CN103638073B - Penthorum chinense pursh extract is preparing the application in hypoglycemic drug - Google Patents
Penthorum chinense pursh extract is preparing the application in hypoglycemic drug Download PDFInfo
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- CN103638073B CN103638073B CN201310608323.4A CN201310608323A CN103638073B CN 103638073 B CN103638073 B CN 103638073B CN 201310608323 A CN201310608323 A CN 201310608323A CN 103638073 B CN103638073 B CN 103638073B
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Abstract
The invention discloses penthorum chinense pursh extracts to prepare the application in hypoglycemic drug therapeutic agent.Penthorum chinense pursh extract of the present invention passes through experiment: (1) external alpha-amylase inhibitory activity experiment, penthorum chinense pursh extract has significant inhibiting effect to alpha-amylase as the result is shown.(2) penthorum chinense pursh extract is to mouse starch tolerance test, the results showed that penthorum chinense pursh extract of the present invention can be substantially reduced mouse to the blood sugar concentration after starch.(3) acute toxicity test of the penthorum chinense pursh extract stomach-filling to mouse, as the result is shown to In Treatment of Hyperglycemia while have no obvious toxic-side effects.Therefore, the present invention provides new approach for clinical prevention diabetes, and penthorum chinense pursh extract preparation method of the present invention is easy, there is biggish clinical value.
Description
Technical field
The present invention relates to Chinese medical extracts, and in particular to the application of Chinese medical extract more particularly to penthorum chinense pursh extract exist
Prepare the application in hypoglycemic drug.
Background technique
Due to improvement of living standard, the change of dietary structure, the rhythm of life being becoming tight day and few dynamic lifes sat more
Factors, global diabetes morbidity rapid development, the diabetes such as mode living have become after tumour, cardiovascular pathological changes
The third-largest chronic disease for seriously threatening human health.When diabetic is after diet and exercise therapy, the control of blood glucose
When cannot still reach therapeutic purpose, drug therapy need to be used.For this purpose, the effective hypoglycemic drug of research and development has extremely
Important meaning.Currently, mainly having oral hypoglycemic drug and injection hypoglycemic medicine for hypoglycemic drug.Wherein orally-taken blood sugar reducing
Drug is divided into alpha-glucosidase inhibitor (acarbose), biguanides (melbine) class based on non-insulin-based drug, promotees pancreas islet
Plain secrete pharmaceutical class and insulin sensitizer.Alpha-glucosidase inhibitor, biguanides and insulin increase income agent exclusive use and generally will not
May still it occur when causing hypoglycemia, but being used in conjunction with other drugs；And the antidiabetic drug of biguanides is larger to the injury of stomach, is easy
Lead to indigestion, may result in beta-oxybutyria and lactic acidosis when serious.Modern pharmacological research proves that many single medicinal materials have
There is blood sugar reducing function, TCM Treatment of Diabetes not only reduces blood glucose, it is often more important that focus on prevention and treatment diabetic complication, play and mention
High quality of life and the effect for extending the service life.Penthorum chinense pursh (Penthorum chinense Pursh) also known as pull root vegetables, Chinese penthorum herb,
Mountain delicacy pearl etc. is recorded according to " Tian Bao book on Chinese herbal medicine ", herbal for Relief of Famines etc., and penthorum chinense pursh has dredging collateral and promoting blood circulation, dissolving stasis dehumidifying, promoting blood circulation to remove blood stasis etc.
Effect.Document report penthorum chinense pursh has the pharmacological activity of prevention and treatment hepatitis, Liver protection, but so far there is not yet penthorum chinense pursh extract is treated
The report of hyperglycemia.
Summary of the invention
Technical problem to be solved by the present invention lies in purposes of the researching and designing penthorum chinense pursh extract in pharmacy.
The present invention provides penthorum chinense pursh extracts to prepare the application in hypoglycemic drug.
