CN106474169A - A kind of Celeryseed extract and its preparation and preparation method - Google Patents
A kind of Celeryseed extract and its preparation and preparation method Download PDFInfo
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Abstract
The present invention relates to a kind of Celeryseed extract and its preparation and preparation method.Celery dry seed is taken, the volume fraction with 24 times of volume amounts is 95% ethanol water refluxing extraction 12 times；Extract is collected, reduced pressure concentration obtains thick medicinal extract；Thick medicinal extract is suspended in the water of 0.5 1 times of volumes of raw material, extracts reagent is extracted 24 times, extraction merges organic phase after finishing, and obtains crude extract；The silica gel of 35 55 times of crude extract quality is weighed, and 1h is activated at 130 DEG C, is filled chromatographic column；Crude extract is taken, with the concentration loading of 0.2 0.5g/ml；With petroleum ether ethyl acetate methylene chloride gradient elution, stream part is collected, after reduced pressure concentration, obtains final product Celeryseed extract.Preparation process is simple of the present invention, extraction time are few, yield is high, and the Celeryseed extract for obtaining has preferably reduction serum uric acid.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, more particularly to a kind of Celeryseed extract and its preparation and preparation method.
Background technology
Celery seed, for the seed of samphire celery Apium graveolens L., celery seed treatment arthralgia is considered Traditional Folk folk prescription in the existing century-old history in Australia, Celeryseed extract has the multiple efficacies such as anti-trioxypurine, hypotensive, blood fat, the most notable with effect of anti-trioxypurine.Most domestic researcher is directed to root, stem, leaf extract and the celery seed essential oil of celery and carries out research and the report of correlation, but shorter mention is to the correlative study of Celeryseed extract；Chinese patent CN100569241C discloses a kind of celery seed acetic acid ethyl ester extract, and preparation method is as follows：Celery dry seed 10kg, is extracted with 15～20 times amount 75～95% (V/V) ethanol percolations or heating extraction 3～4 times with 4～5 times amount 75～95% (V/V) ethanol, heat 1～1.5 hour every time；Extract is evaporated near nothing ethanol in 55 DEG C, obtains concentrate；Jia 1 in concentrate～after the dilution of 2 times amount water is suspended, with the petroleum ether of 60～90 DEG C of boiling ranges of 1/3rd volume of dilution, extracts 2～3 times, separate petroleum ether layer and petroleum ether is reclaimed, obtain petroleum ether extract；Water layer is extracted 4 times with 1/3rd volume of ethylacetate again, is separated ethyl acetate layer and is reclaimed ethyl acetate and obtains celery seed acetic acid ethyl ester extract, and disclose the extract and is prevented and treated the application in gout medicine, anti-inflammatory drug or health food medicine for preparation.It is low, basic without many deficiencies such as process for purification, poor repeatability to there is extraction step complexity, crude drug rate in the extracting method of existing Celeryseed extract, it is difficult to industrialized production.
Content of the invention
It is a feature of the present invention that providing a kind of Celeryseed extract and preparation method thereof, the Celeryseed extract for obtaining has preferably pharmaceutical property, can effectively reduce uric acid；Preparation method process is simple, yield are high, favorable reproducibility.
For achieving the above object, concrete technical scheme of the present invention is as follows：
A kind of Celeryseed extract, the preparation method of the Celeryseed extract are as follows：
A. celery dry seed is taken, is crushed, ethanol water refluxing extraction 1-2 time that volume fraction is 95% is added, it is 2-4 times of volume of celery dry seed to add ethanol water every time, and return time is 0.5-1.5h；Collect and merge extract, be evaporated to nothing alcohol, obtain thick medicinal extract；
B. the thick medicinal extract of step a gained is suspended in the water of celery 0.5-1 times of volume of dry seed, is then extracted 2-4 time with extraction agent, it is thick medicinal extract 0.2-0.4 times volume to add extraction agent amount every time, extraction merges organic phase after finishing, dry, reduced pressure concentration, obtain Celeryseed extract；
Wherein, the extraction agent is selected from：One or more in ethyl acetate, dichloromethane, petroleum ether, n-hexane.
