CN103172696B - Preparation method of perindopril arginine salt of gamma-crystal form - Google Patents
Preparation method of perindopril arginine salt of gamma-crystal form Download PDFInfo
- Publication number
- CN103172696B CN103172696B CN201210555176.4A CN201210555176A CN103172696B CN 103172696 B CN103172696 B CN 103172696B CN 201210555176 A CN201210555176 A CN 201210555176A CN 103172696 B CN103172696 B CN 103172696B
- Authority
- CN
- China
- Prior art keywords
- water
- perindopril
- arginine
- preparation
- hexanaphthene
- 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.)
- Active
Links
Landscapes
- Indole Compounds (AREA)
Abstract
The invention discloses a preparation method of perindopril arginine salt of a gamma-crystal form. The preparation method comprises the following steps of: dissolving perindopril and L-arginine in water; adding an organic solvent after stirring and dissolving the perindopril and L-arginine; heating up the mixture until the mixture is refluxed; distributing water by utilizing a water distributor until no water enters the water distributor; cooling a reaction liquid to the room temperature for carrying out suction filtration; and drying the filter cake to obtain the perindopril arginine salt of the gamma-crystal form. According to the preparation method of the perindopril arginine salt of the gamma-crystal form disclosed by the invention, the organic solvent is added for refluxing and distributing water; the water is extracted by the solvent, so that no water exists in the reaction liquid, and therefore, the water molecule is not packaged by the target product to form a spherical shape, and the suction filtration and separation are easy; and meanwhile, the water is separated out, the yield of the product is 92% or higher.
Description
Technical field
The present invention relates to a kind of preparation method of perindopril arginine salt of γ crystal formation, belong to technical field of pharmaceuticals.
Background technology
Perindopril and arginic acid salt thereof are a kind of ACEI inhibitor (CEI), are mainly used in treatment Arterial Hypertention and heart failure.Perindopril arginine salt has high pharmacy value and satisfactory stability, chemistry is by name: (2S)-2-[(1S)-ethoxycarbonyl butyl is amino]-1-oxo-propyll-(2S, 3As, 7aS) perhydro indoles-carboxylic acid arginine salt, structural formula as shown in the formula (I):
About preparation method and the therepic use thereof of perindopril, existing description in European patent specification EP0049658.Perindopril arginine salt γ crystal formation and multiple preparation method thereof is disclosed in international application WO2009157018, what wherein describe is soluble in water by perindopril, add L-arginine, then take lyophilize or spraying dry except desolventizing, suction filtration obtains γ crystal formation, and the method needs to adopt freeze drier or spray drying device.
The second preparation method be by perindopril and L-arginine soluble in water, then add the first solvent, then add the second solvent in the cooling condition, finally carry out suction filtration separation.
Perindopril is dissolved in the mixed solvent of ketone, alcohol or Isosorbide-5-Nitrae-dioxane and water by the third preparation method, in its solution, then add the aqueous solution of L-arginine, finally carries out the perindopril arginine salt that suction filtration is separated obtained γ crystal formation.
Above-mentioned second and the third preparation method take part in reaction because of there being water, in aftertreatment suction filtration process, target product can wrap up water molecules and be formed and be spherically unfavorable for suction filtration, while also can reduce yield, extend the follow-up baking material time.
Summary of the invention
Technical problem to be solved by this invention is the shortcoming overcome in the perindopril arginine salt preparation process of above-mentioned γ crystal formation, the perindopril arginine salt preparation method of the γ crystal formation that research and design is new.
The technical solution used in the present invention is as follows:
A kind of preparation method of perindopril arginine salt of γ crystal formation as shown in the formula (I), it is characterized in that described method for: by the perindopril shown in formula (II) and L-arginine soluble in water, stir molten clear after add organic solvent, be heated to reflux and utilize fraction water device water-dividing, no longer include to water trap water when entering, solvent no longer layering time-division water complete, reaction solution is down to room temperature suction filtration, filter cake dries the perindopril arginine salt of the γ crystal formation namely obtained as shown in the formula (I);
Described organic solvent is the mixed solvent of hexanaphthene or hexanaphthene and polar solvent, and described polar solvent is ethyl acetate, acetone or Iso Butyl Acetate.The volume ratio of described hexanaphthene and polar solvent is preferably 1 ~ 2:1.
