CN101596422B - Method for preparing polyvinylidene fluoride affinity membrane using amino acid as ligand - Google Patents
Method for preparing polyvinylidene fluoride affinity membrane using amino acid as ligand Download PDFInfo
- Publication number
- CN101596422B CN101596422B CN2009101005675A CN200910100567A CN101596422B CN 101596422 B CN101596422 B CN 101596422B CN 2009101005675 A CN2009101005675 A CN 2009101005675A CN 200910100567 A CN200910100567 A CN 200910100567A CN 101596422 B CN101596422 B CN 101596422B
- Authority
- CN
- China
- Prior art keywords
- membrane
- amino acid
- mixed solution
- concentration
- naoh
- 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
Links
Images
Landscapes
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
The invention discloses a method for preparing a polyvinylidene fluoride affinity membrane using amino acid as a ligand. The affinity membrane is prepared by hydrophilically modifying a polyvinylidene fluoride hollow fiber membrane and grafting the amino acid ligand. The grafting amount of the amino acid is 150 to 250mg/g for each membrane. The invention also discloses application of the affinity membrane in removing endotoxin in blood plasma, which removes the endotoxin in the blood plasma by a dynamic absorption means. The polyvinylidene fluoride affinity membrane prepared by the method has stable performance, good bio-compatibility and high endotoxin removing efficiency, and can be used for whole blood perfusion as well as blood plasma perfusion.
Description
Technical field
The present invention relates to amino acid is the preparation method of the polyvinylidene fluoride affinity membrane of aglucon, be particularly related to by hydrophilic modification and grafting amino acid aglucon to the Kynoar hollow-fibre membrane, preparation is applied to remove the method for endotoxic polyvinylidene fluoride affinity membrane in the blood plasma.
Background technology
Current, endotoxemia exists illness rate height, case fatality rate height, three high phenomenons that medical expense is high, has constituted the great burden to the serious threat and the economic development of human health.Endotoxin (endotoxin) is one of constituent of gram-negative bacteria cell membrane adventitia, its chemical nature be lipopolysaccharides (lipopolysaccharide, LPS).Because the intracellular signal transduction of cell activation is very complicated due to the LPS, in a single day the water fall effect that starts after the corresponding receptors bind of LPS and inflammatory response cell takes place, and will be difficult to control effectively.
Though a large amount of in recent years wide spectrums, the efficient antibiotic clinical treatment infectious diseases that is applied as provide effective measures, fundamentally do not change the present situation of the high case fatality rate of sepsis patient.Reason is that antibiotic can not be contained the whole body property out of control inflammatory reaction that is interacted and caused by endotoxin and body, might cause in kill bacteria that anti-endotoxin discharges, thus the exacerbate inflammation reaction.Also exist the defective of aspects such as dosage is big, cost is high, toxicity is big simultaneously, influenced it in clinical further application.
Lot of domestic and international experiment shows, select for use have the selectivity height, the affine technology of characteristics such as separating rate is fast, energy consumption is low, easy amplification removes endotoxin a kind of effective ways of can yet be regarded as.Romi Lamb etc. add silica particle and prepare endotoxin (Machado RL in immunoglobulin G (IgG) solution of shitosan micropore blend film adsorption removal preparation in shitosan, et al., Process Biochemistry, 41 (11): 2252-2257 (2006)).Sundberg etc. are by the endotoxin (U.S.Pat.20050186218) in immobilized metal affinity chromatography (chromatography) the technology removal protein.It is that affinity chromatography is separated a kind of isolation technics that combines with film that affinity membrane separates, and has the selectivity height, characteristics such as separating rate is fast, its lytic activity is high, easy amplification, and very active to this The Application of Technology research both at home and abroad, coverage is very wide.The blood perfusion that with the polyvinylidene fluoride film is carrier does not appear in the newspapers with endotoxin absorbent.
Summary of the invention
The invention provides a kind of is the preparation method of the polyvinylidene fluoride affinity membrane of aglucon with amino acid, by to Kynoar (PVDF) film hydrophilic modification, grafting amino acid aglucon is prepared stable performance, bio-compatible is good, the PVDF affinity membrane that the endotoxin removal rate is high.Can be used for whole blood perfusion, also can be used for plasma perfusion.
