CN105061468B - A kind of preparation method of amoxicillin slow release crystal - Google Patents
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- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
- C07D499/48—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical
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- C07D499/64—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms
- C07D499/68—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms with aromatic rings as additional substituents on the carbon chain
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Abstract
The invention discloses a kind of preparation method of amoxicillin slow release crystal, step is as follows：Take Amoxicillin original powder, it adds in the water that temperature is 60~80 DEG C, the saturated solution of Amoxicillin is obtained by filtration in constant temperature stirring and dissolving, is then put into rapidly in 25 DEG C~45 DEG C water-baths, it stands and preserves 1h, it then switches into 15 DEG C of environment, precipitation obtains crystal, filters the crystal of precipitation, drying is to get amoxicillin slow release crystal.The Amoxicillin crystal being prepared by the method for the present invention, crystal form is more stable, and solution rate and solubility are lower, and drug release is more slow, the duration of drug effect in vivo is longer, and then administration number of times can be reduced, mitigate to animal stress, increase the utilization rate of drug, reduce treatment cost, also mitigate farm to the workload of animal-use drug, clinical meaning is larger, and Social benefit and economic benefit is more notable.
Description
Technical field
The present invention relates to a kind of preparation methods of amoxicillin slow release crystal for animals.
Background technology
Amoxicillin (Amoxicillin) also known as amoxycillin are semi-synthetic penicillins antibiotic, blue to leather
Positive bacteria and certain gram-negative bacterias all have good antibacterial action.Amoxicillin is a kind of mould with amino side chain
Element, chemical constitution more hydroxyls, the two property in the side-chain benzene ring of adenosine monophosphate are similar.Amoxicillin resists in vivo
Bacterium effect is substantially better than ammonia benzyl mould rope, the basic structure that antibacterial activity plays a major role be β in 6-amino-penicillanic acid-
Lactam nucleus can be combined with target site on bacterial inner membrane in specific manner, inhibit bacteria the activity that cell wall sticks peptide synthetase, so as to
Block cell wall sticks the synthesis of peptide, makes the cell wall defective of bacterium, thalline expansion cracking.Especially to Penicillin-resistant bacterial strain, intestines
The infection such as road bacillus, salmonella, enteron aisle Campylobacter spp curative effect is more notable.Clinically be mainly used for urinary system, respiratory system,
The infection of biliary tract etc..
Amoxicillin belongs to time dependence antibacterials, and the performance of pharmacological property is closely related with reaching the time of MIC, kills
Bacterium effect depends primarily on the exposure duration of time, i.e. bacterium of the blood concentration higher than MIC, and Cmax is not critically important.It is this kind of
For the blood concentration of antibacterials in 4~5 times of MIC, bactericidal effect is most preferably i.e. in saturation state, then increased dosage amount bactericidal effect
It is not further added by；And serum and tissue concentration be when being less than MIC, bacterium then starts continued growth, therefore clinical practice Ah not quickly
Usually a small amount of multiple dosing during XiLin so that time of the blood concentration more than MIC maintain to longest so as to ensure its curative effect.But
Frequent drug administration not only causes or to injure, but also animal clinical multiple dosing is particularly administered to animal on veterinary clinic
Medicine is very inconvenient, and a small amount of multiple dosing can also waste drug, increases treatment cost.Amoxicillin belongs to beta-lactam antibiosis simultaneously
Element is highly prone to the variation of environmental factor and occurs degrading to influence drug effect during beta-lactam nucleus storage for a long time.Cause
It is veterinary clinic problem to be solved that this, which obtains the Wymox with slowly releasing effect and stabilization,.
Substance due to affected by various factors, make intramolecular or intermolecular bonding mode change, causes in crystallization
Molecule or atom arrange difference in lattice vacancy, form different crystal structures.All there are polymorphisms for many crystalline drugs.
In its production process, due to the difference of production technology, different crystal types and amorphous can be formed.Same drug is different
Crystal form, because of lattice structure difference, physical property, such as solubility, dissolution rate, fusing point and stability (chemical stability) can
It can there are significant differences.Thus crystalline pharmaceutical research is increasingly subject to the attention of pharmaceutical field.It is existing research shows that, the dissolution of drug
Speed is proportional to the surface area of solubility and particle, the factors such as the crystalline state and particle size of drug influence drug-eluting and then
Influence the speed of drug absorption.Stablize type crystal structure since intermolecular arrangements rule or Hydrogenbond are regular, it is molten
It is relatively slow with respect to metastability crystal structure to go out speed, release molecular velocity is slack-off in vivo, can extend drug molecule in animal
Internal drug effect.So selecting suitable crystal structure, the stability of Amoxicillin class drug can be not only improved, but also can subtract
The dissolution of slow drug, so as to extend the action time of drug, this has highly important value for veterinary clinic medication.
