CN102091161B - Total lignan extract of stalkedfruit pricklyash bark for treating arthritis - Google Patents
Total lignan extract of stalkedfruit pricklyash bark for treating arthritis Download PDFInfo
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- CN102091161B CN102091161B CN2011100308131A CN201110030813A CN102091161B CN 102091161 B CN102091161 B CN 102091161B CN 2011100308131 A CN2011100308131 A CN 2011100308131A CN 201110030813 A CN201110030813 A CN 201110030813A CN 102091161 B CN102091161 B CN 102091161B
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- cortex zanthoxyli
- zanthoxyli podocarpi
- total lignans
- podocarpi
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Abstract
The invention discloses a total lignan extract of stalkedfruit pricklyash bark, which is characterized in that the content of total lignan is above 30%. The total lignan extract of stalkedfruit pricklyash bark is extracted and refined from the traditional Chinese medicine stalkedfruit pricklyash bark. Proven by pharmacodynamical and toxicological tests, the total lignan extract of stalkedfruit pricklyash bark can obviously improve the collagen induced arthritis of rats, and simultaneously has better analgesis and anti-inflammation effects with small toxic side effects. The invention also discloses a medical application of the total lignan extract of stalkedfruit pricklyash bark.
Description
Affiliated technical field
The invention belongs to the pharmaceutical preparations technology field, relate to the effective site of extracting in a kind of therefrom medicine Cortex Zanthoxyli podocarpi, the invention still further relates to the method for preparing and the medical usage thereof of this effective site.
Background technology
Arthritis is a kind of common chronic disease, and modal is two kinds of rheumatic arthritis and rheumatoid arthritis, and the present arthritic of China estimates at more than 100,000,000, and number is also in continuous increase.According to another statistics, China more than 50 years old among the crowd half suffer from rheumatic arthritis; 90% women and 80% male suffer from rheumatic arthritis among the over-65s crowd.Rheumatoid arthritis is 0.5% in the prevalence of China.
(rheumatoid arthritis RA) is the struvite autoimmune disease of a kind of multisystem to rheumatoid arthritis.And autoimmune disease is the morbid state that self component generation immunoreation is caused because of body immune system, has outbreak and chronic animal migration repeatedly, therefore, needs long-term treatment and monitoring.Still there is not the specific treatment medicine at present; It is normal clinically that what adopt is the inflammation that causes of control autoimmune disease and the medicine that suppresses immune response; Like prednisone, methotrexate, cyclophosphamide, azathioprine, ciclosporin A etc., still, they are in inflammatory reaction and tissue injury that the inhibition immune response causes; Also suppress immune anti-infection ability, will produce a series of untoward reaction therefrom.
Cortex Zanthoxyli podocarpi is the very famous local medication in Hunan Province, records in " Hunan Province's Chinese crude drug standard " (version in 1993), is dry dried bark and the branch skin of rutaceae handle fruit Pericarpium Zanthoxyli Zanthokylum podocarpum Hemsl..Have expelling wind and cold, detoxifcation analgesic effect, be used for bones and muscles pain due to rheumatism, traumatic injury, toothache, venom.
Cortex Zanthoxyli podocarpi all using, is mainly used in wind-damp dispelling in the various places in Hunan Province, especially treats rheumatic arthritis with rheumatoid arthritis is respond well, has wide, the resourceful characteristics of distribution.
Through retrieval, Shang Weijian is about the arthritic bibliographical information of Cortex Zanthoxyli podocarpi total lignans extract for treating.
Summary of the invention
The purpose of this invention is to provide a kind of high-efficiency low-toxicity Cortex Zanthoxyli podocarpi total lignans extract.
Another object of the present invention provides above-mentioned Cortex Zanthoxyli podocarpi total lignans preparation method of extract.
A further object of the invention provide above-mentioned Cortex Zanthoxyli podocarpi total lignans extract medical usage.
