CN101531721A - 一种三萜皂苷单体的工业化制备方法 - Google Patents
一种三萜皂苷单体的工业化制备方法 Download PDFInfo
- Publication number
- CN101531721A CN101531721A CN200910030660A CN200910030660A CN101531721A CN 101531721 A CN101531721 A CN 101531721A CN 200910030660 A CN200910030660 A CN 200910030660A CN 200910030660 A CN200910030660 A CN 200910030660A CN 101531721 A CN101531721 A CN 101531721A
- Authority
- CN
- China
- Prior art keywords
- preparation
- clematis
- ethanol
- root
- filtration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000000178 monomer Substances 0.000 title abstract description 4
- 150000008130 triterpenoid saponins Chemical class 0.000 title abstract description 4
- 241000903946 Clematidis Species 0.000 claims abstract description 20
- 238000000703 high-speed centrifugation Methods 0.000 claims abstract description 20
- 238000001914 filtration Methods 0.000 claims abstract description 17
- 238000010992 reflux Methods 0.000 claims abstract description 16
- 238000010438 heat treatment Methods 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 106
- 241000218158 Clematis Species 0.000 claims description 42
- 239000007788 liquid Substances 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 238000000605 extraction Methods 0.000 claims description 25
- 229930182470 glycoside Natural products 0.000 claims description 19
- 150000002338 glycosides Chemical class 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 16
- 238000010828 elution Methods 0.000 claims description 15
- 239000011347 resin Substances 0.000 claims description 15
- 229920005989 resin Polymers 0.000 claims description 15
- 230000001186 cumulative effect Effects 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- 241000196324 Embryophyta Species 0.000 claims description 10
- 238000001556 precipitation Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 238000007670 refining Methods 0.000 claims description 7
- 229930182490 saponin Natural products 0.000 claims description 7
- 150000007949 saponins Chemical class 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 238000000108 ultra-filtration Methods 0.000 claims description 6
- 230000006837 decompression Effects 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 238000011084 recovery Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000001179 sorption measurement Methods 0.000 claims description 3
- 239000002244 precipitate Substances 0.000 claims description 2
- 238000003860 storage Methods 0.000 claims description 2
- 241000601157 Clematis angustifolia Species 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000000284 extract Substances 0.000 abstract description 16
- 239000003814 drug Substances 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 7
- JFLCHMJGYAFQIU-AOXNNHMFSA-N [(2s,3r,4s,5s,6r)-6-[[(2r,3r,4r,5s,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2r,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxymethyl]-3,4,5-trihydroxyoxan-2-yl] (4as,6ar,6as,6br,8ar,10s,12ar,14bs)-10-[(2s,3r,4s,5s)-3-[(2s,3r,4r,5s,6s)-4-[( Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](O)[C@H](O[C@H]4[C@H]([C@H](O[C@H]5[C@@H](OC[C@H](O)[C@@H]5O)O[C@@H]5C([C@H]6[C@]([C@@H]7[C@@]([C@@]8(CC[C@]9(CCC(C)(C)C[C@H]9C8=CC7)C(=O)O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]8[C@@H]([C@@H](O)[C@H](O[C@H]9[C@@H]([C@H](O)[C@@H](O)[C@H](C)O9)O)[C@@H](CO)O8)O)O7)O)C)(C)CC6)(C)CC5)(C)C)O[C@@H](C)[C@@H]4O)O)OC3)O)[C@H](O)[C@H]2O)CO)O1 JFLCHMJGYAFQIU-AOXNNHMFSA-N 0.000 abstract description 4