Preferably, the preparation method also includes following process for purification：
C. crude extract is dissolved in ethyl acetate with the concentration of 0.2-0.5g/ml, upper silica gel column chromatography；
D. gradient elution：Wash-out flow is 7-10ml/min, first elutes 8-10 column volume with petroleum ether, removes flow point；It is 7 to use volume ratio again:1 petroleum ether and dichloromethane mixed liquor elute 10-12 column volume, collect flow point；It is 9 to use volume ratio again:4:The mixed liquor of 1 petroleum ether, dichloromethane and ethyl acetate elutes 3-5 column volume, removes flow point；It is 5 to use volume ratio again:7:The mixed liquor of 3 petroleum ether, dichloromethane and ethyl acetate elutes 15-20 column volume, collects flow point, the flow point that collects is merged, reduced pressure concentration, obtains final product refined Celeryseed extract.
Celeryseed extract provided by the present invention, with extraordinary effect in terms of uric acid is reduced, is conducive to the treatment to hyperuricemia and the protection of people's kidney.
On the other hand, there is provided a kind of preparation method of Celeryseed extract, the preparation method are comprised the following steps that：
A. celery dry seed is taken, is crushed, ethanol water refluxing extraction 1-2 time that volume fraction is 95% is added, it is 2-4 times of volume of celery dry seed to add ethanol water every time, and return time is 0.5-1.5h；Collect and merge extract, be evaporated to nothing alcohol, obtain thick medicinal extract；
B. the thick medicinal extract of step a gained is suspended in the water of celery 0.5-1 times of volume of dry seed, is then extracted 2-4 time with extraction agent, it is thick medicinal extract 0.2-0.4 times volume to add extraction agent amount every time, extraction merges organic phase after finishing, dry, reduced pressure concentration, obtain crude extract；
Wherein, the extraction agent is selected from：One or more in ethyl acetate (EA), dichloromethane (DCM), petroleum ether (PE) or n-hexane (Hex)；Preferably mass ratio is 1:1-1:4 ethyl acetate and the mixed liquor of n-hexane, further preferably, the mass ratio of ethyl acetate and n-hexane is 1:2；
C. crude extract is dissolved in ethyl acetate with the concentration of 0.2-0.5g/ml, upper silica gel column chromatography；
D. gradient elution：Wash-out flow is 7-10ml/min, preferably 8ml/min；First 8-10 column volume is eluted with petroleum ether, remove flow point；It is 7 to use volume ratio again:1 petroleum ether and dichloromethane mixed liquor elute 10-12 column volume, collect flow point；It is 9 to use volume ratio again:4:The mixed liquor of 1 petroleum ether, dichloromethane and ethyl acetate elutes 3-5 column volume, removes flow point；It is 5 to use volume ratio again:7:The mixed liquor of 3 petroleum ether, dichloromethane and ethyl acetate elutes 15-20 column volume, collects flow point, the flow point that collects is merged, reduced pressure concentration, obtains final product the Celeryseed extract.
Further, in order to improve product yield, ultrasonic assistant is provided with refluxing extraction step, the ultrasonic frequency is 60-80KHz.
The preparation method of Celeryseed extract provided by the present invention, summarizes and goes out through many experiments, rational pool and contrast, and have the advantages that process is simple, extraction time is few, medicine yield is high, mild condition；Rationally, purification yield is higher, and the active component included in the Celeryseed extract of gained after the purification step improves 12-15% compared with prior art, may be adapted to industrialized production for the purifying purification step.
On the other hand, present invention also offers the soft capsule made with pharmaceutically acceptable auxiliary material of Celeryseed extract, the soft capsule includes soft capsule filler and capsule material, and the soft capsule filler includes the raw material of following weight portion：Celeryseed extract 10-25 part, diluent 20-35 part, disintegrant 3-6 part, adhesive 1-2 part.
Preferably, the diluent is 2 for ratio of weight and number:3 N- dodecyl amine xyloside and the mixture of sesame oil；The disintegrant is 1 for ratio of weight and number:2:The mixture of 2 PVPP, sldium lauryl sulfate and Hamposyl L.
It is further preferred that the capsule material is mainly prepared from by the raw material of following parts by weight, gelatin 10, CAP 1.2, pullulan 0.8, water 10, titanium dioxide 2.8, galactolipin 1.9.
