Sustainable Membrane Technologies for By-Product Separation of Non-Pharmaceutical Common Compounds

Round 1

Reviewer 1 Report

1. In this manuscript, the authors are supposed to review the membrane technologies for by-products separation from non-pharmaceutical common polymer materials, such as Traditional Chinese Medicine. However,  membrane membrane fabrication and membrane characterization are very general and not necessary. 

2. The section of membrane separation process, which is relevant to the title, has very little content. 

3. The section of "Application of Membrane Integration Technology in Preparation of Non-Pharmaceutical Common Polymer Materials" also has little content. 

4. Nanotoxicology may be interesting, but it contains very little information. 

Author Response

1. In this manuscript, the authors are supposed to review the membrane technologies for by-products separation from non-pharmaceutical common polymer materials, such as Traditional Chinese Medicine. However, membrane fabrication and membrane characterization are very general and not necessary. 

Response: Thanks for your suggestion. Please see that some new relevant content has been added to the manuscript.

 

The general technological procedure of TCM preparation is shown in Figure 1. The conventional methods of separating and purifying TCMs—sedimentation, centrifugation, ethanol precipitation, salting out, clarifying agents, and macroporous resin adsorption—can be supplemented or even replaced by MF and UF. Figure 5 depicts the concentration process of TCMs, which can be accomplished via NF, RO, or MD.

 

Figure 5. General technological procedure of TCM preparation

 

2. The section of membrane separation process, which is relevant to the title, has very little content. 

 

Response: Thanks for your suggestion. Please see that some new relevant content has been added to the manuscript.

8.1. TCM Extraction Process

The sieving effect of the membrane can separate the substances by the character-istics of the pore size of the membrane, which means that the separation product of the membrane can be multiple components of a certain relative molecular mass section, which is exactly the same as the relative molecular mass distribution characteristics of the medicinal substances of traditional Chinese medicine. Therefore, the most im-portant advantages and characteristics of membrane technology for the traditional Chinese medicine system are: basically maintaining the traditional process of water extraction, and according to the relative molecular mass characteristics of the effective ingredients of traditional Chinese medicine, it will accurately remove starch, pectin, protein, and other polymer substances. At the same time, the small molecule compo-nents in traditional Chinese medicine and their compound prescriptions are used as a group of special chemical drugs for cluster screening.

 

8.1.1. Separation process

Pretreatment technology is a key factor that prevents and controls membrane pollution and affects the effectiveness and economy of membrane separation technol-ogy. Advanced pretreatment technology and its optimized combination can ensure the long-term stable operation of the subsequent membrane system and reduce its operat-ing costs and expand the application field of membrane separation technology. By un-derstanding the characteristics of the materials to be separated, the targeted pretreat-ment process to ensure the long-term stable operation of the subsequent membrane system has become an advanced membrane technology concept. At present, the re-search on the pretreatment of the Traditional Chinese medicine liquid before the membrane mainly focuses on the macroscopic performance of the membrane flux at-tenuation and the retention rate of certain 1 to 2 index components by the relevant methods. However, the understanding of the pretreatment technology to improve the mechanism of membrane separation is unclear, making it difficult for the pretreatment technology to achieve the expected purpose and lacking a scientific evaluation system for its effect. It is often necessary to pass a large number of experiments for different traditional Chinese medicine systems to find a suitable pretreatment method, which requires a lot of work and a narrow range of applications

Gao et al. discovered that purifying Sophorae flavescent radix extract with 0.2 m Al2O3 ceramic filters reduced active ingredient loss compared to ethanol precipitation [76]. The turbid extract was filtered to produce a clear solution with a 39.5% decrease in solids and 79.7% retention of the oxymatrine, and 77.2% retention of the active fla-vonoid ingredients. The solid content of the flavescent radix extract was reduced by 39.9% after precipitation in 70% ethanol, and the retention rates of oxymatrine and total flavonoids were 66.0% and 54.8%, respectively. It demonstrated that membrane technology outperformed ethanol precipitation in terms of reducing active ingredient loss. Wang et al. [77] found that processing a 0.374 mg/mL chinaberry tree extract at 35°C using a 0.45 m polyethersulfone (PES) membrane at a pressure of 0.08 MPa and a cross-flow of 0.15 L/h were optimal conditions. The membrane flux reached 147 L/m2h under optimal conditions, toosendanin retention was 99.4%, solid removal was 8.3%, and toosendanin purity increased from 0.89% to 8.8%.

