CN101296696A - Medicine composition for treating gout, method for making the same and the use thereof - Google Patents
Medicine composition for treating gout, method for making the same and the use thereof Download PDFInfo
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- CN101296696A CN101296696A CNA2006800400510A CN200680040051A CN101296696A CN 101296696 A CN101296696 A CN 101296696A CN A2006800400510 A CNA2006800400510 A CN A2006800400510A CN 200680040051 A CN200680040051 A CN 200680040051A CN 101296696 A CN101296696 A CN 101296696A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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Abstract
A pharmaceutical composition for treating gout and its application in preparation of medicines for treating gout are provided. The said pharmaceutical composition comprises effective amount of febuxostat or its pharmaceutical salts or its solvates and a uric acid eliminant.
Description
It is a kind of to be used to treat pharmaceutical composition of gout and its production and use technical field
The present invention relates to a kind of pharmaceutical composition for being used to treat gout, pharmaceutical composition specifically containing the Febustat of therapeutically effective amount or its officinal salt or its solvate and uricosuric eccritic and preparation method thereof, and purposes of the said composition in the medicine for preparing treatment gout.Background technology
Gout（GOUT it is) because blood uric acid increases Dao Zhi Group and knits damage mono- Group different substantiality diseases.Blood uric acid increases mainly relevant with long-term disorders of purine metabolism and/or underexcretion.Purine is a kind of composition in nucleus, as long as just to contain purine content in purine, animal food and bean food more for the food containing cell.Therefore, the generation of gout and the diet of people have much relations.Increase with the amount of animal food, the rise of the gout incidence of disease.
The pathogenic factor of gout is that purine metabolic disturbance causes the uric acid concentration in blood too high, during formation uric acid crystal Chen Ji Group are knitted.Hyperuricemia is the prelude of gout.When gout is broken out, big toe, instep, heel, ankle, refer to, the Minor articulus such as wrist is likely to red and swollen severe pain.Recurrent exerbation causes joint to become deformity, so as to form " tophus ".
Gout is the most common arthritis disease of more than 40 years old male, and one of big chronic disease of 20th century mankind ten is classified as by the United Nations's health organization.The China national Ministry of Public Health, the latest domestic report display of Chinese gout alliance organization：In China, the problems such as due to weather, eating habit, the incidence of disease of gout surpasses the world average level (3-9%), and national patient with gout is more than 0.9 hundred million people.
The anti-inflammatory drug for the treatment of acute gout mainly has colchicin, non-steroid anti-inflammatory drug and hormone at present.Acute stage i needs the concentration of blood uric acid in control volume.At present, 2 class medicines mainly are used for serum uric acid level in control volume, one of them is the medicine for suppressing uric acid synthesis, decades
Carrying out in the market is available for the product of patient selection there was only allopurinol, and drug side-effect is more and patient is difficult to be resistant to, such as allopurinol allergic rash, stomachache, diarrhoea, leucocyte and decrease of platelet, even there is the side effects such as hepatic disorder；Another kind of is the medicine of uricosuric excretion.The advantage of the medicine is not influence purine and pyrimidine metabolic.Clinical application is based on Benzbromarone and probenecid.
Probenecid (probenecid) is also known as benemid (probalan), for treating graceful property gout, to acute gout without effect.In gastrointestinal absorption completely, its metabolin still has uricotelism to the medicine.Therefore the effect of its maximum therapy betides a few days after medication, there can be gastrointestinal reaction, fash is generated heat, the side effect such as few liver and kidney dysfunctions and hematological.
Benzbromarone (benzbronarone) is also known as narcaricin, is the derivative of benzofuran.The medicine has very strong reduction blood uric acid effect, and mechanism of action is mainly by suppressing reabsorption of the renal tubule to uric acid, so as to reduce uric acid concentration in blood.Benzbromarone does not obstruct metabolism of purine nucleotide, it is adaptable to which chronicity treats hyperuricemia and goat.Side effect is less, and heavy type hepatitis and granulocyte can be caused to reduce once in a while.Benzbromarone is developed by French Labaz companies in the sixties earliest, is listed in Germany within 1971, hereafter respectively in multinational listings such as Australia, Belgium, France, China.
Sulfinpyrazone（Sulfinpyrazone it is) potent promotion uricosuric drug, once takes rear uricotelism sustainable 10 hours.The medicine is applied to treatment chronic gout, has faint anti-inflammatory and analgesic effect, can suppress coagulating platelets.
