CN107903318A - A kind of method for purifying Liraglutide - Google Patents
A kind of method for purifying Liraglutide Download PDFInfo
- Publication number
- CN107903318A CN107903318A CN201711476366.6A CN201711476366A CN107903318A CN 107903318 A CN107903318 A CN 107903318A CN 201711476366 A CN201711476366 A CN 201711476366A CN 107903318 A CN107903318 A CN 107903318A
- Authority
- CN
- China
- Prior art keywords
- liraglutide
- acetonitrile
- solution
- purifying
- mobile phase
- 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.)
- Pending
Links
Classifications
-
- 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
- C07K14/605—Glucagons
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention is a kind of method for purifying Liraglutide, and Liraglutide crude product is dissolved in acetonitrile solution and obtains the thick peptide aqueous solution of Liraglutide；Filter, partial acetonitrile is removed with rotary evaporator water bath after a filtrate HPLC gradient elution of progress；Obtain Liraglutide solution and carry out secondary HPLC linear elutions again, collect the cut containing Liraglutide；Again partial acetonitrile, the Liraglutide solution purified are removed with rotary evaporator water bath.The method of the present invention adopts children's inverted polymer chromatograph packing material, can bear strong alkali solution, and applied sample amount of Liraglutide is big, high income, and purity is high.Purifying number can be so reduced, reduces loss, it is cost-effective.It is secondarily purified adopt eight alkyl silane bonded silica gel of children for stationary phase with selected mobile phase be combined, can once receive purity be more than 99% product.And then efficiently solve the problem of Liraglutide finished product purity is not high, and yield is low.
Description
Technical field
The present invention relates to a kind of purification process of polypeptide compound, more particularly to a kind of method for purifying Liraglutide.
Background technology
Liraglutide, English name：Liraglutide.
Peptide sequence is：
H-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-
Ala-Ala-Lys(Pal-g-Glu)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH
First long-acting GLP-1 analog that Liraglutide is developed by Novo Nordisk Co., Ltd of Denmark, with people's glicentin -1
（GLP-1）Homology is up to 97%.Liraglutide has reduction blood glucose, promotes pancreatic cell regeneration, mild prolonged gastric emptying etc. a variety of
Effect, application prospect are extensive.
Diabetes（Diabetes Mellitus, DM）It is a kind of global high morbidity, is announced according to the World Health Organization
Data are shown：Diabetic's number in 1994 be within 1.20 hundred million, 1997 be within 1.35 hundred million, 2000 1.75 hundred million, 2010 to be
300,000,000 will be broken through within 2.39 hundred million, 2025, this numeral will be close to 600,000,000 by 2035.Diabetes are related to each system of whole body, seriously
The labour capacity of people is influenced, and threatens the life security of people.
Liraglutide is a kind of glucagon-like peptide 1 of long-acting treatment type II diabetes（GLP-1）Analog, is first
For people's glucagon-like peptide -1 of type II diabetes treatment exploitation（GLP-1）Analog, is developed by Novo Nordisk Co., Ltd, and
FDA approval listings are obtained on January 25th, 2010, SFDA approvals are obtained on March 4th, 2011 in Discussion on Chinese Listed.
Liraglutide is as hypoglycemic drug of a new generation based on incretin, not only long action time, but also
The multinomial physiological activity of natural GLP-1 has been sufficiently reserved, can safely and effectively hypoglycemic a variety of cardiovascular risk factors may simultaneously have been risen
Protective effect.Liraglutide injection subcutaneous injection is administered, when peak reaching time of blood concentration is 20~14 small, half-life period 11
~13 it is small when, daily injection is once, there is provided the glycemic control of 24h, its pharmacokinetic properties is from gender or age effects.Profit
It is definitely diabetes B therapy field revolutionary character medicine to draw Shandong peptide.Therefore, purifying research is carried out to Liraglutide with important
Meaning.
The content of the invention
The technical problems to be solved by the invention are in view of the deficiencies of the prior art, there is provided a kind of finished product purity is high, yield
The method of high purifying Liraglutide.
