CN106266019A - A kind of Chinese medicine preparation treating diabetes and preparation method thereof and detection method - Google Patents

Abstract

The invention discloses a kind of Chinese medicine preparation treating diabetes and preparation method thereof, described preparation method includes: calculate by weight, and the section of weighing dies young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, add 6～10 times amount water, soak 30～120 minutes, decoct 1～2 hour, filter, take filtrate standby；Medicinal residues add 6～10 times amount soak by water 1～2 hours, filter；Merge twice filtrate, filter, concentrate, dry, pulverize, add adjuvant, make corresponding Chinese medicine preparation, to obtain final product.The Chinese medicine preparation blood sugar lowering of the treatment diabetes that the present invention is made up of Miao Ethnomedicine secret recipe is notable, has more preferable therapeutic effect.This prescription derives from folk remedy, the use history of existing more than 50 year, it it is the prescription summed up by clinical practice, have consolidate yin nourishing, change turbid promote blood circulation, effect of promoting the production of body fluid to quench thirst, particularly with the diabetes caused by deficiency of both QI and YIN and complication, there is obvious blood sugar reducing function, and this blood sugar reducing function is not entirely dependent on promotion B cell secretion.

Description

A kind of Chinese medicine preparation treating diabetes and preparation method thereof and detection method

Technical field

The present invention relates to a kind of Chinese medicine preparation (the peaceful removing obstruction from collaterals pill of sugar) treating diabetes and preparation method thereof, belong to technical field of Chinese medicines.

Background technology

Diabetes are the common frdquently encountered diseases of serious harm human health, and the bran urine patient of current China increases year by year, has been over ten thousand people more than 2,000, Global diabetics has been over 100,000,000 people, and already, diabetes have become as a worldwide problem.Distribution of diabetes is only second to dislike Property tumor and cardiovascular disease, be the third-largest disease jeopardizing human life.

China is in terms for the treatment of diabetes for thousands of years, have accumulated rich experience.In recent years, there have been many Chinese medicine formula Shens treating diabetes Please patent of invention, such as Application No. 201010259466.5 disclosed " medicines of radical cure diabetes and preparation method thereof ", Application No. 201110346174.X disclosed " a kind of Chinese medicine treating type 2 diabetes mellitus insulin resistant ", Application No. 201110048889.7 are disclosed " a kind of The medicine for the treatment of type 2 diabetes mellitus insulin resistant " etc..But these existing antidiabetic drug effects are not notable, are not reaching to good therapeutic effect. So that people continue to excavate Chinese material medicine resource, develop more efficiently medicine.

Summary of the invention

It is an object of the invention to, it is provided that a kind of Chinese medicine preparation treating diabetes and preparation method thereof, described Chinese medicine preparation hypoglycemic effect is notable, More preferable therapeutic effect can be obtained.

For solving above-mentioned technical problem, the present invention adopts the following technical scheme that: a kind of Chinese medicine preparation treating diabetes, calculates by weight, it Active component be prepared from by following crude drug:

Section dies young Luo Qu 400～300～400 parts of Herba Agrimoniaes of 550 portions of Herba Plantaginiss 300～400 parts of Flos Lonicerae 300～400 parts.

In the Chinese medicine preparation of aforesaid treatment diabetes, it is preferred that calculate by weight, it is prepared from by following crude drug:

Section dies young 480 portions of Herba Plantaginiss of Luo Qu 350 parts

335 parts of Flos Lonicerae of Herba Agrimoniae 335 parts.

In the Chinese medicine preparation of aforesaid treatment diabetes, described section dies young Luo Qu, calculates by weight, by the fresh Fructus Trichosanthis of medical material 2 parts, fresh Sanguis Gallus domesticus 2 parts of rattan and 1 part of mixture formed of fresh Herba Sedi are after squeezing extracting juice, and the dry fine powder of medicinal residues mixes with flour 2 parts, 1 part of wheat bran again, Add medicine juice, carry out zymolysis through song system and form.

In the Chinese medicine preparation of aforesaid treatment diabetes, it is preferred that the dry fine powder of described medicinal residues and flour and the mixture of wheat bran, add medicine juice Stirring evenly and make soft material, steam thoroughly, to keep temperature be 18～26 DEG C, humidity is 45%～65%, adds bent essence fermentation 20 days～30 days, takes out, dry Dry, pulverize, Ji get section dies young Luo Qu.

In the Chinese medicine preparation of aforesaid treatment diabetes, aforementioned section die young Luo Qu preparation method in, water can also be added while adding whole medicine juice.

In the Chinese medicine preparation of aforesaid treatment diabetes, described section dies young Luo Qu, calculates by weight, by the fresh Fructus Trichosanthis of medical material 2 parts, fresh Sanguis Gallus domesticus 2 parts of rattan and 1 part of mixture formed of fresh Herba Sedi are after squeezing extracting juice, and the dry fine powder of medicinal residues mixes with flour 2 parts, 1 part of wheat bran again, Add medicine juice, carry out zymolysis through song system and form.

