CN102093349A - Method for performing industrialized production on moxifloxacin hydrochloride - Google Patents
Method for performing industrialized production on moxifloxacin hydrochloride Download PDFInfo
- Publication number
- CN102093349A CN102093349A CN 201110008996 CN201110008996A CN102093349A CN 102093349 A CN102093349 A CN 102093349A CN 201110008996 CN201110008996 CN 201110008996 CN 201110008996 A CN201110008996 A CN 201110008996A CN 102093349 A CN102093349 A CN 102093349A
- Authority
- CN
- China
- Prior art keywords
- moxifloxacin hydrochloride
- moxifloxacin
- drying
- aqueous solution
- hydrochloride
- 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.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for synthesizing moxifloxacin hydrochloride. The method is characterized in that: moxifloxacin hydrochloride is precipitated from solution according to solubility difference of the moxifloxacin hydrochloride in sodium chloride solution with different concentrations so as to fulfill the aim of separation. The method particularly comprises the following steps of: adding sodium chloride into moxifloxacin hydrochloride-containing aqueous solution; stirring to crystallize; filtering; drying; recrystallizing with water; filtering; and drying to obtain the moxifloxacin hydrochloride. The method is simple and convenient in operation; the product has high purity; a single impurity is less than 0.1 percent; the total impurities are less than 0.2 percent; and the method is suitable for industrialized production.
Description
Technical field
The present invention relates to a kind of method of industrialized production Moxifloxacin hydrochloride.Moxifloxacin hydrochloride is a fluoroquinolone antibiotics, can be used for treating responsive microbial infection.
Formula I
Technical background
Moxifloxacin hydrochloride (Moxifloxacin hydrochloride) is the super wide spectrum quinolone antibiotic of Beyer Co., Ltd's development, chemistry is by name: 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxyl group-7-[(4 α S, 7 α S)-octahydro-6H-pyrrolo-[3,4-b] pyridine-6-yl]-4-oxo-3-quinoline carboxylic acid hydrochloride.Its chemical structural formula as shown in Equation 1.
Moxifloxacin hydrochloride went on the market in Germany first in September, 1999, obtained the FDA approval December and went on the market in the U.S..Keeping on the outstanding active basis of the anti-gram-negative bacteria of early stage fluoroquinolone, anti-gram positive organism and atypia pathogenic agent have obviously been strengthened (as mycoplasma, chlamydozoan, legionella and anerobe etc.) activity, clinical being mainly used in treated acute sinus gland inflammation, the acute attack of chronic bronchitis, community acquired pneumonia, and uncomplicated skin infections and skin soft-tissue infection.
This product has broad-spectrum antibacterial activity, especially Gram-positive, mycoplasma, chlamydozoan, legionella isoreactivity is much better than Ciprofloxacin, and effective to anerobe.The human body long half time, 1 400mg of administration every day can reach encouraging result.Clinical being mainly used in treated acute sinus gland inflammation, the acute attack of chronic bronchitis, community acquired pneumonia, and uncomplicated skin infections and skin soft-tissue infection.The characteristics of this product are almost not have photosensitized reaction, are considered to " the treatment respiratory tract infection is near the ideal medicine ".
The synthetic EP550903 that sees the earliest of Moxifloxacin hydrochloride, structure and a kind of breadboard synthetic method of Moxifloxacin are disclosed, adopted parent nucleus 1-cyclopropyl-6,7-two fluoro-8-methoxyl groups-1, and 4-dihydro-4-Oxoquinoline-3-carboxylic acid ethyl ester and side chain (s, s)-2, the method of 8-diazabicyclo [4.3.0] nonane condensation, can prepare target compound by this method, but post-treating method is the extracting operation and the column chromatogram chromatography purifying of multistep complexity, when suitability for industrialized production, is difficult to realize.
