CN106432149A - Method for preparing medicine ranitidine hydrochloride compound for treating stomach illness - Google Patents
Method for preparing medicine ranitidine hydrochloride compound for treating stomach illness Download PDFInfo
- Publication number
- CN106432149A CN106432149A CN201610823327.8A CN201610823327A CN106432149A CN 106432149 A CN106432149 A CN 106432149A CN 201610823327 A CN201610823327 A CN 201610823327A CN 106432149 A CN106432149 A CN 106432149A
- Authority
- CN
- China
- Prior art keywords
- ranitidine hydrochloride
- compound
- acetone
- hydrochloride compound
- grain
- 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
- 229960001520 ranitidine hydrochloride Drugs 0.000 title claims abstract description 67
- -1 ranitidine hydrochloride compound Chemical class 0.000 title claims abstract description 33
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims abstract description 11
- 210000002784 stomach Anatomy 0.000 title abstract 2
- GGWBHVILAJZWKJ-KJEVSKRMSA-N ranitidine hydrochloride Chemical compound [H+].[Cl-].[O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 GGWBHVILAJZWKJ-KJEVSKRMSA-N 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 8
- 229910017488 Cu K Inorganic materials 0.000 claims abstract description 5
- 229910017541 Cu-K Inorganic materials 0.000 claims abstract description 5
- 230000005260 alpha ray Effects 0.000 claims abstract description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 16
- 239000012046 mixed solvent Substances 0.000 claims description 12
- JYYNAJVZFGKDEQ-UHFFFAOYSA-N 2,4-Dimethylpyridine Chemical class CC1=CC=NC(C)=C1 JYYNAJVZFGKDEQ-UHFFFAOYSA-N 0.000 claims description 11
- 208000012895 Gastric disease Diseases 0.000 claims description 7
- 208000018556 stomach disease Diseases 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 abstract description 18
- 238000010521 absorption reaction Methods 0.000 abstract description 9
- 239000013078 crystal Substances 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 229960000620 ranitidine Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 238000004088 simulation Methods 0.000 description 4
- 229960001380 cimetidine Drugs 0.000 description 3
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical group 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 108010079943 Pentagastrin Proteins 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229960000444 pentagastrin Drugs 0.000 description 2
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010583 slow cooling Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102100021022 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 206010020741 Hyperpyrexia Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 229950002342 bisfentidine Drugs 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000745 gonadal hormone Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- FXJAOWANXXJWGJ-UHFFFAOYSA-N n-[4-(2-methyl-1h-imidazol-5-yl)phenyl]-n'-propan-2-ylmethanimidamide Chemical compound C1=CC(NC=NC(C)C)=CC=C1C1=CN=C(C)N1 FXJAOWANXXJWGJ-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
Abstract
The invention discloses a method for preparing a medicine ranitidine hydrochloride compound for treating stomach illness, which belongs to the technical field of medicines. The compound prepared by the method provided by the invention uses a Cu-K alpha ray for measuring to obtain an X-ray powder diffraction pattern as shown in a figure 1; a new crystal form of the compound is different from a crystal structure in the prior art; an experiment proves that the compound utilizing the new crystal structure cannot easily absorb moisture, is good in stability, fundamentally solves the problems that ranitidine hydrochloride is unstable when being wetted or heated or meeting air, a product can be easily oxidized and discolored due to moisture absorption, the stability is poor and the like, and provides convenience for preparing a preparation.
Description
The application is the joyful Pharmaceutical Technology Co., Ltd of applicant Yantai City Chinese, the invention of Wang Yufeng, Li Xianmeng proposition
Patent application（Invention entitled：A kind of treat medicine ranitidine hydrochloride compound of gastropathy and preparation method thereof, application number
For：201510273209X, the applying date is：On May 26th, 2015）Divisional application.
Technical field
The invention belongs to pharmaceutical technology field, it is related to a kind of preparation of the medicine ranitidine hydrochloride compound treating gastropathy
Method.
Background technology
Ranitidine is the medicine of most widely used treatment Peptic Ulcerss at present as cimetidine.By Britain Ge Lan element
（glaxo）Company develops.1976 by Britain's Price（price）Deng synthesis, Bradshaw in 1979（bradshaw）Illustrate
Its pharmacology, bass tower in 1980（berstad）Report for duodenal ulcer effectively, listing in 1981, in the world more or less a hundred
Countries use.China was produced by Shanghai No.6 Pharmaceutical Factory in 1985.