The technical solution adopted for the present invention to solve the technical problems is:
A kind of Cortex Zanthoxyli podocarpi total lignans extract, it is the lignanoid that therefrom extracts in the medicine Cortex Zanthoxyli podocarpi, wherein total lignans content is more than 30%;
And this Cortex Zanthoxyli podocarpi total lignans extract is through any one therefrom extracts in the medicine Cortex Zanthoxyli podocarpi and makes in following three kinds of methods:
The method I comprises the steps:
(1) preparation Cortex Zanthoxyli podocarpi crude extract: get the Cortex Zanthoxyli podocarpi medical material, add 60%～95% ethanol and extract, filter, extracting solution, this extracting solution is concentrated, promptly get the Cortex Zanthoxyli podocarpi crude extract.
(2) the Cortex Zanthoxyli podocarpi crude extract that (1) step is made adds the suitable quantity of water suspendible, uses defat with petroleum ether earlier, adds ethyl acetate extraction again, the reclaim under reduced pressure ethyl acetate, and drying promptly gets Cortex Zanthoxyli podocarpi total lignans extract.
The method II comprises the steps:
(1) preparation Cortex Zanthoxyli podocarpi crude extract: get the Cortex Zanthoxyli podocarpi medical material, add 60%～95% ethanol and extract, filter, extracting solution, this extracting solution is concentrated, promptly get the Cortex Zanthoxyli podocarpi crude extract.
(2) the Cortex Zanthoxyli podocarpi crude extract that (1) step is made adds an amount of anhydrous alcohol solution, mixes thoroughly with the macroporous adsorbent resin with weight, adds the water of dehydrated alcohol amount more than 10 times; Stir, be added on handled on the low polar macroporous adsorbent resin column, earlier with 30% low-concentration ethanol eluting; With this low-concentration ethanol eluent discard need not, the ethanol elution of reuse 40%～95% is collected eluent; Reclaim ethanol, drying promptly gets Cortex Zanthoxyli podocarpi total lignans extract.
The method III comprises the steps:
(1) preparation Cortex Zanthoxyli podocarpi crude extract: get the Cortex Zanthoxyli podocarpi medical material, be ground into fine powder, put into the carbon dioxide supercritical fluid extraction jar, under certain condition, extracted 2～10 hours, from knockout drum tell the Cortex Zanthoxyli podocarpi crude extract.
(2) the Cortex Zanthoxyli podocarpi crude extract that makes of (1) step is added an amount of anhydrous alcohol solution, be added on the MCI Gel resin column of using water treatment, earlier with 10%～40% ethanol elution; This low-concentration ethanol eluent is discarded need not; The ethanol elution of reuse 50%～95% is collected eluent, reclaims ethanol; Drying promptly gets Cortex Zanthoxyli podocarpi total lignans extract.
If necessary, refining Cortex Zanthoxyli podocarpi total lignans extract, available ethyl acetate is further purified processing, to make the high Cortex Zanthoxyli podocarpi total lignans extract of total lignans content.
In the Cortex Zanthoxyli podocarpi total lignans extract of the present invention, total lignans content is preferably better more than 60%.
In the Cortex Zanthoxyli podocarpi total lignans extract of the present invention, more preferably better more than 90%, 100% is best for total lignans content.
The medical usage of above-mentioned Cortex Zanthoxyli podocarpi total lignans extract is: treatment of arthritis.The above-mentioned Cortex Zanthoxyli podocarpi total lignans extract that contains effective dose in the medicine of said treatment of arthritis.
Described pharmaceutical dosage form can be any existing pharmaceutical dosage forms such as powder pin, drop pill, tablet, slow releasing tablet, hard capsule, soft capsule, granule.
Compared with prior art, the invention has the beneficial effects as follows: prove that through pharmacodynamics and toxicology test this Cortex Zanthoxyli podocarpi total lignans extract can significantly improve the collagen-induced property of rat arthritis, have anti-inflammatory and analgesic effect preferably simultaneously, and toxic and side effects is little.Not only effective ingredient (lignanoids) is clear and definite, and the content of total lignans is high more, and impurity is few more, and its effect is good more, and this can reduce dose, also can reduce toxic and side effects to a certain extent, more helps guaranteeing the safety and the effectiveness of medicine.Simultaneously, this Cortex Zanthoxyli podocarpi total lignans extract is different from the onset of chemicals single component, but the effect of " multicomponent, multipath, many target spots ", and toxic and side effects is little.
