CN102526151B - Medicinal composition and application thereof - Google Patents
Medicinal composition and application thereof Download PDFInfo
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- CN102526151B CN102526151B CN 201210036753 CN201210036753A CN102526151B CN 102526151 B CN102526151 B CN 102526151B CN 201210036753 CN201210036753 CN 201210036753 CN 201210036753 A CN201210036753 A CN 201210036753A CN 102526151 B CN102526151 B CN 102526151B
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Abstract
The invention discloses a medicinal composition and application thereof. The medicinal composition is prepared from an erigeron breviscapus extract and a cyanotis arachnoids extract which serve as active ingredients in a weight ratio of (0.1-10):1. The medicinal composition has the effects of reducing blood sugar, regulating blood fat and improving blood hemorheology under the synergistic action of the erigeron breviscapus extract and the cyanotis arachnoids extract, can be used for preparing medicines for treating or preventing diabetes and also can be used for preparing medicines for improving diabetic complications (namely regulating blood fat, improving microcirculation, improving blood hemorheology and the like).
Description
Technical field
The present invention relates to a kind of Pharmaceutical composition, specifically, is to be the Pharmaceutical composition made of active component and the application in the medicine of preparation treatment or prevent diabetes thereof by Herba Erigerontis extract and Cyanotis arachnoides P.E, belongs to technical field of Chinese medicines.
Background technology
Diabetes are a kind of common incretion metabolism diseases, and whole world prevalence is the trend that rises gradually.China's diabetes prevalence reached 9.7% in 2009, and China has become one of fastest-rising country of global diabetes prevalence.China's diabetics in carbohydrate metabolism disturbance, often with lipometabolic disorder and hemorheological unusual, thereby causes multiple diabetic complication take type ii diabetes as main.Therefore, control sugar, fat metabolic disturbance prevent the generation of complication, are the emphasis for the treatment of diabetes, searching effectively blood sugar lowering, improve lipid metabolism, improve hemorheological medicine, to the treatment of diabetes with prevent all significant.
Diabetes and complication thereof need Long-term taking medicine, so when suffering from diabetes, particularly during slight diabetes, if on the basis of control blood glucose, can improve the symptom relevant with diabetes, as regulate blood fat, improve hemorheology, to the treatment of diabetes with prevent and treat significant.
It is reported, Herba Erigerontis can be treated diabetes (Chinese endocrine metabolism magazine 2000,16 (2): 129; Chinese Journal of New Drugs, 2008,17 (2): 110-113; China's medicine and clinical, 2006,6 (9): 650; Harbin medicine, 2004,24 (1): 24), Main Flavonoids constituents lamp-dish flower acetic is found to block the Cellular Signaling Transduction Mediated system that causes complication after the hyperglycemia in the Herba Erigerontis, is used for control diabetic complications (Chinese invention patent CN1318373A).And Radix Cyanotis vagae (Cyanotis arachnoidea) also can blood sugar lowering (Chinese invention patent CN1070077C), but mechanism of action separately is not fully aware of.This is disadvantageous for treatment and the prevention that the characteristics of scientifically utilizing the two are applied to diabetes.In addition, diabetes and complication thereof all need Long-term taking medicine, so improving on the basis of curative effect, reduce dosage, and be to reducing medical treatment cost and increasing the drug safety aspect, all significant.
The coupling of different pharmaceutical utilizes respectively its advantage, is an effective solution from seeing in logic.Yet, the coupling of medicine, in fact very complicated, also side effect may be increased, or the purpose of expection can not be reached.Most critical be that can drug combination feasible, see whether the mechanism of action between the medicine has adduction, by many target spot effects whether synergism be arranged, and also will observe and whether pick up anti-effect etc. underlying issue.Whether the coupling that prior art can't provide complete scientific basis to carry out between the anticipation and decision Chinese medicine well is reasonable.
So far, Herba Erigerontis and Radix Cyanotis vagae are united and applied in preventing and/or treating of diabetes and complication thereof, there is not yet report.
Summary of the invention
The object of the invention is to, a kind of new Pharmaceutical composition and uses thereof is provided, specifically, is Pharmaceutical composition and the purposes in the medicine of preparation treatment or prevent diabetes thereof that Herba Erigerontis extract and Cyanotis arachnoides P.E are made.