(English is general entitled for Febustat：Febuxostat it is) another blood uric acid medicine for suppressing uric acid synthesis, is also a kind of xanthine oxidase inhibitor of non-yellow fast alcohols of the mat woven of fine bamboo strips, its chemical structural formula is as follows：
Chemistry is entitled:2- [3- cyano group -4- (2- methyl propoxyl group) phenyl】- 4--5-thiazole carboxylic acids of methyl.
United States Patent (USP) US 5,614,520 discloses Febustat and preparation method thereof, and for treating the purposes of the gout caused by being raised because of blood uric acid.Febustat is by suppressing the activity of xanthine oxidase, preventing or reduce to synthesize uric acid by hypoxanthine, xanthine, so as to reach the effect of reduction blood uric acid.Contrast test and clinical test are shown in vitro, blood uric acid（SUA, better tolerance stronger than allopurinol) is acted on, serum uric acid level can be effectively controlled, so as to reach the purpose for the treatment of gout.Febustat is developed by Japanese Supreme Being people's pharmaceutical companies, is just being registered and is being listed in U.S. FDA.
Benzbromarone, probenecid, Sulfinpyrazone three mainly control serum uric acid level by uricosuric excretion, so as to reach the purpose for the treatment of gout.Febustat is then that serum uric acid level is controlled by suppressing the generation of uric acid, and reaches treatment pain wind action.Although they, which are administered alone, can reduce serum uric acid level, its effect being administered alone is unable to reach gratifying degree, and dosage is larger, causes many side effects so that patient's poor resistance, therefore is unfavorable for the therapeutic scheme of long period.Therefore, clinic needs better efficacy, few side effects, and tolerance is more preferable, to be adapted to the medicine of patient's long-term taking.
The research carried out through the present inventor is had shown that, the effect in blood obtained by uric acid level is reduced using the compound preparation of medicine is drained containing Febustat and ^ ^ acid and is substantially better than the effect for applying each individually dosed medicine.Febustat, which combines obtained pharmaceutical composition with medicine for improving uric acid excretion, makes the drug synergism of the different mechanism of action of two classes, can improve drug effect, while reducing the dosage of active medicine, reduces side effects of pharmaceutical drugs, this completes the present invention.The content of the invention
The invention provides a kind of pharmaceutical composition for being used to treat gout for having and acting synergistically, comprising the Febustat of therapeutically effective amount or its pharmaceutical salts or its solvate and uricosuric eccritic, pharmaceutically acceptable auxiliary material or carrier can also be included.
The uricosuric eccritic of the present invention is selected from least one of following medicines：Benzbromarone, third
Transverse Shu, Transverse pyrrones.
It is preferred that uricosuric eccritic be at least one of Benzbromarone and probenecid.The preferred sour eccritics of ^^ are Benzbromarone.The specific pharmaceutical composition of the present invention is the preparation containing Febustat and Benzbromarone.
The pharmaceutical salts of Febustat can be alkali metal or alkali salt such as sodium salt, sylvite, calcium salt etc., or ammonium salt, organic amine salt.
In the Yao Wu Group compounds of the present invention, the weight ratio of Febustat and uricosuric eccritic is 1:50-10:1, preferably 1:25-3:1, more preferably 1:7-2:1, it is further preferably 1:5-2:1.
In the preferred pharmaceutical compositions of the present invention, the weight ratio of Febustat and Benzbromarone is 1:2.5-4.8:1, preferably 1:2.5-2.4:1, more preferably 1:2-2:1.
According to above-mentioned weight ratio, in every 1 dosage pharmaceutical composition, the content of Febustat can be for example 20mg, 40 mg, 80 mg, 120mg, and the content of Benzbromarone can be 25 mg, 40 mg>50 mg, 80 mg, lOOmg, the consumption of both active components can be combined.It is preferred that Febustat is 80 mg or 120 mg, corresponding Benzbromarone is 50 mg.
According to above-mentioned weight ratio, in every 1 dosage pharmaceutical composition, the content of Febustat for example can be that the easypro content of 20mg, 40 mg, 80 mg, 120mg , Bing Continued can be 250mg, 500mg, and the optional consumption of both active components can be combined.It is preferred that Febustat is 80 mg or 120 mg, corresponding third horizontal relaxes for 250 mg.
