CN100551367C - The application of chloride 13-hexyl berberine and HP-13 preparation treatment vaginal infection-inflammation medicine - Google Patents
The application of chloride 13-hexyl berberine and HP-13 preparation treatment vaginal infection-inflammation medicine Download PDFInfo
- Publication number
- CN100551367C CN100551367C CNB200510094086XA CN200510094086A CN100551367C CN 100551367 C CN100551367 C CN 100551367C CN B200510094086X A CNB200510094086X A CN B200510094086XA CN 200510094086 A CN200510094086 A CN 200510094086A CN 100551367 C CN100551367 C CN 100551367C
- Authority
- CN
- China
- Prior art keywords
- chloride
- medicine
- preparation treatment
- application
- hexyl
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 229940093265 berberine Drugs 0.000 title claims abstract description 7
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 title claims abstract description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 title claims abstract description 5
- 206010046914 Vaginal infection Diseases 0.000 title abstract description 7
- 206010061218 Inflammation Diseases 0.000 title description 3
- 208000004926 Bacterial Vaginosis Diseases 0.000 claims abstract description 9
- 239000000829 suppository Substances 0.000 claims abstract description 9
- 206010047799 Vulvovaginitis trichomonal Diseases 0.000 claims abstract description 8
- 208000037009 Vaginitis bacterial Diseases 0.000 claims abstract description 7
- 239000000499 gel Substances 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000000839 emulsion Substances 0.000 claims 2
- 241000894006 Bacteria Species 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 210000001215 vagina Anatomy 0.000 abstract description 6
- 208000033809 Suppuration Diseases 0.000 abstract description 5
- 229940095731 candida albicans Drugs 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 4
- 241000222122 Candida albicans Species 0.000 abstract description 3
- 241000606161 Chlamydia Species 0.000 abstract description 3
- 201000008100 Vaginitis Diseases 0.000 abstract description 3
- -1 chemical compound chloride Chemical class 0.000 abstract description 3
- 208000015181 infectious disease Diseases 0.000 abstract description 3
- 241000204031 Mycoplasma Species 0.000 abstract description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 239000002552 dosage form Substances 0.000 abstract description 2
- 230000002147 killing effect Effects 0.000 abstract description 2
- 208000024891 symptom Diseases 0.000 abstract description 2
- 230000008030 elimination Effects 0.000 abstract 1
- 238000003379 elimination reaction Methods 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 10
- 238000012360 testing method Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001597008 Nomeidae Species 0.000 description 3
- 229960000282 metronidazole Drugs 0.000 description 3
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- RLQYRXCUPVKSAW-UHFFFAOYSA-M 2,3,9,10-tetramethoxy-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium;chloride Chemical compound [Cl-].COC1=C(OC)C=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=C1 RLQYRXCUPVKSAW-UHFFFAOYSA-M 0.000 description 2
- FZAGOOYMTPGPGF-UHFFFAOYSA-N Lambertine Chemical compound C1=C2C3=CC4=CC=C(OC)C(OC)=C4CN3CCC2=CC2=C1OCO2 FZAGOOYMTPGPGF-UHFFFAOYSA-N 0.000 description 2
- 230000001032 anti-candidal effect Effects 0.000 description 2
- 230000001572 anti-trichomonad Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- RIDQRIPSFYHEGL-UHFFFAOYSA-N fibrauretin Natural products CC12CC=C3C(=O)OC(CC3(C)C1C(=O)C=CC2=O)c4cocc4 RIDQRIPSFYHEGL-UHFFFAOYSA-N 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 208000004429 Bacillary Dysentery Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 206010017915 Gastroenteritis shigella Diseases 0.000 description 1
- 241000192035 Peptostreptococcus anaerobius Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 241000191963 Staphylococcus epidermidis Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 241001467018 Typhis Species 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000941 anti-staphylcoccal effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012009 microbiological test Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000001194 polyoxyethylene (40) stearate Substances 0.000 description 1
- 235000011185 polyoxyethylene (40) stearate Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000005113 shigellosis Diseases 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to the purposes of chemical compound chloride 13-hexyl berberine ex hoc genus anne thing HP-13 preparation treatment mucocutaneous infections vaginitis, vaginosis disease external used medicine.Chloride 13-hexyl berberine and HP-13 all have clear and definite killing action to suppuration bacterium, anaerobe, Candida albicans, infusorian and mycoplasma, the chlamydia that causes mycotic, trichomonal vaginitis and bacterial vaginosis, dosage forms such as emulsifiable paste, gel or suppository with this chemical compound effective ingredient are all effective in cure to the mucosal sites of vagina, and the antiinflammatory action of medicine can make the very fast elimination of disease symptoms and shorten the course of disease.
