CN109419832A - Golden pheasant hair grass is preparing the application in hypoglycemic drug - Google Patents
Golden pheasant hair grass is preparing the application in hypoglycemic drug Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
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Abstract
Purposes of the golden pheasant provided by the invention hair grass in hypoglycemic, through experimental results demonstrate the careless extract of golden pheasant hair has significant hypoglycemic effect, while adjustable diabetic mice blood lipid level to diabetic mice.The careless extract of golden pheasant hair can also enhance the expression of target gene adiponectin, accelerate the decomposition of fat.The careless extract of golden pheasant hair of the present invention has good therapeutic effect to diabetes simultaneously.The careless extraction process of active component of golden pheasant hair of the present invention is simple, is suitble to industrialized production.
Description
Technical field
The present invention relates to golden pheasant hair grass, and in particular to golden pheasant hair grass is preparing the application in hypoglycemic drug.
Background technique
It is excessive in overnutrition, static sexuality increase and operating pressure as people's lives level is continuously improved
Under cross influence, the incidence of diabetes is quickly riseing.Global diabetic population has developed to 2.85 hundred million people, China within 2010
Diabetic population is more than 9,000 2 million, separately with the presence of nearly 100,000,000 5 thousand ten thousand population impaired fasting glucose and/or impaired glucose tolerance
Diabetes early stage shows.It is counted according to IMS, global diabetes Market scale breaks through 30,000,000,000 within 2009, reaches 304.06 hundred million dollars;
Reach within 2010 34900000000 dollars, increases by 12.32.Influenced due to being glided by global economy, by 2015 between global diabetes take
Though being down to 4-7% with annual growth, treatment diabetes medicament total expenditure, which allows, is up to 45,000,000,000 dollars, is in all medical diseases
Sick field disease pays second place.
According to different with the distribution in different crowd the reason of leading to disease, diabetes are often divided into I type glycosuria by clinic
Disease, type-2 diabetes mellitus.In China, type 2 diabetes patient accounts for diabetic about 95%, and has extension and rejuvenation to incline
To.Type-2 diabetes mellitus, also referred to as Non-Insulin Dependent Diabetes Mellitus, insulin secretion is normal or increases, but liver, fatty group
Knitting reduces with skeletal muscle, towards insulin sensibility, i.e. insulin resistance, and patient is mostly to grow up.Type-2 diabetes mellitus pathogenesis is main
Have: receptor defects cause insulin sensibility in conjunction with receptor to reduce on the cell membrane of insulin target cell, make extracellular
Glucose, which cannot sufficiently be absorbed to utilize by human body, leads to blood glucose rise;Insulin receptor substrate defect.Insulin receptor substrate category
Adaptor protein in cytoplasm, wide variety of effector molecules, the mediated cell such as main connection insulin receptor are anti-to insulin etc.
It answers;Insulin signal transduction defect.Diabetes can cause the complications such as the heart, brain, kidney, blood vessel, and lethal disability rate is high,
The problem of diabetes are brought gets worse, and seriously threatens human health, how to prevent and treat diabetes and has become the world of medicine and pays close attention to
A problem.
The key agents of clinical treatment type II diabetes are thiazolidinediones (TZDs) insulin sensitizers at present, such as
Rosiglitazone, Pioglitazone etc.;But thiazolidinediones (TZDs) insulin sensitizer, which has, leads to the pairs such as oedema, weight gain
Act on [Malinowski J M, Bolesta S.Rosiglitazone in the treatment oftype 2
Diabetes mellitus:a critical review [J] .Clin Ther, 2000,22 (10): 1151-1168];Simultaneously
Also there is potentially hazardous [Nissen S E, Wolski K.Efect of rosiglitazone on the to angiocarpy aspect
risk ofmyocar-dial infaretion and death from cardiovascular causes[J].N Engl
J Med, 2007,356 (24): 2457-2471];Hipbone and non-spinal bone osteoporosis occurs using 2 years or more patients
Property fracture risk increase two to three times of [Meier C, Kraenzlin ME, BodmerM, et al.Use of
2008 168:820-825 of thiazolidinediones and fracture risk [J] Arch Intern Med].
On the other hand, diabetes are as one group of lifelong participation metabolic as caused by multi-pathogenesis characterized by chronic hyperglycemia
Disease, usually individualism, complication (such as diabetes mellitus hyperlipidemia, diabetes) do not happen occasionally.Diabetes
(Diabetic Foot, DF), also known as diabetic acromelic gangrene refer to diabetic because merging neuropathy and various differences
Degree peripheral vascular disease become caused by limbs blood supply insufficiency, sensory disturbance, concurrent infection, with acrodynia, ulcer formed and
(or) destruction of deep tissue be main feature one group of disease.Diabetes be diabetic's amputation disable, dead and energy
The major reason that power is lost.About diabetes, specific drug there is no at present.It is low to develop side effect, effective novel glycosuria
Medicine and diabetes complicated disease drug are very urgent.
