CN103006554A - Ornidazole injection and preparation method thereof - Google Patents
Ornidazole injection and preparation method thereof Download PDFInfo
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- CN103006554A CN103006554A CN2013100007082A CN201310000708A CN103006554A CN 103006554 A CN103006554 A CN 103006554A CN 2013100007082 A CN2013100007082 A CN 2013100007082A CN 201310000708 A CN201310000708 A CN 201310000708A CN 103006554 A CN103006554 A CN 103006554A
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Abstract
The invention relates to the technical field of medicines, and particularly discloses an ornidazole injection and a preparation method thereof. The ornidazole injection comprises 500 grams of ornidazole and the balance of solvents added till the volume of total liquid medicine is 2000-3000 milliliters. The ornidazole injection and the preparation method thereof which are disclosed by the invention have the advantages of simple process, low cost, safety and reliability. Compared with the traditional ornidazole injection, the ornidazole injection increases the using amount of anhydrous ethanol without adding propanediol, plays cosolvent and stabilizer roles through the anhydrous ethanol, ensures the stability of the injection by reducing the impurity content of the injection, is convenience for clinical application, prevents the toxic and side effects of the propanediol on human bodies because the ethanol is safer than the propanediol and reduces the medical risk.
Description
(1) technical field
The present invention relates to field of pharmaceutical technology, particularly a kind of ornidazole injection and preparation method thereof.
(2) background technology
Its chemistry of ornidazole (0rnidazole) 1-(3-chloro-2-hydroxypropyl) by name-2-5-nitro imidazole, it is the medicine that a kind of powerful anaerobe resistant and protozoacide infect, it is the metronidazole that continues, third generation nitro imidazole derivatives after the tinidazole, its performance microbial action is to be reduced into amino or the formation by free radical by the nitro in its molecule in oxygen-free environment, interact with cell component, thereby cause the death of microorganism, can be widely used in treatment by anaerobe, ameba, giardia lamblia, the various diseases that the infection such as trichomonacide cause has the curative effect height, better tolerance, tissue permeability is good, the advantages such as it is wide to distribute in the body.Since the 20 century 70s listings, because its good anaerobe resistant and protozoa resisting (such as infusorian etc.) infection effect, clinical practice is increasingly extensive.Pharmacokinetic shows that the ornidazole biological half-life is very long, has good clinical use value.Domestic existing ornidazole injection listing, but existing ornidazole injection is behind the process high temperature sterilize, the problem of content decrease can occur in ornidazole, so need to add propylene glycol as stabilizing agent so that ornidazole injection keeps stable, and amount ratio is larger, but adopt the propylene glycol used as stabilizers, has larger side effect, the propylene glycol dosage that surpasses 25mg/kg every day can cause the side effect that human body does not tolerate, as solvent for injection, propylene glycol also has certain stimulation, has increased medical-risk.
(3) summary of the invention
The present invention is in order to remedy the deficiencies in the prior art, provides that a kind of technique is simple, cost is low, safe and reliable, good stability, has been convenient to ornidazole injection of clinical use and preparation method thereof.
The present invention is achieved through the following technical solutions:
A kind of ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total medicine liquid volume to 2000～5000ml.
The percent by volume of dehydrated alcohol is 60%～100% in the described solvent, and surplus is water for injection.
The preparation method of this ornidazole injection comprises the steps:
(1) preparating liquid: first inject the solvent that accounts for total medicine liquid volume 60% in Agitation Tank, then ornidazole is added in the Agitation Tank, stirring and dissolving adds the solvent of surplus again, and stirring and evenly mixing gets total medicinal liquid;
(2) remove impurity, depyrogenation: add active carbon in the total medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes, with 0.22 micron filtering with microporous membrane, check;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The addition of active carbon is in the step (2): the active carbon that adds 0.2～0.5g in per hundred milliliters of total medicinal liquids.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
The another kind of preparation method of this ornidazole injection comprises the steps:
(1) preparating liquid: inject the solvent that accounts for total medicine liquid volume 60% first in Agitation Tank, then ornidazole is added in the Agitation Tank, stirring and dissolving gets the part medicinal liquid;
(2) remove impurity, depyrogenation: add active carbon in the part medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes, with 0.22 micron filtering with microporous membrane, the solvent that adds again surplus gets total medicinal liquid, filters check;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The addition of active carbon is in the step (2): the active carbon that adds 0.2～0.5g in per hundred milliliters of total medicinal liquids.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
The beneficial effect of ornidazole injection of the present invention and preparation method thereof is: technique is simple, and cost is low, and is safe and reliable, compare with existing ornidazole injection, the present invention does not add propylene glycol, increases simultaneously the consumption of dehydrated alcohol, plays the effect of cosolvent and stabilizing agent by dehydrated alcohol, the impurity content of injection is reduced, guaranteed the stability of injection, be convenient to clinical use, ethanol is more safer than propylene glycol, avoid the toxic and side effects of propylene glycol to human body, reduced medical-risk.