Penthorum chinense pursh extract of the present invention is as made from following method:
After penthorum chinense pursh herb crushes, (80 DEG C) are mentioned 3 times with 20%~80% ethyl alcohol heat, and each dosage is penthorum chinense pursh weight
10 times of amount W/L, each extraction time are 1 hour, merge and are concentrated to dryness for 50~60 DEG C after No. 3 extracting solutions, then 50~
Drying to constant weight under 60 DEG C of environment, obtains penthorum chinense pursh extract.
Penthorum chinense pursh raw material can be by being commercially available.
Penthorum chinense pursh extract of the present invention passes through following effect experiment, it was demonstrated that it has the function of hypoglycemic.
(1) external alpha-amylase inhibitory activity test
Sample is dissolved in DMSO, is configured to the solution of 10mg/ml, the activity of alpha-amylase is according to Caraway method
(Am.J.Clin.Path., 1959,32,97-99) detection, the activity of alpha-amylase can be inhibited by measuring penthorum chinense pursh extract.It is real
The inhibitory activity for testing penthorum chinense pursh extract alpha-amylase under 278ug/ml concentration as the result is shown is more than positive drug (acarbose).
Therefore penthorum chinense pursh extract plays the role of relatively strong hypoglycemic, can be used for the treatment of improper hyperglycemic disorder.
(2) internal mouse starch tolerance test
Hypoglycemic effect using mouse starch tolerance model, after observing penthorum chinense pursh extract gastric infusion of the present invention.It is real
It tests the results show that the high, medium and low dosage group of penthorum chinense pursh extract has significant hypoglycemic effect to mouse compared with model group, and
And a certain amount effect relationship is presented in high, medium and low three dosage group.
(3) intragastric administration on mice gives maximal tolerance dose MTD > 8.0g/kg of penthorum chinense pursh extract, is that penthorum chinense pursh extract is effective
40 times of dosage (200mg/kg), and have not seen that mouse has obvious exception.Therefore penthorum chinense pursh extract is to the same of In Treatment of Hyperglycemia
Shi Bingwu obvious toxic-side effects.
Therefore, penthorum chinense pursh extract of the present invention can be used for preparing hypoglycemic drug.
Drug of the present invention is the pharmaceutical composition being made of penthorum chinense pursh extract as active constituent and pharmaceutic adjuvant.
Penthorum chinense pursh extract preparation method of the present invention is easy, has apparent hypoglycemic activity, to prevent and treat improper high blood
Sugar provides the foundation, and new Chinese medicine is provided for clinical treatment hyperglycemia, and curative for effect, Small side effects have biggish clinic to answer
With value.
Detailed description of the invention
Fig. 1 penthorum chinense pursh 20%, 50%, 80% ethanol extract HPLC comparative diagram
Ordinate is response intensity, and unit (AU), abscissa is time, unit (minute)
A: 20% ethanol extract of penthorum chinense pursh；B: 50% ethanol extract of penthorum chinense pursh；C: 80% ethanol extract of penthorum chinense pursh.
Fig. 2 penthorum chinense pursh extract acts on the reduction of mouse postprandial blood sugar
Ordinate is blood glucose value, and unit (m mol), abscissa is time, unit (minute)
A: model control group；B: low dose group；C: positive drug group；D: middle dose group；E: blank control group；F: high dose group
The dose-effect relationship of Fig. 3 penthorum chinense pursh extract drop mouse postprandial blood sugar
Ordinate is AUC: area under the curve, unit (mmol/Lmin)
Horizontal axis is different groups: A: model control group；B: penthorum chinense pursh extract 200mg/kg group；C: penthorum chinense pursh extract
400mg/kg group；D: penthorum chinense pursh extract 600mg/kg group；E: positive controls；F: blank group
Note:**Administration group compares P < 0.05 with model group
Specific embodiment:
Nonlimiting examples are used below, and the invention will be further described.
Embodiment is raw materials used to be commercially available.