Description
Technical field
The invention relates to the application of chemical compound chloride 13-hexyl berberine (being called for short HB-13) ex hoc genus anne thing HP-13 (being called for short HP-13) preparation treatment mucocutaneous infections vaginitis, vaginosis external used medicine.
Background technology
Chloride 13-hexyl berberine (HB-13), molecular formula C
26H
31NO
4HCl, molecular weight 457.98 has following chemical structural formula:
Above-mentioned HB-13 is by hexyl-C by the 13rd-H in parent compound berberine hydrochloride (the being called for short Bo) molecule
6H
13Replace and derivant, adopt Bo in aqueous medium with the sodium borohydride sig water react dihydroberberine, reuse n-hexyl aldehyde and dihydroberberine reacts in ethanol acetate liquid and generate crude product HB-13, then further making with extra care and getting.
As everyone knows, Bo is isolated a kind of monomer in the Rhizoma Coptidis total alkaloids that extracts from plants such as Rhizoma Coptidis, Bo has the activity of anti-dysentery bacterium and certain anti-Bacillus typhi, streptococcus pneumoniae, golden staphylococci, has been widely used in treating diseases such as gastroenteritis, bacillary dysentery, typhoid fever.Report is also arranged, and it has the more weak Chinese People's Anti-Japanese Military and Political College's Mus inflammatory model effect of oral administration, but does not see the practicality report.
The still untapped at present medicine that becomes of the derivant HB-13 of Bo does not also see that it has the activity of mycotic, trichomonal vaginitis and bacterial vaginitis disease and the report of purposes.
HP-13 is called for short HP-13, molecular formula C
27H
35NO
4HCl, molecular weight 474.02 has following chemical structural formula:
HP-13 (being called for short HP-13) is by hexyl-C by the 13rd-H in parent compound hydrochloric acid fibrauretin (the being called for short Po) molecule
6H
13The derivant that replaces and get, the hydrochloric acid fibrauretin is former to be a kind of antimicrobial drug.But HP-13 does not see that it has the report to the activity and the purposes of mycotic, trichomonal vaginitis and bacillary vagina.Experimental results show that HP-13 and HB-13 have quite similar character aspect pharmacologically active and the purposes.
Summary of the invention
The purpose of this invention is to provide the application in preparation treatment mycotic, trichomonal vaginitis and bacterial vaginosis medicine of HB-13 and HP-13.
Gynecological's mycotic, trichomonal vaginitis and bacterial vaginosis are caused by Candida albicans, infusorian and various suppuration bacterium, anaerobe respectively.Therapeutic Method is except that being administered systemically, and common drug and disinfectant are done vaginadouche, soaked and make the vagina intracavitary administration with suppository, tablet, gel and treat.Common drug such as triazole antifungal agent, metronidazole, anti-suppuration bacterium and anaerobism mushroom antibiotic etc.Can be simultaneously except that metronidazole to anaerobe and infusorian effectively, other medicines all are single antifungal or antibacterium effect.
