CN102584793A - Rabeprazole sodium crystal compound and preparing method thereof - Google Patents
Rabeprazole sodium crystal compound and preparing method thereof Download PDFInfo
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Abstract
The invention relates to a rabeprazole sodium crystal compound and a preparing method thereof. The crystal compound is determined by a powder X-ray diffraction determining method, and an X-ray powder diffraction spectrum represented by 2 theta +/- 0.2 degree diffraction angles shows characteristic diffraction peaks at the positions of 5.8 degrees, 7.5 degrees, 12.1 degrees, 12.8 degrees, 13.3 degrees, 15.6 degrees, 16.7 degrees, 18.3 degrees, 20.4 degrees, 25.7 degrees, 26.8 degrees and 31.5 degrees. The preparing method comprises the following steps of: 1) adding rabeprazole sodium serving as a crude drug in water, stirring and dissolving to obtain a rabeprazole sodium water solution; 2) adding a mixed solution of tetrahydrofuran and methanol into the rabeprazole sodium water solution, conducting heat-insulation decoloration at the temperature of 25-35 DEG C by active carbon and filtering to obtain filtrate; and 3) dropping the filtrate into acetonitrile, cooling, crystallizing, filtering and drying in vacuum, thus obtaining the rabeprazole sodium crystal compound. The crystal compound has good stability and strong inhibitory action on Helicobacter pylori.
Description
Technical field
The present invention relates to a kind of Sodium rabeprazole crystalline compounds and preparation method thereof, belong to medical technical field.
Background technology
Sodium rabeprazole, its chemical name is: 2-{ [4-(3-methoxy propoxy)-3-picoline-2-yl] methanesulfinyl }-1H-benzoglyoxaline sodium, molecular formula: C
18H
20N
3NaO
3S, molecular weight: 381.43, structural formula is:
Sodium rabeprazole is a benzimidazoles compound, is s-generation proton pump inhibitor, through suppressing parietal cell H specifically
+, K
+-ATP enzyme system and block the final step of gastric acid secretion.This effect is dosage according to patience, and the gastric acid secretion under basal gastric acid secretion and the stimulation state is all suppressed.These article are to cholic acid and histamine H
2Acceptor does not have the anti-effect of picking up.
The salify of Sodium rabeprazole; The patent documentation report all adopts the reactant aqueous solution of rabeprazole and sodium hydroxide, owing to contain water in the reaction system, and generate water; And Sodium rabeprazole has good solubleness in water; Therefore, dehydration, the crystallization of operation afterwards brought difficulty, also increased very big difficulty for the purification of Sodium rabeprazole.
At present, the purification of Sodium rabeprazole mainly contains following several method: direct decompression dehydration pulp adds ethers (comprising sherwood oil, ether, isopropyl ether etc.) then and separates out crystallization and be able to purify.This method is difficult for removing impurity, and is high to the rabeprazole specification of quality, and anhydrates not exclusively, and crystallization carefully is difficult for filtering.
Repeatedly between the organic phase (like methylene dichloride) and the aqueous solution, utilize the asynchronous solvability difference of pH value to extract, pressure reducing and steaming organic solvent then, recrystallization is purified in acetone.This method can be removed sulfone class impurity well, but complex operation, and solvent toxicity is bigger, is difficult for removing fully.
Through after repeatedly adding ethanol, concentrating under reduced pressure and taking water out of, add ethers (comprising sherwood oil, ether, isopropyl ether etc.), acetone or ETHYLE ACETATE and separate out Sodium rabeprazole.This method long reaction time is prone to oxidation, and organic solvent toxicities such as acetone, ETHYLE ACETATE are bigger simultaneously, and is difficult for removing fully.
Through repeatedly add ETHYLE ACETATE or methylene dichloride, pressurization concentrate take water out of after, add ETHYLE ACETATE or methylene dichloride to dissolving just, be added drop-wise to and separate out Sodium rabeprazole in the isopropyl ether.This method long reaction time Sodium rabeprazole is prone to oxidized, and Sodium rabeprazole is difficult for filtering simultaneously.