In the Chinese medicine preparation of aforesaid treatment diabetes, described section die young Luo Qu by the fresh Fructus Trichosanthis of medical material, fresh Exocarpium Benincasae, Herba Sedi with 2:2:1 Weight ratio mixing；After drying, it is ground into fine powder, then with this fine powder: flour: the weight proportion mixing of wheat bran=5:2:1, add medicine juice, with Shi Jiashui stirs evenly and makes soft material, steams thoroughly, and to keep temperature be 18～26 DEG C, humidity is 45%～65%, adds bent essence fermentation 20～30 days, takes out, Dry, pulverize, to obtain final product.

The preparation method of the Chinese medicine preparation of aforesaid treatment diabetes, calculate by weight, the section of weighing dies young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Shan Yin Flower, adds 6～10 times amount water, soaks 30～120 minutes, decoct 1～2 hour, filters, takes filtrate standby；Medicinal residues add 6～10 times amount decoctings Boil 1～2 hour, filter；Merge twice filtrate, filter, concentrate, dry, pulverize, add adjuvant, make corresponding Chinese medicine preparation, to obtain final product.

The preparation method of the Chinese medicine preparation of aforesaid treatment diabetes, it is preferred that described preparation method includes: calculate by weight, and the section of weighing dies young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, cut into 1.0cm section by Herba Plantaginis and Herba Agrimoniae, adds 8 times amount water, soaks 30 minutes, decocts 2 Hour, filter, take filtrate standby；Medicinal residues add 6 times amount soak by water 1 hour, filter, merge twice filtrate, filter, and are condensed into 60 DEG C relative Density is the clear paste of 1.2～1.3, under conditions of temperature 55～75 DEG C, vacuum 0.08～0.1Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, Add adjuvant, make corresponding Chinese medicine preparation, to obtain final product.

The preparation method of the Chinese medicine preparation of aforesaid treatment diabetes, it is furthermore preferred that described preparation method includes: calculate by weight, weigh section Die young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, Herba Plantaginis and Herba Agrimoniae are cut into 1.0cm section, adds 8 times amount water, soak 30 minutes, decoct Boil 2 hours, filter, take filtrate standby；Medicinal residues add 6 times amount soak by water 1 hour, filter, merge twice filtrate, filter, are condensed into 60 DEG C Relative density is the clear paste of 1.2, under conditions of temperature 65 DEG C, vacuum 0.1Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, granulate, add Enter dry cream gross weight 0.37% silicon dioxide, mixing, load capsule, obtain capsule.

Aforementioned Chinese medicine preparation prepare tablet, also include the filler of active component weight 1%-5%, the disintegrating agent of active component weight 10%-20%, Inventory 40-60% and concentration are the binding agent of 10-15%, inventory 0.1-0.5% lubricant.The binding agent of described inventory 40-60% refers to glue The amount of mixture is the 40-60% of the material total amount after active component addition filler, disintegrating agent；The lubricant of described inventory 0.1-0.5% refers to profit The amount of lubrication prescription is the 0.1-0.5% of the material total amount after active component addition filler, disintegrating agent, binding agent.

The tablet that aforementioned Chinese medicine preparation prepares, described filler is pregelatinized Starch, and described disintegrating agent is carboxymethyl starch or/and microcrystalline Cellulose, Described binding agent is starch slurry, and described lubricant is silicon dioxide or/and magnesium stearate.

The tablet that aforementioned Chinese medicine preparation prepares, described disintegrating agent includes 1-3 part carboxymethyl starch and 10-20 part microcrystalline Cellulose by weight；Institute The lubricant stated includes 1-5 part silicon dioxide and 1-5 part magnesium stearate by weight.

The tablet that aforementioned Chinese medicine preparation prepares, also includes the carboxymethyl starch sodium of active component weight 1.67%, the pregelatinated of active component weight 2.9% Starch, the microcrystalline Cellulose of active component weight 15.67%, inventory 55% and starch slurry that concentration is 12%, the silicon dioxide of inventory 0.16% And magnesium stearate, wherein silicon dioxide: the weight ratio of magnesium stearate is 1:1.

The preparation method of aforementioned tablet, the section of taking dies young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae four taste, soaks 30 minutes, decocts twice, 2 hours for the first time, 1 hour for the second time, collecting decoction, filter, concentrate, be dried to dry cream；Pulverize, cross 100 mesh sieves, add carboxymethyl starch Sodium, pregelatinized Starch and microcrystalline Cellulose, pelletize, and is dried, granulate, adds mix lubricant uniformly, is pressed into 1000, film coating, Obtain.

The preparation method of aforementioned tablet, the section of weighing dies young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, and Herba Plantaginis and Herba Agrimoniae are cut into 1.0cm section, Add 8 times amount water, soak 30 minutes, decoct 2 hours, filter, take filtrate standby；Medicinal residues add 6 times amount soak by water 1 hour, filter, and merge Twice filtrate, filters, is condensed into the clear paste that relative density is 1.2 of 60 DEG C, is subtracted by clear paste under conditions of temperature 65 DEG C, vacuum 0.1Mpa Pressure is dried to dry cream；Pulverize, granulate, cross 100 mesh sieves, add the carboxymethylstach sodium of dry cream gross weight 1.67%, the pregelatinized Starch of 2.9%, 15.67% Microcrystalline Cellulose, with inventory 55% and starch slurry that concentration is 12% be that binding agent is pelletized, take out wet granular and be dried in 65～75 DEG C, Dry granule is with after No. two sieve granulate, and it is uniform that the silicon dioxide of the 1:1 of admixture doses 0.16% and magnesium stearate make mix lubricant, and tabletting wraps thin Film clothing, to obtain final product.