According to above-mentioned weight ratio, in every 1 dosage pharmaceutical composition, the content of Febustat for example can be 20mg, 40 mg, 80 mg, and the content of 120mg , Continued pyrrones can be 100mg, 200mg, and the optional consumption of both active components can be combined.
Above-mentioned 1 described dosage according to different formulations can be regarded as 1,1 glue it is former, 1 bag, parenteral solution can be 1 etc..
The pharmaceutical composition of the present invention, its dosage form can be tablet or glue Nang, buccal tablet, oral cavity
Disintegrated tablet, oral instant-dissolving tablet, piece, masticatory, granule, dry suspensoid agent, injection, solution etc., or Slow translate agent, controlled release agent, quick-release Slow release formulations, and such as Slow releases piece, glue Nang.It is preferred that formulation be tablet or glue Nang.
In the pharmaceutical composition of the present invention, described auxiliary material or carrier is selected from：Filler, disintegrant, adhesive, lubricant, wetting agent and combinations thereof.Other auxiliary materials can also include flavouring, other surfactants and auxiliary material or carrier available for injection.Corresponding auxiliary material may be selected according to the different dosage forms of pharmaceutical composition, the preparation of corresponding formulation can be realized according to the existing conventional techniques in terms of preparation preparation, can also be coated if necessary.
In the Pharmaceutical composition of the present invention, described filler can be starch, converted starch, mannitol, sorbierite, lignocellulosic, microcrystalline cellulose, lactose and carbonic acid hook, they, which can be used alone, to be used in mixed way, its consumption is about the 10%-95.4% of pharmaceutical composition gross weight, preferably 20%-94.2%, more preferably 40%-92.4%.
Described adhesive can be HPMC, polyvinylpyrrolidone, polyvinyl alcohol, they, which can be used alone, to be used in mixed way, its consumption is about the 0-20% of pharmaceutical composition gross weight, preferably 0%-15%, more preferably 0 % -10%.
Described disintegrant can be low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose, sodium carboxymethyl starch, calcium carboxymethylcellulose, starch, converted starch, Ac-Di-Sol and PVPP, they, which can be used alone, to be used in mixed way, it is preferred that low-substituted hydroxypropyl cellulose and PVPP, its consumption is about the 0%-40% of pharmaceutical composition gross weight, preferably 1%-30%, more preferably 3 % -20%.
Described lubricant can be magnesium stearate, stearic acid, palmitic acid, copper stearate and talcum powder, and they, which can be used alone, to be used in mixed way, and its consumption is about the 0.01%-10% of pharmaceutical composition gross weight, more preferably 0.1%-3%.
Described wetting agent can be water or ethanol；Flavouring such as Aspartame or saccharin and its sodium salt
The present invention also provides the method for preparing the pharmaceutical composition of the present invention, including the mixture comprising the Febustat of therapeutically effective amount or its pharmaceutical salts or its solvate and uricosuric eccritic is stirred, and required dosage form is made, wherein the mixture can also include pharmaceutically acceptable auxiliary material or carrier.
It is a further object of the present invention to provide application of the pharmaceutical composition of the present invention in the medicine for preparing treatment gout.Available for treatment gout caused by uric acid concentration rise in blood and other reasons.
Animal experiment is proved：Using the preparation comprising Febustat Yu medicine for improving uric acid excretion (Benzbromarone, Bing Transverse Shu Huo Continued pyrrones)
With it is quick.Febustat can be according to United States Patent (USP) US 5, and method disclosed in 614,520 is made, and Benzbromarone, probenecid, Sulfinpyrazone are commercially available.Gained preparation daily can only administration 1 time, every time 1 dosage unit.Embodiment
Following examples are not limit the scope of the invention to elaborate and understand the present invention.
