Nothing Special   »   [go: up one dir, main page]

CN1826146B - 抗菌活性成分在pmma骨粘固剂中的用途 - Google Patents

抗菌活性成分在pmma骨粘固剂中的用途 Download PDF

Info

Publication number
CN1826146B
CN1826146B CN2004800207073A CN200480020707A CN1826146B CN 1826146 B CN1826146 B CN 1826146B CN 2004800207073 A CN2004800207073 A CN 2004800207073A CN 200480020707 A CN200480020707 A CN 200480020707A CN 1826146 B CN1826146 B CN 1826146B
Authority
CN
China
Prior art keywords
bone cement
polyhexamethylene biguanide
cement
weight
concentration
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Fee Related
Application number
CN2004800207073A
Other languages
English (en)
Other versions
CN1826146A (zh
Inventor
弗兰克·席尔克
贝特霍尔德·尼斯
汉斯·皮奇
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biomet Deutschland GmbH
Original Assignee
Biomet Deutschland GmbH
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 Biomet Deutschland GmbH filed Critical Biomet Deutschland GmbH
Publication of CN1826146A publication Critical patent/CN1826146A/zh
Application granted granted Critical
Publication of CN1826146B publication Critical patent/CN1826146B/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
    • A61L2300/206—Biguanides, e.g. chlorohexidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials For Medical Uses (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Curing Cements, Concrete, And Artificial Stone (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

本发明涉及聚亚己基双胍在PMMA骨粘固剂中的用途，所述骨粘固剂优选不含有抗生素。所述粘固剂中的活性成分浓度不超过粘固剂总重量的1重量％，这个浓度足以阻止粘固剂表面的细菌的繁殖。所述粘固剂并不导致治疗过程耐药性变化。

Description

抗菌活性成分在PMMA骨粘固剂中的用途
本发明涉及抗菌活性成分在聚甲基丙烯酸甲酯骨粘固剂(PMMA粘固剂)中的用途，所述活性成分浓度足以阻止粘固剂表面的细菌繁殖。
传统的含有药剂的骨粘固剂由粉状药剂分散在其中的PMMA或PMMA共聚物粉末组成。单体液体(和催化剂)混合之后，发生聚合反应。然后凝固的骨粘固剂成为聚合物块，药剂在其表面层上释放。
为了防止粘固剂和/或邻近组织的细菌繁殖所引起的脓毒性炎症，抗生素被作为药剂用于传统的骨粘固剂。但是，骨粘固剂中抗生素的广泛使用逐渐地导致耐抗生素细菌菌株的发展，这意味着在某些环境中不再可能完全防止伤口感染。同样地，使用更新的抗生素同样不是长期的解决方法，因为抵抗新药剂的细菌菌株将在可预见的将来形成。
EP701824(Merck Patent GmbH)描述了含有活性成分的骨粘固剂的制备方法，其中也包括抗生素或抗菌剂。
WO98/07456(Merck Patent GmbH)涉及含有活性成分的骨粘固剂和骨替代材料或可植入的药物储库的制备工艺，在其中同样包含抗生素或抗菌剂。
EP202445(Merck Patent GmbH)涉及一种可植入体内用于控制细胞抑制剂的延迟释放的药物储库，除了细胞抑制剂，这种药物储库同样含有抗生素和/或抗菌剂。
EP234004(Merck Patent GmbH)描述了一种用于增加或增长化学治疗剂作用的含有抗生素和抗菌剂的可植入药物储库。
本发明的目的是，在对粘固剂表面的抗菌作用没有负面影响的情况下使用一种新的药剂代替传统骨粘固剂中的抗生素。因为不同的作用原理，所述的新药剂能够长期阻止耐药性细菌的形成。这种新药剂的性质和浓度应该在确保抗菌性但对伤口治疗没有明显削弱的条件下进行选择。
通过在PMMA骨粘固剂中使用浓度足以阻止粘固剂表面的细菌繁殖的抗菌活性成分，来达到本发明目的。优选地，PMMA骨粘固剂中不含有抗生素。
合适的抗菌剂是下列各组化合物：
●季铵化合物，例如磺乙基(ethosulfate)十六烷基二甲基乙基铵或氯化二癸基二甲基铵，
●胺氧化物，例如N-烷基(C10-C18)-N，N-二甲基胺N-氧化物或N-烷基(C10-C18)-N，N-二乙基胺N-氧化物，
●吡啶衍生物，例如奥替尼啶二氢氯化物，
●胍，例如聚亚己基双胍氢氯化物，和/或
●10-十一烯酸酰胺，例如10-十一烯酸N-乙醇酰胺(ethanolamide)。
优选添加最大重量百分比为1％(基于粘固剂的总重量)的聚亚己基双胍。进一步优选最大重量百分比为0.5％，更优选重量百分比为0.025-0.5％。最优选的聚亚己基双胍的最大重量百分比为0.155％。依据本发明，也可以添加一种以上的抗菌剂活性成分。
对比试验的结果：
Figure A20048002070700051
                       图1a
                       图1b
如图1a和1b所示，在PMMA骨粘固剂(纯PALAMED
Figure 200480020707310000210003_0
)中仅混合重量百分比0.155％的聚亚己基双胍对于阻止粘固剂表面的细菌的繁殖的效果相当于(或高于)混合了重量百分比0.86％的庆大霉素(抗生素)的对照物的效果。
本发明的骨粘固剂产品在两个实施例中进行更详细的描述。
实施例1：
将97.3mg的聚亚己基双胍氢氯化物混入18.8g的Palamed的液体(由甲基丙烯酸甲酯，N，N-二甲基-p-甲苯胺和染料组成)中。依照制造商说明在真空混合系统中把该均匀溶液与44g的Palamed粉末(纯的；无庆大霉素)相混合。混合物被引入模具然后固化。
实施例2：
将5.3g的二氧化锆混入在400mg水中含有97.3mg的聚亚己基双胍氢氯化物的溶液中。通过冷冻干燥去除水。含有抗菌剂的二氧化锆随后与38.3g的聚(甲基丙烯酸甲酯共聚丙烯酸甲酯)以及0.44g的过氧化二苯酰相混合。得到的粉末被加到在18.4g甲基丙烯酸甲酯中含有0.4g的N，N-二甲基-p-甲苯胺的溶液中，然后两者充分混合。混合物被引入模具然后固化。