Go up the deficiency of synthesis technique for overcoming above-mentioned technological Sodium rabeprazole purification; And the Sodium rabeprazole purity of producing is relatively poor; The unfavorable factor that causes the preparation stability of Sodium rabeprazole to decline to a great extent easily, CN101704811A discloses a kind of highly purified sodium rabeprazole compound, and its method comprises: rabeprazole and sodium hydroxide reaction synthetic Sodium rabeprazole bullion is water-soluble; Use solid hydrogen salt adjusting pH value extremely neutral, collect the solid of separating out as slightly acidic; With above-mentioned gained solid with organic solvent dissolution after, with eluent wash-out purifying, collect elutriant through macroporous adsorbent resin; It is alkalescence that the gained elutriant is regulated the pH value, collects the solid of separating out, and obtains the rabeprazole sodium pure product.
" salify of Sodium rabeprazole, crystallization " [Liu Shenggao; Li Jun. the salify of Sodium rabeprazole, crystallization. Shandong medicine thing; 2008,27 (10): 685-687] a kind of salify, crystallization method of new Sodium rabeprazole are provided, have been specially: rabeprazole and alkoxide salify in alcohol; Solution behind the salify adds the anti-solvent crystallization of capacity after concentrating.
" synthesizing of proton pump inhibitor Sodium rabeprazole " [Asia, Shandong etc. synthesizing of proton pump inhibitor Sodium rabeprazole. print during chemical industry; 2011; 25 (8): 46-48] relate to the whitening compound that a kind of methylene dichloride/isopropyl ether recrystallization makes, its fusing point is 139～141 ℃.
CN102260244A discloses a kind of stable sodium rabeprazole compound and preparation method thereof, and the sodium rabeprazole compound crystalline fusing point that the present invention obtains is 242～242.5 ℃, is a kind of new crystal formation.This crystal water is divided few, and the advantage that has: chemical purity 99.9%, maximum contaminant are less than 1%, and chemical purity is up to 99.96%ee; Good stability.Compound production cost according to the invention is low, and steady quality is fit to suitability for industrialized production.
Material owing to influenced by various factors, changes intramolecularly or molecular linkage mode when crystallization, and it is different to cause molecule or atom to be arranged at lattice vacancy, forms the crystals with different structure.The medicine polymorphism is one of important factor that influences drug quality and clinical efficacy, and therefore in drug quality control, crystal formation is one of them important quality control index.The polymorphism of medicine is to the quality important influence of product.The crystalline structure different compounds; Because the difference of its molecular arrangement order is in the different energy state respectively, common unformed medicine has bigger potential energy; Interparticle bonding strength is little than crystal formation; Total per surface free energy is bigger, and the surface is prone to aquation between particle, thereby causes the difference with the crystallinity drug solubility.Molecule is different with arrangement in sterie configuration, conformation in the structure cell of different crystal forms; Make its solvability have significant difference; Cause preparation that different dissolution rates is arranged in vivo; Directly influence preparation absorption in vivo, distribution, drainage and metabolism, finally because of the different differences that cause clinical drug effect of its bioavailability.
The inventor is after having carried out a large amount of research to Sodium rabeprazole; Obtained a kind of new crystal formation; This crystal formation has stability preferably equally; And mix the external bacteriostatic action of method research Sodium rabeprazole through using flat board, find that pleasantly surprisedly Sodium rabeprazole has tangible bacteriostatic action external to Helicobacter pylori helicobacter pylori.
Summary of the invention
The object of the present invention is to provide a kind of Sodium rabeprazole crystalline compounds, this crystalline compounds has satisfactory stability property.
For realizing above-mentioned purpose, the present invention adopts following technical scheme:
A kind of Sodium rabeprazole crystalline compounds; Wherein, Described Sodium rabeprazole crystalline compounds is measured with the powder x-ray diffraction assay method, locates to demonstrate characteristic diffraction peak with the X-ray powder diffraction collection of illustrative plates that 2 θ ± 0.2 ° diffraction angle is represented at 5.8 °, 7.5 °, 12.1 °, 12.8 °, 13.3 °, 15.6 °, 16.7 °, 18.3 °, 20.4 °, 25.7 °, 26.8 ° and 31.5 °.