Ranitidine is a selective bisfentidine, can effectively suppress histamine, pentagastrin and food thorn
The gastric acid secretion causing after swashing, reduces the activity of gastric acid and gastric enzyme, but the secretion on gastrin and gonadal hormone no affects.Effect ratio
Cimetidine is strong 5～8 times, high to the curative effect of gastric and duodenal ulcers, has the characteristics that quick-acting and long-acting, Small side effects and
Safety.30～90 minutes after single oral 80mg, average Cmax is 165ng/ml, effect lasts 12 hours.
Ranitidine absorbs fast, the impact of unable to take food thing and antacid.Oral administration biaavailability is about 50%, t1/2 and is about
2～2.7 hours, slightly long compared with cimetidine.Gastric acid secretion minimizing 30% that interior energy make pentagastrin to cause is administered orally latter 12 hours.
Intravenous 1mg/kg, instantaneous blood concentration is 3000ng/ml, maintains more than 100ng/ml up to 4 hours；With 0.5ng/ per hour
After kg speed intravenous infusion, 30～60 minutes blood concentration peakings, are proportionate between peak concentration and dosage.Major part is arranged from kidney with original shape
Let out, renal clearance is every point of 7.2ml/kg.
Ranitidine hydrochloride heat, wet, air extremely unstable, product is easily oxidized and easy decomposed metamorphic during hyperpyrexia.Due to
Crude drug is easy to the moisture absorption, leads to variable color, the reason such as stability difference, has had a strong impact on formulation products quality, to the preparation of preparation
Bring difficulty.
Therefore, it is necessary to develop a kind of ranitidine hydrochloride noval chemical compound, fundamentally solve ranitidine hydrochloride meet wet,
Heat, air unstable, product is easily oxidized, easy moisture absorption variable color, stability difference the problems such as, be the preparation provides convenient of preparation.
Content of the invention
The goal of the invention of the present invention is to provide a kind of medicine ranitidine hydrochloride compound treating gastropathy and its preparation
Method.
In order to realize the purpose of the present invention, the technical scheme of employing is：
A kind of medicine ranitidine hydrochloride compound treating gastropathy is it is characterised in that described ranitidine hydrochloride compound
The X-ray powder diffraction figure being obtained using Cu-K alpha ray measurement is as shown in Figure 1.
A kind of method of the medicine ranitidine hydrochloride compound preparing treatment gastropathy of the present invention, comprises the steps：Will
Ranitidine hydrochloride solid dissolving is in methanol solution；It is initially charged the mixed solvent of ethanol, acetone, stirring while adding, control temperature
20-25 DEG C of degree, growing the grain 0.5-1 hour；Then acetone, the mixed solvent of 2,4- lutidines, growing the grain 1-2 hour are added
Afterwards, lower the temperature, be then kept stirring for speed 120-150 rev/min stirring and crystallizing, growing the grain 2-3 hour；Filter, be dried to obtain hydrochloric acid
Ranitidine crystalline compounds.
Preferably, the volume of described methanol solution is 8-10 times of ranitidine hydrochloride weight.
Preferably, the temperature of described methanol solution is 20-25 DEG C.
Preferably, the volume total amount being initially charged the mixed solvent of ethanol, acetone is the 10-12 of ranitidine hydrochloride weight
Times, ethanol is 1.5 with the volume ratio of acetone:1.
Preferably, adding acetone, the volume total amount of the mixed solvent of 2,4- lutidines is ranitidine hydrochloride
12-25 times of weight, the volume ratio of acetone and 2,4- lutidines is 3:2.
Preferably, described cooling is to be cooled to -5 DEG C with 10-15 DEG C/h of speed.
Preferably, described drying condition is 40-50 DEG C, drying under reduced pressure.
Below technical scheme is made further explanation：
The present invention passes through to change the crystallization condition of ranitidine hydrochloride, prepares a kind of new ranitidine hydrochloride compound, leads to
Cross the X-ray powder diffraction figure obtaining using Cu-K alpha ray measurement as shown in Figure 1.