The present invention follows the trail of the effective site of Cortex Zanthoxyli podocarpi, is that medicine makes an experiment with the Cortex Zanthoxyli podocarpi total lignans extract of different content, and the result has confirmed the arthritic effect of Cortex Zanthoxyli podocarpi total lignans extract for treating.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is made further detailed description.
But should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.
Embodiment 1
Get Cortex Zanthoxyli podocarpi medical material 100kg, add 70% alcohol reflux 2 times, each 1 hour, add the ethanol of 800kg70% the 1st time; Add the ethanol of 600kg70% the 2nd time, filter, merge extractive liquid,, extracting solution reclaims ethanol and is condensed into thick paste; Add an amount of anhydrous alcohol solution, mix thoroughly, add the water of dehydrated alcohol amount more than 10 times with macroporous adsorbent resin with weight; Stir, be added on and handled on the macroporous adsorptive resins, elder generation is eluted to colourless with 30% low-concentration ethanol; This 30% ethanol elution is discarded, and the ethanol elution of reuse 90% is collected this 90% ethanol elution to colourless; Reclaim ethanol and be condensed into the thick paste of relative density 1.25, vacuum drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 30%.
Embodiment 2
Get Cortex Zanthoxyli podocarpi medical material 100kg, add 90% alcohol reflux 2 times, each 1.5 hours, add the ethanol of 700kg90% the 1st time; Add the ethanol of 600kg90% the 2nd time, filter, merge extractive liquid,, extracting solution reclaims ethanol and is condensed into thick paste; Add an amount of anhydrous alcohol solution, mix thoroughly, add the water of dehydrated alcohol amount more than 10 times with macroporous adsorbent resin with weight; Stir, be added on and handled on the macroporous adsorptive resins, elder generation is eluted to colourless with 30% low-concentration ethanol; This 30% ethanol elution is discarded, and the ethanol elution of reuse 80% is collected this 80% ethanol elution to colourless; Reclaim ethanol and be condensed into the clear paste of relative density 1.10, spray drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 60%.
Embodiment 3
Get Cortex Zanthoxyli podocarpi medical material 100kg, add 80% alcohol reflux 2 times, each 2 hours, add the ethanol of 800kg80% the 1st time; Add the ethanol of 600kg80% the 2nd time, filter, merge extractive liquid,, extracting solution reclaims ethanol and is condensed into thick paste; Add an amount of anhydrous alcohol solution, mix thoroughly, add the water of dehydrated alcohol amount more than 10 times, stir with macroporous adsorbent resin with weight; Be added on and handled on the macroporous adsorptive resins, first low-concentration ethanol with 30% is eluted to colourless, and this 30% ethanol elution is discarded, and the ethanol elution of reuse 90% is to colourless; Collect this 90% ethanol elution, reclaim ethanol, vacuum drying promptly gets dry extract.This dry extract is added 5 times of water gagings make suspendible, with ethyl acetate extraction 4 times, the consumption of each ethyl acetate equates with sample volume; The combined ethyl acetate layer; After reclaiming ethyl acetate, vacuum drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 90%.
Embodiment 4
Get Cortex Zanthoxyli podocarpi medical material 100kg, add 90% alcohol reflux 3 times, each 1 hour, add the ethanol of 700kg90% the 1st time; 2nd, add the ethanol of 600kg90% respectively 3 times, filter, merge extractive liquid,, extracting solution reclaims ethanol and is condensed into thick paste; Add an amount of anhydrous alcohol solution, mix thoroughly, add the water of dehydrated alcohol amount more than 10 times with macroporous adsorbent resin with weight; Stir, be added on and handled on the macroporous adsorptive resins, elder generation is eluted to colourless with 30% low-concentration ethanol; This 30% ethanol elution is discarded, and the ethanol elution of reuse 75% is collected this 75% ethanol elution to colourless; Reclaim ethanol, vacuum drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 60%.This Cortex Zanthoxyli podocarpi total lignans extract is added 5 times of water gagings make suspendible, with ethyl acetate extraction 4 times, the consumption of each ethyl acetate equates with sample volume; The combined ethyl acetate layer after the recovery ethyl acetate, adds 5 times of water gagings again and makes suspendible; Reuse ethyl acetate extraction 3 times, the consumption of each ethyl acetate equates the combined ethyl acetate layer with sample volume; Reclaim ethyl acetate, lyophilization promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 100%.
