CN105198950B - A kind of preparation method of Rui Jiadesong crystal forms E - Google Patents
A kind of preparation method of Rui Jiadesong crystal forms E Download PDFInfo
- Publication number
- CN105198950B CN105198950B CN201410269895.9A CN201410269895A CN105198950B CN 105198950 B CN105198950 B CN 105198950B CN 201410269895 A CN201410269895 A CN 201410269895A CN 105198950 B CN105198950 B CN 105198950B
- Authority
- CN
- China
- Prior art keywords
- preparation
- rui jiadesong
- organic solvent
- phase
- crystal forms
- 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.)
- Active
Links
Landscapes
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to crystal form preparation field, more particularly to a kind of preparation method of Rui Jiadesong crystal forms E.The preparation method includes step：Rui Jiadesong is taken to be mixed with the first organic solvent, inverted high-efficient liquid phase chromatogram purification collects the component that retention time is 30min, obtains the first intermediate product；It takes the first intermediate product to be mixed with the second organic solvent, obtains organic phase, it is concentrated, obtain the second intermediate product；Take the second intermediate product to be mixed with DMF, through crystallization to get.Preparation method provided by the invention is greatly improved the purity of Rui Jiadesong crystal forms E.
Description
Technical field
The present invention relates to crystal form preparation field, more particularly to a kind of preparation method of Rui Jiadesong crystal forms E.
Background technology
Myocardial perfusion imaging (MPI) is detection for coronary heart disease and the very useful diagnostic techniques of characterization.Perfusion imaging profit
The region of Insufficience of blood flow is determined with such as radionuclide substance.In MPI, blood flow when detecting static, and should
As a result it is compared with the blood flow detected during treadmill exercise (cardiac pressure experiment).Many patients are due to such as
Peripheral artery disease is unable to provide adequate blood flow progress cardiac pressure experiment.Therefore, increase cardiac flow in short-term
The medicament of amount is essential, will not especially cause the medicament of peripheral vasodilation.
Adenosine is a kind of effective vasodilator, it with adenosine receptor by (being characterized as hypotype A1、A2A、A2BAnd A3's
Adenosine receptor family) it interacts and generates physiological effect.Wherein, A2AReceptor be g protein coupled receptor (GPCR) family at
Member has seven transmembrane spanning α-helices, is mediated by G-protein.A2AReceptor is responsible for adjusting myocardium blood by coronary artery dilator
Guan Liu can increase the blood flow of Cardiomyocytes.
Rui Jiadesong is a kind of adenosine A with high selectivity2AReceptor stimulating agent, its chemical name is (1- 9 [4S,
2R, 3R, 5R] the amyl- 2- yls of -3,4- dihydroxy -5- (methylol) oxa- ring]-adenine -2- bases } pyrazoles -4- bases)-N- first
Base formamide.It is the A developed jointly by CV Therapeutics, Inc. and this pharmacy u s company of Astra2AAdenosine receptor agonist produces
Product, trade name Lexiscan, by activating A2AAdenosine receptor promotes coronary artery diastole and increases coronary blood flow, as radiating
Pharmacology stress agent when property nucleic MPI, the coronary artery disease that cannot receive appropriate exercise stressed patients is detected and determined.In MPI
Show Rui Jiadesong as pharmacology stress agent safely, effectively in research.
Drug due to affected by various factors, makes intramolecular or intermolecular bonding mode change in crystallization, is formed
Crystal structure (crystal form).Drug crystal forms will have a direct impact on the preparation processing performance of drug, and can influence the stability, molten of drug
Xie Du and bioavilability, and then influence quality, safety, validity and its application of drug.Currently, known to Rui Jiadesong
There are a variety of crystal forms, including crystal form A, crystal form B, crystal form C, crystal form D and unformed.Wherein, crystal form E is to be dissolved in Rui Jiadesong
It in DMF, is added in dichloromethane, tetrahydrofuran, ethyl alcohol or acetonitrile, is obtained by being concentrated under reduced pressure.But it is obtained by the preparation method
The purity of the crystal form E obtained is not high.Therefore it provides a kind of preparation method for the Rui Jiadesong crystal forms E that product purity is high, has important
Realistic meaning.
