CN101066267B - Solid oral medicine composition containing aripiprazole microcrystal - Google Patents
Solid oral medicine composition containing aripiprazole microcrystal Download PDFInfo
- Publication number
- CN101066267B CN101066267B CN2007100413235A CN200710041323A CN101066267B CN 101066267 B CN101066267 B CN 101066267B CN 2007100413235 A CN2007100413235 A CN 2007100413235A CN 200710041323 A CN200710041323 A CN 200710041323A CN 101066267 B CN101066267 B CN 101066267B
- Authority
- CN
- China
- Prior art keywords
- aripiprazole
- type
- lactose
- microcrystalline cellulose
- medicine composition
- 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
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to one kind of solid oral medicine composition containing aripiprazole microcrystal. The solid oral medicine composition contains type I microcrystal of aripiprazole in the average grain size below 50 micron in 1-50 mg and pharmaceutically acceptable supplementary material. The medicine composition has obviously raised aripiprazole dissolution, and raised bioavailability and curative effect of aripiprazole. It is used in treating metal diseases, such as schizophrenia.
Description
Technical field
The invention belongs to formulation art, be specifically related to a kind of Peroral solid dosage form pharmaceutical composition that contains aripiprazole crystallite, contain brilliant 1-50mg of Aripiprazole I type and pharmaceutically acceptable pharmaceutic adjuvant, it is characterized in that: the mean diameter of Aripiprazole I type crystalline substance is no more than 50um.The Aripiprazole dissolution of the present composition is improved significantly, and can improve the bioavailability and the curative effect of Aripiprazole.
Background technology
Aripiprazole is a kind of schizoid atypical chlorpromazine that is used for the treatment of, and goes on the market in the whole world.Its chemistry 7-{4-[4-(2, the 3-Dichlorobenzene base) by name-1-piperazinyl]-butoxy }-3,4-dihydro-quinolone or 7-{4-[4-(2, the 3-Dichlorobenzene base)-1-piperazinyl]-butoxy }-3,4-2 (1H)-quinolinones.
Aripiprazole is a kind of insoluble medicine, when it is made oral formulations such as tablet or other and comprises the solid preparation of quick fusing prescription, its size has bigger influence to its active bio availability, existing bibliographical information is made micron order with the crystal formation of Aripiprazole, apply for a patent the particle diameter that CN02801754 discloses A type crystalline substance and Type B crystalline substance as China, mean diameter is 50,40,35,25,20um, China applies for a patent CN200480031386.7 and discloses a kind of compositions that contains the Aripiprazole monohydrate, its mean diameter is 25-100um, be used for injection, Chinese patent CN200480030814 discloses a kind of preparation method for preparing the aripiprazole crystal form microgranule, the mean diameter of the aripiprazole crystal form that this method obtains is 1-25um, can be used for doing oral formulations, compositionss such as injection, the mean diameter of lyophilized formulations are 2.5um.China applies for a patent particle diameter that CN200480041610 discloses a kind of II type crystalline substance (the X diffraction is different with the II type of big tomb company) for less than 300um, and WO200735348 discloses a kind of nanoscale Aripiprazole compositions, and its particle diameter is below 2um.WO200697344 (Holland) discloses a kind of pharmaceutical composition that contains the brilliant 1-5mg of Aripiprazole II type, and wherein II type crystal grain directly is distributed as 50um or accounts for 90% more for a short time.
But the fine particle (micron order) of disclosed Aripiprazole I type crystalline substance does not also have bibliographical information in Japan and Korea S's analytical chemistry annual meeting, discover through the present invention, dissolution in vitro by the I type wafer of CN02801754 disclosed method preparation was lower than 70% in 45 minutes, its bioavailability is lower, therefore, be necessary to make the preparation of particle diameter below 100um, to improve its bioavailability, therefore the present invention finishes.
Summary of the invention
The invention provides a kind of combination of oral medication of high bioavailability, contain brilliant 1-50mg of Aripiprazole I type and acceptable accessories, it is characterized in that the mean diameter of Aripiprazole I type crystalline substance is no more than 50um, preferably be no more than 35um.