Technical scheme of the present invention: a kind of Pharmaceutical composition, it is take weight ratio as 0.1-10: 1 Herba Erigerontis extract and Cyanotis arachnoides P.E are made as active component.
In the aforesaid Pharmaceutical composition, described Herba Erigerontis extract is Herba Erigerontis lower alcohol extraction thing or Herba Erigerontis total phenols extract; Described Cyanotis arachnoides P.E is Radix Cyanotis vagae water extract or Radix Cyanotis vagae lower alcohol extraction thing.
In the aforesaid Pharmaceutical composition, described lower alcohol is methanol or ethanol.
In the aforesaid Pharmaceutical composition, contain scutellarin and list/pair caffeoyl quinic acid in the described Herba Erigerontis extract; Contain ecdyson and 3-acetyl group ecdyson in the described Cyanotis arachnoides P.E.
In the aforesaid Pharmaceutical composition, the weight content of scutellarin is 0.1%-50% in the described Herba Erigerontis extract, and the weight content of list/pair caffeoyl quinic acid is 1%-99%.
In the aforesaid Pharmaceutical composition, the weight content of ecdyson is 10%-98% in the described Cyanotis arachnoides P.E.
Herba Erigerontis extract can prepare like this: get the Herba Erigerontis herb, pulverize, extract 2～3 times with lower alcohol solvent, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, the concentrated solution dilute with water, filter, phenylethylene macroporous adsorbent resin on the filtrate is after water elution is extremely colourless, alcoholic solution eluting with 30%～95%, elution volume are 3～20 times of column volumes; Eluent is concentrated, is 7.0～7.5 with 10% sodium hydroxide solution adjust pH, and then spray drying gets the brown color powder, i.e. Herba Erigerontis total phenols extract.
Herba Erigerontis extract also can prepare like this: get the Herba Erigerontis herb, pulverize, extract 2～3 times with lower alcohol solvent, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, and the concentrated solution dilute with water is used first No. 120 gasoline extraction defats, water layer ethyl acetate extraction 3～4 times, the combined ethyl acetate part, concentrated, desolventizing, get brown color powder, i.e. Herba Erigerontis total phenols extract.
Cyanotis arachnoides P.E can prepare like this: get the dry herb of Radix Cyanotis vagae, pulverize, extract 2～3 times with lower alcohol solvent, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, the concentrated solution dilute with water, filter, phenylethylene macroporous adsorbent resin on the filtrate washes with water first after colourless, use 30%～95% alcoholic solution eluting, elution volume is 3～20 times of column volumes again; The eluent concentrating under reduced pressure gets dry buff powder, i.e. Radix Cyanotis vagae lower alcohol extraction thing.
Cyanotis arachnoides P.E also can prepare like this: get the Radix Cyanotis vagae herb, pulverize, use water extraction 2～3 times, merge extractive liquid,, concentrating under reduced pressure, use first No. 120 gasoline extraction defats, water layer ethyl acetate extraction 3-4 time, combined ethyl acetate part, concentrated, remove ethyl acetate, get buff powder, be i.e. the Radix Cyanotis vagae water extract.
In the aforesaid Pharmaceutical composition, the mixture replacing Herba Erigerontis extract that the list of the scutellarin of available 1%-50% weight or its sodium salt and 99%-50% weight/pair caffeoyl quinic acid or its sodium salt form substitutes Cyanotis arachnoides P.E with ecdyson; Namely make Pharmaceutical composition with mixture 0.1-10 weight portion and ecdyson 1 weight portion of the scutellarin of 1%-50% weight or the list of its sodium salt and 99%-50% weight/pair caffeoyl quinic acid or its sodium salt composition as active component.
Above-described Pharmaceutical composition can be used for preparing the medicine for the treatment of or prevent diabetes, also can be used for preparation and improves the diabetic complication symptom medicine of (as regulating blood fat, improve microcirculation, improving hemorheology etc.).
