CN105037488A - Purification method of melanotan II - Google Patents
Purification method of melanotan II Download PDFInfo
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- CN105037488A CN105037488A CN201510523305.5A CN201510523305A CN105037488A CN 105037488 A CN105037488 A CN 105037488A CN 201510523305 A CN201510523305 A CN 201510523305A CN 105037488 A CN105037488 A CN 105037488A
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Abstract
The invention discloses a purification method of melanotan II, which mainly solves technical problem of chromatographic column damage caused by strong alkalinity. The purification method comprises the following steps: 1) filtering a melanotan II crude product solution through a 0.45-mu m filter membrane, carrying out gradient elution purification by using a polymer-based filler chromatographic column, a mobile-phase trifluoroacetic acid water solution as a phase A, an acetonitrile trifluoroacetate solution as a phase B, and collecting a peptide solution of primary target peak; 2) carrying out gradient elution purification on the primarily collected peptide solution through a reversed phase silica gel column by using octadecyl bonded silica gel as a stationary phase, a mobile-phase trifluoroacetic acid water solution as a phase A and an acetonitrile trifluoroacetate solution as a phase B, and collecting the peptide solution of target peak; 3) exchanging into acetate by an HPLC (high performance liquid chromatography) salt conversion process; and 4) carrying out rotary evaporation concentration on the final high-purity peptide solution under reduced pressure, and carrying out freeze-drying to obtain the powdery finished peptide product. The purification method disclosed by the method has the advantages of high purity and high yield, sufficiently protects the chromatographic column, lowers the cost, and is convenient for industrialized implementation.
Description
Technical field
The invention belongs to HPLC technical field, especially relate to a kind of method of purifying melanotan II.
Background technology
Erective dysfunction (erectiledysfunction, ED) be common disease, the frequently-occurring disease of the male sex, show according to Massachusetts male sex's astogeny research (MMAS) data, in the male sex of 40 ~ 70, sickness rate is up to 52%, there is several hundred million male sex trouble ED in various degree in the whole world, affects the happiness of mankind's family life greatly.
The new analogue melanotan II of a kind of melanotropin researched and developed by Arizona, USA University Medical College, its sequence is Ac-Nle-(Cyclo) Asp-His-D-Phe-Arg-Trp-Lys-NH2, can when not by any stimulation, regulate central nervous system, bring out erection, action time lasts up to 4h, and the good results are evident for treatment ED.Melanotan II is easy to use, can the spray of oral or nose, not only uses the male sex, women is also had to the effect of sexual desire promoting.Its side effect is little, and only showing as and feel sick and yawn, will be the ideal substitute of vigour, is expected to the medicine of new generation becoming treatment ED.Along with the development of scientific and technological level, the requirement of the mankind to health is also more and more higher, pursues high-quality quality of the life, and when current high-quality ED medicine scarcity, melanotan II will have wide market outlook.
In the document delivered and patent, seldom relate to the technique of melanotan II purifying, because the restriction of synthesis technique it is also proposed new requirement to purifying, single method cannot meet Production requirement.
Summary of the invention
The object of the present invention is to provide a purification technique being suitable for large-scale industrial production melanotan II.The separation purification method of general report is all use reverse phase silica gel filler, and there is technical problem is: the crude product Cheng Huanhou of melanotan II is in DMF solution, and its pH is strong basicity.The conventional chromatogram post pH scope of application is 2.5-8.5, if a direct point defection is checked colors, spectrum filler causes very large injury.
For achieving the above object, technical scheme of the present invention is as follows:
A method of purifying melanotan II, comprises the steps:
1) by melanotan II crude product solution with stand-by after 0.45 μm of membrane filtration, take polymkeric substance as the filler chromatographic column of matrix, moving phase is trifluoroacetic acid aqueous solution is A phase, and trifluoroacetic acid acetonitrile solution is B phase, carry out gradient elution purifying, collect the peptide solution of an object peak value;
2) by the peptide solution once collected with stationary phase be the reverse phase silica gel post of octadecyl silane, moving phase: trifluoroacetic acid aqueous solution is A phase, trifluoroacetic acid acetonitrile solution is B phase, carries out gradient elution purifying, collects the peptide solution of secondary object peak value;
3) utilize HPLC to turn the exchange of salt method and change into acetate;
4) final high purity peptide solution vacuum rotary steam concentrated frozen is dry, obtain Powdered finished product peptide.
More preferred scheme is: described polymer packing particle diameter is 10-30 μm.
More preferred scheme is: described B phase is concentration expressed in percentage by volume 0.05-0.1% trifluoroacetic acid acetonitrile solution.
