CN102233078B - A kind of pharmaceutical composition regulates the application improved in microenvironment of pancreas islet medicine in preparation - Google Patents
A kind of pharmaceutical composition regulates the application improved in microenvironment of pancreas islet medicine in preparation Download PDFInfo
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- CN102233078B CN102233078B CN201010156334.XA CN201010156334A CN102233078B CN 102233078 B CN102233078 B CN 102233078B CN 201010156334 A CN201010156334 A CN 201010156334A CN 102233078 B CN102233078 B CN 102233078B
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Abstract
The invention belongs to pharmaceutical field, relate to a kind of pharmaceutical composition and prepare the application improved in microenvironment of pancreas islet medicine, wherein said pharmaceutical composition is that prescription is formulated by the raw material of Chinese medicine medicine of following weight portion: Radix Trichosanthis 5-40 part, Radix Bupleuri 10-30 part, Fructus Aurantii Immaturus 3-15 part, Radix Et Rhizoma Rhei 1-6 part, Rhizoma Pinelliae 1-12 part, Radix Scutellariae 3-15 part, Rhizoma Coptidis 1-12 part, Radix Paeoniae Alba 3-15 part, Fructus Mume 5-20 part.
Description
Technical field
The invention belongs to pharmaceutical field, relate to a kind of pharmaceutical composition and regulate the application improved in microenvironment of pancreas islet medicine in preparation.
Background technology
Type 2 diabetes mellitus (T2DM) is the worldwide public health problem of serious threat human health.The statistical data display that International Diabetes Federation (IDF) 2006 delivers, 20 years in the past, global diabetics number increased severely to 2.3 hundred million from 3,000 ten thousand.World Health Organization's expert expects, will reach 3.5 hundred million to global diabetics in 2025.India, China, the U.S. are followed successively by three maximum countries of global diabetics quantity, estimate diabetes mellitus in China subject population nearly 4,000 ten thousand, are only second to India, occupy second place of the world, account for 29.63% of the world.The control of T2DM foreseeable quite over a long time in will be all the severe challenge of facing mankind.
Type 2 diabetes mellitus is also Adult Onset's patients with type Ⅰ DM, how the sequela of 35 ~ 40 years old, accounts for diabetics more than 90%.The ability producing insulin in type 2 diabetes mellitus ward mate body not completely loses, and in some patient bodies, insulin even produces too much, but the action effect of insulin is had a greatly reduced quality, and the insulin therefore in patient body may be in a kind of state of relative shortage.The secretion of insulin in body can be stimulated by some oral drugs.But still have some patients to need to carry out insulinize as type 1 diabetes to the later stage.Type 2 diabetes mellitus roughly has following 3 features: first feature, and type 2 diabetes mellitus is apt to occur in adult, is especially many with middle-aged and elderly people.Repeatedly diabetes epidemiological study result all shows, type 2 diabetes mellitus morbidity age many 40-60 year, from 40 years old, prevalence increased gradually, peaked to the geratic period.The maturity-onset diabetes of Juvenile-onset is comparatively speaking, still very rare.Second feature is that the state of an illness generally compares mitigation, hidden, that is compared with type 1 diabetes, does not so bear down menacingly.Type 2 diabetes mellitus patient symptom is not obvious, may not be certain each patient have drink many, urinate many, the performance of outeat, majority also do not become thin significantly, and muscle power and body weight decline still more common to some extent certainly.3rd feature is exactly that patient does not often need to sustain life by insulinize.That is, patient does not beat insulin and is unlikely to ketoacidosis to occur soon and threat to life yet.So type 2 diabetes mellitus was non-insulin-dependent diabetes mellitus again originally.Type 2 diabetes mellitus patient also needs use of exogenous insulin sometimes, but majority is because glycemic control is undesirable, or because the chronic complicating diseases that there occurs acute complications or diabetes is heavier, and be to sustain life unlike type 1 diabetes patient.
Type 2 diabetes mellitus is the disease more more complicated than type 1 diabetes, and particularly insulin still can oneself but more easily be treated when producing in body in early days.Distribute due to early symptom slight (as without ketoacidosis and stupor etc.), therefore type 2 diabetes mellitus is many is diagnosed at rear for many years at disease progression more.But the complication that the improper meeting of control of type 2 diabetes mellitus causes such as renal failure, blind, wound healing slow, arteriopathy (comprising coronary artery disease) etc. is serious.
Its principal character of type 2 diabetes mellitus patient is insulin resistant, and relative insulin lacks and hyperglycemia; The increase (as deriving from the degraded of hepatic glycogen) of hepatic glucose production, particularly in the increase (typical reason is that insulin level is disorderly, and one of effect of insulin regulates and controls this function of liver just) on improper opportunity; The minimizing (receptor and post-receptor pathway defect) of the glucose transport of muscle and the middle insulin-mediated of fatty tissue (mainly); Islet beta cell function is impaired---lack the function of early stage insulin releasing when elevated blood glucose levels stimulates.
Islets of langerhans is organically made up of various kinds of cell, and by local Microvascular density cutting link, its physiology and pathological change influence each other, moreover, under pathological state, periphery stellate cell activation, propagation, migration, form fibrous connective tissue hypertrophy, form the important pathological factor of islet cells damage, do not pay close attention to merely function and the structural defence of local β cell, and islets of langerhans is put in the inner, the change of its physiological and pathological is studied in external environment, it is the imbody of the Overall View that the traditional Chinese medical science is traditional, this research is attempted from islets of langerhans microvascular lesions, stellate cell activation, fibrous connective tissue hypertrophy is to inquire into sugared quick spirit to the protection mechanism of beta Cell of islet.
