CN101525319A - Febuxostat and drug combination thereof - Google Patents
Febuxostat and drug combination thereof Download PDFInfo
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- CN101525319A CN101525319A CN200910068558A CN200910068558A CN101525319A CN 101525319 A CN101525319 A CN 101525319A CN 200910068558 A CN200910068558 A CN 200910068558A CN 200910068558 A CN200910068558 A CN 200910068558A CN 101525319 A CN101525319 A CN 101525319A
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Abstract
The invention relates to Febuxostat and a drug combination thereof, wherein the Febuxostat is Febuxostat crystal, belonging to monoclinic system, the space group of the crystal is P2 (1), and cell parameters comprise a=4.7179 (9), b=17.813 (4), c=10.690 (2), alpha=gamma=90 degrees, and beta=99.20 (3) degrees; and the cell volume is 886.8(3) <3>. In addition, the invention also relates to a drug composition containing the Febuxostat crystal and a preparation method of the crystal, and simultaneously the invention further discloses application of the Febuxostat crystal in treating hyperuricemia comprising primary and secondary hyperuricemia, acute and chronic gout, gouty arthritis, gouty nephropathy and renal calculus which are caused by the hyperuricemia.
Description
Technical field
The invention belongs to technical field of medicine synthesis, relate to novel Febustat and pharmaceutical composition thereof, be the Febustat crystal in particular, contain this crystalline pharmaceutical composition and their application in treatment antihyperuricemic disease drug.
Background technology
In recent years, along with the change of people's diet formula, life-time dilatation and to the attention of gout, the sickness rate of gout presents year by year to be increased, and the state of affairs of trend rejuvenation is more arranged.Gout mainly is because the disease due to the purine metabolic disturbance, and its clinical characters is that hyperuricemia and the gouty, the acute arthritis that cause are therefrom shown effect repeatedly, uratoma deposition, uratoma chronic arthritis and joint deformity and kidney cause that chronic interstitial nephritis and uric acid urinary stone disease form.Gout be owing to produce uric acid in the body and too much reach kidney and remove ability drop, the uric acid body accumulation causes urate crystal in the joint and each internal organs deposition.The generation of the interior uric acid of body is relevant with purine metabolism, and in the final step of purine metabolism, xanthoglobulin generates xanthine under the effect of xanthine oxidoreductase enzyme (XOR), further generate uric acid again, and the activity that suppresses XOR can effectively reduce the generation of uric acid.Therefore, the means that gout treatment is taked usually are: promote uric acid excretion and suppress uricogenesis, and adopt adequate measure to improve related symptoms.
Febustat febuxostat (TMX-67) is that (xanthine oxidase, XO) inhibitor are called the inhibitor of non-purine selectivity XO again for a kind of XOD of new classification.The important part that it is different from allopurinol comprises that it is diverse molecular structure, and XO is had stronger specific inhibitory effect, and not in the being seen influence to other purine and pyrimidine metabolic enzyme of allopurinol.TMX-67 mainly forms glucuronide and oxygenizement metabolism by liver, does not discharge and do not rely on kidney.Have data to show, it is light to having, moderate renal insufficiency person is safe and effective.Clinical observation confirmation TMX-67 is evident in efficacy to treatment hyperuricemia and gout, and is subjected to ardent high praise.U.S. Pat 5614529 discloses the preparation method of Febustat, but the crystal data of the compound of not coming into the open, Chinese patent CN1275126A discloses multiple crystal of Febustat and preparation method thereof subsequently, but does not disclose Febustat alcohol solvent crystalline any structure determination data.
Summary of the invention
An object of the present invention is to disclose the Febustat crystal, i.e. Febustat alcohol solvent crystallization, its stable in properties is for preparation several formulations mode provides possibility.
Another object of the present invention is to disclose Febustat crystalline preparation method.
A further object of the present invention is to disclose to contain Febustat crystalline pharmaceutical composition.
The present invention also purpose is to disclose the application of Febustat crystal in the medicine of preparation treatment hyperuricemia and relevant various illnesss thereof.
