化工进展 ›› 2019, Vol. 38 ›› Issue (01): 556-575.DOI: 10.16085/j.issn.1000-6613.2018-1174
收稿日期:
2018-06-05
修回日期:
2018-10-09
出版日期:
2019-01-05
发布日期:
2019-01-05
通讯作者:
陈芬儿
作者简介:
程荡(1985—),男,博士,青年研究员,研究方向为连续流化学制药。E-mail:<email>dcheng@fudan.edu.cn</email>。|陈芬儿,中国工程院院士,教授,研究方向为药物分子设计与化学合成。E-mail:<email>rfchen@fudan.edu.cnmail.</email>
基金资助:
Dang CHENG1,2(),Fen’er CHEN1,2()
Received:
2018-06-05
Revised:
2018-10-09
Online:
2019-01-05
Published:
2019-01-05
Contact:
Fen’er CHEN
摘要:
基于微反应器的连续流微反应技术在化学制药行业还是相对较新的概念,相比于传统釜式合成方式,该反应技术具有传质传热效率高、本质安全、过程重复性好、产品质量稳定、连续自动化操作和时空效率高等诸多优势,其用于化学药物合成中的研究越来越多。本文综述了近年来连续流微反应技术在实现从起始原料到终端原料药或制剂的“端-到-端”连续合成制备方面的研究进展,以典型案例分析的方式具体阐明了它的技术优势和重要意义,分析总结了其应用于化学药物合成目前所存在的问题。总体来说,化学药物合成的工艺路线较长,各步反应间常存在体系兼容性、溶剂置换、分离纯化和加料顺序等方面的问题,造成各单步合成转化之间的工艺衔接和耦合后处理步骤是“端-到-端”多步连续流微反应技术的难点和挑战,亟待进一步发展。同时指出发展能与微反应器有效耦合的工艺衔接及后处理技术与装备将逐步成为该领域的研究热点。
中图分类号:
程荡, 陈芬儿. 连续流微反应技术在药物合成中的应用研究进展[J]. 化工进展, 2019, 38(01): 556-575.
Dang CHENG, Fen’er CHEN. Progress in applied research of the continuous-flow micro-reaction technology in drug synthesis[J]. Chemical Industry and Engineering Progress, 2019, 38(01): 556-575.
1 | 赵临襄, 王志祥 . 化学制药工艺学[M]. 北京: 中国医药科技出版社, 2003. |
ZHAO X L , WANG Z X . Chemical pharmaceutical technology[M]. Beijing: China Medical Science Press, 2003. | |
2 | GUTMANN B , CANTILLO D , KAPPE, C O . Continuous-flow technology: a tool for the safe manufacturing of active pharmaceutical ingredients[J]. Angewandte Chemie: International Edition, 2015, 54: 6688-6728. |
3 | 苏为科, 余志群 . 连续流反应技术开发及其在制药危险工艺中的应用[J]. 中国医药工业杂志, 2017, 48(4): 469-482. |
SU W K , YU Z Q . Research and development of continuous-flow reaction technology and its application in dangerous drug synthesis processes[J]. Chinese Journal of Pharmaceuticals, 2017, 48(4): 469-482. | |
4 | EHRFELD W , HESSEL V , LÖWE H . Microreactors: new technology for modern chemistry[M]. New York: Wiley-VCH, 2000. |
5 | POECHLAUER P , MANLEY J , BROXTERMAN R , et al . Continuous processing in the manufacture of active pharmaceutical ingredients and finished dosage forms: an industry perspective[J]. Organic Process Research & Development, 2012, 16: 1586-1590. |
6 | MASCIA S , HEIDER P L , ZHANG H , et al . End-to-end continuous manufacturing of pharmaceuticals: integrated synthesis, purification, and final dosage formation[J]. Angewandte Chemie: International Edition, 2013, 52: 12359-12363. |
7 | WEGNER J , CEYLAN S , KIRSCHNING . A flow chemistry:a key enabling technology for (multistep) organic synthesis[J]. Advanced Synthesis & Catalysis, 2012, 354: 17-57. |
8 | POE S L , CUMMINGS M A , HAAF M P , et al . Solving the clogging problem: precipitate-forming reactions in flow[J]. Angewandte Chemie: International Edition, 2006, 45: 1544-1548. |
9 | SONG H , CHEN D L , ISMAGILOV R F . Reactions in droplets in microfluidic channels[J]. Angewandte Chemie: International Edition, 2006, 45: 7336-7356. |
10 | ZHAO B , MOORE J S , BEEBE D J . Surface-directed liquid flow inside microchannels[J]. Science, 2001, 291: 1023-1026. |
11 | GHAINI A , MESCHER, A, AGAR, D W . Hydrodynamic studies of liquid-liquid slug flows in circular microchannels[J]. Chemical Engineering Science, 2011, 66: 1168-1178. |
