CN101297803A - Novel medical use of osthole - Google Patents
Novel medical use of osthole Download PDFInfo
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- CN101297803A CN101297803A CNA2008100508282A CN200810050828A CN101297803A CN 101297803 A CN101297803 A CN 101297803A CN A2008100508282 A CNA2008100508282 A CN A2008100508282A CN 200810050828 A CN200810050828 A CN 200810050828A CN 101297803 A CN101297803 A CN 101297803A
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Abstract
The invention discloses an anti-gout drug of using osthole for prevention and treatment, the action target of the osthole is to inhibit xanthine oxidase, reduce the formation of uric acid salts and has stronger anti-inflammatory and analgesic effects, the prepared drug can be the osthole single component and also can be a composition containing the osthole; the drug can be prepared into tablets, capsules, granules, injection and suspension.
Description
Technical field
The present invention relates to Chinese medicine extraction single component osthole, have new medical usage through the pharmacological evaluation proof.Osthole is inhibited to xanthine oxidase specifically, can reduce uricopoiesis, has the effect of prevention and treatment gout.Belong to the field of Chinese medicines.
Background technology
Gout is classified as one of big pertinacious disease of 21 centurys 20 by the United Nations.Up-to-date epidemiological study shows that China's gout sickness rate rises year by year.Gout is the metabolic disease due to the purine metabolic disturbance, and hyperuricemia is its main biochemical character.Uricotelic drugs, xanthine oxidase inhibitor etc. all can be alleviated hyperuricemia to some extent, the PD of control gout.Traditional anti-gout drugs-uricosureic agent (as probenecid, benzbromarone etc.) often is attended by side effect such as erythra, heating, kidney damage.Xanthine oxidase inhibitor can reduce stress or the injury to organizing that free radical causes, and also can reduce the formation of uric acid in the human body.Discover with the xanthine oxidase to be that the inhibitor of action target spot has good gout effect, be the important drugs of treatment gout and can reduce some fatal gout complication.Xanthine oxidase inhibitor is as anti-gout drugs, it mainly is the allopurinol of the listing sixties in last century, still it has a lot of side effect though use till today always, use the back patient heating, allergic rash, stomachache, diarrhoea, leukocyte and thrombocytopenia can be arranged, even side effect (progress of xanthine oxidase inhibitor, foreign medical science pharmacy fascicle, 2006 such as liver dysfunction are arranged, 33 (5), 351-353).Therefore, the new xanthine oxidase inhibitor of research has crucial meaning.We find new xanthine oxidase inhibitor-osthole be extraction from samphire Chinese medicine Fructus Cnidii (cnidium monnieri (L.) cuss.) dry mature fruit, separation, purification and single component.Osthole is natural coumarin kind compound, discovers that both at home and abroad it has multiple pharmacologically actives such as osteoporosis, anticoagulant and antiviral, mutation, blood fat reducing, antiallergic action, antitumor and anti-hepatitis.Do not find before the present invention is open that osthole has the uricopoiesis of inhibition and be the report of the inhibitor of action target spot with the xanthine oxidase.Have good gout effect through pharmacological evaluation proof osthole, and take for a long time and do not have toxic and side effects, have bright development prospect and economic benefit.The structural formula of osthole (osthole)
Summary of the invention
One of purpose of the present invention is to find the xanthine oxidase inhibitor (osthole single component) of the inhibition uricopoiesis that a kind of effect is stronger from natural plants.Advantage is that sarkin oxidase inhibitor is that the single component, the action target spot that extract in the natural plants are clear and definite, has changed and has had only allopurinol could suppress the present situation of uricopoiesis in the market.
Goal of the invention two by pharmacodynamics screening, further separation and purification determines that finally the osthole in the Fructus Cnidii becomes good effect, toxicity is little, can prevent and treat the medicine of gout.And be provided for clinical preparation.
The invention provides the pharmaceutical preparation of osthole, comprising tablet, capsule, granule, oral liquid, injection, drop pill etc.
But it preferably contains osthole and the pharmaceutical excipient of 99%-1% or the medicine of other prescription of 1%-99%.But preferably contain osthole and the pharmaceutical excipient of 70%-20% or the medicine of other prescription of 30%-80%, but preferably select osthole and the excipient of 40%-30% or the medicine of other prescription that contains 60%-70% for use.The medicine that other compatibility in the medicine is used, the osthole that refers to effective dose is certain medicine material, again compatibility other allowed the Chinese medicine or the chemical drugs that share.