Soft capsule provided by the present invention, each auxiliary material and celery are reactionless between extract, and can improve the bioavilability of Celeryseed extract in capsule, give full play to the curative effect of capsule, and uniformity of dosage units is high；Species and technological parameter through strict screening auxiliary material, have chosen above-mentioned raw materials and the capsule material to be formed is prepared, match with Celeryseed extract, solve medicine and meet wet heat-labile problem, the stability of capsule is further ensured that, so that the stability of Celeryseed extract is increased further.
In addition, the present invention also provides application of the Celeryseed extract in the medicine for reducing uric acid is prepared.
Celeryseed extract of the present invention, with extraordinary effect in terms of uric acid is reduced, is conducive to the treatment to hyperuricemia and the protection of people's kidney；In addition, the preparation method of Celeryseed extract provided by the present invention, through many experiments, rational plan as a whole and contrast is summarized and gone out, have the advantages that process is simple, extraction time is few, medicine yield is high, mild condition, be Celeryseed extract can industrialized production provide and preferably select；Celeryseed extract and auxiliary material are prepared into soft capsule by the present invention, the carrying for not only increasing patient and the convenience for using, and optimize accessory formula, are improved the bioavilability of Celeryseed extract, are strengthened the stability of Celeryseed extract and soft capsule；The storage requirement of capsule is made to become gentleer.
Description of the drawings
Impact figure of Fig. 1 return time to yield；
Impact figure of Fig. 2 column chromatography temperature to column chromatography yield.
Specific embodiment
Embodiment 1
A kind of Celeryseed extract, is prepared by following step：
A. celery dry seed is taken, is crushed, the volume fraction for adding 2 times of volumes is 95% ethanol water refluxing extraction 1.5h；Extract is collected, is evaporated to nothing alcohol, obtains thick medicinal extract；
B. the thick medicinal extract of step a gained is suspended in the water of 1 times of volume of raw material, it is 3 then to use volume ratio:The mixed liquor of 1 petroleum ether and ethyl acetate is extracted 2 times, and it is 0.2 times of volume of raw material to add extraction agent amount every time, and extraction merges organic phase after finishing, and dries, reduced pressure concentration, obtains Celeryseed extract；
Embodiment 2
A kind of Celeryseed extract, is prepared by following step：
A. celery dry seed is taken, is crushed, the ethanol water refluxing extraction 2 times that volume fraction is 95% is added, it is 2.5 times of volumes to add ethanol water every time, and return time is 0.5h, collects and merges extract, is evaporated to nothing alcohol, obtains thick medicinal extract；
B. the thick medicinal extract of step a gained is suspended in the water of 0.5 times of volume of raw material, then ethyl acetate or dichloromethane are extracted 4 times, it is 0.4 times of volume of raw material to add extraction agent amount every time, and extraction merges organic phase after finishing, and dries, reduced pressure concentration, obtains crude extract；
C. crude extract is dissolved in ethyl acetate with the concentration of 0.2g/ml, upper silica gel column chromatography；
D. gradient elution：Wash-out flow is 7ml/min, first elutes 10 column volumes with petroleum ether, removes flow point；It is 7 to use volume ratio again:1 petroleum ether and dichloromethane mixed liquor elute 12 column volumes, collect flow point；It is 9 to use volume ratio again:4:The mixed liquor of 1 petroleum ether, dichloromethane and ethyl acetate elutes 3 column volumes, removes flow point；It is 5 to use volume ratio again:7:The mixed liquor of 3 petroleum ether, dichloromethane and ethyl acetate elutes 15 column volumes, collects flow point, the flow point that collects is merged, reduced pressure concentration, obtains final product Celeryseed extract.
