CN105232473A - Pharmaceutical erdosteine composite granules for treating respiratory tract infection - Google Patents
Pharmaceutical erdosteine composite granules for treating respiratory tract infection Download PDFInfo
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- CN105232473A CN105232473A CN201510632961.9A CN201510632961A CN105232473A CN 105232473 A CN105232473 A CN 105232473A CN 201510632961 A CN201510632961 A CN 201510632961A CN 105232473 A CN105232473 A CN 105232473A
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- erdosteine
- weight portion
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- vanillin
- respiratory tract
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Abstract
The invention discloses pharmaceutical erdosteine composite granules for treating respiratory tract infection and belongs to the technical field of medicine. A composite is made from erdosteine, cane sugar, lactitol, vanillin and purified water. The erdosteine is a novel-crystal form compound, an X-ray powder diffraction pattern is obtained by measurement using Cu-KAlpha ray is shown in 1, and this erdosteine is different from that reported in the prior art, and testing shows that the erdosteine novel-crystal form compound has better solubility and higher stability, and the prepared granules are good in stability and very suitable for clinical application.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine erdosteine composition granule for the treatment of respiratory tract infection.
Background technology
Expectorant is the product of respiratory inflammation, can stimulate respiratory mucosa, causes cough and asthma, and can increase the weight of to infect.When acute/chronic bronchitis or chronic lung diseases respiratory failure, spend height as patient's thick sputum or form expectorant bolt, can clogs airways and cause suffocating.Therefore, use sticky expectorant regulator, make patient's phlegm dissolving, thinning, viscosity reduces, and accelerate respiratory mucosa ciliary movement, improve transport function, tool is of great significance.
This is smooth etc. for the sticky expectorant regulator of current listing such as bromhexine, mesna, carboxylic first, all has sticky expectorant regulating action in various degree, but its pharmacology or there are some defects clinically.Sulfydryl free in molecular structure can adsorb gastrointestinal tract mucin, gastrointestinal tract local damage can be produced after oral, side effect is larger, the antibacterial activity of penicillin, cephalosporins, erythromycin, tetracycline etc. can be weakened, unsuitable drug combination, not high to the improvement effect of some respiration parameter as expectorant viscosity etc.
Erdosteine is a kind of prodrug, with the sulfydryl closed of non-free in its structure, to local mucin inactive, after oral through metabolism produce three containing free sulfhydryl groups metabolite and play pharmacological action, thus oral rear without obvious gastrointestinal side effect.Experiment proves; erdosteine cylinder metabolism-ure can make mucinous disulfide bonds in bronchial secretion; and change secretions composition and rheological property; reduce sputum viscosity; improve downtrod respiratory function; this product energy scavenging free radicals, the oxidation deactivation that available protecting a1-antitrypsin brings out from cigarette, dirt, prevents the damage to elastance of lung albumen and neutrophilic granulocyte.This product obviously can also increase IgA/ albumin, lactoferrin/albuminous ratio, weakens local inflammation, strengthens and improves the osmosis of antibiotic to bronchial mucosa, be conducive to the treatment of the various inflammation of respiratory tract.External clinical clinical studies show: with like product as acetylcysteine, this is smooth for carboxylic first, ambroxol etc. compares, this product has good curative effect to acute/chronic bronchitis, more effective to the improvement of some respiratory function parameter, there is not drug accumulation in heavy dose of administration, Liver and kidney function moderate obstacle to this product characteristics of pharmacokinetics without obvious change.
The water solublity of erdosteine is poor, effective bioavailability in human body is low, and medicine in vivo infiltration rate usually determined by the speed dissolved, medicine in solid preparation is before being absorbed, have to pass through disintegrate and dissolve the process then transferring solution to, if medicine not easily discharges from preparation or the dissolution velocity of medicine is very slow, then the infiltration rate of said preparation Chinese medicine or degree just likely have problems.