For achieving the above object, the invention provides following technical scheme:
A kind of Febustat crystal, it is an oblique system, and its spacer is P2 (1), and unit cell parameters is: a=4.7179 (9)
B=17.813 (4)
C=10.690 (2)
α=γ=90 °, β=99.20 (3) °, have 2859 independently point diffraction and unit cell volume be: 886.8 (3)
Crystalline density: 1.357mg/mm
3Profile is needle-like, is of a size of 0.18 * 0.10 * 0.04mm.
The present invention further discloses Febustat crystalline preparation method, it is to get Febustat and aqueous ethanolic solution heating for dissolving, and cooling is placed naturally, separates out crystallization, filters drying.The concentration of wherein said aqueous ethanolic solution is 50-100%.
The by weight/volume of Febustat of the present invention and aqueous ethanolic solution is 1: 20-80.In experiment, if finding the ratio of water in the aqueous ethanolic solution, the inventor surpasses 50%, then resulting crystal is disclosed crystal G (Febustat hydrate) among the CN1275126A.
As typical embodiment of the present invention: get Febustat 2 grams, add 60ml 95% ethanol heating for dissolving, cooling is placed naturally, separates out crystallization, filtration, drying.Carrying out SXRD and X-ray powder diffraction measures.Its monocrystalline X-ray diffraction (SXRD) data are as follows:
1, instrument model and condition determination:
BRUKER SMART 1000 types four garden single crystal diffractometers.
Temperature: 293
0k
Wavelength: 0.71073
Crystal size: 0.18 * 0.10 * 0.04mm
Data gathering and structure cell are modified software: BRUKER SMART.
Data conversion software: BRUKER SHLXTL.
Structure elucidation software: SHELXTL-97 (SHEDRICK-1990).
Structural modification software: SHELXTL-97 (SHEDRICK-1997).
Mapping software: BRUKER SHLXTL.
2, structure elucidation:
Through collecting 6116 point diffractions, 2859 independently point diffraction through the mensuration of peak-seeking, location, unit cell parameters, the data collection program and the systematize data gatherings such as indexing of diffraction peak, structural analysis and modification, the structure cell figure and the molecular structure of synthetic Febustat have been obtained, molecular formula and molecular weight (seeing Fig. 1 and Fig. 2).
Table 1 crystallization data and structural modifications are as follows:
Table 1.Crystal data and structure refinement for r81220g.
Registration number Identification code r81220g
Experience molecular formula Empirical formula C18 H22 N2 04 S
Molecular weight Formula weight 362.44
Temperature T emperature 293 (2) K
Wavelength Wavelength 0.71073A
Crystallographic system spacer Crystal system, space group Monoclinic, P2 (1)
Unit cell size Unit cell dimensions a=4.7179 (9) A alpha=90deg.
b＝17.813(4)A beta＝99.20(3)deg.
c＝10.690(2)A gamma＝90deg.
Volume Volume 886.8 (3) A^3
Unit cell molecule number Z, Calculated density (bulk density) 2,1.357Mg/m^3
Uptake factor Absorption coefficient 0.208mm^-1
F(000) 384
Crystalline size Crystal size 0.18x0.10x0.04mm
Collect data θ angular region Theta range for data collection 3.86to 25.02deg.