Described organic solvent is preferably hexanaphthene.
Described L-arginine is 0.7 ~ 1:1 with the ratio of the amount of substance of perindopril, is preferably 0.9:1.
The volumetric usage of described water counts 1 ~ 2mL/g with the quality of perindopril, is preferably 2mL/g.
The volumetric usage of described organic solvent counts 5 ~ 20mL/g with the quality of perindopril, is preferably 20mL/g.
Described reaction solution is down to room temperature suction filtration, and the filtrate that suction filtration obtains, through simple distillation and the recyclable organic solvent be recycled, can be used in the reaction of next batch.
Concrete, recommendering folder inventive method is carried out according to the following steps: by the perindopril shown in formula (II) and L-arginine soluble in water, stir molten clear after add hexanaphthene, be heated to reflux and utilize fraction water device water-dividing, to water trap, no longer include water enter time-division water and complete, reaction solution is down to room temperature suction filtration, filter cake dries the perindopril arginine salt of the γ crystal formation namely obtained as shown in the formula (I); Described L-arginine is 0.9:1 with the ratio of the amount of substance of perindopril, and the volumetric usage of described water counts 2mL/g with the quality of perindopril; The volumetric usage of described hexanaphthene counts 20mL/g with the quality of perindopril.
Compared with prior art, the beneficial effect of technical solution of the present invention is mainly reflected in:
The present invention carries out reflux water-dividing by adding organic solvent, by moisture via solvent bank water extraction out, does not have moisture in reaction solution, thus target product can not wrap up water molecules is formed spherical, and easy suction filtration is separated; Simultaneously because water is separated, the yield of product is high, can reach more than 92%, and the yield of prior art only has 75%.In addition, namely the organic solvent used in the inventive method can recycle and reuse through simple distillation, environmental protection.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction pattern of the perindopril arginine salt of the γ crystal formation that embodiment 2 obtains.
Embodiment:
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
The preparation of embodiment 1, perindopril
The perindopril tert-butylamine salt of 60.0g is dissolved in 240mL water, add the methylene dichloride of 240mL, stir at 25-30 DEG C, then in above-mentioned solution, drip the hydrochloric acid of 2.0mol/L, the pH value of water transfer phase is 3.8-4.4, finally by separation, with dichloromethane extraction, concentrating under reduced pressure organic phase obtains perindopril.
The preparation of the perindopril arginine salt (I) of embodiment 2, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add hexanaphthene 100mL, start temperature rising reflux and divide water, no longer include water in water trap and enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.36g that the complete filter cake of suction filtration obtains after drying, productive rate is 95.9%, HPLC content: the perindopril arginine salt 99.98%) being final product γ crystal formation, X-ray powder diffraction is shown in accompanying drawing 1, and visible product is the perindopril arginine salt of γ crystal formation.Hexanaphthene in suction filtration gained filtrate is through simple distillation and recyclable.
The preparation of the perindopril arginine salt (I) of embodiment 3, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 1.66g(0.0095mol), water 5mL, is stirred to clearly molten.Then in above-mentioned solution, add hexanaphthene 50mL, start temperature rising reflux and divide water.No longer include water in water trap to enter, solvent no longer layering time-division water completes, and starts cooling.Be cooled to 30 DEG C and start suction filtration, white powder solid (the heavy 4.80g that the complete filter cake of suction filtration obtains after drying, productive rate is 92.8%, HPLC content: the perindopril arginine salt 99.95%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.Hexanaphthene in suction filtration gained filtrate is through simple distillation and recyclable.
