CN102993274B - Purification method of ganirelix acetate - Google Patents
Purification method of ganirelix acetate Download PDFInfo
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Abstract
The invention provides a purification method of ganirelix acetate. The purification method comprises the steps of (1) purification of ganirelix crude peptide, wherein octadecylsilane bonded silica is adopted as a fixed phase, perchlorate/phosphoric acid solution with certain concentration is taken as an A phase and acetonitrile is taken as a B phase, the ganirelix crude peptide is purified by a gradient-elution high performance liquid chromatography (HPLC) method; (2) salt conversion and purification, wherein the alkylsilane bonded silica is taken as the fixed phase, glacial acetic acid solution with a certain concentration is taken as the A phase and the acetonitrile is taken as the B phase, salt conversion and purification are carried out by adopting the gradient elution HPLC method, and the solution collected and subjected to freeze-drying to obtain the ganirelix acetate. The invention aims at providing the purification method of the ganirelix acetate with stable and controllable process, high yield, high purity, and wide practical value and application prospect.
Description
Technical field
The present invention relates to a kind of purification process of polypeptide drugs, the particularly purification process of Ganirelix, belongs to pharmaceutical chemistry field.
Background technology
Ganirelix, English name Ganirelix, molecular formula is C
80h
113clN
18o
13, be synthetic and a similarly decapeptide compound of endogenous gonadoliberin (GnRH) (claiming again interstitialcellstimulating hormone (ICSH) liberin, LHRH), be the antagonist of GnRH, structural formula is as follows:
The gonadotropic GnRH of this product competitive antagonism is subject to stop, thereby variation approach causes fast, reversibly suppresses gonad-stimulating hormone (lutropin LH and follicle stimulating hormone FSH) secretion.It is more remarkable than secretion inhibitor FSH that it suppresses pituitary LH, thus the generation of lowering hormone.By cycle GnRH in suppressing, to LH induction fluctuation, this product can ovulation inhibition, oocyte meiosis and luteinization.To suffering from ovarian hyperstimulation disease women, this product can be prevented LH fluctuation and related stimulus, and improves and implant and pregnant ratio, is a kind of polypeptide drugs that have very much market outlook.
Adopt aminoresin resin for the thick peptide of the Ganirelix of purifying, utilize Fmoc-AA to carry out solid phase manual synthetic, peptide resin TFA cracking, obtains the thick peptide of white solid.
The ripe purification process bibliographical information of at present synthetic Ganirelix is less.Therefore the purifying of Ganirelix is the difficult point in preparation technology, and especially feather weight is prepared purifying above has on a large scale become one of bottleneck of restriction Ganirelix industrialization.
Prior art CN102584945A discloses a kind of purification process of Ganirelix, and the purifying moving phase of employing is 0.1% acetate system, at acetonitrile volume ratio 10% ~ 50% scope internal linear gradient elution; Prepare Ganirelix because adopting prior art synthetic method, can make Ganirelix contain a large amount of trifluoroacetic acids in cleavage step, and because the acidity of trifluoroacetic acid is much larger than acetic acid, there is stronger binding ability with Ganirelix, make the one-tenth salt form of Ganirelix comprise acetate and trifluoroacetate, this mixing salt form makes the salify heterogeneity of smart peptide, is unfavorable for being further purified, and trifluoroacetic acid is also virose to human body, can not be directly used in bulk drug and preparation and produces.
There is for solving prior art the difficult problem that yield is low, improve the purification yield of ganirelix acetate, reduce production costs, also need purification process further to study.
Summary of the invention
The present invention is directed to existing defective workmanship, as unstable in acetate, impurity is difficult to separate, is unfavorable for amplifying and produces etc., aims to provide that a kind of yield with low cost, high, technological process are simple, sample impurity is few and stablize controlled, to be conducive to realize industrialization Ganirelix purifying process.