Very vascular is one of principal character of islets of langerhans, and this is conducive to for islets of langerhans provides sufficient nutrition and oxygen, and promotes that associated hormone is secreted.And the performance of the reconstruct of islets of langerhans blood vessel to islet survival and function has extremely important effect.
Islets of langerhans is mainly made up of four class endocrine cell, the B cell composition islets of langerhans core of excreting insulin, and other cells composition islets of langerhans shell.Islets of langerhans blood is for providing primarily of 1 ~ 3 group of small artery, and these small artery are the islets of langerhans core blood capillary network that arrives through shell, and is circulated to the venule of islets of langerhans periphery.And little islets of langerhans blood capillary and exocrine gland capillary system combine.The importance that the adjustment of islets of langerhans local microenvironment regulates as pancreas B cell function, has received the concern of more and more scholar.
Inventor passes through the deep research of the quick spirit of sugar, and the sugared quick spirit of unexpected discovery can improve microenvironment of pancreas islet, for the therapeutic use of sugared Min Lingxin provides foundation.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition preparing the application improved in microenvironment of pancreas islet medicine.
Pharmaceutical composition of the present invention (is also called the quick clever preparation of sugar, dissipating depression of QI fever-clearing preparation), be that prescription is formulated by the raw material of Chinese medicine medicine of following weight portion: Radix Trichosanthis 5-40 part, Radix Bupleuri 10-30 part, Fructus Aurantii Immaturus 3-15 part, Radix Et Rhizoma Rhei 1-6 part, Rhizoma Pinelliae 1-12 part, Radix Scutellariae 3-15 part, Rhizoma Coptidis 1-12 part, by Chinese herbaceous peony 3-15 part, Fructus Mume 5-20 part.
Middle Fructus Crataegi can also be added in above-mentioned prescription, the formula obtained is: Radix Trichosanthis 10-30 part, Radix Bupleuri 10-30 part, Fructus Aurantii Immaturus 3-15 part, Radix Et Rhizoma Rhei 1-6 part, Rhizoma Pinelliae 1-12 part, Radix Scutellariae 3-15 part, Rhizoma Coptidis 1-12 part, Radix Paeoniae Alba 3-15 part, Fructus Mume 5-20 part, Fructus Crataegi 3-15 part.
Middle Fructus Crataegi can also be added in above-mentioned prescription, Rhizoma Polygonati, Radix Ginseng and Fructus Momordicae charantiae, the formula obtained is: Radix Trichosanthis 10-30 part, Radix Bupleuri 10-30 part, Fructus Aurantii Immaturus 3-15 part, Radix Et Rhizoma Rhei, 1-6 part, Rhizoma Pinelliae 1-12 part, Radix Scutellariae 3-15 part, Rhizoma Coptidis 1-12 part, Radix Paeoniae Alba 3-15 part, Fructus Mume 5-20 part, Fructus Crataegi 3-15 part, Rhizoma Polygonati 3-15 part, Radix Ginseng 3-15 part, Fructus Momordicae charantiae 3-15 part.
Preferred formula of the present invention is: Radix Trichosanthis 9 parts, Radix Bupleuri 12 parts, Fructus Aurantii Immaturus 9 parts, Radix Et Rhizoma Rhei 3 parts, the Rhizoma Pinelliae 6 parts, Radix Scutellariae 9 parts, Rhizoma Coptidis 6 parts, the Radix Paeoniae Alba 9 parts, Fructus Mume 9 parts.
Or:
Radix Trichosanthis 30 parts, Radix Bupleuri 12 parts, Fructus Aurantii Immaturus 9 parts, Radix Et Rhizoma Rhei 3 parts, the Rhizoma Pinelliae 6 parts, Radix Scutellariae 9 parts, Rhizoma Coptidis 6 parts, the Radix Paeoniae Alba 9 parts, Fructus Mume 15 parts, Fructus Crataegi 9 parts.
Or:
Radix Trichosanthis 30 parts, Radix Bupleuri 12 parts, Fructus Aurantii Immaturus 9 parts, Radix Et Rhizoma Rhei 3 parts, the Rhizoma Pinelliae 6 parts, Radix Scutellariae 9 parts, Rhizoma Coptidis 6 parts, the Radix Paeoniae Alba 9 parts, Fructus Mume 15 parts, Fructus Crataegi 9 parts, Rhizoma Polygonati 9 parts, Radix Ginseng 9 parts, 9 parts, Fructus Momordicae charantiae.
More than in composition, weight calculates with crude drug, and part is weight portion, if in grams, above composition can be made into a pharmaceutical preparation 5-50 preparation unit, and described preparation unit refers to, the final drug preparation made, as made solid preparation 5-50 unit, oral liquid 5-50ml etc.
More than composition can be made into the preparation of 1-6 taking dose, and as tablet, make 18, each taking dose can be 3-18 sheet, can take 1-6 time altogether.As granule, making 6 bags, each serving using 1-2 bag, can take 3-6 time altogether.