Embodiment 5
Get Cortex Zanthoxyli podocarpi medical material 20kg, be ground into fine powder, cross 80 mesh sieves, put into the carbon dioxide supercritical fluid extraction jar; Carbon dioxide flow is 12L/min, when temperature reaches 60 ℃, picks up counting when pressure is crossed 30Mpa, extracted 6 hours, from knockout drum tell the Cortex Zanthoxyli podocarpi crude extract; This crude extract is added an amount of anhydrous alcohol solution, be added on the MCI Gel resin column of using water treatment, earlier with 30% ethanol elution; With this low-concentration ethanol eluent discard need not, the ethanol elution of reuse 80% is collected eluent; Reclaim ethanol, vacuum drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 50%.
Embodiment 6
Get Cortex Zanthoxyli podocarpi medical material 20kg, be ground into fine powder, cross 100 mesh sieves, put into the carbon dioxide supercritical fluid extraction jar; Carbon dioxide flow is 15L/min, when temperature reaches 60 ℃, picks up counting when pressure is crossed 30Mpa, extracted 8 hours, from knockout drum tell the Cortex Zanthoxyli podocarpi crude extract; This crude extract is added an amount of anhydrous alcohol solution, be added on the MCI Gel resin column of using water treatment, earlier with 40% ethanol elution; With this low-concentration ethanol eluent discard need not, the ethanol elution of reuse 90% is collected eluent; Reclaim ethanol, vacuum drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 65%.
Embodiment 7
Get Cortex Zanthoxyli podocarpi medical material 100kg, add 80% alcohol reflux 2 times, each 1 hour, add the ethanol of 700kg80% the 1st time; Add the ethanol of 600kg80% the 2nd time, filter, merge extractive liquid,, extracting solution reclaims ethanol and is condensed into thick paste; Add the suitable quantity of water suspendible, add defat with petroleum ether after, add ethyl acetate extraction again 6 times, 6 times of volumes of each material; The reclaim under reduced pressure ethyl acetate, vacuum drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 50%.
Embodiment 8
Get Cortex Zanthoxyli podocarpi medical material 100kg, add 95% alcohol reflux 2 times, each 1.5 hours, add the ethanol of 600kg95% the 1st time; Add the ethanol of 600kg95% the 2nd time, filter, merge extractive liquid,, extracting solution reclaims ethanol and is condensed into thick paste; Add the suitable quantity of water suspendible, add defat with petroleum ether after, add ethyl acetate extraction again 4 times, 6 times of volumes of each material; The reclaim under reduced pressure ethyl acetate, vacuum drying promptly obtains containing the Cortex Zanthoxyli podocarpi total lignans extract of total lignans 65%.
Embodiment 9
Get described Cortex Zanthoxyli podocarpi total lignans extract 300g, dextrin 700g, mix homogeneously adopts existing hard capsule preparation technology, promptly makes the medicine of the hard capsule dosage form that contains Cortex Zanthoxyli podocarpi total lignans extract.
Embodiment 10
Get described Cortex Zanthoxyli podocarpi total lignans extract 3kg, vegetable oil 7kg, mix homogeneously is made capsule casing material with gelatin, adopts existing soft capsule preparation technology, promptly makes the medicine of the soft capsule dosage form that contains Cortex Zanthoxyli podocarpi total lignans extract.
Embodiment 11
Get described Cortex Zanthoxyli podocarpi total lignans extract 300g, Polyethylene Glycol
6000700g, mix homogeneously adopts existing drop pill preparation technology, promptly makes the medicine of the drops that contains Cortex Zanthoxyli podocarpi total lignans extract.
Embodiment 12
Get described Cortex Zanthoxyli podocarpi total lignans extract 300g, soluble starch 500g, sucrose 200g, mix homogeneously is granulated, and sieves, and drying promptly makes the medicine of the granule dosage form that contains Cortex Zanthoxyli podocarpi total lignans extract.Maybe, promptly make the medicine of the tablet that contains Cortex Zanthoxyli podocarpi total lignans extract with the further tabletting of the granule that makes.