The approach of existing solution erdosteine poorly water-soluble mainly comprises change dosage form, as CN101606931B is made into dispersible tablet, although above-mentioned preparation improves the water solublity of medicine to a certain extent, also there is many defects.Therefore, the erdosteine compound that a kind of performance improvement is provided is necessary.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of medicine erdosteine composition granule for the treatment of respiratory tract infection.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine erdosteine composition granule for respiratory tract infection, described composition granule is made up of erdosteine, sucrose, lactose, vanillin, purified water; Described erdosteine is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, described composition granule is made up of the erdosteine of 1.5 weight portions, the sucrose of 1.2-1.4 weight portion, the lactose of 0.3-0.5 weight portion, the vanillin of 0.02-0.04 weight portion, the purified water of 0.5-0.7 weight portion.
Preferably, described composition granule is made up of the erdosteine of 1.5 weight portions, the sucrose of 1.3 weight portions, the lactose of 0.4 weight portion, the vanillin of 0.03 weight portion, the purified water of 0.6 weight portion.
Preferably, the preparation method of described composition granule comprises the following steps:
(1) supplementary material process: sieve erdosteine, lactose, vanillin 80 orders;
(2) weigh: weigh according to prescription;
(3) granulate: erdosteine, sucrose, lactose, vanillin are added in wet mixing pelletizer, are dry mixed 10 minutes; Add wetting agent purified water wet mixing cutting 1-1.5min, 16 orders granulation soft material processed;
(4) drying and screening: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 55-65 DEG C, dry total time is 2.5-3.0 hour, and after dry, material sieves 40 order granulate;
(5) mix: granule after granulate and Pulvis Talci are dropped into three-dimensional motion mixer, premixing speed 10 revs/min, incorporation time 15 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
Preferably, the preparation method of described erdosteine crystal comprises the following steps:
Prepare the saturated methanol solution of erdosteine crude product of 30 DEG C, then the ethanol of 8 times and the mixed solvent of ether that volume is saturated methanol solution volume is added, described ethanol, the volume ratio of ether are 3:1, after stirring, cooling limit, limit is stirred, cooling rate is 15 DEG C/h, mixing speed is 95 revs/min, add the propanol that volume is the mixed solvent volume 4 times of ethanol and ether simultaneously, stop after being cooled to-5 DEG C stirring, leave standstill growing the grain 3 hours, filter, after drying under reduced pressure, obtain erdosteine crystalline compounds.
The present invention is by the precise controlling to crystallization condition, prepare a kind of novel crystal forms unlike the prior art, the X-ray powder diffraction pattern of this erdosteine crystal unlike the prior art, simultaneously due to the ins and outs of this crystal formation, test finds, this erdosteine crystal compound has good dissolubility and higher stability, the granule good stability made, and is very applicable to clinical practice.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the erdosteine crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
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 erdosteine crystal
Prepare the saturated methanol solution of erdosteine crude product of 30 DEG C, then the ethanol of 8 times and the mixed solvent of ether that volume is saturated methanol solution volume is added, described ethanol, the volume ratio of ether are 3:1, after stirring, cooling limit, limit is stirred, cooling rate is 15 DEG C/h, mixing speed is 95 revs/min, add the propanol that volume is the mixed solvent volume 4 times of ethanol and ether simultaneously, stop after being cooled to-5 DEG C stirring, leave standstill growing the grain 3 hours, filter, after drying under reduced pressure, obtain erdosteine crystalline compounds.
The X-ray powder diffraction pattern that the erdosteine crystal prepared uses the measurement of Cu-K alpha ray to obtain as shown in Figure 1.
embodiment 2:the preparation of erdosteine granule
Prescription: erdosteine crystal-form compound, the sucrose of 1.2 weight portions, the lactose of 0.3 weight portion, the vanillin of 0.02 weight portion, the purified water of 0.5 weight portion that the embodiment 1 of 1.5 weight portions is obtained.