8.1.2. Purification process of TCM

Polysaccharides have been purified using fractional precipitation by organic sol-vents [78] salting out [79], quaternary ammonium salt precipitation [80], column chromatography including gel permeation chromatography [81], ion exchange chro-matography [82] and membrane filtration [83, 84]. Table 2 shows a comparison of dif-ferent purification methods. Membrane filtration does not require heating or chemical reagent treatment; it is efficient, energy efficient, and environmentally friendly. Filtra-tion also effectively retains polysaccharide biological activity. Table 4 shows examples of using membrane filtration to purify TCM polysaccharides and other natural poly-saccharides.

8.1.3. Concentration process

The separations attained by NF fall in the middle of those attained by RO and UF [85]. Aqueous solutions of organic solutes with molecular weights of more than 300 Da can be concentrated and purified using NF membranes with pores between 0.5-2 nm in size [86]. The benefits of NF include lower costs than RO and a higher retention capac-ity than UF. NF is a viable substitute for heat treatment to concentrate TCM extracts since the molecular weight of TCM active components, with the exception of polysac-charides and proteins, varies from 100 to 1000 Da. Table 2 provides examples of the application of membrane filtration to concentrate TCM extracts.

Table 2. Examples of applications of membrane technology on the concentration of TCM extracts

TCM Names	Membranes Type	Pore Size (μm)	Concentration (%)	Ref
Glycyrrhizae radix et rhizoma	NF and RO	0.02	90.7	[87]
Leonuri herba	VMD: Hollow fiber membrane	0.2	10	[88]
Scutellariae radix	VMD: PVDF hollow fiber membrane	0.18	100	[89]
Roselle	NF and RO	0.016	99.6	[90]
Salvia officinalis	MF, UF and NF	0.45	100	[91]

 

 

3. The section of "Application of Membrane Integration Technology in Preparation of Non-Pharmaceutical Common Polymer Materials" also has little content. 

Response: Thanks for your suggestion. The author has declared that some new content has been added to the manuscript.

The complexity of polysaccharide extracts makes it challenging to produce high-purity polysaccharides with just one purifying technique. To separate polysaccharides as desired, it is required to combine two or more techniques. Ye et al. [100] started with 0.45 m membranes in their exploration of the combined use of MF, UF, and ion exchange chromatography to extract Sargassum pallidum polysaccharides in order to prevent fouling of the UF membranes. To separate the primary polysaccharide fractions, the filtrate was fractionated using MF membranes with 0.1 m pore size and UF membranes with 100, 50, 10, and 3 kDa MWCO [101].

 

4. Nanotoxicology may be interesting, but it contains very little information.

 

Answer: Thanks for your suggestion. The author has declared that some new content has been added to the manuscript.

 