Embodiment 3
A kind of preparation method for preparing Celeryseed extract, the preparation method step are as follows：
A. extract：Celery dry seed is taken, is crushed, the volume fraction for adding 4 times of volumes is 95% ethanol water refluxing extraction 1h, while carrying out ultrasonic assistant；Extract is collected, is evaporated to nothing alcohol, obtains thick medicinal extract；
B. extract：The thick medicinal extract of step a gained is suspended in the water of 0.9 times of volume of raw material, it is 1 then to use mass ratio:The mixed solution of 2 ethyl acetate and n-hexane is extracted 3 times, and it is 0.3 times of volume of raw material to add extraction agent amount every time, and extraction merges organic phase after finishing, and dries, and reduced pressure concentration obtains final product the Celeryseed extract；
C. crude extract is dissolved in ethyl acetate with the concentration of 0.5g/ml, upper silica gel column chromatography；
D. gradient elution：Wash-out flow is 10ml/min, first elutes 8 column volumes with petroleum ether, removes flow point；It is 7 to use volume ratio again:1 petroleum ether and dichloromethane mixed liquor elute 10 column volumes, collect flow point；It is 9 to use volume ratio again:4:The mixed liquor of 1 petroleum ether, dichloromethane and ethyl acetate elutes 5 column volumes, removes flow point；It is 5 to use volume ratio again:7:The mixed liquor of 3 petroleum ether, dichloromethane and ethyl acetate elutes 20 column volumes, collects flow point, the flow point that collects is merged, reduced pressure concentration, obtains final product Celeryseed extract.
Embodiment 4
A kind of preparation method for preparing Celeryseed extract, the preparation method step are as follows：
A. extract：Celery dry seed is taken, is crushed, the volume fraction for adding 4 times of volumes is 95% ethanol water refluxing extraction 1h, while carrying out ultrasonic assistant；Extract is collected, is evaporated to nothing alcohol, obtains thick medicinal extract；
B. extract：The thick medicinal extract of step a gained is suspended in the water of 0.9 times of volume of raw material, it is 1 then to use mass ratio:The mixed solution of 2 ethyl acetate and n-hexane is extracted 3 times, and it is 0.3 times of volume of raw material to add extraction agent amount every time, and extraction merges organic phase after finishing, and dries, and reduced pressure concentration obtains final product the Celeryseed extract；
C. crude extract is dissolved in ethyl acetate with the concentration of 0.5g/ml, upper silica gel column chromatography；
D. gradient elution：Wash-out flow is 8ml/min, first elutes 9 column volumes with petroleum ether, removes flow point；It is 7 to use volume ratio again:1 petroleum ether and dichloromethane mixed liquor elute 11 column volumes, collect flow point；It is 9 to use volume ratio again:4:The mixed liquor of 1 petroleum ether, dichloromethane and ethyl acetate elutes 4 column volumes, removes flow point；It is 5 to use volume ratio again:7:The mixed liquor of 3 petroleum ether, dichloromethane and ethyl acetate elutes 17 column volumes, collects flow point, the flow point that collects is merged, reduced pressure concentration, obtains final product Celeryseed extract.
5 soft capsule of embodiment
Soft capsule filler：
Capsule material：
Preparation method：
1) gelatin, water, galactolipin and CAP are routinely mixed and heated and are melt into after glue, after adding titanium dioxide and pullulan to mix, rubber is pressed into after crossing colloid mill stand-by；
2), after mixing the PVPP of the Celeryseed extract prepared by embodiment 2, N- dodecyl amine xyloside, sesame oil and 2/3rds, sldium lauryl sulfate and Hamposyl L mixture, micro mist is ground into stand-by；PVP is dissolved in formation solution in the ethanol water of 75% volume fraction, micro mist is dissolved in solution and is mixed, then wet ball is made, wet ball is mixed with remaining PVPP, sldium lauryl sulfate and Hamposyl L mixture, after drying, obtain micropill；
3) by micropill and step 1) the rubber compacting of gained, obtain final product soft capsule.
6 soft capsule of embodiment
Soft capsule filler：
Capsule material：
Preparation method：It is prepared according to the preparation method described in embodiment 4.
7 soft capsule of embodiment
Soft capsule filler：
Capsule material：
Preparation method：Method as described in embodiment 4 is prepared.