Limit factor Limiting indices-4＜=h＜=5 ,-20＜=k＜=21 ,-12＜=1＜=12
Collect point diffraction/independent point diffraction Reflections collected/unique 6116/2859[R (int)=0.1121]
Completeness to theta＝25.02 99.8％
Data integrity Absorption correction None
Absorption correction Max.and min.transmission 0.9917and 0.9635
Modification method Refinement method Full-matrix least-squares on F^2
Data/restriction/parameter Data/restraints/parameters 2859/1/232
Least square fitting Goodness-of-fit on F^2 0.985
Final discrepancy factor Final R indices[I＞2sigma (I)] R1=0.0633, wR2=0.0839
Discrepancy factor R indices (all data) R1=0.1271, wR2=0.0981
Absolute structure parameter A bsolute structure parameter 0.06 (10)
Largest diff.peak and hole 0.281and-0.280e.A^-3
Final difference cloud density climax and ebb
2.1 crystal data:
Crystal system and spacer: oblique system, P2 (1) spacer
Lattice parameter: a=4.7179 (9)
α=90 °
b＝17.813(4)
β＝99.20(3)°
c＝10.690(2)
γ＝90°
Unit cell volume: 886.8 (3)
Crystalline density: 1.357mg/mm
3
Index limit :-4＜=h＜=5 ,-20＜=k＜=21 ,-12＜=1＜=12
2.2 molecular structure data:
According to atoms in space coordinate and effective homogeneity displacement parameter, bond distance, bond angle, anisotropy displacement parameter and hydrogen atom coordinate and twist angle, it is unusual not see that bond distance and bond angle occur) obtained the structure cell figure of Febustat, see chemical structure (solid) figure of Fig. 1, Febustat, see Fig. 2.
2.2.1 reliable in structure sex factor:
R[I＞2sigma(I)]：R1＝0.0633，wR2＝0.0839
R(all data)：R
1＝0.1271，wR2＝0.0981
S(Goodness-of-fit on F
2)：0.985
2.2.2 Febustat molecule arranging in structure cell:
Febustat is shown arrangement with planar extension in structure cell, intermolecular being staggered, comprise four Febustat molecules and four crystallization ethanol molecules in each structure cell, wherein the Sauerstoffatom of 5 one carboxylic acid protons of the thiazole ring of a molecule of Febustat and an ethanol molecule forms hydrogen bond, this alcoholic acid hydroxyl proton forms hydrogen bond with the 3-position nitrogen-atoms of the thiazole ring of another Febustat again, and coming to this connects the Febustat molecule each other by the crystallization ethanol molecule.So repeatedly, just Febustat is and the form of crystallization ethanol with 1: 1 when solid state, and formation polymolecular association body exists, and has formed the distinctive monocrystalline of Febustat.
2.2.3 Febustat crystalline molecular formula, molecular weight, chemical structural formula:
Molecular formula: C18H22N2O4S=C16H16N2O3S+C2H6O
Molecular weight: 362.44=316.37+46.07.
Chemical structural formula:
Febustat crystalline X-ray powder diffraction the results are shown in Figure 3 and Fig. 3-1.Data are as follows:
Instrument: Japanese D/MAX-2500X x ray diffractometer x of science
Target: Cu-K a radiation (λ=1.5405
), 2 θ=2-40 ℃
Pipe is pressed: 40KV
Pipe stream: 100mA
2 θ are 8.10,9.48, and 12.80,17.04,19.14,23.42,25.90 have characteristic peak.
The present invention further discloses and contain Febustat crystal and pharmaceutically acceptable one or more pharmaceutical carriers for the treatment of significant quantity.Wherein said pharmaceutical composition is for containing 1-240mg Febustat crystalline tablet, capsule, injection liquid or freeze-dried powder.
Preferred compositions of the present invention is for containing 20-120mg Febustat crystalline injection liquid or freeze-dried powder.
Another preferred compositions of the present invention is for containing 20-120mg Febustat crystalline tablet or capsule.
Containing the Febustat crystalline pharmaceutical composition as activeconstituents of the present invention can be according to the conventional medicine compounding process, prepares by Febustat crystal and pharmaceutically acceptable carrier are made up.Carrier can adopt various forms, and this depends on the route of administration (for example oral, administered parenterally) of hope.Therefore for oral liquid, suitable carriers and additive comprise water, ethylene glycol, oil, ethanol, seasonings, sanitas, stablizer, tinting material or the like; For oral solid formulation such as powder, capsule or tablet, suitable carriers and additive comprise: thinner, lubricant, tackiness agent, disintegrating agents or the like such as lactose, starch, sucrose, polyvinylpyrrolidone.Oral solid formulation also can be used as material dressings or enteric coated so that adjust the main position that absorbs such as acrylic resins.For parenteral admistration, as preparations such as topical, transdermal administration and mucosa deliveries, carrier generally includes macromolecular material such as carbomer, absorption enhancer azone or the like.Injection liquid also can utilize water carrier and suitable additives such as caffolding agent N.F,USP MANNITOL, glycine, solubilizing agent propylene glycol, oxidation inhibitor Sodium Pyrosulfite or the like preparation.Because be easy to administration, tablet and capsule are represented the oral presented in unit dosage form of most convenient.