In order to obtain the crystal structure of Amoxicillin, the country also have part scientific research personnel to the crystallization processes of Amoxicillin into
Research is gone.Amoxicillin crystallization processes are optimized using isoelectric point crystallizing method as University Of Tianjin Liu Hui is diligent, old lattice are surveyed
Determined the relationship of the crystal forms of 3 enterprise's Amoxicillin bulk pharmaceutical chemicals and external dissolution rate, Shi Yao groups Wang Yan is gorgeous report to Ah
Nucleus is formed in Amdinocillin crystallization process and the research of crystal form developmental process, China Patent No. are 201410274773.9 patent
A kind of Amoxicillin crystal and preparation method thereof is reported, but these researchs only grind the crystallization processes of Amoxicillin
Study carefully, but how to obtain the rarely seen research report of more stable Amoxicillin crystal with slowly releasing effect.
The present invention is directed to by studying influence of the different crystallization conditions to Amoxicillin crystal, so as to change Amoxicillin medicine
Object crystal form obtains the metastable crystal in Amoxicillin, improves the stability of Amoxicillin, slows down Amoxicillin molecule dissolution speed
Degree extends drug retention time in vivo, improves the antibacterial effect of drug.Simultaneously because the slowly releasing effect of drug can also mitigate pair
Animal stress, increase the utilization rate of drug, reduce treatment cost.So the stable crystal of Amoxicillin is produced with bright
Aobvious economy and practical value.
Invention content
For the above-mentioned prior art, the present invention provides a kind of preparation method of amoxicillin slow release crystal, by this hair
The amoxicillin slow release crystal that bright method is prepared, stability is high, and solubility is low.
The present invention is achieved by the following technical solutions：
A kind of preparation method of amoxicillin slow release crystal, step are as follows：Take Amoxicillin original powder, add in temperature for 60~
In 80 DEG C of solvent, constant temperature stirring and dissolving, filtering (filter paper filtering) obtains the saturated solution of Amoxicillin, is then put into 25 rapidly
DEG C~45 DEG C of water-baths in, stand and preserve 1h, then switch into 15 DEG C of environment, precipitation obtains Amoxicillin crystal, filters (with following
Ring water vacuum pump filter) be precipitated crystal, drying (be put into insulating box and dry) to get.
Preferably, the solvent is water, most preferably distilled water.
Preferably, the solution temperature is 60 DEG C or 70 DEG C.
Preferably, the crystallization mode is：15 DEG C are gone to after preserving 1h in 25 DEG C of environment or are kept in 45 DEG C of environment
15 DEG C are gone to after 1h.
The Amoxicillin crystal being prepared by the method for the present invention, crystal form is more stable, and solubility is low (to be reduced
28.2%), drug release is more slow, and the duration of such drug effect in vivo is longer, and then can reduce administration number of times, mitigates
To animal stress, increase the utilization rate of drug, reduce treatment cost, also allow for management of the farm to animal, clinical meaning
Larger, Social benefit and economic benefit is more notable.
Description of the drawings
Fig. 1：Amoxicillin standard curve.
Fig. 2：Amoxicillin solubility curve prepared by distinct methods.
Fig. 3：The solution rate that crystal is precipitated in different solution temperatures compares.
Fig. 4：The solution rate that crystal is precipitated in different recrystallization temperatures compares.
Fig. 5：The solution rate that crystal is precipitated in different crystallization modes compares.
Fig. 6：The Crystallization Process and crystal shape of Amoxicillin, wherein, (a) Crystallization Process；(b) Amoxicillin crystal；(c)
Amoxicillin crystal under microscope.
Specific embodiment
With reference to embodiment, the present invention is further illustrated.
Involved instrument, reagent, material etc., are existing in the prior art unless otherwise noted in following embodiments
Conventional instrument, reagent, material etc., can be obtained by regular commercial sources.Involved experimental method in following embodiments, inspection
Survey method etc. is existing routine experiment method, detection method etc. in the prior art unless otherwise noted.