1 soft capsule of comparative examples
Soft capsule filler：
Capsule material：
Preparation method：
1) gelatin, water and galactolipin are routinely mixed and heated and are melt into after glue, after adding titanium dioxide to mix, rubber is pressed into after crossing colloid mill stand-by；
2), after mixing the PVPP of the Celeryseed extract prepared by embodiment 2, N- dodecyl amine xyloside, sesame oil and 2/3rds, sldium lauryl sulfate and Hamposyl L mixture, micro mist is ground into stand-by；PVP is dissolved in formation solution in the ethanol water of 75% volume fraction, micro mist is dissolved in solution and is mixed, then wet ball is made, wet ball is mixed with remaining PVPP, sldium lauryl sulfate and Hamposyl L mixture, after drying, obtain micropill；
3) by micropill and step 1) the rubber compacting of gained, obtain final product soft capsule.
2 soft capsule of comparative examples
Soft capsule filler：
Capsule material：
Preparation method：
1) gelatin, water and glycerine are routinely mixed and heated and are melt into after glue, after adding titanium dioxide to mix, rubber is pressed into after crossing colloid mill stand-by；
2) after the Celeryseed extract prepared by embodiment 2, sorbierite and alginic acid being mixed, it is ground into micro mist, methylcellulose is dissolved in formation solution in the ethanol water of 75% volume fraction, micro mist is dissolved in solution and is mixed, then wet ball is made, wet ball and the fine element sodium of carboxymethyl are mixed, after drying, obtains micropill；
3) by micropill and step 1) the rubber compacting of gained, obtain final product soft capsule.
Test the drug efficacy study that hyperuricemia drops in 1 Celeryseed extract
1 experimental technique
(1) impact of the Celeryseed extract to Normal Mouse Serum uric acid：ICR mouse 72, SPF level, male and female half and half, 18.2～22.9g of body weight, 6 groups are randomly divided into by sex, body weight, celery seed acetic acid ethyl ester extract respectively disclosed in blank control group, allopurinol tablet group (39mg/kg), Chinese patent CN 100569241 as positive controls (3.3g celery seed/kg), the basic, normal, high dosage group of Celeryseed extract (3.3,9.9,29.7g celery seed/kg), per 12 animals of group.Each group mouse is given the liquid of corresponding dosage by 20mL/kg gavage, and blank control group gavage gives equal-volume peanut oil, 1 times/day, continuous 14 days.Before last dose, water 12h is can't help in fasting, 1h after last dose, and each group mouse orbit veniplex is taken a blood sample, and detects serum uric acid level.
(2) impact of the Celeryseed extract to Oxonic Acid sylvite induced mice hyperuricemia model：ICR mouse 70, SPF level, male, 24.1～27.9g of body weight, 7 groups are randomly divided into by body weight, used as positive controls (9.9g/kg), the basic, normal, high dosage group of Celeryseed extract (3.3,9.9,29.7g/kg), per 10 animals of group for celery seed acetic acid ethyl ester extract respectively disclosed in Normal group, model control group, allopurinol tablet group (39mg/kg), Chinese patent CN100569241.Each group mouse is given the liquid of corresponding dosage by 20mL/kg gavage, and Normal group gavage gives equal-volume distilled water, and model control group gavage gives equal-volume peanut oil, 1 times/day, continuous 7 days.Before last dose, water 12h is can't help in fasting, and 1h before administration, in addition to Normal group, remaining each group mouse peritoneal injection liquid oxygen piperazine acid potassium salt 300mg/kg, each group mouse before modeling and after last dose 1h, take a blood sample by orbital venous plexus, detection serum uric acid level, the results are shown in Table 1.
(3) impact of the Celeryseed extract to rat hyperuricemia model caused by adenine and ethambutol：SD rat 70, SPF level, male, 198.4～228.4g of body weight, the celery seed acetic acid ethyl ester extract disclosed in Normal group, model control group, allopurinol tablet group (27mg/kg), Chinese patent CN100569241 is randomly divided into as positive controls (5.1g/kg) by body weight, the basic, normal, high dosage group of Celeryseed extract (1.7,5.1,15.3g/kg), per 10 animals of group.Each group rat is given the liquid of corresponding dosage by 10mL/kg gavage, and Normal group gavage gives equal-volume distilled water, and model control group gavage gives equal-volume peanut oil, 1 times/day, continuous 17 days.In addition to Normal group, remaining each group rat all starts gavage adenine (300mg/kg) and ethambutol (250mg/kg) in the 10th day morning of administration, rat hyperuricemia model is replicated, and corresponding liquid is given by 10mL/kg gavage afternoon.Before last dose, water 12h is can't help in fasting, 1h after last dose, and each group rat orbital venous plexus are taken a blood sample, and detects serum uric acid level, the results are shown in Table 2.