CN102260244A discloses a kind of stable sodium rabeprazole compound, and this sodium rabeprazole compound is a kind of new crystal of Sodium rabeprazole.Through finding that relatively the X-ray powder diffraction collection of illustrative plates of the Sodium rabeprazole crystalline compounds that the present invention is prepared is different with it, the visible prepared Sodium rabeprazole crystalline compounds of the present invention is the crystal formation different with it.
According to aforesaid Sodium rabeprazole crystalline compounds, wherein, the fusing point of described Sodium rabeprazole crystalline compounds is 162～163 ℃.
Its Measurement of melting point is measured according to the method for Chinese Pharmacopoeia, and this is known in those skilled in the art.
" synthesizing of proton pump inhibitor Sodium rabeprazole " [Asia, Shandong etc. synthesizing of proton pump inhibitor Sodium rabeprazole. print during chemical industry; 2011,25 (8): 46-48] fusing point that relates to the whitening compound Sodium rabeprazole that a kind of methylene dichloride/isopropyl ether recrystallization makes is 139～141 ℃; CN102260244A discloses a kind of stable sodium rabeprazole compound and preparation method thereof, and the sodium rabeprazole compound crystalline fusing point that it obtains is 242～242.5 ℃; And the fusing point of the prepared Sodium rabeprazole crystalline compounds of the present invention with above-mentioned two kinds all different.
The present invention also provides the preparation method of described Sodium rabeprazole crystalline compounds simultaneously, and this method comprises the steps:
1) the bulk drug Sodium rabeprazole is added in the entry, stir, dissolving obtains the rabeprazole sodium water solution;
2) under agitation in the above-mentioned Sodium rabeprazole aqueous solution, add the mixing solutions of THF and methyl alcohol, 25-35 ℃ of following gac insulation decolouring, filtration must be filtrated;
3) filtrating is splashed in the acetonitrile, cooling crystallization filters, and vacuum-drying promptly gets.
According to aforesaid preparation method, wherein, the mass ratio of the volume of water and bulk drug Sodium rabeprazole is 5～10: 1 in the step 1).
According to aforesaid preparation method, wherein, step 2) in the mixing solutions of THF and methyl alcohol and the step 1) volume ratio of water be 1～3: 1.
According to aforesaid preparation method, wherein, the volume ratio of THF and methyl alcohol is 3～6: 1 in the mixing solutions of described THF and methyl alcohol.
According to aforesaid preparation method, wherein, step 2) speed that stirs described in is 250～300r/min.
According to aforesaid preparation method, wherein, the volume ratio of the mixing solutions of the volume of acetonitrile and THF and methyl alcohol is 3～5: 1 in the step 3).
According to aforesaid preparation method, wherein, being cooled to described in the step 3) is cooled to 5～8 ℃.
The prepared Sodium rabeprazole crystalline compounds of the present invention has good stability, and can guarantee the quality of pharmaceutical prepn.
Helicobacter pylori infection (being called for short Hp) is the main reason that causes stomach, duodenal ulcer, and present clinical employing comprises that three or the quadruple chemotherapy treatment Hp of proton pump inhibitor and microbiotic infects.Discover that proton pump suppresses Sodium rabeprazole and the microbiotic combined utilization has good effect to eradicating Hp, wherein the effect of Sodium rabeprazole is except the gastric acid inhibitory secretion and antiulcer agent of generally acknowledging, itself also has very strong restraining effect to Hp.The inventor has studied the restraining effect of Sodium rabeprazole crystalline compounds to helicobacter pylori, finds that pleasantly surprisedly the prepared Sodium rabeprazole crystalline compounds of the present invention has stronger restraining effect to helicobacter pylori.
Description of drawings
Fig. 1 is the X-ray diffractogram of Sodium rabeprazole crystalline compounds of the present invention.
Embodiment
Below be embodiment of the present invention, described embodiment is in order to further describe the present invention, rather than restriction the present invention.
The preparation of [embodiment 1] Sodium rabeprazole crystalline compounds
1) bulk drug Sodium rabeprazole 60g is added in the 300ml water, stir, dissolving obtains the rabeprazole sodium water solution;
2) be the mixing solutions that in the above-mentioned Sodium rabeprazole aqueous solution, adds 480ml THF and methyl alcohol (volume ratio of THF and methyl alcohol is 3: 1) under the stirring of 300r/min in speed, 25 ℃ of following gacs insulations are decoloured, and filtration must be filtrated;
3) filtrating is splashed in the 1440ml acetonitrile, be cooled to 5 ℃, separate out crystal, filter, vacuum-drying obtains the white Sodium rabeprazole crystalline compounds of 54.1g.