Invention content
In view of this, the present invention provides a kind of preparation methods of Rui Jiadesong crystal forms E.The preparation method passes through reverse phase height
Effect liquid phase chromatogram purifies, and the first intermediate product of gained is mixed with the second organic solvent, obtains organic phase, then mix with DMF, through analysis
Crystalline substance, can be made the Rui Jiadesong crystal form E of high-purity, and purity may be up to 99.59%.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme：
The present invention provides a kind of preparation methods of Rui Jiadesong crystal forms E, include the following steps：
Rui Jiadesong is taken to be mixed with the first organic solvent, inverted high-efficient liquid phase chromatogram purification, collecting retention time is
The component of 30min obtains the first intermediate product；
It takes the first intermediate product to be mixed with the second organic solvent, obtains organic phase, it is concentrated, obtain the second intermediate product；
Take the second intermediate product to be mixed with DMF, through crystallization to get.
In the present invention, Rui Jiade loose warps cross reversed-phase high performance liquid chromatography purifying, and the first intermediate product of gained has with second
Solvent mixes, and obtains organic phase, then mix with DMF, Rui Jiadesong crystal forms E is made through crystallization.It is made by the preparation method
The content of crystal form E may be up to 99%, substantially increase the purity of Rui Jiadesong crystal forms E.
Preferably, the condition of reversed-phase high performance liquid chromatography is：Chromatographic column is C18,250 × 4.6mm；Ultraviolet wavelength
254nm；The B phases of mobile phase are acetonitrile, and the A phases of mobile phase are water phase, flow velocity 1mL/min；Gradient elution.
In some embodiments provided by the invention, the method for gradient elution is：
Preferably, the first organic solvent is the mixture of one or both of DMSO or DMF.
Preferably, the first organic solvent is DMSO.
Preferably, the second organic solvent is one or both of dichloromethane, chloroform, ethyl acetate or toluene
Above mixture.
Preferably, the second organic solvent is dichloromethane or toluene.
In some embodiments provided by the invention, in terms of mg/mL, the quality volume of Rui Jiadesong and the first organic solvent
Than for (10~50)：(0.5~2.5).
In some embodiments provided by the invention, in terms of mg/mL, the quality volume of Rui Jiadesong and the second organic solvent
Than for (10~50)：(5~50).
In some embodiments provided by the invention, the concentration for obtaining organic phase and obtaining between the second intermediate is decompression
Concentration.
Preferably, the temperature for obtaining organic phase and obtaining the concentration between the second intermediate is 30 DEG C.
In some embodiments provided by the invention, in terms of mg/mL, the mass volume ratio of Rui Jiadesong and DMF be (10~
50)：(1~10).
In some embodiments provided by the invention, the method for crystallization is to be concentrated under reduced pressure.
Preferably, the temperature of crystallization is 40 DEG C.
In some embodiments provided by the invention, Rui Jiadesong is being taken to be mixed with the first organic solvent and reversed phase high performance liquid
It further include the steps that filtering between phase chromatogram purification.
Preferably, the aperture of filtering is 0.45 μm.
The present invention provides a kind of preparation methods of Rui Jiadesong crystal forms E.The preparation method includes step：Take Rui Jiadesong
It is mixed with the first organic solvent, inverted high-efficient liquid phase chromatogram purification, collects the component that retention time is 30min, obtain first
Intermediate product；It takes the first intermediate product to be mixed with the second organic solvent, obtains organic phase, it is concentrated, obtain the second intermediate product；
Take the second intermediate product to be mixed with DMF, through crystallization to get.By carrying out purity detecting, knot to Rui Jiadesong crystal forms E obtained
Fruit shows that the purity of Rui Jiadesong crystal forms E may be up to 99.95%.The result shows that preparation method provided by the invention is greatly improved
The purity of Rui Jiadesong crystal forms E.
