CN107540630A - A kind of Febustat compound and preparation method - Google Patents
A kind of Febustat compound and preparation method Download PDFInfo
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- CN107540630A CN107540630A CN201610510184.5A CN201610510184A CN107540630A CN 107540630 A CN107540630 A CN 107540630A CN 201610510184 A CN201610510184 A CN 201610510184A CN 107540630 A CN107540630 A CN 107540630A
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- febustat
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000013078 crystal Substances 0.000 claims abstract description 66
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000002904 solvent Substances 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 9
- 229940079593 drug Drugs 0.000 claims abstract description 8
- 238000002425 crystallisation Methods 0.000 claims abstract description 6
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 6
- 230000008025 crystallization Effects 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 238000001291 vacuum drying Methods 0.000 claims abstract 2
- 230000006837 decompression Effects 0.000 claims description 2
- 239000004744 fabric Substances 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 8
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 6
- 230000001988 toxicity Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 238000005755 formation reaction Methods 0.000 description 45
- 238000012360 testing method Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- BQSJTQLCZDPROO-UHFFFAOYSA-N febuxostat Chemical compound C1=C(C#N)C(OCC(C)C)=CC=C1C1=NC(C)=C(C(O)=O)S1 BQSJTQLCZDPROO-UHFFFAOYSA-N 0.000 description 5
- 201000005569 Gout Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 229960005101 febuxostat Drugs 0.000 description 3
- 239000002547 new drug Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000010583 slow cooling Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 2
- 201000001431 Hyperuricemia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 108010093894 Xanthine oxidase Proteins 0.000 description 2
- 102100033220 Xanthine oxidase Human genes 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- ZGWGSEUMABQEMD-UHFFFAOYSA-N 4-methyl-1,3-thiazole-5-carboxylic acid Chemical compound CC=1N=CSC=1C(O)=O ZGWGSEUMABQEMD-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960003459 allopurinol Drugs 0.000 description 1
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
Abstract
The invention provides a kind of Febustat compound and preparation method, it is characterised in that compound crystal form W X-ray powder diffraction is when angle of reflection is 2 θ, in 0.3 ° of 5.8 scholar, 7.9 0.3 ° of scholars, 11.6 0.3 ° of scholars, 12.7 0.3 ° of scholars, 20.5 0.3 ° of scholars, there is characteristic peak at 25.9 0.3 ° of scholars.For the compound using Febustat A crystalline substances bulk drug as raw material, ethyl acetate is solvent, by stirring, dissolving by heating, slow Temperature fall to certain temperature, crystallization, is filtered, vacuum drying obtains described Febustat W crystal formation crystal.The present invention crystal formation W recrystallization method be using toxicity very little ethyl acetate solvent as recrystallization solvent, it is safe and easy to operate.Novel crystal forms W provided by the invention hygroscopicity under high humidity environment is relatively low, and stability is good, is unlikely to deteriorate, suitable for stable pharmaceutical preparation is made;It is and water-soluble preferable so that obtained pharmaceutical preparation is readily susceptible to be absorbed by the patient.
Description
Technical field
The invention belongs to chemical drug to synthesize field, and in particular to a kind of Febustat compound and preparation method.
Background technology
Febustat (Febuxostat) is 2- [3- cyano group -4-（2- methyl propoxyl group）Phenyl] -4- methylthiazol -5- carboxylics
The adopted name of acid；Corresponding English is entitled:2-[3-Cyano-4-(2-methylpropoxy)phenyl]-
4-methyl-1,3-thiazole-5-carboxylic acid, molecular formula are：C16H16N2O3S, relative molecular weight are：
316.38 chemical abstracts number is：144060-53-7；Its structural formula is：
Febustat is a kind of new non-purines selectivity xanthine oxidase（xanthine oxidase XO）Suppress
Agent, is a kind of new drug for treating gout, and its validity and specificity are better than the standard drug Allopurinol for the treatment of gout at present, quilt
《U.S.'s hyperuricemia gout practice guidelines》It is recommended as fiest-tire medication, is the new drug of first treatment hyperuricemia over 40 years,
And curative effect is fast, gout burst can be prevented well, and can long-term prescription, have that good DEVELOPMENT PROSPECT is current, many documents
It has been reported that the synthetic method of Febustat, refer to obtain final products with ethyl alcohol recrystallization, but do not tell about in literary
The problem of crystal formation.And in fact, Febuxostat has a variety of crystal formations, because this compound does not have patent protection, therefore, the country is many
Company is to preparing polymorphic to declare new drug.In recent years, a variety of preparation technologies are simple, the crystal formation patent of safety and stability has been appeared in the newspapers
Road.