12 | ZHAO Y , CHEN G W , YUAN Q . Liquid-liquid two-phase flow patterns in a rectangular microchannel[J]. AIChE Journal, 2006, 52: 4052-4060. |
13 | KASHID M N , AGAR D W . Hydrodynamics of liquid-liquid slug flow capillary microreactor: flow regimes, slug size and pressure drop[J]. Chemical Engineering Journal, 2007, 131: 1-13. |
14 | YAO C Q , LIU Y , XU C , et al . Formation of liquid-liquid slug flow in a microfluidic T-junction: effects of fluid properties and leakage flow[J]. AIChE Journal, 2018, 64: 346-357. |
15 | KAWAHARA A , CHUNG P Y , KAWAJI M . Investigation of two-phase flow pattern, void fraction and pressure drop in a microchannel[J]. International Journal of Multiphase Flow, 2002, 28: 1411-1435. |
16 | TRIPLETT K A , GHIAASIAAN S , ABDEL-KHALIK S , et al . Gas-liquid two-phase flow in microchannels. Part Ⅰ: Two-phase flow patterns[J]. International Journal of Multiphase Flow, 1999, 25: 377-394. |
17 | TRIPLETT K , GHIAASIAAN S , ABDEL-KHALIK S , et al . Gas-liquid two-phase flow in microchannels. PartⅡ: Void fraction and pressure drop[J]. International Journal of Multiphase Flow, 1999, 25: 395-410. |
18 | FRIES D M , TRACHSEL F , VON ROHR P R . Segmented gas-liquid flow characterization in rectangular microchannels[J]. International Journal of Multiphase Flow, 2008, 34: 1108-1118. |
19 | RAJESH V , BUWA V V . Experimental characterization of gas-liquid-liquid flows in T-junction microchannels[J]. Chemical Engineering Journal, 2012, 207: 832-844. |
20 | YUE J , REBROV E V , SCHOUTEN J C . Gas-liquid-liquid three-phase flow pattern and pressure drop in a microfluidic chip: similarities with gas-liquid/liquid-liquid flows[J]. Lab on a Chip, 2014, 14: 1632-1649. |
21 | WANG K , LU Y C , TAN J , et al . Generating gas/liquid/liquid three-phase microdispersed systems in double T-junctions microfluidic device[J]. Microfluidics and Nanofluidics, 2010, 8(6): 813-821. |
22 | WANG K , QIN K , LU Y C , et al . Gas/liquid/liquid three-phase flow patterns and bubble/droplet size laws in a double T-junction microchannel[J]. AIChE Journal, 2015, 61: 1722-1734. |
23 | HOFFMANN M , SCHLÜTER M , RÄBIGER N . Experimental investigation of liquid-liquid mixing in T-shaped micro-mixers using μ-LIF and μ-PIV[J]. Chemical Engineering Science, 2006, 61: 2968-2976. |
24 | FRIES D M , ROHR VON , P R . Liquid mixing in gas-liquid two-phase flow by meandering microchannels[J]. Chemical Engineering Science, 2009, 64: 1326-1335. |
25 | KASHID M , RENKEN A , KIWI-MINSKER L . Mixing efficiency and energy consumption for five generic microchannel designs[J]. Chemical Engineering Journal, 2011, 167: 436-443. |
26 | ALAM A , KIM K Y . Analysis of mixing in a curved microchannel with rectangular grooves[J]. Chemical Engineering Journal, 2012, 181: 708-716. |
27 | KASHID M N , RENKEN A , KIWI-MINSKER L . Gas-liquid and liquid-liquid mass transfer in microstructured reactors[J]. Chemical Engineering Science, 2011, 66: 3876-3897. |
28 | RAIMONDI N D M , PRAT L , GOURDON C , et al . Experiments of mass transfer with liquid-liquid slug flow in square microchannels[J]. Chemical Engineering Science, 2014, 105: 169-178. |
