CN1565467B - Use of cornel and its extract in preparation alpha-glucosidase inhibitor medicine - Google Patents
Use of cornel and its extract in preparation alpha-glucosidase inhibitor medicine Download PDFInfo
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Abstract
The invention provides a dogberry medicament having alpha-glucosaminidase inhibiting activity, and the water or organic solvent extract of dogberry, wherein the dogberry extract comprises total glycosides and poly phenols constitution.
Description
Technical field
The present invention relates to the new pharmaceutical usage of Chinese medicine and extract thereof, specifically, the present invention relates to Chinese medicine Fructus Corni (Cornus officinalis Sieb.et Zucc) and extract thereof the purposes in preparation alpha-glucosidase inhibitor class medicine, can reduce post-prandial glycemia, treatment I, type ii diabetes and diabetic complication.
Background technology
Treat diabetes for many years mainly to control fasting glucose as therapeutic goal, medicine has only sulfonylurea and biguanides for a long time, and sulphanylureas passes through the stimulating pancreas excreting insulin and blood sugar lowering; Then by increasing peripheral tissues to the utilization of glucose and blood sugar lowering, both all have curative effect preferably to the fasting glucose that reduces the type ii diabetes patient to biguanides, but very limited to the effect that reduces post-prandial glycemia.Post-prandial glycemia during diabetes is the blood sugar level acme in one day, its persistent period can be for 8 hour or is longer, long-time high-caliber post-prandial glycemia can increase the weight of diabetes itself, blood glucose is further raise, post-prandial glycemia also is the main hazard factor of diabetic complication, if just can control hyperglycemia well at table, then can avoid its after the meal the sugar in the blood circulation part pile up, therefore, the control post-prandial glycemia can be described as the control hyperglycemia, prevents and treats the important measures of diabetes.
Alpha-glucosidase inhibitor is a class new oral hypoglycemic drug of researching and developing out in the seventies later stage, its mechanism of action is: suppress alpha-glucosidase competitively, delay and hinder the digestion of carbohydrate, delay is from disaccharidase, the glucose absorption of oligosaccharide and polysaccharide, effectively postpone and alleviate the time and the degree of post-prandial glycemia rising, take for a long time also and can reduce fasting blood glucose level, this type of medicine all is suitable for I, type ii diabetes.Alpha-glucosidase inhibitor not only has definite curative effect to diabetes, and for obesity, chronic viral hepatitis B, acquired immune deficiency syndrome (AIDS) and tumor all have certain therapeutical effect.Be used for the clinical acarbose that has, voglibose and miglitol at present.
Most carbohydrates in the food are starch, sucrose etc., starch is earlier after the effect of saliva and pancreatic juice α-Dian Fenmei is decomposed into oligosaccharide, oligosaccharide is decomposed into glucose and after being absorbed, causes the post-prandial glycemia peak by alpha-glucosidase at intestinal epithelial cell brush border place.
Fructus Corni (Cornus officinalis Sieb.et Zucc) is the drying and ripening sarcocarp of Cornaceae plant Fructus Corni, slightly warm in nature, sour in the mouth, has liver and kidney tonifying, restrain astringent or styptic treatment for spontaneous sweating effect. modern study shows, the main chemical of Fructus Corni has glycoside, organic acid, Polyphenols, .20 such as saccharide and amino acids eighties in century, Japan scholar mountain plateau bar is second-class, found that Fructus Corni ether and ethyl acetate extract have tangible blood sugar reducing function to the formed diabetes rat of streptozotocin, its effective ingredient is a ursolic acid [pharmaceutical journal, 1981,101 (1): 86]; The Fructus Corni ethanol extraction has been reported the inhibitory action of Fructus Corni ethanol extract to type ii diabetes to the treatment effect [Nantong Medical College's journal 2000,20 (4): 337-339] of type ii diabetes rat; The blood sugar reducing function experimentation of Fructus Corni different process extract [Beijing traditional Chinese medical science 1997,5:53-54] discloses the Fructus Corni ethanol extract from water precipitation, water extraction reduces the effect of diabetes rat hyperglycemia; Fructus Corni has reported that to the influence [Xianning medical college journal, 1999,13 (1): 12-14] of blood glucose in diabetic mice and tissue glycogen's content Fructus Corni has tangible blood sugar reducing function to diabetes rat due to alloxan, streptozotocin and the epinephrine; Fructus Schisandrae Chinensis, Fructus Corni etc. are to inhibitory action [the Nanjing TCM Universities journal of protein nonenzymatic glycosylation, 2001,17 (3), 166-167] reported the improvement effect of Fructus Corni to diabetic complication. clinical and experimentation has affirmed that the Chinese patent literature of the blood sugar reducing function .CN1053371C of Fructus Corni discloses a kind of Fructus Corni total saponin extracts and extraction process thereof with immunization and antiinflammatory action. has alpha-glucosidase in preparation and suppresses application report in the active medicine but have not yet to see Fructus Corni, do not see that also having alpha-glucosidase suppresses active Fructus Corni total glycosides extract and reduce post-prandial glycemia in preparation, treatment I, application report in the medicine of type ii diabetes and diabetic complication.