Chinese patent CN101671314A discloses a kind of alpha-crystal form of Febustat, and the crystal formation passes through single solvent second two
Alcohol monomethyl ether is recrystallized to give；
Chinese patent CN101824005A discloses a kind of preparation method of the Q crystal formations of Febustat, and this method is sub- with dimethyl
The sulfone aqueous solution is as recrystallization solvent, and the method solvent for use boiling point is higher, and the later stage is difficult to remove, and easily causes dissolvent residual；
Chinese patent CN101824006A discloses a kind of preparation method of the P crystal formations of Febustat, this method using acetone as
Recrystallization solvent is recrystallized to give；
Chinese patent CN1275126A discloses A, B, C, D, BH for being related to this compound of Japanese Di Ren companies invention and without fixed
Type and preparation method thereof.Wherein, crystal formation A is metastable crystal formation, and crystal formation D is methylate, and crystal formation BH is hydrate.
In addition, the mutual transforming relationship between this several crystal formation of the play-by-play such as Mitsutaka Kitamura, to industry
Production has certain directive significance.
At present, many documents are it has been reported that the synthetic method of Febustat, refer to be obtained with ethyl alcohol recrystallization in literary
Final products, but the problem of do not tell about crystal formation.And in fact, Febustat has a variety of crystal formations, Chinese patent
What CN1275126A disclosed the invention of Japanese Di Ren companies is related to A, B, C, D, BH of this compound and unformed and its preparation side
Method.Wherein, crystal formation A is metastable crystal formation, and crystal formation D is methylate, and crystal formation BH is hydrate.The crystal formation master listed at present
If Febustat A crystal formations, but its prepare it is affected by many factors, such as temperature, solvent composition, whipped form and anti-solvent drop
Rate of acceleration etc..
The content of the invention
The present invention is prepared for a kind of new Febustat crystalline substance using acetic acid ethyl ester as recrystallisation solvent, by crystallisation by cooling method
Type-W crystal formations, the principal character peak of its X-ray powder diffraction are 0.3 ° of 5.8 scholar, 7.9 0.3 ° of scholars, 11.6 0.3 ° of scholars, 12.7
0.3 ° of scholar, 20.5 0.3 ° of scholars, there is characteristic peak, crystal formation W of the invention recrystallization method is using poison at 25.9 0.3 ° of scholars
The ethyl acetate solvent of property very little is safe and easy to operate as recrystallization solvent.Novel crystal forms W provided by the invention
Hygroscopicity is relatively low under high humidity environment, and stability is good, is unlikely to deteriorate, suitable for stable pharmaceutical preparation is made;It is and water-soluble
Preferably so that obtained pharmaceutical preparation is readily susceptible to be absorbed by the patient.
A kind of Febustat compound of the present invention and preparation method, concrete technical scheme are：
A kind of Febustat compound and preparation method, it is characterised in that compound crystal form W X-ray powder diffraction is anti-
When firing angle is 2 θ, in 0.3 ° of 5.8 scholar, 7.9 0.3 ° of scholars, 11.6 0.3 ° of scholars, 12.7 0.3 ° of scholars, 20.5 0.3 ° of scholars, 25.9 scholars
There is characteristic peak, the measure of 2 described θ values uses CuK α light sources at 0.3 °.