Summary of the invention
In order to solve the problems in the prior art, according to the first aspect of the invention, the purpose of the present invention is to provide one
The completely new hypoglycemic medicine of kind has significant hypoglycemic effect, while few side effects, highly-safe.
The object of the present invention is achieved like this:
The application of golden pheasant hair grass and its extract in preparation prevention or treatment diabetes medicament.
An embodiment according to the present invention, golden pheasant hair grass and its extract of the present invention are maintaining body glycolipid metabolism flat
Application in weighing apparatus drug.
An embodiment according to the present invention, golden pheasant hair grass and its extract of the present invention are in preparation prevention or treatment glycosuria
Application in foot disease drug.
An embodiment according to the present invention, golden pheasant hair grass and its extract of the present invention are in preparation prevention or treatment glycosuria
Disease is with the application in high blood cholesterol drug.
An embodiment according to the present invention, golden pheasant hair grass and its extract of the present invention are in four oxygen of preparation prevention or treatment
Application in diabetes caused by pyrimidine.
An embodiment according to the present invention, golden pheasant hair grass and its extract of the present invention are in preparation prevention or treatment kidney
Application in diabetes caused by parathyrine.
The present invention provides the preparation method of the careless extract of golden pheasant hair.In the extraction process of the careless blood-sugar decreasing active of golden pheasant hair
In, it was discovered by researchers that the factors such as type, concentration, water temperature, extraction time of acid are directly related to the hypoglycemic effect of extract;
Once controlling bad, in fact it could happen that extract blood sugar decreasing effect is poor, even without hypoglycemic effect.Ironically, micro-
In wave extraction process, the effective component extracted by factors such as different type, concentration, water temperature, the extraction times of acid, Ke Nengbiao
Reveal different therapeutic effects, than if any extract for treating antihypertensive effect it is good, some extract for treating hyperlipidemia effects compared with
It is good.And the present invention finally found that, by many experiments by the acetic acid of 4-7 times of 0.1-1.5M, in conjunction with 70-90 DEG C of water temperature
It is aided with the combination of the raw materials and step such as hydrolysis 10-30 minutes, the careless active constituent of golden pheasant hair of extraction is especially sugared for diabetes
Urinating foot disease and diabetes mellitus hyperlipidemia has good curative effect.
An embodiment according to the present invention, the above-mentioned careless extract of golden pheasant hair are prepared by the following method:
In the aqueous acetic acid for the 0.1-1.5M that golden pheasant hair grass is added 4-7 times, in temperature 70-90 in microwave reactor
DEG C hydrolysis 10-30 minutes;It then cools to room temperature, with macroporous adsorption resin chromatography depickling, is first eluted with water to efflux and is
Property, the ethanol elution of 20-95% is then used, until thin-layer chromatography detection, without purple dot, concentration both obtained.
Preferably, the concentration of above-mentioned aqueous acetic acid is 0.8-1.2M.
The utility model has the advantages that
The purposes that the present invention provides a kind of traditional Chinese medicines (golden pheasant hair grass) in hypoglycemic, through experimental results demonstrate gold
Chicken feather grass extract has significant hypoglycemic effect, while adjustable diabetic mice blood lipid level to diabetic mice.With
Model group compares, and pharmaceutical composition of the present invention can significantly reduce alloxan and cause blood glucose in diabetic mice value (P < 0.05), and energy
It significantly reduces adrenaline and causes blood glucose in diabetic mice value (P < 0.05).Administration group mouse triacylglycerol, low-density lipoprotein contain
Under amount is significant (P < 0.05), hdl concentration significantly increases (P < 0.05).The careless extract of golden pheasant hair can also enhance target base
Because of the expression of adiponectin, accelerate the decomposition of fat.It is verified through a large amount of clinical trials, the careless extract of golden pheasant hair of the present invention is to diabetes
Foot has good therapeutic effect, and especially to 0, I and II diabetes, obvious effective rate is higher than 90%, wherein being even more to control for 0 grade
More rate is 100%.For more serious three, level Four, obvious effective rate is also above 80%, even serious Pyatyi, efficient
Close to 70%.The careless extract of golden pheasant hair of the present invention has wide development prospect to significant effect during diabetes.This hair
The bright careless extraction process of active component of golden pheasant hair is simple, is suitble to industrialized production.