Summary of the invention
At present, the alpha-glucosidase inhibitor class medicine of clinical practice is actually rare, compounds medicine acarbose occupies leading position, the purpose of this invention is to provide Chinese medicine Fructus Corni (Cornusofficinalis Sieb.et Zucc) and extract thereof the new purposes in preparation alpha-glucosidase inhibitor class medicine, so that the route of administration of new alpha-glucosidase inhibitor to be provided.
Technical scheme of the present invention is: Chinese medicine Fructus Corni (Cornus officinalis Sieb.etZucc) and extract thereof the purposes in preparation alpha-glucosidase inhibitor class medicine is provided.
Above-mentioned Fructus Corni extract is water or extractive with organic solvent, further, this Fructus Corni extract contains Fructus Corni total glycosides, and its weight ratio is 10～90%, further, also contain Fructus Corni Polyphenols composition, its weight ratio is 5～30%, and is preferred, contain Fructus Corni total glycosides in the described Fructus Corni extract, its weight ratio is 45～90%, Fructus Corni Polyphenols composition, and weight ratio is 10～30%.
The present invention will provide a kind of preparation method that obtains this Fructus Corni extract, may further comprise the steps:
A, the Chinese medicine Fructus Corni is pulverized, water, methanol or ethanol, or aqueous alcohols is extracted, concentrated, precipitation is centrifugal, supernatant is standby; Particularly, with the suitable pulverizing of raw material process, water, methanol or ethanol, or aqueous alcohols is quiet or down dynamic, room temperature or heating (comprising backflow) are extracted, the extraction solvent is 5～12 times of crude drug in whole weight, can repeat to extract 1～3 time, merge extractive liquid, elimination medicinal residues are concentrated into finite concentration (0.5～2.0 grams per milliliter), by methods such as precipitate with ethanol, flocculations under normal pressure or decompression dynamical state, make contamination precipitation, through centrifugal or filtration (comprising normal pressure, decompression, microfiltration, ultrafiltration), remove insoluble matter again, it is standby to get clear liquid.
B, with the supernatant that obtains after a step process, go up macroporous resin column again, washing clean non-adsorbable impurity, reuse alcohol, ketone or aqueous alcohol eluting are collected eluent, concentrate, the true drying, lyophilization, the direct spray drying of collection liquid held gets dry powder.
In the preparation method of above-mentioned Chinese medicine extract, preferable methods is: the extraction solvent is water, aquiferous ethanol, and macroporous resin is a non-polar macroporous resin, and eluent is 25～95% ethanol.
It is the pharmaceutical preparation of the α one glucosidase inhibition class of effective medicinal component that the present invention also provides with said Chinese medicine Fructus Corni and extract thereof, can be used for reducing post-prandial glycemia, treatment I, type ii diabetes and diabetic complication, also can be used as functional food.
With above-mentioned said Fructus Corni or its extract, after pharmaceutically acceptable auxiliary interpolation composition mixes,, can prepare the medicine of alpha-glucosidase inhibitor class by corresponding conventional medicine formulation method.For example, after in oral formulations, can receivedly mixing as auxiliary interpolation composition commonly used such as disintegrating agent, excipient, lubricant, binding agent, filler, operational approach routinely and process can be made for the medicine of tablet, pill, capsule or solid orally ingestible forms such as multiple corresponding slow releasing agent, controlled release agent; After the surfactants such as solubilizing agent, emulsifying agent, wetting agent, foaming or defoamer of routine, diluent, antiseptic, stabilizing agent, correctives, thickening agent etc. mix, by corresponding conventional method, can be made for oral drugs as liquid preparation forms such as water preparation, syrup.