Embodiment 1:The preparation of preparation comprising Benzbromarone and Febustat
Febustat 80g
Benzbromarone 50g
Lactose 80g
Microcrystalline cellulose 30g
10% polyvinyl pyrrole protective embankment ketone solution is appropriate
Sodium carboxymethyl starch 10g
Magnesium stearate 2.5g
It is made 1000
Febustat, Benzbromarone, lactose and microcrystalline cellulose are mixed, appropriate 10% polyvinylpyrrolidonesolution solution is then added, stirs, is dried after sieving, carboxylic Yue bases sodium starch and the well mixed rear tabletting of magnesium stearate is added.The preparation of preparation of the embodiment 2 comprising Benzbromarone and Febustat
Febustat 120g
Benzbromarone 50g
Lactose 80g
Microcrystalline cellulose 30g
10% polyvinyl pyrrole hole ketone solution is appropriate
Carboxylic Yue base sodium starch 10g
Magnesium stearate 2.9g
It is made 1000
Piece agent is prepared by the technique of embodiment 1.The preparation of preparation of the embodiment 3 comprising Sulfinpyrazone and Febustat
Febustat 80g
Transverse pyrrones 100g
Lactose 80g
Microcrystalline cellulose 30g
10% polyvinylpyrrolidonesolution solution is appropriate
Carboxylic Yue base sodium starch 10g
Magnesium stearate
1000 technique by embodiment 1 is made and prepares piece agent.Preparation of the embodiment 4 comprising Sulfinpyrazone and Febustat prepares Febustat 120g
Continued pyrrones 100g
Lactose 80g
Microcrystalline cellulose 30g
10% polyvinyl pyrrole ridge ketone solution is appropriate
Sodium carboxymethyl starch 10g
Magnesium stearate 3g is made 1000 technique by embodiment 1 and prepares piece agent.Preparation of the embodiment 5 comprising probenecid and Febustat prepares Febustat 80g
Probenecid 250g
L 80g
Microcrystalline cellulose 60g
10% polyvinyl pyrrole Burn ketone solution is appropriate
Sodium carboxymethyl starch 20g
Magnesium stearate 5g
It is made 1000
Piece agent is prepared by the technique of embodiment 1.The test of pesticide effectiveness
Material and method
1st, animal：Choosing body weight is（200 ± 20) g healthy male Wistar rat 70, is randomly divided into 7 groups（Every group 10）：Negative control group, simple hyperuricemia group（Model group）, Benzbromarone+Febustat group A (low dose groups）, Benzbromarone+Febustat group B (middle dose groups）, Benzbromarone+Fei Busita Group C (high dose groups）, Benzbromarone（Positive drug）Group and Febustat（Positive drug）Group.Animal adapts to environment 1 week after fetching.
2nd, trial drug and instrument：
Trial drug：Preparation comprising Benzbromarone and Febustat【Febustat:Benzbromarone=2:1 (weight ratio) 1.
Benzbromarone and Febustat are provided by Chongqing Medicine Industry Academe Co., Ltd.Oxygen urushic acid potassium, is provided, lot number by Aldrich Chemical Compan: 04328DO-231.Sodium carboxymethylcellulose（CMC-Na, is analyzed pure）, provided by Chinese Shanghai Heng Xi Chemical Companies.
The automatic clinical chemistry analyzer of Hitachi 7020, Japan's production.
3rd, experiment weighs rat body weight in first 1 day, determines dosage.Low dose group is administered
7.5mg/ kg (Febustat is that 5 mg/kg, Benzbromarone are 2.5 mg/kg), middle Ji Liang Group administrations 15mg/kg(Febustat is that 10 mg/kg, Benzbromarone are 5 mg/kg), high dose group administration 30mg/kg (Febustat is that 20 mg/kg, Benzbromarone are 10 mg/kg) (are configured to the suspension that concentration is respectively 0.75mg/ml, 1.5mg/mK 3.0mg/ml with 0.8% CMC-Na）；
Negative control group, simple hyperuricemia group give 0.8%CMC-Na emulsions；Benzbromarone group administration 7mg/kg (suspension that concentration is 0.7mg/ml is configured to 0.8% CMC-Na), Febustat group administration 14mg/kg (suspension that concentration is 1.4mg/ml is configured to 0.8% CMC-Na), administered volume is lml/lOOg body weight, successive administration 4 days.CMC-Na emulsions (0.8%) lml/100g body weight i.p (normal salines are given within 5 days to negative control group in the mat woven of fine bamboo strips）, its She's each group gives 2.5% Oteracil Potassium lml/100g i.p.After 1 hour 1 hour after the same gastric infusion, gastric infusion, each rat tail is taken into blood, blood sample is placed in 1.5ml EP pipes, 37 °C incubate 30 minutes, and 2500g X 15min centrifuging and takings supernatant is used for testing uric acid.