The detection method of aforementioned tablet, (1) takes this product and removes coating, grind to form fine powder, weighs 1.3g, ultrasonic 30 minutes of the methanol of addition 10ml Filtering, take filtrate 5ml, add a small amount of magnesium powder, drip 12～14 concentrated hydrochloric acid, water-bath 1～2 minutes, solution becomes reddish violet.

(2) taking this product and remove coating, grind to form fine powder, weigh 3.8g, add 95% ethanol 50ml, reflux, extract, 2 hours, filter, filtrate is dense It is reduced to 5ml, as need testing solution.Separately take luteoloside reference substance, add methanol and make every 1ml solution containing 0.4mg, as reference substance solution. Test according to thin layer chromatography (one annex VI B of " Chinese Pharmacopoeia " version in 2010), draw need testing solution 3.5 μ l, reference substance solution 1 μ l, Put respectively on same silica gel G plate, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, take out, dry, spray With 5% aluminum chloride ethanol solution, 105 DEG C are heated 10 minutes, let cool, put and inspect under uviol lamp (365nm).In test sample chromatograph, with right According on product chromatograph relevant position, show the fluorescence speckle of same color.

(3) taking this product and remove coating, grind to form fine powder, weigh 2.6g, add 95% ethanol 50ml, reflux, extract, 2 hours, filter, filtrate concentrates To 10ml, as need testing solution.Separately take Big Semen Plantaginis glycosides reference substance, add 60% methanol and make every 1ml solution containing 0.1mg, as reference substance Solution.Test according to thin layer chromatography (one annex VI B of " Chinese Pharmacopoeia " version in 2010), draw need testing solution 2 μ l, reference substance solution 2 μ l, Put respectively on same polyamide film, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, open up away from for 5cm, Take out, heat 10 minutes at 60 DEG C, put and inspect under uviol lamp (365nm).In test sample chromatograph, on position corresponding with reference substance chromatograph, The fluorescence speckle of aobvious same color.

(4) taking this product and remove coating, grind to form fine powder, weigh 2.6g, add methanol 30ml, reflux, extract, 3 hours, filter, filtrate is concentrated into 10ml, As need testing solution.Separately take 3,5-Dicaffeoylquinic acid reference substance, add methanol and make every 1ml solution containing 0.4mg, as reference substance solution.According to thin layer Chromatography (" Chinese Pharmacopoeia " 2010 editions one annex VI B) is tested, and draws need testing solution 2 μ l, reference substance solution 1 μ l, puts respectively in same On one polyamide film, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, open up away from for 5cm, take out, 60 DEG C heating 10 minutes, put and inspect under uviol lamp (365nm).In test sample chromatograph, with on reference substance chromatograph relevant position, show same color Fluorescence speckle.

[inspection] should meet every regulation (one annex I D of " Chinese Pharmacopoeia " version in 2010) relevant under tablet item

[extractum] measures according to Extract mensuration (" Chinese Pharmacopoeia " version annex Ⅹ A Extract mensuration hot dipping in 2010), and this product is water-soluble Property extractum must not be less than 25.0%.

[character] this product is Film coated tablets, should show brown to sepia, feeble QI, bitter in the mouth after removing coating.

In order to ensure the effect of the present invention, the applicant has carried out the preparation technology of the series of experiments pharmaceutical preparation to select the present invention to provide, it is ensured that Science, reasonable, feasible.Specific as follows:

Experimental example 1: the selection of dosage form

This product is made up of die young Luo Qu, Herba Plantaginis, Herba Agrimoniae, Flos Lonicerae four Chinese medicine of section, be combine the Empirical formula that Seedling doctor's Long-term clinical uses on the basis of, Combine with dialectical debating disease, in belonging to according to the Therapeutic Method of " treatment through spleen diabetes " and the Seedling medical knowledge opinion of " two sick two guiding principles ", diabetes and complication Cold outer heat symptom-complex, needs that heat is cold takes into account medication to establish method for the treatment of, carries out selecting medicine prescription.Fang Zhongke die young Luo Qu carbon be Seedling doctor peculiar, have replenishing QI to invigorate the spleen, life The effect quenched one's thirst in Tianjin, function of spleen and stomach regulating, benefit liquid fills as the medicine of a warm nature, enters cold warp, owner's medicine；Herba Agrimoniae astringing to arrest bleeding, preventing the attack (or recurrence) of malaria, dysentery relieving, removing toxic substances；Herba Plantaginis Grass clearing away heat and promoting diuresis, eliminates the phlegm, removing heat from blood, removing toxic substances；Flos Lonicerae dispelling wind detoxifies, and stomach function regulating promotes the production of body fluid；Rear three tastes all belong to cold medicine and enter hot warp, are accessory drugs altogether；All medicines Wu Yong, play altogether consolidate yin nourishing, change turbid promote blood circulation, effect of promoting the production of body fluid to quench thirst.Capsule is compared with tablet, and capsule is not added with pressure, so medicine exists Gastrointestinal tract disintegrate is fast, thus effective soon, good absorbing；It addition, capsule is light tight, photosensitive medicine and meet wet heat-labile medicine, load After capsule, the impact of the oxygen in dampness and air and light can be protected the drug from, thus its stability can be improved.Therefore, in retaining as far as possible In the feature that after medicine traditional decoction, decoction is directly taken, it is considered to the dosage form of use capsule and the fewest adds adjuvant to carry out technical study.

