CN103239448A - Esomeprazole sodium freeze-dried powder composition for injection and preparation method thereof - Google Patents
Esomeprazole sodium freeze-dried powder composition for injection and preparation method thereof Download PDFInfo
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- CN103239448A CN103239448A CN2013101867601A CN201310186760A CN103239448A CN 103239448 A CN103239448 A CN 103239448A CN 2013101867601 A CN2013101867601 A CN 2013101867601A CN 201310186760 A CN201310186760 A CN 201310186760A CN 103239448 A CN103239448 A CN 103239448A
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- 229960000496 esomeprazole sodium Drugs 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- 238000002347 injection Methods 0.000 title claims abstract description 13
- 239000007924 injection Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- RYXPMWYHEBGTRV-JIDHJSLPSA-N sodium;5-methoxy-2-[(s)-(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-3-ide Chemical compound [Na+].C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C RYXPMWYHEBGTRV-JIDHJSLPSA-N 0.000 title claims abstract 9
- 239000000843 powder Substances 0.000 title abstract 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
- 238000005303 weighing Methods 0.000 claims abstract description 12
- 239000007788 liquid Substances 0.000 claims abstract description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 9
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000008215 water for injection Substances 0.000 claims abstract description 5
- 239000004695 Polyether sulfone Substances 0.000 claims abstract description 4
- 238000005352 clarification Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 4
- 229920006393 polyether sulfone Polymers 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 16
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 7
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 7
- 229960005261 aspartic acid Drugs 0.000 claims description 7
- 239000003610 charcoal Substances 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 229940105082 medicinal charcoal Drugs 0.000 claims description 3
- 238000010923 batch production Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 6
- 239000012528 membrane Substances 0.000 abstract description 2
- 238000001035 drying Methods 0.000 abstract 1
- 229940124274 edetate disodium Drugs 0.000 abstract 1
- 230000008014 freezing Effects 0.000 abstract 1
- 238000007710 freezing Methods 0.000 abstract 1
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 description 14
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 11
- 229940090044 injection Drugs 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 208000008469 Peptic Ulcer Diseases 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 208000011906 peptic ulcer disease Diseases 0.000 description 5
- 241000590002 Helicobacter pylori Species 0.000 description 4
- 229940037467 helicobacter pylori Drugs 0.000 description 4
- 238000011835 investigation Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000000718 duodenal ulcer Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000011203 antimicrobial therapy Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229960004770 esomeprazole Drugs 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 230000001175 peptic effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000037816 tissue injury Diseases 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 description 1
- 108010083204 Proton Pumps Proteins 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940057216 branchamin Drugs 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 208000006881 esophagitis Diseases 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 238000002575 gastroscopy Methods 0.000 description 1
- 229940093181 glucose injection Drugs 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 210000001711 oxyntic cell Anatomy 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an esomeprazole sodium freeze-dried powder composition for injection and a preparation method thereof. The main medicine of the composition is esomeprazole sodium and L-asparaginic acid. The composition is prepared by the method as follows: (1) weighing water for injection (at 18-20 DEG C) in a proportional liquid container, adding edetate disodium in a prescription amount and stirring to dissolve; weighing 10% sodium hydroxide liquor, adjusting the pH value to 11.5-12.0, and filling high purity nitrogen to the liquor for 5 minutes; (2) then, adding esomeprazole sodium and L-asparaginic acid in a prescription amount, stirring to dissolve, then, adjusting the pH value to 11.6-11.9% by the 10% sodium hydroxide liquor, and then setting the volume to full dose; (3) after adding the main medicine, filling nitrogen to protect the liquid all the way, and maintaining the temperature of the proportional liquid at 18-22 DEG C; weighing 0.1% medicinal carbon, adding a liquid, stirring and adsorbing for 20 minutes, and removing carbon by a 0.45 micron polyether sulfone filter membrane till clarification; (4) filling, introducing nitrogen and arranging a semi-stop; and (5) after freezing and drying, obtaining the esomeprazole sodium freeze-dried powder composition for injection. The composition provided by the invention has the advantages that that the composition is convenient to produce and process, the aseptic operation is simplified, and the quality stability and the compatible stability of products can be ensured at the same time for injections such esomeprazole sodium with higher pH.