A kind of is the preparation method of the polyvinylidene fluoride affinity membrane of aglucon with amino acid, the steps include:
1) preliminary treatment of basement membrane
Be after 30% the ethanol rinse, to soak with deionized water, PVDF hollow-fibre membrane mass percentage concentration with the impurity on flush away film surface;
2) hydrophilic modification
With KMnO
4Under 60-80 ℃, send into PVDF hollow fiber film assembly reaction 30-90min with the mixed solution of KOH, use H then with constant flow pump
2SO
4And NaHSO
3Mixed solution reduction;
KMnO
4With KMnO in the mixed solution of KOH
4Concentration be 40-80g/l, the concentration of KOH is 3-5mol/l; H
2SO
4And NaHSO
3Mixed solution in H
2SO
4Concentration be 50-100g/l, NaHSO
3Concentration be 50-100g/l;
3) hydroxyethylcellulose (HEC) is handled
PVDF hollow-fibre membrane after reduction is handled is handled 10-30min with NaOH and HEC mixed solution at 80-90 ℃, to increase the hydrophily on film surface; In 80-90 ℃ of oven dry, use the Na of 0.5-2mol/l after the drying then
2CO
3Solution washes under 80-90 ℃ of condition, the unreacted HEC in flush away film surface;
The concentration of NaOH is 1-3mol/l in NaOH and the HEC mixed solution, and the concentration of HEC is 10-30g/l;
4) activation for the first time
The PVDF hollow-fibre membrane of handling through step 3) activates under 50-70 ℃ of condition with the mixed solution of epoxychloropropane (ECH) with NaOH, activation back deionized water rinsing;
The mixed solution of described epoxychloropropane and NaOH is according to epoxychloropropane: concentration is that the volume ratio of the NaOH solution of 1mol/l is the mixed solutions of 1: 3～6 preparations;
5) bonding hexamethylene diamine spacerarm
For the first time the PVDF hollow-fibre membrane after the activation in 50-70 ℃ down with hexamethylene diamine (HDA) the reaction 2-3h of 40-80g/l, use deionized water rinsing after the reaction;
6) activation for the second time
The PVDF hollow-fibre membrane that connects spacerarm through step 5) activates under 50-70 ℃ of condition once more with the mixed solution of epoxychloropropane (ECH) with NaOH;
The mixed solution of described epoxychloropropane and NaOH is according to epoxychloropropane: concentration is that the volume ratio of the NaOH solution of 1mol/l is the mixed solutions of 1: 3～6 preparations;
7) bonding amino acid aglucon
For the second time the Freamine of PVDF hollow-fibre membrane after the activation and 2-8g/l (0.2mol/lpH is that 7.2 phosphate buffer is a solvent) reacts 20-24h under 40-50 ℃ of condition, obtains the polyvinylidene fluoride affinity membrane of grafting amino acid aglucon.
Among the described preparation method, amino acid is a kind of in serine, asparagine, arginine, histidine, polylysine or the glutamine.The endotoxin molecule is electronegative owing to have phosphate group, therefore can remove with positively charged adsorbent.Amino acid whose amino and carboxyl can be respectively in conjunction with anion on the endotoxin molecule and hydrophobic groupings.
The amino acid whose grafting amount of the polyvinylidene fluoride affinity membrane of the inventive method preparation is 150～250mg/g film.
To be applied to remove endotoxin in the blood plasma in order to the polyvinylidene fluoride affinity membrane of top method preparation, use the membrane module of this affinity membrane to carry out blood perfusion, comprise the steps: under the room temperature that endotoxemia patient's blood pumps in the membrane module, flow velocity 0.5-2.0mL/min flows out liquid and does not circulate.
Polyvinylidene fluoride affinity membrane of the present invention dynamically adsorbs endotoxemia patient's blood plasma, can reach 61.9% to endotoxic clearance rate, and adsorption efficiency is higher.Can be used for the endotoxin in the clinical whole blood perfusion removing blood, diseases such as treatment endotoxemia.