Description of the drawings
Fig. 1 shows the XRD spectrum for the Rui Jiadesong crystal forms E that embodiment 1 provides；It with copper K alpha-irradiations by being obtained；
Fig. 2 shows the TGA collection of illustrative plates for the Rui Jiadesong crystal forms E that embodiment 1 provides；
Fig. 3 shows the DSC collection of illustrative plates for the Rui Jiadesong crystal forms E that embodiment 1 provides；
Fig. 4 shows the infrared spectrum for the Rui Jiadesong crystal forms E that embodiment 1 provides；
Fig. 5 shows the HPLC collection of illustrative plates for the Rui Jiadesong crystal forms E that embodiment 1 provides.
Specific implementation mode
The invention discloses a kind of preparation method of Rui Jiadesong crystal forms E, those skilled in the art can use for reference in this paper
Hold, is suitably modified technological parameter realization.In particular, it should be pointed out that all similar substitutions and modifications are to those skilled in the art
For be it will be apparent that they are considered as being included in the present invention.The method of the present invention and application are by preferably implementing
Example is described, related personnel obviously can not depart from the content of present invention, in spirit and scope to method described herein and
Using being modified or suitably changing and combine, to realize and apply the technology of the present invention.
Abbreviation and English concrete meaning used in specification and claims is as follows：
Abbreviation and English meaning
DMSO N, N- dimethyl sulfoxide (DMSO)s
DMF dimethylformamides
XRD X-ray diffractions
TGA thermogravimetric analysis
DSC differential scanning calorimetric analysis
HPLC high performance liquid chromatographies
Raw materials used or reagent is available on the market in the preparation method of Rui Jiadesong crystal forms E provided by the invention.
The inspection of XRD detection methods, TGA detection methods, DSC detection methods, infrared spectrum detection method of the present invention
Survey condition is as follows：
XRD detection methods：Instrument and equipment is D/MAX-1200 type X-ray powder diffraction instrument；Determination condition and method：Cu/
K-alpha1 (target), 40KV-40mA (operating voltage and electric current), I (max)=2244,2 θ=5-60 degree (scanning range),
0.005/0.06sec. (sweep speed), λ=1.54056.
TGA detection methods：Detecting instrument is 1 TGA thermogravimetric analyzers of U.S. Pyris；Sample size is 3.7990mg；Nitrogen
The lower heating rate of protection is 10 DEG C/min；30 DEG C to 600 DEG C of temperature range；Nitrogen flow rate：20mL/min.
Differential scanning calorimetric analysis (DSC) detection method：Detecting instrument is DSC 204F1 (Germany) differential scanning calorimetry
Instrument；Example weight is 3.7990mg；Heating rate：2℃/min；250 DEG C of the highest temperature；Nitrogen flow rate：20mL/min.
Infrared spectrum detection method：Detecting instrument is BRUKER TENSOR27 Fourier transform mid-infrared lights spectrometer (Germany
Brooker company)；Assay method：KBr pressed disc methods, spectral region 400cm-1-4000cm-1, resolution ratio 4cm-1。
With reference to embodiment, the present invention is further explained：
The preparation of 1 Rui Jiadesong crystal forms E of embodiment
It is dissolved in 40mg Rui Jiadesong in the DMSO of 2mL, obtains the solution of 20mg/mL.With 0.45 μm of membrane filtration,
Liquid is squeezed into through sample introduction needle in the 2mL quantitative loops of Reversed-phase Chromatographic System, and reverse-phase chromatography condition is：Chromatographic column is C18,250 ×
4.6mm；Ultraviolet wavelength 254nm；Mobile phase, B phases are acetonitrile, and A phases are water phase, flow velocity 1mL/min；Using the side of gradient elution
Method, gradient elution program are specially：
| Time | B Phase Proportions |
| 0-5min | 5% |
| 5-10min | 5%-10% |
| 10-20min | 15% |
| 20-40min | 15%-50% |
| 40-45min | 50%-90% |
It is detached according to above-mentioned blas, collects the main peak sample of retention time 30min, obtain the mixing of acetonitrile and water
Liquid.The dichloromethane of 10mL is added to the mixed liquor of acquisition, gets organic phase, 30 DEG C of reduced pressures, 3mL is added in residual solution
DMF, after dissolved clarification, 40 DEG C of reduced pressures obtain solid.Qualitative detection carried out to the solid of gained, detection method include XRD,
TGA, DSC, infrared spectrum, XRD spectrum as shown in Figure 1, XRD diagram modal data be shown in Table 1, TGA collection of illustrative plates as shown in Fig. 2, DSC collection of illustrative plates such as
Shown in Fig. 3, infrared spectrum is as shown in Figure 4.By Fig. 1~4 it is found that the solid obtained is Rui Jiadesong crystal forms E.
