CN101550144B - Preparation technique for mezlocillin - Google Patents
Preparation technique for mezlocillin Download PDFInfo
- Publication number
- CN101550144B CN101550144B CN2009100156343A CN200910015634A CN101550144B CN 101550144 B CN101550144 B CN 101550144B CN 2009100156343 A CN2009100156343 A CN 2009100156343A CN 200910015634 A CN200910015634 A CN 200910015634A CN 101550144 B CN101550144 B CN 101550144B
- Authority
- CN
- China
- Prior art keywords
- water
- mezlocillin
- add
- slowly
- cooled
- 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
- 229960000198 mezlocillin Drugs 0.000 title claims abstract description 16
- YPBATNHYBCGSSN-VWPFQQQWSA-N mezlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O YPBATNHYBCGSSN-VWPFQQQWSA-N 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- ZWTPALHHEULAPI-UHFFFAOYSA-N 3-methylsulfonyl-2-oxoimidazolidine-1-carbonyl chloride Chemical compound CS(=O)(=O)N1CCN(C(Cl)=O)C1=O ZWTPALHHEULAPI-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000000605 extraction Methods 0.000 claims abstract description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- 239000013078 crystal Substances 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 9
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 8
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 7
- 239000012065 filter cake Substances 0.000 claims description 2
- 239000008213 purified water Substances 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 238000010792 warming Methods 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 abstract description 11
- 230000008025 crystallization Effects 0.000 abstract description 11
- 238000005917 acylation reaction Methods 0.000 abstract description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 8
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 abstract description 5
- 229960003311 ampicillin trihydrate Drugs 0.000 abstract description 5
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- XHXUANMFYXWVNG-ADEWGFFLSA-N (-)-Menthyl acetate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(C)=O XHXUANMFYXWVNG-ADEWGFFLSA-N 0.000 abstract 2
- 230000020477 pH reduction Effects 0.000 abstract 2
- 239000001605 (5-methyl-2-propan-2-ylcyclohexyl) acetate Substances 0.000 abstract 1
- XHXUANMFYXWVNG-UHFFFAOYSA-N D-menthyl acetate Natural products CC(C)C1CCC(C)CC1OC(C)=O XHXUANMFYXWVNG-UHFFFAOYSA-N 0.000 abstract 1
- 239000000890 drug combination Substances 0.000 abstract 1
- 230000007774 longterm Effects 0.000 abstract 1
- 239000012535 impurity Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 230000006837 decompression Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KCVTVKMPZQSSNU-UHFFFAOYSA-N 2-pyridin-4-ylethanethioyl chloride Chemical class ClC(=S)CC1=CC=NC=C1 KCVTVKMPZQSSNU-UHFFFAOYSA-N 0.000 description 1
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 1
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 1
- 0 CC(*)CC*(C(C)C=C)[N+]([O-])=O Chemical compound CC(*)CC*(C(C)C=C)[N+]([O-])=O 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- GTGQRSIMEUWHPA-ZBJAFUORSA-M mezlocillin sodium Chemical compound [Na+].N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O GTGQRSIMEUWHPA-ZBJAFUORSA-M 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention pertains to the technical field of drug combination preparation, more particularly relates to a preparation technique for mezlocillin. The preparation technique for mezlocillin comprisesthe following steps: ampicillin trihydrate and 1-chloroformyl-3-methylsulfonyl-2-imidazolidinone carry out acylation reaction under alkaline condition and then extraction, acidification and crystalli zation are conducted to obtain the mezlocillin. The invention is characterized in that when acylation reaction is conducted, reaction menstruum is water and acetone; after acylation reaction is finished, an ether extractant is added for carrying out extraction; and menthyl acetate is added before acidification so as to carry out acidified crystallization. The synthetic technique has obvious advantages, provides powerful guarantee for synthesizing the mezlocillin with high quality and has relatively great implementation value and long-term social and economic benefit.
Description
(1) technical field
The invention belongs to technical field of medicine synthesis, particularly a kind of preparation technology of mezlocillin.
