WO2007048332A1 - Composition pharmaceutique pour le traitement de la goutte et sa preparation et son utilisation - Google Patents

Composition pharmaceutique pour le traitement de la goutte et sa preparation et son utilisation Download PDF

Info

Publication number
WO2007048332A1
WO2007048332A1 PCT/CN2006/002827 CN2006002827W WO2007048332A1 WO 2007048332 A1 WO2007048332 A1 WO 2007048332A1 CN 2006002827 W CN2006002827 W CN 2006002827W WO 2007048332 A1 WO2007048332 A1 WO 2007048332A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
febuxostat
composition according
benzbromarone
group
Prior art date
Application number
PCT/CN2006/002827
Other languages
English (en)
Chinese (zh)
Inventor
Jie Deng
Bin Fan
Caihua Mu
Yanye Zou
Original Assignee
Chongqing Pharmaceutical Research Institute Co., Ltd.
Shanghai Fosun Pharmaceutical (Group) Co., Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chongqing Pharmaceutical Research Institute Co., Ltd., Shanghai Fosun Pharmaceutical (Group) Co., Ltd filed Critical Chongqing Pharmaceutical Research Institute Co., Ltd.
Priority to CNA2006800400510A priority Critical patent/CN101296696A/zh
Publication of WO2007048332A1 publication Critical patent/WO2007048332A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • 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
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • 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