Described compositions of the present invention is characterized in that the particle size distribution 90% of Aripiprazole I type crystalline substance is not more than 50um.
Above-mentioned said combination of oral medication, said pharmaceutic adjuvant are selected from one or more in following: diluent, disintegrating agent, binding agent and lubricant; Said diluent is selected from the following material one or more: lactose, microcrystalline Cellulose, starch and mannitol, and when compositions is tablet, preferred lactose and microcrystalline Cellulose, its consumption in tablet accounts for 80～95% of composition weight; Said disintegrating agent is selected from the following material one or more: carboxymethylstach sodium, polyvinylpolypyrrolidone and low-substituted hydroxypropyl cellulose, and its consumption accounts for 1～15% of composition weight; Said binding agent is a hypromellose, and polyvidone and starch slurry are an amount of; Said lubricant is magnesium stearate, sodium stearyl fumarate, Pulvis Talci, colloidal silica or their mixture, and its consumption accounts for 0.1～5% of composition weight.
Also can add correctives, as selecting artificial or natural sweeteners such as stevioside, maltose alcohol, A Siba be sweet.
The said combination of oral medication of the present invention, its dosage form are tablet, capsule or oral liquid, preferred tablet or capsule.
Compositions of the present invention, especially tablet and capsule, dissolution height, uniform content are stablized, bioavailability is high.
Aripiprazole I type crystalline substance in the compositions of the present invention, its powder X-ray-diffracting spectrum (cuK α source, α=1.54056
) 2 θ have characteristic peak about following value: 11.1,14.4,16.6,19.5,20.4 and 22.1, see Fig. 1; The scanning of its differential heat has been located endothermic peak (heating rate: 10 ℃/min) about 140.2 ℃.
Combination of oral medication of the present invention can prepare by following method:
The preparation method of applying for a patent the CN03135380.8 description by China makes the Aripiprazole crude product, under the mixed solvent high-speed stirred state of this crude product with ethanol or ethanol and other non-alcohols solvent formation, add water at low temperature recrystallization Aripiprazole, filter, dry, acquisition mean diameter is less than or equal to 50um Aripiprazole I type crystalline substance; This I type crystalline substance is mixed with pharmaceutic adjuvant, and the dress capsule is made capsule, maybe this I type crystalline substance is made granule with the pharmaceutic adjuvant mixing granulation, obtains tablet through tabletting.
Combination of oral medication of the present invention contains Aripiprazole 1-50mg, preferred 2.5mg, 5mg, 10mg, 15mg, 20mg, 25mg, or 30mg, more preferably 5mg, 10mg and 15mg.
The said tablet of the present invention comprises ordinary tablet, oral cavity disintegration tablet, chews sheet, effervescent tablet, buccal tablet etc. that its preparation makes by the conventional technology of preparing of the known corresponding tablet of those skilled in the art.
The dissolution of the aripiprazole crystallite Peroral solid dosage form pharmaceutical composition that the present invention obtains obviously improves, especially when compositions is tablet, when diluent is that lactose and microcrystalline Cellulose and its content are 80-95% (sheet is heavy), be equipped with other pharmaceutic adjuvant, effect is particularly outstanding, can improve the bioavailability and the curative effect of aripiprazole formulations.
Pharmaceutical composition of the present invention is used for the treatment of mental sickness such as schizophrenia, bipolar mania and depression etc.
Description of drawings
Fig. 1 is at the powder X-ray-diffracting spectrum of the Aripiprazole I of 25 ℃ of mensuration type crystalline substance
The specific embodiment
Embodiments of the invention are used for further explaining the present invention, but not the limiting protecting scope in this.
Reference embodiment
Macrocrystalline of Aripiprazole I type:
The method of applying for a patent the reference enforcement 2 of CN02801754 by China makes Aripiprazole I type crystalline substance (coarse-grain).