For achieving the above object, the present invention takes following technical scheme:
A purification process for ganirelix acetate, comprises the following steps:
(1) purifying of the thick peptide of Ganirelix: the purified water that is 3:1 by volume ratio and acetonitrile dissolve the thick peptide of Ganirelix prepares the solution that concentration is 50g/ml-100g/ml, for subsequent use; Adopt taking octadecylsilane chemically bonded silica as stationary phase, the above-mentioned solution of loading, taking finite concentration perchlorate/phosphoric acid solution as A phase, taking acetonitrile as B phase, the thick peptide of HPLC method purifying Ganirelix of gradient elution.
In described step (1), in mobile phase A, perchlorate amount of substance concentration is 20mM-100mM, preferably 50mM; In mobile phase A, adjusting the scope of pH with phosphoric acid is 1.5-2.5, preferably 2.0.
In described step (1), gradient elution is that in 35min, moving phase is changed to 65%A+35%B by 75%A+25%B.。
Wherein, as preferably, described perchlorate is one or more in sodium perchlorate, potassium perchlorate, ammoniumper chlorate.
The selection of moving phase realizes by moving phase screening experiment, and by carrying out purifying by various salt buffer systems respectively, relatively its purification effect, is mainly comparison Impurity removal effect and yield, filters out optimal moving phase.With respect to the moving phase in the present invention, other solvent systems is not so good as the mobile lover in the present invention for the removal effect of impurity in thick peptide especially isomer impurities.
Select sodium perchlorate, potassium perchlorate, ammoniumper chlorate according to being that perchlorate is best for the separating effect of Ganirelix isomer impurities, adopt other hydrochlorate not reach this effect, and for chemically synthesized polypeptide, isomer impurities is the impurity of difficult removal.In mobile phase A, perchlorate amount of substance concentration is that 20mM-100mM provides enough surge capability and rate of ionizations, and purification effect is guaranteed, and peptide can under high salt concn not separated out simultaneously.If perchlorate amount of substance concentration is lower than 20mM, the surge capability of salt system reduces, and rate of ionization may cause elution peak to trail not or purification effect is bad; If perchlorate amount of substance concentration is higher than 100mM, the too high Ganirelix that causes of salt concn may be saltoutd, and has increased meaningless Material Cost simultaneously.Preferred concentration is the trim point concentration that 50mM gets up to find by each advantages, and the purification effect that can ensure under this concentration can ensure that again the physico-chemical property of peptide is stable, reduces Material Cost.
In mobile phase A, adjusting the scope of pH with phosphoric acid is 1.5-2.5 can make wash-out peak shape not trail, the impurity having ensured is isomer impurities separating effect especially, ensure again that peptide do not separate out in moving phase, the physical properties of Ganirelix has determined that moving phase pH value is higher and has just more easily separated out simultaneously.If phosphoric acid adjusts pH scope lower than 1.5, will make chromatograph packing material destroyed, can cause Ganirelix to be separated out in moving phase higher than 2.5.Preferably pH ensures that especially removal effect and the stabilized peptide of isomer impurities obtain optimum combination to impurity.
Gradient is preferably to obtain by a large amount of experiments for " in 35min, moving phase is changed to 65%A+35%B by 75%A+25%B ", improves deimpurity effect on this basis by extending appearance time, obtains thus the gradient in the present invention.If do not adopt this wash-out concentration and gradient, the impurity especially removal of isomer impurities may not reach best effect, and yield and purity all can reduce.
To sum up, removal effect to isomer impurities under this purification condition is best, all impurity can be less than 0.1%, this impurity toxicity research for medicine is all favourable with declaring registration, and prior art does not disclose this technical characterictic to this, all impurity of not indicating the Ganirelix finally obtaining can drop to below 0.1%, and this is very important for pharmaceutical research and production.The present invention simultaneously also has yield high, is applicable to the technique effects such as large-scale production.