(2) background technology
Mezlocillin is a kind of bulk drug of New-type wide-spectrum semi-synthetic penicillins microbiotic Sodium mezlocillin, synthesizing of relevant mezlocillin, reported two kinds of synthetic routes at present, promptly be starting raw material and be two kinds of routes of starting raw material with the three water acid of ammonia benzyl with the 6-amino-penicillanic acid.Wherein, because synthetic complexity, the synthetic route of preceding a kind of route are long, cost investment is higher, national most of enterprise all adopts second kind of route to produce.
At the original synthesis technique that with the three water acid of ammonia benzyl is starting raw material be: the three water acid of ammonia benzyl, water, ethyl acetate add in the four-hole bottle; be cooled to 16-19 ℃; add sodium bicarbonate; under the condition of pH value about 7.0, add 1-chloroformyl-3-methylsulfonyl-2-imidazolidone and carry out acylation reaction; add the back and continue reaction about 30 minutes; drip dilute hydrochloric acid again and transfer about pH value to 2.0, be cooled to 0 ℃, filtration washing, oven dry.
But there is following shortcoming in this synthetic route products obtained therefrom: the product crystalline form is poor, and impurity is higher, and content is on the low side, and solvent is residual higher, and quality stability is poor.
(3) summary of the invention
The present invention provides the preparation technology of a kind of product content height and stay-in-grade mezlocillin in order to remedy the deficiencies in the prior art.
The present invention is achieved through the following technical solutions:
A kind of preparation technology of mezlocillin; under alkaline condition, carry out acylation reaction by the acid of ammonia benzyl three water and 1-chloroformyl-3-methylsulfonyl-2-imidazolidone; again through extraction, acidifying, crystallization and make; its special character is: during acylation reaction; action solvent is water and acetone; after acylation reaction finishes, add the ether extration agent and extract, add methyl acetate during acidifying and carry out acidizing crystal.
The preparation technology of mezlocillin of the present invention, the ratio of quality and the number of copies of described action solvent water and acetone is 1: 0.4-0.6.
The preparation technology of mezlocillin of the present invention, the mol ratio of described ammonia benzyl three water acid and 1-chloroformyl-3-methylsulfonyl-2-imidazolidone is 1: 1-1.2
The preparation technology of mezlocillin of the present invention carries out an ether solvent extraction after the acylation reaction, the ether extration agent of adding is an isopropyl ether.
The preparation technology of mezlocillin of the present invention, described crystalline form are needle-like.
The present invention includes following processing step:
(1) under the room temperature, water, sodium bicarbonate and acetone are added in the four-hole bottle, molten clear back is stirred and is added the three water acid of ammonia benzyl down, is cooled to 15-20 ℃, is slowly adding 1-chloroformyl-3-methylsulfonyl-2-imidazolidone, adds the back and continues reaction 30 minutes;
(2) after reaction finishes, add isopropyl ether and carry out single extraction, water filters, and adds methyl acetate and is warming up to 20-25 ℃, slowly drip dilute hydrochloric acid and transfer pH value at 2.0-2.3, temperature control stirred 30 minutes, slowly was cooled to 0-5 ℃, filter, filter cake purified water washed twice, vacuum drying gets needle crystal.
Reaction equation of the present invention is:
Product quality indicator and stability compare:
Technology of the present invention is owing to changed reaction system when acylation reaction; reaction is carried out thoroughly; with isopropyl ether the relative substance in the reaction solution is extracted once again after acylation reaction finishes simultaneously; related substance has been reduced a lot; single impurity by original 0.3% be reduced to below 0.1%, total impurities by original 0.8% be reduced to below 0.25%, content is promoted to more than 99.0% by original 95%; again the recrystallisation solvent ethyl acetate is changed into methyl acetate before acidizing crystal, solvent is residual to be reduced to below 0.3% by original 0.6%.
The stability of product compares: 40 ℃ of study on the stability results of the high temperature of half a year are: the average content of product reduces by 2.5%, and total impurities, single impurity have on average risen 1.2%, 0.6% respectively.And adopting the product content of explained hereafter of the present invention on average to reduce by 0.8%, total impurities, single impurity have on average risen 0.5%, 0.15% respectively.