Specific embodiment
The present invention is specifically described below by specific embodiment, it is pointed out here that following embodiment is served only for this hair
It is bright to be further described, it should not be understood as limiting the scope of the invention, the person skilled in the art of this field can root
Some nonessential modifications and adaptations are made to the present invention according to foregoing invention content.All raw materials of the present invention and reagent are commercially available
Product.Unless otherwise specified, the number is parts by weight to the present invention, and the percentage is mass percent.
(1) preparation of the careless active constituent of golden pheasant hair of the present invention
Embodiment 1
The golden pheasant hair grass of crushing is added in a reservoir, and the 1.2M acetic acid of 6 times of amounts is added, in 1000W microwave reactor
It is hydrolyzed 25 minutes in 86 DEG C.Reaction solution is cooled to room temperature, and upper resin column AB8 absorption is washed to PH7.2, sequentially with 20%, 60%,
80%, 95% ethyl alcohol is eluted, eluent mixing, is concentrated and dried, and the careless extract of golden pheasant hair has both been obtained.
Embodiment 2
Be added in a reservoir crushing golden pheasant hair grass, and be added 4 times amount 1.5M acetic acid, in 900W microwave reactor in
72 DEG C hydrolyze 30 minutes.Reaction solution is cooled to room temperature, and upper resin column AB8 absorption is washed to PH7.1, sequentially with 20%, 60%,
80%, 95% ethyl alcohol is eluted, eluent mixing, is concentrated and dried, and the careless extract of golden pheasant hair has both been obtained.
Embodiment 3
The golden pheasant hair grass of crushing is added in a reservoir, and the 0.1M acetic acid of 7 times of amounts is added, in 1200W microwave reactor
It is hydrolyzed 10 minutes in 90 DEG C.Reaction solution is cooled to room temperature, and upper resin column AB8 absorption is washed to PH6.9, sequentially with 20%, 60%,
80%, 95% ethyl alcohol is eluted, eluent mixing, is concentrated and dried, and the careless extract of golden pheasant hair has both been obtained.
Embodiment 4
The golden pheasant hair grass of crushing is added in a reservoir, and the 1.0M acetic acid of 5 times of amounts is added, in 1000W microwave reactor
It is hydrolyzed 20 minutes in 82 DEG C.Reaction solution is cooled to room temperature, and upper resin column AB8 absorption is washed to PH7.0, sequentially with 20%, 60%,
80%, 95% ethyl alcohol is eluted, eluent mixing, is concentrated and dried, and the careless extract of golden pheasant hair has both been obtained.
(2) pharmacological experiment of the careless active constituent of golden pheasant hair
Experimental example 5
Drug and reagent
Experimental drug object is the careless extract of golden pheasant hair that embodiment 1-4 is prepared.
Experimental animal
Kunming mouse, weight 18-22g, cleaning grade, half male and half female are provided by Sichuan University's Experimental Animal Center.This reality
It is consistent to test all animal feedings, starts 3d before testing and sets the raising of this laboratory observation, freely ingest, drink water.Each group feed
It is all the same with drinking water source.
Experimental method
The influence of blood glucose in diabetic mice and blood lipid is caused to alloxan
The alloxan 50mg/kg of mouse tail vein injection Fresh causes diabetes model, can't help after 72h fasting
The mouse orbit rear vein beard of water is taken a blood sample, and blood glucose value is surveyed, and chooses mouse of the fasting blood-glucose higher than 11.1mmol/L for testing.It takes
Qualified model mice 40 is randomly divided into 4 groups, each 10 of embodiment 1-4), separately take the normal mouse of similar weight as normal
Group (10), after gastric infusion 15mg/kg, successive administration 14d, mouse is deprived of food but not water 8h before last dose, is administered subsequent
It is continuous to be deprived of food but not water rear 2h, it plucks eyeball and takes blood, measure the fasting blood sugar, total cholesterol level, triacylglycerol content, height of each group
Density lipoprotein level, low-density lipoprotein content.
The influence of blood glucose in diabetic mice is caused to adrenaline
Qualified Kunming mouse 40 (half male and half female) is taken, is randomly divided into 4 groups, each 10 of embodiment 1-4), separately take weight
Similar normal mouse is as normal group (10), after gastric infusion 15mg/kg, successive administration 10d, the mouse before last dose
It is deprived of food but not water 8h, continues to be deprived of food but not water rear 6h after administration, in addition to control group, every mouse peritoneal Injection of Adrenaline
0.2mg, Normal group such as are then injected intraperitoneally at the capacity physiological saline.After 30min, the blood sampling of retroorbital venous clump measures each group
Fasting blood sugar.