2 experimental results
Impact of 1 Celeryseed extract of table to Oxonic Acid sylvite induced mice hyperuricemia model
Note：P compared with positive controlsa＜ 0.05, Pb＜ 0.01, P compared with allopurinol tablet groupc＜ 0.05.
Impact of 2 Celeryseed extract of table to rat hyperuricemia model caused by adenine and ethambutol
Note：P compared with positive controlsa＜ 0.05, Pb＜ 0.01, P compared with allopurinol tablet groupc＜ 0.05.
(1) impact of the Celeryseed extract to Normal Mouse Serum uric acid：The continuous 14 days gavages of mouse give the Celeryseed extract (3.3,9.9,29.7g/kg) of various dose, and wherein low dosage Celeryseed extract can just significantly reduce Normal Mouse Serum uric acid level.
(2) impact of the Celeryseed extract to Oxonic Acid sylvite induced mice hyperuricemia model：Successive administration 7 days, mouse replicate hyperuricemia model using lumbar injection Oteracil Potassium, and after modeling, mice serum UA is significantly raised；The basic, normal, high dosage of Celeryseed extract (3.3,9.9,29.7g/kg) can all significantly reduce serum UA level after mouse modeling, and basic, normal, high dosage can all be substantially reduced mice serum UA elevated-levels after modeling after modeling, low dose group is with otherness compared with positive controls,, with high dose group with the significance difference opposite sex compared with positive controls, high dose group effect compared with existing allopurinol tablet is more excellent for middle dose group.
(3) impact of the Celeryseed extract to rat hyperuricemia model caused by adenine and ethambutol：Rat gives adenine using continuous 7 days gavages and adds ethambutol to replicate hyperuricemia model, after modeling, rat blood serum UA is significantly raised, the basic, normal, high dosage of Celeryseed extract (1.7,5.1,15.3g/kg) can all significantly reduce rat model serum urea nitrogen BUN level, serum creatine CRE level and serum UA level, with significant difference compared with positive controls.
From above-mentioned result of the test, Celeryseed extract has notable prevention and therapeutic action to hyperuricemia, and has certain protective effect to kidney.In experimentation, mouse administration is all nothing death, and other organs are without exception, and toxicity is more micro-.
Test the optimum extraction condition experimental study of 2 Celeryseed extracts
Take 20kg celery seed, extracted using the method described in embodiment 3, in the case of ensureing that other experiment conditions are constant, changed the single factor test such as extracts reagent, return time or column chromatography temperature respectively, the yield change that extracts is investigated, experimental result is shown in Table 3, Fig. 1 and Fig. 2.
Different impacts of the extracts reagent to yield of table 3
From above-mentioned experimental result, EA/Hex is optimal extracts reagent, and, up to 9.2%, used as extracts reagent, amount of crude product is higher, but impurity is more, and gross production rate is slightly worse as extracts reagent with respect to EA/Hex after purification for pure EA for crude drug yield.
The impact of 4 ethyl acetate of table and n-hexane different proportion to yield
From above-mentioned experimental result, with the minimizing of the content of n-hexane, yield is gradually increased, when n-hexane/ethyl acetate=1:When 2, yield reaches highest, and n-hexane content increases further, and yield declines.
As shown in Figure 1, backflow 0.5h yield is relatively low, and the prolongation after the 1h that flows back over time, yield are not further added by, it is contemplated that cost-effective principle, and it is optimal return time that backflow 1h may be selected；As shown in Figure 2, in extracting method of the present invention, cross post purification yield higher, it is ensured that in the case that other conditions are constant, individually change column temperature, investigate the rising with temperature, cross post yield increase, during to 40 DEG C be optimal, temperature raise further after to after 50-55 DEG C, yield declines, and silica gel increases to the adsorptivity of product.
Comprehensive, the preparation method of Celeryseed extract of the present invention, the advantages of extraction time is few, extraction conditions are gentle, method is simple and purification efficiency is high, and substantially increases the crude drug extraction efficiency of natural drug, 9.3% is reached as high as, is that industrialized production provides effective way.