The every dose unit of pharmaceutical composition of the present invention for example sheet, capsule, injection or the like should comprise the essential Febustat crystal that discharges aforesaid effective dose.For example common compressing tablet composition such as W-Gum, lactose, sucrose, sorbyl alcohol, talcum powder, stearic acid, Magnesium Stearate, Lin Suanergai or glue and other medicinal diluents.For example water mixes, and comprises Febustat crystalline solid prescription of the present invention design team compound with formation.Comprise syrup, the water of the aqueous solution, suitable flavouring or contain edible oil for liquid form, for example the emulsion of the flavouring of cottonseed oil, sesame oil and elixir and similar pharmaceutical carrier.
The characteristics that Febustat crystal of the present invention is had:
The crystal form A median size that document CN1642546A introduces requires below 50 μ m more than the 3 μ m; When document crystal form A median size during greater than 50 μ m, the solid preparation stripping of making is incomplete and inhomogeneous, causes administration artifact availability low, and curative effect is bad, and individual difference is big.And contain the made preparation of Febustat crystal of the present invention particle diameter there is not special requirement.For example: with reference to Chinese patent CN1642546A, its prescription: main ingredient 82.05g, lactose 328.61g, pregelatinized Starch 77.03g, hydroxypropylcellulose 12.31g, croscarmellose sodium 10.25g, Magnesium Stearate 2.56g.
The preparation method: ion exchanged water is granulated, 60 ℃ of dryings, the whole grain of 20 mesh sieves, (add-on: every 1200g particle adds 24.6g to add croscarmellose sodium, about 2%), adds Magnesium Stearate (add-on: every 1200g particle adds 6.15g, about 0.5%), mixing, 7mm stamping (about 150mg/ sheet), dressing (distilled water, polyoxyethylene glycol, HPMC are formed).
The inventor according to above prescription, adopts wet granulation with document crystal form A, Febustat crystal (different-grain diameter), and compacting is measured its stripping in flakes, the results are shown in Figure 4, and the result shows: the stripping curve unanimity of the obtained tablet of different-grain diameter Febustat crystal.Therefore, the Febustat crystal has better preparation performance than the disclosed crystal form A of document CN1642546A.
Dissolution determination method:
Get this product, according to dissolution method (two appendix XC of Chinese Pharmacopoeia version in 2005, second method), be solvent with pH 6.8 phosphate buffer 1 000ml, 75 rev/mins of rotating speeds, operation in accordance with the law, sampling 5ml and fluid infusion are in time filtered when 5min, 10min, 15min, 20min, 30min, 45min, precision is measured subsequent filtrate 1ml and is put in the 10ml measuring bottle, add pH 6.8 phosphate buffered saline buffers and be diluted to scale, shake up, as need testing solution.
It is an amount of that in addition precision takes by weighing reference substance, adds 95% ethanolic soln and make the solution that every 1ml contains the 0.2mg Febustat, and precision is measured 1ml and put in the 25ml measuring bottle, adds pH 6.8 phosphate buffered saline buffers and is diluted to scale, shakes up, in contrast solution.
Get need testing solution and contrast solution respectively, measure optical density according to spectrophotometry (two appendix IVA of Chinese Pharmacopoeia version in 2005) at the wavelength place of 314nm, external standard method is calculated every stripping quantity.