The technical problems to be solved by the invention are realized by following technical solution.The present invention is a kind of purifying
The method of Liraglutide, its main feature is that, Liraglutide crude product is dissolved in acetonitrile solution and obtains the thick peptide aqueous solution of Liraglutide；
Filtering, filtrate are that mobile phase carries out HPLC linear gradient elutions using inverted polymer chromatograph packing material as stationary phase, hydrochloric acid and acetonitrile；
Take the cut containing Liraglutide；Revolving removes partial acetonitrile, obtains purification solution of Liraglutide；Take Liraglutide once
Purification solution, is that mobile phase carries out HPLC linear elutions using eight alkyl silane bonded silica gels as stationary phase, phosphoric acid and acetonitrile, collects
Cut containing Liraglutide；Revolving removes partial acetonitrile, the Liraglutide solution purified.
A kind of method for purifying Liraglutide of the present invention, its further preferred technical scheme steps are as follows：
（1）Liraglutide crude product is dissolved in acetonitrile solution and obtains the thick peptide aqueous solution of Liraglutide；
（2）Take Liraglutide aqueous solution 0.22um membrane filtrations to remove insoluble granule, it is spare to collect filtrate；
（3）Filtrate is taken, using inverted polymer chromatograph packing material as stationary phase, Detection wavelength carries out HPLC linear gradients for 230nm and washes
De-, mobile phase A is：0.1% hydrochloric acid, the aqueous solution of ammonium hydroxide tune pH=7.0, Mobile phase B are：Pure acetonitrile；Gradient Initial Gradient B
Phase 5% keeps 5min, then 60min to 45%；Collect the cut containing Liraglutide；
（4）With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa；Obtain profit
Draw purification solution of Shandong peptide；Purification solution is meta-alkalescence；
（5）A purification solution is taken, using eight alkyl silane bonded silica gels as stationary phase, Detection wavelength carries out HPLC lines for 230nm
Property elution, 0.09% phosphoric acid is A phases, and the acetonitrile solution containing 0.09% phosphoric acid is B phases；Gradient Initial Gradient B phases 5% are kept
5min, then 60min to 55%, collects the cut containing Liraglutide；
（6）With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa, obtains pure
The Liraglutide solution of change；Solution is acidity.
The step of above（4）In：Bath temperature is preferably 32 ~ 33 DEG C.
Compared with prior art, the method for the present invention has the following advantages：For the method for the present invention in once purifying, use is anti-phase
Polymer chromatography filler, can bear strong alkali solution, and applied sample amount of Liraglutide is big, high income, and purity is high.So may be used
Number is purified to reduce, reduces loss, it is cost-effective.Adopted when secondarily purified eight alkyl silane bonded silica gel of children for stationary phase with
Selected mobile phase be combined, can once receive purity be more than 99% sterling.And then efficiently solve Liraglutide finished product
The problem of purity is not high, and yield is low.
Brief description of the drawings
Fig. 1 is Liraglutide crude product chromatogram in embodiment 4；
Fig. 2 is the product chromatogram of Liraglutide once after purification in embodiment 4；
Product chromatograms of the Fig. 3 for Liraglutide in embodiment 4 after secondarily purified.
Embodiment
Referring to the drawings, further describe the present invention concrete technical scheme, in order to those skilled in the art into
One step the present invention is understood, without forming the limitation to its right.
Embodiment 1, a kind of method for purifying Liraglutide, its step are as follows：
（1）2g Liraglutide crude products are dissolved in acetonitrile solution, 0.22um membrane filtrations are used after being completely dissolved.After collecting filtering
The thick peptide aqueous solution of Liraglutide is spare.
（2）First step HPLC is purified
Chromatographic condition：Chromatographic column：Inverted polymer chromatograph packing material, the diameter and length of chromatographic column are：30×250mm.Mobile phase
A：0.1% hydrochloric acid, the aqueous solution of ammonium hydroxide tune pH=7.0.Mobile phase B：Acetonitrile.Flow velocity：20mL/min Detection wavelengths are：230nm.
Applied sample amount：1g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 45%.Collect evaporating containing Liraglutide
Point.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain Li Lalu
Purification solution of peptide.
