CN102433364A - 一种微生物发酵法制取雷帕霉素的工艺 - Google Patents
一种微生物发酵法制取雷帕霉素的工艺 Download PDFInfo
- Publication number
- CN102433364A CN102433364A CN2011103562492A CN201110356249A CN102433364A CN 102433364 A CN102433364 A CN 102433364A CN 2011103562492 A CN2011103562492 A CN 2011103562492A CN 201110356249 A CN201110356249 A CN 201110356249A CN 102433364 A CN102433364 A CN 102433364A
- Authority
- CN
- China
- Prior art keywords
- rapamycin
- technology
- produced
- fermentation method
- streptomyces hygroscopicus
- 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
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title claims abstract description 126
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 title claims abstract description 123
- 229960002930 sirolimus Drugs 0.000 title claims abstract description 123
- 238000000855 fermentation Methods 0.000 title claims abstract description 59
- 230000004151 fermentation Effects 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 42
- 238000004519 manufacturing process Methods 0.000 title abstract description 8
- 230000000813 microbial effect Effects 0.000 title abstract description 3
- 238000005516 engineering process Methods 0.000 claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 241000187391 Streptomyces hygroscopicus Species 0.000 claims abstract description 25
- 239000001963 growth medium Substances 0.000 claims abstract description 23
- 238000011218 seed culture Methods 0.000 claims abstract description 23
- 238000001953 recrystallisation Methods 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 4
- 239000007788 liquid Substances 0.000 claims description 70
- 238000000605 extraction Methods 0.000 claims description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 26
- 239000002609 medium Substances 0.000 claims description 24
- 230000001580 bacterial effect Effects 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 239000000047 product Substances 0.000 claims description 20
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
- 239000001888 Peptone Substances 0.000 claims description 18
- 108010080698 Peptones Proteins 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 229940041514 candida albicans extract Drugs 0.000 claims description 18
- 239000013078 crystal Substances 0.000 claims description 18
- 238000002425 crystallisation Methods 0.000 claims description 18
- 230000008025 crystallization Effects 0.000 claims description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 18
- 235000019319 peptone Nutrition 0.000 claims description 18
- 239000012138 yeast extract Substances 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 16
- 239000012065 filter cake Substances 0.000 claims description 14
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 12
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 239000012141 concentrate Substances 0.000 claims description 11
- 206010027146 Melanoderma Diseases 0.000 claims description 10
- 238000011081 inoculation Methods 0.000 claims description 10
- 239000002054 inoculum Substances 0.000 claims description 10
- 230000001954 sterilising effect Effects 0.000 claims description 10
- 238000004659 sterilization and disinfection Methods 0.000 claims description 10