More preferred scheme is: described gradient elution purifying, and Mobile phase B purifying gradient is 20-60%, and secondarily purified gradient is 30-50%, and determined wavelength is 220nm.
More preferred scheme is: the concentration expressed in percentage by volume of described mobile phase A trifluoroacetic acid is 0.05-0.1%.
More preferred scheme is: described HPLC turns salt method, the aqueous acetic acid of concentration expressed in percentage by volume 0.2-0.5% and the two phase liquid of Chromatographic Pure Methanol, and chromatographic column is the reverse phase silica gel post of tetraalkyl silane group silica gel or octadecyl silane.
The invention has the beneficial effects as follows: one of the present invention's proposition is suitable for the purification technique of industrialization melanotan II; use polymer packing flash liberation melanotan II crude product solution; using acetonitrile as organic solvent mobile phase in HPLC method purge process; polymer packing can strong alkali-acid resistance; so both better can protect chromatographic column, and can partial impurities be removed again.Reuse the secondarily purified melanotan II of reversed-phased high performace liquid chromatographic; and with HPLC turn salt method exchange turn salt; the smart peptide that HPLC purity is greater than 98.0% can not only be obtained; and the damage of chromatographic column in production process can effectively be fallen, production cost is low, and technique is simple; environmental pollution is low; yield is high, effectively protects chromatographic column, is convenient to industrializing implementation.
Embodiment
embodiment 1
1. sample preparation: to stir rear aperture be that to collect filtrate after 0.45 μm of membrane filtration for subsequent use by adding a certain amount of ultrasonic extraction with acetic acid in melanotan II crude product solution.
2. a purifying
Purification condition: chromatographic column: the filler chromatographic column taking polymkeric substance as matrix, aperture is 10 μm, and pillar diameter and length are: 5cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid acetonitrile solution.Flow velocity: 80ml/min.Determined wavelength: 220nm.Gradient: B%:20-60%, 60min.Sample size is 5g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 5g.Gradient elution 60min, collects purity and is greater than 95% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to secondary to 25mg/ml and uses.
3. secondarily purified
Purification condition: chromatographic column: the reverse phase silica gel post taking stationary phase as octadecyl silane, pillar diameter and length are: 5cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid acetonitrile solution.Flow velocity: 80ml/min.Determined wavelength: 220nm.Gradient: B%:30-50%, 50min.Sample size is 4g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 4g.Gradient elution 50min, collects purity and is greater than 98% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to 30mg/ml changes salt and use.
4. turn salt: the reverse phase silica gel post with the deionized water rinsing stationary phase of concentration expressed in percentage by volume more than 60% being octadecyl silane, rinse after being neutrality to effluent liquid again with the aqueous acetic acid of concentration expressed in percentage by volume 0.5% and Chromatographic Pure Methanol two phase liquid balance chromatographic column, after chromatographic column balance is thorough, starts loading turns salt, applied sample amount is the object peptide solution gathered, linear gradient elution: the methanol solution of 60-90min concentration expressed in percentage by volume 30-90% again after the aqueous acetic acid of 10-60min concentration expressed in percentage by volume 90-95%, collects the target peak being greater than 98%.
5. will turn the solution of gained after salt, carry out being evaporated to 1g/50ml, thickening temperature is no more than 37 DEG C, and then lyophilize obtains the melanotan II that purity is greater than 98.0%, purification yield 78.2%.
embodiment 2
1. sample preparation: to stir rear aperture be that to collect filtrate after 0.45 μm of membrane filtration for subsequent use by adding a certain amount of ultrasonic extraction with acetic acid in melanotan II crude product solution.
2. a purifying
Purification condition: chromatographic column: the filler chromatographic column taking polymkeric substance as matrix, aperture is 20 μm, and pillar diameter and length are: 5cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.05% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.05% trifluoroacetic acid acetonitrile solution.Flow velocity: 80ml/min.Determined wavelength: 220nm.Gradient: B%:20-60%, 60min.Sample size is 6.5g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 6.5g.Gradient elution 60min, collects purity and is greater than 95% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to secondary to 25mg/ml and uses.
3. secondarily purified
Purification condition: chromatographic column: the reverse phase silica gel post taking stationary phase as octadecyl silane, pillar diameter and length are: 5cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.05% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.05% trifluoroacetic acid acetonitrile solution.Flow velocity: 80ml/min.Determined wavelength: 220nm.Gradient: B%:30-50%, 50min.Sample size is 4.5g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 4.5g.Gradient elution 50min, collects purity and is greater than 98% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to 30mg/ml changes salt and use.