Claims (9)

1.抗细菌聚亚己基双胍在PMMA骨粘固剂中的用途，骨粘固剂中该活性成分的浓度最大为所述粘固剂总量的1重量％，其足以阻止所述粘固剂表面的细菌的繁殖。
2.根据权利要求1所述的聚亚己基双胍在PMMA骨粘固剂中的用途，其中PMMA骨粘固剂中不包含抗生素。
3.根据权利要求1或2所述的聚亚己基双胍的用途，其在长期使用中对伤口的愈合过程无负面影响，并且没有明显地削弱所述骨粘固剂的固化过程。
4.根据权利要求1或2所述的用途，其中聚亚己基双胍的重量百分比为所述粘固剂总量的0.025％至0.5％。
5.根据权利要求4所述的用途，其中聚亚己基双胍的重量百分比最大为所述粘固剂总量的0.155％。
6.由根据权利要求1至5任一项所述的骨粘固剂制备的医用植入物。
7.一种包含聚亚己基双胍的PMMA骨粘固剂，其中所述聚亚己基双胍的浓度最大为1重量％。
8.根据权利要求7的骨粘固剂，其中聚亚己基双胍的浓度为0.025重量％至0.5重量％。
9.根据权利要求8的骨粘固剂，其中聚亚己基双胍的浓度为0.155重量％。
CN2004800207073A 2003-07-18 2004-07-16 抗菌活性成分在pmma骨粘固剂中的用途 Expired - Fee Related CN1826146B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10332680.4 2003-07-18
DE10332680A DE10332680A1 (de) 2003-07-18 2003-07-18 Verwendung von antiseptischen Wirkstoffen in PMMA-Knochenzementen
PCT/DE2004/001571 WO2005009495A1 (de) 2003-07-18 2004-07-16 Verwendung von antiseptischen wirkstoffen in pmma-knochenzementen

Publications (2)

Publication Number Publication Date
CN1826146A CN1826146A (zh) 2006-08-30
CN1826146B true CN1826146B (zh) 2010-12-01

Family

ID=34071754

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2004800207073A Expired - Fee Related CN1826146B (zh) 2003-07-18 2004-07-16 抗菌活性成分在pmma骨粘固剂中的用途

Country Status (15)