29 | LEE P S , GARIMELLA S V , LIU D . Investigation of heat transfer in rectangular microchannels[J]. International Journal of Heat and Mass Transfer, 2005, 48: 1688-1704. |
30 | WU H , CHENG P . An experimental study of convective heat transfer in silicon microchannels with different surface conditions[J]. International Journal of Heat and Mass Transfer, 2003, 46: 2547-2556. |
31 | LIU G , WANG K , LU Y C , et al . Liquid-liquid microflows and mass transfer performance in slit-like microchannels[J]. Chemical Engineering Journal, 2014, 258: 34-42. |
32 | YANG L , TAN J , WANG K , et al . Mass transfer characteristics of bubbly flow in microchannels[J]. Chemical Engineering Science, 2014, 109: 306-314. |
33 | CHERLO S K R , KARIVETI S , PUSHPAVANAM S . Experimental and numerical investigations of two-phase (liquid-liquid) flow behavior in rectangular microchannels[J]. Industrial & Engineering Chemistry Research, 2009, 49: 893-899. |
34 | ADEOSUN J T , LAWAL A . Numerical and experimental studies of mixing characteristics in a T-junction microchannel using residence-time distribution[J]. Chemical Engineering Science, 2009, 64: 2422-2432. |
35 | GUPTA R , FLETCHER, D F, HAYNES, B S . On the CFD modelling of Taylor flow in microchannels[J]. Chemical Engineering Science, 2009, 64: 2941-2950. |
36 | RAIMONDI N D M , PRAT L , GOURDON C , et al . Direct numerical simulations of mass transfer in square microchannels for liquid-liquid slug flow[J]. Chemical Engineering Science, 2008, 63: 5522-5530. |
37 | RAJ R , MATHUR N , BUWA V V . Numerical simulations of liquid-liquid flows in microchannels[J]. Industrial & Engineering Chemistry Research, 2010, 49: 10606-10614. |
38 | WÖRZ O , JÄCKEL K P , RICHTER T , et al . Microreactors—A new efficient tool for reactor development[J]. Chemical Engineering & Technology, 2001, 24: 138-142. |
39 | ZHANG X , STEFANICK S , VILLANI F J . Application of microreactor technology in process development[J]. Organic Process Research & Development, 2004, 8: 455-460. |
40 | BRAUNE S , PÖCHLAUER P , REINTJENS R , et al . Selective nitration in a microreactor for pharmaceutical production under cGMP conditions[J]. Chemistry Today, 2009, 27: 26-29. |
41 | THOMAS W . Microreactors in organic chemistry and catalysis[M]. Weinheim: Wiely-VCH, 2008: 84-122. |
42 | ROBERGE D M , DUCRY L , BIELER N , et al . Microreactor technology: a revolution for the fine chemical and pharmaceutical industries? [J]. Chemical Engineering & Technology, 2005, 28: 318-323. |
43 | MATTHEW B , PLUTSCHACK B P , GILMORE KERRY , et al . The hitchhiker’s guide to flow chemistry[J]. Chemical Reviews, 2017, 117: 11796–11893. |
44 | GUTMANN BERNHARD , KAPPE C O . Continuous-flow technology—A tool for the safe manufacturing of active pharmaceutical ingredients[J]. Angewandte Chemie: International Edition, 2015, 54: 6688-6728. |
45 | ADAMO A , BEINGESSNER, R L, BEHNAM, M, et al . On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system[J]. Science, 2016, 352: 61-67. |
46 | SNEAD D R , JAMISON, T F . End-to-end continuous flow synthesis and purification of diphenhydramine hydrochloride featuring atom economy, in-line separation, and flow of molten ammonium salts[J]. Chemical Science, 2013, 4: 2822-2827. |
