CN106176773A - Berberine hydrochloride and stachyose composition compositions and application - Google Patents
Berberine hydrochloride and stachyose composition compositions and application Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
- A61K36/718—Coptis (goldthread)
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Abstract
The invention discloses a kind of compositions, described compositions is made up of berberine hydrochloride and stachyose.Described compositions is mainly prepared by the raw material of following parts by weight proportioning: berberine hydrochloride 1 part and stachyose 0.2～25 parts, described compositions also includes pharmaceutically acceptable carrier or excipient.The present invention further discloses the application in preparation prevention and/or treatment type 2 diabetes mellitus, hyperlipidemia and/or type 2 diabetes mellitus complication medicine, health product and food of the described compositions.
Description
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to a kind of drug regimen being made up of berberine hydrochloride and stachyose
Thing and the application in preventing and treating type 2 diabetes mellitus, hyperlipidemia and/or type 2 diabetes mellitus complication.
Background technology
Diabetes are the endocrine and metabolic disorders diseases of serious threat human health, with hyperglycemia, hyperlipidemia for main special
Levy.Wherein type 2 diabetes mellitus sickness rate accounts for diabetics more than 90%, shows as insulin resistant, and with diabetes complicated
The generation of disease, the cardiovascular complication being secondary to diabetes is the first cause causing diabetics dead.Epidemiology is adjusted
Looking into discovery, diabetics has 70-80% to die from cardiovascular complication.Diabetic cardiomyopathy is the main heart of diabetics
Dirty complication, this disease is caused cardiac muscle extensively focal necrosis and fibrosis by metabolism disorder and microangiopathies and then causes heart weight
Structure, and finally develop into core function abnormality and heart failure.
At present, the Therapeutic Method of type 2 diabetes mellitus mainly includes blood sugar lowering, blood fat reducing and improves insulin resistant；The diabetic heart
The treatment of myopathy mainly includes the symptomatic treatment methods such as cardiac tonic application and operation, generally there is untoward reaction more, cost
The drawbacks such as costliness, find from the natural product with Metabolism regulation potentiality and can effectively improve type 2 diabetes mellitus and heart thereof
Complication, monomer that structure is clear and definite and safer or compatibility composition, be provided with the clinical treatment for diabetic cardiomyopathy
Effect and brand-new means.
Stachyose (English name: stachyose, molecular formula C24H42O21), it is a kind of natural functional oligosaccharide, Ke Yiqiang
Profitable strain (bacillus bifidus and lactic acid bacteria etc.) in effect propagation human body intestinal canal, has good physiological function.It addition, stachyose is
In traditional Chinese medicine fresh rehmannia root, the chemical composition of content the highest (content is up to 50%, meter of giving money as a gift), degrades during Processing methods
Thus the property of medicine changes.
Berberine hydrochloride (i.e. berberine, English name: berberine, molecular formula C20H18ClNO4), for conventional antimicrobial drug
Thing, is used for clinically treating intestinal infection, such as gastroenteritis etc., also has the report in terms for the treatment of diabetes.Hydrochloric acid Radix Berberidis Amurensis
Alkali is the main chemical compositions of Chinese Drug Rhizomes of Coptis, content about 9% (dry product meter).
The Tang Dynasty written Prescriptions Worth Thousand Gold for Emergencies of doctor's Sun Simiao has the good recipe that multiple treatment is quenched one's thirst, such as:
One says coptis teeta pill, and side carries: Rhizoma Coptidis one jin, Radix Rehmanniae (i.e. Radix Rehmanniae) a jin, right two tastes, twists Radix Rehmanniae extracting juice, leaching Huang
Even, go out the dry of exposure, receive it again, make juice do to the greatest extent it, smash end, honeyed pill such as Firmiana simplex seed.Taking 20 balls, day three, before and after food, nothing exists.Also can be
Dissipate, take tool for weighing medicine in ancient China with wine.This side controls yearningly.
Two say Dihuang Wan, and side carries: Radix Rehmanniae juice, raw radices trichosanthis juice, each two liters, sebum three liters, whitish honey four liters, Rhizoma Coptidis one
Jin, end.The five tastes again, closing pan-fried order can ball.Big five balls of drink-service such as Firmiana simplex seed, day two, add to 20 balls.If suffering from cold and thirsty, be yearningly recovered i.e.