（2）Second step HPLC is purified
Chromatographic condition：Chromatographic column：Eight alkyl silane bonded silica gels, the diameter and length of chromatographic column are：30×250mm.Mobile phase
A：0.09% phosphoric acid.Mobile phase B：Acetonitrile solution containing 0.09% phosphoric acid is B phase flow velocitys：20mL/min Detection wavelengths are：
230nm.Applied sample amount：0.8g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 55%.Collect and draw Shandong containing favourable
The cut of peptide.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain
Liraglutide purification solution.
Embodiment 2, a kind of method for purifying Liraglutide, its step are as follows：
（1）5g Liraglutide crude products are dissolved in acetonitrile solution, 0.22um membrane filtrations are used after being completely dissolved.After collecting filtering
Thick peptide aqueous solution is spare.
（2）First step HPLC is purified
Chromatographic condition：Chromatographic column：Inverted polymer chromatograph packing material, the diameter and length of chromatographic column are：50×250mm.Mobile phase
A：0.1% hydrochloric acid, the aqueous solution of ammonium hydroxide tune pH=7.0.Mobile phase B：Acetonitrile.Flow velocity：60mL/min Detection wavelengths are：230nm.
Applied sample amount：2.8g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 45%.Collect evaporating containing Liraglutide
Point.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain Li Lalu
Purification solution of peptide.
（2）Second step HPLC is purified
Chromatographic condition：Chromatographic column：Eight alkyl silane bonded silica gels, the diameter and length of chromatographic column are：30×250mm.Mobile phase
A：0.09% phosphoric acid.Mobile phase B：Acetonitrile solution containing 0.09% phosphoric acid is B phase flow velocitys：60mL/min Detection wavelengths are：
230nm.Applied sample amount：2.2g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 55%.Collect and draw Shandong containing favourable
The cut of peptide.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain
Liraglutide purification solution.
Embodiment 3：A kind of method for purifying Liraglutide, its step are as follows：
（1）15g Liraglutide crude products are dissolved in acetonitrile solution, 0.22um membrane filtrations are used after being completely dissolved.After collecting filtering
Thick peptide aqueous solution it is spare.
（2）First step HPLC is purified
Chromatographic condition：Chromatographic column：Inverted polymer chromatograph packing material, the diameter and length of chromatographic column are：100×250mm.Mobile phase
A：0.1% hydrochloric acid, the aqueous solution of ammonium hydroxide tune pH=7.0.Mobile phase B：Acetonitrile.Flow velocity：200mL/min Detection wavelengths are：
230nm.Applied sample amount：11g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 45%.Collect and draw Shandong containing favourable
The cut of peptide.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain
Purification solution of Liraglutide.
（3）Second step HPLC is purified
Chromatographic condition：Chromatographic column：Eight alkyl silane bonded silica gels, the diameter and length of chromatographic column are：30×250mm.Mobile phase
A：0.09% phosphoric acid.Mobile phase B：Acetonitrile solution containing 0.09% phosphoric acid is B phase flow velocitys：200mL/min Detection wavelengths are：
230nm.Applied sample amount：8g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 55%.Collect containing Liraglutide
Cut.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain pure
The Liraglutide solution of change.
Embodiment 4, a kind of method for purifying Liraglutide, its step are as follows：
（1）30g Liraglutide crude products are dissolved in acetonitrile solution, 0.22um membrane filtrations are used after being completely dissolved.After collecting filtering
Thick peptide aqueous solution it is spare.The chromatogram of Liraglutide crude product is with reference to Fig. 1, purity 72.54%；
（2）First step HPLC is purified
Chromatographic condition：Chromatographic column：Inverted polymer chromatograph packing material, the diameter and length of chromatographic column are：150×250mm.Mobile phase
A：0.1% hydrochloric acid, the aqueous solution of ammonium hydroxide tune pH=7.0.Mobile phase B：Acetonitrile.Flow velocity：600mL/min Detection wavelengths are：
230nm.Applied sample amount：25g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 45%.Collect and draw Shandong containing favourable
The cut of peptide.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain
Purification solution of Liraglutide.Once the chromatogram of product after purification is with reference to Fig. 2, purity 95.21%.