Advantage of the present invention is:
1) use Kynoar to be carrier, the physicochemical properties of material are stable, and have blood compatibility preferably.
2) be filled in the membrane module with the Kynoar hollow-fibre membrane, make the modification of film and the process simple and convenient of grafting aglucon and blood perfusion, and, can improve the percent grafting of aglucon greatly because the specific area of film is big.And because the advantage of membrane module self, technology is easy to amplify, and can connect simultaneously, satisfies the clinical practice demand.
3) with amino acid be aglucon, contain two functional groups of amido and carboxyl simultaneously, improved sorbing material endotoxic specific adsorption.
Description of drawings
Fig. 1 amino acid affinity membrane is removed endotoxic experiment flow figure in the blood plasma;
1-blood wherein; The 2-pump; The 3-flowmeter; 4-affinity membrane assembly; The 5-water bath with thermostatic control; 6-collects liquid;
Fig. 2 embodiment 1 serine affinity membrane absorption endotoxin breakthrough curve.
The specific embodiment
Contain 16 of PVDF hollow-fibre membranes in the membrane module, the quality of film is 0.42g, effective length 16.70cm, effective area 19.93cm
2
The glass apparatus that test is touched is done in 400 ℃ and was baked 4 hours, and plastic ware is at 30%H
2O
2The middle immersion removed thermal source in 4 hours.The affinity membrane assembly 0.1mol/L NaOH that contains 20% ethanol, 1.5mol/LNaCl, apirogen water is washed successively and was removed thermal source in 2 hours.
1) with the PVDF hollow-fibre membrane with 30% ethanol rinse 30min after, soak 1h with deionized water, with the impurity on flush away film surface.
2) with the KMnO of 40g/l
4Under 80 ℃, send into PVDF hollow fiber film assembly reaction 30min with the KOH mixed liquor of 3mol/l, use the H of 60g/l then with constant flow pump
2SO
4NaHSO with 60g/l
3The mixed liquor reduction.
3) film after reduction is handled is handled 15min with the HEC mixed liquor of 1mol/lNaOH and 10g/l at 90 ℃, to increase the hydrophily on film surface.Place oven dry in 90 ℃ of constant temperature hot air driers, the dry back Na of 0.5mol/l
2CO
3Solution washes 10min under 90 ℃ of conditions, the unreacted HEC in flush away pvdf membrane surface.
4) film of hydrophilic modification is with epoxychloropropane (ECH): the 1mol/lNaOH volume ratio is that 1: 4 mixed liquor activates under 60 ℃ of conditions, and uses deionized water rinsing 1h.
5) following in the 50 ℃ then hexamethylene diamine (HDA) with 50g/l acts on 2h, and uses deionized water rinsing 1h.
6) pvdf membrane that connects spacerarm is with epoxychloropropane (ECH): the 1mol/lNaOH volume ratio is mixed liquor activation once more under 60 ℃ of conditions of 1: 4.
7) under 45 ℃ of conditions, react 24h with the serine solution of 3g/l (0.2mol/lpH is that 7.2 phosphate buffer is a solvent), obtain the polyvinylidene fluoride affinity membrane of grafting serine aglucon.
According to method shown in Figure 1, human plasma 1 is squeezed in the affinity membrane assembly 4 through flowmeter 3 by pump 2, and flow velocity 1.0mL/ minute, affinity membrane assembly 4 peripheral hardwares had water bath with thermostatic control 5.Got liquid collecting 6 in per 3 minutes and survey endotoxic content, draw breakthrough curve, see Fig. 2, flow out liquid and do not circulate.By measuring endotoxic initial concentration and breakthrough curve, can obtain endotoxin removal efficient, as shown in table 1.
The performance of table 1 embodiment 1 prepared affinity membrane
1) with the PVDF hollow-fibre membrane with 30% ethanol rinse 40min after, soak 1h with deionized water, with the impurity on flush away film surface.