A kind of Febustat compound and preparation method of the present invention, the compound using Febustat A crystalline substances bulk drug as
Raw material, ethyl acetate are solvent, by stirring, dissolving by heating, slow Temperature fall to certain temperature, crystallization, are filtered, vacuum is done
It is dry to obtain described Febustat W crystal formation crystal.
The wherein w/v of Febustat A crystalline substances bulk drug and ethyl acetate preferably 1: 40~1:5g/ml, further
It is preferred that 1:20g/m.Stirring and crystallizing speed preferred 100rpm ~ 300rpm, preferably 150rpm ~ 180rpm.Rate of temperature fall：It is preferred that
0.3k/min ~ 0.8k/min, preferably 0.2k/min ~ 0.5k/min.Temperature preferably 30 ~ 80 DEG C, preferably 40 of solvent are extracted in decompression out
℃。
（One）The present invention prepares Febustat W crystal formations using crystallisation by cooling method, and with X-ray powder diffraction instrument, Fu Li
Leaf transformation infrared spectrometer, the brilliant progress analysis and characterizations of Febustat W to gained.
（Two）The principle and foundation that raw material route determines.It is brilliant former with the certain Febustat A of assay balance precise
Medicine is expected in flask, and measuring ethyl acetate with graduated cylinder adds in flask；Huber heating and cooling programs are set, utilize temperature probe control
Reacting liquid temperature in flask processed, adjust agitator speed of agitator, after Febustat is completely dissolved, make solution at 78 DEG C next time
Stream about half an hour, then start to cool with certain rate of temperature fall；When cooling to the crystallization temperature of setting, there is substantial amounts of crystal to analyse
Go out, at this temperature constant temperature growing the grain for a period of time, after terminate to test；Magma is taken out, is filtered with vavuum pump, solid is being dried in vacuo
60 DEG C of dryings 8 hours, are then weighed in case；Dried product Malvern laser particle analyzer Zetasizer Nano
ZS90 tests its granularity cloth.
（Three）The comparison of process technology scheme and selection reason
The crystal formation W of present invention recrystallization method is the ethyl acetate solvent using toxicity very little as recrystallization solvent, safety
Property it is high and easy to operate.Novel crystal forms W provided by the invention hygroscopicity under high humidity environment is relatively low, and stability is good, is not easy
It is rotten, suitable for stable pharmaceutical preparation is made;It is and water-soluble preferable so that obtained pharmaceutical preparation is readily susceptible to be absorbed by the patient.
Figure of description：
Fig. 1 Febustat W crystal formation figures；
Fig. 2 Febustat W crystal formation infrared spectrums.
Embodiment
Example below is only to further illustrate the present invention, and the invention is not limited in any way.
Embodiment 1
2g Febustats are added in 100m1 round-bottomed flasks, 40m1 ethyl acetate solvents is added, stirring, is heated to reflux, until
It is completely dissolved, then slow cooling stirring and crystallizing, obtains 1. 2g Febustat crystal to 40 DEG C.X- is carried out to gained crystal
Ray powder diffractions are tested, and gained spectrogram is as shown in Figure 1.
Embodiment 2
2g Febustats are added in 50m1 round-bottomed flasks, 10ml ethyl acetate solvents is added, stirring, is heated to reflux, until
It is completely dissolved, then slow cooling stirring and crystallizing, obtains 1. 3g Febustat crystal to 40 DEG C.X- is carried out to gained crystal
Ray powder diffractions are tested, and gained spectrogram is as shown in Figure 1.
Embodiment 3
2g Febustats are added in 100m1 round-bottomed flasks, 40m1 ethyl acetate solvents is added, stirring, is heated to reflux, until
It is completely dissolved, then slow cooling stirring and crystallizing, obtains 1. 3g Febustat crystal to 5 DEG C.X-ray is carried out to gained crystal
Powder diffraction is tested, and gained spectrogram is as shown in Figure 1.