The present invention proves through antiinflammatory test and anti-all kinds of microbiological test laboratory researches, and HB-13 is to the main pathogens of above-mentioned three class vaginitis diseases: suppuration bacterium, anaerobe, Candida albicans, infusorian and mycoplasma, chlamydia all have clear and definite killing action.External agar plate method bacteriostatic test result shows: the MIC value of suppuration bacterium such as its anti-staphylococcus aureus, staphylococcus epidermidis, escherichia coli, bacillus pyocyaneus is 3.125 μ g/ml; The anaerobism culture experiment shows: its anti-G-bacteroid, Streptococcus anaerobius, G+ dyspepsiacoccus MIC value are 3.125～1.56 μ g/ml; Its external anti-trichomonal test records IC
50Value is about 80 μ g/ml (metronidazole is 50 μ g/ml, and 100 μ g/ml Bo suppression ratio are 0); HB-13 anti-candida albicans MIC is 50～100 μ g/ml, and anti-other fungus is 25～50 μ g/ml, and the valid density of above anti-trichomonal and anti-candida albicans all is the concentration that can reach in vagina.With the McCoy cell strain medicine desertification chlamydia oculogenitale E Bour strain test is shown: HB-13MIC is 0.39 μ g/ml, and HP-13MIC is 3.125 μ g/ml.In addition, HB-13 has very strong anti-nonspecific inflammation effect, and this helps to eliminate colpitis and eliminates local symptom faster.
Preliminary clinical trial prompting, making solution or the flushing of suppository do and vagina intracavitary administration with HB-13 has clear and definite curative effect.Except that suppository, solution, emulsifiable paste and gel also are applicable to this indication, and these vagina preparations can be used for the treatment to single or blended vaginosis pathogen infection.
(contain effective dose 9.4mg/ bolt with suppository, weight of formulation 2.35g/ bolt, preparation content of dispersion 4mg/g, be equivalent to concentration 0.4%, become 4000 μ g/ml after the dissolving), clinic trial is in infusorian property, colpitis mycotica and bacterial vaginosis, 7 days is a course of treatment, all obtains satisfied curative effect in 1～2 course of treatment.
Dosage forms such as gel, ointment, solution all can play the corresponding treatment effect respectively in theory at the vaginal mucosa position.
Confirm that through above-mentioned identical test HP-13 has the pharmacologically active similar to HB-13, antibacterial activity is close, and former generation compd B o and Po find no this type of effect.
The specific embodiment
The preparation of embodiment one suppository
Take by weighing HB-13 or HP-130.2-1g, add suppository base to 100g, 50 of suppositorys are made in the suppository operation routinely, and every active drug content is 4mg～20mg.
Indication: mycotic, infusorian property, bacterial vaginitis.
Using method: this suppository is put into intravaginal
The preparation of embodiment two gels
Take by weighing:
HB-13 or HP-13 0.2～2g
Surfactant 0.5～1g
Third ethanol, 10～20g
Carpopol
940 0.5～2g
Triethanolamine is an amount of
Distilled water adds to 100g
Press the preparation of gel conventional method.
Using method: be applied to the affected part in right amount with this gel.
The preparation of embodiment three ointments
Take by weighing:
HB-13 or HP-13 0.5～2g, polyoxyethylene (40) stearate 2～5g
Hexadecanol 6～8g glycerol 5～10g
White vaseline 8～10g dehydrated alcohol is an amount of
White oil 8～19g ethyl ester 0.1g
Monoglyceride 2～5g distilled water adds to 100g
Make the o/w emulsifiable paste by the ointment routine operation.
Indication: mycotic, trichomonal vaginitis and bacterial vaginosis.
Using method: be applied to the affected part in right amount with this emulsifiable paste.
Claims (4)
1. the application of chloride 13-hexyl berberine in preparation treatment trichomonal vaginitis or bacterial vaginosis medicine.
2. the application of HP-13 in preparation treatment trichomonal vaginitis or bacterial vaginosis medicine.
3. according to the medicinal application of claim 1, it is characterized in that described medicine is suppository, gel or emulsion agent.