Experimental example 2: Study on Preparation

For making the composition of prescription Chinese crude drug extract as far as possible, with paste-forming rate as inspection target, process of preparing Chinese medicine length, the amount of water to medical material, soak time, Decocting time, decoction number of times are investigated respectively, and its result is as follows:

(1) process of preparing Chinese medicine length of the prescription Chinese crude drug impact on paste-forming rate

Herba Plantaginis, Herba Agrimoniae are concocted into different length, and the decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, with 10 times Medical material is infiltrated 30 minutes by amount water, decocts 2 times, each 2 hours, filters, merging filtrate, and concentration carries out paste-forming rate mensuration, the results are shown in Table 1:

The impact on paste-forming rate of the table 1 medicinal material processing length

As shown in Table 1: the paste-forming rate of medicinal material coarse powder is the highest, but after medicinal material coarse powder is extracted, medicinal liquid is difficult to filter, and during experiment, the method for machinery used drains Medicinal residues, are not suitable for big commercial production；And the paste-forming rate that cuts into 1.0cm section is close with it, therefore Herba Plantaginis, Herba Agrimoniae are cut into 1.0cm section and enter Row extraction is preferred.

(2) soak time impact on paste-forming rate

Herba Plantaginis, Herba Agrimoniae are concocted into 1.0cm section, and the decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, uses 10 times amount Medical material is infiltrated different time by water, decocts 2 times, each 2 hours, filters, merging filtrate, concentrate, carry out paste-forming rate mensuration, the results are shown in Table 2 institutes Show:

The different soak time impact on paste-forming rate of table 2

As shown in Table 2: different soak times, the paste-forming rate of medical material is affected little, from the consideration that saves time and cost, infiltrating 30 minutes be Good.

(3) impact on paste-forming rate of different amount of water, decocting time and the extraction times

Herba Plantaginis, Herba Agrimoniae are concocted into 1.0cm section, and the decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, with different Amount of water, soaks 30 minutes, extracts with different decocting times and extraction time, filters, filtrate, concentrates, and carries out paste-forming rate mensuration, specifically with Scheme in table 3 below is investigated, and result of the test is as shown in table 4:

The extraction scheme that table 3 is different

The different extraction scheme impact on extractum yield of table 4

From table 3, table 4: prescription medicinal material extract 2 times, adding 8 times amount water soaking 30 minutes for the first time, decoct 2 hours, second time adds 6 times amount decoctings After boiling 1 hour, extractum yield almost no longer increases, and from saving the energy and time cost consideration, concocts into 1.0cm section, mountain with Herba Plantaginis, Herba Agrimoniae The decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, decocts 2 times, is infiltrated 30 minutes by medical material with 8 times amount water for the first time, decoction 2 hours；Second time 6 times amount soak by water 1 hour, filtration, the technique of merging filtrate is preferred.

Described paste-forming rate measures method particularly includes: takes and is concentrated into the clear paste that relative density is 1.2～1.3 (mensuration temperature 60 Cs), shifts and fixed Hold to 1000ml volumetric flask, shake up；Precision measures 20ml, is respectively placed in the evaporating dish of constant weight, and water-bath volatilizes, and residue is done in 105 DEG C Dry 3 hours, take out, put in exsiccator and place 30 minutes, weigh, calculate.

(4) concentrate and drying process is studied

Crude extract test use (the 300 mesh filter cloth) method of filtration to carry out, for preventing effective ingredient for a long time by heat damage, in conjunction with industrial process conditions, Triple effect concentrating under reduced pressure equipment is used to concentrate.Result shows: the clear paste that the filtrate reduced in volume of merging becomes relative density to be 1.2～1.3, measures temperature Degree is 60 DEG C；Drying condition is simultaneously: temperature 55～75 DEG C, and during vacuum 0.08～0.1Mpa, effect is best.

(5) lubricant and the screening of consumption

Dried extractum is beaten powder and crosses 60 mesh, directly fill capsule, find that the mobility of powder is the poorest, affect loading amount, therefore consider to add lubrication Agent.Through preliminary experiment, draw and make lubricant best results with silicon dioxide；With powder flowbility as inspection target, the addition of silicon dioxide is entered Row is investigated, and result is as shown in table 5:

The addition experiment investigation result of table 5 silicon dioxide

As shown in Table 5: when the addition of silicon dioxide is the 0.27% of crude drug total amount, powder flowbility is general, adds the 0.37% of total amount and total Amount 0.47% time, powder flowbility is all preferable, from the standpoint of cost-effective, with add total amount 0.37% silicon dioxide as optimum selection.