（3）Second step HPLC is purified
Chromatographic condition：Chromatographic column：Eight alkyl silane bonded silica gels, the diameter and length of chromatographic column are：30×250mm.Mobile phase：
A：0.09% phosphoric acid.Mobile phase B：Acetonitrile solution containing 0.09% phosphoric acid is B phase flow velocitys：600mL/min Detection wavelengths are：
230nm.Applied sample amount：20g.Gradient Initial Gradient B phases 5% keep 5min, then 60min to 55%.Collect and draw Shandong containing favourable
The cut of peptide.With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa.Obtain
The Liraglutide solution of purifying.Chromatogram reference Fig. 3 of product after secondarily purified, purity are：99.65%.
The above is the preferred embodiment of the present invention, it should be pointed out that is come for those skilled in the art
Say, some improvements and modifications made without departing from the principle of the present invention, these improvements and modifications also should be regarded as this hair
Bright protection domain.
Claims (3)
- A kind of 1. method for purifying Liraglutide, it is characterised in that：Liraglutide crude product is dissolved in acetonitrile solution and obtains profit Draw the thick peptide aqueous solution of Shandong peptide；Filtering, filtrate are that mobile phase carries out using inverted polymer chromatograph packing material as stationary phase, hydrochloric acid and acetonitrile HPLC linear gradient elutions；Take the cut containing Liraglutide；Revolving remove partial acetonitrile, obtain Liraglutide once purify it is molten Liquid；Purification solution of Liraglutide is taken, is that mobile phase carries out using eight alkyl silane bonded silica gels as stationary phase, phosphoric acid and acetonitrile HPLC linear elutions, collect the cut containing Liraglutide；Revolving removes partial acetonitrile, the Liraglutide solution purified.
- 2. the method for purifying Liraglutide according to claim 1, it is characterised in that it is comprised the following steps that：（1）Liraglutide crude product is dissolved in acetonitrile solution and obtains the thick peptide aqueous solution of Liraglutide；（2）Take Liraglutide aqueous solution 0.22um membrane filtrations to remove insoluble granule, it is spare to collect filtrate；（3）Filtrate is taken, using inverted polymer chromatograph packing material as stationary phase, Detection wavelength carries out HPLC linear gradients for 230nm and washes De-, mobile phase A is：0.1% hydrochloric acid, the aqueous solution of ammonium hydroxide tune pH=7.0, Mobile phase B are：Pure acetonitrile；Gradient Initial Gradient B Phase 5% keeps 5min, then 60min to 45%；Collect the cut containing Liraglutide；（4）With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa；Obtain profit Draw purification solution of Shandong peptide；（5）Take purification solution of Liraglutide, using eight alkyl silane bonded silica gels as stationary phase, Detection wavelength for 230nm into Row HPLC linear elutions, 0.09% phosphoric acid are A phases, and the acetonitrile solution containing 0.09% phosphoric acid is B phases；Gradient Initial Gradient B Phase 5% keeps 5min, and then 60min to 55%, collects the cut containing Liraglutide；（6）With rotary evaporator water bath temperature at 30 ~ 35 DEG C, vacuum removes partial acetonitrile below -0.09MPa, obtains pure The Liraglutide solution of change.