Not take temperature medicine also.This side controls mountain, south of the Five Ridges miasma, and wind heat poison enters in kidney, become cold and heat flaccidity of the lower limbs, fullness sensation due to deficiency and thirsty.Control again yellowish complexion, Shou Zuhuang,
Parched throat is dry, loses heart, and arteries and veins as the most like a chain of pearls or a string of beads, heat extraction, profit of quenching the thirst, is taken a tonic or nourishing food to build up one's health.
Three say Poria cum Radix Pini's ball, and side carries: Poria cum Radix Pini, Radix Astragali, radices trichosanthis, Radix Ophiopogonis, Radix Ginseng, Radix Glycyrrhizae, each three liang of the Rhizoma Coptidis Rhizoma Anemarrhenae, dry ground
Huang, each six liang of Gypsum Fibrosum, Semen Cuscutae three closes, Herba Cistanches four liang.Right 12 tastes, end, close with Fel Bovis seu Bubali three, and honeyed pill such as Firmiana simplex seed, with thatch
Root soup takes 30 balls, takes day two, gradually adds to 50 balls.Control diabetes involving the kidney thirsty, frequent micturition person.
Looked into patent " a kind of pharmaceutical composition treating diabetes and application thereof " (number of patent application
201210586831.2) respectively Rhizoma Coptidis and Radix Rehmanniae two taste medical material are carried out alcohol reflux, then the extract of the two is mixed
Close, to illustrating that this extracting method has advantage than a thousand pieces of gold coptis teeta pill of traditional handicraft in terms of the rate of transform.Above-mentioned patent and basis
The monomer component compatibility that invention proposes is different.
Looked into patent " berberine hydrochloride is for preparing the medicine of appetite-suppressing " (number of patent application 201410286415.X)
Disclose berberine hydrochloride for preparing the medicine of appetite-suppressing, in particular for reducing diabetes or obesity patient's feed
Amount.Above-mentioned patent uses berberine hydrochloride single component, different from berberine hydrochloride of the present invention and stachyose compatible combination,
For application be reduce appetite, from the present invention propose range of application the most different.
Looked into patent " a kind of compositions and the purposes in medicine thereof " (number of patent application 201410260301.8) is open
A kind of mixed, by chrysophanic acid, berberine hydrochloride, the compositions formed, be used for preventing and treat diabetes, nephropathy.Above-mentioned patent
Use berberine hydrochloride and chrysophanic acid compositions, different from berberine hydrochloride of the present invention and stachyose compositions.
Document " catalpol and berberine hydrochloride and the compatibility impact on insulin resistant 3T3-L1 adipose cell thereof " is investigated
Catalpol and berberine hydrochloride and compatibility thereof to the insulin resistant 3T3-L1 adipose cell glucose consumption of induced by dexamethasone, turn
Fortune and the impact of this Process of Peroxide body proliferator activated receptor (PPAR-C) mrna expression.The catalpol proposed in document
Different with the berberine hydrochloride that the present invention proposes and stachyose compatibility from berberine hydrochloride compatibility.
Chinese Pharmacopoeia (2010 editions) regulation catalpol is the quality control index of Radix Rehmanniae medical material, and therefore scholar is many with catalpol is
Object of study carries out the research and development that Radix Rehmanniae is relevant, unlike this, we using the active component stachyose in Radix Rehmanniae as
Research and development object.
Early-stage Study finds that the stachyose in Radix Rehmanniae has the effects such as certain blood sugar lowering and blood fat reducing and cytotoxicity is low.
The present invention is further discovered that stachyose and berberine hydrochloride drug combination and high fat diet adds the ICR diabetes mice of STZ induction
Model has obvious blood sugar lowering, blood fat reducing and improves the effect of diabetic cardiomyopathy index of correlation, and in most cases both associatings
Medication is more better than being used alone respectively, propose first with stachyose and berberine hydrochloride compositions carry out type 2 diabetes mellitus and
The suitable property of medicine research of related cardiac complication, raw materials used abundance, chemical constitution understands, overcomes Chinese medicine compound material multiple
The miscellaneous problem being difficult to illustrate, to making a kind of new medicinal products by meeting the research and development of modern medicine and pharmacology rule.