4th, Oteracil Potassium is prepared：The physiological saline emulsion suspension liquid of final concentration 2.5% is made into 0.8%CMC-Na, is injected intraperitoneally by 250mg/kg.
5th, blood uric acid is determined according to uricase-EHSPT methods using Biochemical Analyzer.
Result of the test
Simple hyperuricemia group serum uric acid level compared with negative control group is increased significantly ((P<0.001) modeling success, is illustrated.After drug-treated, compared with simple hyperuricemia group, middle dose group, high dose group, the serum uric acid level of Benzbromarone group and Febustat group have substantially reduction (to be respectively P<0.01、 P<0.001、 P<0.05 and P<0.05) it, see the table below 1.Though low dose group serum uric acid level has decline but not statistically significant (Ρ>0. 05), and the serum uric acid level reducing effect of middle and high dosage group is all strong compared with the group that Benzbromarone or Febustat is used alone.In addition, the dosage of Benzbromarone or Febustat in middle dose group is respectively smaller than the dosage being used alone in the group of Benzbromarone or Febustat, shows that the serum uric acid level drop 4Shi effects of compound preparation are actually respectively greater than Benzbromarone group or Febustat group.
Meanwhile, result of the test shows that Fu Fang Ji Group processed do not have obvious Side effect.
In addition, not finding there is reaction, better stability of preparation between Benzbromarone and Febustat in the preparation comprising Benzbromarone and Febustat yet.The bright compatibilities therebetween of Silk are good.
The comparison of the serum uric acid level of table 1.
Number of animals dosage Febustat:Benzbromarone serum uric acid level group
(only） ( mg/kg ) (mg/kg:Mg/kg) (μ ι η ο Ι/L) 10-- 274.38 ± 21.34*** of simple hyperuricemia group of negative control group 10-- 135.65 ± 9.27 low dose groups 10 7.5 5:2.5 250.47 ± 19.86 Δ middle dose groups 10 15 10:5 242.56 ± 2145 Δ Δ high dose groups 10 30 20:The simple hyperuricemia group of Δ of 10 221.59 ± 16.32 10 71 25212 ± 18.65 Δ Febustat group of Δ Δ Α Benzbromarones group 10 14 1 254.32 ± 19.43 is compared with negative control group, * * *:Ρ<0.001;Each group is compared with simple hyperuricemia group, Δ:Ρ<0.05; ΔΔ:Ρ<0.01; ΔΔΔ:Ρ<0.001.Formulations display comprising Benzbromarone and Febustat goes out stronger blood uric acid effect, it is acted on will be good than Benzbromarone or Febustat is used alone, show that Febustat and Benzbromarone, which is used in combination, has synergy, enhances the effect of reduction blood uric acid.
Claims (13)
- Claim1st, a kind of pharmaceutical composition for being used to treat gout, includes the Febustat of therapeutically effective amount or its pharmaceutical salts or its solvate and uricosuric eccritic.2nd, the pharmaceutical composition according to claim 1, wherein the uricosuric eccritic is selected from least one of Benzbromarone, probenecid and Sulfinpyrazone.3rd, the pharmaceutical composition according to claim 2, wherein ^ ^ acid eccritics are to be selected from least one of Benzbromarone and probenecid.4th, pharmaceutical composition according to claim 3, wherein the uricosuric eccritic is Benzbromarone.5th, pharmaceutical composition according to claim 1, wherein the pharmaceutical salts of the Febustat are to be selected from least one of alkali metal or alkali salt, ammonium salt, organic amine salt.6th, pharmaceutical composition according to claim 5, wherein the alkali metal or alkali salt of the Febustat are selected from least one of sodium salt, sylvite and calcium salt.7th, the weight ratio of the pharmaceutical composition according to claim 1, wherein Febustat and uricosuric eccritic is 1:50-10:1.8th, the weight ratio of pharmaceutical composition according to claim 7, wherein Febustat and uricosuric eccritic is 1:25-3:1.9th, the weight ratio of pharmaceutical composition according to claim 8, wherein Febustat and uricosuric eccritic is 1:7-2:1.10th, the weight ratio of pharmaceutical composition according to claim 4, wherein Febustat and Benzbromarone is 1:2.5-4.8:1.11st, the weight ratio of pharmaceutical composition according to claim 10, wherein Febustat and