Statistical procedures
Experimental data is indicated with mean ± standard deviation (X ± S), and the conspicuousness for being compared group difference is examined using t.
As a result
The influence of blood glucose in diabetic mice is caused to alloxan
After successive administration 14d, the mouse blood sugar value of embodiment 1-4 have compared with model group conspicuousness decline (P <
0.05)。
Influence of the careless extract of table 1 golden pheasant hair to alloxan diabetes mouse blood sugar
The influence of blood glucose in diabetic mice is caused to adrenaline
Be administered 10d after, be injected intraperitoneally adrenalin hydrochloride, model group mouse blood sugar value be significantly higher than normal group (P <
0.05);Administration group mouse blood sugar value is substantially less than model group (P<0.05), does not have significant difference (P>0.05) with model group.
It the results are shown in Table 2.
Influence of the careless extract of table 2 golden pheasant hair to alloxan diabetes mouse blood sugar
Group | Dosage (mg/kg) | Number of elements | Blood glucose (mmol/L) before being administered |
Embodiment 1 | 15 | 10 | 6.84±1.23 |
Embodiment 2 | 15 | 10 | 6.56±1.34 |
Embodiment 3 | 15 | 10 | 7.04±1.06 |
Embodiment 4 | 15 | 10 | 7.12±0.87 |
Model group | 0 | 10 | 19.88±1.62 |
Normal group | 0 | 10 | 5.39±1.48 |
The influence of diabetic mice blood lipid level is caused to alloxan
After 14d is administered, compared with normal group, diabetes group mouse TC, TG, LDL-C content significantly increases (P < 0.05),
HDL-C content is remarkably decreased (P < 0.05);Compared with model group, administration group mouse TG, LDL-C content be remarkably decreased (P <
0.05), HDL-C content significantly increases (P < 0.05).It the results are shown in Table 3.
Influence of the careless extract of table 3 golden pheasant hair to alloxan diabetes lipid of mice
The result shows that: the careless extract of golden pheasant of the present invention hair has a significant hypoglycemic effect to diabetic mice, while can be with
Adjust diabetic mice blood lipid level.Compared with model group, pharmaceutical composition of the present invention can significantly reduce alloxan and cause glycosuria
Sick mouse blood sugar value (P < 0.05), and can significantly reduce adrenaline and cause blood glucose in diabetic mice value (P < 0.05).Administration group is small
Mouse triacylglycerol, low-density lipoprotein content are remarkably decreased (P < 0.05), and hdl concentration significantly increases (P < 0.05).
Experimental example 6
Adiponectin (Adiponectin) is a kind of albumen by mature fat cell secretion, has anti-diabetic, resists
The effects of inflammation, antiatherosclerosis.Adiponectin, which also has, increases insulin sensitivity effect, can improve fat and 2 types sugar
The symptoms of insulin resistance for urinating the metabolic diseases such as disease is the key that reduce II diabetes glucose target molecule.Fatty acid binds egg
White (aP2) is also to reduce II diabetes glucose important target, it plays a significant role during fatty acid metabolism, is fatty thin
Born of the same parents differentiation, lipid over-deposit outstanding feature object.Inventor induces differentiation and gene expression analysis with 3T3-L1 fat cell,
Reference literature [OkamotoY, Kihara S, Funahashi T, et al.Adiponectin:a key adipocytokine
in metabolic syndrome[J].Clin Sci(Lond)2006;110:267-278] method, with contain 10% small ox blood
Clear DMEM culture medium culture 3T3-L1 cell uses inductive differentiation medium Cell differentiation inducing activity two after cell is paved with completely
It, hereafter changes the DMEM culture medium culture of 10% fetal calf serum (FBS) containing insulin into, changes the liquid once every three days;It lures
Leading the 8th day cell can break up completely, addition while changing liquid of above compound and Rosiglitazone.After cell induction differentiation, use
Oil red O stain, observation fat cell inner lipid deposition.WithReagent (Invitrogen) extracts total serum IgE.With
PrimeScriptTM RT reagent Kit (TaKaRa) reverse transcription reagent box synthesizes cDNA.With iQ TM
Green Supermix (BIO-RAD) carries out real-time fluorescence quantitative PCR F analysis.1-4 of the embodiment of the present invention as can be seen from the results
The careless extract sample of golden pheasant hair of preparation can enhance the expression of target gene adiponectin, show that sample has good hypoglycemic work
With the effect with Adipose Differentiation.