Experiment prepares Amoxicillin crystal
1. material
1.1 drugs and reagent
Amoxicillin original powder, ammonium hydroxide (Chengdu Ke Long chemical reagents factory, authentication code 20130418, content >=
99.5%), ammonium hydroxide (Chengdu Ke Long chemical reagents factory, authentication code 20091023, content >=99.0%), sodium bicarbonate (my god
Shen Tai chemical reagent Co., Ltd of Jinshi City, authentication code 021219, content >=99.5%) etc..
1.2 main experimental instruments
Water-bath constant temperature oscillator (Harbin City Dongming Medical Instruments factory manufactures, HZS-H), (Shanghai is sub- for vacuum pump using circulatory water
Flourish III D of biochemical instrument factory SHZ-), constant temperature blender with magnetic force, ultraviolet specrophotometer (upper sea otter Ni Ke Instrument Ltd.,
WFZW-2000), (China of state electric appliance has for electronic analytical balance (Shenyang Longteng Electronic Co., Ltd., ESJ200-4), thermostat water bath
Limit company, HH-4) etc..
2. method and result
The foundation of 2.1 Determination of amoxicillin assay methods
The measure of Determination of amoxicillin uses ultraviolet spectrophotometry.Certain density Amoxicillin solution is prepared, in 200
UV scanning is carried out in~400nm wave-length coverages, selects maximum absorption wavelength 272nm as assay wavelength.
Precision weighs a certain amount of Amoxicillin reference substance, be configured to concentration be respectively 52.02,104.04,156.06,
208.08th, 260.10, the Amoxicillin standard solution of 312.22ug/ml, with ultraviolet specrophotometer under 272nm wavelength conditions
Absorbance is measured respectively.Be abscissa with absorbance (x), Amoxicillin concentration (y) be ordinate carry out linear regression analysis, obtain
It is y=398.76x+0.3032 (R to calibration curve equation2=0.9998), the results showed that, Amoxicillin 52.02~
, measure available for Determination of amoxicillin good with absorbance linear relationship in 312.22ug/ml concentration ranges.Standard curve is such as
Shown in Fig. 1.
The detection of 2.2 Amoxicillin solution rates
It it is 25 DEG C by thermostatic control oscillator vibration temperature setting, rotating speed is set as 150r/min.Weigh 0.3g Amoxicillins original powder
Or Amoxicillin crystal, it is put into the beaker equipped with 100ml distilled water, beaker is put into thermostatic control oscillator vibration and is constantly shaken
It shakes, samples 5ml in 1min, 2min, 4min, 6min, 8min, 10min, 15min, 30min, 1h, 2h, 4h, 6h respectively, use is micro-
Distilled water constant volume in 50ml volumetric flasks is transferred to after the membrane filtration of hole, absorbance is detected under 272nm wavelength conditions, according to A Moxi
Concentration is obtained in woods standard curve, and draws solubility curve.
The preparation method of 2.3 amoxicillin slow release crystal
2.3.1 acid-base method prepares Amoxicillin crystal
1g Amoxicillins original powder is weighed in 100ml distilled water, place it in water bath with thermostatic control blender (T=25 DEG C, r
=150r/min) and Amoxicillin when pH is adjusted to 2 or so by certain density hydrochloric acid solution is slowly added dropwise thereto dissolves substantially,
It is fully precipitated at this point, certain density ammonia spirit to Amoxicillin crystal is slowly added dropwise to beaker.The crystal being precipitated is filtered, is put
Enter and dried in insulating box, it is spare.
2.3.2 change temperature method and prepare Amoxicillin crystal
It measures 100ml distilled water to add in beaker, is placed in constant temperature blender with magnetic force, adjusts to preference temperature, and keep
Constant speed stirs.It weighs 1g Amoxicillins original powder to add in beaker, being stirred continuously down dissolves Amoxicillin, is obtained by filtration with filter paper
The saturated solution of Amoxicillin, then placing the saturated solution after filtering rapidly makes Amoxicillin stand analysis in low temperature water-bath
Go out to obtain Amoxicillin crystal, the crystal being precipitated filtered with vacuum pump using circulatory water, after be put into insulating box and dry, it is spare.