The preparation method of the present invention, finely controls to crystallization condition, has obtained a kind of new crystalline compounds.The present invention is led to
Cross the control to temperature, mixing speed etc., thus the crystallization process of stricter control solution.
In ranitidine hydrochloride crystallization process, add the mixed of two kinds of solvents formation in the methanol solution of ranitidine hydrochloride
Bonding solvent, then pass through gradient crystallize, growing the grain, the means such as slow cooling, stirring, thus control the crystallization of ranitidine hydrochloride
Journey.Simultaneously by the way of gradient crystallize, organic solvent carries out slow cooling after adding, the speed of cooling be with 10-15 DEG C/
The speed of hour is cooled to -5 DEG C.Strict control by multiple crystallize and to Crystallization Process, has obtained a kind of new hydrochloric acid
Ranitidine compound.
Through it is experimentally confirmed that prepared by the present invention ranitidine hydrochloride compound is difficult moisture absorption, good stability, from basic
On solve ranitidine hydrochloride and meet that wet, hot, air is unstable, product is easily oxidized, easy moisture absorption variable color, and stability difference etc. is asked
Topic, is that the preparation of preparation provides conveniently.
As well known to those skilled in the art：Volume and weight is that g/ml, kg/L so mate, and the volume of above-mentioned solvent is salt
The statement of the multiple of sour ranitidine weight may be interpreted as every ml solvent and corresponds to ranitidine hydrochloride how many g or every L solvent pair
Answered ranitidine hydrochloride how many kg.
Brief description
Fig. 1 is the X-ray powder diffraction collection of the ranitidine hydrochloride compound of the embodiment of the present invention 1 preparation.
Specific embodiment
Below by specific embodiment, the content of the invention of the present invention is described in further detail, but does not therefore limit
Determine present disclosure.
Embodiment 1：The preparation method of ranitidine hydrochloride compound, step is as follows：
By ranitidine hydrochloride solid dissolving in 20 DEG C of volumes be ranitidine hydrochloride weight 8 times of methanol solutions in；It is initially charged
Volume total amount is 10 times of ethanol of ranitidine hydrochloride weight, the mixed solvent of acetone, and ethanol with the volume ratio of acetone is
1.5:1, stirring while adding, control 20 DEG C of temperature, growing the grain 0.5 hour；Then adding volume total amount is ranitidine hydrochloride weight
12 times of acetone of amount, the mixed solvent of 2,4- lutidines, the volume ratio of acetone and 2,4- lutidines is 3:2, support
After brilliant 1 hour, it is cooled to -5 DEG C with 10 DEG C/h of speed, is then kept stirring for speed 120 revs/min of stirring and crystallizing, growing the grains
2 hours；Filter, 40 DEG C, drying under reduced pressure obtain ranitidine hydrochloride crystalline compounds.
The X-ray powder diffraction that the ranitidine hydrochloride compound crystal preparing is obtained using Cu-K alpha ray measurement
Figure is as shown in Figure 1.
Embodiment 2：The preparation method of ranitidine hydrochloride compound, step is as follows：
By ranitidine hydrochloride solid dissolving in 22.5 DEG C of volumes be ranitidine hydrochloride weight 9 times of methanol solutions in；First plus
Entering volume total amount is 11 times of ethanol of ranitidine hydrochloride weight, the mixed solvent of acetone, and ethanol with the volume ratio of acetone is
1.5:1, stirring while adding, control 22.5 DEG C of temperature, growing the grain 0.75 hour；Then adding volume total amount is ranitidine hydrochloride
18.5 times of acetone of weight, the mixed solvent of 2,4- lutidines, the volume ratio of acetone and 2,4- lutidines is 3:
2, growing the grain, after 1.5 hours, is cooled to -5 DEG C with 12.5 DEG C/h of speed, is then kept stirring for 135 revs/min of stirrings of speed
Crystallize, growing the grain 2.5 hours；Filter, 45 DEG C, drying under reduced pressure obtain ranitidine hydrochloride crystalline compounds.
The X-ray powder diffraction figure of the crystal that the ranitidine hydrochloride compound crystal preparing is prepared with embodiment 1
The characteristic peak of spectrum is identical.