Country Link
US (1) US20060275339A1 (zh)
EP (1) EP1648531B1 (zh)
JP (1) JP2006528008A (zh)
CN (1) CN1826146B (zh)
AT (1) ATE409499T1 (zh)
AU (1) AU2004259159B2 (zh)
CA (1) CA2531488C (zh)
CY (1) CY1108640T1 (zh)
DE (2) DE10332680A1 (zh)
DK (1) DK1648531T3 (zh)
ES (1) ES2313046T3 (zh)
PL (1) PL1648531T3 (zh)
PT (1) PT1648531E (zh)
SI (1) SI1648531T1 (zh)
WO (1) WO2005009495A1 (zh)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4907643B2 (ja) * 2005-03-07 2012-04-04 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 医療用インプラント
DE102005048131A1 (de) * 2005-10-06 2007-04-12 Bayer Innovation Gmbh Antimikrobielle Kunststoffzusammensetzung mit niedriger Elutionsrate und langer Wirksamkeit
DE102008021473A1 (de) * 2008-04-29 2009-11-12 Heraeus Kulzer Gmbh Mit Antiplaque-Wirkstoff(en) ausgestattete Dentalmaterialien
WO2009143236A1 (en) * 2008-05-20 2009-11-26 Albert Einstein Healthcare Network Compositions and methods for the treatment of skeletal metastatic lesions and fractures
DE102009004368A1 (de) * 2009-01-08 2010-07-15 Heraeus Kulzer Gmbh Dentalmaterialien enthaltend antimikrobielle Wirkstoffe zur Verhinderung von Plaque-Anlagerungen
DE102009035970A1 (de) * 2009-08-04 2011-02-17 Heraeus Kulzer Gmbh Antimikrobiell ausgestattete Dentalmaterialien, insbesondere zur Verhinderung von Plaqueanlagerungen
EP2384733B1 (de) * 2010-05-07 2016-07-27 Ivoclar Vivadent AG Antimikrobielle Dentalwerkstoffe
US8834772B2 (en) 2011-12-07 2014-09-16 Biomet Manufacturing, Llc Antimicrobial methacrylate cements
DE102012022419A1 (de) 2012-11-16 2014-05-22 Heraeus Medical Gmbh Antiseptischer Polymethylmethacrylat-Knochenzement
DE102016212091A1 (de) 2016-07-04 2018-01-04 Heraeus Medical Gmbh Antiseptischer Polymethylmethacrylat-Knochenzement
CN114053477B (zh) * 2020-08-03 2023-06-06 首都医科大学附属北京朝阳医院 一种抗骨髓瘤纳米骨水泥及其制备方法与应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4797282A (en) * 1985-04-18 1989-01-10 Merck Patent Gesellschaft Mit Beschrankter Haftung Drug depot containing cytostatics
EP0450117A1 (de) * 1990-04-02 1991-10-09 Infectless S.A. Ringerlösung und dessen Anwendung als bakterizid wirkendes lokales Wundbehandlungsmedikament
US5942218A (en) * 1993-05-26 1999-08-24 Fresenius Ag Anti-infective material
EP0985413A1 (de) * 1998-08-06 2000-03-15 Jörg Michael Dr. Dr. Schierholz Medizinprodukte mit retardierter pharmakologischer Aktivität und Verfahren zu ihrer Herstellung
WO2001012242A1 (de) * 1999-08-14 2001-02-22 Ivoclar Vivadent Ag Zusammensetzung zur implantation in den menschlichen und tierischen körper
WO2002013871A2 (en) * 2000-08-15 2002-02-21 Surmodics, Inc. Medicament incorporation matrix
US6494717B1 (en) * 1998-09-24 2002-12-17 Advantage Dental Products, Inc. Calcified tissue facing preparation containing an antimicrobial agent

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL98435C (zh) * 1954-09-10
DE3542972A1 (de) * 1985-12-05 1987-06-11 Merck Patent Gmbh Pharmakadepot
US5019096A (en) * 1988-02-11 1991-05-28 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US5143934A (en) * 1990-11-21 1992-09-01 A/S Dumex (Dumex Ltd.) Method and composition for controlled delivery of biologically active agents
GB9322137D0 (en) * 1993-10-27 1993-12-15 Logical Water Limited A system and method for defining a process structure for performing a task
US6046143A (en) * 1994-08-22 2000-04-04 Becton Dickinson And Company Water soluble lubricant for medical devices
DE19641775A1 (de) * 1996-08-22 1998-02-26 Merck Patent Gmbh Verfahren zur Herstellung von wirkstoffhaltigen Knochenzementen
DE19718648A1 (de) * 1997-05-02 1998-11-05 Merck Patent Gmbh Verfahren und Vorrichtung zur Herstellung von steril verpacktem Knochenzement
US6245111B1 (en) * 1997-05-12 2001-06-12 Richard L. Shaffner Method and apparatus for fighting infection and maintaining joint spacing in a prosthesis implant area
US5980573A (en) * 1997-05-12 1999-11-09 Shaffner; Richard L. Method and apparatus for fighting infection and maintaining joint spacing in a prosthesis implant area
AUPO907697A0 (en) * 1997-09-09 1997-10-02 Day, Robert Edward Chemical supplementation of bone
US6020396A (en) * 1998-03-13 2000-02-01 The Penn State Research Foundation Bone cement compositions
AU5814699A (en) * 1998-09-08 2000-03-27 Microban Products Company Antimicrobial acrylic material
ES2192141B1 (es) * 2002-02-08 2005-02-16 Consejo Sup. Investig. Cientificas Formulaciones acrilicas de curado en frio con activadores derivados de diaminodifenilcarbinol de baja toxicidad.