List of references:
Liu Fangfang, Yang Mingwei, Wang Xiaoqiang, etc. catalpol and berberine hydrochloride and compatibility thereof are to insulin resistant 3T3-L1 fat
The impact of fat cell. Chinese herbal medicine, 2007,38 (10): 1523-1526.
Summary of the invention
Present invention solves the technical problem that be to provide a kind of compositions being made up of berberine hydrochloride and stachyose and
Preparation prevents and/or in treatment type 2 diabetes mellitus, hyperlipidemia and/or type 2 diabetes mellitus complication medicine, health product or food
Application.
On the one hand technical scheme provides a kind of compositions being made up of berberine hydrochloride and stachyose, hydrochloric acid
Berberine and stachyose formulation weight number proportioning are 1:0.1～50, and preferred weight number proportioning is 1:0.2～25, most preferably
Parts by weight proportioning is 1:1.
Technical scheme second aspect provides a kind of compositions being made up of berberine hydrochloride and stachyose, its
Described in compositions also include pharmaceutically acceptable salt or excipient.
Described compositions can be prepared according to method well known in the art.Time for this purpose, can by the present composition with
One or more solids or liquid pharmaceutical excipients and/or adjuvant combine, make can as people's medicine or veterinary drug use suitable
Administration form or dosage form.Form of administration can be liquid dosage form, solid dosage forms, as liquid dosage form can be true solution class,
Colloidal type, particulate formulations, emulsion dosage form, mixed suspension form.Other dosage forms such as tablet, capsule, drop pill, aerosol, pill, powder
Agent, solution, suspensoid, Emulsion, granule, suppository, lyophilized injectable powder, buccal tablet, oral cavity disintegration tablet, soft gelatin capsule, soft capsule, dispersion
Sheet, solution, aerosol or spray etc..Described compositions can make ordinary preparation, it is also possible to is slow releasing preparation, controlled release system
Agent, targeting preparation and various particulate delivery system.In addition it is also possible in pharmaceutical preparation add coloring agent, preservative, spice,
Correctives, sweeting agent or other material.
The third aspect of technical solution of the present invention provides a kind of compositions being made up of berberine hydrochloride and stachyose and exists
Preparation prevents and/or in treatment type 2 diabetes mellitus, hyperlipidemia and/or type 2 diabetes mellitus complication medicine, health product or food
Application.Described type 2 diabetes mellitus shows as hyperglycemia or insulin resistant；Described type 2 diabetes mellitus complication is selected from diabetes
Cardiomyopathy；Described type 2 diabetes mellitus cardiomyopathy is the abnormal reconstruct of ventricle that type 2 diabetes mellitus causes, the mental and physical efforts that type 2 diabetes mellitus causes
Exhaustion, the heart tissue fibrosis that type 2 diabetes mellitus causes.
Advantageous Effects:
Berberine hydrochloride and stachyose are carried out compatibility with certain proportion by the present invention can treat type 2 diabetes mellitus in various degree
Blood glucose or insulin resistant, and metabolism disorder of blood lipid can obviously improve and treat type 2 diabetes mellitus complication, especially 2
The myocardiac cardiac remodeling of patients with type Ⅰ DM and anergy, can improve type 2 diabetes mellitus model mice survival rate simultaneously.Especially hydrochloric acid is little
Bark of a cork tree alkali and compositions that stachyose parts by weight proportioning is 1:1 improve type 2 diabetes mellitus model mice survival rate, reduce blood glucose,
Reduce triglyceride and T-CHOL, improve insulin resistant, improve the many-sides such as myocardial function relative to being individually administered
Better, it was demonstrated that berberine hydrochloride and stachyose compatibility have a certain degree of synergism.
Accompanying drawing explanation
Fig. 1: streptozotocin (streptozocin, STZ) is increased fat diet induced type 2 diabetes mellitus mouse model and is prepared, moves
Thing packet, berberine hydrochloride and stachyose carry out compatibility administration by each 1:0,5:1,1:1,1:2.5,1:5,1:10,1:25 and 0:1
Arrange.