The preparation of the perindopril arginine salt (I) of embodiment 4, γ crystal formation
5.0g(0.0136mol is added in 100mL four-hole bottle) perindopril, L-arginine 2.37g(0.0136mol), water 7.5mL, is stirred to clearly molten.Then in above-mentioned solution, add hexanaphthene 25mL, start temperature rising reflux and divide water.No longer include water in water trap to enter, solvent no longer layering time-division water completes, and starts cooling.Lower the temperature 25 DEG C and start suction filtration, (heavy 7.0g, productive rate is 94.8%, HPLC content to the white powder solid that the complete filter cake of suction filtration obtains after drying: the perindopril arginine salt 99.98%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.Hexanaphthene in suction filtration gained filtrate is through simple distillation and recyclable
The preparation of the perindopril arginine salt (I) of embodiment 5, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add ethyl acetate 50mL and hexanaphthene 50mL, start temperature rising reflux and divide water, no longer include water in water trap and enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.25g that the complete filter cake of suction filtration obtains after drying, productive rate is 94.2%, HPLC content: the perindopril arginine salt 99.96%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.Hexanaphthene in suction filtration gained filtrate and the mixed solution of ethyl acetate, through simple distillation and the recyclable mixed solution obtaining hexanaphthene and ethyl acetate, adopt its ratio of gas chromatography determination, can reuse.
The preparation of the perindopril arginine salt (I) of embodiment 6, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 5mL, is stirred to clearly molten.Then in above-mentioned solution, add hexanaphthene 50mL and acetone 25mL, start temperature rising reflux and divide water.No longer include water in water trap to enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.15g that the complete filter cake of suction filtration obtains after drying, productive rate is 92.7%, HPLC content: the perindopril arginine salt 99.95%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.
The preparation of the perindopril arginine salt (I) of embodiment 7, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add hexanaphthene 50mL and Iso Butyl Acetate 25mL, start temperature rising reflux and divide water.No longer include water in water trap to enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.2g that the complete filter cake of suction filtration obtains after drying, productive rate is 93.4%, HPLC content: the perindopril arginine salt 99.98%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.
The preparation of the perindopril arginine salt (I) of embodiment 8, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add hexanaphthene 50mL and acetone 50mL, start temperature rising reflux and divide water.No longer include water in water trap to enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.2g that the complete filter cake of suction filtration obtains after drying, productive rate is 93.4%, HPLC content: the perindopril arginine salt 99.97%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.
The preparation of the perindopril arginine salt (I) of embodiment 9, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add the hexanaphthene and ethyl acetate 100mL that reclaim in embodiment 5, start temperature rising reflux and divide water, no longer include water in water trap and enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.3g that the complete filter cake of suction filtration obtains after drying, productive rate is 95.0%, HPLC content: the perindopril arginine salt 99.98%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.
The preparation of the perindopril arginine salt (I) of embodiment 10, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 1.89g(0.0108mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add the hexanaphthene 100mL of recovery, start temperature rising reflux and divide water, in water trap, solvent no longer includes water and enters, and no longer water completes the layering time-division, starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 5.56g that the complete filter cake of suction filtration obtains after drying, productive rate is 94.5%, HPLC content: the perindopril arginine salt 99.98%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.
The preparation of the perindopril arginine salt (I) of embodiment 11, γ crystal formation
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add the hexanaphthene 100mL of recovery, start temperature rising reflux and divide water, no longer include water in water trap and enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.33g that the complete filter cake of suction filtration obtains after drying, productive rate is 95.4%, HPLC content: the perindopril arginine salt 99.96%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.
The preparation of the perindopril arginine salt (I) of embodiment 12, γ crystal formation
The ethyl acetate of recovery and hexanaphthene mixed solvent are mixed with the mixed solution of 1:1 according to the result of gas phase external standard method.
5.0g(0.0136mol is added in 150mL four-hole bottle) perindopril, L-arginine 2.13g(0.0122mol), water 10mL, is stirred to clearly molten.Then in above-mentioned solution, add the 1:1 mixed solvent (100mL) of recovery ethyl acetate and the hexanaphthene prepared, start temperature rising reflux and divide water, no longer include water in water trap and enter, solvent no longer layering time-division water completes, and starts cooling.Suction filtration is started after being cooled to room temperature, white powder solid (the heavy 6.29g that the complete filter cake of suction filtration obtains after drying, productive rate is 94.8%, HPLC content: the perindopril arginine salt 99.97%) being final product γ crystal formation, and X-ray powder diffraction is consistent with accompanying drawing 1.