The inventor according to following Mechanism Design drug combination of the present invention: 1) Radix Cyanotis vagae has remarkable hypoglycemic activity, and its blood sugar lowering mechanism is relevant with insulin, is similar to the islets of langerhans sensitization; 2) flavones ingredients such as scutellarin in the Herba Erigerontis have the aldose reductase inhibitory action, can suppress the abnormal metabolism of polyhydric alcohol in the diabetes, can keep diabetes lower NADH/NAD in I/R process cardiac myocyte
+, keep ATP higher in the cell, promote K
+-Na
+Exchange, thus the cytosolic free calcium concentration in cardiomyocyte overload suppressed to the damage of diabetic cardiac muscle; 3) flavones ingredient in the Herba Erigerontis such as scutellarin energy dilating coronary blood vessel, increase coronary flow; 4) in the Herba Erigerontis flavones ingredient such as scutellarin and caffeoyl quinic acid esters composition such as 1,3-dicaffeoyl-quinic acid ester, 3,4-dicaffeoyl-quinic acid ester etc. can reduce blood viscosity, anticoagulant, increase ischemic myocardium collateral circulation blood supply, thereby improve myocardial ischemia; 5) Herba Erigerontis can improve microcirculation; 6) caffeoyl quinic acid ester composition has protective effect to neurocytes such as optic nervies in the Herba Erigerontis, and teleneuron pathological changes, oculopathy in the diabetic complication are improved effect.
In the present composition, when active component was used as medicine with form of extract, the content of scutellarin in Herba Erigerontis extract was 0.1%-50%, is preferably 1%, 5%, 10% or 30%; The content of list/pair caffeoyl quinic acid in Herba Erigerontis extract is 1%-80%, is preferably 10%, 20%, 40% or 50%; The content of ecdyson in Cyanotis arachnoides P.E is 10%-98%, is preferably 40%, 50%, 80% or 90%.
In order to ensure effect of the present invention, the applicant has carried out pharmacological experiment study to described Pharmaceutical composition, and is specific as follows:
After 8 weeks, with a week behind the lumbar injection STZ 40mk/kg, measure rat fasting blood-glucose at the high glucose and high fat forage feed, the rat that the screening fasting glucose is higher than 7mmol/L is the rat of modeling success.The rat of modeling success is divided into 5 groups at random, is respectively model group, sample 1, sample 2,3 groups in sample and positive drug matched group, add with normal rat as the blank group.Respectively 2 weeks of administration (blank group and model group give the distilled water of equal volume), water 12h is can't help in fasting after the last administration, and the tail venous blood sampling is surveyed fasting blood sugar with blood glucose meter, the results are shown in Table 1; Simultaneously, venous blood sampling is measured serum lipids, the results are shown in Table 2; And the situation of inspection rat serum rheology, the results are shown in Table 3.
Wherein sample 1 is Pharmaceutical composition I, and sample 2 is the Herba Erigerontis extract powders A among the embodiment 1, and sample 3 is the Cyanotis arachnoides P.E powder B among the embodiment 1.The positive control medicine is metformin.
Table 1 Pharmaceutical composition of the present invention is on the impact of blood glucose in diabetic rats
Annotate: * * and model group compare, P＜0.01.
Table 2 Pharmaceutical composition of the present invention is on the impact of diabetes rat blood fat
Annotate: * * and model group compare, P＜0.01.
The impact that table 3 Pharmaceutical composition of the present invention becomes the diabetes rat blood flow
Annotate: * * and model group compare, P＜0.01.
Can find out according to above-mentioned experimental result, Pharmaceutical composition of the present invention can reduce the blood sugar concentration of diabetes rat, and the doses dependency characteristic is arranged.But the powders A that forms Pharmaceutical composition in, low dose is all without hypoglycemic activity, heavy dose of group has certain hypoglycemic activity, powder B in, heavy dose of group all shows certain hypoglycemic activity.Powders A and powder B that the hypoglycemic activity explanation of Pharmaceutical composition I forms Pharmaceutical composition I have certain synergism, so that Pharmaceutical composition I has certain hypoglycemic activity.But with positive control drug phase ratio, hypoglycemic activity intensity a little less than.So Pharmaceutical composition of the present invention is fit to be applied to the diabetes patient that blood sugar level has necessarily been controlled, and is not suitable for be used to the case of needing fast reducing blood glucose badly.