Prescription: (prescription is with reference to CN02801754 embodiment 22)
Aripiprazole (I type coarse-grain) 15g
Lactose 57g
Starch 10g
Microcrystalline Cellulose 10g
Hyprolose 2g
Magnesium stearate 0.9g
94.9g 1000
Preparation technology: Aripiprazole I type coarse-grain is crossed 80 mesh sieves,, add hyprolose liquid, mixing granulation with starch, lactose and microcrystalline cellulose mix homogeneously, oven dry is sieved, and adds magnesium stearate then, mix, use the tablet machine tabletting, be pressed into every tablet of tablet that contains Aripiprazole 15mg.
Embodiment 1
The preparation of Aripiprazole I type crystallite
20g Aripiprazole crude product and the adding of 240ml ethanol are taken back in three mouthfuls of reaction bulbs of flow condenser, be heated to backflow under stirring, treat to stop after Aripiprazole dissolves fully heating, line transfer speed to 500 meter/minute adds 1 ℃ water at low temperature 37ml simultaneously, with the mixture of ice and water 30min that lowers the temperature rapidly, sucking filtration, washing obtains crystallization in 80 ℃ of exsiccators with institute, and drying under reduced pressure obtained powdery aripiprazole crystals 19.2g in 10 hours.By being dispersant with water, measure its volume average particle size 26.456um with Mastersizer 2000 laser particle analyzers.
Embodiment 2
Aripiprazole I type microwafer (except that I type crystallite, prescription is with reference embodiment, and the crystallite method for making is seen embodiment)
Prescription:
Aripiprazole (I type crystallite) 15g
Lactose 57g
Starch 10g
Microcrystalline Cellulose 10g
Hyprolose 2g
Magnesium stearate 0.9g
94.9g 1000
Preparation technology: with reference embodiment.
Embodiment 3
Aripiprazole I type microwafer
Prescription
Aripiprazole (I type crystallite) 5g
Lactose 75g
Microcrystalline Cellulose 11g
Carboxymethylstach sodium 2.8g
Hypromellose 2.2g
Carboxymethylstach sodium (adding) 3.2g
Magnesium stearate 0.8g
1000 of 100g
Preparation: with Aripiprazole I type crystallite, sodium carboxymethylstarch, microcrystalline Cellulose, starch and lactose mix homogeneously, add hydroxypropyl first fiber dilute alcohol solution, mix pelletize, oven dry is sieved, and adds carboxymethyl starch sodium, mixing again, add magnesium stearate then, mix homogeneously, tabletting.
Embodiment 4
Aripiprazole I type microwafer
Prescription
Aripiprazole (I type crystallite) 10g
Lactose 70g
Microcrystalline Cellulose 28g
Carboxymethylstach sodium 3g
30 POVIDONE K 30 BP/USP-30 2.5g
Polyvinylpolypyrrolidone 2g
Sodium stearyl fumarate 1g
Pulvis Talci 3.5g
1000 of 120g
Preparation: with Aripiprazole I type crystallite, sodium carboxymethylstarch, microcrystalline Cellulose and lactose mix homogeneously, add the polyvidone dilute alcohol solution, mix, pelletize, oven dry is sieved, and adds sodium stearyl fumarate and Pulvis Talci, mix homogeneously, tabletting.
Embodiment 5
Aripiprazole I type crystallite capsule
Prescription
Aripiprazole (I type crystallite) 5g
Lactose 80g
Microcrystalline Cellulose 30g
Starch 30g
30 POVIDONE K 30 BP/USP-30 2g
Carboxymethylstach sodium 1.8g
Magnesium stearate 1g
Colloidal silica 0.2g
1000 of 150g
Preparation:, add magnesium stearate and colloidal silica mix homogeneously with Aripiprazole I type crystallite, starch, lactose, microcrystalline Cellulose, polyvidone and carboxymethylstach sodium mix homogeneously.Encapsulated, make capsule.