(4) specific embodiment
Embodiment 1:
This ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total liquor capacity to 2000ml.
Solvent is the mixed solution of dehydrated alcohol and water for injection, dehydrated alcohol 1600ml wherein, and surplus is water for injection.
The preparation method of this ornidazole injection, adopt following steps:
(1) preparating liquid: first inject the 1200ml solvent in Agitation Tank, then the 500g ornidazole is added in the Agitation Tank, stirring and dissolving adds the solvent of surplus again, and stirring and evenly mixing gets total medicinal liquid;
(2) remove impurity, depyrogenation: add the 7g active carbon in the total medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes with 0.22 micron filtering with microporous membrane, is checked;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
Testing result:
| Inspection item | Standard code | Assay |
| Character | This product is the yellow green clear liquid | This product is the yellow green clear liquid |
| Differentiate | Up to specification | Up to specification |
| Content | 90%～110% of labelled amount | 99.8％ |
| Acidity | 4～8 | 6.5 |
| The related substance list is assorted | ≤0.2 | 0.024 |
| Visible foreign matters | Up to specification | Up to specification |
| Pyrogen | Up to specification | Up to specification |
| Aseptic | Up to specification | Up to specification |
Embodiment 2:
This ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total liquor capacity to 2000ml.
Solvent is the mixed solution of dehydrated alcohol and water for injection, dehydrated alcohol 1300ml wherein, and surplus is water for injection.
The preparation method of this ornidazole injection, adopt following steps:
(1) preparating liquid: first inject the 1200ml solvent in Agitation Tank, then the 500g ornidazole is added in the Agitation Tank, stirring and dissolving adds the solvent of surplus again, and stirring and evenly mixing gets total medicinal liquid;
(2) remove impurity, depyrogenation: add the 4g active carbon in the total medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes with 0.22 micron filtering with microporous membrane, is checked;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
Testing result:
| Inspection item | Standard code | Assay |
| Character | This product is the yellow green clear liquid | This product is the yellow green clear liquid |
| Differentiate | Up to specification | Up to specification |
| Content | 90%～110% of labelled amount | 99.9％ |
| Acidity | 4～8 | 6.6 |
| The related substance list is assorted | ≤0.2 | 0.019 |
| Visible foreign matters | Up to specification | Up to specification |
| Pyrogen | Up to specification | Up to specification |
| Aseptic | Up to specification | Up to specification |
Embodiment 3:
This ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total liquor capacity to 2000ml.
Solvent is dehydrated alcohol.
The preparation method of this ornidazole injection, adopt following steps:
(1) preparating liquid: first inject the 1200ml solvent in Agitation Tank, then the 500g ornidazole is added in the Agitation Tank, stirring and dissolving adds the solvent of surplus again, and stirring and evenly mixing gets total medicinal liquid;
(2) remove impurity, depyrogenation: add the 10g active carbon in the total medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes with 0.22 micron filtering with microporous membrane, is checked;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
Testing result:
| Inspection item | Standard code | Assay |
| Character | This product is the yellow green clear liquid | This product is the yellow green clear liquid |
| Differentiate | Up to specification | Up to specification |
| Content | 90%～110% of labelled amount | 99.8％ |
| Acidity | 4～8 | 6.6 |
| The related substance list is assorted | ≤0.2 | 0.035 |
| Visible foreign matters | Up to specification | Up to specification |
| Pyrogen | Up to specification | Up to specification |
| Aseptic | Up to specification | Up to specification |
Embodiment 4:
This ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total liquor capacity to 3000ml.
Solvent is the mixed solution of dehydrated alcohol and water for injection, dehydrated alcohol 2100ml wherein, and surplus is water for injection.