Patent CN02131962 discloses and has a kind ofly reacted the method that makes Moxifloxacin hydrochloride with 8-BAY 128039 carboxylic acid derivative and potassium tert.-butoxide or sodium tert-butoxide in water and alcoholic solution.Its post-treating method is to be added dropwise to dilute hydrochloric acid in reaction solution, and adds crystal seed, stirring and crystallizing.The gained crystal filters, and aqueous solution recrystallization can obtain the Moxifloxacin hydrochloride product.This method is simpler relatively, but product loss is bigger in reaction solution, has reduced yield, and needs to add the crystal seed crystallization.
Patent CN101817820 discloses the side chain compound (s with the Boc protection; s)-2; 8-diazabicyclo [4.3.0] nonane prepares the method for Moxifloxacin hydrochloride; its method is that gained Moxifloxacin crude product is added stirring and crystallizing in the dilute hydrochloric acid; filter, a large amount of frozen water washings obtain the Moxifloxacin hydrochloride crude product.There is the big shortcoming of product loss in same this method.
The prescription of Moxifloxacin hydrochloride sodium-chlor preparation is disclosed among the patent CN1368891, and in specification sheets, provide the solubleness of 5 ℃ of following Moxifloxacin hydrochlorides in the sodium chloride solution of 0～0.9% concentration, the solubleness of Moxifloxacin hydrochloride reduces with sodium chloride concentration from 0 to 0.9%.But this patent does not relate to the influence to Moxifloxacin hydrochloride solubleness of other temperature and 0.9% above concentration sodium chloride aqueous solution, finds to utilize saltouing of high density to prepare highly purified Moxifloxacin hydrochloride industrial.
In research process, the discovery that we are surprised, the solubleness of Moxifloxacin hydrochloride in water is along with the reduction of temperature and the increase of sodium chloride concentration descend rapidly, in 1% above sodium chloride solution, can reach fully, from the aqueous solution, precipitate and isolate the purpose of highly purified Moxifloxacin hydrochloride with acceptable yield.This method is never seen and is applied in Moxifloxacin hydrochloride synthetic.
Utilize this characteristic, we have invented a kind of method of industrialized production Moxifloxacin hydrochloride, and through the Moxifloxacin hydrochloride yield height that this method is produced, quality is good, can guarantee the single impurity of products obtained therefrom less than 0.1%, and total impurities is less than 0.2%.
Summary of the invention
The purpose of this invention is to provide a kind of simple to operate, mild condition, yield is higher and be easy to the production method of industrialized Moxifloxacin hydrochloride.Through a large amount of evidences, present method has extremely strong industrialization feasibility, can stablize the control quality product, obtains that highly purified Moxifloxacin hydrochloride list is assorted to be no more than 0.1%, always assortedly is no more than 0.2%.
Particularly, production method of the present invention is: will contain following solid sodium chloride or sodium chloride aqueous solution, the insulated and stirred crystallization of adding of aqueous solution stirring of Moxifloxacin hydrochloride through synthetic, filter water recrystallization, 0～40 ℃ of crystallization, filter, air blast or vacuum-drying promptly get product.
Moxifloxacin hydrochloride production method of the present invention, the add-on of solid sodium chloride or sodium chloride aqueous solution is: the mass percent that adding post chlorization sodium accounts for overall solution volume is 1～36% (W/V), is preferably 5～10% (W/V);
Moxifloxacin hydrochloride production method of the present invention, recrystallization temperature is 0～40 ℃ behind the adding sodium-chlor, is preferably 5～20 ℃, most preferably is 15 ℃;
Moxifloxacin hydrochloride production method of the present invention, the crystallization time is 0.5～36h behind the adding sodium-chlor, is preferably 12～24h;
Moxifloxacin hydrochloride production method of the present invention, Heating temperature is 50～100 ℃ during recrystallization, is preferably 80～90 ℃;
Moxifloxacin hydrochloride production method of the present invention, the add-on of water is 7～20 times (W/W) during recrystallization, is preferably 8～10 times;
Moxifloxacin hydrochloride production method of the present invention, temperature was 60 ℃～110 ℃ when the Moxifloxacin hydrochloride highly finished product were dry, was preferably 80 ℃.
Embodiment
Embodiment only is described further summary of the invention, is not limited to the embodiment content.