(2) turn salt and purifying: then adopt taking alkyl silane bonded silica gel as stationary phase, taking finite concentration glacial acetic acid solution as A phase, taking acetonitrile as B phase, the HPLC method of gradient elution turns salt purifying, collect solution freeze-drying and obtain ganirelix acetate.In described step (2), the Glacial acetic acid concentration of mobile phase A is 0.2-0.5%v/v, preferably 0.35%.
In described step (2), gradient elution be 95%A+5%B as moving phase wash-out 20min after, moving phase is changed to 50%A+50%B by 95%A+5%B in 2min, then carries out wash-out with 50%A+50%B as moving phase.
As preferably, in described step of the present invention (2), alkyl silane bonded silica gel stationary phase is eight alkyl silane bonded silica gel or octadecylsilane chemically bonded silicas.
Turning salt step adopts moving phase of the present invention according to being that the final salify of Ganirelix is for becoming acetate, therefore first get rid of perchlorate, the phosphate radical etc. in Ganirelix with ammonium acetate wash-out, finally make Ganirelix become acetate state with acetum wash-out, if use other solvent, salify is not acetate, and the finished product just can not become ganirelix acetate.The Glacial acetic acid concentration of mobile phase A adopts 0.2 ~ 0.5%v/v can make Ganirelix to elute from chromatographic column completely, can too highly not cause its stability bad by the acetic acid content that can well control Ganirelix.If concentration lower than 0.2%v/v Ganirelix can not be completely from chromatographic column elute or elution volume very large, if concentration will too highly cause the unstable of peptide higher than the acetic acid content of 0.5%v/v Ganirelix.
The elution system of prior art CN102584945A does not openly turn salt step, therefore the finished product that it obtains are not simple ganirelix acetates, may also contain the acid groups such as trifluoroacetic acid, and the method that the present invention adopts can make the acid group of Ganirelix more single, be more suitable for for research.The method that the present invention simultaneously adopts can make Ganirelix elute from chromatographic column better, and yield is higher, and isomer impurities also still less.
The first technical problem underlying solved by the invention is to remove the impurity in smart peptide: Ganirelix is amino acid contained L-type and D type, there are natural amino acid and alpha-non-natural amino acid, in thick peptide, contain and cause thering is isomer impurities in thick peptide just like easy isomerized amino acid in the building-up process such as Ser, Pro.In peptide order, contain amino acid and the stronger amino acid of hydrophobicity that side chain is grown, caused peptide solubleness in the aqueous solution not high, and the larger aftertreatment trouble of viscosity.The present invention is by adopting taking octadecylsilane chemically bonded silica as stationary phase, carry out HPLC method purifying taking perchlorate/phosphoric acid solution as moving phase, can disposable difficult to isomer impurities in thick peptide and other separating impurity well be separated and be removed, and effectively solved the problem of the large aftertreatment trouble of viscosity.Then utilize Reversed phase HPLC method to change into ganirelix acetate, improved yield and the purity of product, simultaneously easy and simple to handle, be conducive to realize the preparation of mass-producing.
Another technical problem underlying solved by the invention is: the purification technique of the extensive thick peptide of Ganirelix; Solve the impurity method of removing synthetic Ganirelix; Preparation method is simple to operate, cost is low, and Ganirelix yield is high, is suitable for Ganirelix large-scale industrialized production, and the Ganirelix purity making is high, foreign matter content is low, has considerable economical and practical value and application prospect widely.
With respect to the elution system of prior art CN102584945A, elution system of the present invention can be removed especially isomer impurities of impurity substantially, and salify is single, in smart peptide, substantially not containing trifluoroacetic acid, is easier to the production of bulk drug and preparation; Yield of the present invention also can reach 90%, and purity can be higher than 99.5%, but elution system of the present invention can better be removed isomer impurities, and prove that by experiment present method is better than the method wash-out peak shape in documents, efficiency is higher, and purifying scale significantly improves, and is easier to industrialization and produces.
Embodiment
Embodiment 1: the purifying of ganirelix acetate
(1) purifying of the thick peptide of Ganirelix:
By purified water and acetonitrile (v:v=3:1) 100ml dissolving altogether for thick Ganirelix peptide 2.0g, to filter, collection filtrate is for subsequent use.