4. turn salt: the reverse phase silica gel post with the deionized water rinsing stationary phase of concentration expressed in percentage by volume more than 60% being octadecyl silane, rinse after being neutrality to effluent liquid again with the aqueous acetic acid of concentration expressed in percentage by volume 0.3% and Chromatographic Pure Methanol two phase liquid balance chromatographic column, after chromatographic column balance is thorough, starts loading turns salt, applied sample amount is the object peptide solution gathered, linear gradient elution: the methanol solution of 60-90min concentration expressed in percentage by volume 30-90% again after the aqueous acetic acid of 10-60min concentration expressed in percentage by volume 90-95%, collects the target peak being greater than 98%.
5. will turn the solution of gained after salt, carry out being evaporated to 1g/50ml, thickening temperature is no more than 37 DEG C, and then lyophilize obtains the melanotan II that purity is greater than 98.0%, purification yield 76.4%.
embodiment 3
1. sample preparation: to stir rear aperture be that to collect filtrate after 0.45 μm of membrane filtration for subsequent use by adding a certain amount of ultrasonic extraction with acetic acid in melanotan II crude product solution.
2. a purifying
Purification condition: chromatographic column: the filler chromatographic column taking polymkeric substance as matrix, aperture is 10 μm, and pillar diameter and length are: 10cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid acetonitrile solution.Flow velocity: 200ml/min.Determined wavelength: 220nm.Gradient: B%:20-60%, 90min.Sample size is 25g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 25g.Gradient elution 90min, collects purity and is greater than 95% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to secondary to 25mg/ml and uses.
3. secondarily purified
Purification condition: chromatographic column: the reverse phase silica gel post taking stationary phase as octadecyl silane, pillar diameter and length are: 10cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid acetonitrile solution.Flow velocity: 200ml/min.Determined wavelength: 220nm.Gradient: B%:30-50%, 120min.Sample size is 15g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 15g.Gradient elution 120min, collects purity and is greater than 98% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to 30mg/ml changes salt and use.
4. turn salt: the reverse phase silica gel post with the deionized water rinsing stationary phase of concentration expressed in percentage by volume more than 60% being octadecyl silane, rinse after being neutrality to effluent liquid again with the aqueous acetic acid of concentration expressed in percentage by volume 0.3% and Chromatographic Pure Methanol two phase liquid balance chromatographic column, after chromatographic column balance is thorough, starts loading turns salt, applied sample amount is the object peptide solution gathered, linear gradient elution: the methanol solution of 60-90min concentration expressed in percentage by volume 30-90% again after the aqueous acetic acid of 10-60min concentration expressed in percentage by volume 90-95%, collects the target peak being greater than 98%.
5. will turn the solution of gained after salt, carry out being evaporated to 1g/50ml, thickening temperature is no more than 37 DEG C, and then lyophilize obtains the melanotan II that purity is greater than 98.0%, purification yield 79.1%.
embodiment 4
1. sample preparation: to stir rear aperture be that to collect filtrate after 0.45 μm of membrane filtration for subsequent use by adding a certain amount of ultrasonic extraction with acetic acid in melanotan II crude product solution.
2. a purifying
Purification condition: chromatographic column: the filler chromatographic column taking polymkeric substance as matrix, aperture is 20 μm, and pillar diameter and length are: 15cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.05% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.05% trifluoroacetic acid acetonitrile solution.Flow velocity: 500ml/min.Determined wavelength: 220nm.Gradient: B%:20-60%, 90min.Sample size is 25g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 25g.Gradient elution 90min, collects purity and is greater than 95% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to secondary to 25mg/ml and uses.
3. secondarily purified
Purification condition: chromatographic column: the reverse phase silica gel post taking stationary phase as octadecyl silane, pillar diameter and length are: 15cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid acetonitrile solution.Flow velocity: 500ml/min.Determined wavelength: 220nm.Gradient: B%:30-50%, 120min.Sample size is 15g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 15g.Gradient elution 120min, collects purity and is greater than 98% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to 30mg/ml changes salt and use.
4. turn salt: the reverse phase silica gel post with the deionized water rinsing stationary phase of concentration expressed in percentage by volume more than 60% being octadecyl silane, rinse after being neutrality to effluent liquid again with the aqueous acetic acid of concentration expressed in percentage by volume 0.2% and Chromatographic Pure Methanol two phase liquid balance chromatographic column, after chromatographic column balance is thorough, starts loading turns salt, applied sample amount is the object peptide solution gathered, linear gradient elution: the methanol solution of 60-90min concentration expressed in percentage by volume 30-90% again after the aqueous acetic acid of 10-60min concentration expressed in percentage by volume 90-95%, collects the target peak being greater than 98%.