2) with the KMnO of 50g/l
4Under 60 ℃, send into PVDF hollow fiber film assembly reaction 30min with the KOH mixed liquor of 3mol/l, use the H of 60g/l then with constant flow pump
2SO
4With 60g/l NaHSO
3The mixed liquor reduction.
3) film after reduction is handled is handled 10min with the HEC mixed liquor of 1.5mol/lNaOH and 15g/l at 80 ℃, to increase the hydrophily on film surface.Place oven dry in 80 ℃ of constant temperature hot air driers, the dry back Na of 0.5mol/l
2CO
3Solution washes 10min under 80 ℃ of conditions, the unreacted HEC in flush away pvdf membrane surface.
4) film of hydrophilic modification is with epoxychloropropane (ECH): 1mol/l NaOH volume ratio is that 1: 3 mixed liquor activates under 50 ℃ of conditions, and uses deionized water rinsing 1h.
5) following in the 60 ℃ then hexamethylene diamine (HDA) with 40g/l acts on 2h, and uses deionized water rinsing 1h.
6) pvdf membrane that connects spacerarm is with epoxychloropropane (ECH): the 1mol/lNaOH volume ratio is mixed liquor activation once more under 50 ℃ of conditions of 1: 3.
7) under 40 ℃ of conditions, react 20h with the serine solution of 2g/l (0.2mol/lpH is that 7.2 phosphate buffer is a solvent), obtain the polyvinylidene fluoride affinity membrane of grafting serine aglucon.
With embodiment 1, aglucon grafting density and endotoxin removal efficient see Table 2 to endotoxic removal experimental procedure in the blood plasma.
The performance of table 2 embodiment 2 prepared affinity membranes
Step 1-6 is with embodiment 1
7) under 45 ℃ of conditions, react 24h with the asparagine solution of 3g/l (0.2mol/lpH is that 7.2 phosphate buffer is a solvent), obtain the polyvinylidene fluoride affinity membrane of grafting asparagine aglucon.
With embodiment 1, aglucon grafting density and endotoxin removal efficient see Table 3 to the polyvinylidene fluoride affinity membrane of asparagine aglucon to endotoxic removal experimental procedure in the blood plasma.
The performance of table 3 embodiment 3 prepared affinity membranes
Step 1-6 is with embodiment 1
7) under 45 ℃ of conditions, react 24h with the arginine solution of 3g/l (0.2mol/lpH is that 7.2 phosphate buffer is a solvent), obtain the polyvinylidene fluoride affinity membrane of grafting arginine aglucon.
With embodiment 1, aglucon grafting density and endotoxin removal efficient see Table 4 to the polyvinylidene fluoride affinity membrane of arginine aglucon to endotoxic removal experimental procedure in the blood plasma.
The performance of table 4 embodiment 4 prepared affinity membranes
Claims (7)
1. one kind is the preparation method of the polyvinylidene fluoride affinity membrane of aglucon with amino acid, it is characterized in that comprising the steps:
1) preliminary treatment of basement membrane
Be after 30% the ethanol rinse, to soak Kynoar hollow-fibre membrane mass percentage concentration with deionized water;
2) hydrophilic modification
With KMnO
4Send into the membrane module that the Kynoar hollow-fibre membrane is formed with the mixed solution of KOH under 60-80 ℃, reaction 30-90min uses H then
2SO
4And NaHSO
3Mixed solution reduction;
3) hydroxyethylcellulose is handled
Kynoar hollow-fibre membrane after reduction is handled is handled 10-30min with NaOH and hydroxyethylcellulose mixed solution at 80-90 ℃; In 80-90 ℃ of oven dry, use the Na of 0.5-2mol/l after the drying then
2CO
3Solution washes under 80-90 ℃ of condition;
4) activation for the first time
The Kynoar hollow-fibre membrane of handling through step 3) activates under 50-70 ℃ of condition with the mixed solution of epoxychloropropane and NaOH, activates and then uses deionized water rinsing;
5) bonding hexamethylene diamine spacerarm
For the first time the Kynoar hollow-fibre membrane after the activation in 50-70 ℃ down with the hexamethylene diamine reaction 2-3h of 40-80g/l, use deionized water rinsing after the reaction;
6) activation for the second time
Use the mixed solution of epoxychloropropane and NaOH under 50-70 ℃ of condition, to activate once more through the Kynoar hollow-fibre membrane of step 5) bonding hexamethylene diamine spacerarm, activation back deionized water rinsing;
7) bonding amino acid aglucon
Kynoar hollow-fibre membrane after the activation and the Freamine of 2-8g/l react 20-24h under 40-50 ℃ of condition for the second time, obtain the polyvinylidene fluoride affinity membrane of grafting amino acid aglucon, and described Freamine is solvent with the phosphate buffer;
Described amino acid is serine, asparagine, arginine, histidine, polylysine or glutamine.