Purifying chromatographic condition:
Chromatographic column: 50 × 250mm, in-built octadecylsilane chemically bonded silica is fixed phase stuffing.
Flow velocity: 80ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 20mM sodium perchlorate solution, adjusting pH with phosphoric acid is 1.5.
Mobile phase B phase: acetonitrile.
Gradient:
Applied sample amount: 2.0g (100ml).
By loading after 75%A+25%B balance chromatographic column 5min, operation gradient purifying, collects object peak cuts for three sections before monitoring swarming, after summit, peak.Before peak, peak after cut reclaims purifying after removing most of acetonitrile; Summit cut turns round salt after removing most of acetonitrile.
(2) turn salt and purifying:
Turn salt chromatographic condition:
Chromatographic column: 50 × 250mm, in-built anti-phase C8 chromatograph packing material.
Flow velocity: 80ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 0.20% Glacial acetic acid (V/V) solution.
Mobile phase B phase: trifluoroacetic acid aqueous solution.
Gradient:
Loading volume: 200ml.
Purge process: by loading after chromatographic column balance 5min, operation gradient purifying, monitors and collect object peak cut.Object peak cut vacuum rotary steam is concentrated into freeze-drying after 20ml.
After freeze-drying, obtain white powder solid essence peptide ganirelix acetate 0.64g.Purity 99.71%, single impurity is all less than 0.1%.Calculate with Ganirelix in thick peptide, purification yield is 91.3%.
Embodiment 2: the purifying of ganirelix acetate
(1) purifying of the thick peptide of Ganirelix:
By purified water and acetonitrile (v:v=3:1) 100ml dissolving altogether for thick Ganirelix peptide 2.0g, to filter, collection filtrate is for subsequent use.
Purifying chromatographic condition:
Chromatographic column: 50 × 250mm, in-built octadecylsilane chemically bonded silica is fixed phase stuffing.
Flow velocity: 80ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 50mM sodium perchlorate solution, adjusting pH with phosphoric acid is 2.0.
Mobile phase B phase: acetonitrile.
Gradient:
Applied sample amount: 2.0g (100ml).
By loading after 75%A+25%B balance chromatographic column 5min, operation gradient purifying, collects object peak cuts for three sections before monitoring swarming, after summit, peak.Before peak, peak after cut reclaims purifying after removing most of acetonitrile; Summit cut turns round salt after removing most of acetonitrile.
(2) turn salt and purifying:
Turn salt chromatographic condition:
Chromatographic column: 50 × 250mm, in-built anti-phase C18 chromatograph packing material.
Flow velocity: 80ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 0.50% Glacial acetic acid (V/V) solution.
Mobile phase B phase: trifluoroacetic acid aqueous solution.
Gradient:
Loading volume: 200ml.
Purge process: by loading after chromatographic column balance 5min, operation gradient purifying, monitors and collect object peak cut.Object peak cut vacuum rotary steam is concentrated into freeze-drying after 20ml.
After freeze-drying, obtain white powder solid essence peptide ganirelix acetate 0.61g, purity 99.63%, single impurity is all less than 0.1%.Calculate with Ganirelix in thick peptide, purification yield is 90.5%.
Embodiment 3: the purifying of ganirelix acetate
(1) purifying of the thick peptide of Ganirelix:
By purified water and acetonitrile (v:v=3:1) 100ml dissolving altogether for thick Ganirelix peptide 2.0g, to filter, collection filtrate is for subsequent use.
Purifying chromatographic condition:
Chromatographic column: 50 × 250mm, in-built octadecylsilane chemically bonded silica is fixed phase stuffing.
Flow velocity: 80ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 100mM sodium perchlorate solution, adjusting pH with phosphoric acid is 2.5.
Mobile phase B phase: acetonitrile.
Gradient:
Applied sample amount: 2.0g (100ml).