Embodiment 4
Stability analysis:After the crystal formation W of the gained of above-described embodiment 1 is placed 6 months under conditions of 75 % humidity, do again
Powder x-ray diffraction analysis, collection of illustrative plates are shown in Fig. 2, and the Fig. 2 is compared to Figure 1 almost unchanged, illustrate what is do not changed to other crystal formations
Sign, and the total impurities during whole experiment in the crystal formation crystal do not change, and illustrate that crystal formation W stability is good
It is good.
The solubility test of the Febustat W crystal formations of embodiment 5 and A crystal formations
Febustat W is brilliant and A is brilliant fully finely ground respectively, respectively with water, 0. I NHC1, PH5.0 phosphate buffer solutions and
PH6.8 phosphate buffer solutions prepare saturated solution, with the content of Febustat in determined by ultraviolet spectrophotometry saturated solution,
It the results are shown in Table 1.As can be seen from Table 1：The solubility of W crystal formations than A crystal formation be doubled left and right.
The W crystal formations of table 1 and A crystal formation solubility test results
The Dissolution Rate Testing of the Febustat W crystal formations of embodiment 5 and A crystal formations
The W crystal formations and crystal formation A prepared to embodiment 2 carries out preparation preparation and Dissolution Rate Testing respectively, as a result see the table below 2
The Dissolution Rate Testing of Febustat W crystal formations and A crystal formations
Febustat W crystalline substances/A crystalline substances 30g
Lactose 53.2g
Pregelatinized starch 15g
Hydroxypropyl methylcellulose 27.5g
Ac-Di-Sol 2.25g
Magnesium stearate 0.75g
Take Febuxostat W brilliant or the brilliant and above-mentioned various auxiliary materials of A cross 100 mesh sieves respectively, Febustat W is put into wet granulator
Brilliant or A crystalline substance 30g, lactose 53.2g, pregelatinized starch 15g, uniformly after mixing, 5% township the third methylcellulose 27.5g granulations are sprayed into,
Crosslinking is added after 60 DEG C of dryings, whole grain and takes advantage of sodium carboxymethylcellulose pyce 2.25g, magnesium stearate 0.75g, tabletting after mixing.
The W crystal formations of table 2 and A crystal formation dissolution test results
Can learn the Febustat W crystal formations that prepare of the present invention and medicinal crystal-form A crystalline phases seemingly from the data of table 2, can reach compared with
Good dissolution rate.Dissolution rate of the Febustat at 60 minutes is 84.52%, has exceeded A brilliant 80.02%.
Claims (6)
1. a kind of Febustat compound and preparation method, it is characterised in that compound crystal form W X-ray powder diffraction exists
When angle of reflection is 2 θ, in 0.3 ° of 5.8 scholar, 7.9 0.3 ° of scholars, 11.6 0.3 ° of scholars, 12.7 0.3 ° of scholars, 20.5 0.3 ° of scholars, 25.9
There is characteristic peak at 0.3 ° of scholar.
2. a kind of Febustat compound and preparation method according to claim 1, it is characterised in that the compound is with non-cloth
It is raw material to take charge of his A crystalline substances bulk drug, and ethyl acetate is solvent, by stirring, dissolving by heating, slow Temperature fall to certain temperature,
Crystallization, filter, vacuum drying obtains described Febustat W crystal formation crystal.
3. a kind of Febustat compound and preparation method according to claim 2, it is characterised in that Febustat A is brilliant former
Expect the w/v preferably 1 of medicine and ethyl acetate: 40~1:5g/ml, further preferred 1:20g/ml.
4. a kind of Febustat compound and preparation method according to claim 2, it is characterised in that stirring and crystallizing speed is excellent
Select 100rpm ~ 300rpm, preferably 150rpm ~ 180rpm.
