CN105669696B - A kind of prasugrel hydrochloride compound - Google Patents
A kind of prasugrel hydrochloride compound Download PDFInfo
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- CN105669696B CN105669696B CN201410670472.8A CN201410670472A CN105669696B CN 105669696 B CN105669696 B CN 105669696B CN 201410670472 A CN201410670472 A CN 201410670472A CN 105669696 B CN105669696 B CN 105669696B
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- Prior art keywords
- prasugrel
- risk
- prasugrel hydrochloride
- crystal
- hydrochloride compound
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- 229960004947 prasugrel hydrochloride Drugs 0.000 title claims abstract description 15
- -1 prasugrel hydrochloride compound Chemical class 0.000 title abstract description 5
- JALHGCPDPSNJNY-UHFFFAOYSA-N [5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl] acetate;hydron;chloride Chemical compound Cl.C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 JALHGCPDPSNJNY-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000002441 X-ray diffraction Methods 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims 6
- 238000004458 analytical method Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000005465 B01AC22 - Prasugrel Substances 0.000 abstract description 16
- 229960004197 prasugrel Drugs 0.000 abstract description 16
- DTGLZDAWLRGWQN-UHFFFAOYSA-N prasugrel Chemical compound C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 DTGLZDAWLRGWQN-UHFFFAOYSA-N 0.000 abstract description 16
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 abstract description 4
- 208000032843 Hemorrhage Diseases 0.000 abstract description 4
- 208000034158 bleeding Diseases 0.000 abstract description 4
- 230000000740 bleeding effect Effects 0.000 abstract description 4
- 229960003009 clopidogrel Drugs 0.000 abstract description 4
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 abstract description 4
- 208000004476 Acute Coronary Syndrome Diseases 0.000 abstract description 3
- 229940127218 antiplatelet drug Drugs 0.000 abstract description 3
- 230000000302 ischemic effect Effects 0.000 abstract description 3
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 2
- 241000282414 Homo sapiens Species 0.000 abstract description 2
- 208000007718 Stable Angina Diseases 0.000 abstract description 2
- 208000007536 Thrombosis Diseases 0.000 abstract description 2
- 230000006502 antiplatelets effects Effects 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 150000003222 pyridines Chemical class 0.000 abstract description 2
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 abstract description 2
- 230000005923 long-lasting effect Effects 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- 206010003178 Arterial thrombosis Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000007214 atherothrombosis Effects 0.000 description 2
- 229930006722 beta-pinene Natural products 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 235000011167 hydrochloric acid Nutrition 0.000 description 2
- 229920001684 low density polyethylene Polymers 0.000 description 2
- 239000004702 low-density polyethylene Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- 238000013146 percutaneous coronary intervention Methods 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229940125670 thienopyridine Drugs 0.000 description 2
- 239000002175 thienopyridine Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- WTARULDDTDQWMU-UHFFFAOYSA-N β-pinene Chemical compound C1C2C(C)(C)C1CCC2=C WTARULDDTDQWMU-UHFFFAOYSA-N 0.000 description 2
- ZWUQVNSJSJHFPS-UHFFFAOYSA-N 2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene]acetic acid Chemical compound C1CC(S)C(=CC(=O)O)CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 ZWUQVNSJSJHFPS-UHFFFAOYSA-N 0.000 description 1
- 229910017488 Cu K Inorganic materials 0.000 description 1
- 229910017541 Cu-K Inorganic materials 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 238000005360 mashing Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to pharmaceutical technology fields, and in particular to a kind of prasugrel hydrochloride compound.Prasugrel is the potent thianthrene of a new generation and pyridines antiplatelet drug.It is applied by the observation to healthy volunteer and in stable angina pectoris and acute coronary syndrome intervention operation, it was found that it has faster stronger more longlasting antiplatelet effects than clopidogrel, the incidence of ischemic event can be substantially reduced, but the risk of bleeding increased.It should be noted that identification thrombus high-risk patient and bleeding risk people at highest risk in clinical use.
Description
Technical field
The invention belongs to medical research fields, and in particular to a kind of prasugrel hydrochloride compound.