It is 162～163 ℃ that this crystalline compounds uses capillary tube technique to detect its fusing point.
Adopt the U.S. PE 2400II of Perkin-Elmer company elemental analyser, ultimate analysis (%) is: measured value (calculated value), C:56.68 (56.68), H:5.29 (5.30), N:11.02 (11.00), O:12.58 (12.59), S:8.41 (8.40).
The Sodium rabeprazole crystalline compounds of gained is measured with the powder x-ray diffraction assay method; X-ray powder diffraction collection of illustrative plates so that 2 θ ± 0.2 ° diffraction angle is represented locates to demonstrate characteristic diffraction peak at 5.8 °, 7.5 °, 12.1 °, 12.8 °, 13.3 °, 15.6 °, 16.7 °, 18.3 °, 20.4 °, 25.7 °, 26.8 ° and 31.5 °, sees shown in Figure 1.
Below be embodiment 2-9, the technological operation step is with embodiment 1, and concrete processing parameter is seen table 1.
Table 1, embodiment 2-9
Its fusing point of crystalline compounds use capillary tube technique detection to embodiment 2-9 gained is 162～163 ℃, adopts the U.S. PE2400II of Perkin-Elmer company elemental analyser to carry out ultimate analysis, and the result is similar with embodiment 1.
Simultaneously the crystalline compounds of embodiment 2-9 is measured with the powder x-ray diffraction assay method, similar with the X-ray powder diffraction collection of illustrative plates that 2 θ ± 0.2 ° diffraction angle is represented with embodiment 1.
Test Example 1
Stability test
The inventor studies the stability of the prepared Sodium rabeprazole crystalline compounds of the embodiment of the invention 1; The investigation condition be high temperature (60 ℃ ± 2 ℃), strong illumination (4500Lx ± 500Lx), high humidity (92.5%, RH); The investigation index is outward appearance, content and related substance.
The result: from 0-15 days, outward appearance, related substance, content did not change, and explain that chemicalstability is good, are fit to the manufacturing and the standing storage of pharmaceutical prepn under high light, high temperature, super-humid conditions.
At 40 ℃, under different relative humidity (RH) conditions (75%, 92.5%), the mensuration of moisture in the sodium rabeprazole compound crystal, the result sees table 2:
Table 2
The result: at 40 ℃, under different relative humidity (RH) conditions (75%, 92.5%), it is constant that moisture keeps, and explanation has good stability, and is fit to the manufacturing and the standing storage of pharmaceutical prepn.
Stability to the prepared Sodium rabeprazole crystalline compounds of other embodiment of the present invention is also investigated, and the result of its acquisition is similar.
Test Example 2
This Test Example has been studied the restraining effect of Sodium rabeprazole to helicobacter pylori with reference to " Sodium rabeprazole is observed the external fungistatic effect of helicobacter pylori ".
One, materials and methods
1, bacterium source: helicobacter pylori NCTC11637, NCTC11639 are the international standard strain.
2, reagent instrument: trial drug (according to the method preparation of the embodiment of the invention 1); Control drug A (reference " synthesizing of proton pump inhibitor Sodium rabeprazole " [Asia, Shandong etc. synthesizing of proton pump inhibitor Sodium rabeprazole. print during chemical industry; 2011; 25 (8): 46-48] method in is got the bulk drug Sodium rabeprazole, with methylene dichloride/isopropyl ether recrystallization preparation); Control drug B (according to embodiment 1 preparation of CN102260244A); Colombia's agar, sheep whole blood, spiral coating appearance, mixed gas incubator.
3, flat board mixes test: 1) plate preparation: preparation contains the serial blood agar that the rabeprazole na concn is 0.225 μ g/ml-225 μ g/ml (containing 7% sheep whole blood); 2) be coated with bacterium: PBS dilution Hp (helicobacter pylori) is about 10 to bacterial concentration
7Cfu/ml uses spiral coating appearance to be coated with bacterium, and each concentration of every kind of bacterium of every medicine is coated with two flat boards (every dull and stereotyped 50 μ l bacterium liquid), places mixed gas (N
285%, CO
210%, O
25%) cultivates observations after 72 hours for 37 ℃ in; 3) above experimentation triplicate.