Wherein pharmaceutical excipient comprises filler, disintegrating agent etc.Filler is selected from starch, lactose, microcrystalline Cellulose, dextrin etc.; Described disintegrating agent is selected from carboxymethyl starch sodium, hyprolose, polyvinylpolypyrrolidone; Optional adhesive, wetting agent and the lubricant of adding.
Osthole of the present invention extracts by following method and gets (the medicine of a kind of prevention and treatment prostatic hyperplasia, nonbacterial prostatitis disease, application number: 200810050697.8) get Fructus Cnidii medical material 1kg, add calcium oxide (CaO) 10g, 90% alcohol reflux of 6 times of amounts of usefulness medical material 3 times, each 2 hours, filter, merging filtrate, filtrate recycling ethanol is not to there being the alcohol flavor, and concentrated solution adds water move to 1000ml, be heated to 80 ℃, add sodium carbonate (NaCo
3) 15g, stirring 15 minutes, 80 ℃ of deionized waters of reuse are diluted to 1500ml, room temperature left standstill 48 hours, sucking filtration, and filter cake adds ethanol 500ml, be heated to 80 ℃ and make dissolving, add active carbon 5g, fully stir, filter, filtrate recycling ethanol is placed to 100ml, crystallize, elimination supernatant, filtration cakes torrefaction get light yellow osthole 8.6g, and content is 96.3% (HPLC method mensuration).
Osthole and pharmaceutical preparation thereof have the effect of diseases such as prevention and treatment gout, and these pharmacological actions are confirmed by following pharmacodynamics test example.
1, acute toxicity testing research
Select 20 of white mice for use, 18～20g, male and female half and half.With gastric infusion in the tolerant maximum administration concentration of animal (0.5g/ml), maximum administration volume (0.4ml/10g body weight) a day 1 time, observing continuously has non-toxic reaction and animal dead in 7 days.Recording the result is: none death of animal in the mice 7 days, under this dosage, do not observe obvious acute toxic reaction.Its mice maximum dosage-feeding is 20g medicated powder/kg body weight/d.Press the 60kg body weight and calculate, this dosage is about clinical day and intends 4000 times of consumptions.
2, osthole is to the influence of mice hyperuricemia (oxonic acid potassium salt method)
Get 60 of Kunming mouses.Male and female half and half.Be divided into 9 groups at random.By group administration 5 days, every day 1 time.After the last administration 1 hour, except that the blank group, all the other each treated animal lumbar injection oxonic acid potassium salt 300mg/kg cause the mice hyperuricemia.Behind the injection 1h, each treated animal is plucked eyeball and is got blood, and the centrifugal 5min of 2500r/min gets serum and surveys the hematuria acid number, carries out group difference relatively.The results are shown in Table 1.
Table 1 osthole is to the influence of mice hyperuricemia (n=10, X ± S)
Annotate:
△Compare P＜0.01 with the blank group, * * and model group be P＜0.01 relatively
Illustrate that each dosage group of osthole has good inhibition effect to hyperuricemia model blood uric acid due to the mice (oxonic acid potassium salt).
3, osthole is to the influence of mice blood uric acid (xanthine method)
Get 60 male mices, be divided into 6 groups (normal control group, model group, the high, medium and low dosage group of osthole, allopurinol groups) at random, 10 every group.All irritate stomach by 0.1mL/10g every day.Behind the 6d, except that the normal control group, other 5 groups of mices are lumbar injection 10% xanthine 0.1mL/10g respectively, gets blood behind the 30min and surveys the hematuria acid number, the results are shown in Table 2.
Table 2 osthole is to the influence of mice blood uric acid (n=10, X ± S)
△Compare with the blank group: P＜0.01; , compare * * P＜0.01 with model group.
Model group blood uric acid content is significantly higher than the normal control group, difference significance (P＜0.01), and medication group and model group be blood uric acid content difference highly significant relatively, all is lower than model group (P＜0.01).The mechanism that further specifies osthole reduction blood uric acid content is the same with allopurinol, is to reduce uricopoiesis.Alleviate its infringement, thereby effectively control the gout outbreak tissue.