More than composition is by weight as proportioning, can increase according to corresponding proportion when producing or reduce, as large-scale production can by kilogram in units of, or in units of ton, small-scale production also can in units of milligram, weight can increase or reduce, but the constant rate of raw medicinal herbs weight proportion between each composition.
The ratio of above weight proportion is through that science screening obtains, and for especial patient, as serious symptom or mild, fat or modest patient, can the proportioning of amount of corresponding adjustment composition, and increase or reduce being no more than 300%, drug effect is constant.
Single medicinal material more than in composition, especially ministerial drug and adjuvant drug, also can be replaced by the suitable Chinese medicine with the identical property of medicine, its drug effect of the Chinese medicine preparation after replacement is constant.
Chinese medicine composition of the present invention, being that the raw material of Chinese medicine by being formed by above-mentioned formula is processed through extraction or other modes, making pharmaceutically active substance, subsequently, with this material for raw material, when needing, add medicine acceptable carrier, make according to the routine techniques of galenic pharmacy.Described active substance can obtain by extracting raw material of Chinese medicine respectively, also can be obtained by the common raw material of Chinese medicine that extracts, also can obtain by other means, as: by pulverizing, squeezing, calcine, grind, sieve, percolation, extraction, water extraction, alcohol extraction, ester carry, the material that method obtains, these active substances can be extractum form such as ketone is carried, chromatography, can be dry extract also can be fluid extract, need to determine to make different concentration according to the difference of preparation.
Pharmaceutically active substance in Chinese medicine composition of the present invention, its in the formulation shared percentage by weight can be 0.1-99.9%, all the other are medicine acceptable carrier.Pharmaceutical composition of the present invention, exists in a unit, and described unit dosage form refers to the unit of preparation, as every sheet of tablet, and every capsules of capsule, every bottle of oral liquid, granule every bag etc.
Chinese medicine composition of the present invention can be any pharmaceutically useful dosage form, and these dosage forms comprise: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, cream, spray, drop, patch.Preparation of the present invention, preferably peroral dosage form, as: capsule, tablet, oral liquid, granule, pill, powder, sublimed preparation, unguentum etc.
Chinese medicine composition of the present invention, the preparation of its oral administration can containing conventional excipient, and such as binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, flavoring agent and wetting agent, can carry out coating to tablet if desired.
The filler be suitable for comprises cellulose, mannitol, lactose and other similar filler.Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivatives, such as sodium starch glycollate.Suitable lubricant comprises, such as magnesium stearate.The suitable acceptable wetting agent of medicine comprises sodium lauryl sulphate.
By mixing, fill, the method that tabletting etc. are conventional prepares solid oral composition.Repeatedly mix and active substance can be made to be distributed in those compositionss of a large amount of filler of whole use.
The form of oral liquid can be such as aqueous or oily suspensions, solution, Emulsion, syrup or elixir, or can be the composite dry products of a kind of available water before use or other suitable carrier.This liquid preparation can containing conventional additive, such as suspending agent, such as sorbitol, syrup, methylcellulose, gelatin, hydroxyethyl-cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agent, such as lecithin, anhydro sorbitol monooleate or arabic gum; Non-aqueous carrier (they can comprise edible oil), the oily ester of the such as ester of almond oil, fractionated coconut oil, such as glycerol, propylene glycol or ethanol; Antiseptic, such as para hydroxybenzene methyl ester or propyl p-hydroxybenzoate or sorbic acid, and if need, can containing conventional flavouring agent or coloring agent.
For injection, the fluid unit dosage form of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this compound can be suspended or dissolve.The preparation of solution is normally by being dissolved in a kind of carrier by active substance, filter-sterilized before being loaded a kind of suitable bottle or ampoule, then seals.Adjuvant such as a kind of local anesthetic, antiseptic and buffer agent also can be dissolved in this carrier.In order to improve its stability, by freezing for this compositions after loading bottle, and under vacuo water can be removed.
Chinese medicine composition of the present invention, applicable medicine acceptable carrier is optionally added when being prepared into medicament, described medicine acceptable carrier is selected from: mannitol, sorbitol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin C, EDETATE SODIUM, Ethylenediaminetetraacetic Acid Calcium Salt, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and its derivates, alginate, gelatin, polyvinylpyrrolidone, glycerol, POLYSORBATE 80, agar, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
Compositions of the present invention according to the situation determination usage and dosage of patient, can take three every day in use, each 1-20 agent, as: 1-20 bag or grain or sheet.
Compositions of the present invention is through following methods preparation, and concrete steps are as follows:
The preparation method of the quick clever preparation of sugar of the present invention is: (1) gets above-mentioned raw materials in proportion, (2) ethanol of 4 times amount 70-90% is added, 50-80 DEG C of decompression recycling ethanol, 70-90 DEG C of vacuum drying, pulverize 80 mesh sieves, obtain drug extract; Add adjuvant and make acceptable dosage form on any number of pharmaceutics.
Pharmaceutical composition of the present invention and preparation method thereof can with reference to Chinese patent CN1726929.
The therapeutic effect of pharmaceutical composition of the present invention is further illustrated by following experiment.
1. materials and methods
1.1 laboratory animal
With spontaneous type 2 diabetes mellitus rat model OLETF Mus and its homology non diabetic controls Mus LETO Mus for experimental subject.Rat is all male, and only, LETO rat 10, surrounding age, is introduced by Japanese Otsuka Pharmaceutical Co., Ltd. Tokushima institute OLETF40.