- 3. the method for purifying Liraglutide according to claim 2, it is characterised in that step（4）In：Bath temperature is 32 ~33℃。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711476366.6A CN107903318A (en) | 2017-12-29 | 2017-12-29 | A kind of method for purifying Liraglutide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711476366.6A CN107903318A (en) | 2017-12-29 | 2017-12-29 | A kind of method for purifying Liraglutide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107903318A true CN107903318A (en) | 2018-04-13 |
Family
ID=61872059
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711476366.6A Pending CN107903318A (en) | 2017-12-29 | 2017-12-29 | A kind of method for purifying Liraglutide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107903318A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108794618A (en) * | 2018-06-25 | 2018-11-13 | 杭州诺泰澳赛诺医药技术开发有限公司 | A method of purifying Liraglutide |
| CN109354622A (en) * | 2018-12-05 | 2019-02-19 | 苏州汇通色谱分离纯化有限公司 | A kind of Suo Malu peptide purification filler special and its purification process |
| CN109438569A (en) * | 2018-09-28 | 2019-03-08 | 苏州纳微科技股份有限公司 | A kind of process for separation and purification of Liraglutide |
| CN109503705A (en) * | 2018-12-26 | 2019-03-22 | 苏州天马医药集团天吉生物制药有限公司 | A kind of isolation and purification method of Liraglutide |
| CN110540587A (en) * | 2019-08-30 | 2019-12-06 | 杭州诺泰澳赛诺医药技术开发有限公司 | Chromatographic method for effectively improving purification yield of synthetic peptide |
| CN111718407A (en) * | 2020-08-14 | 2020-09-29 | 北京质肽生物医药科技有限公司 | Purification method of glucagon-like peptide-1 analogue |
| CN113024658A (en) * | 2019-12-25 | 2021-06-25 | 翰宇药业（武汉）有限公司 | Method for purifying liraglutide |
| CN113045640A (en) * | 2019-12-27 | 2021-06-29 | 翰宇药业（武汉）有限公司 | Purification method of GLP-1 analogue |
| CN113984911A (en) * | 2020-07-27 | 2022-01-28 | 宁波鲲鹏生物科技有限公司 | Chromatographic method for simultaneously analyzing liraglutide and Boc-liraglutide main chain thereof |
| CN114605523A (en) * | 2020-12-03 | 2022-06-10 | 中国科学院大连化学物理研究所 | Method for preparing liraglutide through reversed phase chromatography purification |
| WO2023123591A1 (en) * | 2021-12-28 | 2023-07-06 | 深圳翰宇药业股份有限公司 | Method for purifying glp-1 analog and use thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102584982A (en) * | 2012-02-10 | 2012-07-18 | 深圳翰宇药业股份有限公司 | Method for purifying solid-phase synthetic coarse liraglutide |
| WO2014199397A3 (en) * | 2013-06-11 | 2015-01-29 | Mylan Laboratories Ltd | Process for the preparation of liraglutide |
| CN105017381A (en) * | 2015-07-20 | 2015-11-04 | 吉尔生化（上海）有限公司 | Purification method of liraglutide |
| WO2016067271A1 (en) * | 2014-10-31 | 2016-05-06 | Auro Peptides Ltd | A process for the preparation of liraglutide |
| WO2017162653A1 (en) * | 2016-03-23 | 2017-09-28 | Bachem Holding Ag | Purification of glucagon-like peptide 1 analogs |
-
2017
- 2017-12-29 CN CN201711476366.6A patent/CN107903318A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102584982A (en) * | 2012-02-10 | 2012-07-18 | 深圳翰宇药业股份有限公司 | Method for purifying solid-phase synthetic coarse liraglutide |
| WO2014199397A3 (en) * | 2013-06-11 | 2015-01-29 | Mylan Laboratories Ltd | Process for the preparation of liraglutide |
| WO2016067271A1 (en) * | 2014-10-31 | 2016-05-06 | Auro Peptides Ltd | A process for the preparation of liraglutide |
| CN105017381A (en) * | 2015-07-20 | 2015-11-04 | 吉尔生化（上海）有限公司 | Purification method of liraglutide |
| WO2017162653A1 (en) * | 2016-03-23 | 2017-09-28 | Bachem Holding Ag | Purification of glucagon-like peptide 1 analogs |
Non-Patent Citations (2)
| Title |
|---|
| S MERANI，等: "Liraglutide, a long-acting human glucagon-like peptide 1 analog, improves glucose homeostasis in marginal mass islet transplantation in mice", 《ENDOCRINOLOGY》 * |