Can find out according to table 2, Pharmaceutical composition I can improve every leading indicator of blood fat in the diabetes rat blood effectively, can reduce total TG, CHO and LDL content, the content of rising HDL, and also this effect is more remarkable than using separately the effect of powders A or powder B.Positive controls is little on the impact of the indices in the diabetes rat blood.Because the diabetes patient is general all with hyperlipemia, thus Pharmaceutical composition I for reducing diabetes patient's serum lipid concentrations, thereby improve the diabetic complication symptom that causes thus, therapeutical effect may be arranged.
Can find out according to table 3, Pharmaceutical composition I can improve the hemorheology feature of diabetes rat, this is to improving diabetes patient's hemorheology feature, thereby improves because the complication that the microcirculation disturbance that diabetes cause, blood viscosity increase cause has positive effect.And this effect is more remarkable than using separately the effect of powders A or powder B.Positive controls is little on the indices impact of diabetes rat hemorheology.
This shows, Pharmaceutical composition of the present invention can effectively reduce the blood sugar concentration of diabetes rat, and effectively reduces TG in the rat blood, CHO and LDL concentration, increases HDL content, effectively improves the hemorheology feature simultaneously; These effects are Herba Erigerontis extract (powders A) and the synergistic effects of Cyanotis arachnoides P.E (powder B) that form Pharmaceutical composition, and wherein any effect is more obvious than single use.
The specific embodiment
Can understand further the present invention by the following specific embodiments, but not be the restriction to content of the present invention.
Embodiments of the invention 1: the preparation of Pharmaceutical composition I
Get Herba Erigerontis herb 5kg, pulverize, add approximately 15 liters of 70% ethanol, be as the criterion to flood medical material and slightly to exceed, reflux 1 hour, inclining liquid, continues to add an amount of 70% ethanol, repeats same operation, extracts 3 times, for the last time medicinal residues is filtered.Merging filtrate, 40～60 ℃ are evaporated to approximately 5 liters of volumes, and concentrated solution is diluted with water to 10 liters, filters, and removes filtering residue.Filtrate is distributed in pretreated AB-8 macroporous adsorptive resins absorption, uses first 30 premium on currency eluting, uses 20 liter of 80% ethanol eluting again.80% ethanol eluent is concentrated into about 1 liter, be about 7.0 with 10% sodium hydroxide solution adjust pH, spray drying gets brown color powders A (being Herba Erigerontis extract), must measure and be that 126g, yield are 2.52% (in Herba Erigerontis herb raw material).In the brown color powders A, analyzing mensuration flavones Content Measurement of Scutellarin through HPLC is 10.5%, and measuring the caffeoyl quinic acid constituent content by the UV method is 63.5%.
Get the dry herb 10kg of Radix Cyanotis vagae, pulverize, add 60% alcohol-pickled flooding, reflux 1 hour leaches extracting solution, continues to add 60% ethanol, repeats same operation, extracts 3 times, for the last time medicinal residues is filtered.Merging filtrate, 40～60 ℃ are evaporated to approximately 5 liters of volumes, and concentrated solution is diluted with water to 10 liters, filters, and removes filtering residue.Filtrate is distributed in pretreated AB-8 macroporous adsorptive resins absorption, washes with water first, uses 80% ethanol eluting again, and elution volume is 5 times of column volumes.80% ethanol eluent concentrating under reduced pressure gets dry buff powder B (being Cyanotis arachnoides P.E) 91g, and yield is 0.91% (in Radix Cyanotis vagae herb raw material).Among the buff powder B, analyzing mensuration ecdyson content through HPLC is that 63.4%, 3-acetyl group ecdyson content is 8.2%.
Get powders A 50g and powder B 50g mix homogeneously, get Pharmaceutical composition I.Content Measurement of Scutellarin is 5.3% among the Pharmaceutical composition I, and caffeoyl quinic acid constituent content (UV method) is 31.8%, and ecdyson content is that 31.7%, 3-acetyl group ecdyson content is 4.1%.