The above-mentioned said Fructus Corni extract that effective medicinal ingredient uses that can be used as of the present invention, its raw material is the natural drug Fructus Corni, medicine source abundance, method is simple to extract preparation. and experimental result shows, with this extract at effective active composition as the alpha-glucosidase inhibitor medicine, can have the effect that suppresses alpha-glucosidase more by force, not only can be used for reducing post-prandial glycemia, also can be used for I, the treatment of type ii diabetes and diabetic complication, good effect, toxic and side effects is little. and Chinese medicine Fructus Corni of the present invention and extract thereof can suppress enteral alpha-glucosidase activity effectively, confirm by experiment in vivo and vitro, can suppress external alpha-glucosidase activity significantly, reduce normal mouse and diabetic mice post-prandial glycemia peak, be used for diabetes, particularly control of diabetes people post-prandial glycemia raises very effective.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Description of drawings
Fig. 1 is Fructus Corni extract SZY-1, Fructus Corni extract SZY-2, the Fructus Corni extract SZY-3 measurement result to the depression effect of alpha-glucosidase activity.Ordinate is represented the enzymatic activity suppression ratio, and abscissa is represented SZY-1, SZY-2, SZY-3, acarbose.Compared among the figure with maltose, sucrose, when starch is substrate, Fructus Corni extract SZY-1, Fructus Corni extract SZY-2, Fructus Corni water boiling and extraction thing SZY-3, acarbose are to the inhibition activity of alpha-glucosidase.
The specific embodiment
The preparation of embodiment 1 Fructus Corni extract SZY-1 (alcohol dipping):
After the dry Fructus Corni of 200 grams is pulverized, successively with 70% alcohol reflux that adds 5 times of amounts 3 times, each 0.5 hour; Will ethanol extract filter the back and merge, be evaporated to dried, extractum SZY-1 45g altogether.
With morroniside is reference standards, with spectrophotography (Zheng Huzhan etc., Chinese medicine modern study and application, the 48th page), the Fructus Corni total glycosides content in the powdered product is measured, and Fructus Corni total glycosides (weight ratio) is 15%.With indigo carmine liquid is the index agent, uses standard K M
nO
4The solution titration, recording Polyphenols content is 9%.
The preparation of embodiment 2 Fructus Corni extract SZY-2:
After the dry Fructus Corni of 200 grams is pulverized, successively with 60% alcohol reflux that adds 5 times of amounts 3 times, each 0.5 hour; Ethanol extract is filtered the back merge, ethanol is removed in distilling under reduced pressure, gets concentrated aqueous solution, is diluted to 1600 milliliters with deionized water, and is centrifugal standby.Get 200 gram D-140 type non-polar macroporous resin dress posts, with above-mentioned aqueous solution with the flow velocity of 20 ml/min by this macroporous resin column, wash post with 500 ml deionized water with the flow velocity of 20 ml/min then, 1000 milliliter of 75% ethanol elution of reuse, merge eluent, concentrating under reduced pressure, vacuum drying get Fructus Corni extract SZY-2 8.593g altogether, are brown ceramic powder.Suitable adjuvant be can add and tablet, capsule, granule made.
With morroniside is reference standards, uses spectrophotography, and the Fructus Corni total glycosides content in the above Fructus Corni extract SZY-2 powdered product is measured, and Fructus Corni total glycosides (weight ratio) is 81%.With indigo carmine liquid is the index agent, uses standard K M
nO
4The solution titration, recording Polyphenols content is 15%.
The preparation of embodiment 3 Fructus Corni extract SZY-3:
The dry Fructus Corni of 200 grams after crushed, the decocting that adds 10 times of amounts boiled 30 minutes, decoct altogether three times. three decoction liquor are merged, centrifugal standby. get 200 gram D-140 type non-polar macroporous resin dress posts, with above-mentioned decoction liquor with the flow velocity of 20 ml/min by this macroporous resin column, wash post with 500 ml deionized water with the flow velocity of 20 ml/min then, 1000 milliliter of 75% ethanol elution of reuse, merge eluent, concentrating under reduced pressure, vacuum drying get Fructus Corni extract SZY-3 altogether 8.789g. can add suitable adjuvant and make tablet, capsule, granule.