Background technique
2 months 2009, EU Committee had approved by a mouth of two company's joint development of the first-three republicanism EliLilly
Antiplatelet new drug prasugrel (prasugrel) is taken, receive emergency treatment for pre- tetrandra root and delay percutaneous coronary intervention will be carried out
Atherothrombosis (atherothrombosis) event of the Acute Coronary Syndrome Patients of art.This is pula
Gray gets the Green Light for the first time in the world.
Prasugrel is a new oral effective Thienopyridines drug.As clopidogrel, prasugrel is also
One inactive pro-drug could need to irreversibly press down after cytochrome P 450 Enzyme metabolic conversion to active metabolite
P2Y12 adenosine diphosphate (ADP) receptor on blood platelet processed.The curative effect of prasugrel is better than clopidogrel, this can be with its pharmacokinetics
Improvement is explained: prasugrel has higher pro-drug to active metabolite conversion ratio and higher biological utilisation
Degree reduces main ischemic cardiovascular event hair so working faster and can reduce the Different therapeutical effect between individual to a greater degree
Raw rate.
Prasugrel is the potent thianthrene of a new generation and pyridines antiplatelet drug.By observation to healthy volunteer and
It is applied in stable angina pectoris and acute coronary syndrome intervention operation, it is found that it has than clopidogrel and faster stronger more hold
Long antiplatelet effects can substantially reduce the incidence of ischemic event, but the risk of bleeding increased.In clinical use
In it should be noted that identification thrombus high-risk patient and bleeding risk people at highest risk.
On July 10th, 2009, Food and Drug Adminstration of the US (FDA) publication statement allow antiplatelet drug prasugrel
(prasugrel) for reducing the thrombotic risk in percutaneous coronary intervention (pci).
The DA angiocarpy benefit for thinking the medicine consistent with renal drug Advisory Board has exceeded its risk, and supports to ratify
Prasugrel.Prasugrel hydrochloride is the Thienopyridines that Li Lai company and the first pharmacy Sankyo Co., Ltd research and develop jointly
Medicine.It has passed through the license of European commission.In Europe, the medicine is with trade name Efient sale.
The document of prasugrel related to the present invention discloses: WO2014092589, CN103772408,
CN103012427、WO2013010502、CN102838618、WO2012175031、JP2012180280、WO2012023145、
EP2409689、CZ302833、WO2011124124、WO2011127300、WO2011092720、WO2011057593、
WO2011057592、WO2011052500、WO2011052499、WO2011004392、WO2010137613、
WO2010070677, CN101177430, WO2008000418, WO2007114526 and WO2004098713.But these documents are equal
It is different from substantial contribution and content of the invention.
Summary of the invention
It is an object of the present invention to provide a kind of prasugrel hydrochloride compound, structural formula is as follows:
Above compound is to have X-ray diffraction peak at 7.3,14.7,16.6,18.3,26.0 in 2 θ.
There is above compound the X-ray similar with attached drawing 1 to spread out map.
Above compound has the differential thermal analysis map similar with attached drawing 2.
Above compound can be used for preparing tablet, capsule, granule, injection and freeze-dried powder.
It is another object of the present invention to be to provide a kind of pharmaceutical composition, it includes above compound and pharmaceutically may be used
The auxiliary material of receiving.
Another object of the present invention is to provide above compounds to prepare the application in cardiovascular and cerebrovascular diseases medicament.
Another object of the present invention is to provide aforementioned pharmaceutical compositions to prepare the application in cardiovascular and cerebrovascular diseases medicament.
Above-mentioned compound can often use auxiliary material, injection with pharmaceutically acceptable auxiliary material or carrier, such as oral preparation
Common auxiliary material etc. together, is prepared into oral preparation such as tablet, capsule, granule, the preparations such as injection such as injection, freeze-dried powder
Form.
Detailed description of the invention
Fig. 1 is the x-ray diffractogram of powder of the Prasugrel Hydrochloride form of the embodiment of the present invention 1；
Fig. 2 is the DSC figure of the Prasugrel Hydrochloride form of the embodiment of the present invention 1；
Specific embodiment
The invention will be further described with reference to embodiments, and professional and technical personnel in the field may be better understood
The present invention, but the embodiment range that simultaneously the invention is not limited in any way.