The present invention further discloses the application of Febustat crystal in the medicine of preparation treatment hyperuricemia and relevant various illnesss thereof.Wherein said hyperuricemia comprises: former and secondary hyperuricemia.The various illnesss that described hyperuricemia is relevant comprise the acute and chronic gout that is caused by hyperuricemia, urarthritis, gouty nephropathy and urinary stone disease.Be the experiment situation and the result of Febustat crystal treatment hyperuricemia animal model below:
1 experiment material
1.1 medicine and reagent
The Febustat crystal, white crystals, Taipu Medicine Science ﹠ Technology Development Co., Ltd., Tianjin provides.Face with the preceding suspendible soup that is configured to desired concn with 0.5% Xylo-Mucine (CMC-Na) and use for the animal gastric infusion.
Benzbromarone, white powder, Taipu Medicine Science ﹠ Technology Development Co., Ltd., Tianjin provides.Face with the preceding suspendible soup that is configured to desired concn with 0.5% Xylo-Mucine (CMC-Na) and use for the animal gastric infusion.
Uric acid detection kit, Nanjing are built up bio-engineering research institute product, lot number 20080516.
1.2 animal
Kunming mouse, SPF, Institute of Radiation Medicine, Chinese Academy of Medical Sciences's Experimental Animal Center provides, and credit number is SCXK Tianjin 2005-0001.
1.3 instrument
PK121R cryogenic freezing whizzer, Italian ALC company produces.
722 grating spectrophotometers, Shanghai the 3rd analytical instrument factory produces.
2 methods and result
2.1 influence to normal animal urine acid
Behind the mouse overnight fasting, by the body weight random packet.Give Febustat crystal, benzbromarone, the administration volume is 20ml/kg.6h after the administration plucks eyeball and gets blood 0.5mL, and after room temperature left standstill 1h, the centrifugal preparation serum of 3000rpm was got serum kit measurement uric acid level.The results are shown in Table 1.
Table 1 Febustat crystal and benzbromarone are to the influence of normal mice serum uric acid (x ± s)
| Group | Dosage (mg/kg) | Serum uric acid concentration | Inhibiting rate (%) |
| Contrast (n=10) | - | 2.33±0.30 | 0 |
| Febustat crystal (n=10) | 4 | 1.64±0.42 ** | 29.6 |
| Benzbromarone (n=10) | 2 | 2.29±0.48 | 1.71 |
Compare (variance analysis) with control group:
*P＜0.01.
2.2 influence to hyperuricemia mouse uric acid
Behind the mouse overnight fasting, by the body weight random packet.Give Febustat crystal, benzbromarone, the administration volume is 20ml/kg.3h after the administration irritates stomach and gives xanthoglobulin 1000mg/kg, and the Oteracil Potassium of subcutaneous injection simultaneously 300mg/kg causes hyperuricemia model, after 3h, pluck eyeball and get blood 0.5ml, after room temperature leaves standstill 1h, the centrifugal preparation serum of 3000rpm is got serum kit measurement uric acid level.
2.2.1 the effect situation of Febustat crystal and benzbromarone is relatively:
The hyperuricemia mouse stomach gives Febustat crystal and benzbromarone respectively, the results are shown in Table 2.
Table 2 Febustat crystal and benzbromarone are to the influence of hyperuricemia mice serum uric acid (x ± s)
| Group | Dosage (mg/kg) | Serum uric acid concentration | Inhibiting rate (%) |
| Normal control (n=10) | 2.27±0.35 | ||
| Model contrast (n=10) | - | 10.69±2.17 | |
| Febustat crystal (n=10) | 4 | 8.26±2.82 * | 28.9 |
| Benzbromarone (n=10) | 2 | 10.08±2.17 | 7.3 |
*P＜0.05.
3. experiment conclusion: test-results shows: the Febustat crystal can reduce the concentration of uric acid in normal mouse and the hyperuricemia mice serum fast.
Description of drawings:
Fig. 1 is the structure cell figure of synthetic Febustat;
Fig. 2 is the molecular structure of synthetic Febustat;
Fig. 3 is a Febustat crystal X-ray powder diffraction pattern, and wherein Fig. 3-1 is Febustat crystal X-ray powder diffraction pattern data;
Fig. 4 is the stripping curve of different-grain diameter Febustat crystal gained preparation.