The preparation method of this ornidazole injection, adopt following steps:
(1) preparating liquid: inject the 1800ml solvent first in Agitation Tank, then the 500g ornidazole is added in the Agitation Tank, stirring and dissolving gets the part medicinal liquid;
(2) remove impurity, depyrogenation: add the 9g active carbon in the part medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes, with 0.22 micron filtering with microporous membrane, the solvent that adds again surplus gets total medicinal liquid, filters, and checks;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
Testing result:
| Inspection item | Standard code | Assay |
| Character | This product is the yellow green clear liquid | This product is the yellow green clear liquid |
| Differentiate | Up to specification | Up to specification |
| Content | 90%～110% of labelled amount | 99.8％ |
| Acidity | 4～8 | 6.5 |
| The related substance list is assorted | ≤0.2 | 0.041 |
| Visible foreign matters | Up to specification | Up to specification |
| Pyrogen | Up to specification | Up to specification |
| Aseptic | Up to specification | Up to specification |
Embodiment 5:
This ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total liquor capacity to 3000ml.
Solvent is the mixed solution of dehydrated alcohol and water for injection, dehydrated alcohol 2700ml wherein, and surplus is water for injection.
The preparation method of this ornidazole injection, adopt following steps:
(1) preparating liquid: inject the 1800ml solvent first in Agitation Tank, then the 500g ornidazole is added in the Agitation Tank, stirring and dissolving gets the part medicinal liquid;
(2) remove impurity, depyrogenation: add the 12g active carbon in the part medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes, with 0.22 micron filtering with microporous membrane, the solvent that adds again surplus gets total medicinal liquid, filters, and checks;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
Testing result:
| Inspection item | Standard code | Assay |
| Character | This product is the yellow green clear liquid | This product is the yellow green clear liquid |
| Differentiate | Up to specification | Up to specification |
| Content | 90%～110% of labelled amount | 99.8％ |
| Acidity | 4～8 | 6.5 |
| The related substance list is assorted | ≤0.2 | 0.016 |
| Visible foreign matters | Up to specification | Up to specification |
| Pyrogen | Up to specification | Up to specification |
| Aseptic | Up to specification | Up to specification |
Embodiment 6:
This ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total liquor capacity to 5000ml.
Solvent is the mixed solution of dehydrated alcohol and water for injection, dehydrated alcohol 3000ml wherein, and surplus is water for injection.
The preparation method of this ornidazole injection, adopt following steps:
(1) preparating liquid: first inject the 3000ml solvent in Agitation Tank, then the 500g ornidazole is added in the Agitation Tank, stirring and dissolving adds the solvent of surplus again, and stirring and evenly mixing gets total medicinal liquid;
(2) remove impurity, depyrogenation: add the 22.5g active carbon in the total medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes with 0.22 micron filtering with microporous membrane, is checked;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
Testing result:
| Inspection item | Standard code | Assay |
| Character | This product is the yellow green clear liquid | This product is the yellow green clear liquid |
| Differentiate | Up to specification | Up to specification |
| Content | 90%～110% of labelled amount | 99.8％ |
| Acidity | 4～8 | 6.5 |
| The related substance list is assorted | ≤0.2 | 0.027 |
| Visible foreign matters | Up to specification | Up to specification |
| Pyrogen | Up to specification | Up to specification |
| Aseptic | Up to specification | Up to specification |
Embodiment 7:
This ornidazole injection comprises ornidazole 500g, and the surplus solubilizer makes total liquor capacity to 5000ml.
Solvent is the mixed solution of dehydrated alcohol and water for injection, dehydrated alcohol 4750ml wherein, and surplus is water for injection.
The preparation method of this ornidazole injection, adopt following steps:
(1) preparating liquid: first inject the 3000ml solvent in Agitation Tank, then the 500g ornidazole is added in the Agitation Tank, stirring and dissolving adds the solvent of surplus again, and stirring and evenly mixing gets total medicinal liquid;
(2) remove impurity, depyrogenation: add the 12.5g active carbon in the total medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes with 0.22 micron filtering with microporous membrane, is checked;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
The pH value that remains medicinal liquid in the above-mentioned preparation process is 4.0～7.0.