Embodiment 3：The preparation method of ranitidine hydrochloride compound, step is as follows：
By ranitidine hydrochloride solid dissolving in 25 DEG C of volumes be ranitidine hydrochloride weight 10 times of methanol solutions in；It is initially charged
Volume total amount is 12 times of ethanol of ranitidine hydrochloride weight, the mixed solvent of acetone, and ethanol with the volume ratio of acetone is
1.5:1, stirring while adding, control 25 DEG C of temperature, growing the grain 1 hour；Then adding volume total amount is ranitidine hydrochloride weight
25 times of acetone, the mixed solvent of 2,4- lutidines, the volume ratio of acetone and 2,4- lutidines is 3:2, growing the grain 2
After hour, it is cooled to -5 DEG C with 15 DEG C/h of speed, be then kept stirring for 150 revs/min of stirring and crystallizing of speed, growing the grain 3 little
When；Filter, 50 DEG C, drying under reduced pressure obtain ranitidine hydrochloride crystalline compounds.
The X-ray powder diffraction figure of the crystal that the ranitidine hydrochloride compound crystal preparing is prepared with embodiment 1
The characteristic peak of spectrum is identical.
Experimental example 1
1. hot test
Three batches of the ranitidine hydrochloride compound that Example 1 prepares 101,102,103, simulation listing packaging, put
In sealing clean container, place 10 days at a temperature of 40 ± 2 DEG C, sampled in the 5th day and the 10th day, by stability high spot reviews item
Mesh is detected, result of the test was compared with 0 day.
2. high humility test
Three batches of the ranitidine hydrochloride compound that Example 1 prepares 101,102,103, simulation listing packaging, put
In sealing clean container, place 10 days under conditions of 25 ± 2 DEG C of relative humiditys 90% ± 5%, sampled in the 5th day and the 10th day,
Detected by stability high spot reviews project, result of the test compared 3. strong illumination tests with 0 day
Three batches of the ranitidine hydrochloride compound that Example 1 prepares 101,102,103, simulation listing packaging, put
In sealing clean container, it is placed in illumination for placing 10 days under conditions of 4500lx, sampled in the 5th day and the 10th day, by stability
High spot reviews project is detected, result was compared with 0 day, and result is as shown in table 1.
Table 1 high temperature, high humidity, the illumination impact result of the test to ranitidine hydrochloride compound
Result shows：The ranitidine hydrochloride compound that the present invention prepares, its stability is good, in high temperature, high humidity, strong
Under illumination condition, all keep stable performance.The ranitidine hydrochloride compound of other embodiments of the present invention preparation is affected
Factor Experiment, has obtained identical experimental result.
Experimental example 2：Acceleration study
Three batches 201,202,203 of the ranitidine hydrochloride compound of Example 2 gained, simulation listing packaging, put close
In envelope clean container, place 6 months under the conditions of 42 DEG C, 80%RH, during testing, sample one respectively at 1,2,3,6 the end of month
Secondary, each stability high spot reviews project is tested.Result of the test is as shown in table 2：
Table 2 ranitidine hydrochloride compound of the present invention each stability high spot reviews item-test result
Result shows：The ranitidine hydrochloride compound that the present invention prepares, accelerated result of the test understands, its stability
Well.Acceleration study is carried out to the ranitidine hydrochloride compound of other embodiments preparation, has obtained identical experimental result.
Experimental example 3：Moisture absorption comparative test
1 instrument and reagent
1.1 instrument
PL203 electronic balance, LRH-250-S constant temperature and humidity incubator, HH-400SD testing chamber for medicine stability；
1.2 reagent
Investigational agent：The ranitidine hydrochloride compound that embodiment 1 prepares；Comparative example 1：Singapore imported raw material hydrochloric acid thunder Buddhist nun
For fourth（Manufacturer：GlaxoWellcome Manufacturing Pte Ltd）；Comparative example 2：Domestic raw material hydrochloric acid thunder Buddhist nun replace
Fourth（Manufacturer：Changzhou Kangpu Pharmaceutical Co., Ltd.）
2 methods：Bottom is taken to fill the glass desicator of salt supersaturated solution（For ensureing saline solution saturation, exsiccator bottom should have
Excessive salt exists）, the built-in weighing botle of exsiccator, place 48h in calorstat to constant humidity.Take sample about 2g, put in weighing botle,
Accurately weighed, bottle cap is opened, puts into exsiccator top, put 25 DEG C of constant temperature and humidity incubators or 20 DEG C by different temperatures requirement steady
Preserve in qualitative test case, 3 parts of operation repetitive, weigh respectively in different time, calculate the hydroscopicity of different time.