With morroniside is reference standards, uses spectrophotography, and the Fructus Corni total glycosides content in the above powdered product is measured, and Fructus Corni total glycosides (weight ratio) is 63%.With indigo carmine liquid is the index agent, uses standard K M
nO
4The solution titration, recording Polyphenols content is 24%.
Embodiment 4 Fructus Corni extract SZY-1, SZY-2, SZY-3 are to the vitro inhibition effect of alpha-glucosidase;
When 1) being substrate with starch, Fructus Corni extract is to the inhibition determination of activity of alpha-glucosidase:
Fructus Corni extract SZY-1 with embodiment 1 gained, embodiment 2 resulting Fructus Corni extract SZY-2, the Fructus Corni extract SZY-3 of embodiment 3 gained is dissolved in normal saline respectively, being mixed with concentration is 0.1mg/ml Fructus Corni extract solution, again respectively with these three kinds of solution 20 microlitres and 2 microlitre α-Dian Fenmei (0.4U/ul, available from SIGMA company) mix, 37 ℃ of incubations 10 minutes, add 1% starch solution, incubated at room 3-5 minute, use the iodometric titration development process, under the 630nm wavelength, measure the OD value, calculate the alpha-glucosidase activity suppression ratio by the consumption of starch amount; Set blank, negative control, positive control (acarbose (manufacturer: Beijing Bayer HealthCare Co)), suppression ratio=(sample-feminine gender/blank-feminine gender) * %.
When 2) being substrate with maltose, Fructus Corni extract is to the inhibition determination of activity of alpha-glucosidase:
Be dissolved in normal saline respectively with Fructus Corni extract SZY-1, the embodiment 2 Fructus Corni extract SZY-2 of embodiment 1 gained, the Fructus Corni extract SZY-3 of embodiment 3 gained, be mixed with 0.28mg/ml solution, again respectively with these three kinds of solution 20 microlitres and 2 microlitre alpha-glucosidase (0.02U/ul, available from SIGMA company) mix, 37 ℃ of incubations 10 minutes, add maltose then, 37 ℃ were continued incubation 10 minutes; Adopt glucose oxidase method, under the 490nm wavelength, measure the OD value,, calculate the alpha-glucosidase activity suppression ratio with the growing amount of glucose; Set blank, negative control, positive control (acarbose).Enzymatic activity suppression ratio=(feminine gender-sample)/(feminine gender-blank) * 100%.
When 3) being substrate with sucrose, Fructus Corni extract is to the inhibition determination of activity of alpha-glucosidase:
Fructus Corni extract solution S ZY-1, Fructus Corni extract solution S ZY-2, the Fructus Corni of 20 microlitres are extracted SZY-3 (concentration is 0.28mg/ml), respectively with 2 microlitre invertase (0.106U/ul, available from SIGM A company) mix, 37 ℃ of incubations 10 minutes, add sucrose then, 37 ℃ were continued incubation 10 minutes; Adopt glucose oxidase method, under 490 wavelength, measure the OD value,, calculate the alpha-glucosidase activity suppression ratio with the growing amount of glucose; Set blank simultaneously, negative control, positive control (acarbose).Enzymatic activity suppression ratio=(feminine gender-sample)/(feminine gender-blank well) * 100%.
Conclusion: above experimental result shows, Fructus Corni extract SZY-1, SZY-2, SZY-3 is external that alpha-glucosidase is had remarkable inhibitory action.Experiment in vitro the results are shown in Figure 1.
Embodiment 5 normal mouse starch-bearing carbohydrate tolerance tests:
The Fructus Corni extract SZY-3 of embodiment 3 gained is dissolved in normal saline makes into 5% solution, stand-by.Get body weight 22～26 gram Kunming mouses, the vena orbitalis posterior clump is gathered fasting blood, separation of serum is measured blood glucose, choose the less Mus of blood glucose value difference, by 10 every group, male and female half and half are divided into 6 groups, it is the starch-bearing group, acarbose group (manufacturer: Beijing Bayer HealthCare Co) (Western medicine positive control), Fructus Corni extract (SZY-3) high dose group, middle dosage group, low dose group, Ramulus Mori granule (manufacturer: Haier's Pharmaceutical) (Chinese medicine positive control) height, middle dosage group, acarbose dosage is 20 milligrams/kilogram (body weight), the Fructus Corni high dose group is 400 milligrams/kilogram, middle dosage group is 200 milligrams/kilogram, low dose group is 100 milligrams/kilogram, Ramulus Mori granule high dose group is 400 milligrams/kilogram, and middle dosage group is 200 milligrams/kilogram; Administration is after 10 minutes (model group is irritated the stomach normal saline), and each group is all irritated stomach starch 5 gram/kilograms, gets vena orbitalis posterior clump blood respectively at 30,60,90,120 minutes, measures blood sugar content with glucose oxidase method in 96 orifice plates, the results are shown in Table 1.