Embodiment 13
Get described Cortex Zanthoxyli podocarpi total lignans extract 420g, hypromellose 60g, carboxymethyl starch sodium 8g; Microcrystalline Cellulose 10g, mix homogeneously adds magnesium stearate 1g again as lubricant; Tabletting promptly makes the medicine of the slow releasing tablet dosage form that contains Cortex Zanthoxyli podocarpi total lignans extract.
Embodiment 14
Get described Cortex Zanthoxyli podocarpi total lignans extract 300g, be dissolved in the 10000ml water for injection and (add a little ethanol and make dissolving), adopt the injectable powder freeze-drying preparation technology, promptly make the medicine of the injectable powder type that contains Cortex Zanthoxyli podocarpi total lignans extract.
For investigating the effectiveness and the safety of Cortex Zanthoxyli podocarpi total lignans extract of the present invention; The inventor is a trial drug with the described extract of above-mentioned part embodiment respectively; Carried out pharmacodynamics test and toxicology test and investigated, test method and result etc. distinguish as follows:
Pharmacodynamics test:
Test one, antiinflammatory test
Animal: the ICR mice, the cleaning level, in Mus 8～9 weeks of age, body weight 18～22g is provided by Hunan University of Traditional Chinese Medicine's animal center; The SD rat, the cleaning level, body weight 180～220g is provided by Hunan University of Traditional Chinese Medicine's animal center.
Medicine: Cortex Zanthoxyli podocarpi total lignans extract (what contain total lignans 30% makes, contains being made by embodiment 3 of total lignans 90% by what embodiment 1 made, contains total lignans 60% by embodiment 2) is mixed with solution with normal saline during experiment; Dexamethasone sodium phosphate injection, specification: a 1g/ml, produced lot number: 68070013 by Xinan Pharmaceutical Co., Ltd.; Xylene (analytical pure), specification: 500ml/ bottle, Chengdu section dragonization reagent plant produced, lot number: 20091128; Carrageenin is produced lot number: 17H1148 by Sigma company.
1, on Carrageenan causes the influence of rat paw edema
Test method: 50 of SD rats, be divided into 5 groups at random by body weight, 10 every group, be respectively: 1. blank group: distilled water 1ml/100g body weight is irritated stomach; 2.～4. Cortex Zanthoxyli podocarpi total lignans extract contains total lignans 30%, contains total lignans 60%, contains 90% 3 group of total lignans: irritate stomach 200mg/kg respectively; 5. Dexamethasone group: 5mg/kg, lumbar injection, administration volume are the 0.5ml/100g body weight.Except that Dexamethasone group test intraperitoneal injection on the same day, all the other respectively organize gastric infusion 1 time every day, continuous 7 days.Test was respectively organized rat and measure right back sufficient normal foot volume 2 times the same day; Average as causing scorching front foot volume; Administration then; Administration after 30 minutes the subcutaneous injection 1% carrageenin 0.1ml of rat toes portion cause inflammation, cause scorching back rat and measured sufficient volume in 30,60,180,360 minutes, calculate paw swelling.
Result: see table 1.
Table 1 on Carrageenan causes the influence
of rat paw edema
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01
2, xylol causes the influence of mice auricle swelling
Test method: get 60 of mices, be divided into 5 groups, 12 every group, be respectively: 1. blank group: distilled water 0.2ml/10g body weight by the body weight stratified random; 2.～4. Cortex Zanthoxyli podocarpi total lignans extract contains total lignans 30%, contains total lignans 60%, contains 90% 3 group of total lignans: irritate stomach 200mg/kg respectively; 5. Dexamethasone group: 5mg/kg, lumbar injection.The continuous gastric infusion of each treated animal 3 days, 1 time/day.Behind the last administration 30min, get xylene 20 μ l and evenly coat the mouse right ear two sides and cause inflammation.Put to death mice after causing scorching 30min, cut left and right sides auricle, with the card punch of diameter 9mm respectively about the same area of two auricles lay circular auricle, precision takes by weighing two auricle weight.With about the difference (mg) of two auricle weight as inflammation swelling degree.
Result: see table 2.