Computing formula：Hydroscopicity=（Medicated powder weight-moisture absorption prodrug grain weight amount after moisture absorption）/ moisture absorption prodrug grain weight amount × 100%.
Result is as shown in table 3：
Table 3 present invention is compared in the hydroscopicity of different time with comparative example 1,2
According to above-mentioned experiment, the hygroscopicity of the ranitidine hydrochloride compound of present invention preparation is less than prior art, that is, should
The stability of compound is higher than prior art.
Claims (1)
1. a kind of method of the medicine ranitidine hydrochloride compound preparing treatment gastropathy is it is characterised in that comprise the steps：
By ranitidine hydrochloride solid dissolving in 25 DEG C of volumes be ranitidine hydrochloride weight 10 times of methanol solutions in；It is initially charged volume
Total amount is 12 times of ethanol of ranitidine hydrochloride weight, the mixed solvent of acetone, and ethanol is 1.5 with the volume ratio of acetone:1,
Stirring while adding, control 25 DEG C of temperature, growing the grain 1 hour；Then 25 times that volume total amount is ranitidine hydrochloride weight are added
Acetone, the mixed solvent of 2,4- lutidines, the volume ratio of acetone and 2,4- lutidines is 3:2, growing the grain 2 hours
Afterwards, it is cooled to -5 DEG C with 15 DEG C/h of speed, be then kept stirring for 150 revs/min of stirring and crystallizing of speed, growing the grain 3 hours；
Filter, 50 DEG C, drying under reduced pressure obtain ranitidine hydrochloride crystalline compounds；
X-ray powder diffraction figure such as Fig. 1 institute that obtained ranitidine hydrochloride compound is obtained using Cu-K alpha ray measurement
Show.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610823327.8A CN106432149B (en) | 2015-05-26 | 2015-05-26 | A kind of method for the medicine ranitidine hydrochloride compound for preparing treatment stomach trouble |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610823327.8A CN106432149B (en) | 2015-05-26 | 2015-05-26 | A kind of method for the medicine ranitidine hydrochloride compound for preparing treatment stomach trouble |
| CN201510273209.XA CN104817523B (en) | 2015-05-26 | 2015-05-26 | A kind of medicine ranitidine hydrochloride compound treating gastropathy and preparation method thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510273209.XA Division CN104817523B (en) | 2015-05-26 | 2015-05-26 | A kind of medicine ranitidine hydrochloride compound treating gastropathy and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106432149A true CN106432149A (en) | 2017-02-22 |
| CN106432149B CN106432149B (en) | 2018-04-17 |
Family
ID=53728024
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610807242.0A Withdrawn CN106397374A (en) | 2015-05-26 | 2015-05-26 | Method for preparing ranitidine hydrochloride compound as drug for treating stomach diseases |
| CN201610823158.8A Active CN106432147B (en) | 2015-05-26 | 2015-05-26 | A kind of method for the medicine ranitidine hydrochloride compound for preparing treatment stomach trouble |
| CN201610823211.4A Active CN106432148B (en) | 2015-05-26 | 2015-05-26 | A kind of preparation method for the medicine ranitidine hydrochloride compound for treating stomach trouble |
| CN201510273209.XA Active CN104817523B (en) | 2015-05-26 | 2015-05-26 | A kind of medicine ranitidine hydrochloride compound treating gastropathy and preparation method thereof |
| CN201610823327.8A Active CN106432149B (en) | 2015-05-26 | 2015-05-26 | A kind of method for the medicine ranitidine hydrochloride compound for preparing treatment stomach trouble |
Family Applications Before (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610807242.0A Withdrawn CN106397374A (en) | 2015-05-26 | 2015-05-26 | Method for preparing ranitidine hydrochloride compound as drug for treating stomach diseases |