Test 3 soft capsule stability tests research
3.1 accelerated test
Soft capsule described in Example 5, embodiment 7, comparative examples 1 and comparative examples 2, at 40 DEG C ± 2 DEG C of constant temperature, relative humidity is for placing 6 months under the conditions of 75% ± 5% constant humidity, 1 month during testing, 2 months, 3 months, 6 the end of month separately sampled once, by the regulation in Chinese Pharmacopoeia, the proterties, the labelled amount (%) containing apiolin of detection capsule, accelerated test the results are shown in Table 5；
The sample of 5 present invention of table and the accelerated test result of reference substance
The soft capsule of the present invention as can be seen from the table, embodiment 7 under hot and humid environment, after placing 6 months, not rupture and slight crack, and the labelled amount containing apiolin does not occur significantly change；Embodiment 7 is different from the weight proportion for differing only in capsule material raw material of embodiment 5, and the stability of embodiment 5 is slightly worse, and the labelled amount containing apiolin declines 6% or so；From the difference of comparative examples, embodiment 7 is that capsule material raw material is different, after placing 2-3 month under the Celeryseed extract soft capsule hot and humid environment described in comparative examples, rough surface, and the labelled amount containing apiolin is remarkably decreased；It follows that the soft capsule stability of the present invention is significantly improved.
3.2 long term test
Soft capsule described in Example 5, embodiment 7, comparative examples 1 and comparative examples 2, at 25 DEG C ± 2 DEG C of temperature, relative humidity be 60% ± 10% under conditions of place 24 months, sampled once per 3 months, sample respectively at 0 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, the proterties, the labelled amount (%) containing apiolin of detection capsule, long-term test results are shown in Table 6；
The sample of 6 present invention of table and the long-term test results of reference substance
The soft capsule of the present invention, long-time placement as can be seen from the table, the proterties of the soft capsule meets standard, the amount containing apiolin not to be occurred significantly to change；And after comparative examples soft capsule long-time places 9-12 month, there is spot in the surface of the capsule, and fracture phenomena occurs；And the amount containing red apiolin is remarkably decreased；Show that the soft capsule of the present invention, compared with control soft capsule, is placed stable in properties for a long time.
Claims (10)
1. a kind of Celeryseed extract, it is characterised in that the preparation method of the Celeryseed extract is such as
Under：
A. celery dry seed is taken, is crushed, add the ethanol water backflow that volume fraction is 95%
Extract 1-2 time, it is 2-4 times of volume of celery dry seed to add ethanol water every time,
Return time is 0.5-1.5h；Collect and merge extract, be evaporated to nothing alcohol, obtain thick
Medicinal extract；
B. the thick medicinal extract of step a gained is suspended in the water of celery 0.5-1 times of volume of dry seed,
Then extracted 2-4 time with extraction agent, it is thick medicinal extract 0.2-0.4 to add extraction agent amount every time
Times volume, extraction merge organic phase after finishing, and dry, reduced pressure concentration, obtain celery seed and carry
Take thing；
Wherein, the extraction agent is selected from：Ethyl acetate, dichloromethane, petroleum ether, n-hexane
In one or more.
2. Celeryseed extract as claimed in claim 1, it is characterised in that the preparation method is also
Including following method of purification：
C. the Celeryseed extract of step b gained is dissolved in acetic acid second with the concentration of 0.2-0.5g/ml
In ester, upper silica gel column chromatography；
D. gradient elution：Wash-out flow is 7-10ml/min, first elutes 8-10 post with petroleum ether
Volume, removes flow point；It is 7 to use volume ratio again:1 petroleum ether and dichloromethane mixed liquor are washed
De- 10-12 column volume, collects flow point；It is 9 to use volume ratio again:4:1 petroleum ether, two
The mixed liquor of chloromethanes and ethyl acetate elutes 3-5 column volume, removes flow point；Body is used again
Product is than being 5:7:The mixed liquor wash-out 15-20 of 3 petroleum ether, dichloromethane and ethyl acetate
Individual column volume, collects flow point, the flow point that collects is merged, reduced pressure concentration, obtains final product refined celery
Vegetable seed extract.