The preparation of 1 penthorum chinense pursh extract of embodiment
After 5kg penthorum chinense pursh (commercially available) herb is crushed, with 80% ethyl alcohol 50L soaked overnight, 80% ethyl alcohol heat mentions (80
DEG C) 3 times, each dosage 50L, each extraction time is 1 hour, merges and is concentrated to dryness for 50~60 DEG C after No. 3 extracting solutions, so
Drying to constant weight under 50~60 DEG C of environment afterwards (564g), is 11.3% by crude drug meter yield.The penthorum chinense pursh extract being prepared into
HPLC(efficient liquid phase is carried out by embodiment 4) detection.
The preparation of 2 penthorum chinense pursh extract of embodiment
After 5kg penthorum chinense pursh (commercially available) herb is crushed, with 50% ethyl alcohol 50L soaked overnight, 50% ethyl alcohol heat mentions (80
DEG C) 3 times, each dosage 50L, each extraction time is 1 hour, merges and is concentrated to dryness for 50~60 DEG C after No. 3 extracting solutions, so
Drying to constant weight under 50~60 DEG C of environment afterwards (541g), is 10.8% by crude drug meter yield.The penthorum chinense pursh extract being prepared into
HPLC(efficient liquid phase is carried out by embodiment 4) detection.
The preparation of 3 penthorum chinense pursh extract of embodiment
After 5kg penthorum chinense pursh (commercially available) herb is crushed, with 20% ethyl alcohol 50L soaked overnight, 20% ethyl alcohol heat mentions (80
DEG C) 3 times, each dosage 50L, each extraction time is 1 hour, merges and is concentrated to dryness for 50~60 DEG C after No. 3 extracting solutions, so
Drying to constant weight under 50~60 DEG C of environment afterwards (516g), is 10.3% by crude drug meter yield.The penthorum chinense pursh extract being prepared into
HPLC(efficient liquid phase is carried out by embodiment 4) detection.
4 penthorum chinense pursh 20% of embodiment, 50%, 80% ethanol extract HPLC comparative diagram
The penthorum chinense pursh extract that embodiment 1,2,3 obtains is compared into efficient liquid phase respectively, as a result, it has been found that 3 kinds of extractions
The penthorum chinense pursh extract ingredient that method obtains is shown in Fig. 1 almost without difference.
Used HPLC condition is as follows: chromatographic column: Diamonsil C18column (4.6mm × 250mm, 5 μm,
Dikma)；Mobile phase: A phase is acetonitrile, and B phase is 0.2% formic acid buffer (pH=3.0)；Gradient elution: 0min-65min-
70min, mobile phase A: the ratio of B is 10:90-50:50-90:10；Flow velocity: 1.0ml/min, runing time 70min detect wave
Long 280nm, column temperature are 30 DEG C；10 μ l of sample volume.
The external alpha-amylase inhibitory activity test of 5 penthorum chinense pursh extract of embodiment
1 materials and methods
1.1 trial drug
Penthorum chinense pursh extract prepared by embodiment 1
1.2 experimental material
Acarbose (Bayer, 50mg/ piece), glucose determination reagent box (glucose oxidase-enzymatic peroxidation, Shanghai
Rong Sheng Bioisystech Co., Ltd) alpha-amylase (Wako Pure Chemicals Ind., Osaka, Japan), microplate reader
(EIx800, Biotek), 96 porocyte culture plates (Corning/Costar)
1.3 experimental method
1.3.1 color developing agent: first by 10.8 grams of sodium benzoate, 5 grams of potassium iodide are dissolved in 400ml water, are then settled to
500ml。
1.3.2 alpha-amylase is configured to 27.8mg/L solution (PH=6.9) with the PIPES buffer of 25mM.Huang is caught up in weighing
Careless extract (embodiment 1 is made) is made into the solution of 10mg/ml with DMSO, then be diluted to respectively with water 139ug/ml and
278ug/ml, while it is 278ug/ml solution that acarbose, which is configured to concentration with distilled water,；Starch is configured to distilled water
The starch solution that concentration is 0.16%.
1.3.3 it with 96 porocyte culture plates, tests and is divided into 4 groups, respectively blank group control (distilled water), positive controls
(acarbose), 2 sample measurement groups, every group sets 6 multiple holes.
