridge chain, and a self-shielding peroxidation regulatory group, the problem of energy metabolism imbalance caused by the long-term action of dual-target mitochondrial fatty acid oxidation activators in the liver and heart was solved, achieving dynamic balance and stability of energy metabolism in the liver and heart, and improving energy transfer efficiency and system stability.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ZHE JIANG XI DAO SHENG WU KE JI YOU XIAN GONG SI
- Filing Date
- 2026-03-10
- Publication Date
- 2026-06-16
AI Technical Summary
Existing dual-target mitochondrial fatty acid oxidation activators for the liver and heart are prone to causing phase coupling imbalances in the cross-organ energy metabolism chain during long-term action. This leads to synchronous oscillations and feedback superposition effects of mitochondrial membrane potentials in hepatocytes and cardiomyocytes, which in turn causes irreversible breaks in the energy transfer chain, affecting the maintenance of tissue energy homeostasis and functional continuity.
Employing a dual-state isomeric acyl cluster core, comprising a cis-carboxylic acid tail-reversibly foldable acyl unit and a trans-keto-bridged acyl unit, the system achieves temporal separation of the fatty acid β-oxidation pathway between the liver and heart through adaptive adjustment of the isomer ratio. The quantum self-regulating coenzyme bridge chain, consisting of alternating Fe-S clusters and flavin fragments, senses membrane potential differences and performs real-time fine-tuning through an electron tunneling phase drift mechanism. The self-shielding peroxidation regulating group self-polymerizes to form a transient shielding layer at high ROS concentrations, blocking the oxidative chain reaction.
It achieves dual-targeted homeostatic activation of the liver and heart mitochondrial β-oxidation pathway and phase synchronization control of energy metabolism, prevents cross-organ energy chain imbalance, improves energy transfer efficiency and system stability, improves mitochondrial function and enhances tolerance to metabolic or ischemic stress.
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Figure CN122208587A_ABST
Abstract
Claims
1. A liver- and heart-targeting mitochondrial fatty acid oxidation activator, characterized in that, The activator comprises the following synergistic composite structure: The bimorphic acyl cluster core is composed of two types of long-chain acyl units that are conformations mirror images of each other. Among them, the cis-carboxylic acid tail-reversibly foldable acyl units bind to carnitine palmitoyltransferase-1 in hepatocytes, promoting the transport of fatty acids to the mitochondrial matrix; the trans-keto-bridged acyl units preferentially bind to the acyl-CoA dehydrogenase complex in cardiomyocytes, delaying the rate of fatty acid β-oxidation. By adaptively adjusting the isomer ratio, the temporal separation and dynamic balance of energy flow of the fatty acid β-oxidation pathway between the liver and the heart are achieved. The quantum self-regulating coenzyme bridge chain, embedded in the acyl cluster core, is composed of alternating iron-sulfur clusters and flavin fragments. It is used to sense the potential difference of the inner membrane of mitochondria in the liver and heart. It can fine-tune the cross-organ electron flow in real time through the electron tunneling phase drift mechanism, and inhibit the mitochondrial membrane potential population resonance and phase superposition effect. Self-shielding peroxide regulating groups are distributed on the outer layer of acyl clusters and contain nitrogen-containing alkoxide free radicals with self-polymerization ability. When the concentration of reactive oxygen species is high, they undergo self-polymerization reaction to form a transient shielding layer to interrupt the oxidation chain reaction and prevent reverse electron leakage across the organ respiratory chain.
2. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 1, characterized in that, The molar ratio of the cis-carboxylic acid tail-reversibly foldable acyl unit to the trans-keto-bridged acyl unit is (1.2-2.8):1, which achieves time-staggered control of the liver fatty acid oxidation leader and the cardiac oxidation response.
3. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 1, characterized in that, A polar spacer group -(CH2)_n-O-(CH2)_m- is introduced into the bimorphic acyl cluster core, where n=2-5 and m=1-3, to regulate the selective permeation rate of the molecule between the liver cell and cardiomyocyte membranes.
4. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 1, characterized in that, The alternating arrangement of iron-sulfur clusters and flavin fragments in the quantum self-regulated coenzyme bridge chain has a period of 2-4 units. By controlling the length of the electron tunneling path, the electronic phase drift amplitude can be stabilized within ±15°.
5. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 1, characterized in that, The coenzyme bridge chain self-regulates through changes in the mitochondrial membrane potential difference ΔΨm between the liver and heart. When the difference in ΔΨm exceeds 20 mV, the Fe-S clusters in the bridge chain automatically enter the Fe³⁺ state to reverse the direction of electron flow.
6. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 1, characterized in that, The nitrogen-containing alkoxides in the self-shielding peroxide regulating group undergo self-polymerization when the active oxygen concentration is higher than 10 μM, generating a semi-stable azo polymer layer with a lifetime of 30-180 seconds, which is used to transiently block the propagation of free radicals.
7. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to any one of claims 1-6, characterized in that, The activator contains a nanolipid carrier for the targeted delivery of the bimorphic isoacyl cluster core to the outer membrane surface of hepatocytes and myocardial mitochondria.
8. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 7, characterized in that, The nanolipid carrier is a self-assembled vesicle with a bilayer structure, the outer layer of which is a phospholipid molecule and the inner layer is a polyethylene glycol-phospholipid copolymer.
9. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 1, characterized in that, The activator achieves adaptive regulation through the AMPK signaling pathway in the liver-heart energy metabolism feedback regulation system. When the AMP / ATP ratio increases, the activator spontaneously increases the proportion of trans units to reduce the overall β-oxidation rate.
10. The liver and heart dual-targeting mitochondrial fatty acid oxidation activator according to claim 1, characterized in that, Activators can be used in combination with metabolic aids containing coenzyme Q10 or L-carnitine to form a synergistic regulatory system.