Embodiment 6
Aripiprazole I type crystallite capsule
Prescription
Aripiprazole (I type crystallite) 5g
Lactose 80g
Microcrystalline Cellulose 30g
Pregelatinized Starch 30g
30 POVIDONE K 30 BP/USP-30 2g
Carboxymethylstach sodium 2g
Sodium stearyl fumarate 1g
1000 of 150g
Preparation:, add the sodium stearyl fumarate mix homogeneously with Aripiprazole I type crystallite, pregelatinized Starch, lactose, microcrystalline Cellulose, polyvidone and carboxymethylstach sodium mix homogeneously.Encapsulated, make capsule.
Embodiment 7
Aripiprazole I type microwafer
Prescription:
Aripiprazole (I type crystallite) 5g
Lactose 77g
Microcrystalline Cellulose 30g
Carboxymethylstach sodium 3g
30 POVIDONE K 30 BP/USP-30 1.7g
Polyvinylpolypyrrolidone 2g
Magnesium stearate 0.8g
Colloidal silica 0.5g
1000 of 120g
Preparation: with lactose, microcrystalline Cellulose and sodium carboxymethylstarch, mix homogeneously, add the polyvidone dilute alcohol solution, mixing granulation, oven dry is sieved, and adds Aripiprazole I type crystallite, polyvinylpolypyrrolidone, colloidal silica and magnesium stearate, mix homogeneously, tabletting.
Determination of dissolution rate (1)
Get the sheet of embodiment 2,4 and reference embodiment gained, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2005), (get sodium lauryl sulphate 5g with sodium lauryl sulphate-sodium-acetate buffer, sodium acetate 2g, add water to 1000ml, adding acetic acid adjust pH to 4.7 again) 500ml is solvent, rotating speed is that per minute 75 changes.Measurement result sees Table 1
Table 1. dissolution data list position: %
Under identical prescription condition, the dissolution of I type microwafer is apparently higher than I type coarse-grain sheet, illustrate that the compositions (tablet) that contains crystallite I is better than containing the compositions (tablet) of coarse-grain I, and the dissolution of the crystallite pharmaceutical composition (sheet) of the embodiment of the invention 4 is more excellent than embodiment 2.
Embodiment 9
Determination of dissolution rate (2)
Get the sheet of embodiment 2,3,4,5,6,7 and reference embodiment gained, adopt relatively mild leaching condition to measure comparison.According to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2005 C, second method), 500ml is a solvent with sodium dodecyl sulfate solution (get sodium lauryl sulphate 3g, add water to 1000ml), and rotating speed is that per minute 75 changes.Measurement result sees Table 2
Table 2: dissolution data table
Unit: %
The dissolution of pharmaceutical composition of the present invention (sheet or capsule) is apparently higher than the tablet of reference embodiment, and employing high-load lactose and the embodiment 3,4 of microcrystalline Cellulose prescription and 7 tablet, and the dissolution of capsule obviously is better than embodiment 2, therefore, the dissolution of compositions of the present invention is improved significantly, and can improve the bioavailability and the curative effect of Aripiprazole.
Embodiment 10
Stability test
Sample is packed into and is sealed in the high-density polyethylene bottle, and room temperature is placed.
Content assaying method: with octadecylsilane chemically bonded silica is filler; With methanol-0.1% triethylamine solution (90: 10) is mobile phase; The detection wavelength is 255nm.Number of theoretical plate calculates by the Aripiprazole peak should be not less than 1000.Get 20 of this product, the accurate title, decide, porphyrize, and precision takes by weighing in right amount (being equivalent to Aripiprazole 10mg approximately), put in the 200ml measuring bottle, it is an amount of to add methanol, and ultrasonic jolting made the Aripiprazole dissolving in 15 minutes, put cold, add methanol and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 20 μ l and is injected chromatograph of liquid; Other the Aripiprazole reference substance that is dried to constant weight of learning from else's experience 105 ℃ is an amount of, accurate claim fixed, add dissolve with methanol and quantitatively dilution make the solution that contains 50 μ g among every 1ml, measure with method.Press external standard method with calculated by peak area, promptly.
Dissolution determination method is with embodiment 9.