Rat no-special pathogen level (SPF level, specificpathogen-free) condition place an order cage raise, raise with standard feed.Ambient temperature controls at 22-25 DEG C, and humidity is 55 ± 5%, 12/12 h light dark cycle (light application time 7:00-19:00), freely obtains food and drinking-water.
Raise place: Institute of Radiation Medicine, Chinese Academy of Medical Sciences Experimental Animal Center SPF level animal feeding room.
1.2 grouping and administrations
1.2.1OLETF diabetes diagnosis grouping standard
The regular row oral glucose tolerance test (OGTT) of rat.Test front fasting overnight 15 hours, can't help water, give 30% glucose solution gavage (get glucose powder 82.5g, adding distil water is settled to 250ml, and heating for dissolving is clear liquid, and obtaining concentration is 30% glucose solution) by 2g/kg.
In on an empty stomach and after glucose load 30,60,90 and 120min get blood, measure blood glucose value with card BIOSEN5030 rapid glucose analyser in Germany.After glycemic peaks > 16.7mmol/L and load, 120min blood glucose > 11.1mmol/L examines as diabetes, possesses an above-mentioned person for impaired glucose tolerance.
1.2.2 laboratory animal grouping and administration
During to 30 weeks, have into mould OLETF Mus 27, be divided into model group, rosiglitazone group, quick clever group of sugar at random, LETO is blank group.
Rosiglitazone group: rosiglitazone (Avandia): the every sheet of Tianjin company limited of Smithkline Beecham product is containing rosiglitazone maleate 4mg, purchased from by U.S.'s GlaxoSmithKline PLC (China) Investment Co., Ltd, be stirred to before use and dissolve completely, with distilled water diluting, dosage is 3mg/kg/d
-1.
Sugar quick clever group (that is: dissipating depression of QI heat clearing away group), adopt the formulated of the embodiment of the present invention 1 to become extractum, 4 DEG C of Refrigerator stores, with distilled water diluting, given low is 9mg/kg/d
-1(calculating by contained crude drug gauge).
Model group and blank group with equivalent distilled water gavage, the equal gastric infusion of each group 12 weeks, every day 1 time.
2 indexs and detection
2.1OGTT
Oral glucose tolerance test
Within every 4 weeks, oral glucose tolerance test (OGTT) is carried out before rat administration and after administration.Fasting overnight 15 hours before test, can't help water, give 30% glucose solution gavage by 2g/kg, on an empty stomach and after glucose load 30,60,90 and 120min cut tail and get blood, measure blood glucose.During oral carbohydrate tolerance experiment in 32 weeks, synchronous inner canthus gets blood, measures insulin.
Blood glucose is measured by card BIOSEN5030 rapid glucose analyser in Germany.
Insulin assay is with putting the method for exempting from (with Linco company rat insulin medicinal box special, special messenger is with batch mensuration).
Insulin, Area under the curve of blood glucose calculate (AUC): the computing formula adopting approximate trapezoid, and 0-120min blood glucose AUC=1/2 (0min value+120min is worth)+30min is worth+60min and is worth+90min value.
The synchronous insulin releasing of 2.2OGTT
2.3 insulin dyeing
2.3.1 sugared quick spirit is on the impact of experimental rat islet cells insulin expression
Select each group of rat pancreas routine paraffin wax embedding, carry out continuous paraffin section with SAKURA paraffin slicing machine, thickness 4 microns is got four adjacent sheets continuously and is extended piece, and is respectively used to HE dyeing, SABC detection.
Get pancreatic tissue section, with the anti-Iletin II (Lilly) antibody 1: 100 of Cavia porcellus, glicentin antibody 1: 100 carries out β cell, α cell dyeing.Two resist: EnVisionTM system, DAB nitrite ion (all reagent is DAKO Products)
Envision operation sequence
Dewaxing, aquation tissue slice.
Distilled water rinsing, is placed in TBS.
Drip 0.3%H
2o
2block endogenous peroxydase, hatch 15 minutes.
Distilled water rinsing, is placed in TBS 5 minutes X3 time.
Primary antibodie hatches 2 hours
In TBS rinsing TBS 5 minutes X3 time
Drip EnvisionTM and hatch 60 minutes.
TBS rinsing 5 minutes X3 time.
Color source DAB solution develops the color 3 minutes, distilled water color development stopping.
Gradient alcohol dehydration, mounting rubber seal sheet.
Basis of microscopic observation result.
Establish negative control during experiment simultaneously, adopt TBS to replace primary antibodie as blank negative control.
Result judges: occur in islet cells slurry that brown yellow granule is as positive.
Graphical analysis: graphical analysis center, Department Of Medicine, Peking University.
2.3.2 sugared quick spirit is on the impact of experimental rat B cell apoptosis rate
B cell apoptosis: original position art end labelling method (TUNEL) detects apoptotic cell (Roche company).Apoptotic nucleus dye dark-brown, and the cell simultaneously contrasting insulin stained positive in serial section is decided to be the B cell of apoptosis.In each islets of langerhans B cell apoptosis rate=each islets of langerhans in B cell apoptosis number/this islets of langerhans in sum × 100% of B cell, often open section and choose 5 islets of langerhans, average as the apoptosis rate of this sample B cell after calculating apoptosis rate respectively.