| CN201610823158.8A Active CN106432147B (en) | 2015-05-26 | 2015-05-26 | A kind of method for the medicine ranitidine hydrochloride compound for preparing treatment stomach trouble |
| CN201610823211.4A Active CN106432148B (en) | 2015-05-26 | 2015-05-26 | A kind of preparation method for the medicine ranitidine hydrochloride compound for treating stomach trouble |
| CN201510273209.XA Active CN104817523B (en) | 2015-05-26 | 2015-05-26 | A kind of medicine ranitidine hydrochloride compound treating gastropathy and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (5) | CN106397374A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055396A (en) * | 2015-09-17 | 2015-11-18 | 青岛华之草医药科技有限公司 | Ranitidine hydrochloride composition freeze-dried powder injection for treating stomach illness |
| CN107382922A (en) * | 2017-08-03 | 2017-11-24 | 江苏汉斯通药业有限公司 | The preparation method of high-transmittance ranitidine hydrochloride |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521431A (en) * | 1980-10-01 | 1985-06-04 | Glaxo Group Limited | Aminoalkyl furan derivative |
| CN1098720A (en) * | 1991-12-20 | 1995-02-15 | 多坎化学有限公司 | The preparation of form 1 ranitidine hydrochloride |
| US5523423A (en) * | 1994-04-08 | 1996-06-04 | Acic (Canada) Inc. | Form of form 1 Ranitidine |
| US5621120A (en) * | 1994-05-13 | 1997-04-15 | Ranbaxy Laboratories Limited | Process for the manufacture of form 1 ranitidine hydrochloride |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR852557B (en) * | 1985-10-23 | 1985-11-27 | Chemica Farmakeutiki Viomihani | |
| KR0152469B1 (en) * | 1995-07-13 | 1998-10-15 | 이승웅 | Process for manufacturing form -ñ‹ ranitidine hydrochloride |
| AU1972097A (en) * | 1996-03-25 | 1997-10-17 | Hoechst Marion Roussel, Inc. | Process for the preparation of form 1 ranitidine hydrochloride |
| US20020151729A1 (en) * | 1997-02-26 | 2002-10-17 | Cheng Wen J. | Novel process for the preparation of form 1 ranitidine hydrochloride |
| IE990387A1 (en) * | 1998-06-17 | 2000-12-13 | Russinsky Ltd | A ranitidine base water adduct |
| CN1315818C (en) * | 2005-07-11 | 2007-05-16 | 石药集团中诺药业（石家庄）有限公司 | Synthesis method of ranitidine alkali and its hydrochloride |
| CN102010389B (en) * | 2009-09-04 | 2012-11-14 | 江苏汉斯通药业有限公司 | Method for preparing ranitidine hydrochloride |
| MX345168B (en) * | 2010-06-02 | 2017-01-19 | Laboratorios Senosiain S A De C V * | Process for preparing ranitidine hydrochloride form 2. |
-
2015
- 2015-05-26 CN CN201610807242.0A patent/CN106397374A/en not_active Withdrawn
- 2015-05-26 CN CN201610823158.8A patent/CN106432147B/en active Active
- 2015-05-26 CN CN201610823211.4A patent/CN106432148B/en active Active
- 2015-05-26 CN CN201510273209.XA patent/CN104817523B/en active Active
- 2015-05-26 CN CN201610823327.8A patent/CN106432149B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521431A (en) * | 1980-10-01 | 1985-06-04 | Glaxo Group Limited | Aminoalkyl furan derivative |
| CN1098720A (en) * | 1991-12-20 | 1995-02-15 | 多坎化学有限公司 | The preparation of form 1 ranitidine hydrochloride |
| US5523423A (en) * | 1994-04-08 | 1996-06-04 | Acic (Canada) Inc. | Form of form 1 Ranitidine |
| US5621120A (en) * | 1994-05-13 | 1997-04-15 | Ranbaxy Laboratories Limited | Process for the manufacture of form 1 ranitidine hydrochloride |
Non-Patent Citations (1)
| Title |
|---|
| 黄龙祥 等: "盐酸雷尼替丁精制方法的改进", 《中国医药工业杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106432148A (en) | 2017-02-22 |
| CN106432148B (en) | 2018-04-17 |
| CN106432147B (en) | 2018-04-17 |
| CN106432147A (en) | 2017-02-22 |
| CN104817523A (en) | 2015-08-05 |
| CN104817523B (en) | 2016-11-09 |
| CN106397374A (en) | 2017-02-15 |
| CN106432149B (en) | 2018-04-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109081839B (en) | Berberine-phthalic acid drug salt monocrystal and preparation method thereof | |