Claims (4)
1. the preparation method such as formula the perindopril arginine salt of the γ crystal formation shown in (I), it is characterized in that described method for: by the perindopril shown in formula (II) and L-arginine soluble in water, stir molten clear after add organic solvent, be heated to reflux and utilize fraction water device water-dividing, to water trap, no longer include water enter time-division water and complete, reaction solution is down to room temperature suction filtration, filter cake dries the perindopril arginine salt namely obtained such as formula the γ crystal formation shown in (I);
Described organic solvent is the mixed solvent of hexanaphthene or hexanaphthene and polar solvent, and described polar solvent is ethyl acetate, acetone or Iso Butyl Acetate; The volume ratio of described hexanaphthene and polar solvent is 1 ~ 2:1
Described L-arginine is 0.7 ~ 1:1 with the ratio of the amount of substance of perindopril;
The volumetric usage of described water counts 1 ~ 2mL/g with the quality of perindopril;
The volumetric usage of described organic solvent counts 5 ~ 20mL/g with the quality of perindopril.
2. the method for claim 1, is characterized in that described L-arginine is 0.9:1 with the ratio of the amount of substance of perindopril.
3. preparation method according to claim 1, is characterized in that the volumetric usage of described organic solvent counts 20mL/g with the quality of perindopril.
4. preparation method according to claim 1, it is characterized in that described method for: by the perindopril shown in formula (II) and L-arginine soluble in water, stir molten clear after add hexanaphthene, be heated to reflux and utilize fraction water device water-dividing, to water trap, no longer include water enter time-division water and complete, reaction solution is down to room temperature suction filtration, filter cake dries the perindopril arginine salt namely obtained such as formula the γ crystal formation shown in (I); Described L-arginine is 0.9:1 with the ratio of the amount of substance of perindopril, and the volumetric usage of described water counts 2mL/g with the quality of perindopril; The volumetric usage of described hexanaphthene counts 20mL/g with the quality of perindopril.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210555176.4A CN103172696B (en) | 2012-12-19 | 2012-12-19 | Preparation method of perindopril arginine salt of gamma-crystal form |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210555176.4A CN103172696B (en) | 2012-12-19 | 2012-12-19 | Preparation method of perindopril arginine salt of gamma-crystal form |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103172696A CN103172696A (en) | 2013-06-26 |
| CN103172696B true CN103172696B (en) | 2014-12-17 |
Family
ID=48632946
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210555176.4A Active CN103172696B (en) | 2012-12-19 | 2012-12-19 | Preparation method of perindopril arginine salt of gamma-crystal form |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103172696B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112047999B (en) * | 2020-09-18 | 2022-12-02 | 天津力生制药股份有限公司 | Preparation method of gamma-crystal form arginine perindopril salt |
| SI26268A (en) | 2021-11-18 | 2023-05-31 | Zupet Rok | Procedure for the preparation of the hydrated form of perindopril L-arginine |
| CN114149357B (en) * | 2021-12-29 | 2024-06-25 | 江苏嘉逸医药有限公司 | Preparation method of gamma-crystal form perindopril arginine salt |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1451656A (en) * | 2002-04-18 | 2003-10-29 | 瑟维尔实验室 | Novel salt of perindopril and pharmaceutical composition contg. same |
| CN101389603A (en) * | 2006-02-28 | 2009-03-18 | 瑟维尔实验室 | Crystalline form of the arginine salt of perindopril, process for preparing it, and pharmaceutical compositions comprising it |
| CN101389604A (en) * | 2006-02-28 | 2009-03-18 | 瑟维尔实验室 | Beta-crystalline form of perindopril arginine salt, method for making same, and pharmaceutical compositions containing same |