From quality index and study on the stability result, products obtained therefrom content height of the present invention, impurity is low, crystalline form good, residual low, the good stability of solvent, synthesis technique is with the obvious advantage, for synthetic high-quality mezlocillin sodium salt provides sound assurance, have bigger implementary value and far-reaching economic results in society.
(4) embodiment
Embodiment 1:
Under 20 ℃, water 100mL, sodium bicarbonate 6g and acetone 40mL join in the 250mL four-hole bottle; stir and add Ampicillin Trihydrate 12.5g down successively; be cooled to 16 ℃, moltenly slowly add 1-chloroformyl-3-methylsulfonyl-2-imidazolidone 6.6g after clear, continue reaction 30 minutes again.After the complete reaction, add isopropyl ether 60mL and extract, water is filtered to crystallization kettle after the layering.
Add methyl acetate 50mL, be cooled to 20 ℃ and slowly drip dilute hydrochloric acid, carry out acidizing crystal, regulate PH=2.0, temperature control stirred 30 minutes, after the crystallization fully, slowly was cooled to 0 ℃ of growing the grain and stirred 2h, carried out centrifuging, washing.Vacuum-0.08,40 a ℃ decompression oven dry 4h gets needle crystal 16.0g.
Quality index: content 99.5%, single impurity 0.09%, total impurities 0.25%, solvent residual 0.28%.
Embodiment 2:
Under 25 ℃, water 110mL, sodium bicarbonate 6g and acetone 45mL join in the 250mL four-hole bottle; stir and add Ampicillin Trihydrate 12.5g down successively; be cooled to 17 ℃, moltenly slowly add 1-chloroformyl-3-methylsulfonyl-2-imidazolidone 6.5g after clear, continue reaction 30 minutes again.After the complete reaction, add isopropyl ether 50mL and extract, water is filtered to crystallization kettle after the layering.
Add methyl acetate 55mL, be cooled to 22 ℃ and slowly drip dilute hydrochloric acid, carry out acidizing crystal, regulate PH=2.2, temperature control stirred 40 minutes, after the crystallization fully, slowly was cooled to 3 ℃ of growing the grains and stirred 2h, carried out centrifuging, washing.Vacuum-0.09,35 a ℃ decompression oven dry 5h gets 16.3g needle crystal.
Quality index: content 99.56%, single impurity 0.1%, total impurities 0.26%, solvent residual 0.25%.
Embodiment 3:
Under 25 ℃, water 120mL, sodium bicarbonate 6g and acetone 50mL join in the 250mL four-hole bottle; stir and add Ampicillin Trihydrate 12.5g down successively; be cooled to 16 ℃, moltenly slowly add 1-chloroformyl-3-methylsulfonyl-2-imidazolidone 6.8g after clear, continue reaction 30 minutes again.After the complete reaction, add isopropyl ether 50mL and extract, water is filtered to crystallization kettle after the layering.
Add methyl acetate 40mL, be cooled to 23 ℃ and slowly drip dilute hydrochloric acid, carry out acidizing crystal, regulate PH=2.2, temperature control stirred 30 minutes, after the crystallization fully, slowly was cooled to 0 ℃ of growing the grain and stirred 2h, carried out centrifuging, washing.Vacuum-0.08,50 a ℃ decompression oven dry 3h gets needle crystal 16.0g.
Quality index: content 99.2%, single impurity 0.08%, total impurities 0.27%, solvent residual 0.29%.
Embodiment 4:
Under 22 ℃, water 110mL, sodium bicarbonate 6g and acetone 55mL join in the 250mL four-hole bottle; stir and add Ampicillin Trihydrate three water acid 12.5g down successively; be cooled to 19 ℃, moltenly slowly add 1-chloroformyl-3-methylsulfonyl-2-imidazolidone 6.8g after clear, continue reaction 30 minutes again.After the complete reaction, add isopropyl ether 60mL and extract, water is filtered to crystallization kettle after the layering.