The preparation of embodiment 1- prasugrel hydrochloride
2.2 kilograms of prasugrel free alkalis are added into reaction kettle, 7.7 liters of ethyl acetate is heated with stirring to about 50 DEG C,
Dissolution clarification.Stop heating, be slowly stirred and be cooled to 25 ± 5 DEG C, insulated and stirred 1h, filters.Filter cake ether/ethanol (0.5
Rise/1 liter) mashing, then 2L × 2 time are rinsed with ethyl alcohol, it drains, about 1.6 kilograms of weight in wet base.45 ± 5 DEG C of vacuum drying 12 hours or more,
Obtain about 1.3 kilograms of prasugrel free alkali fine work.
Reaction kettle is separately taken, 1.20 kilograms of above-mentioned gained prasugrel free alkali fine work are added and 12 liters contain 10% nopinene
Acetone (weight ratio) is warming up to about 30 DEG C of stirring and dissolvings.It filters, acetone (weight ratio) of the filter paper with 2L containing 10% nopinene floats
It washes, merging filtrate, pours into clean reaction kettle.40 DEG C are continuously heating to, starts that 200g concentrated hydrochloric acid (about 10 minutes) are added dropwise.It protects
40 DEG C of temperature are stirred 1 hour.Kept for 40 DEG C continue that 150 grams of concentrated hydrochloric acids (about 1 hour) are added dropwise.Drop keeps the temperature crystallization 2 hours after finishing.It takes out
Filter, filter cake Acetone rinse 0.5L × 2 time drain, 35 DEG C vacuum drying 12 hours or more, yield is about 1.2 kilograms.
Powder x-ray diffraction: being radiated using Cu-K, X-ray ray powder diffraction (XRPD) map of prasugrel hydrochloride
See attached drawing 1.
Differential scanning calorimetric analysis: the differential scanning calorimetric thermogram spectrum of prasugrel hydrochloride is shown in attached drawing 2.
The metabolism of experimental example 1- raw material and drug effect
Experimental animal: male Wistar rat 32,200~230g of weight is purchased from Sichuan University.
Experimental method: rat is randomly divided into 4 groups, and every group 8, normal condition is raised, free water, after fasting 12h, every group
It is given prasugrel hydrochloride (embodiment 1) with solid irrigation stomach device respectively, 25,50,100 and 150mgkg of dosage-1.When taking blood
Between point: in administration before and administration after 5,15,30 minutes and 1,2,3,4,6,8,10,12,24,36,48 hour by eyeball after vein
Clump takes 300-500 microlitres of blood, sets in test tube of hepari Ep pipe.
Handle sample method: anticoagulant heparin venous blood is centrifuged 10 minutes in 5000 revs/min of room temperature, takes 100 microlitres of blood plasma,
1300 microlitres of ethyl acetate are added, vortex oscillation 3 minutes, 14000 revs/min were centrifuged 10 minutes, took upper organic phase 1200 micro-
It rises, nitrogen volatilizes.With aqueous 40 microlitres, 40 microlitres of methanol and 20 microlitres of acetonitrile 100 microlitres of dissolution residual substances of mixed liquor, whirlpool
After oscillation 1 minute, 13400 revs/min are centrifuged 1 minute.Take 20 microlitres of progress HPLC detections of supernatant.
After rat oral gavage gives embodiment 1, metabolite (prasugrel active metabolite R, CAS:204204-73- in blood
9) reached peak value at 6-7 hours.Rat platelet aggregation rate ED50 is 0.35mgkg-1。
The study on the stability of experimental example 2- raw material
The present invention is carried out 6 months accelerated tests (40 DEG C ± 2 DEG C, 75% ± 5%RH) of example 1,6 months long-term
It tests (30 DEG C ± 2 DEG C, 65% ± 5%RH).Long term test study on the stability will be continued for embodiment 1, inspection target
It include character, specific rotation, acid value, moisture, related substance, chlorinty and content.