2.3.3 quantitative real-time PCR detects the impact that pancreas in rat caseaspe3mRNA expresses
Key instrument
AppliedBiosystems company of the GeneAmp5700TaqMANPCR instrument U.S.
PharmaciaBiotech company of the gel image analysis instrument ImageMasterVDS U.S.
High speed refrigerated centrifuge Germany BACKMAN company Allagra.21RCentrifcige
Ultraviolet spectrophotometer Germany BACKMAN company DU640 type
Electrophresis apparatus Liuyi Instruments Plant, Beijing OYY-III-5 type
Main agents:
Trizol(Invitrogen)
RevertAidTMFirstStrandcDNASynthesisKit(Fermentas)
SYBRGreenPCRMasterMix(AppliedBiosystems)
Primer adopts primerpremier5.0 design, and by match, Parkson company synthesizes.
2.3.4 from tissue, total serum IgE is extracted
● get after about 100mg tissue adds 1mlTrizol, be ground to tissue completely fragmentation, liquid thickness, room temperature places 5 minutes, makes its abundant cracking.
● add chloroform by 200ul chloroform/mlTrizol, shake up 15 seconds, room temperature places 15 minutes.
● centrifugal 15 minutes of 4 DEG C of 12000g.
● draw upper strata aqueous phase, in the centrifuge tube of another pre-cooling.
● add isopropyl alcohol (pre-cooling) mixing by 0.5ml isopropyl alcohol/mlTrizol, room temperature places 5-10min.
● 4 DEG C of centrifugal 10min of 12000g, abandon supernatant, RNA is sunken at the bottom of pipe.
● add 75% ethanol (pre-cooling) by 1ml75% ethanol/mlTrizol, gentle concussion centrifuge tube, suspend precipitation.
● 4 DEG C of centrifugal 5min of 7500g, abandon supernatant as far as possible.
● room temperature dries 5-10min.
● with 50 μ lRNase-freeH
2o, dissolves RNA sample, 55-60 DEG C of 10min.
● survey the quantitative RNA concentration of O.D value.
2.3.5 the concentration of spectrophotometry nucleic acid
With the spectrophotometer of argon lamp, before using thermally-stabilised 15 minutes in advance.
● draw 6 μ lRNA samples, after adding water to 1.5ml mixing, proceed in spectrophotometric quartz cuvette.
● 1ml water suppressed zero first used by spectrophotometer.
● read optical density respectively at 260nm and 280nm, the concentration of RNA sample is: OD260* nucleic acid extension rate * 40/1000; Concentration unit is μ g/ μ l.
Times 2.3.6RNA sample reverse transcription
● take out RNA template, reagent, after room temperature is melted, be placed on immediately in ice bath, DL device mixes, of short duration centrifugal.
● template denaturation:
TemplateRANxul(5.0ug)
Oligo(dT)
18primer0.5ug/ul1.0ul
DEPC treated water is to 12.0ul
Mixing, of short duration centrifugal, 70 DEG C of temperature baths 10 minutes, to be placed in ice bath at least 1 minute immediately.
● preparation reaction mixture (often pipe is by following amounts preparation)
5×reactionbuffer4.0ul
10mMdNTPMix2.0ul
RNaseInhibitor(20U/ul)1.0ul
Compound mixed solution amount is sample number N+2.
● often pipe adds the above-mentioned mixed liquor mixing of 7.0uL.37 DEG C of temperature are bathed 5 minutes.
● often pipe adds 1.0uLM-MuLVReverseTransciptase (200u/uL), and 42 DEG C of temperature are bathed 60 minutes, and 70 DEG C of temperature are bathed 10 minutes.-20 DEG C save backup.
2.3.7 fluorescence quantitative PCR detection
● primer and reagent
SYBRGreenPCRMasterMix:ABI (AppliedBiosystems), CatalogNo.43049155 primer sequence:
β-actin-FP：5’-GAGACCTTCAACACCCCAGCC-3’
β-actin-RP:5 '-AATGTCACGCACGATTTCCC-3 ' amplified fragments is 263bp.
Casepase3
Upstream: 5 '-AATTCAAGGGACGGGTCATG-3 '
Downstream: 5 '-GCTTGCGCGTACAGTTTC-3 ' amplified fragments is 475bp
● primer dilutes: diluted by final concentration 10pmol/ul by primer, and concrete grammar is V (ul)=O.D. value × 33ug/10M (DEPC process water volume needed for V=, M=primer molecule amount)
● the preparation of reaction mixture:
Taking out 2 × Buffer, RNase-freewater, cDNA puts at room temperature, melts, is placed on immediately in ice bath, DL device mixes, of short duration centrifugal.
The contained reagent of every person-portion mixed liquor (reaction system V=25ul) sees the following form
ComponentVolnme
2×SYBRGreenPCRMasterMix，12.5ul
xxx-Fprimer(10pmol/ul)1ul
xxx-Rprimer(10pmol/ul)1ul
Nuclease-freeH
2O8.5ul
TotalVolume23ul
After preparing mixed liquor, in each reaction tube, add 23ul mixed liquor.
● application of sample: each reaction tube adds 2.0ulcDNA template, DL device mixes, of short duration centrifugal (being less than 5sec).