A lot of serious and light toxic polymers (Chemical composition, Surface structure, Solubility and Functional groups) and solvents have been used to fabricate the membrane, such as N-methyl-2-pyrrolidone (NMP), dimethylacetamide (DMAc), dimethylformamide (DMF), benzene, carbon tetrachloride, and trichloroethylene, 2-ethoxyethanol, 2-methoxyethanol, and methyl chloride, neurotoxins include n-hexane, tetrachloroethylene, and toluene. For example, the side effects of DMAc are: Dimethyl Acetamide can irritate the nose and throat when inhaled and can irritate the skin and eyes when it comes into contact. Brain effects, such as depression, sluggishness, hallucinations, and other personality changes, can be brought on by high or repetitive exposure. Dimethyl Acetamide may cause nausea and/or jaundice by harming [105]. Due to their reduced effects on both human health and the environment, greener/low-toxicity solvents are beginning to gain attention [106]. Opportunities for novel and bio-derived, less hazardous solvents are only anticipated to grow globally as the globe transitions to a more bio-derived manufacturing base. Recently, green solvents such as methyl lactate, triethylphosphate, ionic liquids, organic carbonates, PolarClean, -valerolactone, and others have been researched for membrane manufacturing.

 

Reviewer 2 Report

Manuscript titled with “Sustainable membrane technologies for by-products separation from non-pharmaceutical common polymer materials” (ID: water-1978562) summarized the current use and future possibilities of membrane technology in non-pharmaceutical common polymer materials separation, such as traditional Chinese medicine (TCM). Interestingly, the authors investigated the specific separation efficiency of different membranes on the non-pharmaceutical polymer from the point of view of membrane materials and membrane structure. Different membrane filtration technologies, membrane fabrication methods and membrane characterization and their effect on the separation performance of different TCMs were introduced orderly. Totally speaking, the viewpoint and content of this article were interesting. However, some defect needs to be modified to make this article become better.

1) In the “Abstract” part, the significative and specific summarized content and future perspectives should be added. The current content was not deep-going.

2) Can all the different normal membrane filtration process be used for the separation of non-pharmaceutical common polymer materials? I think the authors need to selectively introduce the important filtration process that be more likely to be applied in TCMs separation in part 2.

3) During the part of “6 Membrane Separation Process”, we did not get the idea or the purpose of these content. The detailed influence mechanism and the corresponding existing studies or practical examples should be added.

4) The mind and order of the whole content of this article was chaotic. The connection between the neighboring part was unclear and their contribution to the purpose of this article need to be described and emphasized in detail.

5) Does a large number of biological by-products (and bacteria) exist on the TCMs or generate during the preparation of TCMs? TCMs their selves have the ability to inhibit the bacteria or virus to some extent. The authors need to explain.

Author Response

• In the “Abstract” part, the significative and specific summarized content and future perspectives should be added. The current content was not deep-going.

 

Answer: Thanks for your suggestion. The author has declared that some new content has been added to the manuscript.

 

However, for future perspectives, it is necessary to carry out an in-depth analysis of its molecular spatial structure; on the other hand, it is essential to select membrane materials according to local conditions and micro-control the internal structure of membrane pores; in addition to the basic "pore size sieving" principle. The researchers pay more attention to the choice of membrane pore size when selecting membranes but often ignore the influence of membrane materials and membrane structure on separation, resulting in certain blindness in the membrane selection process.

 

 

• Can all the different normal membrane filtration process be used for the separation of non-pharmaceutical common polymer materials? I think the authors need to selectively introduce the important filtration process that be more likely to be applied in TCMs separation in part 2.

 

Answer: Thanks for your suggestion. The author has declared that the authors have already added this information as per the first reviewer's comment.  

 

• During the part of “6 Membrane Separation Process”, we did not get the idea or the purpose of these content. The detailed influence mechanism and the corresponding existing studies or practical examples should be added.

 

Answer: Thanks for your suggestion. The author has confirmed that this section has been added to clarify the membrane pore size and TCM solution condition for the filtration experiment.

 

• The mind and order of the whole content of this article was chaotic. The connection between the neighboring part was unclear and their contribution to the purpose of this article need to be described and emphasized in detail.

 

Answer: Thanks for your suggestion. The author has declared that some new content has been added to the manuscript to clarify the contribution to the purpose of TCM. 

 

 

• Does a large number of biological by-products (and bacteria) exist on the TCMs or generate during the preparation of TCMs? TCMs their selves have the ability to inhibit the bacteria or virus to some extent. The authors need to explain.