Embodiment
The present invention is described further below in conjunction with embodiment, and embodiment only is indicative, means that never it limits the scope of the invention by any way.Febustat wherein can be referring to preparation method's preparation of U.S. Pat 5614529.
The preparation of Febustat crystalline:
Get Febustat 2 gram, 60ml 95% ethanol thermosol, cooling is placed naturally, separates out crystallization, filters, and drying obtains Febustat crystal 1.94 grams, and yield 85% carries out SXRD and X-ray powder diffraction mensuration then, the results are shown in Figure 1, Fig. 2, Fig. 3 and Fig. 3-1.
Its monocrystalline X-ray diffraction (SXRD) data are as follows:
Oblique system, its spacer are P2 (1), and unit cell parameters is: a=4.7179 (9)
B=17.813 (4)
C=10.690 (2)
α=γ=90 °, β=99.20 (3) °, have 2859 independently point diffraction and unit cell volume be: 886.8 (3)
Crystalline density: 1.357mg/mm
3Profile is needle-like, is of a size of 0.18 * 0.10 * 0.04mm.
Febustat crystalline X-ray powder diffraction the results are shown in Figure 3 and Fig. 3-1.Data are as follows:
Instrument: Japanese D/MAX-2500X x ray diffractometer x of science
Target: Cu-Ka radiation (λ=1.5405
), 2 θ=2-40 ℃
Pipe is pressed: 40KV; Pipe stream: 100mA
2 θ are 8.10,9.48, and 12.80,17.04,19.14,23.42,25.90 have characteristic peak.
Embodiment 2
The preparation of Febustat crystalline:
Get Febustat 5 grams, add 300ml 60% ethanol thermosol, cooling is placed naturally, separates out crystallization, filters, and drying obtains Febustat crystal 5 .1 gram, and yield 89.2% carries out SXRD and X-ray powder diffraction then and measures, and the result is with embodiment 1.
Embodiment 3
The preparation of Febustat crystalline:
Get Febustat 2 grams, add 45ml dehydrated alcohol thermosol, cooling is placed naturally, separates out crystallization, filters, and drying obtains Febustat crystal 1.83 grams, and yield 80.0% carries out SXRD and X-ray powder diffraction then and measures, and the result is with embodiment 1.
Example of formulations
With Febustat crystal 80.19g (being equivalent to Febustat 70g), add lactose 43g, Microcrystalline Cellulose 16g mixes, adding an amount of 10% HPMC solution granulates, drying adds sodium starch glycolate 5.3g again, Magnesium Stearate 1.5g, mixing, compressing tablet, the bag film-coat is made 1000.
Embodiment 2
Febustat crystal 114.6g (being equivalent to Febustat 100g) adds lactose 397g, starch,pregelatinized 93g, hydroxypropylcellulose 15g, croscarmellose sodium 29.8g, Magnesium Stearate 7.5g mixes, and pure water is granulated, drying, compressing tablet, the bag film-coat is made 1000.
Embodiment 3
Febustat crystal 6 8.7g (being equivalent to Febustat 60g), add lactose 28.5g, Microcrystalline Cellulose 10.5g mixes, adding an amount of 10% polyvinylpyrrolidonesolution solution granulates, drying adds sodium starch glycolate 4.7g again, Magnesium Stearate 1.2g, mixing, compressing tablet, the bag film-coat is made 1000.
Embodiment 4
Febustat crystal 114.6g (being equivalent to Febustat 100g) adds dextrin 100g, and lactose 270g uses 70% alcohol granulation, and drying is encapsulated, makes 1000 seed lac wafers.
Embodiment 5 (1000)
Febustat crystal 4 5.8g (being equivalent to Febustat 40g), add in the 100g fused Macrogol 4000, in the fused Macrogol 4000, stirring makes whole dissolvings and mixes, and keeps under 60 ℃ of constant temperatures, splashes in the whiteruss (5～10 ℃), be condensed into dripping pill, exhaust whiteruss, the choosing grain, promptly.