Experimental example 7
The careless extract of golden pheasant hair of the present invention is for treating diabetes experiment.
Treatment object is to be included in the patient of case to meet " diabetes (acromelic gangrene inspection method and diagnostic criteria (grass
Case)) " patient, treatment time 10d-90d.
The patient with diabetic feet state of an illness after diagnosing is by six grades of tcm clinical practice classifications:
0 grade: skin is without open lesion.Show as acra blood supply insufficiency, color cyanosis or pale, acra sends out cool, is numb,
Insensitive or forfeiture, acra shouting pain or cusalgia, are often accompanied by toes or the deformity of foot etc.;
Level-one: acra skin has open lesion.Blister, blood blister, corn or callosity, frostbite or scald and other skins damage
The caused superficial ulcer of wound, but lesion not yet involves deep tissue;
Second level: infection focus has invaded deep muscle tissue.Often there are slight cellulitis, multiple purulence stove and sinus shape
At, or infection expands along spatium intermusculare, causes vola, instep connectivity ulcer or gangrene, purulent secretion is more, foot or refers to toe skin
Skin dry gangrene, but tendon ligament there is no destruction;
Three-level: tendon ligament tissue destroys.Cellulitis merges to form big vomica, and purulent secretion and necrotic tissue increase
It is more, foot or a small number of toes dry gangrenes, but destruction of bone is still unobvious;
Level Four: severe infections have resulted in destruction of bone.Osteomyelitis, Bones and joints destroy or have been formed pseudarthrosis, part toes
Or the serious gangrene of moist or stemness or necrosis occur for part brothers;
Pyatyi: sufficient most or all infection or ischemic lead to serious moist or dry gangrene, acra blackening, ordinary wave
And ankle-joint and shank.
Treatment method: all cases are all made of strict glycemic control, while dredging microcirculation, will use after necrotic tissue cleaning
The sterilization of 0.01% Hydrogen Peroxide Dilute Solution after drying, smears the careless extract of golden pheasant hair prepared by the embodiment of the present invention 1 and glycerol
Mixture (mass ratio 1:10), four times a day, treatment cycle 10 days to 90 days.
Criterion of therapeutical effect is drafted referring to Standards for Diagnosis and Curative Effect of Chinese Medical Symptom, and recovery from illness: the surface of a wound heals substantially, effective: surface of a wound face
Product reduces the scope > 50%, effectively: surface of a wound area reduces the scope > 30%;Invalid: surface of a wound area color slightly improves or without bright
Aobvious variation.Treatment results are shown in Table 4.
Treatment of the careless extract of table 4 golden pheasant hair to diabetes
.Above-mentioned experiment shows that the careless extract of golden pheasant hair of the present invention has good therapeutic effect to diabetes, especially right
0, I and II diabetes, obvious effective rate are higher than 90%, wherein being 100% for 0 grade of even more cure rate.For more serious
Three, level Four, obvious effective rate is also above 80%, even serious Pyatyi, and effective percentage is also close to 70%.The method of reference embodiment 7,
The careless extract of golden pheasant hair of investigation embodiment 2-4 preparation is to the curative effect of diabetes, the golden pheasant that as the result is shown prepared by embodiment 2-4
The careless extract of hair is also to diabetic foot significant effect.
Claims (8)
1. the application of golden pheasant hair grass and its extract in preparation prevention or treatment diabetes medicament.
2. golden pheasant hair grass and its extract are maintaining the application in body glycolipid metabolism Balance Pharmaceuticals.
3. the application of golden pheasant hair grass and its extract in preparation prevention or treatment diabetes drug.
4. the application of golden pheasant hair grass and its extract in preparation prevention or treatment diabetes mellitus high blood cholesterol drug.
5. the application of golden pheasant hair grass and its extract in the diabetes caused by preparation prevention or treatment alloxan.
6. the application of golden pheasant hair grass and its extract in the diabetes caused by preparation prevention or treatment adrenaline.
7. a kind of preparation method of the careless extract of golden pheasant hair, using following steps:
In the aqueous acetic acid for the 0.1-1.5M that golden pheasant hair grass is added 4-7 times, in 70-90 DEG C of water of temperature in microwave reactor
Solution 10-30 minutes;It then cools to room temperature, with macroporous adsorption resin chromatography depickling, being first eluted with water to efflux is neutrality, so
The ethanol elution of 20-95% is used afterwards, until thin-layer chromatography detection, without purple dot, concentration both obtained.
8. method as claimed in claim 7, it is characterised in that: the concentration of the aqueous acetic acid is 0.8-1.2M.
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Cited By (1)
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