Inflammation suppression ratio (%)=[(matched group swelling degree-administration group swelling degree)/matched group swelling degree] * 100%
The influence of table 2 xylol induced mice ear swelling
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01.
The result shows: Cortex Zanthoxyli podocarpi total lignans extract has tangible antiinflammatory action, and is dose-effect relationship, and along with increasing of total lignans content wherein, its effect strengthens.
Test two, analgesic test
Animal: the ICR mice, the cleaning level, in Mus 8～9 weeks of age, body weight 18～22g is provided by Hunan University of Traditional Chinese Medicine's animal center.
Medicine: Cortex Zanthoxyli podocarpi total lignans extract (what contain total lignans 30% makes, contains being made by embodiment 3 of total lignans 90% by what embodiment 1 made, contains total lignans 60% by embodiment 2); The tramadol capsule, specification: the hydrochloric tramadol 50mg of every capsules, produced lot number: 20090612 by Jinzhou Gekko Swinhonis pharmaceutcal corporation, Ltd.Be mixed with solution with normal saline during experiment.
1, hot plate method
Test method: will screen 60 of qualified female mices, and be divided into 5 groups at random, and 12 every group, be respectively: 1. matched group: distilled water 0.2ml/10g body weight by normal pain threshold height; 2.～4. Cortex Zanthoxyli podocarpi total lignans extract contains total lignans 30%, contains total lignans 60%, contains 90% 3 group of total lignans: irritate stomach 200mg/kg respectively; 5. tramadol hydrochloride capsule (positive control medicine) is organized: 50mg/kg (concentration is 2.5mg/ml, and the administration volume is the 0.2ml/10g body weight).Each treated animal gastric infusion 2 times; Two minor ticks 1 hour; After the last administration 60,90,120min respectively with YLS6B type hot plate dolorimeter measure each mice pain threshold (the normal pain threshold of mice be determined at grouping before carry out; Measure twice, get the normal pain threshold of twice meansigma methods before as administration.Second then stop test like pain threshold to 60 and take out mice, in order to avoid scald the mice vola, the pain threshold of this mice calculated with 60 seconds).
Result: see table 3.
Table 3 analgesic activity (mice hot plate method)
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01.
2, writhing method
Test method: get 60 of mices, be divided into 5 groups at random, 12 every group, be respectively: 1. matched group: distilled water 0.2ml/10g body weight; 2.～4. Cortex Zanthoxyli podocarpi total lignans extract contains total lignans 30%, contains total lignans 60%, contains 90% 3 group of total lignans: irritate stomach 200mg/kg respectively; 5. tramadol hydrochloride capsule (positive control medicine) is organized: 50mg/kg (concentration is 2.5mg/ml, and the administration volume is the 0.2ml/10g body weight).Each treated animal gastric infusion every day 1 time, for three days on end.Behind the last gastric infusion 30min; The glacial acetic acid solution 0.2ml of every mouse peritoneal injection 0.7%; And writhing response (abdominal part indent takes place in the observed and recorded mice immediately; Stretch hind leg, buttocks is raised) incubation period (from injecting acetic acid) to the blanking time that writhing response takes place and the number of times of writhing response appearred in 15 minutes.
Rate elongation (%)=[(administration group incubation period-matched group incubation period)/matched group incubation period] * 100%
Analgesia percentage rate (%)=[(matched group is turned round body number of times-administration group and turned round the body number of times)/matched group is turned round the body number of times] * 100%
Result: see table 4.
Table 4 analgesic activity (mouse writhing method)
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01.
The result shows: Cortex Zanthoxyli podocarpi total lignans extract has significant analgesia role, and is dose-effect relationship, and along with increasing of total lignans content wherein, its effect strengthens.
The test three, to the arthritic effect of the collagen-induced property of rat
Animal: the SD male rat, the cleaning level, body weight 180～220g is provided by Hunan University of Traditional Chinese Medicine's animal center.
Medicine: Cortex Zanthoxyli podocarpi total lignans extract (what contain total lignans 30% makes, contains being made by embodiment 3 of total lignans 90% by what embodiment 1 made, contains total lignans 60% by embodiment 2); The sinomenine hydrochloride enteric coatel tablets, specification: the 20mg/ sheet, produce lot number: 20091105 by Sichuan Central Pharmaceutical Co., Ltd..Be mixed with solution with normal saline during experiment.Chicken II-type collagen (chickentype II collagen, CC II) is provided by Chengdu Rui Fensi bio tech ltd.