● carry out at GeneAmp5700 quantitative real time PCR Instrument, reaction condition is as follows:
95.0℃：10min
/2.0℃：50sec
72.0℃：5min
More than reaction setting is all carried out on the computer be connected with PCR instrument, and each circulation computer records the fluorescence signal value in reaction tube automatically, and describes curve.Reaction terminates by PE5700 software analysis result, automatic calculation in quantity numerical value.
Experimental result is using the Ct value ratio of reference gene and genes of interest as the mRNA relative expression quantity of genes of interest, (because Ct value and actual expression are inversely, in order to intuitively, the Ct value ratio of genes of interest and Beta-actin is got inverse when analytical data by us, and namely the Ct value ratio of Beta-actin and target gene is as the relative expression quantity of its mRNA)
2.3.8 pancreatic tissue paraffin section cytochrome C immunohistochemical staining
Each 15 minutes of paraffin section dimethylbenzene I, II dewaxing, namely graded ethanol goes out namely to enter to water;
Flowing water embathes 5 minutes;
The H of 0.3%
2o
2solution oxide 15 minutes;
Flowing water embathes 5 minutes, and PBS washes 5 minutes × 3 times;
Drip 1: 100 cytochrome C primary antibodie of suitably dilution, 4 DEG C of refrigerator overnight incubation;
PBS washes 5 minutes × 3 times;
Drip 1: 400 biotin labeling two to resist, indwelling 1.5 hours (room temperature) in wet box;
PBS washes 5 clock × 3 time;
DAB solution develops the color 2 minutes;
Flowing water embathes 5 minutes;
Gradient alcohol dehydration, transparent each 15 minutes of dimethylbenzene I, II;
DPX mounting;
2.3.9 sugared quick spirit is to the Ultrastructural observation of experimental rat B cell
Get each 5 pieces of the fresh pancreatic tissue of rat, be fixed on 2.5% (volume fraction) glutaraldehyde solution immediately, then use 1% (volume fraction) osmic acid to fix.Acetone serial dehydration, Epon812 embeds.Ultrathin section color is done after the islets of langerhans of semithin section location.
JBVI-1230 type transmission electron microscope observing.
2.4 ultramicroscope Ultrastructural observation
2.5 pancreas MASSON dye
2.6 pancreas α-SMA dyes
ImmunohistochemistryMethods Methods is the same.
3. result
Pancreas pathology shows
The B cell quantity of the model group insulin labelling positive obviously reduces, and cell arrangement is disorderly, and insulin stained positive granule understain in endochylema, fibrosis region islets of langerhans is negative staining, and two treatment groups are improved in various degree.(see Fig. 1-3)
Wherein, Fig. 1 model group insulin positive cells reduces, fall into disarray,
Fig. 2 cell is not limited to periphery, and distribution is mixed and disorderly,
Fig. 3 model group islets of langerhans split by the fibrous connective tissue hypertrophy of green dye encirclement
Fig. 4 pancreas α-SMA dyes expression, model group islets of langerhans stellate cell activation hypertrophy continuous expression α-SMA
Electron microscope observation islets of langerhans thin vessels ultrastructure
Electronic Speculum result shows, and model group compares with LETO, and the apparition of islets of langerhans microangiopathy increases the weight of, and two treatment groups alleviate in various degree, and microangiopathies degree and diabetic lesions have conforming trend.(see Fig. 5-8)
Wherein, Fig. 5 LETO group blood capillary basement membrane is more even; Fig. 6 OLETF group blood capillary basement membrane became uneven is even, tube wall thickening, short texture, and collagen fiber and fibroblast increase, visible layer structure; Fig. 7 rosiglitazone group blood capillary basement membrane became uneven is even, tube wall thickening, short texture; Fig. 8 dissipating depression of QI heat clearing away group blood capillary basement membrane slightly thickens.
By the above-mentioned experiment of the present invention, prove the quick minimizing islets of langerhans microvascular lesions of having quick access to information of medicine sugar further, suppress stellate cell activation in islets of langerhans; thus alleviate islets of langerhans fibrous connective tissue hypertrophy; protection blood vessel islets of langerhans endothelium, and then improve microenvironment of pancreas islet, finally reach treatment and prevention type 2 diabetes mellitus.
Type 2 diabetes mellitus of the present invention is the type 2 diabetes mellitus that Fatty toxicity causes, or the type 2 diabetes mellitus that sugared toxicity causes.
Accompanying drawing explanation
Fig. 1 tests each group of pancreatic insulin dyeing
Fig. 2 tests each group of pancreas glucagon dyeing
Fig. 3 tests each group of pancreas pancreas MASSON and dyes
Fig. 4 tests each group of pancreas α-SMA and dyes
Fig. 5 LETO group
Fig. 6 OLETF group
Fig. 7 rosiglitazone group
Fig. 8 dissipating depression of QI heat clearing away group
Detailed description of the invention
By following specific embodiment, the invention will be further described, but not as limitation of the present invention.
The preparation of embodiment 1, the quick curing capsule of sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add lactose and make capsule.
The preparation of the quick clever tablet of embodiment 2, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add dextrin and make tablet.
The preparation of the quick clever granule of embodiment 3, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
60 DEG C of forced air dryings, granulate, granulate, obtains granule.
The preparation of embodiment 4, the quick drop pills of sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
The Polyethylene Glycol added, mix homogeneously, melting, upper pill dripping machine, makes drop pill.