1.3.4 the phase organized into groups on plate hole is added in the penthorum chinense pursh extract of above-mentioned 2 concentration and acarbose solution respectively
Answer each hole, every hole 25ul sample solution, blank control group adds equal amount of distilled water, respectively at every group wherein three holes 12.5ul is added
12.5ul distilled water is added in alpha-amylase solution, the other three hole, and 37 DEG C of temperature incubate 10min, and it is aobvious that 500uL finally is added respectively at each hole
Color reagent terminates reaction, measures absorbance (A) under microplate reader 630nm wavelength, presses Liu Fangfa and calculates inhibiting rate (%): inhibiting
Rate (%)=[1- (ASample is not enzyme-ASample is enzyme)/(ABlank control is not enzyme-ABlank control is enzyme)]×100%
2 experimental results
The external alpha-amylase inhibitory activity of 2 penthorum chinense pursh extract of table (n=3,)
3 conclusions
For the external alpha-amylase inhibitory activity of penthorum chinense pursh extract the results showed that after administration, penthorum chinense pursh extract can be bright
It is aobvious to inhibit alpha-amylase activity；Under 139ug/ml, 278ug/ml concentration, alpha-amylase inhibitory activity is even more than positive drug for it
(acarbose) shows stronger hypoglycemic effect.
Mouse starch tolerance test in 6 penthorum chinense pursh extract body of embodiment
1 materials and methods
1.1 experimental material
Acarbose (Bayer, 50mg/ piece), cornstarch (one recruits fresh, packed, 458g), blood sugar detection test paper (Major
II)
1.2 experimental animal
ICR mouse (Shanghai Slac Experimental Animal Co., Ltd., animal certificate number: the Shanghai SCXK() 2012-0002；Body
Weight: 20g or so；Gender: male；Every group 10).
1.3 penthorum chinense pursh extract
Penthorum chinense pursh extract is prepared by embodiment 1, is dried (drying to constant weight under 50~60 DEG C of environment), then accurate respectively
Penthorum chinense pursh extract 400mg, 800mg, 1200mg are weighed, 10ml0.5% sodium carboxymethylcellulose is added, being made into concentration respectively is
After the suspension of 40mg/ml, 80mg/ml and 120mg/ml mix in equal volume with 2.5g/kg starch, as penthorum chinense pursh extract
Low, middle and high dose groups, the concentration of penthorum chinense pursh extract are respectively 20mg/ml, 40mg/ml and 60mg/ml.
1.4 medication
Administered volume is 0.1ml/10g weight, and model control group is given isometric starch, all given using administration by gavage
Medicine.The dosage for determining penthorum chinense pursh extract is respectively 200mg/kg, 400mg/kg and 600mg/kg.
1.5 experimental method
60 ICR mouse are randomly divided into 6 groups, after adaptive feeding 2-3 days, weigh weight, are grouped at random by weight
(every group of weight is equal), every group 10.Remove food and padding starvation 12h, be divided into blank group, model group, positive controls (Ah
Card wave sugar, dosage 25mg/kg), penthorum chinense pursh extract low, middle and high dose groups, then gastric infusion together.Blank group is pressed
0.1ml/10g weight gives 0.5% sodium carboxymethylcellulose.To measuring blood glucose before sugar, 30min, 60min, 120min after to sugar
When respectively measure blood glucose
Once, AUC (area under the curve) then is calculated, calculation formula is as follows:
Note: BG:blood glucose blood glucose
Experimental data is for statistical analysis using spss13.0, and multinomial data compare using single factor test between group
Variance analysis, data withIt indicates, P < 0.05 is used as significant difference.
2 experimental results
Mouse each group body weights, are shown in Table 3
(data are with mean for the body weights of mouse before table 3 is administeredIt indicates, g, n=10)
Mouse is shown in Table 4, Fig. 2, Fig. 3 to the blood glucose and AUC value of 30min, 60min, 120min after sugar to (0min) before sugar.