By loading after 75%A+25%B balance chromatographic column 5min, operation gradient purifying, collects object peak cuts for three sections before monitoring swarming, after summit, peak.Before peak, peak after cut reclaims purifying after removing most of acetonitrile; Summit cut turns round salt after removing most of acetonitrile.
(2) turn salt and purifying:
Turn salt chromatographic condition:
Chromatographic column: 50 × 250mm, in-built anti-phase C18 chromatograph packing material.
Flow velocity: 80ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 0.35% Glacial acetic acid (V/V) solution.
Mobile phase B phase: trifluoroacetic acid aqueous solution.
Gradient:
Loading volume: 200ml.
Purge process: by loading after chromatographic column balance 5min, operation gradient purifying, monitors and collect object peak cut.Object peak cut vacuum rotary steam is concentrated into freeze-drying after 20ml.
After freeze-drying, obtain white powder solid essence peptide ganirelix acetate 0.65g, purity 99.69%, single impurity is all less than 0.1%.Calculate with Ganirelix in thick peptide, purification yield is 91.8%.
Embodiment 4: the purifying of ganirelix acetate
(1) purifying of the thick peptide of Ganirelix:
By purified water and acetonitrile (v:v=3:1) 5000ml dissolving altogether for thick Ganirelix peptide 50g, to filter, collection filtrate is for subsequent use.
Purifying chromatographic condition:
Chromatographic column: 300 × 250mm, in-built octadecylsilane chemically bonded silica is fixed phase stuffing.
Flow velocity: 2000ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 50mM sodium perchlorate solution, adjusting pH with phosphoric acid is 2.0.
Mobile phase B phase: acetonitrile.
Gradient:
Applied sample amount: 50g (5000ml).
By loading after 75%A+25%B balance chromatographic column 5min, operation gradient purifying, collects object peak cuts for three sections before monitoring swarming, after summit, peak.Before peak, peak after cut reclaims purifying after removing most of acetonitrile; Summit cut turns round salt after removing most of acetonitrile.
(2) turn salt and purifying:
Turn salt chromatographic condition:
Chromatographic column: 300 × 250mm, in-built anti-phase C18 chromatograph packing material.
Flow velocity: 2000ml/min.
Monitoring wavelength: 280nm.
Mobile phase A phase: 0.50% Glacial acetic acid (V/V) solution.
Mobile phase B phase: trifluoroacetic acid aqueous solution.
Gradient:
Loading volume: 5000ml.
Purge process: by loading after chromatographic column balance 5min, operation gradient purifying, monitors and collect object peak cut.Object peak cut vacuum rotary steam is concentrated into freeze-drying after 20ml.
After freeze-drying, obtain white powder solid essence peptide ganirelix acetate 14.7g, purity 99.73%, single impurity is all less than 0.1%.Calculate with Ganirelix in thick peptide, purification yield is 91.1%.
Claims (5)
1. a purification process for ganirelix acetate, comprises the following steps:
(1) purifying of the thick peptide of Ganirelix: the purified water that is 3:1 by volume ratio and acetonitrile dissolve the thick peptide of Ganirelix prepares the solution that concentration is 1g/50ml-1g/100ml, for subsequent use; Adopt taking octadecylsilane chemically bonded silica as stationary phase, the above-mentioned solution of loading, taking finite concentration perchlorate/phosphoric acid solution as A phase, taking acetonitrile as B phase, the thick peptide of HPLC method purifying Ganirelix of gradient elution, in mobile phase A, perchlorate concentration is 20mM-100mM; In mobile phase A, adjusting the scope of pH with phosphoric acid is 1.5-2.5; Gradient elution is: in 35min, moving phase is changed to 65%A+35%B by 75%A+25%B, and described perchlorate is sodium perchlorate;
(2) turn salt and purifying: then adopt taking alkyl silane bonded silica gel as stationary phase, taking finite concentration glacial acetic acid solution as A phase, taking acetonitrile as B phase, the HPLC method of gradient elution turns salt purifying, and the volume by volume concentration of the Glacial acetic acid of mobile phase A is 0.2-0.5%; Gradient elution be 95%A+5%B as moving phase wash-out 20min after, moving phase is changed to 50%A+50%B by 95%A+5%B in 2min, then carries out wash-out with 50%A+50%B as moving phase, the freeze-drying of collection solution obtains ganirelix acetate.