Testing result:
| Inspection item | Standard code | Assay |
| Character | This product is the yellow green clear liquid | This product is the yellow green clear liquid |
| Differentiate | Up to specification | Up to specification |
| Content | 90%～110% of labelled amount | 99.8％ |
| Acidity | 4～8 | 6.5 |
| The related substance list is assorted | ≤0.2 | 0.032 |
| Visible foreign matters | Up to specification | Up to specification |
| Pyrogen | Up to specification | Up to specification |
| Aseptic | Up to specification | Up to specification |
Ornidazole is easily molten in ethanol, chloroform, slightly soluble in water, and experiment finds that the ornidazole pH value of solution is influential to the dissolubility of ornidazole, pH and the raising temperature of turning down solution can improve the dissolubility of ornidazole in water.Active carbon also has absorption to the principal agent ornidazole, so will suitably reduce the consumption of active carbon in the preparation process in absorption impurity and thermal source.The beneficial effect of ornidazole injection of the present invention and preparation method thereof is: technique is simple, and cost is low, and is safe and reliable, compare with existing ornidazole injection, the present invention does not add propylene glycol, increases simultaneously the consumption of dehydrated alcohol, plays the effect of cosolvent and stabilizing agent by dehydrated alcohol, the impurity content of injection is reduced, guaranteed the stability of injection, be convenient to clinical use, ethanol is more safer than propylene glycol, avoid the stimulation of propylene glycol to human body, reduced medical-risk.
Stability test:
Embodiment 1-embodiment 7 is carried out accelerated test, method is: temperature is under 40 ± 2 ℃, the condition of humidity 75 ± 5%, embodiment 1-7 is investigated, time is 6 months, respectively at 0,1,3, the sampling in June, the detection index is character, related substance, pH value, visible foreign matters and content (%); Carry out with reference to the Pharmacopoeia of the People's Republic of China 2010 editions.
Wherein ornidazole injection is no more than 2.0% through content decrease behind the study on the stability, and character, pH value and visible foreign matters etc. all meet the national drug standards simultaneously.
The Accelerated stability test result
Claims (8)
1. ornidazole injection, it is characterized in that: comprise ornidazole 500g, the surplus solubilizer makes total medicine liquid volume to 2000～5000ml.
2. a kind of ornidazole injection according to claim 1, it is characterized in that: the percent by volume of dehydrated alcohol is 60%～100% in the described solvent, surplus is water for injection.
3. the preparation method of a claim 1 or 2 described a kind of ornidazole injections is characterized in that: comprise the steps:
(1) preparating liquid: first inject the solvent that accounts for total medicine liquid volume 60% in Agitation Tank, then ornidazole is added in the Agitation Tank, stirring and dissolving adds the solvent of surplus again, and stirring and evenly mixing gets total medicinal liquid;
(2) remove impurity, depyrogenation: add active carbon in the total medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes, with 0.22 micron filtering with microporous membrane, check;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
4. the preparation method of a kind of ornidazole injection according to claim 3 is characterized in that: the addition of active carbon is in the step (2): the active carbon that adds 0.2～0.5g in per hundred milliliters of total medicinal liquids.
5. the preparation method of a kind of ornidazole injection according to claim 3, it is characterized in that: the pH value that remains medicinal liquid in the preparation process is 4.0～7.0.
6. the preparation method of a claim 1 or 2 described a kind of ornidazole injections is characterized in that: comprise the steps:
(1) preparating liquid: inject the solvent that accounts for total medicine liquid volume 60% first in Agitation Tank, then ornidazole is added in the Agitation Tank, stirring and dissolving gets the part medicinal liquid;
(2) remove impurity, depyrogenation: add active carbon in the part medicinal liquid that makes to step (1), stirring and adsorbing 30 minutes, with 0.22 micron filtering with microporous membrane, the solvent that adds again surplus gets total medicinal liquid, filters check;
(3) embedding, packing: total medicinal liquid embedding, sterilization, leak detection, lamp inspection, the packing that step (2) is up to the standards and get final product.
7. the preparation method of a kind of ornidazole injection according to claim 6 is characterized in that: the addition of active carbon is in the step (2): the active carbon that adds 0.2～0.5g in per hundred milliliters of total medicinal liquids.