Fig. 2: berberine hydrochloride and the various compatible composition of stachyose (respectively 1:0,5:1,1:1,1:2.5,1:5,1:
10,1:25 and 0:1) STZ is increased the impact of fat diet induced type 2 diabetes mellitus mouse survival rate.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Fig. 3: berberine hydrochloride and the various compatible composition of stachyose
The impact of carbohydrate tolerance.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Fig. 4: berberine hydrochloride and the various compatible composition of stachyose
The impact of stable state insulin resistant evaluation number.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Fig. 5: berberine hydrochloride and the various compatible composition of stachyose
The impact of serum triglycerides.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Fig. 6: berberine hydrochloride and the various compatible composition of stachyose
The impact of serum total cholesterol.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Fig. 7: berberine hydrochloride and the various compatible composition of stachyose
The impact of serum high-density LP.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Fig. 8: berberine hydrochloride and the various compatible composition of stachyose
The impact of serum low-density LP.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Fig. 9: berberine hydrochloride and the various compatible composition of stachyose
Ventricular wall thickness and the impact of cardiac function.From left to right, be followed successively by from top to bottom matched group, model group, 1:0,5:1,1:1,1:
2.5, the exemplary ultrasonic kinetocardiogram of 1:5,1:10,1:25 and 0:1 compatible composition administration group mice.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Figure 10: berberine hydrochloride and the various compatible composition of stachyose
The impact of relaxing period left ventricle antetheca (LVAWd).
STZ is increased fat diet induced type 2 diabetes mellitus mice by Figure 11: berberine hydrochloride and the various compatible composition of stachyose
The impact of relaxing period left ventricular posterior wall (LVPWd).
STZ is increased fat diet induced type 2 diabetes mellitus mice by Figure 12: berberine hydrochloride and the various compatible composition of stachyose
The impact of cardiac ejection fraction (EF).
STZ is increased fat diet induced type 2 diabetes mellitus mice by Figure 13: berberine hydrochloride and the various compatible composition of stachyose
The impact of cardiac short axis LVFS (FS).
STZ is increased fat diet induced type 2 diabetes mellitus mice by Figure 14: berberine hydrochloride and the various compatible composition of stachyose
The Fibrotic impact of heart tissue.From left to right, be followed successively by from top to bottom matched group, model group, 1:0,5:1,1:1,1:2.5,
1:5,1:10,1:25 and 0:1 compatible composition administration group mouse heart tissue collagen representativeness after Masson trichrome stain
Picture.
STZ is increased fat diet induced type 2 diabetes mellitus mice by Figure 15: berberine hydrochloride and the various compatible composition of stachyose
The statistical result of heart tissue area of collagen impact.
Detailed description of the invention
Further illustrate the present invention below by the mode of embodiment, but the most therefore limit the present invention to described reality
Execute among example scope.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or according to business
Product description selects.
In following embodiment, berberine hydrochloride and stachyose are by separation and Extraction artificial in Rhizoma Coptidis and Radix Rehmanniae.
In following embodiment, full name or the corresponding Chinese of moieties are as follows:
STZ: streptozotocin
PBS: phosphate buffer
Described in following embodiment, room temperature is as described in the routine of this area, refers generally to 15～25 DEG C.
The ICR mice sugar that STZ and high fat diet are induced by the compatibility of embodiment 1 berberine hydrochloride and stachyose different proportion
The impact of urine disease model
(1) prepared by model, experiment is grouped and dosage regimen
SPF level ICR mice (male and female half and half, 3-4 week old) is purchased from Beijing Vital River Experimental Animals Technology Co., Ltd., raises
Support in institute of Materia Medica,Chinese Academy of Medical Sciences Experimental Animal Center, constant temperature and humidity, free diet.Mice adaptability is raised one week
After, it is randomly divided into 2 groups by sex and body weight: 1. matched group 10, persistently gives normal feedstuff until experiment terminates；The highest fat+
STZ group 90, gives high-sugar-fat-diet (containing 35% fat, 18% protein, 47% carbohydrate), after continuing 4 weeks
Lumbar injection streptozotocin STZ 100mg/kg (is dissolved in 0.1M citrate buffer solution, PH 4.5), and continues to give high fat height sugar
Feedstuff；Matched group lumbar injection solvent 0.1M citrate buffer solution.Tail venous blood sampling detection blood glucose (BG) after continuing 8 weeks, by height
Fat+STZ treated animal is by blood glucose > mice of 11.1mM is randomly divided into 9 groups and persistently gives high-sugar-fat-diet: model group (glycosuria
Sick) and administration group (berberine hydrochloride and stachyose proportion compatibility be respectively 1:0,5:1,1:1,1:2.5,1:5,1:10,1:25 and
The compositions of 0:1).