Definitions

  • the present invention relates to a pharmaceutical composition for treating gout, in particular a pharmaceutical composition comprising a therapeutically effective amount of febuxostat or a pharmaceutically acceptable salt thereof, or a solvate thereof and a uric acid excretion agent, and a process for the preparation thereof, and Use of the composition in the manufacture of a medicament for the treatment of gout.
  • a pharmaceutical composition for treating gout in particular a pharmaceutical composition comprising a therapeutically effective amount of febuxostat or a pharmaceutically acceptable salt thereof, or a solvate thereof and a uric acid excretion agent
  • Gout is a heterogeneous disease of tissue damage caused by increased blood uric acid. Increased blood uric acid is mainly associated with long-term dyslipidemia and/or reduced uric acid excretion. Earthworm is a component of the nucleus. As long as the food containing cells contains strontium, animal foods and legumes contain more strontium. Therefore, the occurrence of gout has a lot to do with people's diet. As the consumption of animal foods increases, the incidence of gout increases.
  • the cause of gout is that the sputum metabolism disorder causes the uric acid concentration in the blood to be too high, and the formation of uric acid crystals is deposited in the tissue.
  • Hyperuricemia is a prelude to gout. When gout occurs, the small joints of the big toe, the back of the foot, the heel, the ankle, the finger, the wrist, etc. may be red and swollen. Repeated episodes cause the joint to become deformed, resulting in a "goutstone.”
  • Gout is the most common arthritic disease in men over 40 years old and has been listed by the United Nations Health Organization as one of the top ten chronic diseases in the 20th century.
  • the latest domestic report by the Chinese Ministry of Health and the China Gout Alliance shows that in China, the incidence of gout is higher than the world average (3-9%) due to climate, eating habits, etc., and the number of gout patients in the country exceeds 0.9 billion.
  • anti-inflammatory drugs for treating acute gout mainly include colchicine, non-steroidal anti-inflammatory drugs and hormones.
  • the acute phase i1 ⁇ 2 needs to control the concentration of blood uric acid in the body.
  • drugs used to control blood uric acid levels in the body one of which is a drug that inhibits uric acid synthesis for decades.
  • the products available to patients on the market are only allopurinol, which have many side effects and are difficult for patients to tolerate, such as allergic rash, abdominal pain, diarrhea, white blood cells and thrombocytopenia, and even side effects such as liver damage.
  • One type of drug is uric acid excretion.
  • the drug has the advantage of not affecting the metabolism of purines and pyrimidines.
  • the clinical drugs are mainly benzbromarone and probenecid.
  • Probenecid also known as probalan
  • probalan is used to treat gout and has no effect on acute gout.
  • the drug is completely absorbed in the gastrointestinal tract, and its metabolites still have a uric acid action. Therefore, its maximum therapeutic effect occurs several days after taking the drug, and may have gastrointestinal reactions, fever of the rash, and few side effects such as liver and kidney dysfunction and blood system damage.
  • Benzbronarone also known as gout, is a derivative of benzofuran.
  • the drug has a strong blood uric acid lowering effect, and the mechanism of action is mainly to reduce the uric acid concentration in the blood by inhibiting the reabsorption of uric acid by the renal tubule.
  • Benzolamazole does not block the metabolism of purine nucleotides and is suitable for long-term treatment of hyperuricemia and gout. Less side effects can occasionally cause severe hepatitis and neutropenia.
  • the benzbromarone was first developed by the French company Labaz in the 1960s. It was listed in Germany in 1971 and has since been listed in Australia, Belgium, France, China and other countries.
  • Sulfinpyrazone is a potent uric acid excretion agent that lasts for 10 hours after one administration.
  • the drug is suitable for the treatment of chronic gout, has a weak anti-inflammatory and analgesic effect, and can inhibit platelet coagulation.
  • Febuxastat (English name: febuxostat) is another blood-lowering uric acid drug that inhibits uric acid synthesis. It is also a non-xanthine-based xanthine oxidase inhibitor. Its chemical structure is as follows:
  • U.S. Patent No. 5,614,520 discloses the use of febuxostat and its methods of preparation, as well as for the treatment of gout due to elevated blood uric acid.
  • Febuxostat reduces blood uric acid by inhibiting the activity of xanthine oxidase and preventing or reducing the synthesis of uric acid from hypoxanthine and xanthine.
  • Benzobromarone, probenecid and sulfinpyrazone mainly control blood uric acid level through uric acid excretion, so as to achieve the purpose of treating gout.
  • Ibubbuttan is used to treat gout by controlling the production of uric acid by inhibiting the production of uric acid.
  • the present invention provides a synergistic pharmaceutical composition for treating gout comprising a therapeutically effective amount of febuxostat or a pharmaceutically acceptable salt thereof or a solvate thereof and a uric acid excretion agent, and may also comprise a pharmaceutically acceptable Excipient or carrier.
  • the uric acid excretion agent of the present invention is selected from at least one of the following drugs: benzbromarone, c Hengshu, dipyridone.
  • a preferred uric acid excretion agent is at least one of benzbromarone and probenecid.
  • a more preferred acid excretion agent is benzbromarone.
  • a specific pharmaceutical composition of the present invention is a preparation containing febuxostat and benzbromarone.
  • the pharmaceutically acceptable salt of febuxostat may be an alkali metal or alkaline earth metal salt such as a sodium salt, a potassium salt, a calcium salt or the like, or an ammonium salt or an organic amine salt.
  • the weight ratio of febuxostat to the uric acid excretion agent is from 1:50 to 10:1, preferably from 1:25 to 3:1, more preferably from 1:7 to 2:1. Further preferably, it is 1:5-2:1.
  • the weight ratio of febuxostat to benzbromarone is from 1:2.5 to 4.8:1, preferably from 1:2.5 to 2.4:1, more preferably 1:2-2: 1.
  • the content of febuxostat may be 20 mg, 40 mg, 80 mg, 120 mg per 1 dose of the pharmaceutical composition, and the content of benzbromarone may be 25 mg, 40 mg> 50 mg, 80 mg, 100 mg, the amounts of the two active ingredients can be arbitrarily combined.
  • the non-buxostat is 80 mg or 120 mg, and the corresponding benzbromarone is 50 mg.
  • the content of febuxostat may be, for example, 20 mg, 40 mg, 80 mg, 120 mg per 1 dose of the pharmaceutical composition, and the content of the propionate may be 250 mg, 500 mg, of the two active ingredients.
  • the optional dosage can be combined in any combination.
  • febuxostat is 80 mg or 120 mg, and the corresponding propanol is 250 mg.
  • the content of febuxostat may be, for example, 20 mg, 40 mg, 80 mg, 120 mg per 1 dose of the pharmaceutical composition, and the content of the pirulone may be 100 mg, 200 mg, of the two active ingredients.
  • the optional dosage can be combined in any combination.
  • the above-mentioned dose of 1 can be understood as 1 tablet, 1 capsule, 1 bag, and 1 injection for different dosage forms.
  • the pharmaceutical composition of the present invention may be in the form of a tablet or a capsule, a buccal tablet, or an oral cavity.