 

Answer: Thanks for your suggestion. The author has confirmed that we meant biological by-products such as bacteria and viruses in the surface peel of trees. When peeled and blended by machine, some biological can be present in the solution of TCMs. 

 

Reviewer 3 Report

The review article “Sustainable membrane technologies for by-products separation from non-pharmaceutical common polymer materials” looks interesting. However, the authors could further improve the manuscripts as per bellow comments:

1.      Please check spelling mistakes and the English language throughout the text.

2.      Abstract: please rewrite the main results and the purpose

3.      Please cite more state-of-the-art references from the host journal.

4.      Introduction: the advance added to the area must be clearly stated. Particularly Introduction could be enlarged.

5.      Change the figure 1 background color.

6.      Authors may incorporate further information on traditional Chinese medicine filtration.

7.      Please check the reference format

8.      Conclusion: please add the key points with the further implication

 

 

Author Response

1. Please check spelling mistakes and the English language throughout the text.

 

Answer: Thanks for your suggestion. The author has confirmed that a native English speaker has corrected this review article.

 

2. Abstract: please rewrite the main results and the purpose

 

Answer: Thanks for your suggestion. The author has confirmed that the abstract has been changed as per the reviewer's aspect.

 

3. Please cite more state-of-the-art references from the host journal.

 

Answer: Thanks for your suggestion. The author has confirmed that some references have been added as per the reviewer aspect.

4. Introduction: the advance added to the area must be clearly stated. Particularly Introduction could be enlarged.

 

Answer: Thanks for your suggestion. The author has confirmed that some changes have been shown as per the reviewer aspect.

 

5. Change the figure 1 background color.

 

Answer: Thanks for your suggestion. The author has confirmed that the figure color has been changed as per the reviewer's aspect.

 

 

 

6. Authors may incorporate further information on traditional Chinese medicine filtration.

Answer: Thanks for your suggestion. The author has declared that some new content has been added to the manuscript.

 

 

7. Please check the reference format

 

Answer: Thanks for your suggestion. The author has confirmed that the reference format has been changed as per the reviewer aspect.

 

8. Conclusion: please add the key points with the further implication

 

Answer: Thanks for your suggestion. The author has confirmed that the reference format has been changed as per the reviewer aspect.

 

In short, the modernization of Chinese medicine is a huge system of engineering, which requires cross-cooperation among multiple disciplines, and polymer materials have a broad application prospect in Chinese medicine. To fully integrate polymer materials science and traditional Chinese medicine require both the efforts of materials science and the efforts of traditional Chinese medicine and pharmacy. The popularization and application of new materials and new technologies in traditional Chinese medicine rely more on the basic research of traditional Chinese medicine, such as chemistry, analysis, and pharmacology.

 

Reviewer 4 Report

The authors presented a review paper entitled “Sustainable membrane technologies for by-products separation from non-pharmaceutical common polymer materials”.

I don’t think that this Review article presents something novel or new opportunities in membrane filtration systems. The content of the Review is common. From my point of novelty is necessary to overview the above-integrated processes (electromembrane or ion-exchange membrane separation) and compare them. The authors mentioned this in 7.2. but in a few words. 

 

Author Response

I don’t think that this Review article presents something novel or new opportunities in membrane filtration systems. The content of the Review is common. From my point of novelty is necessary to overview the above-integrated processes (electromembrane or ion-exchange membrane separation) and compare them. The authors mentioned this in 7.2. but in a few words.

 

Answer: Thanks for your suggestion. The authors are grateful to the reviewers for their valuable comments. As per reviewer comments, many changes and new sections have been added to the revised manuscript.

Round 2

Reviewer 1 Report

1. The authors have carefully answered the queries from the reviewers and made necessary amendments. 

2. The part of membrane technologies used in TCM production and nano-toxicology have been significantly improved. 

Author Response

Comments and Suggestions for Authors

Reviewer 1:

1. The authors have carefully answered the queries from the reviewers and made necessary amendments. 

Answer: Thank you for your comment.