Test method: an amount of chicken II-type collagen is dissolved in the glacial acetic acid of 0.1mol/L, concentration is 2mg/ml, stirs fully dissolving down at 4 ℃, puts 4 ℃ of refrigerator overnight.Again with 80 ℃, the bacillus calmette-guerin vaccine of l h deactivation place liquid paraffin be made into 0.5mg/ml Freund's complete adjuvant (Complete Freund adjuvant, CFA), with the two equal-volume mix, emulsifying, process C II Emulsion (be every 0.1ml, contain 0.1mg C II).Putting 4 ℃ of refrigerators preserves subsequent use.
Get 60 rats; Divide 8 of normal group, all the other 52 rats are a group greatly, and the Emulsion that has made is caused inflammation in the right back sufficient sole of the foot of every Mus, back, the Intradermal multi-point injection 1ml of root of the tail portion; Get after one week commensurability Emulsion again booster injection once, normal group is injected with method with normal saline.13d after injecting C II Emulsion first; Get blood and survey anti-C II antibody, the rat of anti-C II antibody positive is divided into model group, positive controls and Cortex Zanthoxyli podocarpi total lignans extract at random contains total lignans 30%, contain total lignans 60%, contain 90% 3 group of total lignans.14d begins gastric infusion after first immunisation, once a day, continuous 14d, the treatment group is irritated stomach medicine 200mg/kg respectively, and positive controls is irritated stomach and is given sinomenine hydrochloride enteric coatel tablets 50mg/kg, and normal group and model group give the normal saline of equivalent.
Cause scorching back d7, d14, d19, d24, d29, d34 observation and record whole body arthropathy degree, by 5 grades of point system evaluations, calculate the polyarthritis index: 0=does not have redness; The 1=toe joint is red and swollen; 2=toe joint and toes swelling; Sufficient pawl swelling below the 3=ankle joint; 4=comprises the whole sufficient pawl swelling of ankle joint.According to the lesion degree scores accumulated in all the other 3 joints of not injecting collagen, be the polyarthritis index of every rat.
Result: see table 5.
The arthritic influence of the collagen-induced property of table 5 pair rat
The result shows: Cortex Zanthoxyli podocarpi total lignans extract can obviously improve collagen-induced rat polyarthritis symptom, and is dose-effect relationship, and along with increasing of total lignans content wherein, its effect strengthens.
Acute toxicity test:
In order to investigate the safety of Cortex Zanthoxyli podocarpi total lignans extract, the spy has carried out investigating of acute toxicity to it, and test method result is following:
Medicine: the Cortex Zanthoxyli podocarpi total lignans extract (containing total lignans 60%) that makes by embodiment 2.
Animal: ICR mice, one-level, Mus 8～9 weeks of age, body weight 18～22g.
Method: improvement bandit method (with reference to " herbal pharmacology research methodology " the 113rd page, People's Health Publisher, the 1st edition, Qi Chen chief editor).
Result: LD
50Be 15.54g/kg, 95% the credible 14.75～16.30g/kg that is limited to.
The result shows that medicine acute toxicity of the present invention is little, and degree of safety is big.
Result by above-mentioned pharmacodynamics and toxicology test can draw: Cortex Zanthoxyli podocarpi total lignans extract has the effect of treatment of arthritis preferably, and LD
50Be 15.54g/kg, toxicity is very low.