Description
Technical field
The present invention relates to medical technical field, relate in particular to a kind of injection esomeprazole sodium freeze dry composition and method of making the same.
Background technology
Peptic ulcer refers to the tissue injury that surpasses muscular layer of mucosa that gastrointestinal mucosa is caused by peptic digestion liquid autodigestion, can betide gastral any position, wherein common with stomach and duodenum, be gastric ulcer and duodenal ulcer, its cause of disease, clinical symptoms and Therapeutic Method are similar substantially, and it is main by gastroscopy to clarify a diagnosis.Gastric ulcer is modal a kind of in the peptic ulcer, mainly refers to the tissue injury that surpasses muscular layer of mucosa that gastric mucosa is caused by peptic digestion liquid autodigestion.
Esomeprazole sodium can be used for the treatment of gastro oesophageal reflux disease (GORD) (GERD)-erosive reflux esophagitis; The long term maintenance treatment that the esophagitis patient who has cured prevents from recurring; The symptom control of gastro oesophageal reflux disease (GORD) (GERD); With suitable antimicrobial therapy drug combination eradicate helicobacter pylori, and healing is infected relevant duodenal ulcer with helicobacter pylorus, is prevented the recurrent peptic ulcer relevant with helicobacter pylori.
At present, to the higher injection of this class of esomeprazole sodium pH, be badly in need of a kind of product quality stability that namely can guarantee and guarantee the technical scheme of compatibility stability again on the market.
Summary of the invention
The present invention relates to a kind of injection esomeprazole sodium freeze dry composition and method of making the same, said composition can be treated gastro oesophageal reflux disease (GORD) (GERD) clinically, with suitable antimicrobial therapy drug combination eradicate helicobacter pylori, and the duodenal ulcer that healing is relevant with helicobacter pylori infections prevents the recurrent peptic ulcer relevant with helicobacter pylori.
The present invention is prepared from by the following method:
The water for injection (18～22 ℃) that takes by weighing full dose 80% according to batch production instruction places in the proportion liquid container, adds the disodium edetate of recipe quantity, stirs and makes its dissolving;
The sodium hydroxide solution of weighing 10% is transferred pH value to 11.5 ~ 12.0, and solution filled high purity nitrogen 5 minutes.Add esomeprazole sodium and the L-aspartic acid of recipe quantity then, be stirred to dissolving, the sodium hydroxide solution of reuse 10% is transferred pH value to 11.5 ~ 12.0, is settled to full dose then.Solution needs inflated with nitrogen protection always after adding major ingredient;
Weighing 0.1%(g/ml) medicinal charcoal adds solution, stirring and adsorbing 20 minutes, and the carbon removal of 0.45 micron polyether sulfone filter element is to clarification;
Fill, inflated with nitrogen, add half plug;
Fill nitrogen, tamponade, outlet after lyophilization is finished, roll lid and get product.
The L-aspartic acid is Branchamin, can be used for the treatment of heart disease, hepatopathy, and vascular hypertension has the effect that prevents and set up and several amino acids together, makes amino acid transfusion, as ammonia detoxicant, liver function-promoter, fatigue recovery agent.
Esomeprazole is the laevoisomer of omeprazole, is global first isomer proton pump inhibitor (PPI), suppresses the parietal cell proton pump by specificity and reduces gastric acid secretion.It is the choice drug of acid related disorders such as treatment peptic ulcer, gastroesophageal reflux disease, confirm through a large amount of clinical experiments and drug research: it keeps gastric pH〉time of 4 is longer, it is higher to press down sour efficient, curative effect is better than preceding two generation PPI, individual variation is little, as PPI of new generation, the many acid related disorders of clinical treatment now have been widely used in.