The measurement result of stability test content and dissolution (45 minutes) sees Table 3.
Table 3: stability data table
The content and the dissolution of pharmaceutical composition of the present invention (sheet or capsule) are all more stable.
Claims (1)
1. Peroral solid dosage form pharmaceutical composition, it is characterized in that: the mean diameter of Aripiprazole I type crystalline substance is no more than 50um; Said compositions is a tablet, and per 1000 compositing formula is any in following:
Aripiprazole I type crystallite 5g, lactose 75g, microcrystalline Cellulose 11g, carboxymethylstach sodium 2.8g, hypromellose 2.2g, add carboxymethylstach sodium 3.2g, magnesium stearate 0.8g; Perhaps
Aripiprazole I type crystallite 10g, lactose 70g, microcrystalline Cellulose 28g, carboxymethylstach sodium 3g, 30 POVIDONE K 30 BP/USP-30 2.5g, polyvinylpolypyrrolidone 2g, sodium stearyl fumarate 1g, Pulvis Talci 3.5g; Perhaps
Aripiprazole I type crystallite 5g, lactose 77g, microcrystalline Cellulose 30g, carboxymethylstach sodium 3g, 30 POVIDONE K 30 BP/USP-30 1.7g, polyvinylpolypyrrolidone 2g, magnesium stearate 0.8g, colloidal silica 0.5g.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100413235A CN101066267B (en) | 2007-05-28 | 2007-05-28 | Solid oral medicine composition containing aripiprazole microcrystal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100413235A CN101066267B (en) | 2007-05-28 | 2007-05-28 | Solid oral medicine composition containing aripiprazole microcrystal |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010119171 Division CN101791287B (en) | 2007-05-28 | 2007-05-28 | Solid oral drug composite containing aripiprazole microcrystalline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101066267A CN101066267A (en) | 2007-11-07 |
| CN101066267B true CN101066267B (en) | 2010-08-11 |
Family
ID=38879047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100413235A Active CN101066267B (en) | 2007-05-28 | 2007-05-28 | Solid oral medicine composition containing aripiprazole microcrystal |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101066267B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102218040A (en) * | 2010-04-13 | 2011-10-19 | 齐鲁制药有限公司 | Oral disintegrating tablets of microcrystallites of aripiprazole composition and preparation method thereof |
| CN102846616B (en) * | 2011-06-27 | 2015-05-06 | 上海中西制药有限公司 | Aripiprazole preparation and preparation method thereof |
| CN102850268B (en) | 2011-06-27 | 2015-07-15 | 上海中西制药有限公司 | Aripiprazole I-type crystallite, aripiprazole solid preparation and preparation methods thereof |
| CN104230799A (en) * | 2013-06-21 | 2014-12-24 | 江苏豪森药业股份有限公司 | Method for preparing aripiprazole crystal |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1676517A (en) * | 2004-04-02 | 2005-10-05 | 北京德众万全药物技术开发有限公司 | Aripiprazole crystal form |
-
2007
- 2007-05-28 CN CN2007100413235A patent/CN101066267B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1676517A (en) * | 2004-04-02 | 2005-10-05 | 北京德众万全药物技术开发有限公司 | Aripiprazole crystal form |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101066267A (en) | 2007-11-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11396558B2 (en) | Hypromellose acetate succinate powder excellent in dissolved state and production method thereof, and production methods for composition for solid dispersion, coating composition, drug-containing particle, and solid | |
| CN112076192A (en) | Pharmaceutical composition containing quinoline derivative or salt thereof and process for producing the same | |
| WO2020249001A1 (en) | Oral solid tablet comprising bruton's tyrosine kinase inhibitor and preparation method therefor | |
| CN106102716A (en) | The solid composite medicament of androgen receptor antagonists | |
| CN102631347A (en) | Gefinitib medicinal composite and method for preparing same | |
| CN104650091A (en) | Micronization and crystal form of ticagrelor and preparation method and pharmaceutical application of crystal form of ticagrelor | |