Embodiment 6
Febustat crystal 91.6g (being equivalent to Febustat 80g) adds 2M NaOH and regulates pH8.0, adds the injection water to 5000ml, 0.22 μ m millipore filtration micro-filtration, and packing (every bottle of 5ml), sterilization promptly gets the Febustat injection liquid.
Embodiment 7
Febustat crystal 4 5.8g (being equivalent to Febustat 40g) adds 2MNaOH and regulates pH8.0, adds glycine 200g, add the injection water to 2000ml, 0.22 μ m millipore filtration micro-filtration, packing under the aseptic condition (every bottle of 2ml), lyophilize, gland promptly gets and contains Febustat crystalline freeze-dried powder.
Claims (10)
1, a kind of Febustat crystal, it is an oblique system, and its spacer is P2 (1), and unit cell parameters is:
α=γ=90 °, β=99.20 (3) °, unit cell volume is:
2, the described Febustat crystalline of a kind of preparation claim 1 method is characterized in that getting Febustat and aqueous ethanolic solution heating for dissolving, and cooling is placed naturally, separates out crystallization, filters drying.
3, the described preparation method of claim 2, the by weight/volume of wherein said Febustat and aqueous ethanolic solution is 1: 20-80.
4, claim 2 or 3 described preparation methods, the concentration of wherein said aqueous ethanolic solution is 50-100%.
5, a kind of pharmaceutical composition is characterized in that said composition contains the described Febustat crystal of the claim 1 for the treatment of significant quantity and pharmaceutically acceptable one or more pharmaceutical carriers.
6, the described pharmaceutical composition of claim 5, composition wherein is for containing 1-240mg Febustat crystalline tablet, capsule, injection liquid or freeze-dried powder.
7, claim 5 or 6 described pharmaceutical compositions, composition wherein is for containing 20-120mg Febustat crystalline injection liquid or freeze-dried powder.
8, claim 5 or 6 described pharmaceutical compositions, composition wherein is for containing 20-120mg Febustat crystalline tablet or capsule.
9, the application of the defined Febustat crystal of claim 1 in preparation treatment hyperuricemia and relevant various illness medicines thereof.
10, the described application of claim 9, hyperuricemia wherein comprise former and secondary hyperuricemia; Described various illness comprises the acute and chronic gout that is caused by hyperuricemia, urarthritis, gouty nephropathy and urinary stone disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910068558A CN101525319A (en) | 2009-04-22 | 2009-04-22 | Febuxostat and drug combination thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910068558A CN101525319A (en) | 2009-04-22 | 2009-04-22 | Febuxostat and drug combination thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101525319A true CN101525319A (en) | 2009-09-09 |
Family
ID=41093414
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|---|---|---|---|
| CN200910068558A Pending CN101525319A (en) | 2009-04-22 | 2009-04-22 | Febuxostat and drug combination thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102070558B (en) * | 2009-11-23 | 2012-08-22 | 欣凯医药化工中间体（上海）有限公司 | New crystal form of febuxostat and preparation method thereof |
| WO2016091230A1 (en) | 2014-12-12 | 2016-06-16 | Zentiva, K.S. | Formulations containing a solid solution of febuxostat |
| CN113773361A (en) * | 2021-10-25 | 2021-12-10 | 深圳弘汇生物医药有限公司 | Compound for treating hyperuricemia, composition thereof, preparation method and medical application |
-
2009
- 2009-04-22 CN CN200910068558A patent/CN101525319A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102070558B (en) * | 2009-11-23 | 2012-08-22 | 欣凯医药化工中间体（上海）有限公司 | New crystal form of febuxostat and preparation method thereof |
| WO2016091230A1 (en) | 2014-12-12 | 2016-06-16 | Zentiva, K.S. | Formulations containing a solid solution of febuxostat |
| CN113773361A (en) * | 2021-10-25 | 2021-12-10 | 深圳弘汇生物医药有限公司 | Compound for treating hyperuricemia, composition thereof, preparation method and medical application |
| CN113773361B (en) * | 2021-10-25 | 2022-06-24 | 深圳弘汇生物医药有限公司 | Compound for treating hyperuricemia, composition thereof, preparation method and medical application |
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