(6) section dies young the preparation method research of Luo Qu:

Research shows, section dies young, and to prepare effect preferable for sieve Qu Caiyong following methods:

Weigh the fresh Fructus Trichosanthis of medical material, fresh Caulis Spatholobi and fresh Herba Sedi by proportioning, squeeze extracting juice, standby；Medicinal residues are dried, it is ground into fine powder； Weigh flour and wheat bran by proportioning, flour and wheat bran are mixed with medicinal residues fine powder, add medicine juice and water stirs evenly and makes soft material, steam thoroughly, keep the temperature to be 18～26 DEG C, humidity be 45%～65%, add bent essence fermentation 20～30 days, take out, dry, pulverize, to obtain final product.

Section die young Luo Qu preparation method in:

One,

1, leaven embryo arrangement pitch: 3-4cm () under the palm bar of side freely；

2, fermentation culture origin temp 23-25 DEG C (summer is the lowest more good)；

3, room culture requirement Caulis et Folium Oryzae is depending on season, winter: pad and lid reaches 3 centimeters of thickness；Summer: pad and lid reaches 2 centimeters of thickness；

4, fermentation culture, product temperature Gao Shida 56 DEG C (latter three days will be according to the suitable humidity discharging of weather)；

5, upper wallette requires as the most rectangular row, highly 4-7 layer；

6, later stage fermentation cultivation temperature 28-30 DEG C, and carry out ventilation；

7, ferment complete, upper big-wall height 6-8 layer.

Two, fermentation management:

1, primary fermentation is in 2-3 days, insulation, water conservation so that it is normal fermentation；

2, ferment middle is in 4-7 days, and ventilation humidity discharging is proper, keeps bent embryo surface humidity, moist, cracking；

3, turn over and bent upper and lower change face, as temperature is too high, pull open the distance between bent embryo.

Three, critical process:

1, early stage cultivation:

Along with season and the difference of room temperature, bent embryo heats up the most different, and summer heats up hurry up, and winter is slowly, when being gradually increasing along with temperature, more bent Aqueous humor vapour increases, humid, and bent room temperature is raised to 30-45 DEG C, bent embryo surface have mycelia (when presenting white dot, should spare no effort to check, and according to Indoor temperature, humidity condition, carry out humidity discharging).If bent embryo surface moisture content is evaporated to a certain degree, and band is hard, tack-free, can carry out turning over song, Its method is to translate into bottom knee-piece above, surrounding turn to centre, middle turns to surrounding, according to determining the distance of knee-piece season, and builds one Layer Caulis et Folium Oryzae, insulation of closing the doors and windows.

2, middle term management:

1. after turning over song, closing the doors and windows, bent room temperature can be gradually increasing, and when temperature rises to more than 45-50 DEG C, (depending on medium and high temperature Qu Erding) is entered Row second time turns over song, closes the doors and windows after having turned over.

2. when temperature continuously rises to 35-45 DEG C again, door and window to be opened, and want humidity discharging, regulate temperature, when temperature drops to 30 DEG C, (summer is with room Temperature is as the criterion) carry out turning over song for the second time.

3. according to ramp case, the degree of drying of bent embryo, turns over bent 4-6 time；Often turning over once, after upper wallette, knee-piece is high one layer, when bent room heats up basic At the end of, when having obvious Qu Xiangqi taste, knee-piece is mature on the whole.

3, final-period management:

Different depending on season, when bent room temperature is gradually decreased to 10-35 DEG C, can above big-wall, i.e. the knee-piece being mature on the whole gradually is concentrated and is deposited between one In room, it is desirable to pendulum is real, be close to (ground backing plate to be added).Whole fermentation time was at 16-25 days, it is desirable to interior nothing amass wet, mildew good, moisture≤20.0%； Use after storing three months, physical and chemical index: moisture≤14.0%.

It addition, die young Luo Qu for section:

Check: moisture must not cross 9.0% (one annex Ⅸ H the first method of " Chinese Pharmacopoeia " version in 2010)；Acid-insoluble ash must not cross 1.0% (in " State's pharmacopeia " 2010 years one annex Ⅸ K of version)；

Character: become thoroughly decomposed thing for irregular fine powder or fine particle shape, surface canescence is to the most slightly yellow, and coarse, matter is crisp frangible, and gas is fragrant；

Nature and flavor with return through sweet, acrid, warm；Return spleen, stomach warp；

Function with cure mainly: replenishing QI to invigorate the spleen, promote the production of body fluid and quench one's thirst, function of spleen and stomach regulating, benefit liquid fill.For thirst and liking drink, polyphagia, polyuria, become thin, breathe hard, Fatigue and asthenia；

Usage and consumption: 3～6g；

Storage: put the shady and cool place that is dried, mothproof.