Table 1 Fructus Corni extract SZY-3 is to the influence of normal mouse starch-bearing carbohydrate tolerance
Compare with matched group,
*P＜0.05,
*P＜0.01
Interpretation of result: as can be seen from Table 1, the Fructus Corni extract of three kinds of dosage to the normal mouse starch-bearing after the blood glucose value of each time point significant reduction is all arranged, and suppressed the blood sugar increasing effect at 1.5 hours and 2 hours and be better than the Western medicine acarbose that dosage is 20mg/ml; Fructus Corni and Chinese medicine Ramulus Mori granule compare, and at 0.5 and 1 hour, the Fructus Corni effect of three kinds of dosage all was better than the Ramulus Mori granule, and at 1.5 and 2 hours, Fructus Corni was a little less than the Ramulus Mori granule.
Embodiment 6 alloxan are induced the carbohydrate tolerance test of diabetic mice starch-bearing
Get body weight 22-26 gram Kunming mouse, 200 milligrams of/kilogram alloxan of lumbar injection, measure blood glucose after 72 hours, choose blood glucose value 13 mMs/liter more than mice, by 10 every group, male and female half and half are divided into 6 groups, it is diabetic model group, the acarbose group, the Fructus Corni extract SZY-3 high dose group of embodiment 3 gained, middle dosage group, low dose group, the Ramulus Mori groups of grains, acarbose dosage is 20 milligrams/kilogram (body weight), Fructus Corni extract (SZY-3) high dose group is 400 milligrams/kilogram, low dose group is 400 milligrams/kilogram, and the Ramulus Mori groups of grains is 400 milligrams/kilogram; Administration is after 10 minutes (model group is irritated the stomach normal saline), and each group is all irritated stomach starch 5 gram/kilograms, gets vena orbitalis posterior clump blood respectively at 30,60,90,120 minutes, measures blood sugar content with glucose oxidase method in 96 orifice plates, the results are shown in Table 2.
Table 2 Fructus Corni extract SZY-3 induces the influence of diabetic mice starch-bearing carbohydrate tolerance to alloxan
Compare with matched group,
*P＜0.05,
*P＜0.01,
Interpretation of result: as can be seen from Table 2, after diabetic mice gave starch, blood glucose value obviously raise.Fructus Corni extract SZY-3 high dose all significantly suppresses the blood sugar increasing of diabetic mice at each time point, and except that effect in 0.5 hour was more weak, the effect and the acarbose of all the other time points were suitable; Fructus Corni extract (SZY-3) compares with the Ramulus Mori granule, and the effect of Fructus Corni extract SZY-3 significantly is better than the Ramulus Mori granule, and the blood glucose in diabetic mice that the Ramulus Mori granule only caused starch-bearing at high dose in 0.5 hour raises inhibitory action is arranged.
Pass through the foregoing description, Fructus Corni extract is external that alpha-glucosidase is had remarkable inhibitory action through experiment in vitro proof, zoopery shows by the starch-bearing carbohydrate tolerance test, after giving dosage and being the 100-400mg/kg Fructus Corni extract, blood sugar increasing behind remarkable reduction normal mouse and the diabetic mice starch-bearing, rising to the control post-prandial glycemia is very effective, can be used for the particularly treatment of type ii diabetes and diabetic complication of I type.
The capsular preparation of embodiment 7 Fructus Corni crude drug in whole:
Get the dry Fructus Corni of 200g, in 110 ℃ of following moist heat sterilizations 30 minutes, drying was ground into fine powder, crosses 100 mesh sieves, adds starch 40g in steriliser, y magnesium stearate 0.4g, and mixing is dressed up 30 capsules.Human oral dosage: each 1, every day 3 times.