5. will turn the solution of gained after salt, carry out being evaporated to 1g/50ml, thickening temperature is no more than 37 DEG C, and then lyophilize obtains the melanotan II that purity is greater than 98.0%, purification yield 77.6%.
embodiment 5
1. sample preparation: to stir rear aperture be that to collect filtrate after 0.45 μm of membrane filtration for subsequent use by adding a certain amount of ultrasonic extraction with acetic acid in melanotan II crude product solution.
2. a purifying
Purification condition: chromatographic column: the filler chromatographic column taking polymkeric substance as matrix, aperture is 30 μm, and pillar diameter and length are: 20cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid acetonitrile solution.Flow velocity: 800ml/min.Determined wavelength: 220nm.Gradient: B%:20-60%, 100min.Sample size is 50g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 50g.Gradient elution 100min, collects purity and is greater than 95% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to secondary to 25mg/ml and uses.
3. secondarily purified
Purification condition: chromatographic column: the reverse phase silica gel post taking stationary phase as octadecyl silane, pillar diameter and length are: 20cm × 25cm. moving phase: A phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid aqueous solution; B phase: concentration expressed in percentage by volume 0.1% trifluoroacetic acid acetonitrile solution.Flow velocity: 800ml/min.Determined wavelength: 220nm.Gradient: B%:30-50%, 120min.Sample size is 35g.
Purge process: rinse chromatographic column concentration expressed in percentage by volume 90% trifluoroacetic acid acetonitrile solution well back balance good loading, applied sample amount is 35g.Gradient elution 120min, collects purity and is greater than 98% cut, and cut underpressure distillation under not higher than 37 DEG C of conditions gives over to 30mg/ml changes salt and use.
4. turn salt: the reverse phase silica gel post with the deionized water rinsing stationary phase of concentration expressed in percentage by volume more than 60% being octadecyl silane, rinse after being neutrality to effluent liquid again with the aqueous acetic acid of concentration expressed in percentage by volume 0.2% and Chromatographic Pure Methanol two phase liquid balance chromatographic column, after chromatographic column balance is thorough, starts loading turns salt, applied sample amount is the peptide solution gathered, linear gradient elution: the methanol solution of 60-90min concentration expressed in percentage by volume 30-90% again after the aqueous acetic acid of 10-60min concentration expressed in percentage by volume 90-95%, collects the target peak being greater than 98%.
5. will turn the solution of gained after salt, carry out being evaporated to 1g/50ml, thickening temperature is no more than 37 DEG C, and then lyophilize obtains the melanotan II that purity is greater than 98.0%, purification yield 78.8%.
Claims (4)
1. a purification process of melanotan II, adopts high performance liquid chromatography, it is characterized in that comprising the steps:
1) by melanotan II crude product solution with stand-by after 0.45 μm of membrane filtration, take polymkeric substance as the filler chromatographic column of matrix, moving phase is trifluoroacetic acid aqueous solution is A phase, and trifluoroacetic acid acetonitrile solution is B phase, carry out gradient elution purifying, collect the peptide solution of an object peak value;
2) by the peptide solution once collected with stationary phase be the reverse phase silica gel post of octadecyl silane, moving phase: trifluoroacetic acid aqueous solution is A phase, trifluoroacetic acid acetonitrile solution is B phase, carries out gradient elution purifying, collects the peptide solution of object peak value;
3) utilize HPLC to turn the exchange of salt method and change into acetate;
4) final high purity peptide solution vacuum rotary steam concentrated frozen is dry, obtain Powdered finished product peptide.
2. the method for purifying melanotan II according to claim 1, it is characterized in that: in described step, mobile phase A is concentration expressed in percentage by volume 0.05-0.1% trifluoroacetic acid aqueous solution, B is concentration expressed in percentage by volume 0.05-0.1% trifluoroacetic acid acetonitrile solution.
3. the method for purifying melanotan II according to claim 1, it is characterized in that: described gradient elution purifying, a purifying gradient of Mobile phase B is 20-60%, and secondarily purified gradient is 30-50%, and determined wavelength is 220nm.