4, osthole is to the influence of rat foot claw swelling due to the MSU
60 rats are divided into 6 groups at random by body weight, and specifically grouping and dosage see Table 3.Each organizes continuous gastric infusion, and once a day, administration is 7 days altogether.Blank group and model group are given normal saline.Test the same day and survey each rat right back sufficient pawl volume 2 times (2 minor tick 1h) earlier, average as causing the scorching preceding right back sufficient volume of normal rat, administration is 1 time then.Except that the blank group, 1h after the administration of rat last, right back toes subcutaneous injection 0.1mL (100mg/ml) MSU suspension causes inflammation, calculates the foot swelling percentage rate.
5, osthole is to the influence of mice chondrus ocellatus Holmes colloidality foot swelling
Get 50 of mices, by being divided into 5 groups at random, press gastric infusion every day of dosage shown in the table 2 once, administration is 7 days altogether, 30min after the last administration, only inject 1% carrageenin 0.03ml/ down in the right back vola aponeurosis (aponeuroses) of mice, behind the 6h dislocation of mice cervical vertebra is put to death behind the Yu Zhiyan, cut the bilateral metapedes, weigh respectively, ask the poor of left and right heavy sensation in the foot amount, be the swelling degree.See Table 4.
Table 4 osthole is to the influence of mice chondrus ocellatus Holmes colloidality foot swelling (n=10, X ± S)
Compare * P＜0.05 with matched group; * P＜0.01; * * P＜0.001.
The result shows: osthole can obviously suppress the mice foot swelling that carrageenin causes, and high, there were significant differences for middle dosage group.
6, the influence of osthole xylol induced mice auricle edema
Get 50 of mices, by being divided into 5 groups at random, press gastric infusion every day of dosage shown in the table 3 once, administration is 7 days altogether, and 2h after the last administration drips dimethylbenzene 0.05ml in mouse right ear, and left ear is a normal control.Behind the 4h dislocation of mice cervical vertebra is put to death, cut two ears, lay round auricle at the same position of left and right ear respectively, weigh, ask the poor of left and right auricle weight, be the swelling degree with the card punch of diameter 8mm along the auricle baseline.See Table 5.
The influence of table 5 osthole xylol induced mice auricle edema (n=10, X ± S)
Compare * P＜0.05 with matched group; * P＜0.01
The result shows: the high, medium and low dosage of osthole all can obviously suppress the mice auricle swelling that dimethylbenzene causes, and has significant difference.
7, to the influence of mice granuloma induced by implantation of cotton pellets
Get agar 2g and add human physiology saline 30ml, in 40 ℃ of insulations, extract 0.1ml agar with syringe under the sterile working and annotate the subcutaneous inflammation that causes of axil before people's right side of mice after the heat fused.50 of mices were divided into 5 groups in causing the scorching same day at random, pressed table 4 dosed administration, and successive administration 7d put to death mice in the 8th day, peeled off the agar granuloma, weighed behind 80 ℃ of baking 2h.The results are shown in Table 6.
Table 6 osthole is to the influence of mice granuloma induced by implantation of cotton pellets (n=10, X ± S)
Compare * P＜0.05 with matched group; * P＜0.01
The result shows that each dosage group of osthole can obviously suppress the hypertrophy of granulation tissue, makes the weight saving of granulation cotton balls.Compare significant difference with matched group.
From above toxicity and pharmacodynamic experiment as can be known, Fructus Cnidii has that the carbamide of inhibition generates, antiphlogistic effect, thereby can treat and prevent gout, and therapeutic effect is remarkable, takes for a long time and is free from side effects, and can make oral formulations, taking convenience.
The specific embodiment
In conjunction with the embodiments the present invention is further described, but the present invention is not subjected to any restriction of embodiment.
Embodiment 1 (capsule)
Prescription: osthole: 150g
Starch 30g
Carboxymethyl starch sodium 20g
3% hydroxypropyl methylcellulose aqueous solution is an amount of
Osthole raw material, starch, carboxymethyl starch sodium, mix homogeneously is granulated with 3% hydroxypropyl methylcellulose aqueous solution, drying, granulate, the capsule of packing into No. 1 is made 1000, promptly.Every contains osthole 150mg.Each 1.Every day 2 times.