  • Disintegrating tablets, oral instant tablets, tablets, chewables, granules, dry suspensions, injections, solutions, etc. may also be slow-translation agents, controlled release agents, immediate release sustained release preparations, such as sustained release tablets, glues Hey.
  • a preferred dosage form is a tablet or capsule.
  • the adjuvant or carrier is selected from the group consisting of fillers, disintegrators, binders, lubricants, wetting agents, and combinations thereof.
  • Other excipients may also contain flavoring agents, other surfactants, and excipients or carriers that can be used for injection.
  • the respective excipients can be selected according to different dosage forms of the pharmaceutical composition, and the preparation of the corresponding dosage forms can be carried out according to the conventional conventional techniques in the preparation of the preparation, and if necessary, coating can also be carried out.
  • the filler may be starch, modified starch, mannitol, sorbitol, lignocellulose, microcrystalline cellulose, lactose and carbonated hooks, which may be used alone or in combination. It is used in an amount of from 10% to 95.4%, preferably from 20% to 94.%, more preferably from 40% to 92.4%, based on the total weight of the pharmaceutical composition.
  • the binder may be hydroxypropylmethylcellulose, polyvinylpyrrolidone or polyvinyl alcohol, which may be used singly or in combination, in an amount of from 0 to 20%, preferably 0, based on the total weight of the pharmaceutical composition. %-15%, more preferably 0% -10%.
  • the disintegrant may be low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, sodium carboxymethyl starch, calcium carboxymethyl cellulose, starch, modified starch, croscarmellose sodium and Divinylpyrrolidone, which may be used singly or in combination, preferably low-substituted hydroxypropylcellulose and cross-linked polyvinylpyrrolidone, in an amount of from 0% to 40%, preferably from 1% to 30% based on the total weight of the pharmaceutical composition. %, more preferably 3% to -20%.
  • the lubricant may be magnesium stearate, stearic acid, palmitic acid, copper stearate and talc, which may be used singly or in combination, in an amount of about 0.01% by weight based on the total weight of the pharmaceutical composition. % is more preferably 0.1% to 3%.
  • the wetting agent may be water or ethanol; a flavoring agent such as aspartame or saccharin and its sodium salt
  • the present invention also provides a method of preparing a pharmaceutical composition of the present invention, comprising: stirring a mixture comprising a therapeutically effective amount of febuxostat or a pharmaceutically acceptable salt thereof or a solvate thereof and a uric acid excretion agent, and preparing the desired In the form of a formulation, wherein the mixture may also comprise a pharmaceutically acceptable adjuvant or carrier.
  • Another object of the present invention is to provide a use of the pharmaceutical composition of the present invention for the preparation of a medicament for treating gout. It can be used to treat gout caused by elevated blood uric acid levels and other causes.
  • Animal test demonstrates the administration of a formulation containing febuxostat and a urinary excretion drug (benbromumone, propyl sulphate or piracetone)
  • Febuxostat can be obtained by the method disclosed in U.S. Patent No. 5,614,520, and benzbromarone, probenecid, and sulfinpyrazone are commercially available. The resulting preparation can be administered only once a day, 1 dose unit at a time. detailed description
  • Example 1 Preparation of a formulation comprising benzbromarone and febuxostat
  • Example 3 Preparation of a formulation comprising sulfinpyrazone and febuxostat
  • Example 4 Preparation of a formulation containing sulfinpyrazone and febuxostat febuxostat 120g
  • Magnesium stearate 3 g was made into 1000 tablets. A tablet was prepared according to the procedure of Example 1.
  • Example 5 Preparation of a formulation containing probenecid and febuxostat febuxostat 80g
  • mice Seventy healthy male Wistar rats weighing (200 ⁇ 20) g were randomly divided into 7 groups (10 in each group): negative control group, hyperuricemia group (model group), benzene Bromomaron + febuxostat group A (low dose group), benzbromarone + febuxostat group B (middle dose group), benzbromarone + febuxostat group C (high dose group), The benzbromarone (positive drug) group and the febuxostat (positive drug) group. Animals were adapted to the environment for 1 week.
  • the negative control group was given CMC-Na emulsion (0.8%) 1 ml/100 g body weight ip (prepared in physiological saline) for 5 days, and the rats in each group were given 2.5% potassium oxonate 1 ml/100 g ip. After 1 hour, the same dose was administered by intragastric administration. One hour after the intragastric administration, each rat was sacrificed for blood sampling. The blood sample was placed in a 1.5 ml EP tube, incubated at 37 ° C for 30 minutes, and centrifuged at 2500 g X for 15 minutes. The supernatant was used for uric acid determination.
  • Potassium oxonate preparation 0.5% CMC-Na was used to prepare a 2.5% physiological saline emulsion, and was intraperitoneally injected at 250 mg/kg.
  • Blood uric acid was measured by a phytase-EHSPT method using a biochemical analyzer.
  • the serum uric acid level in the hyperuricemia group was significantly higher (P ⁇ 0.001), indicating successful modeling.
  • the middle dose group high The blood uric acid levels in the dose group, the benzbromarone group and the febuxostat group were significantly lower (P ⁇ 0.01, P ⁇ 0.001, P ⁇ 0.05, and P ⁇ 0.05, respectively), as shown in Table 1.
  • Low dose group blood Although the uric acid level decreased but not statistically significant ( ⁇ >0.05), the lowering of serum uric acid level in the middle and high dose groups was stronger than that of the benzbromarone or febuxostat alone.
  • the doses of benzbromarone or febuxostat in the group were lower than those in the group using benzbromarone or febuxostat, respectively, indicating that the effect of blood uric acid level in the combination was lower than that of phenyl bromide. Marlon group or febuxostat group.
  • Negative control group 10 ⁇ 135.65 ⁇ 9.27 Simple hyperuricemia group 10 ⁇ 274.38 ⁇ 21.34*** Low dose group 10 7.5 5:2.5 250.47 ⁇ 19.86 ⁇ medium dose group 10 15 10:5 242.56 ⁇ 21 ⁇ 45 ⁇ high dose group 10 30 20:10 221.59 ⁇ 16.32 ⁇ benzbromarone group 10 7 252 ⁇ 12 ⁇ 18.65 ⁇ His group 10 14 -254.32 ⁇ 19.43 ⁇ in the hyperuricemia group compared with the negative control group, ***: ⁇ ⁇ 0.001; compared with the group of hyperuricemia alone, ⁇ : ⁇ ⁇ 0.05; ⁇ : ⁇ 0.01; ⁇ : ⁇ ⁇ 0.001.
  • Formulations containing benzbromarone and febuxostat showed a strong lowering of uric acid, which was better than either benzbromarone or febuxostat alone, indicating a combination of febuxostat and benzbroma
  • the dragon has a synergistic effect and enhances the effect of lowering blood uric acid.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une composition pharmaceutique destiné au traitement de la goutte et son application dans la préparation de médicaments permettant de traiter cette maladie. Ladite composition pharmaceutique comprend une quantité effective de febuxostat ou ses sels ou solvates pharmaceutiques et une substance d’élimination de l’acide urique.
PCT/CN2006/002827 2005-10-26 2006-10-23 Composition pharmaceutique pour le traitement de la goutte et sa preparation et son utilisation WO2007048332A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNA2006800400510A CN101296696A (zh) 2005-10-26 2006-10-23 一种用于治疗痛风的药物组合物及其制备方法和用途