Amoxicillin crystal obtained by 2.3.1 and 2.3.2 is measured to the solution rate of Amoxicillin by 2.2 methods respectively, than
Compared with the speed of the two solution rate, Fig. 2 is as a result seen.
From figure 2 it can be seen that Amoxicillin its dissolving in 6h has reached balance substantially, solubility is about 329.28
μ g/ml, and solubility of the Amoxicillin crystal prepared by acid-base method and change temperature method in 6h is respectively 275.05 μ g/
Ml and 230.03 μ g/ml.It can be seen that Amoxicillin its rate of dissolution after recrystallization significantly slows down, obtained wherein changing temperature method
The dissolution of Amoxicillin crystal it is more slow.It is current most of texts that acid-base method (i.e. isoelectric point crystallizing), which prepares Amoxicillin crystal,
The method for offering report, it be under certain temperature, corresponding stirring using certain density ammonium hydroxide as regulation system pH substance with
Certain flow rate is added in Amoxicillin hydrochloride aqueous solution.Aqueous solution changes with the addition pH of ammonium hydroxide and is gradually increasing, A Mo
The solubility in XiLin changes with pH is constantly precipitated Amoxicillin crystallization, until Amoxicillin isoelectric point.It is to utilize to change temperature method
The variation of temperature leads to the change of Amoxicillin solubility and Amoxicillin crystal is precipitated.The dissolving of drug is that drug molecule is earned
Constraint between de- molecule and be distributed to the process in solvent, the size of drug solubility and the speed of solution rate and drug are brilliant
Type is related, that is, arrangement mode of the drug molecule in space is related.The study show that change the Amoxicillin that temperature method obtains
Dissolution of crystals speed is slower, illustrates that this method obtains that Amoxicillin crystal is more stable, the space of Amoxicillin molecule
Arrangement is more regular, is conducive to the slow release of Amoxicillin and reaches long-acting.
For this purpose, the technique that this research further prepares Amoxicillin crystal to changing temperature method optimizes, to obtain more
For stable Amoxicillin crystal.
2.4 change the process optimization that temperature method prepares Amoxicillin crystal
2.4.1 the screening of different solution temperatures
It keeps other conditions constant, Amoxicillin original powder under the conditions of 60 DEG C, 70 DEG C, 80 DEG C is dissolved respectively, is then dropped
Temperature is to 15 DEG C to obtain Amoxicillin crystal.Solubility when using the solution rate in 15min and reaching balance as inspection target,
Method according to 2.3.2 investigates different solution temperatures i.e. 60 DEG C, 70 DEG C, 80 DEG C of influences to crystal is precipitated respectively, the results are shown in Table 1
And Fig. 3.
Influence of the different solution temperatures of table 1 to Crystallization Process
By table 1 and Fig. 3 it is found that respectively in 60 DEG C, 70 DEG C, 80 DEG C of dissolving Amoxicillin original powders, when being cooled to 15 DEG C,
For drug molecule due to being recrystallized, obtained crystal is more more stable than Amoxicillin active compound, and rate of dissolution is relatively slow,
The Amoxicillin crystal of wherein 70 DEG C, 60 DEG C acquisitions is more more stable than 80 DEG C.(60 DEG C, 70 DEG C, 80 DEG C) dissolving systems of different temperatures
The solubility of the Amoxicillin crystal obtained reduces about 18.7%, 20.1%, 16.3% with respect to original powder respectively.Analyzing reason may
It is that Amoxicillin molecular motion is violent at 80 DEG C, when being down to 15 DEG C, molecule has little time regularly arranged i.e. precipitation, thus it is brilliant
Body structure does not have lower temperature dissolving gained crystalchecked, is separately also possible to due to the too high destruction Amoxicillin beta-lactam of temperature
Ring makes crystal molecule misaligned.And under the conditions of 60 DEG C dissolve Amoxicillin may not enough completely, Amoxicillin concentration compared with
It is low, thus molecules align space is larger is not easy to attract each other and fails to be formed more stable crystal when recrystallizing.
2.4.2 the screening of different recrystallization temperatures
It keeps other conditions constant, selects 70 DEG C of condition dissolving Amoxicillins, difference is investigated respectively according to the method for 2.3.2
Crystal is precipitated under the conditions of 5 DEG C, 15 DEG C, 25 DEG C respectively in Amoxicillin by recrystallization temperature, with the solution rate in 15min and
Solubility when reaching balance is inspection target, investigates influence of the recrystallization temperature to precipitation crystal.It the results are shown in Table shown in 2 and Fig. 4.
