Alpha-Lipoic Acid (α-Lipoic Acid) （cas 62-46-4）
Alpha-Lipoic Acid (α-Lipoic Acid) is a water- and fat-soluble antioxidant used to treat diabetic neuropathy, neurodegenerative diseases, and aging-related conditions. This article details its mechanisms, clinical applications, synthesis, and market trends.α-硫辛酸（Alpha-Lipoic Acid）是一种兼具水溶性与脂溶性的强效抗氧化剂，广泛用于糖尿病神经病变、抗衰老及美容领域。本文详述其药理机制、临床应用、合成工艺及市场动态。
1. Basic Information
- Chemical Name: (±)-5-[3-(1,2-dithiolan-3-yl)pentanoic acid
- Molecular Formula: C₈H₁₄O₂S₂
- Molecular Weight: 206.33 g/mol
- CAS Number: 62-46-4 (racemic mixture), 1077-28-7 (R-enantiomer)
- Appearance: Pale yellow crystalline powder, melting point 48–52°C, slightly soluble in water, highly soluble in ethanol and chloroform.
2. Pharmacological Mechanisms
- Core Actions:
- Antioxidant: Directly scavenges free radicals (e.g., hydroxyl radical, singlet oxygen) and regenerates vitamin C, E, and glutathione, forming an antioxidant network.
- Anti-inflammatory: Inhibits the NF-κB pathway, reducing pro-inflammatory cytokines (e.g., IL-6, TNF-α).
- Anti-glycation: Suppresses protein glycosylation, lowering advanced glycation end products (AGEs).
- Metabolic Regulation:
- Acts as a mitochondrial coenzyme in pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes, enhancing glucose metabolism.
- Improves insulin sensitivity and reduces blood glucose levels in diabetic patients.
3. Clinical Applications
| Indication | Application Scenario | Efficacy Evidence |
|---|---|---|
| Diabetic neuropathy | Alleviates sensory abnormalities and pain | Clinical guidelines recommend; >60% symptom relief |
| Liver injury (hepatitis/cirrhosis) | Reduces transaminases, promotes regeneration | Enhanced efficacy when combined with hepatoprotectants |
| Neurodegenerative diseases | Alzheimer’s (cognitive improvement), Parkinson’s (tremor reduction) | Inhibits Aβ aggregation, protects neurons |
| Anti-aging/cosmetics | Skin whitening (tyrosinase inhibition), anti-wrinkle (collagen preservation) | 0.1% concentration inhibits melanin by 71.5% |
| Cardiovascular diseases | Improves endothelial function, reduces atherosclerosis risk | Lowers oxidative stress markers (e.g., MDA) |
- Dosage:
- Oral: Diabetic neuropathy: 600 mg/day (divided into 3 doses); Antioxidant: 20–50 mg/day.
- Injection: 300–600 mg/day intravenously for severe cases (2–4 weeks).
4. Synthesis and Production
- Synthetic Routes:
- Total Synthesis: Octanoic acid is methylated, sulfurized, and cyclized to form the racemic mixture.
- Enzymatic Synthesis: Lipase-catalyzed synthesis of R-enantiomer with >99% purity.
- Manufacturing:
- China Dominates: 70% global production in Shandong and Jiangsu provinces (total yield ~65%).
- Quality Control: Compliant with Chinese Pharmacopoeia (heavy metals ≤10 ppm, residue on ignition ≤0.1%).
5. Safety and Precautions
- Adverse Effects:
- Common: Gastrointestinal discomfort (nausea, diarrhea, <5%), transient headache.
- Rare: Allergic reactions (rash, dyspnea), thrombocytopenia.
- Contraindications:
- Hypersensitivity, pregnancy/lactation, severe hepatic/renal impairment.
- Drug Interactions:
- Hypoglycemics: May enhance insulin effects; monitor blood glucose.
- Chemotherapy: Reduced cisplatin efficacy when co-administered.
6. Research Advances
- New Indications:
- Anticancer: Induces apoptosis in hepatocellular carcinoma via NF-κB inhibition, enhanced by CPUL1 nanoparticles.
- Anti-aging: Activates SIRT1 pathway to delay mitochondrial aging (lifespan extended by 15% in animal models).
- Formulation Innovations:
- Liposomal nanoparticles: Brain-targeted delivery improves bioavailability 4-fold for Alzheimer’s treatment.
- Transdermal patches: Stabilizes plasma concentrations for skin aging management.
7. Market and Policy
- Global Market:
- Size: Over $1.2 billion in 2024, growing at 8.5% annually.
- Regions: China holds 60% of raw material production; Europe/US focus on formulations.
- Regulatory Updates:
- China: Included in Diabetes Prevention Guidelines, partially covered by insurance.
- EU: Approved as novel food ingredient for functional foods.
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