- 244000068988 Glycine max Species 0.000 claims description 9
- 235000010469 Glycine max Nutrition 0.000 claims description 9
- 229920002472 Starch Polymers 0.000 claims description 9
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 9
- 235000011187 glycerol Nutrition 0.000 claims description 9
- 239000008107 starch Substances 0.000 claims description 9
- 235000019698 starch Nutrition 0.000 claims description 9
- 238000012546 transfer Methods 0.000 claims description 9
- 239000000284 extract Substances 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000011097 chromatography purification Methods 0.000 claims description 6
- 230000007935 neutral effect Effects 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229960001866 silicon dioxide Drugs 0.000 claims description 6
- 238000002703 mutagenesis Methods 0.000 claims description 5
- 231100000350 mutagenesis Toxicity 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 241000187747 Streptomyces Species 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 238000011534 incubation Methods 0.000 claims description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
- 238000005267 amalgamation Methods 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- 238000002203 pretreatment Methods 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 abstract description 5
- 238000002054 transplantation Methods 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 2
- 238000012258 culturing Methods 0.000 abstract 3
- 239000000243 solution Substances 0.000 description 29
- 238000002360 preparation method Methods 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 5
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 101000634900 Homo sapiens Transcriptional-regulating factor 1 Proteins 0.000 description 3
- 241001506137 Rapa Species 0.000 description 3
- 102100029446 Transcriptional-regulating factor 1 Human genes 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000000819 hypertonic solution Substances 0.000 description 2
- 229940021223 hypertonic solution Drugs 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 241000187844 Actinoplanes Species 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 108010064696 N,O-diacetylmuramidase Proteins 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 241001655322 Streptomycetales Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003409 anti-rejection Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000012214 genetic breeding Methods 0.000 description 1
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 239000013028 medium composition Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 238000009400 out breeding Methods 0.000 description 1
- 238000005554 pickling Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
Claims (11)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 201110356249 CN102433364B (zh) | 2011-11-10 | 2011-11-10 | 一种微生物发酵法制取雷帕霉素的工艺 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 201110356249 CN102433364B (zh) | 2011-11-10 | 2011-11-10 | 一种微生物发酵法制取雷帕霉素的工艺 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102433364A true CN102433364A (zh) | 2012-05-02 |
CN102433364B CN102433364B (zh) | 2013-10-23 |
Family
ID=45981710