Claims (6)
1. the Cortex Zanthoxyli podocarpi total lignans extract with treatment of arthritis effect is characterized in that wherein total lignans content is more than 30%; And this Cortex Zanthoxyli podocarpi total lignans extract is through any one therefrom extracts in the medicine Cortex Zanthoxyli podocarpi and makes in following three kinds of methods:
Method I comprises the steps:
(1) preparation Cortex Zanthoxyli podocarpi crude extract: get the Cortex Zanthoxyli podocarpi medical material, add 60%～95% ethanol and extract, filter, extracting solution, this extracting solution is concentrated, promptly get the Cortex Zanthoxyli podocarpi crude extract;
(2) the Cortex Zanthoxyli podocarpi crude extract that (1) step is made adds the suitable quantity of water suspendible, uses defat with petroleum ether earlier, adds ethyl acetate extraction again, the reclaim under reduced pressure ethyl acetate, and drying promptly gets Cortex Zanthoxyli podocarpi total lignans extract;
Method II comprises the steps:
(1) preparation Cortex Zanthoxyli podocarpi crude extract: get the Cortex Zanthoxyli podocarpi medical material, add 60%～95% ethanol and extract, filter, extracting solution, this extracting solution is concentrated, promptly get the Cortex Zanthoxyli podocarpi crude extract;
(2) the Cortex Zanthoxyli podocarpi crude extract that (1) step is made adds an amount of anhydrous alcohol solution, mixes thoroughly with the macroporous adsorbent resin with weight, adds the water of dehydrated alcohol amount more than 10 times; Stir, be added on handled on the low polar macroporous adsorbent resin column, earlier with 30% low-concentration ethanol eluting; With this low-concentration ethanol eluent discard need not, the ethanol elution of reuse 40%～95% is collected eluent; Reclaim ethanol, drying promptly gets Cortex Zanthoxyli podocarpi total lignans extract;
Method III comprises the steps:
(1) preparation Cortex Zanthoxyli podocarpi crude extract: get the Cortex Zanthoxyli podocarpi medical material, be ground into fine powder, put into the carbon dioxide supercritical fluid extraction jar, when temperature reaches 60 ℃, picks up counting when pressure is crossed 30Mpa, carbon dioxide flow is 12L/min, extracts 6 hours; Perhaps, carbon dioxide flow is 15L/min, extracted 8 hours, from knockout drum tell the Cortex Zanthoxyli podocarpi crude extract;
(2) the Cortex Zanthoxyli podocarpi crude extract that makes of (1) step is added an amount of anhydrous alcohol solution, be added on the MCI Gel resin column of using water treatment, earlier with 10%～40% ethanol elution; This low-concentration ethanol eluent is discarded need not; The ethanol elution of reuse 50%～95% is collected eluent, reclaims ethanol; Drying promptly gets Cortex Zanthoxyli podocarpi total lignans extract.
2. Cortex Zanthoxyli podocarpi total lignans extract according to claim 1 is characterized in that: total lignans content is more than 60% in the described Cortex Zanthoxyli podocarpi total lignans extract.
3. Cortex Zanthoxyli podocarpi total lignans extract according to claim 1 is characterized in that: total lignans content is more than 90% in the described Cortex Zanthoxyli podocarpi total lignans extract.
4. Cortex Zanthoxyli podocarpi total lignans extract according to claim 1 is characterized in that: make in the method for this extract, refining Cortex Zanthoxyli podocarpi total lignans extract is further purified processing with ethyl acetate.
5. the medical usage of each described Cortex Zanthoxyli podocarpi total lignans extract among the claim 1-3 is characterized in that: the medicine of using it for the preparation treatment of arthritis.
6. Cortex Zanthoxyli podocarpi total lignans extract medical usage according to claim 5 is characterized in that: described pharmaceutical dosage form is any pharmaceutical dosage form in powder pin, drop pill, tablet, capsule, the granule.
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| CN1742886A (en) * | 2005-09-19 | 2006-03-08 | 蓝子花 | Medicated liquor of cortex Zanthoxyli podocarpi |
| CN1814052A (en) * | 2005-12-02 | 2006-08-09 | 蓝子花 | Damp-repellent pain-relieving medicine liquor of cortex zanthoxyli podocarpi |
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| CN1742886A (en) * | 2005-09-19 | 2006-03-08 | 蓝子花 | Medicated liquor of cortex Zanthoxyli podocarpi |
| CN1814052A (en) * | 2005-12-02 | 2006-08-09 | 蓝子花 | Damp-repellent pain-relieving medicine liquor of cortex zanthoxyli podocarpi |
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| 陈兴等.麻口皮子药总黄酮醇提工艺研究.《中南药学》.2008,第06卷(第04期),434-436. * |
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