Two, result
Experimental result is seen table 3 and table 4:
Table 3, medicine are to the fungistatic effect (μ g/ml) of NCTC11637
| Antibacterial medicines | MIC 99 | MIC 80 |
| Trial drug | 2.25 | 0.225 |
| Control drug A | 22.5 | 2.25 |
| Control drug B | 22.5 | / |
Table 4, medicine are to the fungistatic effect (μ g/ml) of NCTC11639
| Antibacterial medicines | MIC 99 | MIC 80 |
| Trial drug | 2.25 | 0.225 |
| Control drug A | 22.5 | 2.25 |
| Control drug B | 22.5 | / |
It is thus clear that the prepared rabeprazole of the present invention has stronger fungistatic effect by crystalline compounds to helicobacter pylori.
The Sodium rabeprazole crystalline compounds prepared to other embodiment of the present invention also carried out identical test, and the result of its acquisition is similar.
Claims (9)
1. Sodium rabeprazole crystalline compounds; It is characterized in that; Described Sodium rabeprazole crystalline compounds is measured with the powder x-ray diffraction assay method, locates to demonstrate characteristic diffraction peak with the X-ray powder diffraction collection of illustrative plates that 2 θ ± 0.2 ° diffraction angle is represented at 5.8 °, 7.5 °, 12.1 °, 12.8 °, 13.3 °, 15.6 °, 16.7 °, 18.3 °, 20.4 °, 25.7 °, 26.8 ° and 31.5 °.
2. Sodium rabeprazole crystalline compounds according to claim 1 is characterized in that, the fusing point of described Sodium rabeprazole crystalline compounds is 162～163 ℃.
3. the preparation method of claim 1 or 2 described Sodium rabeprazole crystalline compounds is characterized in that described preparation method comprises the steps:
1) the bulk drug Sodium rabeprazole is added in the entry, stir, dissolving obtains the rabeprazole sodium water solution;
2) under agitation in the above-mentioned Sodium rabeprazole aqueous solution, add the mixing solutions of THF and methyl alcohol, 25-35 ℃ of following gac insulation decolouring, filtration must be filtrated;
3) filtrating is splashed in the acetonitrile, cooling crystallization filters, and vacuum-drying promptly gets.
4. preparation method according to claim 3 is characterized in that, the mass ratio of the volume of water and bulk drug Sodium rabeprazole is 5～10: 1 in the step 1).
5. preparation method according to claim 3 is characterized in that step 2) in mixing solutions and the step 1) of THF and methyl alcohol the volume ratio of water be 1～3: 1.
6. preparation method according to claim 5 is characterized in that, the volume ratio of THF and methyl alcohol is 3～6: 1 in the mixing solutions of described THF and methyl alcohol.
7. preparation method according to claim 3 is characterized in that step 2) described in the speed that stirs be 250～300r/min.
8. preparation method according to claim 3 is characterized in that, the volume ratio of the mixing solutions of the volume of acetonitrile and THF and methyl alcohol is 3～5: 1 in the step 3).
