CN112584853A - 一种新型门冬胰岛素原的结构和制备门冬胰岛素的方法 - Google Patents

一种新型门冬胰岛素原的结构和制备门冬胰岛素的方法 Download PDF

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CN112584853A
CN112584853A CN201880090551.8A CN201880090551A CN112584853A CN 112584853 A CN112584853 A CN 112584853A CN 201880090551 A CN201880090551 A CN 201880090551A CN 112584853 A CN112584853 A CN 112584853A
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sequence
insulin
seq
aspart
proinsulin
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CN112584853B (zh
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汤传根
潘尚书
刘晓锐
李宬
崔怀言
陈松
张昊宁
丁捷飞
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Meiyaoxing Nanjing Pharmaceutical Co ltd
Amphastar Nanjing Pharma Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70—Vectors or expression systems specially adapted for E. coli
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/62—Insulins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y115/00—Oxidoreductases acting on superoxide as acceptor (1.15)
    • C12Y115/01—Oxidoreductases acting on superoxide as acceptor (1.15) with NAD or NADP as acceptor (1.15.1)
    • C12Y115/01001—Superoxide dismutase (1.15.1.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
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  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)

Abstract

本发明提供了一种新型门冬胰岛素原的结构设计和门冬胰岛素制备方法。其中主要步骤包括设计门冬胰岛素原的序列，构建重组门冬胰岛素工程菌，通过工程菌诱导以包涵体形式表达门冬胰岛素融合蛋白，再经过变性、复性、酶切和分离纯化得到成熟的门冬胰岛素原料药。发明通过改变重组前导肽和C‑肽序列，避免使用溴化氢切割这种危险而繁琐的步骤；缩短C‑肽为1个氨基酸，减少酶切转化的质量损失。

Description

PCT国内申请，说明书已公开。

Claims (11)

  1. PCT国内申请，权利要求书已公开。
CN201880090551.8A 2018-09-12 2018-09-12 一种新型门冬胰岛素原的结构和制备门冬胰岛素的方法 Active CN112584853B (zh)

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PCT/CN2018/105314 WO2020051812A1 (zh) 2018-09-12 2018-09-12 一种新型门冬胰岛素原的结构和制备门冬胰岛素的方法

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113896784A (zh) * 2021-10-18 2022-01-07 合肥天麦生物科技发展有限公司 一种胰岛素结晶的制备方法及其产品

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113773400B (zh) * 2020-06-09 2023-08-18 宁波鲲鹏生物科技有限公司 一种门冬胰岛素衍生物及其应用
CN113773391B (zh) * 2020-06-09 2023-10-20 宁波鲲鹏生物科技有限公司 一种门冬胰岛素的制备方法
CN113105536B (zh) * 2020-09-11 2023-07-18 美药星（南京）制药有限公司 一种新甘精胰岛素原及其制备甘精胰岛素的方法
CN113074519B (zh) * 2021-06-07 2021-10-29 美药星（南京）制药有限公司 一种高效去除门冬胰岛素中残留有机溶剂的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1177928A (zh) * 1994-12-29 1998-04-01 生物技术通用公司 生产人胰岛素
US20060035316A1 (en) * 2002-11-12 2006-02-16 Sang-Yong Lee Plasmids expressing human insulin and the preparation method for human insuling thereby
CN1873006A (zh) * 2005-05-30 2006-12-06 上海新生源医药研究有限公司 一种重组人胰岛素原的生产方法
CN101519446A (zh) * 2009-03-31 2009-09-02 上海一就生物医药有限公司 一种重组人胰岛素及其类似物的制备方法
US20160168226A1 (en) * 2013-07-31 2016-06-16 Biogenomics Limited Process for production of insulin and insulin analogues

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NZ199391A (en) 1981-01-02 1985-12-13 Genentech Inc Chimeric polypeptides comprising a proinsulin sequence,and preparation by recombinant dna technique;production of human insulin
DK58285D0 (da) 1984-05-30 1985-02-08 Novo Industri As Peptider samt fremstilling og anvendelse deraf
PH25772A (en) * 1985-08-30 1991-10-18 Novo Industri As Insulin analogues, process for their preparation
US6875589B1 (en) 1988-06-23 2005-04-05 Hoechst Aktiengesellschaft Mini-proinsulin, its preparation and use
DK72793D0 (da) 1993-06-21 1993-06-21 Novo Nordisk As Nyt produkt
US6001604A (en) * 1993-12-29 1999-12-14 Bio-Technology General Corp. Refolding of proinsulins without addition of reducing agents
US6777207B2 (en) * 1999-12-29 2004-08-17 Novo Nordisk A/S Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast

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Publication number Priority date Publication date Assignee Title
CN1177928A (zh) * 1994-12-29 1998-04-01 生物技术通用公司 生产人胰岛素
US20060035316A1 (en) * 2002-11-12 2006-02-16 Sang-Yong Lee Plasmids expressing human insulin and the preparation method for human insuling thereby
CN1873006A (zh) * 2005-05-30 2006-12-06 上海新生源医药研究有限公司 一种重组人胰岛素原的生产方法
CN101519446A (zh) * 2009-03-31 2009-09-02 上海一就生物医药有限公司 一种重组人胰岛素及其类似物的制备方法
US20160168226A1 (en) * 2013-07-31 2016-06-16 Biogenomics Limited Process for production of insulin and insulin analogues

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113896784A (zh) * 2021-10-18 2022-01-07 合肥天麦生物科技发展有限公司 一种胰岛素结晶的制备方法及其产品
CN113896784B (zh) * 2021-10-18 2024-04-16 合肥天麦生物科技发展有限公司 一种胰岛素结晶的制备方法及其产品

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EP3845240A4 (en) 2021-11-03
US20210332100A1 (en) 2021-10-28
EP3845240A1 (en) 2021-07-07
CN112584853B (zh) 2021-12-10
WO2020051812A1 (zh) 2020-03-19

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