4. according to the medicinal application of claim 2, it is characterized in that described medicine is solution, gel or emulsion agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510094086XA CN100551367C (en) | 2005-08-29 | 2005-08-29 | The application of chloride 13-hexyl berberine and HP-13 preparation treatment vaginal infection-inflammation medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510094086XA CN100551367C (en) | 2005-08-29 | 2005-08-29 | The application of chloride 13-hexyl berberine and HP-13 preparation treatment vaginal infection-inflammation medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1923200A CN1923200A (en) | 2007-03-07 |
| CN100551367C true CN100551367C (en) | 2009-10-21 |
Family
ID=37816143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200510094086XA Expired - Fee Related CN100551367C (en) | 2005-08-29 | 2005-08-29 | The application of chloride 13-hexyl berberine and HP-13 preparation treatment vaginal infection-inflammation medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100551367C (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1629159A (en) * | 2003-12-15 | 2005-06-22 | 李耐三 | Preparation of 13-hexyl fibrauretine and its anti-virus and antibacterial action |
| CN1629160A (en) * | 2003-12-15 | 2005-06-22 | 李耐三 | Preparation of 13-hexyl berberine salt and its anti-virus and antibacterial action |
-
2005
- 2005-08-29 CN CNB200510094086XA patent/CN100551367C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1629159A (en) * | 2003-12-15 | 2005-06-22 | 李耐三 | Preparation of 13-hexyl fibrauretine and its anti-virus and antibacterial action |
| CN1629160A (en) * | 2003-12-15 | 2005-06-22 | 李耐三 | Preparation of 13-hexyl berberine salt and its anti-virus and antibacterial action |
Non-Patent Citations (2)
| Title |
|---|
| 复方黄藤素栓的制备及临床应用观察. 罗光富.西北药学杂志，第4卷第4期. 1989 * |
| 黄连的药理学研究进展及其临床应用. 朱松樵，李禹.中国乡村医生杂志，第9期. 1998 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1923200A (en) | 2007-03-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20110135713A1 (en) | Antimicrobial and Antiviral Compounds and Methods for Their Use | |
| CN102573858B (en) | A skin external composition comprising a salt and sugar as active ingredients for preventing and treating vaginosis and the use thereof | |
| US20220395481A1 (en) | Bacteriostatic composition, preparation method therefor, and use thereof | |
| EP2421531B1 (en) | Use of nifuratel to treat infections caused by atopobium species | |
| CN105232526B (en) | Purposes of the drug containing catechin in preparing antibacterial medicines | |
| CN101780082A (en) | Use of imidazole alkaloids as anti-Infective medicament synergists and medicinal composition containing anti-Infective medicament synergists | |
| CN1879661B (en) | Use of nocardia rubra cell wall skeleton in preparation of medicine for resisting mycotic infection | |
| CN100551367C (en) | The application of chloride 13-hexyl berberine and HP-13 preparation treatment vaginal infection-inflammation medicine | |
| CN102716407A (en) | Application of amomum tsao-ko oil on preparing medicaments with functions of restraining or killing candida albicans | |
| CN102048729A (en) | Preparation for treating vaginitis | |
| CN102824337B (en) | A gel for treating livestock endometritis and preparation method thereof | |
| CN100441183C (en) | Use of chloride 13-hexyl berberine and chloride 13-hexyl palmatine in preparation of medicine for treating moist tetter, dermatitis and psoriasis | |
| RU2368609C1 (en) | Silver salt of n-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-5h-pyrimidinesulphone)-n'-isonicotinoylhydrazide, which exhibits immunotropic, antimicrobial, antifungal (antimycotic) activity and medicinal agent based on said salt | |
| CN1257715C (en) | Clindamycin metronidazole vagina effervescent tablet and its preparing method and use | |
| CN1304002C (en) | Vaginal effervescence tablet of secnidazole and its preparation | |
| CN100572380C (en) | Berberine ion-pair compound, preparation method and contain the medicine of this compound | |
| Collier et al. | Further observations on the biological properties of dequalinium (dequadin) and hedaquinium (teoquel) | |
| CN1301106C (en) | Sterilizing gel | |
| US4459307A (en) | Antibacterial drug | |
| US8309103B2 (en) | Association of fluconazole-tinidazole for the treatment of vaginal infections, its composition, preparation process and usage | |
| CN115025209B (en) | A private care gel containing lysozyme | |
| CN102552304B (en) | Externally applied medicament for treating mite infection of pets | |
| CN1732967A (en) | Vaginal tablet with clindamycin and metronidazole | |
| CN118021888A (en) | Organic silicon gynecological gel | |
| CN1535698A (en) | Chinese medicine compound preparation and its preparation process |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20091021 Termination date: 20210829 |