CN104873484A - Medicine, namely, ranitidine hydrochloride composition capsule, for treating digestive system disease - Google Patents
Medicine, namely, ranitidine hydrochloride composition capsule, for treating digestive system disease Download PDFInfo
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- CN104873484A CN104873484A CN201510273382.XA CN201510273382A CN104873484A CN 104873484 A CN104873484 A CN 104873484A CN 201510273382 A CN201510273382 A CN 201510273382A CN 104873484 A CN104873484 A CN 104873484A
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- ranitidine hydrochloride
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- ranitidine
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Abstract
The invention discloses a medicine, namely, a ranitidine hydrochloride composition capsule, for treating a digestive system disease, and belongs to the technical field of medicines. The composition capsule is prepared from ranitidine hydrochloride and talcum powder. Ranitidine hydrochloride is a new crystal type compound, an X-ray powder diffraction diagram obtained by adopting Cu-K alpha ray measurement is as shown in the Figure1, and ranitidine hydrochloride is different from ranitidine hydrochloride reported in the prior art. Tests prove that as compared with the ranitidine hydrochloride capsule in the prior art, the capsule prepared from the new crystal type ranitidine hydrochloride compound not only solves the problems that ranitidine hydrochloride has high possibility of deliquescing, absorbing moisture and changing color as well as poor stability, but also has the advantages that the component is simple, the adverse reaction is reduced greatly, and the stability, the medicine effect and the bioavailability of the capsule preparation are improved.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease.
Background technology
Ranitidine is the same with cimetidine is the medicine of current most widely used treatment Peptic Ulcers.Developed by Britain Ge Lan element (glaxo) company.1976 by synthesis such as Britain's Prices (price), 1979 Bradshaw (bradshaw) illustrate its pharmacology, it is effective that bass tower (berstad) report in 1980 is used for duodenal ulcer, and listing in 1981 years, in the world more or less a hundred countries use.China was produced in 1985 by Shanghai No.6 Pharmaceutical Factory.
Ranitidine is an optionally bisfentidine, and the gastric acid secretion caused after effectively suppressing histamine, pentagastrin and food stimulus reduces the activity of gastric acid and gastric enzyme, but on the secretion of gastrin and gonadal hormone without impact.Act on than the strong 5-8 of cimetidine doubly, high to the curative effect of gastric and duodenal ulcers, there is quick-acting and long-acting feature, the little and safety of side effect.30-90 minute after single oral 80mg, mean 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 hour, and comparatively cimetidine is slightly long.The gastric acid secretion that pentagastrin can be made to cause in oral latter 12 hours reduces 30%.Quiet note 1mg/kg, instantaneous blood concentration is 3000ng/ml, maintains more than 100ng/ml and can reach 4 hours; With 30-60 minute blood concentration peaking after quiet of 0.5ng/kg speed per hour, be proportionate between peak concentration and dosage.Major part is with original shape from renal excretion, and renal clearance is per minute 7.2ml/kg.
Ranitidine hydrochloride is deliquescence very easily, causes instability after moisture absorption, darkens, and content declines, and drug effect declines.The pharmaceutical preparation of the ranitidine hydrochloride gone on the market has capsule, conventional tablet, injection, effervescent granule, chewable tablet, effervescent tablet, oral liquid, syrup etc., wherein ranitidine hydrochloride capsules supplementary product kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive etc., and at least with 4 kinds of adjuvants.Increasing research shows that impurity in the incompatibility of the toxic and side effects of adjuvant itself, adjuvant and principal agent, adjuvant etc. all can have an impact to the safety of medicine,
Therefore, select suitable adjuvant and technique, reduce supplementary product kind and the consumption of ranitidine hydrochloride capsules, improve bioavailability and the stability of ranitidine hydrochloride capsules, for ensureing that the safety of clinical application has positive effect.