Embodiments of the invention 2: the preparation of Pharmaceutical composition II
Get Herba Erigerontis herb 5kg, pulverize, add approximately 15 liters of 70% ethanol, be as the criterion to flood medical material and slightly to exceed; Reflux 1 hour, inclining liquid, continues to add an amount of 70% ethanol, repeats same operation, extracts 3 times, for the last time medicinal residues is filtered.Merging filtrate, 40～60 ℃ are evaporated to approximately 5 liters of volumes, concentrated solution is diluted with water to 10 liters, uses first No. 120 gasoline extraction defats, water layer ethyl acetate extraction 3-4 time, the combined ethyl acetate part, concentrating under reduced pressure is removed ethyl acetate, gets brown color powder C (being Herba Erigerontis extract), must measure and be that 138g, yield are 2.76% (in Herba Erigerontis herb raw material).In the brown color powder, analyzing mensuration flavones Content Measurement of Scutellarin through HPLC is 6.5%, and measuring the caffeoyl quinic acid constituent content by the UV method is 67.2%.
Get Radix Cyanotis vagae herb 10kg, pulverize, add entry, be as the criterion to flood medical material and slightly to exceed; Reflux 1 hour, inclining liquid, continues to add suitable quantity of water, repeats same operation, extracts 3 times, for the last time medicinal residues is filtered.Merging filtrate, 40～60 ℃ are evaporated to approximately 10 liters of volumes, use first No. 120 gasoline extraction defats, water layer ethyl acetate extraction 3-4 time, combined ethyl acetate part, concentrating under reduced pressure, remove ethyl acetate, get buff powder D (being Cyanotis arachnoides P.E), the amount of getting is 85g, and yield is 0.85% (in Radix Cyanotis vagae herb raw material).Among the buff powder D, analyzing mensuration ecdyson content through HPLC is that 72.6%, 3-acetyl group ecdyson content is 8.8%.
Get powder C 80g and powder D 20g mix homogeneously, get Pharmaceutical composition II.Content Measurement of Scutellarin is 5.2% among the Pharmaceutical composition II, and caffeoyl quinic acid constituent content (UV method) is 53.8%, and ecdyson content is that 14.5%, 3-acetyl group ecdyson content is 1.8%.
Embodiments of the invention 3: the application of Pharmaceutical composition I
The preparation of medicinal tablet: get it filled with composition I 100g, starch 50g, 10% starch slurry 10g and magnesium stearate 2g; Behind Pharmaceutical composition I and starch mix homogeneously, add 10% starch slurry and make soft material, cross 14 mesh sieves and granulate, dry under 70-80 ℃ of temperature, cross 12 mesh sieve granulate, after adding magnesium stearate and mixing, be pressed into 1000, and get final product.Every contains medicinal composition I 100mg, can be used for treatment or prevent diabetes.
Embodiments of the invention 4: the application of Pharmaceutical composition II
The preparation of medicament capsule: get it filled with composition I I 100g, starch 50g and magnesium stearate 2g; Behind the starch and magnesium stearate mix homogeneously with Pharmaceutical composition II and 80 ℃ of dryings, be distributed into 1000 capsules, and get final product.Every capsules contains medicinal composition I I100mg, can be used for improving the diabetic complication symptom, as regulating blood fat, improve microcirculation, improving hemorheology etc.
Embodiments of the invention 5: the preparation of Pharmaceutical composition III and application
Get scutellarin or its sodium salt 16g, list/pair caffeoyl quinic acid or its sodium salt 24g and ecdyson 60g, mix homogeneously gets Pharmaceutical composition III.Scutellarin or its sodium salt content are 16% among the Pharmaceutical composition III, and list/pair caffeoyl quinic acid or its sodium salt content are 24%, and ecdyson content is 60%.Behind Pharmaceutical composition III100g and starch 50g and magnesium stearate 2g mix homogeneously, be distributed into 1000 capsules, namely get capsule.Every capsules contains medicinal composition I II100mg, can be used for treatment or prevent diabetes.