Add methyl acetate 35mL, temperature control slowly drips dilute hydrochloric acid at 20 ℃, carries out acidizing crystal, regulates PH=2.0, and temperature control stirred 30 minutes, after the crystallization fully, slowly is cooled to 2 ℃ of growing the grains and stirs 2h, carries out centrifuging, washing.Vacuum-0.09,45 a ℃ decompression oven dry 3h gets needle crystal 16.1g.
Quality index: content 99.8%, single impurity 0.1%, total impurities 0.28%, solvent residual 0.3%.
Claims (1)
1. the preparation technology of a mezlocillin is characterized by, and comprises following processing step:
(1) under the room temperature, water, sodium bicarbonate and acetone are added in the four-hole bottle, molten clear back is stirred and is added the three water acid of ammonia benzyl down, be cooled to 15-20 ℃, slowly add 1-chloroformyl-3-methylsulfonyl-2-imidazolidone acidylate again, add the back and continue reaction 30 minutes, the ratio of quality and the number of copies of water and acetone is 1: 0.4-0.6, and the mol ratio of the acid of ammonia benzyl three water and 1-chloroformyl-3-methylsulfonyl-2-imidazolidone is 1: 1-1.2;
(2) after reaction finishes, add isopropyl ether and carry out single extraction, water filters, and adds methyl acetate and is warming up to 20-25 ℃, slowly drip the dilute hydrochloric acid adjust pH at 2.0-2.3, temperature control stirred 30 minutes, slowly was cooled to 0-5 ℃, filter, filter cake purified water washed twice, vacuum drying gets needle crystal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100156343A CN101550144B (en) | 2009-05-22 | 2009-05-22 | Preparation technique for mezlocillin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100156343A CN101550144B (en) | 2009-05-22 | 2009-05-22 | Preparation technique for mezlocillin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101550144A CN101550144A (en) | 2009-10-07 |
| CN101550144B true CN101550144B (en) | 2011-05-11 |
Family
ID=41154660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100156343A Active CN101550144B (en) | 2009-05-22 | 2009-05-22 | Preparation technique for mezlocillin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101550144B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106932347B (en) * | 2017-05-17 | 2019-04-12 | 浙江遂昌利民科技有限公司 | A kind of mezlocillin and its quality index detection method |
| CN113121569A (en) * | 2021-04-20 | 2021-07-16 | 海南通用三洋药业有限公司 | Preparation method of mezlocillin sodium |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3974142A (en) * | 1971-10-23 | 1976-08-10 | Bayer Aktiengesellschaft | Penicillins |
| US4229349A (en) * | 1978-04-20 | 1980-10-21 | Bayer Aktiengesellschaft | Production of semi-synthetic β-lactam antibiotics |
| CN1239717A (en) * | 1998-06-19 | 1999-12-29 | 山东沂蒙新华制药厂 | Preparation process of Meloxine sodium |
| CN1634929A (en) * | 2004-10-27 | 2005-07-06 | 山东瑞阳制药有限公司 | Preparation process of mezlocillin sodium |
| CN101328187A (en) * | 2007-06-20 | 2008-12-24 | 瑞阳制药有限公司 | Preparing process of mezlocillin |
-
2009
- 2009-05-22 CN CN2009100156343A patent/CN101550144B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3974142A (en) * | 1971-10-23 | 1976-08-10 | Bayer Aktiengesellschaft | Penicillins |
| US4229349A (en) * | 1978-04-20 | 1980-10-21 | Bayer Aktiengesellschaft | Production of semi-synthetic β-lactam antibiotics |
| CN1239717A (en) * | 1998-06-19 | 1999-12-29 | 山东沂蒙新华制药厂 | Preparation process of Meloxine sodium |
| CN1634929A (en) * | 2004-10-27 | 2005-07-06 | 山东瑞阳制药有限公司 | Preparation process of mezlocillin sodium |
| CN101328187A (en) * | 2007-06-20 | 2008-12-24 | 瑞阳制药有限公司 | Preparing process of mezlocillin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101550144A (en) | 2009-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101830852B (en) | Edaravone compound synthesized by new method | |