47 | BOGDAN A R , POE S L , KUBIS D C , et al . The continuous-flow synthesis of Ibuprofen[J]. Angewandte Chemie: International Edition, 2009, 48: 8547-8550. |
48 | BAUMANN M , BAXENDALE, I R . The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry[J]. Beilstein Journal of Organic Chemistry, 2015, 11: 1194-1219. |
49 | SNEAD D R , JAMISON T F . A three-minute synthesis and purification of Ibuprofen: pushing the limits of continuous-flow processing[J]. Angewandte Chemie: International Edition, 2015, 54: 983-987. |
50 | CAPDEVILLE R , BUCHDUNGER E , ZIMMERMANN J , et al . Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug[J]. Nature Reviews Drug Discovery, 2002, 1: 493. |
51 | ARORA A , SCHOLAR E M . Role of tyrosine kinase inhibitors in cancer therapy[J]. Journal of Pharmacology and Experimental Therapeutics, 2005, 315: 971-979. |
52 | ZIMMERMANN J . Pyrimidine derivatives and processes for the preparation thereof: US5521184A[P]. 1996-05-28. |
53 | LEONETTI F , CAPALDI C , CAROTTI A . Microwave-assisted solid phase synthesis of Imatinib, a blockbuster anticancer drug[J]. Tetrahedron letters, 2007, 48: 3455-3458. |
54 | LOISELEUR O , KAUFMANN D , ABEL S , et al . N-phenyl-2-pyrimidine-amine derivatives: WO03066613[P]. 2003-08-14. |
55 | ZIMMERMANN J . Pyrimidin derivatives and process for their preparation: EP0564409[P]. 1993-10-06. |
56 | KOMPELLA A , BHUJANGA R A K S , VENKAIAH C N , et al . Process for the preparation of the anti-cancer drug Imatinib and its analogues: WO2004108699[P]. 2004-12-16. |
57 | HUANG A L , LIU X , LIOR Z , et al . Process for preparing imatinib: US7507821[P]. 2009-05-24. |
58 | HOPKIN M D , BAXENDALE I R , LEY S V . A flow-based synthesis of Imatinib: the API of Gleevec[J]. Chemical Communications, 2010, 46: 2450-2452. |
59 | HOPKIN M D , BAXENDALE I R , STEVEN V L . An expeditious synthesis of Imatinib and analogues utilising flow chemistry methods[J]. Organic & Biomolecular Chemistry, 2013, 11: 1822-1839. |
60 | WONG D T , PERRY K W , BYMASTER, F P . The discovery of fluoxetine hydrochloride (Prozac)[J]. Nature Reviews Drug Discovery, 2005, 4: 764-774. |
61 | GELLER D A , HOOG S L , HEILIGENSTEIN J H , et al . Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial[J]. Journal of the American Academy of Child & Adolescent Psychiatry, 2001, 40: 773-779. |
62 | BREMNER J D . Fluoxetine in depressed patients: a comparison with imipramine[J]. The Journal of Clinical Psychiatry, 1984, 45: 414-419. |
63 | GORMAN J M , LIEBOWITZ M R , FYER A J , et al . An open trial of fluoxetine in the treatment of panic attacks[J]. Journal of Clinical Psychopharmacology, 1987, 7: 329-332. |
64 | AHMED-OMER B , SANDERSON A J . Preparation of fluoxetine by multiple flow processing steps[J]. Organic & Biomolecular Chemistry, 2011, 9: 3854-3862. |
65 | WHITE N . Assessment of the pharmacodynamic properties of antimalarial drugs in vivo [J]. Antimicrobial Agents and Chemotherapy, 1997, 41: 1413-1422. |
66 | TU Y Y . The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine[J]. Nature Medicine, 2011, 17: 1217-1220. |
67 | World Health Organization . World malaria report[R]. Geneva: WHO, 2012. |