The maximum dosage of administration group determines with reference to clinical and daily health caring common dose, specific as follows: hydrochloric acid Radix Berberidis Amurensis
(adult's 1.2g/ day, be converted into adult human dose is 18mg/kg to alkali, the more maximum dosage being converted into mice is set to 200mg/
kg.(health treatment for adults dosage is 6g/ day to stachyose, and being converted into adult human dose is 85mg/kg, then is converted into mice maximum to medicament
Amount is set to 1000mg/kg).This experimental administration group is divided into 8 groups, and concrete each group dosage design table is shown in Table 1.
Concrete dosage regimen is: compositions is dissolved in pure water by each administration group respectively by above-mentioned dosage, every day gastric infusion 1
Secondary；Model group gives control solvent PBS, every day gastric infusion 1 time, Fig. 1 is concrete modeling and administration time arrangement.It is administered continuously
8 weeks.
Table 1
(2) experimental result
(1) compatibility of berberine hydrochloride and the stachyose different proportion impact on type 2 diabetes mellitus mouse survival rate
Fig. 2 is that berberine hydrochloride and stachyose are by 1:0,5:1,1:1,1:2.5,1:5,1:10,1:25 and 0:1 proportion compatibility
The result that after treatment, the survival rate of mice compares with matched group, model group mouse survival rate.
Result shows, after being administered continuously eight weeks, the mice of model group has maximum death, and berberine hydrochloride and water
Threose is individually administered and the most all has after major part different proportion compatibility treatment death in various degree, but berberine hydrochloride and
The administration group of stachyose 1:1 proportion compatibility does not has death, and survival rate is the highest, joins with certain proportion to a certain extent both explanation
The advantage place of 5.
(2) type 2 diabetes mellitus mouse blood sugar, blood fat, insulin are referred to by the compatibility of berberine hydrochloride and stachyose different proportion
Target affects
After mice fasting 12h, tail venous blood sampling, use blood-sugar detecting instrument to measure fasting glucose, by 2g/kg gavage glucose
Solution, and with 30,60,120min time point tail venous blood sampling measure blood glucose, according to formula AUC (mmol/L/h)=(0min blood
Sugar value+30min blood glucose value) × 0.5/2+ (30min blood glucose value+60min blood glucose value) × 0.5/2+ (60min blood glucose value+120min
Blood glucose value) area evaluates the carbohydrate tolerance (Fig. 3) of mice under × 1/2 calculated curve.Mice takes blood 1mL by eyeball, and room temperature stands
30min, 3000rpm are centrifugal, separate serum, by ELISA kit description detection insulin content (Fig. 4), by biochemistry detection
Test kit description use Hitachi 7600-020 automatic clinical chemistry analyzer detection triglyceride (Fig. 5), T-CHOL (Fig. 6),
The blood lipids index such as HDL-C (Fig. 7), low density cholesterol (Fig. 8), concrete mensuration is shown in Table 2 with statistic.
Testing result finds: STZ increases the diabetic model group mice of fat diet induced and occurs that obvious blood glucose, total gallbladder are solid
Alcohol, triglyceride raise and insulin resistant increases.Berberine hydrochloride and stachyose press 1:0,5:1,1:1,1:2.5,1:5 and 1:
10 proportion compatibilities all show the blood glucose effect that significantly reduces, especially the two to press 1:1 compatibility optimal.Berberine hydrochloride and stachyose are by 1:
0,5:1,1:1,1:2.5,1:5,1:10 and 1:25 proportion compatibility all shows and significantly improves Insulin Resistance, and especially the two is pressed
1:1 compatibility is optimal.Berberine hydrochloride and stachyose are all shown significantly by 1:0,5:1,1:1,1:5,1:10 and 1:25 proportion compatibility
Reduce the effect of triglyceride levels.1:0,5:1,1:1,1:2.5,1:5 and 1:10 compatibility ratio pressed by berberine hydrochloride and stachyose
Example all shows the effect significantly reducing total cholesterol level, especially the two to press 1:1 compatibility optimal.Result shows that the two is with a definite proportion
Example compatibility has synergism.