4. the method for purifying melanotan II according to claim 1, it is characterized in that: described HPLC turns salt method, moving phase is the aqueous acetic acid of concentration expressed in percentage by volume 0.2-0.5% and the two phase liquid of Chromatographic Pure Methanol, and chromatographic column is the reverse phase silica gel post of octadecyl silane.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646669A (en) * | 2016-03-30 | 2016-06-08 | 吉尔生化（上海）有限公司 | Carbetocin purification method |
| CN105646671A (en) * | 2016-02-25 | 2016-06-08 | 吉尔生化（上海）有限公司 | Gonadorelin purification method |
| CN108864249A (en) * | 2018-06-19 | 2018-11-23 | 南京肽业生物科技有限公司 | A kind of purification process of hydrophobic peptides |
| CN109748948A (en) * | 2018-11-27 | 2019-05-14 | 珠海冀百康生物科技有限公司 | A kind of purification process of palmityl tetrapeptide -7 |
| CN111057142A (en) * | 2018-10-17 | 2020-04-24 | 深圳市健元医药科技有限公司 | Purification method of teriparatide |
| CN112526051A (en) * | 2020-12-18 | 2021-03-19 | 上海吉奉生物科技有限公司 | Fmoc-lysine high performance liquid chromatography determination method |
| CN112851746A (en) * | 2019-11-26 | 2021-05-28 | 深圳翰宇药业股份有限公司 | Desalination method utilizing freeze-drying principle |
| CN113621022A (en) * | 2021-07-18 | 2021-11-09 | 甘肃瑞德林生物有限公司 | Synthetic method of cyclic peptide |
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| WO2001046217A3 (en) * | 1999-12-22 | 2002-01-17 | Conselho Nacional Cnpq | Synthesis of a potent paramagnetic agonist (epm-3) of the melanocyte stimulating hormone containing amino acid-type stable free radical |
| CN101195654A (en) * | 2006-12-08 | 2008-06-11 | 吉尔生化（上海）有限公司 | Solid phase synthesis technique for melanotan-II |
| CN102260327A (en) * | 2010-05-28 | 2011-11-30 | 吉尔生化（上海）有限公司 | Preparation method of Melanotan II |
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| WO2001046217A3 (en) * | 1999-12-22 | 2002-01-17 | Conselho Nacional Cnpq | Synthesis of a potent paramagnetic agonist (epm-3) of the melanocyte stimulating hormone containing amino acid-type stable free radical |
| CN101195654A (en) * | 2006-12-08 | 2008-06-11 | 吉尔生化（上海）有限公司 | Solid phase synthesis technique for melanotan-II |
| CN102260327A (en) * | 2010-05-28 | 2011-11-30 | 吉尔生化（上海）有限公司 | Preparation method of Melanotan II |
Cited By (13)
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| CN105646671A (en) * | 2016-02-25 | 2016-06-08 | 吉尔生化（上海）有限公司 | Gonadorelin purification method |
| CN105646669A (en) * | 2016-03-30 | 2016-06-08 | 吉尔生化（上海）有限公司 | Carbetocin purification method |
| CN108864249A (en) * | 2018-06-19 | 2018-11-23 | 南京肽业生物科技有限公司 | A kind of purification process of hydrophobic peptides |
| CN111057140B (en) * | 2018-10-17 | 2023-06-13 | 深圳市健元医药科技有限公司 | Selepress purification method |
| CN111057142A (en) * | 2018-10-17 | 2020-04-24 | 深圳市健元医药科技有限公司 | Purification method of teriparatide |
| CN111057140A (en) * | 2018-10-17 | 2020-04-24 | 深圳市健元医药科技有限公司 | Selepressin purification method |
| CN111057142B (en) * | 2018-10-17 | 2023-08-29 | 深圳市健元医药科技有限公司 | Purification method of teriparatide |
| CN109748948A (en) * | 2018-11-27 | 2019-05-14 | 珠海冀百康生物科技有限公司 | A kind of purification process of palmityl tetrapeptide -7 |
| CN112851746A (en) * | 2019-11-26 | 2021-05-28 | 深圳翰宇药业股份有限公司 | Desalination method utilizing freeze-drying principle |
| CN112526051A (en) * | 2020-12-18 | 2021-03-19 | 上海吉奉生物科技有限公司 | Fmoc-lysine high performance liquid chromatography determination method |
| CN112526051B (en) * | 2020-12-18 | 2022-08-09 | 上海吉奉生物科技有限公司 | Fmoc-lysine high performance liquid chromatography determination method |
| CN113621022A (en) * | 2021-07-18 | 2021-11-09 | 甘肃瑞德林生物有限公司 | Synthetic method of cyclic peptide |
| CN113621022B (en) * | 2021-07-18 | 2024-05-28 | 甘肃瑞德林生物有限公司 | Synthesis method of cyclic peptide |
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