Mouse postprandial blood sugar after 4 penthorum chinense pursh extract stomach-filling of table (mmol/L, n=10,)
Note: administration group is compared with model group**P<0.05
3 conclusions
Before administration, each experimental mice weight does not have significant difference；After administration, compared with model group, penthorum chinense pursh is extracted
Object low, middle and high dose groups gastric infusion can significantly reduce the postprandial blood sugar of mouse, and high, medium and low three dosage group is presented centainly
Dose-effect relationship.Therefore penthorum chinense pursh extract has therapeutic effect to hyperglycemia.
Acute toxicity test (MTD method) of the 7 penthorum chinense pursh extract stomach-filling of embodiment to mouse
1, materials and methods
1.1 experimental animal
ICR mouse (Shanghai Slac Experimental Animal Co., Ltd., animal certificate number: the Shanghai SCXK() 2012-0002；Body
Weight: 20g or so；Gender: male).
1.3 penthorum chinense pursh extract
Penthorum chinense pursh extract is prepared by embodiment 1, is dried (drying to constant weight under 50~60 DEG C of environment), precision, which weighs, catches up with Huang
10ml0.5% sodium carboxymethylcellulose (0.5%CMC-Na) is added in careless extract 2.0g, and being made into concentration is respectively the outstanding of 0.2g/ml
Supernatant liquid.
1.4 medication
Administered volume is 0.4ml/10g, determines that the dosage of mouse penthorum chinense pursh extract is 8.0g/kg.Control group
To isometric solvent (0.5%CMC-Na), all it is administered using administration by gavage.
2, experimental result
Mouse is quieter after gastric infusion, and activity is normal.The equal nothing such as other situations such as diet, activity, hair color, excrement
Anomaly.Every the weight of animals has increase (being shown in Table 5) after 14 days, has no dead.
5 penthorum chinense pursh extract stomach-filling of table to mouse weight influence (g, n=8,)
3, experiment conclusion
Intragastric administration on mice gives maximal tolerance dose MTD > 8.0g/kg of penthorum chinense pursh extract, is that penthorum chinense pursh extract is hypoglycemic
40 times of effective dose (200mg/kg), and have not seen that mouse has obvious exception.Therefore penthorum chinense pursh extract is to In Treatment of Hyperglycemia
While have no obvious toxic-side effects.
Claims (2)
1. penthorum chinense pursh extract is preparing the application in hypoglycemic drug；The penthorum chinense pursh extract is made by following method:
It after penthorum chinense pursh herb crushes, is mentioned 3 times with 20%~80% 80 DEG C of heat of ethyl alcohol, the dosage of each ethyl alcohol is 10 times of penthorum chinense pursh weight
W/V is measured, each extraction time is 1 hour, merges and is concentrated to dryness for 50~60 DEG C after No. 3 extracting solutions, then 50~60 DEG C of rings
It is further dried under border to constant weight, obtains penthorum chinense pursh extract.
2. application as described in claim 1, which is characterized in that the drug is by penthorum chinense pursh extract as sole active agent
With the pharmaceutical composition of pharmaceutic adjuvant composition.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1431011A (en) * | 2003-01-20 | 2003-07-23 | 四川绿色药业科技发展股份有限公司 | Oral medicine for curing hepatitis |
| CN102093459A (en) * | 2011-01-10 | 2011-06-15 | 中国人民解放军第二军医大学 | Penthorum chinense pursh extract and preparation method and application thereof |
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| KR100523441B1 (en) * | 2002-08-19 | 2005-10-25 | 주식회사 엠디바이오알파 | Active extracts from natural plants having anti-obesity and anti-diabetes |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1431011A (en) * | 2003-01-20 | 2003-07-23 | 四川绿色药业科技发展股份有限公司 | Oral medicine for curing hepatitis |
| CN102093459A (en) * | 2011-01-10 | 2011-06-15 | 中国人民解放军第二军医大学 | Penthorum chinense pursh extract and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 肝苏颗粒治疗非酒精性脂肪性肝炎临床观察;张长法等;《药物流行病学杂志》;20071231;第16卷(第1期);第5-7页，尤其是第5页摘要结论部分和第7页左栏第1段 |
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