Embodiment 1
Add sodium-chlor 55kg in the aqueous solution 1100L that contains the 43kg Moxifloxacin hydrochloride of having an appointment, 15 ℃ are stirred the 24h crystallization, centrifugal, and 60 ℃ of vacuum-drying 12h get faint yellow Moxifloxacin hydrochloride crude product 29.3kg, yield: 68.1%.
Moxifloxacin hydrochloride crude product 29.3kg is dropped in the 650L water, be heated to backflow, all the dissolving back is centrifugal, and mother liquor leaves standstill crystallization 12h in 5 ℃, and centrifugal, 80 ℃ of forced air drying 5h promptly get Moxifloxacin hydrochloride finished product 21.2kg, yield: 71.7%.
Inspection after construction: content is greater than 99.5%, and the related substance list is assorted less than 0.1%, and total impurities is less than 0.2%.
Embodiment 2
Add sodium-chlor 25kg to the aqueous solution 250L that contains the 10kg Moxifloxacin hydrochloride of having an appointment, stirring at room 8h crystallization, centrifugal, 110 ℃ of forced air dryings get faint yellow Moxifloxacin hydrochloride crude product 7.15kg, yield: 71.5%.
To go up step gained crude product and drop in the 200L water, and be heated to backflow, all the dissolving back is centrifugal, and mother liquor leaves standstill crystallization 12h in 25 ℃, and centrifugal, 110 ℃ of forced air drying 5h promptly get Moxifloxacin hydrochloride finished product pale yellow powder 4.5kg, yield: 63.8%.
Inspection after construction: content is greater than 99.5%, and the related substance list is assorted less than 0.1%, and total impurities is less than 0.2%.
Embodiment 3
Add sodium-chlor 2.4kg to the aqueous solution 300L that contains the 20kg Moxifloxacin hydrochloride, 0 ℃ of stirring and crystallizing 12h, centrifugal, 60 ℃ of forced air dryings get faint yellow Moxifloxacin hydrochloride crude product 17.8kg, yield: 89%.
To go up step gained crude product and drop in the 320L water, and be heated to backflow, all the dissolving back is centrifugal, and mother liquor leaves standstill crystallization 8h in 0 ℃, and centrifugal, 90 ℃ of forced air drying 5h promptly get Moxifloxacin hydrochloride finished product pale yellow powder 12.6kg, yield: 71%.
Inspection after construction: content is greater than 99.5%, and the related substance list is assorted less than 0.1%, and total impurities is less than 0.2%.
Embodiment 4
Add sodium-chlor 12.5kg to the aqueous solution 250L that contains the 10kg Moxifloxacin hydrochloride, 40 ℃ of stirring and crystallizing 12h, centrifugal, 80 ℃ of forced air dryings get faint yellow Moxifloxacin hydrochloride crude product 3.81kg, yield: 38.1%.
To go up step gained crude product and drop in the 75L water, and be heated to backflow, all the dissolving back is centrifugal, and mother liquor leaves standstill crystallization 8h in 5 ℃, and centrifugal, 110 ℃ of forced air drying 5h promptly get Moxifloxacin hydrochloride finished product pale yellow powder 2.72kg, yield: 70.3%.
Inspection after construction: content is greater than 99.5%, and the related substance list is assorted less than 0.1%, and total impurities is less than 0.2%.
Embodiment 5
In the aqueous solution 30L that contains the 1kg Moxifloxacin hydrochloride, add sodium-chlor 10.8kg, 10 ℃ of stirring and crystallizing 6h, centrifugal, 60 ℃ of forced air dryings get faint yellow Moxifloxacin hydrochloride crude product 0.9kg, yield: 90%.
To go up step gained crude product and drop in the 20L water, and be heated to backflow, all the dissolving back is centrifugal, and mother liquor leaves standstill crystallization 8h in 5 ℃, and centrifugal, 80 ℃ of forced air drying 5h promptly get Moxifloxacin hydrochloride finished product pale yellow powder 0.63kg, yield: 69.7%.