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 201110356249 Active CN102433364B (zh) | 2011-11-10 | 2011-11-10 | 一种微生物发酵法制取雷帕霉素的工艺 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102433364B (zh) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103396975A (zh) * | 2013-05-15 | 2013-11-20 | 中国人民解放军军事医学科学院基础医学研究所 | 基于载体pSVK的乙肝治疗性质粒DNA疫苗的发酵生产方法及其专用工程菌及高产发酵培养基 |
CN103740614A (zh) * | 2013-12-18 | 2014-04-23 | 天津北洋百川生物技术有限公司 | 一株高产雷帕霉素的游动放线菌诱变菌株 |
CN103937853A (zh) * | 2014-04-29 | 2014-07-23 | 秦燕 | 一种发酵生产雷帕霉素的培养基及其方法 |
CN104388492A (zh) * | 2014-11-24 | 2015-03-04 | 苏州嘉禧萝生物科技有限公司 | 利用吸水链霉菌生产雷帕霉素的方法 |
CN104844620A (zh) * | 2015-04-10 | 2015-08-19 | 鲁南新时代生物技术有限公司 | 一种雷帕霉素的分离纯化方法 |
CN105585578A (zh) * | 2014-10-23 | 2016-05-18 | 重庆乾泰生物医药有限公司 | 一种高纯度雷帕霉素的制备方法 |
CN106800593A (zh) * | 2017-01-09 | 2017-06-06 | 博瑞生物医药泰兴市有限公司 | 一种提纯阿尼芬净前体化合物的方法 |
CN107573362A (zh) * | 2017-10-31 | 2018-01-12 | 无锡福祈制药有限公司 | 一种从发酵液中分离提纯西罗莫司的方法 |
CN108976245A (zh) * | 2017-11-09 | 2018-12-11 | 北大方正集团有限公司 | 一种雷帕霉素的提取方法 |
CN109536543A (zh) * | 2018-12-25 | 2019-03-29 | 鲁东大学 | 一种微生物发酵法制备咔唑霉素b的方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1436447A (en) * | 1972-09-29 | 1976-05-19 | Ayerst Mckenna & Harrison | Rapamycin and process of preparation |
CN102070652A (zh) * | 2011-02-21 | 2011-05-25 | 西南大学 | 一种从发酵液中分离提取西罗莫司的方法 |
CN102229968A (zh) * | 2011-06-07 | 2011-11-02 | 华东理工大学 | 一种利用吸水链霉菌累积生产西罗莫司的方法 |
-
2011
- 2011-11-10 CN CN 201110356249 patent/CN102433364B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1436447A (en) * | 1972-09-29 | 1976-05-19 | Ayerst Mckenna & Harrison | Rapamycin and process of preparation |
CN102070652A (zh) * | 2011-02-21 | 2011-05-25 | 西南大学 | 一种从发酵液中分离提取西罗莫司的方法 |
CN102229968A (zh) * | 2011-06-07 | 2011-11-02 | 华东理工大学 | 一种利用吸水链霉菌累积生产西罗莫司的方法 |
Non-Patent Citations (1)
Title |
---|
陈希杨等: "培养条件优化和菌种选育提高雷帕霉素发酵水平", 《化学工程》, vol. 39, no. 1, 31 January 2011 (2011-01-31), pages 81 - 84 * |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103396975A (zh) * | 2013-05-15 | 2013-11-20 | 中国人民解放军军事医学科学院基础医学研究所 | 基于载体pSVK的乙肝治疗性质粒DNA疫苗的发酵生产方法及其专用工程菌及高产发酵培养基 |
CN103740614B (zh) * | 2013-12-18 | 2016-07-13 | 天津北洋百川生物技术有限公司 | 一株高产雷帕霉素的游动放线菌诱变菌株 |
CN103740614A (zh) * | 2013-12-18 | 2014-04-23 | 天津北洋百川生物技术有限公司 | 一株高产雷帕霉素的游动放线菌诱变菌株 |
CN103937853A (zh) * | 2014-04-29 | 2014-07-23 | 秦燕 | 一种发酵生产雷帕霉素的培养基及其方法 |
CN105585578B (zh) * | 2014-10-23 | 2017-12-05 | 重庆乾泰生物医药有限公司 | 一种雷帕霉素的制备方法 |
CN105585578A (zh) * | 2014-10-23 | 2016-05-18 | 重庆乾泰生物医药有限公司 | 一种高纯度雷帕霉素的制备方法 |
CN104388492A (zh) * | 2014-11-24 | 2015-03-04 | 苏州嘉禧萝生物科技有限公司 | 利用吸水链霉菌生产雷帕霉素的方法 |
CN104844620A (zh) * | 2015-04-10 | 2015-08-19 | 鲁南新时代生物技术有限公司 | 一种雷帕霉素的分离纯化方法 |
CN106800593A (zh) * | 2017-01-09 | 2017-06-06 | 博瑞生物医药泰兴市有限公司 | 一种提纯阿尼芬净前体化合物的方法 |
CN106800593B (zh) * | 2017-01-09 | 2021-04-27 | 博瑞生物医药泰兴市有限公司 | 一种提纯阿尼芬净前体化合物的方法 |
CN107573362A (zh) * | 2017-10-31 | 2018-01-12 | 无锡福祈制药有限公司 | 一种从发酵液中分离提纯西罗莫司的方法 |
CN108976245A (zh) * | 2017-11-09 | 2018-12-11 | 北大方正集团有限公司 | 一种雷帕霉素的提取方法 |
CN108976245B (zh) * | 2017-11-09 | 2020-08-07 | 北大方正集团有限公司 | 一种雷帕霉素的提取方法 |
CN109536543A (zh) * | 2018-12-25 | 2019-03-29 | 鲁东大学 | 一种微生物发酵法制备咔唑霉素b的方法 |
Also Published As
Publication number | Publication date |
---|---|