| CN104817523B (en) | A kind of medicine ranitidine hydrochloride compound treating gastropathy and preparation method thereof | |
| CN105193819A (en) | Medicine cefotiam hydrochloride composition for treating bacterial infection | |
| CN109776416B (en) | Bulleyaconitine A C crystal form and preparation method and application thereof | |
| CN104971053A (en) | Ranitidine hydrochloride composition tablet medicine for treating digestive system diseases | |
| CN104906069A (en) | Medicinal ranitidine hydrochloride composition capsule for treating gastric ulcer | |
| CN105055406A (en) | Antibacterial drug aztreonam composition | |
| CN105030694A (en) | Ranitidine hydrochloride composition dry suspension for treating gastric ulcer | |
| CN105125558A (en) | Antibacterial cefotiam hydrochloride drug composition | |
| CN104945397B (en) | Medicine Tropiseiron hydrochloride compound for the treatment of nausea and vomiting and preparation method thereof | |
| CN111671750A (en) | Levamlodipine maleate eutectic drug crystallized in triclinic system and preparation method and application thereof | |
| CN105055442A (en) | Ranitidine hydrochloride composition for treating gastric diseases | |
| CN104650065A (en) | Teneligliptin compound | |
| Niu et al. | Preparation, characterization and crystal structure of an intermolecular compound based on H3PMo12O40· nH2O and diethylamine | |
| CN103360457B (en) | A kind of androstanedione derivative crystal formation and preparation method thereof | |
| CN105001215A (en) | Aztreonam compound serving as sterilization medicine and preparation method thereof | |
| CN105055331A (en) | Ranitidine hydrochloride composition granule for treating peptic ulcer | |
| CN106432272A (en) | Method for preparing drug ceftibuten crystal compound for treating surgical operation infection | |
| CN104873484A (en) | Medicine, namely, ranitidine hydrochloride composition capsule, for treating digestive system disease | |
| CN105085548A (en) | Pharmaceutical cefotiam composition for treating infectious diseases | |
| CN105193737A (en) | Medicinal tropisetron hydrochloride composition dry suspension for treating nausea and emesis | |
| CN105232519A (en) | Pharmaceutical ranitidine hydrochloride composition for treating digestive diseases | |
| CN105106122A (en) | Ranitidine hydrochloride combination for inhibiting generation of gastric acid | |
| CN105106125A (en) | Medicinal ranitidine hydrochloride composition for treating peptic ulcer | |
| CN104693180A (en) | Sodium rabeprazole monohydrate crystal form and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wang Lingzhang Inventor after: Wang Yufeng Inventor before: Wang Yufeng |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20180320 Address after: 264003 high tech Zone, Shandong, Yantai science and technology Avenue, No. 39 Applicant after: YANTAI HUAWEN XINXIN PHARMACEUTICAL CO., LTD. Applicant after: Wang Lingzhang Address before: 264003 high tech Zone, Shandong, Yantai science and technology Avenue, No. 39 Applicant before: YANTAI HUAWEN XINXIN PHARMACEUTICAL CO., LTD. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20181010 Address after: 276017 Shandong Linyi high tech Zone, double moon road science and Technology Pioneer Park A321 Patentee after: LINYI CAOZHIMEI PHARMACEUTICAL TECHNOLOGY CO., LTD. Address before: 264003 No. 39 science and technology Avenue, hi tech Zone, Yantai, Shandong Co-patentee before: Wang Lingzhang Patentee before: YANTAI HUAWEN XINXIN PHARMACEUTICAL CO., LTD. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201124 Address after: 276017 A320, shuangyueyuan Road, high tech Industrial Development Zone, Linyi City, Shandong Province Patentee after: LINYI HIGH-TECH ZONE JINDI TECHNOLOGY INFORMATION SERVICE CENTER Address before: 276017 Shandong city of Linyi province high tech Zone Technology Park Road bimonthly A321 Patentee before: LINYI CAOZHIMEI PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right |