Inspection after construction: content is greater than 99.5%, and the related substance list is assorted less than 0.1%, and total impurities is less than 0.2%.
Embodiment 6
In the aqueous solution 20L that contains the 2kg Moxifloxacin hydrochloride, add sodium chloride saturated solution (36%) 20L, 15 ℃ of stirring and crystallizing 36h, centrifugal, 60 ℃ of forced air dryings get faint yellow Moxifloxacin hydrochloride crude product 1.45kg, yield: 72.5%.
To go up step gained crude product and drop in the 15L water, and be heated to backflow, all the dissolving back is centrifugal, and mother liquor leaves standstill crystallization 8h in 5 ℃, and centrifugal, 80 ℃ of forced air drying 5h promptly get Moxifloxacin hydrochloride finished product pale yellow powder 1.01kg, yield: 69.7%.
Inspection after construction: content is greater than 99.5%, and the related substance list is assorted less than 0.1%, and total impurities is less than 0.2%.
Claims (5)
1. the method for a suitability for industrialized production Moxifloxacin hydrochloride is characterized in that utilizing the dissolubility difference of Moxifloxacin hydrochloride in different concentrations of sodium chloride solution, and Moxifloxacin hydrochloride is precipitated from solution, reaches isolating purpose.Concrete operation method is: in containing the aqueous solution of Moxifloxacin hydrochloride, add sodium-chlor, and the stirring and crystallizing after-filtration, drying with the water recrystallization, is filtered, and is drying to obtain.
2. according to claim 1, in containing the aqueous solution of Moxifloxacin hydrochloride, the amount of the sodium-chlor of adding is 0.8～36% (W/V).
3. according to claim 1, behind the adding sodium-chlor, the temperature that contains the aqueous solution crystallization of Moxifloxacin hydrochloride is 0～60 ℃.
4. according to claim 1, drying means is 60 ℃～120 ℃ air blast or vacuum-drying.
5. according to claim 1, the ratio of water is 1: 8～1: 20 (W/V) during recrystallization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100089967A CN102093349B (en) | 2011-01-17 | 2011-01-17 | Method for performing industrialized production on moxifloxacin hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100089967A CN102093349B (en) | 2011-01-17 | 2011-01-17 | Method for performing industrialized production on moxifloxacin hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102093349A true CN102093349A (en) | 2011-06-15 |
| CN102093349B CN102093349B (en) | 2012-03-07 |
Family
ID=44126638
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100089967A Active CN102093349B (en) | 2011-01-17 | 2011-01-17 | Method for performing industrialized production on moxifloxacin hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102093349B (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321083A (en) * | 2011-07-14 | 2012-01-18 | 福建省福抗药业股份有限公司 | A kind of anhydrous hydrochloric acid Moxifloxacin new crystal F and preparation method thereof |
| CN102344447A (en) * | 2011-07-20 | 2012-02-08 | 北京赛科药业有限责任公司 | Moxifloxacin hydrochloride monohydrate crystal form and preparation method thereof |
| CN102603738A (en) * | 2012-02-24 | 2012-07-25 | 天津市汉康医药生物技术有限公司 | Stable moxifloxacin hydrochloride compound |
| CN102924449A (en) * | 2012-10-30 | 2013-02-13 | 重庆福安药业集团庆余堂制药有限公司 | H crystal form of moxifloxacin hydrochloride, preparation method thereof and medical composition |
| CN103183671A (en) * | 2011-12-29 | 2013-07-03 | 天津康鸿医药科技发展有限公司 | Novel moxifloxacin hydrochloride crystal, and preparation method and application thereof |
| CN103183672A (en) * | 2011-12-29 | 2013-07-03 | 天津康鸿医药科技发展有限公司 | Novel moxifloxacin hydrochloride crystal, and preparation method and application thereof |
| CN103869033A (en) * | 2012-12-14 | 2014-06-18 | 南京长澳医药科技有限公司 | Liquid chromatography method for separating and determining moxifloxacin hydrochloride and impurity thereof |