Experimental example 3: the present invention is treated the physical property research of the capsule preparations of diabetes

1. character: describe dosage form color, profile, abnormal smells from the patient etc. with 3 batches of formulation samples for foundation, as shown in table 6:

The character description of table 6 three batch sample

Conclusion: by the shape description to three batch samples, illustrates that the character of this medicine is stable, determines that the character of this medicine is hard capsule；Remove softgel shell Rear aobvious brown is to sepia, bitter in the mouth.

Wherein, the die young character of Luo Qu of section is as shown in table 7:

Table 7

2. bulk density: weigh constant weight conforming particle, loads in 10ml graduated cylinder, falls for several times (control condition as far as possible is consistent) with certain altitude, Making degree of tightness appropriateness, obtain bulk density with weight divided by volume, result is as shown in table 8:

Table 8 granular pile density measurement result

3. the mensuration of angle of repose: taking conforming particle and flow down and in cone shape through funnel, measure its angle of repose, result is as shown in table 9:

Table 9 granule measurement result angle of repose

As shown in Table 9: the angle of repose of granule is less than 45.0 °, has good mobility, it is suitable for filling the requirement of capsule.

4. the critical relative humidity of granule measures, and as shown in table 10, table 11, critical relative humidity measures curve as shown in Figure 3:

The relative humidity table of table 10 different solutions

Table 11 critical relative humidity determination data

Can be tried to achieve by the sucting wet curve of Fig. 3, critical relative humidity is about 58%；In conjunction with producing, should be by phase when beating powder, mixing, fill and store To humid control below 55%, to reduce moisture to pharmaceutical properties and the impact of stability.

Experimental example 4: scale up test is tested

According to the preparation technology of the present invention, carrying out the engineer testing of pilot-scale, feed intake 3 batches altogether, three batches of pilot products detect data such as table 12 institute Showing, assay is as shown in table 13:

12 3 batches of pilot plant test data of table

13 3 batches of pilot sample assays of table

Carrying out the checking of three batch scale up test, such as table 12, table 13, result shows: the technique of the Chinese medicine preparation of the treatment diabetes of the present invention is to close Reason, feasible.

Experimental example 5: determination of extractives

This product is not containing toxic medical material, and assay really acquires a certain degree of difficulty, according to " Guizhou Province's Preparation in medical units Technical Review main points-Chinese medicine ethnic drug " (trying) increases the mensuration of this project, and assay method gives according to one annex Ⅹ A Extract mensuration hot dipping of " Chinese Pharmacopoeia " version in 2010 Measuring, test agent extract content in testing 3 batches, result see table 14:

The determination of extractives of table 14 3 batches of Chinese medicine preparation of the present invention

Therefore this product water-soluble extractives content is fixed tentatively as being not less than 50.0%.

Experimental example 6: pharmacodynamics test

One, the Chinese medicine preparation of the present invention impact on db/db Spontaneous Diabetic mice

1. instrument and reagent

The Chinese medicine preparation of 1.1 present invention

(lot number: 20130401, specification: 0.3g/ grain are equivalent to 1.5g crude drug/grain to the Chinese medicine preparation of the present invention, and people's consumption is each 3, often Day 3 times, Braun Guizhou Pharmaceutical Enterprise Group Co provide).

Test sets 3 dosage groups: low dose group (4 times of clinical equivalent dosage) 1.8g/kg, middle dosage group (8 times of clinical equivalent dosage) 3.6g/kg, High dose group (16 times of clinical equivalent dosage) 7.2g/kg, it is 0.1ml/10g body weight that animal is administered volume；Therefore medicine compound concentration is respectively 7.2g/kg/10ml=0.72g/ml, 3.6g/kg/10ml=0.36g/ml, 1.8g/kg/10ml=0.18g/ml.

Compound method: capsule every is 0.3g, therefore every time take 24,12,6 respectively, adding distilled water, to be configured to 10ml stand-by.

2.2 metformin hydrochloride tablet

Metformin hydrochloride tablet is produced (lot number: 1303107) by Shanghai Shi Guibao pharmaceutical Co. Ltd of Sino-U.S.；Indication: hyperinsulinemia, 2 Patients with type Ⅰ DM.Usage and dosage: generally the initial dose of this product (metformin hydrochloride tablet) is 0.5 gram, and every day 2 times, dosage on the one is 1g. Body weight for humans calculates according to 60kg, and being converted to animal dosage is 120mg/kg；It is 0.1ml/10g body weight that animal is administered volume；Therefore medicine preparation Concentration is 120mg/kg/10ml/kg=12mg/ml.

Compound method: tablet format is 0.5g, therefore takes 1 every time, adding distilled water, to be configured to 41.70ml stand-by.

2.3. reagent and instrument

Glucose, purchased from Beijing Chemical Plant (lot number: 20121205)；Four items of blood lipid tests CHO (lot number: 120971), TG (lot number: 125161), HDL (lot number: 120331), LDL (lot number: 120411), test kit is purchased from high-tech trade (Shanghai) Co., Ltd. of Hitachi；Mouse islets Element ELISA kit (lot number: 13061201), purchased from Crystal Chem company of the U.S.；Steady person of outstanding talent's type blood sugar test paper (lot number: 3462320) With steady person of outstanding talent's type blood glucose meter, purchased from Johnson (Shanghai) Medical Appliance Co., Ltd.；Microplate reader, agree (Shanghai) company purchased from Supreme Being；Hitachi 7080 is complete Automatic biochemical analyzer, purchased from FDAC Co., Ltd.；Electronic balance, purchased from Mei Teletuo benefit instrument (Shanghai) Co., Ltd..