5. a kind of Febustat compound and preparation method according to claim 2, it is characterised in that rate of temperature fall：It is preferred that
0.3k/min ~ 0.8k/min, preferably 0.2k/min ~ 0.5k/min.
6. a kind of Febustat compound and preparation method according to claim 2, it is characterised in that solvent is extracted in decompression out
Preferably 30 ~ 80 DEG C, preferably 40 DEG C of temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610510184.5A CN107540630A (en) | 2016-06-29 | 2016-06-29 | A kind of Febustat compound and preparation method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610510184.5A CN107540630A (en) | 2016-06-29 | 2016-06-29 | A kind of Febustat compound and preparation method |
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Family
ID=60965694
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1275126A (en) * | 1998-06-19 | 2000-11-29 | 帝人株式会社 | Polymorphic modifications of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole-carboxylic acid and processes for the preparation thereof |
| CN101386605A (en) * | 2008-10-23 | 2009-03-18 | 中国科学院上海药物研究所 | Febustat novel crystal and preparation method thereof |
| CN101412700A (en) * | 2007-10-19 | 2009-04-22 | 上海医药工业研究院 | Crystal form and preparation of febuxostat |
| CN101671314A (en) * | 2009-09-17 | 2010-03-17 | 中国药科大学 | Uloric crystal and preparation method thereof |
| CN101759656A (en) * | 2008-12-12 | 2010-06-30 | 重庆医药工业研究院有限责任公司 | Febuxostat new crystal forms and preparation method thereof |
| CN101817801A (en) * | 2009-08-12 | 2010-09-01 | 北京红惠新医药科技有限公司 | Preparation method of new crystal form K of 2-(3-cyano-4-isobutoxy)-4-methyl-5-thiazole formic acid and other crystal forms |
| CN101824006A (en) * | 2010-04-27 | 2010-09-08 | 上海凯米侬医药科技有限公司 | New crystal form P of Febuxostat and preparation method thereof |
| CN101824005A (en) * | 2010-04-27 | 2010-09-08 | 上海凯米侬医药科技有限公司 | New crystal form Q of Febuxostat and preparation method thereof |
| CN106565627A (en) * | 2016-10-10 | 2017-04-19 | 扬子江药业集团有限公司 | Preparation method for pharmaceutical crystal form of febuxostat |
-
2016
- 2016-06-29 CN CN201610510184.5A patent/CN107540630A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1275126A (en) * | 1998-06-19 | 2000-11-29 | 帝人株式会社 | Polymorphic modifications of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole-carboxylic acid and processes for the preparation thereof |
| CN101412700A (en) * | 2007-10-19 | 2009-04-22 | 上海医药工业研究院 | Crystal form and preparation of febuxostat |
| CN101386605A (en) * | 2008-10-23 | 2009-03-18 | 中国科学院上海药物研究所 | Febustat novel crystal and preparation method thereof |
| CN101759656A (en) * | 2008-12-12 | 2010-06-30 | 重庆医药工业研究院有限责任公司 | Febuxostat new crystal forms and preparation method thereof |
| CN101817801A (en) * | 2009-08-12 | 2010-09-01 | 北京红惠新医药科技有限公司 | Preparation method of new crystal form K of 2-(3-cyano-4-isobutoxy)-4-methyl-5-thiazole formic acid and other crystal forms |
| CN101671314A (en) * | 2009-09-17 | 2010-03-17 | 中国药科大学 | Uloric crystal and preparation method thereof |
| CN101824006A (en) * | 2010-04-27 | 2010-09-08 | 上海凯米侬医药科技有限公司 | New crystal form P of Febuxostat and preparation method thereof |
| CN101824005A (en) * | 2010-04-27 | 2010-09-08 | 上海凯米侬医药科技有限公司 | New crystal form Q of Febuxostat and preparation method thereof |
| CN106565627A (en) * | 2016-10-10 | 2017-04-19 | 扬子江药业集团有限公司 | Preparation method for pharmaceutical crystal form of febuxostat |
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