Single esomeprazole can only rely on exciting human self repair ability and reach its therapeutical effect.Single L-aspartic acid is few of therapeutical effect.And both combinations are not only had therapeutical effect, and can also the repairing ulcer part, improve therapeutic effect.
Advantage of the present invention: production and processing is convenient, and simplify the sterile working, and to the higher injection of this class of esomeprazole sodium pH, the present invention can guarantee product quality stability and compatibility stability simultaneously.
The specific embodiment
Do further below in conjunction with the present invention of embodiment and to elaborate.
Embodiment, injection esomeprazole sodium freeze dry preparation of compositions are in 10000.
1. write out a prescription
Esomeprazole sodium 552.5g
L-aspartic acid 552.5g
Disodium edetate 19.5g
10% sodium hydroxide solution adjust pH to 11.5～11.8
Active carbon 13.0g
Water for injection adds to 13L
2. preparation technology
(1) water for injection (18～22 ℃) that takes by weighing full dose 80% places in the proportion liquid container, adds the disodium edetate of recipe quantity, stirs and makes its dissolving; High purity nitrogen was filled 5 minutes in sodium hydroxide solution adjust pH to 11.5 ~ 12.0 of weighing 10%, solution; (2) add esomeprazole sodium and the L-aspartic acid of recipe quantity then, be stirred to dissolving, the sodium hydroxide solution of reuse 10% is transferred pH value to 11.6 ~ 11.9, is settled to full dose then; (3) solution needs inflated with nitrogen protection always after the adding major ingredient, and the proportion liquid temperature remains at 18～22 ℃; Weighing 0.1%(g/ml) medicinal charcoal adds solution, stirring and adsorbing 20 minutes, and the carbon removal of 0.45 micron polyether sulfone filter membrane is to clarification; (4) fill, inflated with nitrogen, add half plug; (5) fill nitrogen, tamponade, outlet, Zha Gai after lyophilization is finished, namely get injection esomeprazole sodium freeze dry compositions.
Experimental data:
With reference to " pertinent regulations under the Chinese pharmacopoeia pharmaceutical preparation item have been carried out conventional study on the stability test to this product, mainly comprise influence factor's test, accelerated test and long-term stable experiment.Detailed content sees the following form:
Conventional study on the stability result
This product needs so need to investigate the stability of product in the use, mainly to have investigated the compatibility test with normal saline dilution posterior vein drop, and research contents sees the following form:
Product stability result of study in the use
| Project | The placement condition | The investigation time | The investigation project | Analytical method and checking thereof | Result of study |
| Compatibility stability | 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% | 8h | Character, basicity, color, related substance, content, visible foreign matters, particulate matter | All verify | With stable in the glucose injection compatibility 2 hours, stable in the 8h with the normal saline compatibility, with stable in the lactated Ringer's injection compatibility 6h |
| The multiple-unit container product is opened rear stability | Inapplicable | Inapplicable | Inapplicable | Inapplicable | Inapplicable |
| The compatibility test of preparation and medication utensil | Inapplicable | Inapplicable | Inapplicable | Inapplicable | Inapplicable |
| Other tests | Inapplicable | Inapplicable | Inapplicable | Inapplicable | Inapplicable |
Data shows by experiment, tests the investigation result according to this product influence factor, and sample appearance does not change, measure each index and do not have significant change, placed 10 days under high temperature, high humidity, illumination condition, related substance has the increase slightly under illumination condition, and other each indexs have no significant change.Carried out accelerated test and long term test investigation by commercially available back, the result shows this product under this terms of packing, and significant change does not take place every index, can satisfy medicine to the requirement of storage, traffic condition.
More than show and described advantage of the present invention: production and processing is convenient, and simplify the sterile working, and to the higher injection of this class of esomeprazole sodium pH, the present invention can guarantee product quality stability and compatibility stability simultaneously.