| WO2009157018A3 (en) * | 2008-06-24 | 2010-07-29 | Matrix Laboratories Ltd | Novel polymorphic forms of perindopril (l)-arginine and process for the preparation thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009212902A1 (en) * | 2008-09-03 | 2010-03-18 | Apotex Pharmachem Inc. | Amorphous form of an L-arginine salt of perindopril and processes of preparation thereof |
-
2012
- 2012-12-19 CN CN201210555176.4A patent/CN103172696B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1451656A (en) * | 2002-04-18 | 2003-10-29 | 瑟维尔实验室 | Novel salt of perindopril and pharmaceutical composition contg. same |
| CN101389603A (en) * | 2006-02-28 | 2009-03-18 | 瑟维尔实验室 | Crystalline form of the arginine salt of perindopril, process for preparing it, and pharmaceutical compositions comprising it |
| CN101389604A (en) * | 2006-02-28 | 2009-03-18 | 瑟维尔实验室 | Beta-crystalline form of perindopril arginine salt, method for making same, and pharmaceutical compositions containing same |
| WO2009157018A3 (en) * | 2008-06-24 | 2010-07-29 | Matrix Laboratories Ltd | Novel polymorphic forms of perindopril (l)-arginine and process for the preparation thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103172696A (en) | 2013-06-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103172696B (en) | Preparation method of perindopril arginine salt of gamma-crystal form | |
| CN103626642A (en) | Method for preparing vanillin | |
| CN104736540B (en) | The preparation method of pemetrexed and its lysine salt | |
| CN105111197B (en) | Synthesis method of raltitrexed | |
| CN103570621B (en) | Preparation method of (-)-huperzine A | |
| CN109701032A (en) | A kind of supercritical CO2Anti-solvent technology prepares myricetin/HP- beta-CD inclusion ultra-fine grain method | |
| CN104292238A (en) | Method for extracting sesamin from sesame cake meals | |
| CN115784981A (en) | Preparation process of piroctone olamine salt | |
| CN105669429A (en) | Preparation method of rhodium octanoate dimer | |
| CN105330560A (en) | Enzalutamide intermediate preparation method | |
| CN104193638A (en) | Method for preparing (S)-2',6'-dimethyl tyrosine and derivative of (S)-2',6'-dimethyl tyrosine, and derivative | |
| CN104402973A (en) | Method for preparing carfilzomib amorphous crystal | |
| CN103351376B (en) | Synthetic method of 2-thiophene ethylamine | |
| CN101717352B (en) | Method for synthesizing agmatine sulfate | |
| CN106316974B (en) | A kind of production technology of hymexazol active compound | |
| CN104974051A (en) | Synthetic method for (1S,4R)-cis-4-amino-2-cyclopentene-1-methanol hydrochloride | |
| CN114736154A (en) | Preparation method of N- (3-chloro-4- (2-pyridylmethoxy) phenyl) -2-cyanoacetamide | |
| CN110683992B (en) | Method for synthesizing econazole nitrate by one-pot method | |
| CN107721899B (en) | Eutectic solvent and preparation method thereof | |
| CN107382875A (en) | A kind of synthetic method of rosuvastain calcium chiral isomer impurity | |
| CN102010345A (en) | Method for preparing D-phenylalanine through dynamic kinetic resolution | |
| CN103333110B (en) | Production method of medicinal laurocapram | |
| CN106349145A (en) | Method for preparing intelligence-improving medicine (S)-oxiracetam | |
| CN106831499B (en) | A kind of preparation method of benzylidene camphor sulfonic acid | |
| CN103724250B (en) | A kind of preparation method of (S)-Olaxiracetam |
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 | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190506 Address after: 315100 4-5 floors of No. 378 Dongqing Road, Ningbo High-tech Zone, Zhejiang Province Patentee after: Ningbo High-tech Zone Menova Medical Innovation Research Institute Co., Ltd. Address before: 315040 Yangfan Road 999, Ningbo Hi-tech Zone, Ningbo City, Zhejiang Province, 12B Floor, Building 1, Ningbo R&D Park Patentee before: Ningbo Menovo Pharmaceutical Co., Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191227 Address after: 1406, room 1, No. 999, Lane 315048, sailing Road, hi tech Zone, Zhejiang, Ningbo Patentee after: Ningbo Menovo Pharmaceutical Co., Ltd. Address before: 315100 4-5 floors of No. 378 Dongqing Road, Ningbo High-tech Zone, Zhejiang Province Patentee before: Ningbo High-tech Zone Menova Medical Innovation Research Institute Co., Ltd. |
|
| TR01 | Transfer of patent right |