- 238000005119 centrifugation Methods 0.000 abstract 1
- 238000001704 evaporation Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- SMRPGWBDLOQHOS-UHFFFAOYSA-N 5-[4,5-dihydroxy-6-(hydroxymethyl)-3-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxy-3,4-dihydroxy-6-[[9-hydroxy-4-(hydroxymethyl)-4,6a,6b,8a,11,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]oxane-2-carboxylic acid Chemical compound OC1C(O)C(O)C(C)OC1OC1C(OC2C(OC(C(O)C2O)C(O)=O)OC2C(C3C(C4C(C5(CCC6(C)C(O)CC(C)(C)CC6C5=CC4=O)C)(C)CC3)(C)CC2)(C)CO)OC(CO)C(O)C1O SMRPGWBDLOQHOS-UHFFFAOYSA-N 0.000 description 20
- PPRSVUXPYPBULA-UHFFFAOYSA-N saponin A Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(O)C6=O)C(C)(C)C5CCC34C)C2C1)C(=O)O PPRSVUXPYPBULA-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 13
- 241001256368 Clematis chinensis Species 0.000 description 12
- 239000000463 material Substances 0.000 description 10
- 238000004090 dissolution Methods 0.000 description 6
- 235000017709 saponins Nutrition 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 241000725146 Clematis hexapetala Species 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000001473 noxious effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 description 2
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 241000915582 Clematis manshurica Species 0.000 description 1
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002021 butanolic extract Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 229930182495 oleanane-type triterpene Natural products 0.000 description 1
- 229940100243 oleanolic acid Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Landscapes
- Steroid Compounds (AREA)
Abstract
Description
# | 保留时间 | 峰面积 | 峰高 | 峰宽 | 面积百分比 |
1 | 2.483 | 687.1 | 138.4 | 0.0739 | 5.9160 |
2 | 8.244 | 10771.9 | 571.4 | 0.2759 | 92.7406 |
3 | 9.325 | 156 | 9.4 | 0.2817 | 1.3434 |
TOTAL: | 11615.0 | 719.21068 | 100.0 |
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009100306603A CN101531721B (zh) | 2009-04-28 | 2009-04-28 | 一种三萜皂苷单体的工业化制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009100306603A CN101531721B (zh) | 2009-04-28 | 2009-04-28 | 一种三萜皂苷单体的工业化制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101531721A true CN101531721A (zh) | 2009-09-16 |
CN101531721B CN101531721B (zh) | 2011-07-20 |
Family
ID=41102596
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2009100306603A Expired - Fee Related CN101531721B (zh) | 2009-04-28 | 2009-04-28 | 一种三萜皂苷单体的工业化制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101531721B (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102120778A (zh) * | 2010-12-20 | 2011-07-13 | 大兴安岭嘉迪欧营养原料有限公司 | 一种富集纯化铁线莲中铁线莲皂苷的方法 |
CN102327335A (zh) * | 2011-07-26 | 2012-01-25 | 苏州宝泽堂医药科技有限公司 | 一种从威灵仙中提取总皂苷的方法 |
CN104072626A (zh) * | 2013-03-26 | 2014-10-01 | 正大天晴药业集团股份有限公司 | 一种灵仙新苷的制备方法 |
CN115671123A (zh) * | 2021-07-21 | 2023-02-03 | 苏州凯祥生物科技有限公司 | 威灵仙皂苷在制备降嘌呤药物中的应用 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100355424C (zh) * | 2003-12-11 | 2007-12-19 | 岐黄药业科技投资有限责任公司 | 治疗糖尿病的楤木提取物及楤木皂苷在制备治疗糖尿病的药物中的应用 |