2. method according to claim 1, is characterized in that: in described step (1) mobile phase A, perchlorate concentration is 50mM, with phosphoric acid adjust pH be 2.0.
3. according to method described in claim 1 to 2 any one, it is characterized in that: in described step (2), the Glacial acetic acid concentration of mobile phase A is 0.35%.
4. according to method described in claim 1 to 2 any one, it is characterized in that: in described step (2), alkyl silane bonded silica gel stationary phase is eight alkyl silane bonded silica gel or octadecylsilane chemically bonded silicas.
5. method according to claim 3, is characterized in that: in described step (2), alkyl silane bonded silica gel stationary phase is eight alkyl silane bonded silica gel or octadecylsilane chemically bonded silicas.
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| CN104231055A (en) * | 2013-06-18 | 2014-12-24 | 深圳翰宇药业股份有限公司 | Ganirelix precursor and method for preparing ganirelix acetate by using ganirelix precursor |
| CN104844694A (en) * | 2014-02-17 | 2015-08-19 | 深圳翰宇药业股份有限公司 | Ganirelix acetate preparation method |
| CN104761620A (en) * | 2015-01-06 | 2015-07-08 | 苏州天马医药集团天吉生物制药有限公司 | Triptorelin purification preparation method |
| CN106932498B (en) * | 2015-12-29 | 2019-12-03 | 深圳翰宇药业股份有限公司 | A kind of detection method of ganirelix acetate |
| CN109879938B (en) * | 2017-12-06 | 2023-05-23 | 正大天晴药业集团股份有限公司 | Preparation method of ganirelix acetate |
| CN112730703A (en) * | 2021-01-25 | 2021-04-30 | 南京诺卡医药技术有限公司 | Method for detecting substances related to ganirelix acetate injection |
| CN113720955A (en) * | 2021-08-31 | 2021-11-30 | 哈尔滨吉象隆生物技术有限公司 | Method for detecting ganirelix acetate high-molecular polymer |
| CN115260293B (en) * | 2022-08-22 | 2023-06-06 | 南京汉欣医药科技有限公司 | Method for purifying ganirelix acetate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101981048A (en) * | 2008-02-06 | 2011-02-23 | 拜康有限公司 | A method of purifying a peptide |
| CN102382188A (en) * | 2011-11-07 | 2012-03-21 | 深圳翰宇药业股份有限公司 | Method for preparing carperitide acetate |
| CN102584945A (en) * | 2012-02-09 | 2012-07-18 | 深圳翰宇药业股份有限公司 | Preparation method for ganirelix acetate |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101463080B (en) * | 2009-01-09 | 2011-09-14 | 深圳翰宇药业股份有限公司 | Method for purifying nesiritide |
| CN101531705B (en) * | 2009-04-21 | 2012-05-23 | 深圳翰宇药业股份有限公司 | Method for purifying Carbetocin |
| CN101798334B (en) * | 2010-03-30 | 2013-02-13 | 深圳翰宇药业股份有限公司 | Purification method of human parathyroid hormone (1-34) |
| CN102731625B (en) * | 2012-06-27 | 2014-10-15 | 深圳翰宇药业股份有限公司 | Method for purifying terli |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101981048A (en) * | 2008-02-06 | 2011-02-23 | 拜康有限公司 | A method of purifying a peptide |
| CN102382188A (en) * | 2011-11-07 | 2012-03-21 | 深圳翰宇药业股份有限公司 | Method for preparing carperitide acetate |
| CN102584945A (en) * | 2012-02-09 | 2012-07-18 | 深圳翰宇药业股份有限公司 | Preparation method for ganirelix acetate |
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