Influence of the different recrystallization temperatures of table 2 to Crystallization Process
By table 2 and Fig. 4 it is found that when after Amoxicillin is dissolved for 70 DEG C, Precipitation Temperature is in 5 DEG C, 15 DEG C, 25 DEG C of three kinds of situations
Under, crystal is precipitated in early period 10min clocks that solubility is relatively small at 25 DEG C, and later stage solubility slowly increases, with respect to other two
Kind temperature dissolution rate is relatively low.The Amoxicillin Crystal solubility that three kinds of different recrystallization temperatures obtain reduces respectively about than original powder
16.1%th, 20.6%, 25.2%.Analysis is the reason is that recrystallization temperature is lower, and solubility is also low at low temperature for Amoxicillin, thus Ah
Amdinocillin is easier to be precipitated.Also faster, the molecule crystallization arrangement time shortens Amoxicillin solution cooling rate in this course,
Thus crystal arrangement is irregularly neat, causes the Amoxicillin crystal obtained under low temperature more unstable, so its solution rate is bright
It is aobvious to accelerate.But the excessively high precipitation for being also unfavorable for Amoxicillin crystal of temperature, because the high Amoxicillin solubility of recrystallization temperature is too
Greatly, crystal is precipitated with regard to seldom, such yield is also less, influences the preparation of crystal instead and increases production cost.
2.4.3 the screening of different crystallization modes
In order to slow down the precipitation time of Amoxicillin, molecules align is more regular when making Amoxicillin crystallization, so as to obtain
More stable Amoxicillin crystal, we have further investigated shadow of cooling rate when changing temperature method crystallization to crystal
It rings.Keep other conditions constant, solubility when using the solution rate in 15min and reaching balance as inspection target, according to
2.3.2 method investigates different crystallization modes respectively, i.e., is directly cooled to 15 DEG C, goes to 15 after preservation 1h in 25 DEG C of environment
DEG C, in 45 DEG C of environment keep 1h after go to 15 DEG C, to be precipitated crystal influence.It the results are shown in Table 3 and Fig. 5.
Influence of the different crystallization modes of table 3 to Crystallization Process
It can be obtained by table 3 and Fig. 5, the crystal being precipitated with different precipitation modes, in the case of 70 DEG C to 45 DEG C to 15 DEG C, crystal phase
To stabilization, solution rate is slower.Three kinds of different modes crystallizations directly cool down, 70 DEG C -25 DEG C -15 DEG C, 70 DEG C -45
DEG C -15 DEG C of solution rates reduce about 20.6%, 23.1%, 28.2% than original powder respectively, wherein 70 DEG C -45 DEG C -15 DEG C of dissolution speed
Degree is the slowest.Its reason may be the larger crystallization condition of temperature difference in Crystallization Process, for example directly cool down (70 DEG C-
15 DEG C), Amoxicillin solution cooling rate is too fast, and the molecules align time shortens, thus crystal arrangement is irregular, leads to crystal not
Stablize, so dissolution rate is also fast.The crystallization in 45 DEG C of environment, elements collection form crystal speeds and relatively delay, and form what is relatively stablized
Nucleus has time enough to attract each other between molecule, thus forms crystal stability and increase, in this course medium temperature
If lower (such as 25 DEG C), the stability of crystal is also weaker, and reason is also existing a large amount of Amoxicillins precipitations under the conditions of 25 DEG C,
It is also very fast to be equivalent to cooling rate, the change of molecular thermalmotion speed is too big, thus molecules align is just irregular, natural solution rate
It is just fast.
3. it discusses
Amoxicillin belongs to beta-lactam antibiotic, and the beta-lactam nucleus of intramolecular is unstable, easily by nucleophilic, electrophilic examination
Agent is attacked, and is easily opened under the influence of soda acid, and molecular rearrangement occurs, generates a series of catabolites.But it in peracid or crosses in alkali
Amoxicillin decomposition rate is accelerated, and is 6.2~7.2 decomposition rate minimums in PH.Amoxicillin crystal delays in phosphate simultaneously
It rushes in solution and relatively stablizes, it is most unstable in the buffer solution of borate.Temperature also has an impact the stability of beta-lactam nucleus, high
Temperature is larger to the stability influence of Amoxicillin, and fast cooling makes that the crystal form of product is tiny, and content is relatively low.