3. a kind of preparation method of Celeryseed extract as claimed in claim 1, it is characterised in that
The preparation method step is as follows：
A. celery dry seed is taken, is crushed, add the ethanol water backflow that volume fraction is 95%
Extract 1-2 time, it is 2-4 times of volume of celery dry seed to add ethanol water every time,
Return time is 0.5-1.5h；Collect and merge extract, be evaporated to nothing alcohol, obtain thick
Medicinal extract；
B. the thick medicinal extract of step a gained is suspended in the water of celery 0.5-1 times of volume of dry seed,
Then extracted 2-4 time with extraction agent, it is thick medicinal extract 0.2-0.4 to add extraction agent amount every time
Times volume, extraction merge organic phase after finishing, and dry, reduced pressure concentration, obtain crude extract；
Wherein, the extraction agent is selected from：Ethyl acetate, dichloromethane, petroleum ether, n-hexane
In one or more；
C. crude extract is dissolved in ethyl acetate with the concentration of 0.2-0.5g/ml, upper silica gel column chromatography；
D. gradient elution：Wash-out flow is 7-10ml/min, first elutes 8-10 post with petroleum ether
Volume, removes flow point；It is 7 to use volume ratio again:1 petroleum ether and dichloromethane mixed liquor are washed
De- 10-12 column volume, collects flow point；It is 9 to use volume ratio again:4:1 petroleum ether, two
The mixed liquor of chloromethanes and ethyl acetate elutes 3-5 column volume, removes flow point；Body is used again
Product is than being 5:7:The mixed liquor wash-out 15-20 of 3 petroleum ether, dichloromethane and ethyl acetate
Individual column volume, collects flow point, the flow point that collects is merged, reduced pressure concentration, obtains final product the celery
Vegetable seed extract.
4. the preparation method described in claim 3, it is characterised in that the extraction agent is mass ratio
For 1:2-1:4 ethyl acetate and the mixed liquor of n-hexane.
5. preparation method as claimed in claim 3, it is characterised in that the wash-out flow is 8
ml/min.
6. the preparation method as described in claim 2-5 is arbitrary, it is characterised in that refluxing extraction step
Ultrasonic assistant is provided with, the ultrasonic frequency is 60-80KHz.
7. Celeryseed extract as claimed in claim 1 is soft with what pharmaceutically acceptable auxiliary material was made
Capsule, it is characterised in that the soft capsule includes soft capsule filler and capsule material, institute
Stating soft capsule filler includes the raw material of following weight portion：Celeryseed extract 10-25 part,
Diluent 20-35 part, disintegrant 3-6 part, adhesive 1-2 part.
8. soft capsule as claimed in claim 7, it is characterised in that the diluent is weight portion
Number is than being 2:3 N- dodecyl amine xyloside and the mixture of sesame oil；The disintegrant is attached most importance to
Amount portion rate is 1:2:2 PVPP, sldium lauryl sulfate and Hamposyl L
Mixture.
9. soft capsule as claimed in claim 8, it is characterised in that the capsule material is mainly by as follows
The raw material of parts by weight is prepared from, and gelatin 10, CAP 1.2, sprouts
Short stalk spore sugar 0.8, water 10, titanium dioxide 2.8, galactolipin 1.9.
10. Celeryseed extract as claimed in claim 1 is in the medicine for reducing uric acid is prepared
Application.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107997184A (en) * | 2017-12-13 | 2018-05-08 | 国药肽谷有限公司 | The preparation method of one seed oyster oligopeptide product |
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| CN110585252A (en) * | 2019-08-27 | 2019-12-20 | 杨凌萃健生物工程技术有限公司 | Celery seed extract and preparation method thereof |
| CN112716989A (en) * | 2020-10-26 | 2021-04-30 | 山东大学 | Celery seed extract and preparation method and application thereof |
| WO2022089450A1 (en) * | 2020-10-26 | 2022-05-05 | 山东大学 | Celery seed extract, and preparation method therefor and use thereof |
| CN113893269A (en) * | 2021-10-05 | 2022-01-07 | 浙江省农业科学院 | Preparation and purification method of celery seed extracting solution with blood pressure lowering effect |
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