Claims (8)
1. Pharmaceutical composition, it is characterized in that: it is take weight ratio as 0.1-10: 1 Herba Erigerontis extract and Cyanotis arachnoides P.E are made as active component; Described Herba Erigerontis extract adopts the method preparation of one of following A, B, and described Cyanotis arachnoides P.E adopts the method preparation of one of following C, D:
A, get the Herba Erigerontis herb, pulverize, extract 2～3 times with lower alcohol solvent, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, the concentrated solution dilute with water, filter, phenylethylene macroporous adsorbent resin on the filtrate is after water elution is extremely colourless, alcoholic solution eluting with 30%～95%, elution volume are 3～20 times of column volumes; Eluent is concentrated, is 7.0～7.5 with 10% sodium hydroxide solution adjust pH, and then spray drying gets the brown color powder, and get final product;
B, get the Herba Erigerontis herb, pulverize, extract 2～3 times with lower alcohol solvent, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, and the concentrated solution dilute with water is used first No. 120 gasoline extraction defats, water layer ethyl acetate extraction 3～4 times, the combined ethyl acetate part, concentrated, desolventizing, get the brown color powder, and get final product;
C, get the dry herb of Radix Cyanotis vagae, pulverize, extract 2～3 times with lower alcohol solvent, merge extractive liquid,, concentrating under reduced pressure reclaims solvent, the concentrated solution dilute with water, filter, phenylethylene macroporous adsorbent resin on the filtrate washes with water first after colourless, use 30%～95% alcoholic solution eluting, elution volume is 3～20 times of column volumes again; The eluent concentrating under reduced pressure gets dry buff powder, and get final product;
D, get the Radix Cyanotis vagae herb, pulverize, with water extraction 2～3 times, merge extractive liquid,, concentrating under reduced pressure is used first No. 120 gasoline extraction defats, and water layer is with ethyl acetate extraction 3-4 time, and the combined ethyl acetate part is concentrated, removes ethyl acetate, gets buff powder, and get final product.
2. Pharmaceutical composition according to claim 1, it is characterized in that: described lower alcohol is methanol or ethanol.
3. Pharmaceutical composition according to claim 1 and 2 is characterized in that: contain scutellarin and list/pair caffeoyl quinic acid in the described Herba Erigerontis extract; Contain ecdyson and 3-acetyl group ecdyson in the described Cyanotis arachnoides P.E.
4. Pharmaceutical composition according to claim 3, it is characterized in that: the weight content of scutellarin is 0.1%-50% in the described Herba Erigerontis extract, the weight content of list/pair caffeoyl quinic acid is 1%-99%.
5. Pharmaceutical composition according to claim 3, it is characterized in that: the weight content of ecdyson is 10%-98% in the described Cyanotis arachnoides P.E.
6. Pharmaceutical composition according to claim 4; it is characterized in that: the mixture replacing Herba Erigerontis extract with the scutellarin of 1%-50% weight or the list of its sodium salt and 99%-50% weight/pair caffeoyl quinic acid or its sodium salt composition substitutes Cyanotis arachnoides P.E with ecdyson.
7. such as the purposes of each described Pharmaceutical composition among the claim 1-6 in the medicine of preparation treatment or prevent diabetes.
8. improve purposes in the medicine of diabetic complication symptom such as each described Pharmaceutical composition among the claim 1-6 in preparation.
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| CN 201210036753 CN102526151B (en) | 2012-02-19 | 2012-02-19 | Medicinal composition and application thereof |
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| CN102526151B true CN102526151B (en) | 2013-10-16 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1246363A (en) * | 1999-08-04 | 2000-03-08 | 中国科学院昆明植物研究所 | Medicine for treating diabets mellitus and its preparing process |
| CN1280010A (en) * | 2000-06-12 | 2001-01-17 | 昆明制药股份有限公司 | Oral medicine for treating diabetes and its production method |
| CN1833668A (en) * | 2005-12-06 | 2006-09-20 | 深圳市生物谷科技有限公司 | Medicinal compsns. having cooperative action |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1246363A (en) * | 1999-08-04 | 2000-03-08 | 中国科学院昆明植物研究所 | Medicine for treating diabets mellitus and its preparing process |
| CN1280010A (en) * | 2000-06-12 | 2001-01-17 | 昆明制药股份有限公司 | Oral medicine for treating diabetes and its production method |
| CN1833668A (en) * | 2005-12-06 | 2006-09-20 | 深圳市生物谷科技有限公司 | Medicinal compsns. having cooperative action |
Non-Patent Citations (2)
| Title |
|---|
| 孙宏伟等.灯盏细辛治疗老年糖尿病并发脑梗死.《中西医结合心脑血管病杂志》.2006,第4卷(第6期),第559-561页. |
| 灯盏细辛治疗老年糖尿病并发脑梗死;孙宏伟等;《中西医结合心脑血管病杂志》;20060630;第4卷(第6期);第559-561页 * |
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