2. The part of membrane technologies used in TCM production and nano-toxicology have been significantly improved. 

Answer: Thank you for your comment.

Reviewer 4 Report

Dear authors,

After section 2. Membrane filtration. I recommend adding information about electromembrane processes (ED, EDBM etc.) and concentration methods (diffusion dialysis) in the different industries. This is very important for sustainable technologies. Section 7.2. even without any changes. I mentioned this in the last review. 

Figure 5. Please increase the quality of the figure and visualization (crooked arrows).

Line 556: check the index (L/m2h)

 

 

Author Response

Reviewer 4:

 

After section 2. Membrane filtration. I recommend adding information about electromembrane processes (ED, EDBM etc.) and concentration methods (diffusion dialysis) in the different industries. This is very important for sustainable technologies. Section 7.2. even without any changes. I mentioned this in the last review. 

 

Answer: Thank you. Please see that we added ED technology based on your suggestion.  

              

 Many studies have been done on the use of electrodialysis in TCM separation to recover valuable TCM compounds. Due to its complex TCM quality and high content of various macromolecules and impurities, electroplating macromolecules has always been a difficult point in the membrane concentration process (Figure 6). The use of a homogeneous membrane electrodialysis device effectively solves this problem. After the raw water is pretreated by sedimentation, oxidation, and ultrafiltration. It enters the electrodialysis concentration, and after reaching 12%, it enters the MVR evaporation, the fresh water is reused after reverse osmosis treatment, and the electroplating wastewater is effectively treated to achieve near zero discharge. The reverse osmosis concentrated water of the thermal power plant is treated by electrodialysis to meet the boiler water standard. The conductivity of reverse osmosis concentrated water is 3700 μS cm^-1, and the water volume is 150 m³ h^-1. After electrodialysis treatment, the effluent of electrodialysis concentrated water is 26 m³ h^-1, with a salt content of 11118 mg L^-1. Further, the electrodialysis fresh water enters the reverse osmosis system, and the reverse osmosis fresh water is further processed into boiler water by EDI. The conductivity of EDI water is ≤0.2 μS cm^-1, and the pH value is 7±1.

Electrochemical oxidation in the electrodialysis process has been used for antibiotics removal during nutrient recovery from pig manure digestate. Lin shi et al. have examined that antibiotics in the anode-ED were removed much more efficiently, with SD and TC removed in 30 and 60 min [92]. The electrodialysis process might be improved the efficiency of traditional CMM production when it has used in the pharmaceutical industry of CMM. The diffusion dialysis flow process has been employed here. The process describes the wastewater/non-ingredients from traditional Chinese medicine extracts as filtered by a ceramic membrane and then enters a diffusion dialysis device for treatment, and the residual liquid of diffusion dialysis is discharged to a biochemical treatment system for biochemical treatment. The homogeneous membrane electrodialysis for concentration and desalination, the freshwater can be reused as a diffusion dialysis receiving solution, and the concentrated water is concentrated to a sulfuric acid content of more than 9% and reused in the production process of traditional Chinese medicine extrication. Through the combination of membrane integration technology and traditional biochemical process, the wastewater/ non-ingredients of the traditional Chinese medicine extract can be utilized as a resource.

 

 

Figure 6. Electrodialysis process for TCM concentrate process.

 

 

Regarding section 7.2, we just provided a preliminary concept here and the following discussion has been mentioned in the latter parts.

 

Figure 5. Please increase the quality of the figure and visualization (crooked arrows).

 

Answer: Thank you for your comment. The author declared that the quality of the figure has been updated in the manuscript.

 

 

Line 556: check the index (L/m2h)

 

Answer: Thank you for your comment. The author declared that the index (L/m2h) has been changed by L∙m^-2 ∙h^-1.