The XRD diagram modal data of 1 Rui Jiadesong crystal forms E of table
As shown in Figure 2, weightlessness 5.3%, weight loss rate 2.1%/min at 80 DEG C；The weightlessness at 182.21 DEG C
4.5%, weight loss rate 0.39%/min；When temperature reaches 237 DEG C, occur continuing weightlessness, weightless ratio carries rapidly later
It is high.Analysis result thinks that 80 DEG C should be low boiling-point and polarity dissolvent residual in sample, and 182.21 DEG C should be the crystallization water in sample, and
237 DEG C of weightlessness should be that sample starts to decompose.The result shows that Rui Jiadesong crystal forms E heat provided by the invention is just decomposed at 237 DEG C,
Stability is good, is suitble to long term storage.
From the figure 3, it may be seen that when temperature reaches 173.71 DEG C, there is significant temperature absorption to react, when temperature reaches 221 DEG C, have
Minimal temperature absorbs, and sample starts to decompose later.The solvent of Rui Jiadesong crystal forms E provided by the invention is low boiling point solvent,
Therefore 173.71 DEG C should be thermotonus caused by crystallization water dehydration.
Content detection is carried out to Rui Jiadesong crystal forms E, HPLC collection of illustrative plates is as shown in figure 5, HPLC spectrum datas are shown in Table 2.
The HPLC spectrum datas of 2 Rui Jiadesong crystal forms E of table
As a result it shows that the content of Rui Jiadesong crystal forms E is 99.91%, shows that the purity of Rui Jiadesong crystal forms E obtained is high.
The preparation of 2 Rui Jiadesong crystal forms E of embodiment
It is dissolved in 10mg Rui Jiadesong in the DMF of 1mL, obtains the solution of 27mg/mL.With 0.45 μm of membrane filtration, liquid
Body is squeezed into through sample introduction needle in the 2mL quantitative loops of Reversed-phase Chromatographic System, and reverse-phase chromatography condition is：Chromatographic column is C18,250 ×
4.6mm；Ultraviolet wavelength 254nm；Mobile phase, B phases are acetonitrile, and A phases are water phase, flow velocity 1mL/min；Using the side of gradient elution
Method, gradient elution program are specially：
| Time | B Phase Proportions |
| 0-5min | 5% |
| 5-10min | 5%-10% |
| 10-20min | 15% |
| 20-40min | 15%-50% |
| 40-45min | 50%-90% |
It is detached according to above-mentioned blas, collects the main peak sample of retention time 30min, obtain the mixing of acetonitrile and water
Liquid.The ethyl acetate of 50mL is added to the mixed liquor of acquisition, gets organic phase, 30 DEG C of reduced pressures, 1mL is added in residual solution
DMF, after dissolved clarification, 40 DEG C of reduced pressures obtain solid.Qualitative detection is carried out to the solid of gained, detection method includes X-ray
Diffraction (XRD), infrared spectrum, TGA, DSC, testing result are close with the testing result of embodiment 1, it is known that the solid of acquisition is auspicious
Jia Desong crystal forms E.Content detection is carried out to Rui Jiadesong crystal forms E, HPLC collection of illustrative plates is close with the testing result of embodiment.Knot
Fruit shows that the content of Rui Jiadesong crystal forms E is 99.89%, shows that the purity of Rui Jiadesong crystal forms E obtained is high.