68 | MUTABINGWA T K . Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy![J]. Acta Tropica, 2005, 95: 305-315. |
69 | KREEFTMEIJER-VEGTER A R , VAN GENDEREN P J , VISSER L G , et al . Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium[J]. Malaria Journal, 2012, 11: 102. |
70 | LÉVESQUE F , SEEBERGER, P H . Continuous-flow synthesis of the anti-Malaria drug Artemisinin[J]. Angewandte Chemie: International Edition, 2012, 51: 1706-1709. |
71 | KOPETZKI D , LEVESQUE F , SEEBERGER P H . A continuous-flow process for the synthesis of Artemisinin[J]. Chemistry: a European Journal, 2013, 19: 5450-5456. |
72 | GILMORE K , KOPETZKI D , LEE J W , et al . Continuous synthesis of artemisinin-derived medicines[J]. Chemical Communications, 2014, 50: 12652-12655. |
73 | POTEWAR T M , INGALE S A , SRINIVASAN K V . Efficient synthesis of 2,4-disubstituted thiazoles using ionic liquid under ambient conditions: a practical approach towards the synthesis of Fanetizole[J]. Tetrahedron, 2007, 63: 11066-11069. |
74 | STYRT B , ROCKLIN R E , KLEMPNER M S . Inhibition of neutrophil superoxide production by Fanetizole[J]. Inflammation, 1985, 9(3): 233-244. |
75 | PASTRE J C , BROWNE D L , O’BRIEN M , et al . Scaling up of continuous flow processes with gases using a tube-in-tube reactor: Inline titrations and fanetizole synthesis with ammonia[J]. Organic Process Research & Development, 2013, 17: 1183-119 |
76 | KUDO Y , KURIHARA M . Clinical evaluation of diphenhydramine hydrochloride for the treatment of insomnia in psychiatric patients: a double-blind study[J]. The Journal of Clinical Pharmacology, 1990, 30: 1041-1048. |
77 | TANG A W . A practical guide to anaphylaxis[J]. American Family Physician, 2003, 68: 1325-1332. |
78 | BROWN H E , STOKLOSA J , FREUDENREICH O . How to stabilize an acutely psychotic patient: in psychiatric emergencies, use a stepwise approach to provide safe, effective treatment[J]. Current Psychiatry, 2012, 11: 10-17. |
79 | KRINSKY D L , FERRERI S P , HEMSTREET B , et al . Insomnia, handbook of nonprescription drugs: an interactive approach to self-care[M]. Washington: American Pharmaceutical Association, 2006. |
80 | LEMMON M E , KOSSOFF E H . New treatment options for lennox-gastaut syndrome[J]. Current Treatment Options in Neurology, 2013, 15:519-528. |
81 | SUTER M R , KIRSCHMANN G , LAEDERMANN, C J, et al . Rufinamide attenuates mechanical allodynia in a model of neuropathic pain in the mouse and stabilizes voltage-gated sodium channel inactivated state[J]. Anesthesiology: The Journal of the American Society of Anesthesiologists 2013, 118: 160-172. |
82 | HAKIMIAN S , CHENG-HAKIMIAN A , ANDERSON G D , et al . Rufinamide: a new anti-epileptic medication[J]. Expert Opinion on Pharmacotherapy, 2007, 8: 1931-1940. |
83 | ROGAWSKI M A . Diverse mechanisms of antiepileptic drugs in the development pipeline[J]. Epilepsy Research, 2006, 69: 273-294. |
84 | ROGAWSKI M A , LÖSCHER W . The neurobiology of antiepileptic drugs[J]. Nature Reviews Neuroscience, 2004, 5: 553-564. |
85 | BORUKHOVA S , NOËL T , METTEN B , et al . Solvent-and catalyst-free huisgen cycloaddition to Rufinamide in flow with a greener, less expensive dipolarophile[J]. ChemSusChem, 2013, 6: 2220-2225. |