| CN106256824B (en) | Preparation method of high-purity delafloxacin meglumine salt | |
| CN109369478B (en) | Synthesis method of zinc methionine chelate | |
| CN103420881B (en) | A kind of preparation method of medicinal racemization hydroxyl Methionine calcium salt newly | |
| CN102702232A (en) | Method for preparation of fine cefamandole nafate | |
| CN102001992B (en) | Method for preparing clevidipine butyrate | |
| CN103601735B (en) | A kind of method of mosictin of purifying | |
| CN101550144B (en) | Preparation technique for mezlocillin | |
| CN104926709A (en) | L-tryptophan refining method | |
| CN106749226B (en) | Preparation method of avatrombopag maleate crystal form C | |
| CN105315198A (en) | Crystal form of pirfenidone and preparation method of crystal form | |
| EP1832593A1 (en) | Direct process for the production of sterile Cefepime dihydrochloride monohydrate | |
| CN106946676B (en) | Purification method of high-purity trichloroacetone for preparing folic acid | |
| CN106565776A (en) | Separating and purifying method for 4-(methyl hydroxyl phosphoryl)-2-carbonyl butyric acid | |
| CN102731340A (en) | Preparation method of demethyl aureomycin hydrochloride | |
| CN102344392B (en) | Method for refining histone deacetylase (HDAC) inhibitor vorinostat | |
| CN102532125A (en) | Synthesis method for aztreonam compound | |
| CN103755577A (en) | Method for recovering ambroxol base from ambroxol hydrochloride refined mother solution | |
| CN114195761B (en) | Preparation method of high-purity sitafloxacin hydrate 3/2 | |
| CN110483270B (en) | Preparation method for efficient green synthesis of fenofibric acid | |
| CN109761801B (en) | Novel method for preparing ketovaline calcium | |
| CN109134385A (en) | A kind of purification process of uracil compounds | |
| CN109897002B (en) | Preparation of 1-phenyl-2, 3-dimethyl-4-methylaminopyrazolin-5-one-N-methyl magnesium sulfonate hexahydrate | |
| CN107501216B (en) | Novel synthesis method of high-stability bismuth citrate ranitidine | |
| CN109956886B (en) | Preparation method of ethyl (Z) - [ (4-methoxyphenyl) hydrazono ] chloroacetate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: SHANDONG RUNZE PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: HEZE RUICHANG CHEMICAL CO., LTD. Effective date: 20110113 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 274000 HEZE RUICHANG CHEMICAL CO., LTD., HELOU DEVELOPMENT AREA, MUDAN DISTRICT, HEZE CITY, SHANDONG PROVINCE TO: 274000 NORTH SECTION OF KUNMING ROAD, MUDAN INDUSTRIAL PARK, HEZE CITY, SHANDONG PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20110113 Address after: 274000 north section of Kunming Road, peony Industrial Park, Shandong, Heze Applicant after: SHANDONG RUNZE PHARMACEUTICAL Co.,Ltd. Address before: 274000, Mudan District, Shandong City, Heze Province Development Zone, Heze Rui Chang Chemical Co., Ltd. Applicant before: HEZE RUICHANG CHEMICAL Co.,Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190419 Address after: 274039 No. 1777 Kunming Road, Mudan District, Heze City, Shandong Province Patentee after: Shandong Ruiying Pharmaceutical Group Co.,Ltd. Address before: 274000 North Section of Kunming Road, Heze Mudan Industrial Park, Shandong Province Patentee before: SHANDONG RUNZE PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| PP01 | Preservation of patent right |
Effective date of registration: 20210416 Granted publication date: 20110511 |
|
| PP01 | Preservation of patent right | ||
| PD01 | Discharge of preservation of patent | ||
| PD01 | Discharge of preservation of patent |
Date of cancellation: 20221125 Granted publication date: 20110511 |