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CNA2005100573485A CN1954814A (zh) 2005-10-26 2005-10-26 一种具有协同作用治疗痛风的药物组合物及其制备方法
CN200510057348.5 2005-10-26

Publications (1)

Publication Number Publication Date
WO2007048332A1 true WO2007048332A1 (fr) 2007-05-03

Family

ID=37967410

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2006/002827 WO2007048332A1 (fr) 2005-10-26 2006-10-23 Composition pharmaceutique pour le traitement de la goutte et sa preparation et son utilisation

Country Status (2)

Country Link
CN (2) CN1954814A (fr)
WO (1) WO2007048332A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2881116A1 (fr) 2013-12-05 2015-06-10 Ranbaxy Laboratories Limited Composition de febuxostat

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101658520B (zh) * 2008-08-26 2011-07-27 天津泰普药品科技发展有限公司 用于治疗高尿酸血症的药物组合物
CN101658519B (zh) * 2008-08-26 2011-06-08 天津泰普药品科技发展有限公司 用于治疗高尿酸血症的药物组合物
CN101716132B (zh) * 2008-10-09 2012-01-11 北京方策方程医药科技有限公司 非布索坦肠溶制剂
CN101862326B (zh) * 2009-04-20 2013-12-04 北京德众万全药物技术开发有限公司 一种含非布索坦的药物组合物
CN101929988B (zh) * 2009-06-26 2014-05-07 北京德众万全药物技术开发有限公司 一种用高效液相色谱法测定非布索坦有关物质的方法
CN101953814A (zh) * 2009-07-17 2011-01-26 北京本草天源药物研究院 一种非布索坦固体制剂
CN102372679A (zh) * 2010-08-27 2012-03-14 北京润德康医药技术有限公司 一种非布司他水溶性衍生物及其制备方法
CN104042577B (zh) * 2014-06-13 2016-08-24 安徽省逸欣铭医药科技有限公司 一种稳定的托匹司他片及其制备方法
CN104856975A (zh) * 2015-05-26 2015-08-26 青岛海之星生物科技有限公司 一种丙磺舒缓释胶囊及制备方法
CN113425718A (zh) * 2021-05-13 2021-09-24 浙江歌文达生物医药科技有限公司 一种治疗高尿酸血症和痛风的复方制剂