It can be obtained from vitro test interpretation of result, when with acid-base method combinations body, phosphoric acid solution dissolving original powder, high concentration
When the ammonia spirit of (75% molal volume) adjusts crystallization, crystal obtained is relatively stablized, and solution rate about reduces by 20.0%.With
When changing temperature method combinations body, 70 DEG C of dissolving original powder solution go to the crystal being precipitated at 15 DEG C in 45 DEG C of environment after crystallization 1h
Most stable, solution rate about reduces by 28.2%.This experiment by studying influence of the different crystallization conditions to Amoxicillin crystal, from
And change Amoxicillin drug crystal forms, the metastable crystal in Amoxicillin is obtained, improves the stability of drug, it is molten to slow down molecule
Solve speed.Because of Amoxicillin half-life short, the drug of normal injection agent is noted can quickly be decomposed into internal rear drug, and drug effect maintains
Time is short.If amoxicillin slow release crystal obtained is made injection administration, it is allowed to be stored in that the internal time is elongated, and drug delays
On The Drug Release, duration of efficacy is long, and for this time dependence drug in Amoxicillin, clinical meaning is larger.Simultaneously as Ah
Amdinocillin sustained release crystal injection extended durations of action can also reduce administration number of times, mitigate to animal stress, increase drug
Utilization rate reduces treatment cost, also allows for management of the farm to animal.
4. conclusion
It is that the poor drug of stability improves the important method of stability and extends drug release to obtain stable crystal
The important channel of time.Amoxicillin belongs to beta-lactam antibiotic and Time dependence antibiotic, and bactericidal effect takes
Certainly it is higher than the time of MIC in blood concentration.Time of the blood concentration higher than MIC is the key of this kind of antibacterials curative effect of decision
Index.It obtains longer antibacterial time and must assure that the sustained release of Amoxicillin in vivo, thus study Amoxicillin
Sustained release preparation is of great significance.Compared with isoelectric point crystallizing technique (acid-base method), the change temperature method that this research obtains is made
Amoxicillin crystal have better stability and slowly releasing effect, especially by change crystallization mode, Amoxicillin drops
Temperature slows, its molecule is allow to have the sufficient time to carry out, and molecule is regularly arranged, so obtained more stablize, sustained release
The better Amoxicillin crystal of effect (Fig. 6 is the Crystallization Process and crystal shape of Amoxicillin).The operation letter of this Crystallization method
Single, gained crystalchecked is conducive to further promote and apply in big production.
Although above-mentioned be described the specific embodiment of the present invention in conjunction with the embodiments, not the present invention is protected
The limitation of range, those skilled in the art should understand that, based on the technical solutions of the present invention, those skilled in the art
The various modifications or changes that can be made are not needed to make the creative labor still within protection scope of the present invention.
Claims (1)
1. a kind of preparation method of amoxicillin slow release crystal, it is characterised in that：Step is as follows：Amoxicillin original powder is taken, is added in
Temperature is in 70 DEG C of water, and the saturated solution of Amoxicillin is obtained by filtration in constant temperature stirring and dissolving, filter paper, is then put into water-bath rapidly
In pot, stand, 15 DEG C gone to after keeping 1h in 45 DEG C of environment, precipitation obtains crystal, filters the crystal of precipitation, dry to get
Amoxicillin slow release crystal.
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| CN102838620A (en) * | 2012-09-05 | 2012-12-26 | 河北科技大学 | Preparation process of amoxicillin sodium crystal |
| CN104059086A (en) * | 2014-06-19 | 2014-09-24 | 河南牧翔动物药业有限公司 | Amoxicillin crystal and preparation method thereof |
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| CN102838620A (en) * | 2012-09-05 | 2012-12-26 | 河北科技大学 | Preparation process of amoxicillin sodium crystal |
| CN104059086A (en) * | 2014-06-19 | 2014-09-24 | 河南牧翔动物药业有限公司 | Amoxicillin crystal and preparation method thereof |
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| 阿莫西林结晶工艺优化;刘慧勤;《天津大学硕士学位论文》;20041215;第5页第1段，第18页图3-3，第28页"4.3 实验步骤"部分，36-38页"4.4.5 最佳结晶操作条件的确定"部分 * |
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