Embodiment 2 (tablet)
Prescription: osthole: 150g
Lactose 30g
Carboxymethyl starch sodium 20g
3% hydroxypropyl methylcellulose aqueous solution is an amount of
Pulvis Talci 2.5g
Osthole raw material, microcrystalline Cellulose, carboxymethyl starch sodium, mix homogeneously is granulated with 3% hydroxypropyl methylcellulose aqueous solution, drying, granulate adds the Pulvis Talci mixing, and tabletting is made 1000, promptly.Every contains osthole 150mg.Each 1.Every day 2 times.
Embodiment 3 (granule)
Prescription: osthole 150g
Icing Sugar: 350g
Osthole raw material, Icing Sugar, mix homogeneously is used an amount of alcohol granulation, and drying, granulate, packing are made 500 bags, promptly.Each 1 bag.Every day 2 times
Embodiment 4 (drop pill)
Prescription: osthole 15g
Polyethylene glycol 6000 25g
Macrogol 4000 10g
Take by weighing the 25g polyethylene glycol 6000, the 10g Macrogol 4000 melts in water-bath, add osthole raw material 15g, stir, in the impouring insulating tube, regulate thermostat, in the liquid paraffin (12-14 ℃) that medicinal liquid is splashed into cooled off, after dripping off, will blot paraffin oil on the pill impouring filter paper under 80-90 ℃, make 1000, promptly.
Claims (6)
1, the application of a kind of xanthine oxidase inhibitor-osthole in prevention and treatment gout medicine.
2, application according to claim 1 is characterized in that: contain the osthole of dose therapeutically effective and one or more pharmaceutically acceptable pharmaceutical excipients, or the preparation that can make with the other medicines of osthole prescription.
3, pharmaceutical preparation according to claim 2, but it is characterized in that preferably containing osthole and the pharmaceutical excipient of 99%-1% or the medicine of other prescription of 1%-99%.But preferably contain osthole and the pharmaceutical excipient of 70%-20% or the medicine of other prescription of 30%-80%, but preferably select osthole and the excipient of 40%-30% or the medicine of other prescription that contains 60%-70% for use.
4, pharmaceutical preparation according to claim 2 is characterized in that said medicine is the dosage form of oral formulations.
5, pharmaceutical preparation according to claim 4 is characterized in that said oral formulations is selected from any in the middle of the tablet, pill, capsule, soft capsule, granule, suspensoid, drop pill, oral liquid.
6, the described pharmaceutical excipient of claim 2 comprises filler, disintegrating agent etc., and filler is selected from starch, lactose, microcrystalline Cellulose, dextrin, calcium phosphate etc.; Disintegrating agent is selected from carboxymethyl starch sodium, hyprolose, polyvinylpolypyrrolidone; Also optional adhesive, wetting agent and the lubricant of adding.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100508282A CN101297803A (en) | 2008-06-16 | 2008-06-16 | Novel medical use of osthole |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100508282A CN101297803A (en) | 2008-06-16 | 2008-06-16 | Novel medical use of osthole |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101780071A (en) * | 2010-03-30 | 2010-07-21 | 苏州大学 | Application of osthole in preparation of medicament for preventing and treating myocardial fibrosis |
| CN103432279A (en) * | 2013-08-07 | 2013-12-11 | 许春桂 | Method for preparing soaking agent for preventing and treating gout with decoction dregs and product |
| CN110585250A (en) * | 2019-09-29 | 2019-12-20 | 吉林省多维医药健康发展有限公司 | Application of larch root total flavonoids in inhibiting increase of uric acid and preventing and treating gout |
-
2008
- 2008-06-16 CN CNA2008100508282A patent/CN101297803A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101780071A (en) * | 2010-03-30 | 2010-07-21 | 苏州大学 | Application of osthole in preparation of medicament for preventing and treating myocardial fibrosis |
| CN103432279A (en) * | 2013-08-07 | 2013-12-11 | 许春桂 | Method for preparing soaking agent for preventing and treating gout with decoction dregs and product |
| CN103432279B (en) * | 2013-08-07 | 2015-05-27 | 许春桂 | Method for preparing soaking agent for preventing and treating gout with decoction dregs and product |
| CN110585250A (en) * | 2019-09-29 | 2019-12-20 | 吉林省多维医药健康发展有限公司 | Application of larch root total flavonoids in inhibiting increase of uric acid and preventing and treating gout |
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Open date: 20081105 |