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5614520A (en) * 1990-11-30 1997-03-25 Teijin Limited 2-arylthiazole derivatives and pharmaceutical composition thereof
CN1615875A (zh) * 2004-09-10 2005-05-18 武汉健民中药工程有限责任公司 一种含有别嘌醇和苯溴马隆的分散片

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5614520A (en) * 1990-11-30 1997-03-25 Teijin Limited 2-arylthiazole derivatives and pharmaceutical composition thereof
CN1615875A (zh) * 2004-09-10 2005-05-18 武汉健民中药工程有限责任公司 一种含有别嘌醇和苯溴马隆的分散片

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2881116A1 (fr) 2013-12-05 2015-06-10 Ranbaxy Laboratories Limited Composition de febuxostat

Also Published As

Publication number Publication date
CN101296696A (zh) 2008-10-29
CN1954814A (zh) 2007-05-02

Similar Documents

Publication Publication Date Title
WO2007048332A1 (fr) Composition pharmaceutique pour le traitement de la goutte et sa preparation et son utilisation
KR101697800B1 (ko) 니타족사니드의 서방성 제약 제형
US20100152250A1 (en) Capsule formulation of pirfenidone and pharmaceutically acceptable excipients
EA014707B1 (ru) Новая форма введения рацекадотрила
TW201302198A (zh) 含有納布啡（ｎａｌｂｕｐｈｉｎｅ）之藥學組成物及其用途
AU2018347990B2 (en) Bi-layer pharmaceutical tablet formulation
WO2008122190A1 (fr) Composition comprenant de la l-carnitine ou ses dérivés et son utilisation
CN101175477A (zh) 碘塞罗宁的控释药物组合物及其制备和使用方法
TWI784575B (zh) 一種複合物的藥物組合物及其製備方法
WO2010022580A1 (fr) Composé médicamenteux utilisé dans le traitement de l’hyperuricémie et ses applications
WO2010022581A1 (fr) Composition pharmaceutique destinée au traitement de l'hyperuricémie et son utilisation
CN111202731B (zh) 联合用药应用以及一种药用组合物及其应用
JP2001521553A (ja) ５−［４−［２−（ｎ−メチル−ｎ−２−ピリジル）アミノ）エトキシ］ベンジル］チアゾリジン−２，４−ジオンを含む組成物
CN110251473B (zh) 羟哌吡酮口服缓释制剂
AU2011339150B2 (en) Complex formulation comprising lercanidipine hydrochloride and valsartan and method for the preparation thereof
JP5504263B2 (ja) 高血圧と代謝症候群の治療に用いられる医薬組成物及びその使用
JP5241511B2 (ja) 溶出性の改善された医薬組成物
CN101982174A (zh) 一种镇咳平喘复方药物制剂的组方及其制备方法
WO2008148359A1 (fr) Utilisations thérapeutiques de dérivés d'acide imidazol-5-carboxylique
WO2005105109A1 (fr) Pastilles a liberation orale modifiee et leur procede de preparation
CN113425718A (zh) 一种治疗高尿酸血症和痛风的复方制剂
JP2023514786A (ja) 経口投与用の医薬組成物
JP2022541178A (ja) （ｓ）－３－アミノ－６－メトキシ－ｎ－（３，３，３－トリフルオロ－２－ヒドロキシ－２－メチルプロピル）－５－（トリフルオロメチル）ピコリンアミド製剤
JP2003519172A (ja) プラジカンテルを含む徐放性駆虫剤組成物
JPWO2004017954A1 (ja) ジクロフェナクの副作用軽減剤

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200680040051.0

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06805034

Country of ref document: EP

Kind code of ref document: A1