| 马艳池，等: "利拉鲁肽的制备", 《中国医药工业杂志》 * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108794618A (en) * | 2018-06-25 | 2018-11-13 | 杭州诺泰澳赛诺医药技术开发有限公司 | A method of purifying Liraglutide |
| CN108794618B (en) * | 2018-06-25 | 2021-08-17 | 杭州诺泰澳赛诺医药技术开发有限公司 | Method for purifying liraglutide |
| CN109438569A (en) * | 2018-09-28 | 2019-03-08 | 苏州纳微科技股份有限公司 | A kind of process for separation and purification of Liraglutide |
| CN109354622A (en) * | 2018-12-05 | 2019-02-19 | 苏州汇通色谱分离纯化有限公司 | A kind of Suo Malu peptide purification filler special and its purification process |
| CN109503705A (en) * | 2018-12-26 | 2019-03-22 | 苏州天马医药集团天吉生物制药有限公司 | A kind of isolation and purification method of Liraglutide |
| CN110540587A (en) * | 2019-08-30 | 2019-12-06 | 杭州诺泰澳赛诺医药技术开发有限公司 | Chromatographic method for effectively improving purification yield of synthetic peptide |
| CN113024658A (en) * | 2019-12-25 | 2021-06-25 | 翰宇药业（武汉）有限公司 | Method for purifying liraglutide |
| CN113045640A (en) * | 2019-12-27 | 2021-06-29 | 翰宇药业（武汉）有限公司 | Purification method of GLP-1 analogue |
| CN113984911A (en) * | 2020-07-27 | 2022-01-28 | 宁波鲲鹏生物科技有限公司 | Chromatographic method for simultaneously analyzing liraglutide and Boc-liraglutide main chain thereof |
| CN111718407A (en) * | 2020-08-14 | 2020-09-29 | 北京质肽生物医药科技有限公司 | Purification method of glucagon-like peptide-1 analogue |
| CN114605523A (en) * | 2020-12-03 | 2022-06-10 | 中国科学院大连化学物理研究所 | Method for preparing liraglutide through reversed phase chromatography purification |
| WO2023123591A1 (en) * | 2021-12-28 | 2023-07-06 | 深圳翰宇药业股份有限公司 | Method for purifying glp-1 analog and use thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107903318A (en) | A kind of method for purifying Liraglutide | |
| CN108640985B (en) | Method for purifying somaglutide | |
| CN107892717A (en) | A kind of method of purifying Suo Malu peptides | |
| CN108794618A (en) | A method of purifying Liraglutide | |
| CN102584982B (en) | Method for purifying solid-phase synthetic coarse liraglutide | |
| CN110526982B (en) | Purification method of human glucagon-like peptide-1 analogue fusion protein | |
| CN109503705B (en) | Method for separating and purifying liraglutide | |
| CN103275208B (en) | Preparation method for liraglutide | |
| CN105017381A (en) | Purification method of liraglutide | |
| CN103613655B (en) | Method for low-cost purification of exenatide | |
| CN101538323B (en) | Method for purifying Exenatide | |
| CN110540587A (en) | Chromatographic method for effectively improving purification yield of synthetic peptide | |
| CN109354622A (en) | A kind of Suo Malu peptide purification filler special and its purification process | |
| CN103304655A (en) | Method for preparing ziconotide | |
| CN103275209A (en) | Liraglutide preparation method | |
| CN108659068A (en) | A kind of isolation and purification method of Cyanidin -3-O- rutinosides and its application | |
| CN111269309B (en) | Purification method of GLP-1 analog polypeptide | |
| CN104998263B (en) | A kind of method of the quick separating α glucosidase inhibitors from camellia pollen | |
| CN102851265B (en) | A kind of bull testis is prepared the method for hyaluronidase | |
| CN105061558A (en) | Tuna cooking liquid active peptide, preparation method and diabetes treatment uses thereof | |
| CN106905387A (en) | A kind of preparation method of GM1 | |
| CN114736294B (en) | Purification method of tetanus immunoglobulin and affinity chromatography packing thereof | |
| CN111363024A (en) | Method for purifying polypeptide | |
| CN107022039A (en) | A kind of new method that liquaemin is prepared by raw material of chitterlings | |
| CN118221750B (en) | Preparation and separation method of γ-aminobutyric acid disaccharide GABAFG in ginseng |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180413 |
|
| RJ01 | Rejection of invention patent application after publication |