The preparation of the quick clever oral cavity disintegration tablet of embodiment 5, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add 5% polyvinylpolypyrrolidone, the magnesium stearate of 0.1%, the microcrystalline Cellulose of 50%, make soft material with ethanol in proper amount solution, granulate, 60 DEG C of forced air dryings, granulate, granulate, tabletted, obtains oral cavity disintegration tablet.
The preparation of the quick curing capsule agent of embodiment 6, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add appropriate amount of starch, sucrose and magnesium stearate, granulate, incapsulate, obtain capsule.
The preparation of the quick clever tablet of embodiment 7, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
With starch, sodium carboxymethyl cellulose, Pulvis Talci mix homogeneously, granulate, namely tabletting obtains tablet.
The preparation of embodiment 8, the quick Ling oral liquid of sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
With syrup 4g, be dissolved in the pure water of 100ml, homogenizing, filter, through high-temperature short-time sterilization (135 DEG C, 4s).Sterile filling, subpackage, obtained oral liquid.
The preparation of embodiment 9, the quick Ling oral liquid of sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
With syrup 5g, be dissolved in the pure water of 100ml, homogenizing, filter, through high-temperature short-time sterilization (135 DEG C, 4s).Sterile filling, subpackage, obtained oral liquid.
The preparation of embodiment 10, the quick curing capsule of sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add lactose and make capsule.
The preparation of embodiment 11, the quick curing capsule of sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add lactose and make capsule.
The preparation of the quick clever tablet of embodiment 12, sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add dextrin and make tablet.
The preparation of the quick clever tablet of embodiment 13, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add dextrin and make tablet.
The preparation of the quick clever granule of embodiment 14, sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
60 DEG C of forced air dryings, granulate, granulate, obtains granule.
The preparation of the quick clever granule of embodiment 15, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
60 DEG C of forced air dryings, granulate, granulate, obtains granule.
The preparation of embodiment 16, the quick drop pills of sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
The Polyethylene Glycol added, mix homogeneously, melting, upper pill dripping machine, makes drop pill.
The preparation of embodiment 17, the quick drop pills of sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
The Polyethylene Glycol added, mix homogeneously, melting, upper pill dripping machine, makes drop pill.
The preparation of the quick clever oral cavity disintegration tablet of embodiment 18, sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add 5% polyvinylpolypyrrolidone, the magnesium stearate of 0.1%, the microcrystalline Cellulose of 50%, make soft material with ethanol in proper amount solution, granulate, 60 DEG C of forced air dryings, granulate, granulate, tabletted, obtains oral cavity disintegration tablet.
The preparation of the quick clever oral cavity disintegration tablet of embodiment 19, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add 5% polyvinylpolypyrrolidone, the magnesium stearate of 0.1%, the microcrystalline Cellulose of 50%, make soft material with ethanol in proper amount solution, granulate, 60 DEG C of forced air dryings, granulate, granulate, tabletted, obtains oral cavity disintegration tablet.
The preparation of the quick curing capsule agent of embodiment 20, sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add appropriate amount of starch, sucrose and magnesium stearate, granulate, incapsulate, obtain capsule.
The preparation of the quick curing capsule agent of embodiment 21, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add appropriate amount of starch, sucrose and magnesium stearate, granulate, incapsulate, obtain capsule.
The preparation of the quick curing capsule agent of embodiment 22, sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
With syrup 4g, be dissolved in the pure water of 100ml, homogenizing, filter, through high-temperature short-time sterilization (135 DEG C, 4s).Sterile filling, subpackage, obtained oral liquid.
The preparation of the quick curing capsule agent of embodiment 23, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
With syrup 4g, be dissolved in the pure water of 100ml, homogenizing, filter, through high-temperature short-time sterilization (135 DEG C, 4s).Sterile filling, subpackage, obtained oral liquid.
The preparation of the quick curing capsule agent of embodiment 24, sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
With syrup 4g, be dissolved in the pure water of 100ml, homogenizing, filter, through high-temperature short-time sterilization (135 DEG C, 4s).Sterile filling, subpackage, obtained oral liquid.
The preparation of the quick curing capsule agent of embodiment 25, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
With syrup 4g, be dissolved in the pure water of 100ml, homogenizing, filter, through high-temperature short-time sterilization (135 DEG C, 4s).Sterile filling, subpackage, obtained oral liquid.
The preparation of the quick clever injectable powder of embodiment 26, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g, Rhizoma Polygonati 9g, Radix Ginseng 9g, Fructus Momordicae charantiae 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add glucose 4.5g, sodium thiosulfate 0.9g and distilled water 1ml again, after said components mix homogeneously, lyophilization, subpackage, obtains injectable powder.
The preparation of the quick clever injectable powder of embodiment 27, sugar of the present invention
Get Radix Trichosanthis 9g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add glucose 4.5g, sodium thiosulfate 0.9g and distilled water 1ml again, after said components mix homogeneously, lyophilization, subpackage, obtains injectable powder.