The preparation of 3 Rui Jiadesong crystal forms E of embodiment
It is dissolved in 30mg Rui Jiadesong in the DMSO of 2.5mL, obtains the solution of 16mg/mL.With 0.45 μm of filter membrane mistake
Filter, liquid are squeezed into through sample introduction needle in the 2mL quantitative loops of Reversed-phase Chromatographic System, and reverse-phase chromatography condition is：Chromatographic column is C18,250 ×
4.6mm；Ultraviolet wavelength 254nm；Mobile phase, B phases are acetonitrile, and A phases are water phase, flow velocity 1mL/min；Using the side of gradient elution
Method, gradient elution program are specially：
It is detached according to above-mentioned blas, collects the main peak sample of retention time 30min, obtain the mixing of acetonitrile and water
Liquid.The toluene of 20mL is added to the mixed liquor of acquisition, gets organic phase, 30 DEG C of reduced pressures, 5mL DMF are added in residual solution, molten
After clear, 40 DEG C of reduced pressures obtain solid.Qualitative detection is carried out to the solid of gained, detection method includes X-ray diffraction
(XRD), infrared spectrum, TGA, DSC, testing result are close with the testing result of embodiment 1, it is known that the solid of acquisition is Rui Jiade
Loose crystal form E.Content detection is carried out to Rui Jiadesong crystal forms E, HPLC collection of illustrative plates is close with the testing result of embodiment.As a result it shows
Show that the content of Rui Jiadesong crystal forms E is 99.95%, shows that the purity of Rui Jiadesong crystal forms E obtained is high.
The preparation of 4 Rui Jiadesong crystal forms E of embodiment
It is dissolved in 50mg Rui Jiadesong in the DMF of 0.5mL, obtains the solution of 22mg/mL.With 0.45 μm of membrane filtration,
Liquid is squeezed into through sample introduction needle in the 2mL quantitative loops of Reversed-phase Chromatographic System, and reverse-phase chromatography condition is：Chromatographic column is C18,250 ×
4.6mm；Ultraviolet wavelength 254nm；Mobile phase, B phases are acetonitrile, and A phases are water phase, flow velocity 1mL/min；Using the side of gradient elution
Method, gradient elution program are specially：
| Time | B Phase Proportions |
| 0-5min | 5% |
| 5-10min | 5%-10% |
| 10-20min | 15% |
| 20-40min | 15%-50% |
| 40-45min | 50%-90% |
It is detached according to above-mentioned blas, collects the main peak sample of retention time 30min, obtain the mixing of acetonitrile and water
Liquid.The toluene of 5mL is added to the mixed liquor of acquisition, gets organic phase, 30 DEG C of reduced pressures, 10mL DMF are added in residual solution, molten
After clear, 40 DEG C of reduced pressures obtain solid.Qualitative detection is carried out to the solid of gained, detection method includes X-ray diffraction
(XRD), infrared spectrum, TGA, DSC, testing result are close with the testing result of embodiment 1, it is known that the solid of acquisition is Rui Jiade
Loose crystal form E.Content detection is carried out to Rui Jiadesong crystal forms E, HPLC collection of illustrative plates is close with the testing result of embodiment.As a result it shows
Show that the content of Rui Jiadesong crystal forms E is 99.89%, shows that the purity of Rui Jiadesong crystal forms E obtained is high.