The present invention develops a kind of ranitidine hydrochloride noval chemical compound, capsule prepared by this ranitidine hydrochloride noval chemical compound is compared compared with the ranitidine hydrochloride capsules of prior art, not only solve the problem of ranitidine hydrochloride very easily deliquescence, moisture absorption, variable color, poor stability, and component is simple, greatly reduce the generation of untoward reaction, improve the stability of capsule preparations, drug effect and bioavailability.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease.
In order to complete object of the present invention, the technical scheme of employing is:
The present invention relates to a kind of medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease, described composition capsule is made up of ranitidine hydrochloride, Pulvis Talci; Described ranitidine hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
First optimal technical scheme of the present invention is: with parts by weight, and described composition capsule is made up of the ranitidine hydrochloride of 1-2 weight portion, the Pulvis Talci of 0.04-0.06 weight portion.
Second optimal technical scheme of the present invention is: with parts by weight, and described composition capsule is made up of the ranitidine hydrochloride of 1.5 weight portions, the Pulvis Talci of 0.05 weight portion.
3rd optimal technical scheme of the present invention is: the preparation method of described compositions comprises the following steps:
1) Feedstock treating: ranitidine hydrochloride is sieved with vibration screen-dividing machine;
2) weigh: carry out weighing supplementary material according to prescription;
3) mix: load weighted supplementary material is joined in mixer, motor rotation frequency is set, open mixer and mix 50 minutes;
4) Autocapsulefillingmachine fill, content uniformity need meet national standard;
5) pack.
4th optimal technical scheme of the present invention is: in described step 1), ranitidine hydrochloride is crossed 60 mesh sieves.
5th optimal technical scheme of the present invention is: arranging motor rotation frequency in described step 3) is 200r/min.
The preparation method of the ranitidine hydrochloride crystal in the present composition comprises the following steps:
(1) added by ranitidine hydrochloride solid in the mixed solvent of methanol, 2-methyltetrahydrofuran and acetonitrile, the volume of mixed solvent is 10 times of ranitidine hydrochloride weight, and the volume ratio of methanol, 2-methyltetrahydrofuran and acetonitrile is 8:3.5:1.5;
(2) control temperature is under the condition of 35-45 DEG C, adds the mixed solvent of acetoneand ethyl acetate in the solution that step (1) obtains, and the volume of mixed solvent is 9 times of ranitidine hydrochloride weight, and the volume ratio of acetoneand ethyl acetate is 4:1.5;
(3) after adding the mixed solvent of acetoneand ethyl acetate, be that 12 DEG C/min is cooled to-10-DEG C with speed, leave standstill 3 hours, crystallize out at-10-DEG C, filter, filter cake washing with acetone, obtains ranitidine hydrochloride compound after vacuum drying.
Below technical scheme of the present invention is made further explanation:
The present invention is by the precise controlling to crystallization condition, and prepared a kind of ranitidine hydrochloride novel crystal forms unlike the prior art, the X-ray powder diffraction pattern of this ranitidine hydrochloride crystal unlike the prior art.Simultaneously due to the ins and outs of this crystal formation, find through test, capsule prepared by this ranitidine hydrochloride noval chemical compound is compared compared with the ranitidine hydrochloride capsules of prior art, not only solve the problem of ranitidine hydrochloride very easily deliquescence, moisture absorption, variable color, poor stability, and component is simple, greatly reduce the generation of untoward reaction, improve the stability of capsule preparations, drug effect and bioavailability.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction of ranitidine hydrochloride crystal prepared by the embodiment of the present invention 1.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of ranitidine hydrochloride crystal
(1) added by ranitidine hydrochloride solid in the mixed solvent of methanol, 2-methyltetrahydrofuran and acetonitrile, the volume of mixed solvent is 10 times of ranitidine hydrochloride weight, and the volume ratio of methanol, 2-methyltetrahydrofuran and acetonitrile is 8:3.5:1.5;
(2) control temperature is under the condition of 35-45 DEG C, adds the mixed solvent of acetoneand ethyl acetate in the solution that step (1) obtains, and the volume of mixed solvent is 9 times of ranitidine hydrochloride weight, and the volume ratio of acetoneand ethyl acetate is 4:1.5;
(3) after adding the mixed solvent of acetoneand ethyl acetate, be that 12 DEG C/min is cooled to-10-DEG C with speed, leave standstill 3 hours, crystallize out at-10-DEG C, filter, filter cake washing with acetone, obtains ranitidine hydrochloride compound after vacuum drying.