Table 2
(3) compatibility of berberine hydrochloride and stachyose different proportion is to type 2 diabetes mellitus mouse heart function and the shadow of form
Ring
Before experiment terminates, after mice is anaesthetized by 45mg/kg dosage lumbar injection pentobarbital sodium, its thorax abdomen is entered
Row depilation processes, and dorsal position is fixed on ultrasound detection platform, and (VisualSonics adds and takes to use VisualSonics Vevo 770
Ultrasonic system greatly) detects: first with 10M Hz ultrasonic probe, mouse heart long axis direction is carried out Type B ultrasonic monitoring, determines
Behind papillary muscles of left ventricle position, then transfer cardiac short axis direction to and be monitored, and the M type recording its 10～20 cardiac cycles surpasses
Sound variation diagram；Left room anterior wall thickness diastasis (LVAWd), Left ventricular posterior wall thickness is measured respectively with Vevo 770 software
(LVPWd), interventricular septal thickness (LVSd), ejection fraction (Ejection Fraction, EF), shortening fraction (Fractional
Shortening, FS) etc. every cardiac structure and parameters of left ventricular function.
The abnormal reconstruct of ventricle is the cardiac structure pathological change that diabetic cardiomyopathy is important.The ultrasonic heart of VasualSonics
Dynamic testing result finds: STZ increases after fat diet induced diabetic cardiomyopathy the 20th week, the model group mice obvious heart of appearance
Locular wall is thickening and the pathological change such as cardiac function reduction.Berberine hydrochloride and stachyose can significantly inhibit LVAWd's by 1:1 compatibility
Increase.Berberine hydrochloride and stachyose can significantly inhibit the increase of LVPWd by 1:1 and 1:10 compatibility.Berberine hydrochloride and water
Threose can significantly improve FS and the EF index of heart by 1:1 and 1:10 compatibility.Result shows that the two is with certain proportion further
Compatibility has concertedness.Fig. 9 is representative ultrasoundcardiogram, Figure 10 and Figure 11 is cardiac structure index LVAWd and LVPWd statistics knot
Really, Figure 12, Figure 13 are parameters of left ventricular function EF and FS statistical result, and concrete mensuration is shown in Table 2 with statistic.
(4) compatibility of berberine hydrochloride and stachyose different proportion shadow Fibrotic to type 2 diabetes mellitus mouse heart tissue
Ring
The mouse heart obtained by embodiment experimental result (3) is fixed through 4% paraformaldehyde, and paraffin embedding also carries out horizontal stroke
Cut, dye through Hematoxylin-eosin (HE), evaluate overall cardiac structure and change.Tissue slice through Masson dye after at microscope
Lower observation, determines that heart collagen deposition situation judges fibrosis, and applies high-resolution color pathological picture and text to analyze system
Spot Advanced 3.0 obtains the pathological picture (400 times of amplifications) of the Masson dyeing of high-resolution.Use Image-Pro
Plus 5.1 measures each visual field collagen stained area.Every group analysis 6-8 specimen, each specimen randomly selects 10 visuals field,
Take average and represent content and the expression intensity that an animal collagen is organized in heart tissue.Compared by nonparametric variance analysis
Each group " collagen absolute area ".
Heart tissue fibrosis is one of lethal major reason of heart disease.Collagen absolute area percentage rate is to evaluate tissue
The reliability index of fibrosis, utilizing Masson dyeing to detect heart tissue collagen deposition can be to a certain degree reflecting myocardium
Fibrotic situation.Normal group cardiac muscular tissue collagen tissue is relatively fewer, and it is little that STZ increases fat diet induced diabetic cardiomyopathy
Mus cardiac muscular tissue collagen substantially increases, and forms severe cardiac muscle fiber, and collagen absolute area percentage rate increases to 3 times of normal value, salt
Acid berberine and stachyose all can significantly reduce STZ according to 1:0,5:1,1:1,1:2.5,1:5,1:10,1:25 proportion compatibility
Increase fat diet induced diabetic cardiomyopathy murine myocardium collagen deposition, especially the two to press 1:1 compatibility optimal.Result is entered
One step explanation berberine hydrochloride and stachyose have concertedness with certain proportion compatibility.Figure 14 is Masson dyeing representative picture, figure
15 is each group of area of collagen statistical result, and concrete mensuration is shown in Table 2 with statistic.