86 | ZHANG P , RUSSELL, M G, JAMISON T F . Continuous flow total synthesis of rufinamide[J]. Organic Process Research & Development, 2014, 18: 1567-1570. |
87 | FULTON B , GOA K L . Olanzapine[J]. Drugs, 1997, 53: 281-298. |
88 | GOODMAN G . Goodman and Gilman's the pharmacological basis of therapeutics[M]. New York: Macmillan, 2001. |
89 | HARTWIG J , CEYLAN S , KUPRACZ L , et al . Heating under high-frequency inductive conditions: application to the continuous synthesis of the Neurolepticum Olanzapine (Zyprexa)[J]. Angewandte Chemie: International Edition, 2013, 52: 9813-9817. |
90 | LEUCHT C , HUHN M , LEUCHT S . Amitriptyline versus placebo for major depressive disorder[J]. Cochrane Database of Systematic Reviews, 2012, 12: CD009138. |
91 | MOORE R A , DERRY S , ALDINGTON D , et al . Amitriptyline for neuropathic pain in adults[J]. Cochrane Database of Systematic Reviews, 2015, 1: CD011209. |
92 | KUPRACZ L , KIRSCHNING A . Multiple organolithium generation in the continuous flow synthesis of Amitriptyline[J]. Advanced Synthesis & Catalysis, 2013, 355: 3375-3380. |
93 | INGELFINGER J R . Aliskiren and dual therapy in type 2 diabetes mellitus[J]. The New England Journal of Medicine, 2008, 358: 2503-2505. |
94 | MAIBAUM J , STUTZ S , GÖSCHKE R , et al . Structural modification of the P2 ‘position of 2,7-dialkyl-substituted 5 (S)-amino-4 (S)-hydroxy-8-phenyl-octanecarboxamides: the discovery of aliskiren, a potent nonpeptide human renin inhibitor active after once daily dosing in marmosets[J]. Journal of Medicinal Chemistry, 2007, 50: 4832-4844. |
[1] | 时永兴, 林刚, 孙晓航, 蒋韦庚, 乔大伟, 颜彬航. 二氧化碳加氢制甲醇过程中铜基催化剂活性位点研究进展[J]. 化工进展, 2023, 42(S1): 287-298. |
[2] | 杨霞珍, 彭伊凡, 刘化章, 霍超. 熔铁催化剂活性相的调控及其费托反应性能[J]. 化工进展, 2023, 42(S1): 310-318. |
[3] | 赵巍, 赵德银, 李世瀚, 刘洪达, 孙进, 郭艳秋. 三嗪型天然气管道缓蚀型减阻剂合成与应用[J]. 化工进展, 2023, 42(S1): 391-399. |
[4] | 王正坤, 黎四芳. 双子表面活性剂癸炔二醇的绿色合成[J]. 化工进展, 2023, 42(S1): 400-410. |
[5] | 邓建, 王凯, 骆广生. 面向硝基化学品安全生产的绝热连续微反应技术发展及思考[J]. 化工进展, 2023, 42(8): 3923-3925. |
[6] | 向阳, 黄寻, 魏子栋. 电催化有机合成反应的活性和选择性调控研究进展[J]. 化工进展, 2023, 42(8): 4005-4014. |
[7] | 徐沛瑶, 陈标奇, KANKALA Ranjith Kumar, 王士斌, 陈爱政. 纳米材料用于铁死亡联合治疗的研究进展[J]. 化工进展, 2023, 42(7): 3684-3694. |
[8] | 关红玲, 杨辉, 井红权, 刘玉琼, 谷守玉, 王好斌, 侯翠红. 木质素基控释材料及其在药物输送和肥料控释中的应用[J]. 化工进展, 2023, 42(7): 3695-3707. |
[9] | 陆洋, 周劲松, 周启昕, 王瑭, 刘壮, 李博昊, 周灵涛. CeO2/TiO2吸附剂煤气脱汞产物的浸出规律[J]. 化工进展, 2023, 42(7): 3875-3883. |
[10] | 陈森, 殷鹏远, 杨证禄, 莫一鸣, 崔希利, 锁显, 邢华斌. 功能固体材料智能合成研究进展[J]. 化工进展, 2023, 42(7): 3340-3348. |
[11] | 刘卫孝, 刘洋, 高福磊, 汪伟, 汪营磊. 微反应器在含能材料合成与品质提升中的应用[J]. 化工进展, 2023, 42(7): 3349-3364. |
[12] | 俞俊楠, 俞建峰, 程洋, 齐一搏, 化春键, 蒋毅. 基于深度学习的变宽度浓度梯度芯片性能预测[J]. 化工进展, 2023, 42(7): 3383-3393. |
[13] | 王帅旗, 王从新, 王学林, 田志坚. 无溶剂快速合成ZSM-12分子筛[J]. 化工进展, 2023, 42(7): 3561-3571. |
[14] | 余希希, 张金帅, 雷文, 刘承果. 基于动态共价键自修复的光固化高分子材料研究进展[J]. 化工进展, 2023, 42(7): 3589-3599. |
[15] | 王知彩, 刘伟伟, 周璁, 潘春秀, 闫洪雷, 李占库, 颜井冲, 任世彪, 雷智平, 水恒福. 基于煤基腐殖酸的高效减水剂合成与性能表征[J]. 化工进展, 2023, 42(7): 3634-3642. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||
京ICP备12046843号-2;京公网安备 11010102001994号 版权所有 © 《化工进展》编辑部 地址:北京市东城区青年湖南街13号 邮编:100011 电子信箱:hgjz@cip.com.cn 本系统由北京玛格泰克科技发展有限公司设计开发 技术支持:support@magtech.com.cn |