The preparation of 1 Rui Jiadesong crystal forms E of comparative example
1g Rui Jiadesong are dissolved in 10mL DMF, 10mL dichloromethane is added, is concentrated under reduced pressure at 50 DEG C, it is auspicious to obtain 1g
Jia Desong crystal form E, content 92%.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (6)
1. a kind of preparation method of Rui Jiadesong crystal forms E, which is characterized in that include the following steps：
Step 1：Rui Jiadesong is taken to be mixed with the first organic solvent, inverted high-efficient liquid phase chromatogram purification, collecting retention time is
The component of 30min obtains the first intermediate product；
Step 2：It takes first intermediate product to be mixed with the second organic solvent, obtains organic phase, it is concentrated, it obtains among second
Product；
Step 3：Take second intermediate product to be mixed with DMF, through crystallization to get；
The condition of the reversed-phase high performance liquid chromatography is：Chromatographic column is C18,250 × 4.6mm；Ultraviolet wavelength 254nm；Mobile phase
B phases be acetonitrile, the A phases of mobile phase are water phase, flow velocity 1mL/min；Gradient elution；
The method of the gradient elution is：
First organic solvent is the mixture of one or both of DMSO or DMF；
Second organic solvent is the mixed of one or both of dichloromethane, chloroform, ethyl acetate or toluene or more
Close object.
2. preparation method according to claim 1, which is characterized in that in terms of mg/mL, the Rui Jiadesong and described first
The mass volume ratio of organic solvent is (10-50)：(0.5~2.5).
3. preparation method according to claim 1, which is characterized in that in terms of mg/mL, the Rui Jiadesong and described second
The mass volume ratio of organic solvent is (10-50)：(5~50).
4. preparation method according to claim 1, which is characterized in that in terms of mg/mL, in the Rui Jiadesong and step 3
The mass volume ratio of the DMF is (10-50)：(1~10).
5. preparation method according to claim 1, which is characterized in that the method for the crystallization is to be concentrated under reduced pressure.
6. preparation method according to claim 5, which is characterized in that the temperature of the crystallization is 40 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410269895.9A CN105198950B (en) | 2014-06-17 | 2014-06-17 | A kind of preparation method of Rui Jiadesong crystal forms E |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410269895.9A CN105198950B (en) | 2014-06-17 | 2014-06-17 | A kind of preparation method of Rui Jiadesong crystal forms E |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105198950A CN105198950A (en) | 2015-12-30 |
| CN105198950B true CN105198950B (en) | 2018-10-02 |
Family
ID=54946937
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410269895.9A Active CN105198950B (en) | 2014-06-17 | 2014-06-17 | A kind of preparation method of Rui Jiadesong crystal forms E |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105198950B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110117305B (en) * | 2018-02-06 | 2023-06-02 | 上海键合医药科技有限公司 | Method for purifying regadenoson and novel crystal form thereof |
| WO2019191389A1 (en) | 2018-03-29 | 2019-10-03 | Johnson Matthey Public Limited Company | Solid-state forms of regadenoson, their use and preparation |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101379073A (en) * | 2006-02-03 | 2009-03-04 | Cv医药有限公司 | Process for preparing an a2a-adenosine receptor agonist and its polymorphs |
| CN101668768A (en) * | 2007-05-17 | 2010-03-10 | Cv医药有限公司 | Process for preparing an a2a-adenosine receptor agonist and its polymorphs |
| CN102260311A (en) * | 2006-02-03 | 2011-11-30 | 吉利德帕洛阿尔托股份有限公司 | Process for preparing an A2A-adenosine receptor agonist and its polymorphs |
| WO2012149196A1 (en) * | 2011-04-27 | 2012-11-01 | Reliable Biopharmaceutical Corporation | Improved processes for the preparation of regadenoson and a new crystalline form thereof |
| WO2014083580A2 (en) * | 2012-11-30 | 2014-06-05 | Leiutis Pharmaceuticals Pvt. Ltd. | Pharmaceutical compositions of regadenoson |
-
2014