Claims (10)
1. a compositions, it is characterised in that described compositions comprises berberine hydrochloride and stachyose, wherein, hydrochloric acid Radix Berberidis Amurensis
The parts by weight proportioning of alkali and stachyose is 1:0.1～50；
2. compositions as claimed in claim 1, it is characterised in that the parts by weight proportioning of described berberine hydrochloride and stachyose is
1:0.2～25.
3. compositions as claimed in claim 2, it is characterised in that the parts by weight proportioning of described berberine hydrochloride and stachyose is
1:1。
4. the compositions as any one of claim 1-3, it is characterised in that described compositions also includes physiologically can accept
Carrier or excipient.
5. compositions as claimed in claim 4, it is characterised in that the dosage form of described compositions include granule, capsule, tablet,
Oral liquid, pill, suspensoid, drop pill, pellet, buccal tablet, oral cavity disintegration tablet, soft gelatin capsule, soft capsule, dispersible tablet, solution, aerosol
Agent or spray.
6. the compositions of claim 1-5 any one is in preparation prevention and/or treatment type 2 diabetes mellitus, hyperlipidemia and/or 2
Application in patients with type Ⅰ DM complication product.
Application the most according to claim 6, it is characterised in that described product is selected from medicine, health product or food.
8. the application as any one of claim 6-7, it is characterised in that described type 2 diabetes mellitus shows as hyperglycemia or pancreas
Insulin resistance.
9. the application as any one of claim 6-7, it is characterised in that described type 2 diabetes mellitus complication is selected from 2 type glycosurias
Sick cardiomyopathy.
Apply the most as claimed in claim 9, it is characterised in that described type 2 diabetes mellitus cardiomyopathy is the heart that type 2 diabetes mellitus causes
The room heart failure that reconstruct, type 2 diabetes mellitus cause extremely or the heart tissue fibrosis that type 2 diabetes mellitus causes.
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| CN (1) | CN106176773A (en) |
Cited By (4)
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| JP2020045338A (en) * | 2018-09-12 | 2020-03-26 | 大正製薬株式会社 | External composition |
| CN111821311A (en) * | 2019-04-18 | 2020-10-27 | 中国医学科学院药物研究所 | Application of berberine hydrochloride and stachyose composition in regulating intestinal flora |
| CN114177172A (en) * | 2020-09-14 | 2022-03-15 | 北京伟峰益民科技有限公司 | Medicine composition and application thereof |
| CN115364142A (en) * | 2022-06-06 | 2022-11-22 | 中国医学科学院药用植物研究所 | Application of Qidong Yixin oral liquid in preparation of medicine for treating diabetic cardiomyopathy |
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| US20050019435A1 (en) * | 2003-07-21 | 2005-01-27 | Jeffrey Young | Method of treating non-insulin dependent diabetes mellitus and related complications |
| CN103893361A (en) * | 2012-12-28 | 2014-07-02 | 天津药物研究院 | Pharmaceutical composition for treating diabetes and application thereof |
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| US20050019435A1 (en) * | 2003-07-21 | 2005-01-27 | Jeffrey Young | Method of treating non-insulin dependent diabetes mellitus and related complications |
| CN103893361A (en) * | 2012-12-28 | 2014-07-02 | 天津药物研究院 | Pharmaceutical composition for treating diabetes and application thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020045338A (en) * | 2018-09-12 | 2020-03-26 | 大正製薬株式会社 | External composition |
| CN111821311A (en) * | 2019-04-18 | 2020-10-27 | 中国医学科学院药物研究所 | Application of berberine hydrochloride and stachyose composition in regulating intestinal flora |
| CN114177172A (en) * | 2020-09-14 | 2022-03-15 | 北京伟峰益民科技有限公司 | Medicine composition and application thereof |
| CN115364142A (en) * | 2022-06-06 | 2022-11-22 | 中国医学科学院药用植物研究所 | Application of Qidong Yixin oral liquid in preparation of medicine for treating diabetic cardiomyopathy |
| CN115364142B (en) * | 2022-06-06 | 2023-05-12 | 中国医学科学院药用植物研究所 | Application of Qihuangyi heart oral liquid in preparation of medicine for treating diabetic cardiomyopathy |
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Application publication date: 20161207 |
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