| CN103965189A (en) * | 2013-12-30 | 2014-08-06 | 西安万隆制药股份有限公司 | Novel moxifloxacin hydrochloride compound |
| CN104725377A (en) * | 2014-04-04 | 2015-06-24 | 江苏天一时制药有限公司 | New crystal form of moxifloxacin hydrochloride and preparation method thereof |
| CN104817557A (en) * | 2014-04-04 | 2015-08-05 | 江苏天一时制药有限公司 | Moxifloxacin hydrochloride stable crystal form and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1368891A (en) * | 1999-08-06 | 2002-09-11 | 拜尔公司 | Moxilfloxacin formulation containing common salt |
| CN101817820A (en) * | 2009-07-30 | 2010-09-01 | 重庆博腾精细化工有限公司 | Method for synthesizing moxifloxacin hydrochloride |
-
2011
- 2011-01-17 CN CN2011100089967A patent/CN102093349B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1368891A (en) * | 1999-08-06 | 2002-09-11 | 拜尔公司 | Moxilfloxacin formulation containing common salt |
| CN101817820A (en) * | 2009-07-30 | 2010-09-01 | 重庆博腾精细化工有限公司 | Method for synthesizing moxifloxacin hydrochloride |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321083A (en) * | 2011-07-14 | 2012-01-18 | 福建省福抗药业股份有限公司 | A kind of anhydrous hydrochloric acid Moxifloxacin new crystal F and preparation method thereof |
| CN102321083B (en) * | 2011-07-14 | 2013-05-15 | 福建省福抗药业股份有限公司 | Preparation method of new anhydrous moxifloxacin hydrochloride crystal F |
| CN102344447A (en) * | 2011-07-20 | 2012-02-08 | 北京赛科药业有限责任公司 | Moxifloxacin hydrochloride monohydrate crystal form and preparation method thereof |
| CN103183671A (en) * | 2011-12-29 | 2013-07-03 | 天津康鸿医药科技发展有限公司 | Novel moxifloxacin hydrochloride crystal, and preparation method and application thereof |
| CN103183672A (en) * | 2011-12-29 | 2013-07-03 | 天津康鸿医药科技发展有限公司 | Novel moxifloxacin hydrochloride crystal, and preparation method and application thereof |
| CN102603738B (en) * | 2012-02-24 | 2013-12-11 | 天津市汉康医药生物技术有限公司 | Stable moxifloxacin hydrochloride compound |
| CN102603738A (en) * | 2012-02-24 | 2012-07-25 | 天津市汉康医药生物技术有限公司 | Stable moxifloxacin hydrochloride compound |
| CN102924449A (en) * | 2012-10-30 | 2013-02-13 | 重庆福安药业集团庆余堂制药有限公司 | H crystal form of moxifloxacin hydrochloride, preparation method thereof and medical composition |
| CN102924449B (en) * | 2012-10-30 | 2015-08-12 | 重庆福安药业集团庆余堂制药有限公司 | Moxifloxacin hydrochloride H crystal form and preparation method thereof and pharmaceutical composition |
| CN103869033A (en) * | 2012-12-14 | 2014-06-18 | 南京长澳医药科技有限公司 | Liquid chromatography method for separating and determining moxifloxacin hydrochloride and impurity thereof |
| CN103965189A (en) * | 2013-12-30 | 2014-08-06 | 西安万隆制药股份有限公司 | Novel moxifloxacin hydrochloride compound |
| CN103965189B (en) * | 2013-12-30 | 2015-09-09 | 西安万隆制药股份有限公司 | A kind of new moxifloxacin hydrochloride compound |
| CN104725377A (en) * | 2014-04-04 | 2015-06-24 | 江苏天一时制药有限公司 | New crystal form of moxifloxacin hydrochloride and preparation method thereof |
| CN104817557A (en) * | 2014-04-04 | 2015-08-05 | 江苏天一时制药有限公司 | Moxifloxacin hydrochloride stable crystal form and preparation method thereof |
| CN104725377B (en) * | 2014-04-04 | 2017-06-06 | 江苏天一时制药有限公司 | Crystal form of moxifloxacin hydrochloride and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102093349B (en) | 2012-03-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102093349B (en) | Method for performing industrialized production on moxifloxacin hydrochloride | |
| CN101941969B (en) | Preparation method of moxifloxacin hydrochloride | |
| CN101786971B (en) | Preparation process of doxycycline hydrochloride | |
| CN104230924B (en) | A kind of synthetic method of moxifloxacin hydrochloride | |
| CN104098548B (en) | A kind of Delafloxacin process for purification | |
| CN102180892B (en) | Novel method for purifying cefmetazole sodium | |