The X-ray powder diffraction pattern that the ranitidine hydrochloride crystal prepared uses the measurement of Cu-K alpha ray to obtain as shown in Figure 1.
embodiment 2:the preparation of ranitidine hydrochloride capsules:
Prescription: with parts by weight, the ranitidine hydrochloride compound 1.5 parts that embodiment 1 is obtained, Pulvis Talci 0.04 part.
1) Feedstock treating: ranitidine hydrochloride is sieved with vibration screen-dividing machine;
2) weigh: carry out weighing supplementary material according to prescription;
3) mix: load weighted supplementary material is joined in mixer, motor rotation frequency is set, open mixer and mix 50 minutes;
4) Autocapsulefillingmachine fill, content uniformity need meet national standard;
5) pack.
embodiment 3:the preparation of ranitidine hydrochloride capsules:
Prescription: with parts by weight, the ranitidine hydrochloride compound 1.5 parts that embodiment 1 is obtained, Pulvis Talci 0.05 part.
1) Feedstock treating: ranitidine hydrochloride is sieved with vibration screen-dividing machine;
2) weigh: carry out weighing supplementary material according to prescription;
3) mix: load weighted supplementary material is joined in mixer, motor rotation frequency is set, open mixer and mix 50 minutes;
4) Autocapsulefillingmachine fill, content uniformity need meet national standard;
5) pack.
embodiment 4:the preparation of ranitidine hydrochloride capsules:
Prescription: with parts by weight, the ranitidine hydrochloride compound 1.5 parts that embodiment 1 is obtained, Pulvis Talci 0.06 part.
1) Feedstock treating: ranitidine hydrochloride is sieved with vibration screen-dividing machine;
2) weigh: carry out weighing supplementary material according to prescription;
3) mix: load weighted supplementary material is joined in mixer, motor rotation frequency is set, open mixer and mix 50 minutes;
4) Autocapsulefillingmachine fill, content uniformity need meet national standard;
5) pack.
experimental example 1: 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
Embodiment 1: the ranitidine hydrochloride that the embodiment of the present invention 1 is obtained;
Comparative example 1: Singapore's imported raw material ranitidine hydrochloride (manufacturer: GlaxoWellcome Manufacturing Pte Ltd);
Comparative example 2: domestic raw material ranitidine hydrochloride (manufacturer: Changzhou Kangpu Pharmaceutical Co., Ltd.
2 methods
Get the glass desicator (for ensureing that saline solution is saturated, excessive salt should be had bottom exsiccator to exist) that bottom fills salt supersaturated solution, the built-in weighing botle of exsiccator, places 48h to constant humidity in calorstat.Sample thief is about 2g, puts in weighing botle, accurately weighed, bottle cap is opened, puts into exsiccator top, put in 25 DEG C of constant temperature and humidity incubators or 20 DEG C of stability test casees by different temperatures requirement and preserve, operation repetitive 3 parts, weighs respectively at different time, calculates the hydroscopicity of different time.
Computing formula: hydroscopicity=(medicated powder weight after moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount × 100%.Result is as shown in the table:
According to above-mentioned experiment, the hygroscopicity of ranitidine hydrochloride compound prepared by the present invention is variant compared with prior art, lower than prior art, points out the stability of this compound higher than prior art.
experimental example 2: stability test
The ranitidine hydrochloride capsules agent that Example 2-4 is obtained and listing preparation ranitidine hydrochloride capsules (Beijing Qin Wu Tian Pharmaceutical Co., Ltd.'s production), under high temperature 40 DEG C, relative humidity 75% ± 5% condition 6 months, carry out accelerated test investigation, result is as following table:
From above result, accelerated test is after 6 months, and the sample dissolution of embodiment of the present invention 2-4, content and related substance significant change do not occur, and the preparation dissolution that goes on the market declines larger, related substance raises obviously, and the good stability of the ranitidine hydrochloride capsules that the present invention obtains is described.
experimental example 3:bioavailability study
This experimental example has investigated the bioavailability of ranitidine hydrochloride capsules by pharmacokinetic.