- 2014-06-17 CN CN201410269895.9A patent/CN105198950B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101379073A (en) * | 2006-02-03 | 2009-03-04 | Cv医药有限公司 | Process for preparing an a2a-adenosine receptor agonist and its polymorphs |
| CN102260311A (en) * | 2006-02-03 | 2011-11-30 | 吉利德帕洛阿尔托股份有限公司 | Process for preparing an A2A-adenosine receptor agonist and its polymorphs |
| CN101668768A (en) * | 2007-05-17 | 2010-03-10 | Cv医药有限公司 | Process for preparing an a2a-adenosine receptor agonist and its polymorphs |
| WO2012149196A1 (en) * | 2011-04-27 | 2012-11-01 | Reliable Biopharmaceutical Corporation | Improved processes for the preparation of regadenoson and a new crystalline form thereof |
| WO2014083580A2 (en) * | 2012-11-30 | 2014-06-05 | Leiutis Pharmaceuticals Pvt. Ltd. | Pharmaceutical compositions of regadenoson |
Non-Patent Citations (1)
| Title |
|---|
| Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A2A Adenosine Receptor;Francesca Deflorian，等;《Journal of Medicinal Chemistry》;20111121;第55卷;第538-562页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105198950A (en) | 2015-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Preparative separation of dryofragin and aspidin BB from Dryopteris fragrans extracts by macroporous resin column chromatography | |
| Yin et al. | A green and efficient protocol for industrial-scale preparation of dioscin from Dioscorea nipponica Makino by two-step macroporous resin column chromatography | |
| CN102980961A (en) | Pretreatment method of detection on malachite green, crystal violet and residues of malachite green and crystal violet in eels | |
| EP3141540B1 (en) | Preparation of a crystalline form of chlorogenic acid | |
| CN102516096B (en) | Refining method of hydrochloric acid ambroxol compound | |
| CN101629937A (en) | Quantitative detection method of pentachlorophenol in soil | |
| CN105198950B (en) | A kind of preparation method of Rui Jiadesong crystal forms E | |
| CN104447904B (en) | Stable gastrodine crystal that a kind of oral administration biaavailability is high and preparation method thereof, preparation and application | |
| CN105175468B (en) | A kind of preparation method of Rui Jiadesong crystal forms B | |
| Wang et al. | Simultaneous LC determination of major constituents in red and white peony root | |
| Feng et al. | An efficient and target-oriented sample enrichment method for preparative separation of minor alkaloids by pH-zone-refining counter-current chromatography | |
| CN109490446B (en) | A method for the simultaneous determination of five flavonoids in the medicinal material of Centipede | |
| CN114184716B (en) | High performance liquid chromatography analysis method for determining related substance components in halominosone cream | |
| CN111454127B (en) | Extraction and purification method of honokiol | |
| CN109239253B (en) | High performance liquid detection method for impurities of abacavir | |
| CN103130817B (en) | Bilobalide B compound and preparation method thereof | |
| CN103130818A (en) | Bilobalide B compound and preparation method thereof | |
| CN110716000B (en) | Method for measuring content of p-hydroxyphenylacetic acid in rhodiola crenulata injection | |
| CN109490448B (en) | A kind of preparation method of digoxin standard substance | |
| CN113563326A (en) | Atropine separated and purified from alkaloid extract and preparation method thereof | |
| Liu et al. | Simultaneous determination of seven major diterpenoids in Pseudolarix kaempferi by high-performance liquid chromatography DAD method | |
| CN108727417B (en) | Polycyclic compound sodium salt, and polycrystalline type, preparation method and application thereof | |
| CN106946973B (en) | A kind of compound and preparation method thereof, purposes | |
| Hu et al. | Effects of tween-80 on the dissolution properties of daidzein solid dispersion in vitro | |
| CN114224929B (en) | Erigeron multiradiatus extract and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20241008 Address after: No. 37 Xihuanhe Road, Jinshan District, Shanghai, December 2015 Patentee after: Shanghai Shangyao Pharmaceutical Technology Co.,Ltd. Country or region after: China Address before: 201108 No. 749 Guanghua Road, Shanghai, Minhang District Patentee before: SHANGHAI ZIYUAN PHARMACEUTICAL Co.,Ltd. Country or region before: China |