3. animal and rearing conditions

3.1 experimental animals: SPF level Spontaneous Diabetic mouse model C57BL/KsJ-db/db mice (is called for short db/db mice), 6～8 week old, body Weigh 45～55g, male；Thered is provided by Chinese Academy of Sciences's Shanghai Experimental Animal Center/Shanghai Slac Experimental Animal Co., Ltd..

3.2 rearing conditions: carry out animal feeding in China Medical Sciences Academy Medical Plants Institute's animal center, animal facility persistently keeps screen Barrier environmental standard.The span of control of main environment index: room temperature 20～26 DEG C, temperature difference per day≤4 DEG C；Relative humidity 40%～70%；Minimum ventilation Number of times 15 time/hour；Optical illumination: dark=12h, bright=12h.Animal feeding is in base box, and 5, every box, its cultured space meets the China people About the regulation of minimum space needed for laboratory animal in republic's standard GB/T 14925-2010.All animals are carried out by training qualified personnel Feeding and management, keeps animal diet followed freedom of movement in whole feeding process.

3.3 quarantines and domestication process: the animal quarantine phase 3 newly received～5 days.Observe drinking water for animals at quarantine, ingest and health status, And whether there is disease and intimations of mortality.Healthy animal fur is smooth, be quick on the draw, secretions without exception etc..Find that any abnormal phenomena all needs To special topic director and clinical veterinarian report, under veterinary instructs, confirm through special topic director, reject ill animal, carry out generation by healthy animal Replace.Confirm that animal health is anosis, can use.Animal adaptability can be tested after raising 1 week.

4 test methods

4.1 impacts on db/db mice fasting glucose

Being blank group with week old C57/BL male mice, 25 male db/db mices are randomly divided into 5 groups, 6-8 week old, and test is respectively mould Dosage group, Chinese medicine preparation low dose group of the present invention in type group, metformin hydrochloride group, Chinese medicine preparation high dose group of the present invention, Chinese medicine preparation of the present invention, Totally 5 groups, often group 5.All giving standard particle feedstuff adaptability to feed after 14d, blood glucose value is more than starting after 13.9mmol/L to give medicine to do In advance, gastric infusion, every day 1 time, gavage volume 0.1ml/10g, successive administration 35 days, wherein blank group and model group gavage every day are respectively organized The drinking water of 0.1ml/10g.After water 5h is can't help in animal fasting, measure mouse tail vein blood blood glucose value by full-automatic blood glucose meter, during administration, weekly Measure once.

4.2 the impact on db/db mouse glucose tolerance

Being blank group with week old C57/BL male mice, 25 male db/db mices are randomly divided into 5 groups, respectively model group, hydrochloric acid two Dosage group, Chinese medicine preparation low dose group of the present invention in first biguanide group, Chinese medicine preparation high dose group of the present invention, Chinese medicine preparation of the present invention, totally 5 groups, Often group 5.After all giving standard particle feedstuff adaptability nursing 14d, blood glucose value is all more than starting after 13.9mmol/L to give pharmaceutical intervention, respectively Group gastric infusion, every day 1 time, gavage volume 0.1ml/10g, successive administration 35 days, wherein blank group and model group gavage every day The drinking water of 0.1ml/10g.Water is can't help in animal fasting, after 5h, and 0min after 2.5g/kg glucose gavage, 30min, 60min, 90min, 120min Tail vein blood glucose value is measured by full-automatic blood glucose meter.

4.3 impacts on db/db mice serum insulin level

Being administered and process ibid 4.2, water is can't help in animal fasting, and after measuring fasting glucose and carbohydrate tolerance after 5h, Animal Anesthesia, ventral aorta is taken a blood sample 500 μ L, 3500rpm is centrifuged 15min, takes supernatant, insulin ELISA kit detection serum insulin.

Four CHO of 4.4 pairs of db/db lipid of mices, the impact of TG, HDL, LDL

Being administered and process ibid 4.2, water is can't help in animal fasting, and after measuring fasting glucose and carbohydrate tolerance after 5h, Animal Anesthesia, ventral aorta is taken a blood sample 500 μ L, 3500rpm is centrifuged 15min, takes supernatant, full automatic biochemical apparatus detection four items of blood lipid tests.

5 experimental results

5.1 impacts on db/db mice general state

Comparing with C57/BL matched group, db/db model group build is fat, and body weight dramatically increases, and movable reduces, other states such as hair color, diet without Change；Comparing with db/db model, db/db mice build, activity, hair color, diet are changed by metformin and Chinese medicine preparation of the present invention without significance Become.Chinese medicine preparation group body weight of the present invention is partially light, but no difference of science of statistics.