CN1751676B (zh) * | 2004-09-22 | 2010-04-28 | 天津天士力制药股份有限公司 | 一种中药的膜超滤精制方法 |
CN1300176C (zh) * | 2005-06-29 | 2007-02-14 | 中国药科大学 | 一种新皂苷及其衍生物、其制备方法及其医药用途 |
-
2009
- 2009-04-28 CN CN2009100306603A patent/CN101531721B/zh not_active Expired - Fee Related
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102120778A (zh) * | 2010-12-20 | 2011-07-13 | 大兴安岭嘉迪欧营养原料有限公司 | 一种富集纯化铁线莲中铁线莲皂苷的方法 |
CN102120778B (zh) * | 2010-12-20 | 2014-04-02 | 大兴安岭嘉迪欧营养原料有限公司 | 一种富集纯化铁线莲中铁线莲皂苷的方法 |
CN102327335A (zh) * | 2011-07-26 | 2012-01-25 | 苏州宝泽堂医药科技有限公司 | 一种从威灵仙中提取总皂苷的方法 |
CN104072626A (zh) * | 2013-03-26 | 2014-10-01 | 正大天晴药业集团股份有限公司 | 一种灵仙新苷的制备方法 |
CN115671123A (zh) * | 2021-07-21 | 2023-02-03 | 苏州凯祥生物科技有限公司 | 威灵仙皂苷在制备降嘌呤药物中的应用 |
CN115671123B (zh) * | 2021-07-21 | 2024-03-22 | 苏州凯祥生物科技有限公司 | 威灵仙皂苷在制备降嘌呤药物中的应用 |
Also Published As
Publication number | Publication date |
---|---|
CN101531721B (zh) | 2011-07-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101559088B (zh) | 穿心莲总内酯与新穿心莲内酯、脱水穿心莲内酯、去氧穿心莲内酯的生产工艺 | |
CN102258588B (zh) | 芍药总苷的制备方法 | |
CN104592341A (zh) | 一种从积雪草中提取积雪草苷、羟基积雪草苷的方法 | |
CN101531721B (zh) | 一种三萜皂苷单体的工业化制备方法 | |
CN101856435B (zh) | 一种祖师麻总香豆素提取物的制备方法和含量测定方法 | |
CN101317883B (zh) | 夏枯草活性部位及其在制备药物组合物中的应用 | |
WO2012061984A1 (zh) | 制备芍药内酯苷和芍药苷的方法 | |
CN102372750A (zh) | 一种同时制备芍药内酯苷和芍药苷的方法 | |
CN101234147B (zh) | 注射用金莲花总黄酮的制备方法 | |
CN101418025A (zh) | 一种芍药苷的制备方法 | |
CN102070683B (zh) | 同时制备parishin、parishin B、parishin C化学对照品的方法 | |
CN107929544B (zh) | 白及属植物中militarine部位及单体的制备方法及其应用 | |
CN104447910A (zh) | 从中药山茱萸中制备马钱苷的方法 | |
CN101703669B (zh) | 菝葜有效部位群及其提取纯化工艺 | |
CN102040500B (zh) | 一种黄腐酚和黄酮类化合物的萃取分离方法 | |
CN103242422A (zh) | 一种从青钱柳叶中提取青钱柳酸a的方法 | |
CN102311466A (zh) | 一种从车前子中提取苯乙醇苷类活性成分的方法 | |
CN102329345A (zh) | 垂盆草中垂盆草苷的提取纯化方法 | |
CN103083392B (zh) | 一种分离富集山豆根中具异戊烯基黄酮部位的方法 | |
CN112250655B (zh) | 两种新的环状二苯基庚烷类化合物及其制备方法和用途 | |
CN104857245A (zh) | 紫萼玉簪花总皂苷的制备方法和应用 | |
CN102108072B (zh) | 从当归提取物中制备洋川芎内酯i的方法 | |
CN103497229B (zh) | 从地乌药材中同时制备地乌皂苷w1和w3的方法 | |
CN102389456A (zh) | 一种提取蓝萼香茶菜总二萜或蓝萼甲素的方法 | |
CN101747402B (zh) | 一种富集纯化费菜中熊果酸的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: JIANGSU ZHENGDA TIANQING PHARMACEUTICAL CO., LTD. Effective date: 20111207 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20111207 Address after: No. 639 road in Nanjing city in Jiangsu province 211198. Co-patentee after: Jiangsu Chiatai Tianqing Pharmaceutical Co., Ltd. Patentee after: China Pharmaceutical University Address before: No. 639 road in Nanjing city in Jiangsu province 211198. Patentee before: China Pharmaceutical University |
|
C56 | Change in the name or address of the patentee | ||
CP01 | Change in the name or title of a patent holder |
Address after: No. 639 road in Nanjing city in Jiangsu province 211198. Patentee after: China Pharmaceutical University Patentee after: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Address before: No. 639 road in Nanjing city in Jiangsu province 211198. Patentee before: China Pharmaceutical University Patentee before: Jiangsu Chiatai Tianqing Pharmaceutical Co., Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110720 Termination date: 20180428 |
|
CF01 | Termination of patent right due to non-payment of annual fee |