Claims (8)
1. the purposes of Fructus Corni Cornus officinalis Sieb.et Zucc extract in preparation alpha-glucosidase inhibitor class medicine, wherein the preparation method of Fructus Corni extract is:
A, the Chinese medicine Fructus Corni is pulverized, water or 60% ethanol extraction, concentrate, precipitation is centrifugal, supernatant is standby;
B, with the supernatant that obtains after a step process, go up the non-polar macroporous resin post again, washing clean non-adsorbable impurity, reuse 75% ethanol elution is collected eluent, concentrate drying obtains finished product.
2. purposes according to claim 1 is characterized in that: described medicine is the medicine that reduces post-prandial glycemia.
3. purposes according to claim 1 and 2 is characterized in that: described medicine is to the medicative medicine of I, type ii diabetes and diabetic complication.
4. purposes according to claim 1 and 2 is characterized in that: contain Fructus Corni total glycosides in the described Fructus Corni extract, its weight ratio is 10%～90%.
5. purposes according to claim 4 is characterized in that: also contain Fructus Corni Polyphenols composition in the extract, its weight ratio is 5～30%.
6. purposes according to claim 5 is characterized in that: contain Fructus Corni total glycosides in the described Fructus Corni extract, weight ratio is 45～90%, Fructus Corni Polyphenols composition, and weight ratio is 10～30%.
7. purposes according to claim 5 is characterized in that: described medicine is to be active component by Fructus Corni extract, adds that acceptable accessories or carrier form.
8. purposes according to claim 7 is characterized in that: the dosage form of described medicine is an oral formulations.
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| CN100435810C (en) * | 2005-08-15 | 2008-11-26 | 江苏吴中苏药医药开发有限责任公司 | Dogwood fruit extract and its preparation process |
| CN102389162A (en) * | 2011-08-04 | 2012-03-28 | 深圳烟草工业有限责任公司 | Method for preparing cornus officinalis extract, application in cigarettes and cigarette |
| CN103169751A (en) * | 2013-03-15 | 2013-06-26 | 陕西师范大学 | Extracting process for optimizing alpha-glucosidase inhibitor in nanometer dogwood by response surface method |
| CN105267944A (en) * | 2015-11-11 | 2016-01-27 | 安徽生物肽产业研究院有限公司 | Hirudo small peptide effective part medicine for treating diabetes and complications thereof |
| CN110090243B (en) * | 2019-05-21 | 2021-07-30 | 江西农业大学 | Gorgon fruit extract for controlling postprandial blood sugar, preparation method and application |
| CN112274550A (en) * | 2019-07-22 | 2021-01-29 | 陕西师范大学 | Ultrasonic enzymolysis composite method for extracting blood sugar reducing component from dogwood pulp and application |
| CN114177213A (en) * | 2021-11-16 | 2022-03-15 | 四川省一片叶药业有限公司 | Preparation method of wine-processed cornus pulp |
| CN115040558B (en) * | 2022-06-25 | 2023-05-12 | 美宝医药科技集团有限公司 | Hypoglycemic natural extract and application thereof in preparing diabetes and diabetes related metabolic syndrome products |
| CN115232009A (en) * | 2022-08-24 | 2022-10-25 | 中日友好医院(中日友好临床医学研究所) | Phenolic acid compound, preparation method thereof, pharmaceutical composition and application |
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| CN1424319A (en) * | 2002-12-30 | 2003-06-18 | 首都医科大学宣武医院 | Extracts of cornus officinalis and its preparation and use |
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| CN1424319A (en) * | 2002-12-30 | 2003-06-18 | 首都医科大学宣武医院 | Extracts of cornus officinalis and its preparation and use |
Non-Patent Citations (4)
| Title |
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| 皮文霞等.大孔树脂与活性炭富集山茱萸总苷的实验研究..中国中药杂志27 8.2002,27(8),583-584. |
| 皮文霞等.大孔树脂与活性炭富集山茱萸总苷的实验研究..中国中药杂志27 8.2002,27(8),583-584. * |
| 郝海平等.山茱萸环烯醚萜总苷对由链脲佐菌素诱导的糖尿病血管并发症大鼠血清sICAM-1、TNF-α的影响..中药药理与临床18 4.2002,18(4),13-14. |
| 郝海平等.山茱萸环烯醚萜总苷对由链脲佐菌素诱导的糖尿病血管并发症大鼠血清sICAM-1、TNF-α的影响..中药药理与临床18 4.2002,18(4),13-14. * |
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