Benzbromarone is 1:2.5-2.4:1.12nd, Yao Wu Group compounds according to claim 11, wherein Febustat and benzene bromine horse Grand weight ratio is 1:1-2:1.13rd, pharmaceutical composition according to claim 1, also comprising pharmaceutically acceptable auxiliary material or carrier.14th, the pharmaceutical composition according to any one of preceding claims, its dosage form is tablet, glue Nang, buccal tablet, oral disnitegration tablet, oral instant-dissolving tablet, ^^ pieces, masticatory, granule, dry suspensoid agent, injection, solution, Slow release agent, controlled release agent or quick-release Slow release formulations.15th, the pharmaceutical composition according to any one of preceding claims is preparing the purposes in being used to treat the medicine of gout.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510057348.5 | 2005-10-26 | ||
| CNA2005100573485A CN1954814A (en) | 2005-10-26 | 2005-10-26 | Medical composite with co-action for treating gout and its preparation method |
| PCT/CN2006/002827 WO2007048332A1 (en) | 2005-10-26 | 2006-10-23 | A pharmaceutical composition for treating gout and its preparation and use |
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| Publication Number | Publication Date |
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| CN101296696A true CN101296696A (en) | 2008-10-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2005100573485A Pending CN1954814A (en) | 2005-10-26 | 2005-10-26 | Medical composite with co-action for treating gout and its preparation method |
| CNA2006800400510A Pending CN101296696A (en) | 2005-10-26 | 2006-10-23 | Medicine composition for treating gout, method for making the same and the use thereof |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2005100573485A Pending CN1954814A (en) | 2005-10-26 | 2005-10-26 | Medical composite with co-action for treating gout and its preparation method |
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| CN (2) | CN1954814A (en) |
| WO (1) | WO2007048332A1 (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101658519B (en) * | 2008-08-26 | 2011-06-08 | 天津泰普药品科技发展有限公司 | Medicinal composition for treating hyperuricemia |
| CN101658520B (en) * | 2008-08-26 | 2011-07-27 | 天津泰普药品科技发展有限公司 | Medicinal composition for treating hyperuricemia |
| CN101716132B (en) * | 2008-10-09 | 2012-01-11 | 北京方策方程医药科技有限公司 | Febuxostat enteric preparation |
| CN101862326B (en) * | 2009-04-20 | 2013-12-04 | 北京德众万全药物技术开发有限公司 | Medicine compound containing febuxostat |
| CN101929988B (en) * | 2009-06-26 | 2014-05-07 | 北京德众万全药物技术开发有限公司 | Method for detecting febuxostat-associated matters by using high performance liquid chromatography |
| CN101953814A (en) * | 2009-07-17 | 2011-01-26 | 北京本草天源药物研究院 | Febuxostat solid preparation |
| CN102372679A (en) * | 2010-08-27 | 2012-03-14 | 北京润德康医药技术有限公司 | Febuxostat water-soluble derivative and preparation method thereof |
| EP2881116A1 (en) | 2013-12-05 | 2015-06-10 | Ranbaxy Laboratories Limited | Febuxostat composition |
| CN104042577B (en) * | 2014-06-13 | 2016-08-24 | 安徽省逸欣铭医药科技有限公司 | A kind of stable Topiroxostat tablet and preparation method thereof |
| CN104856975A (en) * | 2015-05-26 | 2015-08-26 | 青岛海之星生物科技有限公司 | Probenecid slow release capsule and preparation method thereof |
| CN113425718A (en) * | 2021-05-13 | 2021-09-24 | 浙江歌文达生物医药科技有限公司 | Compound preparation for treating hyperuricemia and gout |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE122008000051I1 (en) * | 1990-11-30 | 2009-02-05 | Teijin Ltd | 2-ARYLTHIAZOL DERIVATIVE AND MEDICAMENT CONTAINING THEREOF |
| CN1615875A (en) * | 2004-09-10 | 2005-05-18 | 武汉健民中药工程有限责任公司 | Dispersive tablet having allopurinol and benzbromarone |
-
2005
- 2005-10-26 CN CNA2005100573485A patent/CN1954814A/en active Pending
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2006
- 2006-10-23 CN CNA2006800400510A patent/CN101296696A/en active Pending
- 2006-10-23 WO PCT/CN2006/002827 patent/WO2007048332A1/en active Application Filing
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| Publication number | Publication date |
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| CN1954814A (en) | 2007-05-02 |
| WO2007048332A1 (en) | 2007-05-03 |
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