CN102433364B (zh) | 2013-10-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102433364B (zh) | 一种微生物发酵法制取雷帕霉素的工艺 | |
CN103416223B (zh) | 一种提高北冬虫夏草发酵液中虫草素产量的方法 | |
CN102586358B (zh) | 一种提高埃博霉素b产率的生物合成方法 | |
CN102888351B (zh) | 一种灵菌红素高产菌株及其生产方法 | |
CN106978350A (zh) | 一株黑曲霉及其在普洱茶素类化合物的制备中的应用 | |
CN103255061B (zh) | 灰黄青霉、由其产生的抗菌活性化合物及应用 | |
CN101486976B (zh) | 一种吸水链霉菌及其应用 | |
CN103898004A (zh) | 假诺卡氏菌及其发酵生产骨化二醇的方法 | |
CN101085989A (zh) | 一种利用细菌发酵生产番茄红素的方法 | |
CN107189949B (zh) | 米根霉ljh3及在生物转化槐角苷制备染料木素中的应用 | |
CN112094750B (zh) | 一种用于生产麦角硫因的米根霉 | |
CN106047713A (zh) | 一株嗜松篮状菌菌株Li‑93及其应用 | |
CN108841889B (zh) | 利用微生物发酵生产松刚霉素主份——灰黄霉素的方法 | |
CN108823110B (zh) | 一株产灰黄霉素的菌株及其应用 | |
CN102965288A (zh) | 一株生物合成3β,7α,15α-三羟基雄甾-5-烯-17-酮的菌株及其应用 | |
CN104726347A (zh) | 一株狐粪青霉真菌菌株以及利用该菌株制备左旋7-羟基丁苯酞的方法 | |
CN110438015A (zh) | 产橙皮苷酶的枳实内生真菌及其发酵产橙皮苷酶的方法 | |
CN103695325B (zh) | 一种热带假丝酵母及一种微生物法制备l-缬氨酸的方法 | |
CN104876945A (zh) | 一种生物碱二聚体及其制备方法与作为抗病毒剂的应用 | |
CN102417883A (zh) | 产喜树碱的新菌种筛选及制备喜树碱的方法 | |
CN112011464B (zh) | 一种用于生产麦角硫因的里氏木霉 | |
CN110699263B (zh) | 黑曲霉yh-6及其应用于提高淫羊藿中淫羊藿素的含量 | |
CN110358687B (zh) | 一株产d泛解酸内酯水解酶的赤霉菌及应用、发酵方法 | |
CN109182180B (zh) | 一种灰棕褐链霉菌及其发酵生产巴弗洛霉素a1的应用 | |
CN102584615A (zh) | 一种生物碱化合物及其制备方法和应用 |
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 | ||
DD01 | Delivery of document by public notice |
Addressee: Xiao Jiapu Document name: Notification that Application Deemed not to be Proposed |
|
ASS | Succession or assignment of patent right |
Owner name: HUAYUAN MEDICAL RESEARCH INSTITUTE CO., LTD. Free format text: FORMER OWNER: ZHONGKE MEDICAL INDUSTRY PRODUCTIVITY AND PROMOTION CENTER CO., LTD. Effective date: 20150112 |
|
C41 | Transfer of patent application or patent right or utility model | ||
C53 | Correction of patent of invention or patent application | ||
CB03 | Change of inventor or designer information |
Inventor after: Xu Lixin Inventor before: Wang Fuqing Inventor before: Xu Li Inventor before: Zhang Tong |
|
COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: WANG FUQING XU LI ZHANG TONG TO: XU LIXIN Free format text: CORRECT: ADDRESS; FROM: 100038 HAIDIAN, BEIJING TO: 102600 DAXING, BEIJING |
|
TR01 | Transfer of patent right |
Effective date of registration: 20150112 Address after: 102600 Beijing City, Daxing District Zhongguancun Science Park Daxing biomedical industry base Tianhua Street No. 21 Building No. 7 hospital room 203 Patentee after: Huayuan Medical Research Institute Co., Ltd. Address before: 100038, Beijing, Haidian District, Fang Fang Road, No. 18 Haitian building, block N (North Section) 9, two, 903 Patentee before: Zhongke Medical Industry Productivity and Promotion Center Co., Ltd. |
|
TR01 | Transfer of patent right |
Effective date of registration: 20200508 Address after: 903, floor 9, block n (North Section), phase II, Haitian building, No. 18, YANGFANGDIAN Road, Haidian District, Beijing 100006 Patentee after: Zhongke Medical Industry Productivity and Promotion Center Co.,Ltd. Address before: 102600 Beijing City, Daxing District Zhongguancun Science Park Daxing biomedical industry base Tianhua Street No. 21 Building No. 7 hospital room 203 Patentee before: HUAYUAN MEDICAL RESEARCH INSTITUTE Co.,Ltd. |
|
TR01 | Transfer of patent right |