The preparation of the quick clever injectable powder of embodiment 28, sugar of the present invention
Get Radix Trichosanthis 30g, Radix Bupleuri 12g, Fructus Aurantii Immaturus 9g, Radix Et Rhizoma Rhei 3g, Rhizoma Pinelliae 6g, Radix Scutellariae 9g, Rhizoma Coptidis 6g, Radix Paeoniae Alba 9g, Fructus Mume 15g, Fructus Crataegi 9g;
Add the ethanol of 4 times amount 80%, 60 DEG C of reflux, extract, 3 times, each 1.5 hours, merge extractive liquid, ethanol are reclaimed in 70 DEG C of pressurizations, and 80 DEG C of vacuum dryings, pulverized 80 mesh sieves, and obtained drug extract;
Add glucose 4.5g, sodium thiosulfate 0.9g and distilled water 1ml again, after said components mix homogeneously, lyophilization, subpackage, obtains injectable powder.
Group component in above-described embodiment can expand or reduce in scale according to need of production simultaneously.
Claims (6)
1. a pharmaceutical composition is preparing the application improved in hyperinsulinemia disease drug, wherein said pharmaceutical composition is that prescription is formulated by the raw material of Chinese medicine medicine of following weight portion: Radix Trichosanthis 5-40 part, Radix Bupleuri 10-30 part, Fructus Aurantii Immaturus 3-15 part, Radix Et Rhizoma Rhei 1-6 part, Rhizoma Pinelliae 1-12 part, Radix Scutellariae 3-15 part, Rhizoma Coptidis 1-12 part, Radix Paeoniae Alba 3-15 part, Fructus Mume 5-20 part
Wherein, described pharmaceutical composition, by protection islets of langerhans Β cell, reduces islets of langerhans microvascular lesions, suppresses stellate cell activation in islets of langerhans, alleviate islets of langerhans fibrous connective tissue hypertrophy, protection blood vessel islets of langerhans endothelium, thus improves microenvironment of pancreas islet.
2. application according to claim 1, it is characterized in that, middle Fructus Crataegi can also be added in pharmaceutical composition prescription, the formula obtained is: Radix Trichosanthis 10-30 part, Radix Bupleuri 10-30 part, Fructus Aurantii Immaturus 3-15 part, Radix Et Rhizoma Rhei 1-6 part, Rhizoma Pinelliae 1-12 part, Radix Scutellariae 3-15 part, Rhizoma Coptidis 1-12 part, Radix Paeoniae Alba 3-15 part, Fructus Mume 5-20 part, Fructus Crataegi 3-15 part.
3. application according to claim 1, it is characterized in that, middle Fructus Crataegi can also be added in pharmaceutical composition prescription, Rhizoma Polygonati, Radix Ginseng and Fructus Momordicae charantiae, the formula obtained is: Radix Trichosanthis 10-30 part, Radix Bupleuri 10-30 part, Fructus Aurantii Immaturus 3-15 part, Radix Et Rhizoma Rhei, 1-6 part, Rhizoma Pinelliae 1-12 part, Radix Scutellariae 3-15 part, Rhizoma Coptidis 1-12 part, Radix Paeoniae Alba 3-15 part, Fructus Mume 5-20 part, Fructus Crataegi 3-15 part, Rhizoma Polygonati 3-15 part, Radix Ginseng 3-15 part, Fructus Momordicae charantiae 3-15 part.
4. application according to claim 1, is characterized in that, pharmaceutical composition prescription is: Radix Trichosanthis 9 parts, Radix Bupleuri 12 parts, Fructus Aurantii Immaturus 9 parts, Radix Et Rhizoma Rhei 3 parts, the Rhizoma Pinelliae 6 parts, Radix Scutellariae 9 parts, Rhizoma Coptidis 6 parts, the Radix Paeoniae Alba 9 parts, Fructus Mume 9 parts.
5. application according to claim 2, is characterized in that, pharmaceutical composition prescription is: Radix Trichosanthis 30 parts, Radix Bupleuri 12 parts, Fructus Aurantii Immaturus 9 parts, Radix Et Rhizoma Rhei 3 parts, the Rhizoma Pinelliae 6 parts, Radix Scutellariae 9 parts, Rhizoma Coptidis 6 parts, the Radix Paeoniae Alba 9 parts, Fructus Mume 15 parts, Fructus Crataegi 9 parts.
6. application according to claim 3, it is characterized in that, pharmaceutical composition prescription is: Radix Trichosanthis 30 parts, Radix Bupleuri 12 parts, Fructus Aurantii Immaturus 9 parts, Radix Et Rhizoma Rhei 3 parts, the Rhizoma Pinelliae 6 parts, Radix Scutellariae 9 parts, Rhizoma Coptidis 6 parts, the Radix Paeoniae Alba 9 parts, Fructus Mume 15 parts, Fructus Crataegi 9 parts, Rhizoma Polygonati 9 parts, Radix Ginseng 9 parts, 9 parts, Fructus Momordicae charantiae.
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| CN201010156334.XA CN102233078B (en) | 2010-04-27 | 2010-04-27 | A kind of pharmaceutical composition regulates the application improved in microenvironment of pancreas islet medicine in preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100493572C (en) * | 2004-07-30 | 2009-06-03 | 天津天士力制药股份有限公司 | Composition of medication for treating diabetes |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100493572C (en) * | 2004-07-30 | 2009-06-03 | 天津天士力制药股份有限公司 | Composition of medication for treating diabetes |
Non-Patent Citations (1)
| Title |
|---|
| 中医药治疗2型糖尿病胰岛素抵抗用药分析;莫娜，等;《陕西中医》;20090131;第30卷(第1期);第88-90页 * |
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