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4797282A (en) * 1985-04-18 1989-01-10 Merck Patent Gesellschaft Mit Beschrankter Haftung Drug depot containing cytostatics
EP0450117A1 (de) * 1990-04-02 1991-10-09 Infectless S.A. Ringerlösung und dessen Anwendung als bakterizid wirkendes lokales Wundbehandlungsmedikament
US5942218A (en) * 1993-05-26 1999-08-24 Fresenius Ag Anti-infective material
EP0985413A1 (de) * 1998-08-06 2000-03-15 Jörg Michael Dr. Dr. Schierholz Medizinprodukte mit retardierter pharmakologischer Aktivität und Verfahren zu ihrer Herstellung
US6494717B1 (en) * 1998-09-24 2002-12-17 Advantage Dental Products, Inc. Calcified tissue facing preparation containing an antimicrobial agent
WO2001012242A1 (de) * 1999-08-14 2001-02-22 Ivoclar Vivadent Ag Zusammensetzung zur implantation in den menschlichen und tierischen körper
WO2002013871A2 (en) * 2000-08-15 2002-02-21 Surmodics, Inc. Medicament incorporation matrix

Also Published As

Publication number Publication date
DE502004008161D1 (de) 2008-11-13
EP1648531B1 (de) 2008-10-01
US20060275339A1 (en) 2006-12-07
DK1648531T3 (da) 2009-01-12
ATE409499T1 (de) 2008-10-15
AU2004259159A1 (en) 2005-02-03
CA2531488A1 (en) 2005-02-03
DE10332680A1 (de) 2005-02-17
JP2006528008A (ja) 2006-12-14
AU2004259159B2 (en) 2008-11-20
CN1826146A (zh) 2006-08-30
EP1648531A1 (de) 2006-04-26
CY1108640T1 (el) 2014-04-09
WO2005009495A1 (de) 2005-02-03
PL1648531T3 (pl) 2009-03-31
PT1648531E (pt) 2008-12-05
SI1648531T1 (sl) 2009-02-28
ES2313046T3 (es) 2009-03-01
CA2531488C (en) 2010-09-28

Similar Documents

Publication Publication Date Title
CN1826146B (zh) 抗菌活性成分在pmma骨粘固剂中的用途
Wu et al. Anti‐swelling, robust, and adhesive extracellular matrix‐mimicking hydrogel used as intraoral dressing
Gerhart et al. Antibiotic release from an experimental biodegradable bone cement
Wininger et al. Antibiotic-impregnated cement and beads for orthopedic infections
CA1087984A (en) Synthetic resin-base, antibiotic compositions containing amino acids
CA1338980C (en) Bone cement for sustained release of substances
JPS5912293B2 (ja) 外科用合成樹脂材料
JP4944809B2 (ja) 修正手術用ポリメチルメタクリレート骨用セメント
JPH08103491A (ja) 活性化合物を含む骨セメントの調製法
SK11362001A3 (sk) Stabilný ireverzibilný hydrofilný gél a spôsob jeho prípravy
Carvalho et al. Doxycycline release and antibacterial activity from PMMA/PEO electrospun fiber mats
JP2006102512A (ja) 抗生物質／抗生物質類を含有するｐｍｍａ−骨セメント
KR20160033897A (ko) 조직 수복용 조성물 및 이의 제조방법
CN104857556A (zh) 一种化学接枝型长效缓释抗菌真丝缝合线及其制备方法
Ueng et al. In vivo study of hot compressing molded 50: 50 poly (DL‐lactide‐co‐glycolide) antibiotic beads in rabbits
Firsov et al. Biodegradable implants containing gentamicin: drug release and pharmacokinetics
AU3703699A (en) Self-defining plastics and the use thereof in dentistry and dental technology
EP3700589A1 (en) Temperature-responsive degradable hydrogels
WO1999053754A1 (en) Subversion of bacterial resistance by low solubility antibiotics
RU2834659C1 (ru) Раствор лантибиотика против бактериальных инфекций
EP3056227B1 (de) Antimykotischer polymerisierbarer knochenzement und ein verfahren zu seiner herstellung
CN115926197A (zh) 一种抗菌水凝胶及其制备方法和应用
Hutchinson Medical and pharmaceutical applications of water soluble polymers
TR202013709A1 (tr) İlaç yüklü nanokapsül katkili pmma sementi̇
Hosseinzadeh Interpenetrating network polymer hydrogels of sodium alginate and poly (acrylic acid) for controlled release of prazosin hydrochloride

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20101201

Termination date: 20120716