| CN102850268A (en) | Aripiprazole I-type crystallite, aripiprazole solid preparation and preparation methods thereof | |
| CN108135853A (en) | Pharmaceutical composition comprising Afatinib | |
| KR20220061952A (en) | Coated granules, solid dispersions and formulations containing vortioxetine hydrobromide for oral taste masking | |
| CN102949359B (en) | A kind of Cefditoren pivoxil Cephalosporins sheet and preparation method thereof | |
| MX2007005427A (en) | Solid dispersion composition of pranlukast with improved bioavailibility and the method of preparing the solid dispersion. | |
| WO2011079609A1 (en) | Preparation method of solid formulations and solid formulations prepared thereby | |
| CN101066267B (en) | Solid oral medicine composition containing aripiprazole microcrystal | |
| CN101370484B (en) | Solid pharmaceutical composition comprising irbesartan | |
| CN106349192B (en) | The eutectic of orlistat and amino acid and include eutectiferous pharmaceutical composition | |
| CN105801568B (en) | One maleate crystal form of Afatinib and preparation method thereof and pharmaceutical composition | |
| CN106913529A (en) | A kind of preparation method of HKI-272 or its officinal salt pharmaceutical composition | |
| CN101791287B (en) | Solid oral drug composite containing aripiprazole microcrystalline | |
| CN104473901B (en) | Cefdinir capsule and preparation method thereof | |
| WO2012088992A1 (en) | Process for preparing solid medicine preparation and solid medicine preparation therefrom | |
| CN105732517A (en) | Medicine preparation containing 5-fluorouracil drug eutectic with nicotinamide as precursor and preparation method of medicine preparation | |
| CN115137705A (en) | Indobufen tablet | |
| CN103845332A (en) | Medicinal dasatinib composition and preparation method thereof | |
| CN108440456A (en) | The eutectic of orlistat and calcium of organic acid and include eutectiferous pharmaceutical composition | |
| JP2020518611A (en) | Compositions with improved water solubility and bioavailability |
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 | ||
| ASS | Succession or assignment of patent right |
Owner name: SHANGHAI ZHONGXI PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: CHONGQING PHARMACEUTICAL RESEARCH INSTITUTE CO., LTD. Effective date: 20110216 Free format text: FORMER OWNER: SHANGHAI ZHONGXI PHARMACEUTICAL CO., LTD. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 400061 NO. 565, TUSHAN ROAD, NAN AN DISTRICT, CHONGQING CITY TO: 201823 NO.446, WAIQINGSONG HIGHWAY, JIADING DISTRICT, SHANGHAI |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20110216 Address after: 201823, Shanghai, Jiading District outer Pine Road No. 446 Patentee after: Shanghai Zhongxi Pharmaceutical Co., Ltd. Address before: 400061 No. 565, Tu Shan Road, Nan'an District, Chongqing Co-patentee before: Shanghai Zhongxi Pharmaceutical Co., Ltd. Patentee before: Chongqing Pharmaceutical Research Institute Co., Ltd. |
|
| ASS | Succession or assignment of patent right |
Owner name: SHANGHAI ZHONGXI SUNVE PHARMACEUTICAL CO., LTD. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20110721 Address after: 201823, Shanghai, Jiading District outer Pine Road No. 446 Co-patentee after: Shanghai Zhongxi Sunve Pharmaceutical Co., Ltd. Patentee after: Shanghai Zhongxi Pharmaceutical Co., Ltd. Address before: 201823, Shanghai, Jiading District outer Pine Road No. 446 Patentee before: Shanghai Zhongxi 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: 201823, Shanghai, Jiading District outer Pine Road No. 446 Patentee after: Shanghai Chinese Medicine Pharmaceutical Co. Ltd. Patentee after: Shanghai Zhongxi Sunve Pharmaceutical Co., Ltd. Address before: 201823, Shanghai, Jiading District outer Pine Road No. 446 Patentee before: Shanghai Zhongxi Pharmaceutical Co., Ltd. Patentee before: Shanghai Zhongxi Sunve Pharmaceutical Co., Ltd. |