Preparation method:
(1) supplementary material process: sieve erdosteine, lactose, vanillin 80 orders;
(2) weigh: weigh according to prescription;
(3) granulate: erdosteine, sucrose, lactose, vanillin are added in wet mixing pelletizer, are dry mixed 10 minutes; Add wetting agent purified water wet mixing cutting 1-1.5min, 16 orders granulation soft material processed;
(4) drying and screening: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 55-65 DEG C, dry total time is 2.5-3.0 hour, and after dry, material sieves 40 order granulate;
(5) mix: granule after granulate and Pulvis Talci are dropped into three-dimensional motion mixer, premixing speed 10 revs/min, incorporation time 15 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
embodiment 3:the preparation of erdosteine granule
Prescription: erdosteine crystal-form compound, the sucrose of 1.3 weight portions, the lactose of 0.4 weight portion, the vanillin of 0.03 weight portion, the purified water of 0.6 weight portion that the embodiment 1 of 1.5 weight portions is obtained.
Preparation method:
(1) supplementary material process: sieve erdosteine, lactose, vanillin 80 orders;
(2) weigh: weigh according to prescription;
(3) granulate: erdosteine, sucrose, lactose, vanillin are added in wet mixing pelletizer, are dry mixed 10 minutes; Add wetting agent purified water wet mixing cutting 1-1.5min, 16 orders granulation soft material processed;
(4) drying and screening: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 55-65 DEG C, dry total time is 2.5-3.0 hour, and after dry, material sieves 40 order granulate;
(5) mix: granule after granulate and Pulvis Talci are dropped into three-dimensional motion mixer, premixing speed 10 revs/min, incorporation time 15 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
embodiment 4:the preparation of erdosteine granule
Prescription: erdosteine crystal-form compound, the sucrose of 1.4 weight portions, the lactose of 0.5 weight portion, the vanillin of 0.04 weight portion, the purified water of 0.7 weight portion that the embodiment 1 of 1.5 weight portions is obtained.
Preparation method:
(1) supplementary material process: sieve erdosteine, lactose, vanillin 80 orders;
(2) weigh: weigh according to prescription;
(3) granulate: erdosteine, sucrose, lactose, vanillin are added in wet mixing pelletizer, are dry mixed 10 minutes; Add wetting agent purified water wet mixing cutting 1-1.5min, 16 orders granulation soft material processed;
(4) drying and screening: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 55-65 DEG C, dry total time is 2.5-3.0 hour, and after dry, material sieves 40 order granulate;
(5) mix: granule after granulate and Pulvis Talci are dropped into three-dimensional motion mixer, premixing speed 10 revs/min, incorporation time 15 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
experimental example 1:
The stability test of product of the present invention
1, accelerated test
Three batches of products of Example 1, in temperature be 40 ± 2 DEG C, relative humidity be the condition of 75 ± 5% under place 6 months, respectively at 0,1,2,3,6 the end of month sampling once, measure, in table 1 by high spot reviews project.
Table 1 accelerated test result (temperature 40 ± 2 DEG C, relative humidity 75% ± 5%)
Result shows, this product temperature be 40 ± 2 DEG C, relative humidity be 75 ± 5% conditions under place 6 months, its related substances is low, and each index has no significant change, and this product quality stability is good.
2, long term test
Example 1 product, in temperature be 25 DEG C, relative humidity be 60% ± 10% place, respectively at 0,3,6,9,12,18,24 the end of month sampling and measuring.Measure character, content and related substance according to pertinent regulations under " quality standard " item, record result (the results are shown in following table 2), and compare with criticizing to record for 0 month.
Table 2 long-term test results (temperature 25 ± 2 DEG C, relative humidity 60% ± 5%)
Shown by long-term test results: erdosteine compound of the present invention is 25 ± 2 DEG C in temperature, relative humidity is place under the condition of 60% ± 5% to stablize for 24 months, and indices is without significant change.
experimental example 2:
The water solublity that this experimental example carries out the 3 batch sample erdosteine compounds testing the embodiment of the present invention 1 is tested, compared with commercially available erdosteine.Specific experiment method is: in the low capacity bottle of constant temperature jacket, add appropriate distilled water, erdosteine is added to no longer dissolving at 25 DEG C, start magnetic stirrer, Keep agitation under constant temperature, in experimentation, system is in the state of two-phase coexistent all the time, after 70 minutes system liquid phase in the concentration of erdosteine be dissolubility at this temperature.Carry out sample analysis after 2 hours, get the close meansigma methods of adjacent two times result as measured value of experiment, before sampling, in order to make solid-liquid fully be separated, after stopping stirring, not molten erdosteine is deposited to the bottom of low capacity bottle, extract a small amount of upper clear supernate with syringe, filter with the filter of 0.45 micron, sample thief from filtrate, the content of erdosteine is measured, specifically in table 3 by HPLC.