| CN86102363A (en) | The preparation method of Carbostyril carboxylic acid derivatives and application thereof | |
| CN103396416B (en) | Preparation method of moxifloxacin impurity F | |
| TWI762573B (en) | Purification of pleuromutilin | |
| CN102079765B (en) | 9-O-glucoside-berberine salt, and preparation method and application thereof | |
| WO2017021975A1 (en) | Process for the preparation of crystalline forms of rifaximin | |
| CN106349218B (en) | A kind of preparation method of sitafloxacin | |
| CN104274454B (en) | A kind of anti-medicine resistant Staphylococcus aureus composition of medicine and purposes | |
| CN105566322A (en) | Preparation method of moxifloxacin impurity G compound | |
| CN111018887B (en) | Method for purifying rifampicin | |
| CN101962367A (en) | Method for purifying bendamustine hydrochloride | |
| CN102382007B (en) | Doxycycline hydrochloride compound and preparation method thereof | |
| CN102285986B (en) | Industrialized purification method of moxifloxacin | |
| CN104031040B (en) | The synthetic method of 2-sulfydryl-4-pyridyl thiazole | |
| CN104860944A (en) | Production method of moxifloxacin hydrochloride | |
| US8871927B2 (en) | Method for purifying Ceftizoxime sodium | |
| CN104031043A (en) | Novel synthesis method of moxifloxacin hydrochloride | |
| CN110878082B (en) | Gatifloxacin and its synthesis method | |
| CN103755726A (en) | Cefalonium refinement purification method | |
| CN101993449A (en) | Preparation methods of high-purity cefotiam hexetil and dihydrochloride of high-purity cefotiam hexetil |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant after: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant after: NANJING YOKO BIOMEDICAL R & D Ltd. Co-applicant after: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant before: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant before: Nanjing uniclever Biological Medicine Research Co.,Ltd. Co-applicant before: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant after: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant after: Nanjing uniclever Biological Medicine Research Co.,Ltd. Co-applicant after: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Applicant before: NANJING XINGANG MEDICAL Co.,Ltd. Co-applicant before: NANJING ACEAN MEDICINE RESEARCH Co.,Ltd. Co-applicant before: NANJING ACEAN PHARMACEUTICAL Co.,Ltd. |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: NANJING YOKO PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: NANJING XINGANG PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Patentee after: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Patentee after: NANJING YOKO BIOMEDICAL R & D Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Patentee before: NANJING XINGANG MEDICAL Co.,Ltd. Patentee before: NANJING YOKO BIOMEDICAL R & D Ltd. Patentee before: NANJING YOKO PHARMACEUTICAL Co.,Ltd. |
|
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Patentee after: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Patentee after: NANJING YOKO BIOMEDICAL R & D Ltd. Patentee after: NANJING YOKO BIOLOGICAL PHARMACEUTICAL GROUP Co.,Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Patentee before: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Patentee before: NANJING YOKO BIOMEDICAL R & D Ltd. Patentee before: Nanjing uniclever biological pharmaceutical Limited by Share Ltd. Address after: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Patentee after: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Patentee after: NANJING YOKO BIOMEDICAL R & D Ltd. Patentee after: Nanjing uniclever biological pharmaceutical Limited by Share Ltd. Address before: 210046 Nanjing economic and Technological Development Zone, Jiangsu Heng Road, No. 28 Patentee before: NANJING YOKO PHARMACEUTICAL Co.,Ltd. Patentee before: NANJING YOKO BIOMEDICAL R & D Ltd. |