Ethanol-containing traditional Chinese medicine (TCM) liquids can be concentrated using nanofiltration (NF) technology, but it requires specific process design and membrane module selection. The following is a detailed analysis integrating technical principles, application schemes, and practical benefits:

I. Feasibility and Principles of Ethanol Concentration by Nanofiltration

Separation Mechanism

Nanofiltration (NF) membranes have a molecular weight cut-off (MWCO) range of 200-1000 Da and achieve separation based on pore size sieving and charge effects (Donnan effect). In ethanol-containing solutions:

1. Ethanol (molecular weight 46 Da) is a small molecule and can partially permeate through the NF membrane into the permeate;
2. TCM active ingredients (such as flavonoids, phenolic acids, MW > 200 Da) are selectively retained in the concentrate.
   By adjusting operating pressure (0.8-2.0 MPa) and membrane parameters, the ethanol removal rate can be controlled to achieve the concentration target.

Impact of Ethanol on Separation Efficiency

1. Altered Solution Environment: Ethanol changes the interfacial microenvironment of the NF membrane, causing membrane pore swelling and affecting the effective pore size. For example, low-concentration ethanol (5%-20%) can enhance the dissociation state of phenolic acid components, improving their charge interaction with the membrane and thereby increasing the retention rate.
2. Component Association: In ethanol solutions, some small phenolic acid molecules may form multi-molecular associations (increasing apparent molecular weight), further enhancing retention efficiency.

II. Technical Scheme and Process Flow

For concentrating ethanol-containing TCM liquids, a typical scheme uses an integrated "Ultrafiltration (UF) Pretreatment + Nanofiltration (NF) Concentration" process:

Pretreatment Stage

1. Coarse Filtration: Use 100~200 mesh screens to remove large particles like herb residues and fibers;
2. Centrifugation/Sedimentation: Reduce colloid content;
3. pH Adjustment: Adjust to neutral (pH 6~8) to avoid extreme pH damaging the membrane or causing component precipitation.

Ultrafiltration (UF) Pretreatment

1. Purpose: Retain large molecular impurities (polysaccharides, proteins) to protect the subsequent NF membrane;
2. Membrane Selection: Fouling-resistant tubular UF membrane (PVDF/PES material), MWCO 5~10 kDa;
3. Operating Parameters: 40~60°C, 0.2~0.6 MPa.

Nanofiltration (NF) Concentration of Ethanol

(See Parameter Table below for key NF operating parameters)

Post-Treatment

1. De-alcoholized Liquid Sterilization: Low-temperature pasteurization (60~80°C) or sterilization via 0.22 μm microfiltration;
2. Drying: Spray drying or vacuum drying to produce extract paste.

III. Technical Advantages and Economic Benefits

Component Retention and Quality Improvement

1. Protection of Thermosensitive Components: Room temperature operation prevents degradation of thermosensitive components like phenolic acids and saponins (e.g., ferulic acid retention rate ≥95%);
2. Impurity Removal: Simultaneously removes inorganic salts and small molecular impurities, improving the clarity and stability of oral liquids/injections.

Significant Energy Saving and Consumption Reduction

1. Energy Consumption Comparison: NF concentration consumes only about 8.89 kWh per ton of water, reducing energy use by over 50% compared to traditional evaporation concentration (e.g., multi-effect evaporation);
2. Ethanol Recovery Rate: Closed operation reduces ethanol thermal loss (traditional processes lose 1%-3%). Based on daily processing of 9m³ of feed liquid, this can save costs of approximately 1440 RMB/day.

Operational Convenience

1. Automation control (PLC system) supports continuous production. Online cleaning (UF backwash every 30~60 minutes, NF backwash every 2~4 hours) reduces membrane fouling.

IV. Limitations and Countermeasures

Concentration Endpoint Limitation

1. Problem: Osmotic pressure limitations prevent concentration to high-viscosity liquids (e.g., dry solids content >30% requires combination with evaporation or freeze-drying);
2. Countermeasure: Adopt an integrated "NF + Vacuum Evaporation" process to balance efficiency and final concentration.

Membrane Fouling and Compatibility

1. Fouling Sources: Aggregation of phenolic components and polysaccharides on the membrane surface leading to flux decline;
2. Cleaning Protocol: UF membrane: Clean with 0.1%~0.5% NaOH + 0.1% NaOCl mixture; NF membrane: Clean with 0.5% citric acid or EDTA.

Organic Solvent Compatibility

1. Challenge: High ethanol concentration (>20%) may cause membrane swelling, requiring solvent-resistant specialty membranes (e.g., cross-linked polyimide);
2. Parameter Optimization: Determine optimal ethanol concentration, pH, and pressure combination through pilot-scale tests (refer to Response Surface Methodology).

V. Application Recommendations

1. Process Design: For liquids containing small phenolic acids (e.g., p-coumaric acid), adding 10%~15% ethanol combined with pH adjustment (near pKa value) can increase retention rate to over 95%.
2. Equipment Selection: Prioritize explosion-proof NF systems (e.g., CD-RS8040-6X), compatible with ethanol environments and supporting automation control.
3. Economic Evaluation: For large-scale production, NF's energy-saving benefits (50% reduction) and ethanol recovery value can offset equipment investment costs within 6~12 months.

Conclusion: Nanofiltration technology can efficiently concentrate ethanol-containing TCM liquids, achieving selective ethanol removal and active ingredient enrichment. However, process integration (e.g., UF pretreatment, ethanol concentration/pH control) is necessary to address membrane fouling and high-viscosity concentration bottlenecks, ultimately achieving energy savings, consumption reduction, and quality improvement.

Parameters