The water solublity of erdosteine compound of the present invention under table 3 room temperature
From upper table analysis, the water solublity of erdosteine compound provided by the invention improves greatly.
Claims (5)
1. treat a medicine erdosteine composition granule for respiratory tract infection, it is characterized in that: described composition granule is made up of erdosteine, sucrose, lactose, vanillin, purified water; Described erdosteine 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 erdosteine composition granule for the treatment of respiratory tract infection according to claim 1, is characterized in that: described composition granule is made up of the erdosteine of 1.5 weight portions, the sucrose of 1.2-1.4 weight portion, the lactose of 0.3-0.5 weight portion, the vanillin of 0.02-0.04 weight portion, the purified water of 0.5-0.7 weight portion.
3. the medicine erdosteine composition granule for the treatment of respiratory tract infection according to claim 2, is characterized in that: described composition granule is made up of the erdosteine of 1.5 weight portions, the sucrose of 1.3 weight portions, the lactose of 0.4 weight portion, the vanillin of 0.03 weight portion, the purified water of 0.6 weight portion.
4. the medicine erdosteine composition granule of the treatment respiratory tract infection according to any one of claim 1-3, it is characterized in that, the preparation method of described composition granule comprises the following steps:
(1) supplementary material process: sieve erdosteine, lactose, vanillin 80 orders;
(2) weigh: weigh according to prescription;
(3) granulate: erdosteine, sucrose, lactose, vanillin are added in wet mixing pelletizer, are dry mixed 10 minutes; Add wetting agent purified water wet mixing cutting 1-1.5min, 16 orders granulation soft material processed;
(4) drying and screening: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 55-65 DEG C, dry total time is 2.5-3.0 hour, and after dry, material sieves 40 order granulate;
(5) mix: granule after granulate and Pulvis Talci are dropped into three-dimensional motion mixer, premixing speed 10 revs/min, incorporation time 15 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
5. the medicine erdosteine composition granule for the treatment of respiratory tract infection according to claim 1, it is characterized in that, the preparation method of the crystal of described erdosteine comprises the following steps:
Prepare the saturated methanol solution of erdosteine crude product of 30 DEG C, then the ethanol of 8 times and the mixed solvent of ether that volume is saturated methanol solution volume is added, described ethanol, the volume ratio of ether are 3:1, after stirring, cooling limit, limit is stirred, cooling rate is 15 DEG C/h, mixing speed is 95 revs/min, add the propanol that volume is the mixed solvent volume 4 times of ethanol and ether simultaneously, stop after being cooled to-5 DEG C stirring, leave standstill growing the grain 3 hours, filter, after drying under reduced pressure, obtain erdosteine crystalline compounds.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510632961.9A CN105232473A (en) | 2015-09-30 | 2015-09-30 | Pharmaceutical erdosteine composite granules for treating respiratory tract infection |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510632961.9A CN105232473A (en) | 2015-09-30 | 2015-09-30 | Pharmaceutical erdosteine composite granules for treating respiratory tract infection |
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| CN105232473A true CN105232473A (en) | 2016-01-13 |
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| CN201510632961.9A Withdrawn CN105232473A (en) | 2015-09-30 | 2015-09-30 | Pharmaceutical erdosteine composite granules for treating respiratory tract infection |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180039492A (en) * | 2016-10-10 | 2018-04-18 | 한미약품 주식회사 | Erdosteine granular medicine with reduced bitter taste and foreign body sensation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180039492A (en) * | 2016-10-10 | 2018-04-18 | 한미약품 주식회사 | Erdosteine granular medicine with reduced bitter taste and foreign body sensation |
| KR102647471B1 (en) | 2016-10-10 | 2024-03-14 | 한미약품 주식회사 | Erdosteine granular medicine with reduced bitter taste and foreign body sensation |
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Application publication date: 20160113 |
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