2. preparation method as claimed in claim 1 is characterized in that: amino acid whose grafting amount is 150～250mg/g film.
3. preparation method as claimed in claim 1 is characterized in that: described KMnO
4With KMnO in the mixed solution of KOH
4Concentration be 40-80g/l, the concentration of KOH is 3-5mol/l.
4. preparation method as claimed in claim 1 is characterized in that: described H
2SO
4And NaHSO
3Mixed solution in H
2SO
4Concentration be 50-100g/l, NaHSO
3Concentration be 50-100g/l.
5. preparation method as claimed in claim 1 is characterized in that: the concentration of NaOH is 1-3mol/l in described NaOH and the hydroxyethylcellulose mixed solution, and the concentration of hydroxyethylcellulose is 10-30g/l.
6. preparation method as claimed in claim 1 is characterized in that: the mixed solution of described epoxychloropropane and NaOH is according to epoxychloropropane: concentration is that the volume ratio of the NaOH solution of 1mol/l is the mixed solutions of 1: 3～6 preparations.
7. the polyvinylidene fluoride affinity membrane application in the endotoxin in removing blood plasma for preparing as the arbitrary described preparation method of claim 1-6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101005675A CN101596422B (en) | 2009-07-07 | 2009-07-07 | Method for preparing polyvinylidene fluoride affinity membrane using amino acid as ligand |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101005675A CN101596422B (en) | 2009-07-07 | 2009-07-07 | Method for preparing polyvinylidene fluoride affinity membrane using amino acid as ligand |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101596422A CN101596422A (en) | 2009-12-09 |
| CN101596422B true CN101596422B (en) | 2011-08-10 |
Family
ID=41418128
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101005675A Expired - Fee Related CN101596422B (en) | 2009-07-07 | 2009-07-07 | Method for preparing polyvinylidene fluoride affinity membrane using amino acid as ligand |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101596422B (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201002824D0 (en) | 2010-02-19 | 2010-04-07 | Temasek Polytechnic | A method of preparing a substrate for immobilization of functional substances thereon and the substrate obtained therefrom |
| CN102786140B (en) * | 2011-05-20 | 2014-04-30 | 北京师范大学 | Surface modification method of polypropylene biological filling material |
| CN102553467B (en) * | 2011-12-29 | 2014-06-11 | 浙江工业大学 | Sulfadimidine affinity membrane and application of sulfadimidine affinity membrane in antibody separation and purification |
| CN104984664A (en) * | 2015-06-20 | 2015-10-21 | 杭州汉膜新材料科技有限公司 | Method for preparing amino acid modified polyether sulfone hematodialysis membrane |
| CN105504320B (en) * | 2015-12-29 | 2018-01-26 | 河南大学 | A kind of affine biomembrane, preparation method and applications |
| CN105727760B (en) * | 2016-03-31 | 2018-08-03 | 北京理工大学 | A kind of antipollution ultrafiltration membrane and preparation method thereof of amino acid grafting compound cellulose |
| CN106310970B (en) * | 2016-09-23 | 2019-03-05 | 天津工业大学 | A kind of modified polyvinilidene fluoride hollow-fibre membrane for haemodialysis |
| CN106492640A (en) * | 2016-11-18 | 2017-03-15 | 哈尔滨商业大学 | Based on the method that bioinformatics slows down membrane biological pollution |
| CN108404684B (en) * | 2018-03-14 | 2021-06-11 | 同济大学 | Preparation method of super-hydrophilic modified anti-pollution PVDF separation membrane |
| CN108579698B (en) * | 2018-04-11 | 2021-08-31 | 成都艾伟孚生物科技有限公司 | Preparation of endotoxin specific adsorption membrane and application of membrane in assisted reproduction field |