Test method: reference literature " Pharmacokinetic of ranitidine hydrochloride chewable tablets and relative bioavailability " (Journal of Chinese Hospital Pharmacy the 24th volume the 8th phase 456-458 page in 2004) method measures.
Sampling: respectively before taking medicine and after taking medicine 0. 5,1,1. 5,2,3,4,5,6,8,10,12 h each moment gathered venous blood 3mL, and detect according to above-mentioned literature method, result is as following table:
Commercially available ranitidine hydrochloride capsules pharmacokinetic studies data
Ranitidine hydrochloride capsules of the present invention is for dynamic experiment data
From upper table result, the blood drug level of ranitidine hydrochloride capsules of the present invention is significantly higher than the blood drug level of ranitidine hydrochloride capsules, shows that ranitidine hydrochloride capsules of the present invention bioavailability is in vivo significantly improved.
Claims (6)
1. treat a medicine hydrochloric acid ranitidine compositions capsule for digestive system disease, it is characterized in that: described composition capsule is made up of ranitidine hydrochloride, Pulvis Talci; Wherein said ranitidine hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. the medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease according to claim 1, is characterized in that: be made up of the ranitidine hydrochloride of 1-2 weight portion, the Pulvis Talci of 0.04-0.06 weight portion with composition capsule described in parts by weight.
3. the medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease according to claim 2, is characterized in that: be made up of the ranitidine hydrochloride of 1.5 weight portions, the Pulvis Talci of 0.05 weight portion with composition capsule described in parts by weight.
4. prepare a method for the medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease according to claim 1, it is characterized in that comprising the following steps:
1) Feedstock treating: ranitidine hydrochloride is sieved with vibration screen-dividing machine;
2) weigh: carry out weighing supplementary material according to prescription;
3) mix: load weighted supplementary material is joined in mixer, motor rotation frequency is set, open mixer and mix 50 minutes;
4) Autocapsulefillingmachine fill, content uniformity need meet national standard;
5) pack.
5. the preparation method of the medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease according to claim 4, is characterized in that: in described step 1), ranitidine hydrochloride is crossed 60 mesh sieves.
6. the preparation method of the medicine hydrochloric acid ranitidine compositions capsule for the treatment of digestive system disease according to claim 4, is characterized in that: arranging motor rotation frequency in described step 3) is 200r/min.
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| CN201510273382.XA CN104873484A (en) | 2015-05-26 | 2015-05-26 | Medicine, namely, ranitidine hydrochloride composition capsule, for treating digestive system disease |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101623258A (en) * | 2009-07-23 | 2010-01-13 | 海南美大制药有限公司 | Ranitidine hydrochloride lipidosome capsule and new application thereof |
| CN102138913A (en) * | 2011-03-24 | 2011-08-03 | 江苏苏南药业实业有限公司 | Ranitidine hydrochloride capsules and production method thereof |
| CN103330688A (en) * | 2013-07-16 | 2013-10-02 | 成都天台山制药有限公司 | Ranitidine freeze-dried powder injection for curing gastropathy |
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2015
- 2015-05-26 CN CN201510273382.XA patent/CN104873484A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101623258A (en) * | 2009-07-23 | 2010-01-13 | 海南美大制药有限公司 | Ranitidine hydrochloride lipidosome capsule and new application thereof |
| CN102138913A (en) * | 2011-03-24 | 2011-08-03 | 江苏苏南药业实业有限公司 | Ranitidine hydrochloride capsules and production method thereof |
| CN103330688A (en) * | 2013-07-16 | 2013-10-02 | 成都天台山制药有限公司 | Ranitidine freeze-dried powder injection for curing gastropathy |
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Application publication date: 20150902 |