Accelerated test
Packaging: medicinal low density polyethylene (LDPE) bag inner packing adds housing aluminum-plastic composite membrane bag after desiccant
Investigation condition: 40 DEG C ± 2 DEG C, 75% ± 5%RH
- 3 prasugrel hydrochloride accelerated test result of table (40 DEG C ± 2 DEG C, 75% ± 5%RH)
Long term test
- 4 prasugrel hydrochloride long-term test results of table (30 DEG C ± 2 DEG C, 60% ± 5%RH)
Claims (3)
1. a kind of prasugrel hydrochloride crystal, it is characterised in that its structural formula is as follows:
The crystal is to have X-ray diffraction peak, the differential thermal of the crystal at 7.3 °, 14.7 °, 16.6 °, 18.3 °, 26.0 ° in 2 θ
Analysis chart has map as shown in Fig. 2, and the x-ray diffraction pattern of the crystal has map as shown in Fig. 1.
2. a kind of pharmaceutical composition, it is characterised in that containing prasugrel hydrochloride crystal described in claim 1 and pharmaceutically may be used
The auxiliary material of receiving.
3. prasugrel hydrochloride crystal described in claim 1 or claim 2 described pharmaceutical composition are preparing cardiovascular and cerebrovascular
Application in disease medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410670472.8A CN105669696B (en) | 2014-11-21 | 2014-11-21 | A kind of prasugrel hydrochloride compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410670472.8A CN105669696B (en) | 2014-11-21 | 2014-11-21 | A kind of prasugrel hydrochloride compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105669696A CN105669696A (en) | 2016-06-15 |
| CN105669696B true CN105669696B (en) | 2019-03-26 |
Family
ID=56957429
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410670472.8A Expired - Fee Related CN105669696B (en) | 2014-11-21 | 2014-11-21 | A kind of prasugrel hydrochloride compound |
Country Status (1)
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011069473A1 (en) * | 2009-12-09 | 2011-06-16 | Zentiva, K.S. | A method for the preparation of prasugrel hydrochloride in polymorphous form b |
| WO2012023145A2 (en) * | 2010-08-18 | 2012-02-23 | Hetero Research Foundation | Prasugrel hydrochloride crystalline particles |
| CN102838618A (en) * | 2011-06-22 | 2012-12-26 | 广东东阳光药业有限公司 | Method for preparing prasugrel, and prasugrel hydrochloride novel crystal forms |
| CN103694251A (en) * | 2014-01-06 | 2014-04-02 | 南京简成医药科技有限公司 | Novel preparation process of prasugrel hydrochloride |
| WO2014092589A1 (en) * | 2012-12-12 | 2014-06-19 | Instytut Farmaceutyczny | Process for preparation of prasugrel hydrochloride polymorphic form b of pharmaceutical purity |
-
2014
- 2014-11-21 CN CN201410670472.8A patent/CN105669696B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011069473A1 (en) * | 2009-12-09 | 2011-06-16 | Zentiva, K.S. | A method for the preparation of prasugrel hydrochloride in polymorphous form b |
| WO2012023145A2 (en) * | 2010-08-18 | 2012-02-23 | Hetero Research Foundation | Prasugrel hydrochloride crystalline particles |
| CN102838618A (en) * | 2011-06-22 | 2012-12-26 | 广东东阳光药业有限公司 | Method for preparing prasugrel, and prasugrel hydrochloride novel crystal forms |
| WO2014092589A1 (en) * | 2012-12-12 | 2014-06-19 | Instytut Farmaceutyczny | Process for preparation of prasugrel hydrochloride polymorphic form b of pharmaceutical purity |
| CN103694251A (en) * | 2014-01-06 | 2014-04-02 | 南京简成医药科技有限公司 | Novel preparation process of prasugrel hydrochloride |
Non-Patent Citations (4)
| Title |
|---|
| Effects of Solvent on Polymorph Formation and Nucleation of Prasugrel Hydrochloride;Wei Du等;《Cryst. Growth Des.》;20140730;第4519-4525页，Figure 2. Figure 4. |
| 合成盐酸普拉格雷的工艺改进;段妍琴，等;《合成化学》;20121231;第2卷(第1期);第125-127页，1.2节 |
| 盐酸普拉格雷合成工艺的改进;代黎，等;《药学实践杂志》;20130525;第31卷(第3期);第195-197页，1.5节 |
| 盐酸普拉格雷的合成工艺改进;张雅然，等;《中国新药杂志》;20140228;第23卷(第3期);第275-277页，2.3节 |
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| CN105669696A (en) | 2016-06-15 |
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