Claims (2)
1. an injection esomeprazole sodium freeze dry compositions is characterized in that, the principal agent of said composition is esomeprazole sodium and L-aspartic acid.
2. one kind with the described preparation of compositions method of claim 1, it is characterized in that the concrete operations step is as follows:
(1) instructs the water for injection (18～22 ℃) that takes by weighing full dose 80% to place in the proportion liquid container according to batch production, add the disodium edetate of recipe quantity, stir and make its dissolving;
(2) sodium hydroxide solution of weighing 10% is transferred pH value to 11.5 ~ 12.0, and solution filled high purity nitrogen 5 minutes; Add esomeprazole sodium and the L-aspartic acid of recipe quantity then, be stirred to dissolving, the sodium hydroxide solution of reuse 10% is transferred pH value to 11.5 ~ 12.0, is settled to full dose then; Solution needs inflated with nitrogen protection always after adding major ingredient;
(3) medicinal charcoal weighing 0.1%(g/ml) adds solution, stirring and adsorbing 20 minutes; 0.45 the carbon removal of micron polyether sulfone filter element is to clarification;
(4) fill, inflated with nitrogen, add half plug;
(5) fill nitrogen, tamponade, outlet after lyophilization is finished, roll lid and get product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013101867601A CN103239448A (en) | 2013-05-20 | 2013-05-20 | Esomeprazole sodium freeze-dried powder composition for injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2013101867601A CN103239448A (en) | 2013-05-20 | 2013-05-20 | Esomeprazole sodium freeze-dried powder composition for injection and preparation method thereof |
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| CN103239448A true CN103239448A (en) | 2013-08-14 |
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| CN2013101867601A Pending CN103239448A (en) | 2013-05-20 | 2013-05-20 | Esomeprazole sodium freeze-dried powder composition for injection and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11318123B2 (en) | 2015-12-08 | 2022-05-03 | Luoda Pharma Limited | Methods and compositions for treating gastric ulcers |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102357082A (en) * | 2011-11-01 | 2012-02-22 | 南京新港医药有限公司 | Esomeprazole sodium freeze-dried powder injection and preparation method thereof |
| CN102657650A (en) * | 2012-05-29 | 2012-09-12 | 海南卫康制药(潜山)有限公司 | Esomeprazole sodium lyophilized powder composition for injection and preparation method thereof |
| CN102973524A (en) * | 2012-11-30 | 2013-03-20 | 深圳海王药业有限公司 | Esomeprazole sodium lyophilized powder injection and preparation method thereof |
| CN103070834A (en) * | 2013-01-16 | 2013-05-01 | 青岛正大海尔制药有限公司 | Lyophilized powder containing esomeprazole |
-
2013
- 2013-05-20 CN CN2013101867601A patent/CN103239448A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102357082A (en) * | 2011-11-01 | 2012-02-22 | 南京新港医药有限公司 | Esomeprazole sodium freeze-dried powder injection and preparation method thereof |
| CN102657650A (en) * | 2012-05-29 | 2012-09-12 | 海南卫康制药(潜山)有限公司 | Esomeprazole sodium lyophilized powder composition for injection and preparation method thereof |
| CN102973524A (en) * | 2012-11-30 | 2013-03-20 | 深圳海王药业有限公司 | Esomeprazole sodium lyophilized powder injection and preparation method thereof |
| CN103070834A (en) * | 2013-01-16 | 2013-05-01 | 青岛正大海尔制药有限公司 | Lyophilized powder containing esomeprazole |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11318123B2 (en) | 2015-12-08 | 2022-05-03 | Luoda Pharma Limited | Methods and compositions for treating gastric ulcers |
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Address after: 266000, unity Road, Qingdao economic and Technological Development Zone, Qingdao, Shandong 3601, China Applicant after: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. Address before: 266103 Haier Industrial Park, No. 1, Haier Road, Laoshan District, Shandong, Qingdao Applicant before: Qingdao Zhengda Haier Pharmaceutical Co., Ltd. |
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Application publication date: 20130814 |