8. the preparation method of a kind of ornidazole injection according to claim 6, it is characterized in that: the pH value that remains medicinal liquid in the preparation process is 4.0～7.0.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104013571A (en) * | 2014-05-30 | 2014-09-03 | 江苏南山医药有限公司 | Ornidazole injection and preparing method thereof |
| CN104127379A (en) * | 2014-08-14 | 2014-11-05 | 珠海亿邦制药股份有限公司 | Ornidazole injection and preparation method thereof |
| CN104188903A (en) * | 2014-09-01 | 2014-12-10 | 北京蓝丹医药科技有限公司 | Ornidazole injection and preparation method thereof |
| CN111888328A (en) * | 2020-08-21 | 2020-11-06 | 山东致泰医药技术有限公司 | Ornidazole injection with rapid and stable performance and preparation method thereof |
| CN114353444A (en) * | 2022-01-14 | 2022-04-15 | 成都市海通药业有限公司 | Method for reducing impurity B in ornidazole injection |
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| CN1686116A (en) * | 2005-04-29 | 2005-10-26 | 南京圣和药业有限公司 | Levo ornidazole vein administration agent and its preparation method |
| CN102552127A (en) * | 2012-01-31 | 2012-07-11 | 石家庄开发区博欣医药科技开发有限公司 | Ornidazole injection |
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2013
- 2013-01-05 CN CN201310000708.2A patent/CN103006554B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1686116A (en) * | 2005-04-29 | 2005-10-26 | 南京圣和药业有限公司 | Levo ornidazole vein administration agent and its preparation method |
| CN102552127A (en) * | 2012-01-31 | 2012-07-11 | 石家庄开发区博欣医药科技开发有限公司 | Ornidazole injection |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104013571A (en) * | 2014-05-30 | 2014-09-03 | 江苏南山医药有限公司 | Ornidazole injection and preparing method thereof |
| CN104127379A (en) * | 2014-08-14 | 2014-11-05 | 珠海亿邦制药股份有限公司 | Ornidazole injection and preparation method thereof |
| CN104188903A (en) * | 2014-09-01 | 2014-12-10 | 北京蓝丹医药科技有限公司 | Ornidazole injection and preparation method thereof |
| CN104188903B (en) * | 2014-09-01 | 2016-09-21 | 北京蓝丹医药科技有限公司 | Ornidazole injection and preparation method thereof |
| CN111888328A (en) * | 2020-08-21 | 2020-11-06 | 山东致泰医药技术有限公司 | Ornidazole injection with rapid and stable performance and preparation method thereof |
| CN111888328B (en) * | 2020-08-21 | 2022-12-30 | 山东致泰医药技术有限公司 | Ornidazole injection with rapid and stable performance and preparation method thereof |
| CN114353444A (en) * | 2022-01-14 | 2022-04-15 | 成都市海通药业有限公司 | Method for reducing impurity B in ornidazole injection |
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| CN103006554B (en) | 2014-06-11 |
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Owner name: BEIJING GUORENTANG MEDICAL SCIENCE DEVELOPING CO., Free format text: FORMER OWNER: BEIJING GUORENTANG MEDICAL SCIENCE DEVELOPING CO., LTD. ZHUHAI EBANG PHARMACEUTICAL CO., LTD. Effective date: 20140528 |
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Effective date of registration: 20140528 Address after: Licheng District 250100 Shandong city of Ji'nan Province General Road No. 171-1 Patentee after: Jinan Ruifeng Pharmaceutical Co., Ltd. Patentee after: Beijing Guorentang Medical Science Developing Co., Ltd. Patentee after: Zhuhai Ebang Pharmaceutical Co., Ltd. Patentee after: YIBANG GUOCHUANG INSTITUTE OF MATERIA MEDICA (BEIJING) CO., LTD. Address before: Licheng District 250100 Shandong city of Ji'nan Province General Road No. 171-1 Patentee before: Jinan Ruifeng Pharmaceutical Co., Ltd. Patentee before: Beijing Guorentang Medical Science Developing Co., Ltd. Patentee before: Zhuhai Ebang Pharmaceutical Co., Ltd. |
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Address after: Licheng District 250100 Shandong city of Ji'nan Province General Road No. 171-1 Co-patentee after: BEIJING GUORENTANG PHARMACEUTICAL SCIENCE AND TECHNOLOGY DEVELOPMENT Co.,Ltd. Patentee after: JINAN RUIFENG PHARMACEUTICAL Co.,Ltd. Co-patentee after: Zhuhai Yibang Pharmaceutical Co.,Ltd. Co-patentee after: YIBANG GUOCHUANG INSTITUTE OF MATERIA MEDICA (BEIJING) Co.,Ltd. Address before: Licheng District 250100 Shandong city of Ji'nan Province General Road No. 171-1 Co-patentee before: BEIJING GUORENTANG PHARMACEUTICAL SCIENCE AND TECHNOLOGY DEVELOPMENT Co.,Ltd. Patentee before: JINAN RUIFENG PHARMACEUTICAL Co.,Ltd. Co-patentee before: ZHUHAI EBANG PHARMACEUTICAL Co.,Ltd. Co-patentee before: YIBANG GUOCHUANG INSTITUTE OF MATERIA MEDICA (BEIJING) Co.,Ltd. |
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