| CN113350589B (en) * | 2020-03-05 | 2023-04-14 | 中国科学院宁波材料技术与工程研究所 | Anti-fouling modification method of hemodialyzer and application thereof |
| CN112892250B (en) * | 2021-01-31 | 2022-06-03 | 天津工业大学 | Chlorine-resistant amino acid modified polyether sulfone reverse osmosis membrane and preparation method thereof |
| CN114713052A (en) * | 2022-03-23 | 2022-07-08 | 中山大学 | Anti-pollution modified polyvinylidene fluoride membrane and preparation method and application thereof |
-
2009
- 2009-07-07 CN CN2009101005675A patent/CN101596422B/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 虞骥.聚偏氟乙烯中空纤维亲和膜分离γ－球蛋白的研究（I）.《高等学校化学学报》.2003,第24卷(第5期),936页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101596422A (en) | 2009-12-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101596422B (en) | Method for preparing polyvinylidene fluoride affinity membrane using amino acid as ligand | |
| CN105424931B (en) | Helicobacter Pylori urease antibody IgM, IgG associating device for fast detecting and preparation method thereof | |
| CN104096544A (en) | Chromatographic medium using amino benzimidazole as function ligand and preparation method thereof | |
| CN106902655A (en) | A kind of preparation method and application of mercapto-functionalized polymer separation film | |
| CN104801278A (en) | Preparation method of AIDS (acquired immune deficiency syndrome) virus affinity adsorbent | |
| CN104959120B (en) | Inflammatory factor adsorbing agent for blood perfusion and preparation method | |
| CN103611504B (en) | A kind of sorbing material for blood perfusion removal rheumatoid factor and preparation method thereof | |
| CN104624171A (en) | Polymer grafting type hydrophobic charge-induced chromatography medium and preparation method thereof | |
| CN103406111A (en) | Adsorbent for removing endotoxin by blood perfusion and preparation method thereof | |
| CN103230781A (en) | Heparin-phenylalanine adsorption material for blood purification method for removing endotoxin | |
| CN100493695C (en) | Endotoxin adsorption material for curing endotoxemia | |
| CN103191702A (en) | Preparation method and application of sulfydryl palm bark adsorbent | |
| CN102743985B (en) | Preparation method for polysulfone-serine affinity membrane used for removing endotoxin | |
| CN107262077B (en) | A kind of preparation method being bonded organic polymer overmold silicon ball chromatographic stationary phases | |
| CN108745287A (en) | The preparation method of three-dimensional graphene oxide group carbonic anhydride adsorption agent | |
| CN108514864A (en) | A kind of chitin/graphene oxide composite sponge and the preparation method and application thereof | |
| CN101224413A (en) | Water-soluble cationic polymer adsorption material and applications thereof | |
| CN103613684B (en) | A kind of isolation and purification method of N-acetylation shell six sugar of different acetyl degree | |
| CN101787143B (en) | Method for preparing layer-by-layer self-assembled protein-imprinted polymer of chitosan | |
| CN105195115A (en) | DEAE dextran-modified agarose gel-based chromatography medium and preparation method and application thereof | |
| CN102018955A (en) | Purification method for producing viral vaccine in large scale | |
| CN104801279A (en) | Method for modifying activated carbon particles with sol-gel method | |
| CN109794172A (en) | A kind of preparation method of the antibacterial hollow-fibre membrane for blood purification | |
| CN104741086A (en) | Preparation method for hepatitis c virus adsorbent | |
| CN103252177A (en) | Glycosyl/sulfonated modified affiliative polymer hollow fiber separating membrane, and preparation method and use thereof |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110810 Termination date: 20140707 |
|
| EXPY | Termination of patent right or utility model |