9. preparation method according to claim 3 is characterized in that, being cooled to described in the step 3) is cooled to 5～8 ℃.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709141A (en) * | 2013-10-14 | 2014-04-09 | 寿光富康制药有限公司 | Crystal forms and amorphous forms of rabeprazole sodium |
| CN105085481A (en) * | 2014-05-19 | 2015-11-25 | 南京长澳医药科技有限公司 | Recrystallization method of rabeprazole sodium |
| CN105085486A (en) * | 2015-09-09 | 2015-11-25 | 上海汇伦生命科技有限公司 | Refining method of dexrabeprazole sodium |
| CN109111428A (en) * | 2017-06-23 | 2019-01-01 | 南京海润医药有限公司 | A kind of dextral-rabeprazole sodium compound and its pharmaceutical composition |
| CN109111429A (en) * | 2017-06-23 | 2019-01-01 | 南京海润医药有限公司 | Dextral-rabeprazole sodium compound and its pharmaceutical composition |
| CN113336741A (en) * | 2021-05-07 | 2021-09-03 | 湖南德虹制药有限公司 | Rabeprazole sodium anhydrate crystal form and preparation method thereof |
| CN114933588A (en) * | 2022-06-16 | 2022-08-23 | 岳阳职业技术学院 | Refining method of rabeprazole sodium crude product |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101580502A (en) * | 2009-06-30 | 2009-11-18 | 常州康丽制药有限公司 | Method for preparing Rabeprazole sodium |
| WO2010006904A2 (en) * | 2008-06-23 | 2010-01-21 | Krka, Tovarna Zdravil, D.D., Novo Mesto | New crystalline forms of rabeprazole sodium |
| CN101704811A (en) * | 2009-12-09 | 2010-05-12 | 陶灵刚 | High-purity sodium rabeprazole compound |
| CN101805327A (en) * | 2010-04-29 | 2010-08-18 | 郝志艳 | Rabeprazole sodium compound and novel preparation method thereof |
| CN102219777A (en) * | 2010-04-19 | 2011-10-19 | 江苏豪森药业股份有限公司 | Method for preparing sodium rabeprazole |
-
2012
- 2012-01-13 CN CN 201210011134 patent/CN102584793B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010006904A2 (en) * | 2008-06-23 | 2010-01-21 | Krka, Tovarna Zdravil, D.D., Novo Mesto | New crystalline forms of rabeprazole sodium |
| CN101580502A (en) * | 2009-06-30 | 2009-11-18 | 常州康丽制药有限公司 | Method for preparing Rabeprazole sodium |
| CN101704811A (en) * | 2009-12-09 | 2010-05-12 | 陶灵刚 | High-purity sodium rabeprazole compound |
| CN102219777A (en) * | 2010-04-19 | 2011-10-19 | 江苏豪森药业股份有限公司 | Method for preparing sodium rabeprazole |
| CN101805327A (en) * | 2010-04-29 | 2010-08-18 | 郝志艳 | Rabeprazole sodium compound and novel preparation method thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103709141A (en) * | 2013-10-14 | 2014-04-09 | 寿光富康制药有限公司 | Crystal forms and amorphous forms of rabeprazole sodium |
| CN105085481A (en) * | 2014-05-19 | 2015-11-25 | 南京长澳医药科技有限公司 | Recrystallization method of rabeprazole sodium |
| CN105085481B (en) * | 2014-05-19 | 2017-09-29 | 南京长澳医药科技有限公司 | A kind of recrystallization method of RABEPRAZOLE SODIUM |
| CN105085486A (en) * | 2015-09-09 | 2015-11-25 | 上海汇伦生命科技有限公司 | Refining method of dexrabeprazole sodium |
| CN105085486B (en) * | 2015-09-09 | 2018-02-16 | 上海汇伦生命科技有限公司 | A kind of process for purification of dextral-rabeprazole sodium |
| CN109111428A (en) * | 2017-06-23 | 2019-01-01 | 南京海润医药有限公司 | A kind of dextral-rabeprazole sodium compound and its pharmaceutical composition |
| CN109111429A (en) * | 2017-06-23 | 2019-01-01 | 南京海润医药有限公司 | Dextral-rabeprazole sodium compound and its pharmaceutical composition |
| CN113336741A (en) * | 2021-05-07 | 2021-09-03 | 湖南德虹制药有限公司 | Rabeprazole sodium anhydrate crystal form and preparation method thereof |
| CN114933588A (en) * | 2022-06-16 | 2022-08-23 | 岳阳职业技术学院 | Refining method of rabeprazole sodium crude product |
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Owner name: SHANDONG LUOXIN PHARMACY GROUP CO., LTD. Free format text: FORMER NAME: SHANDONG LUOXIN PHARMACY STOCK CO., LTD. |
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| CP01 | Change in the name or title of a patent holder |
Address after: Seven of 276017 Shandong province Linyi city Luozhuang District Patentee after: Shandong Luo Xin Pharmaceutical Group Plc Address before: Seven of 276017 Shandong province Linyi city Luozhuang District Patentee before: SHANDONG LUOXIN PHARMACY STOCK Co., LTD. |