5.2 impacts on db/db mice fasting glucose

Result shows, after giving drug treating 1 week, comparing fasting glucose with model group has the trend of reduction, but no difference of science of statistics；Give medicine After processing 2 weeks, comparing fasting glucose with model group has the trend of reduction, Chinese medicine preparation high dose group of the present invention to have significant difference.Give at medicine After managing 4 weeks, positive drug and Chinese medicine preparation group of the present invention compare fasting glucose with model group all significant difference, Chinese medicine preparation group dosage of the present invention With hypoglycemic effect amount effect relationship；After giving drug treating 5 weeks, it is equal that positive drug and Chinese medicine preparation group of the present invention compare fasting glucose with model group There are significant difference, Chinese medicine preparation group dosage of the present invention and hypoglycemic effect amount effect relationship.Chinese medicine preparation high dose group of the present invention is after being administered 2 weeks Variant with model group fasting glucose, in, low dose group be administered after 4 weeks variant with model group fasting glucose.High dose group is after being administered 2 weeks Blood glucose value is close to normal (less than 13.9mmol/L), and hereafter fasting glucose maintains this level always.Low dose group along with the prolongation of administration time, Hypoglycemic effect is gradually strengthened, and comparing with model group in 4th week has significant difference.The results are shown in Table 15:

The Chinese medicine preparation of table 15 metformin and the present invention on the impact of db/db mice fasting glucose (mmol/L,N=5)

^*, p ＜ 0.05；^**, p ＜ 0.01, and compare with time point db/db model group.

5.3 impacts on db/db mouse glucose tolerance

Result shows, compares with C57 Normal group, and the blood glucose of model group different time points significantly raises.When administration group is each after taking glucose Between put blood glucose value and all raise, comparing with model group has reduction trend, all but no difference of science of statistics, be shown in Table 16:

The Chinese medicine preparation of table 16 metformin and the present invention on the impact of db/db mouse glucose tolerance (different time points blood glucose value, mmol/L,N=5)

^*, p ＜ 0.05, compares with Normal group.#, p ＜ 0.05；##, p ＜ 0.01, compares with model group.

Compare with C57 Normal group, model group take glucose after under blood glucose-time graph area (AUC) significantly raise.With model group Relatively, administration group take glucose after under blood glucose-time graph area (AUC) reduce, compare with model group and have significant difference, be shown in Table 17:

The Chinese medicine preparation of table 17 metformin and the present invention on the impact of db/db mouse glucose tolerance (area under curve, AUC, min mmol/L,N=5)

^*, p ＜ 0.05, compares with Normal group；#, p ＜ 0.05；##, p ＜ 0.01, compares with model group.

5.4 the impact on db/db mice serum insulin

Result shows, with C₅₇Normal group compares, and db/db mouse model group serum insulin declines, but does not has significant difference, with db/db Mouse model group compares, and administration group can increase serum insulin, but does not has significant difference, is shown in Table 18:

The Chinese medicine preparation of table 18 metformin and the present invention on the impact of db/db mice serum insulin (N=5)

5.5 impacts on db/db lipid of mice four

Result shows, compares with C57 Normal group, and db/db mouse model group CHO declines, and it is obvious that TG raises trend, but does not has significance Difference；Comparing with db/db mice, administration group TG downward trend is obvious, does not has significant difference；The change of other indexs is inconspicuous, is shown in Table 19:

The Chinese medicine preparation of table 19 metformin and the present invention on the impact of four items of blood lipid tests (N=5)

6. conclusion

After giving drug treating 5 weeks, comparing with model group, positive drug and Chinese medicine preparation group fasting glucose of the present invention significantly reduce；Chinese medicine of the present invention Preparation group dosage and hypoglycemic effect amount effect relationship.Chinese medicine preparation high dose group of the present invention, after being administered 2 weeks, compares with model group, fasting glucose Significantly reduce；In, low dose group be substantially less than model group being administered fasting glucose after 4 weeks.High dose group fasting blood sugar after being administered 2 weeks is close Normally (less than 13.9mmol/L), hereafter fasting glucose maintains this level always.Low dose group along with the prolongation of administration time, hypoglycemic effect by Fade in existing, be substantially less than model group in 4th week fasting glucose.On this model (db/db), Chinese medicine preparation of the present invention shows blood sugar lowering and improves sugar The effect of tolerance, higher dosage relatively early occurs that hypoglycemic effect, low dosage administration certain time (4 weeks) also show preferable hypoglycemic effect, this medicine There is lasting blood sugar reducing function in thing performance.During the impact of db/db mice serum insulin, four items of blood lipid tests is tested by Chinese medicine preparation of the present invention, to serum Islets of langerhans have rising trend, and TG has reduction trend, owing to size of animal is less, compares with db/db mouse model, the effect of Chinese medicine preparation of the present invention There was no significant difference.

Having preferable hypoglycemic activity by the Chinese medicine preparation of the above-mentioned result of the test preliminary proof present invention, high dose group is slightly better than metformin group, It is significantly improved effect simultaneously for carbohydrate tolerance；Thus this Chinese medicine preparation has preferable DEVELOPMENT PROSPECT.

Two, the Chinese medicine preparation of the present invention experimentation to type 2 diabetes mellitus rat blood sugar reducing function

1. materials and methods

1.1 material

1.1.1 animal cleaning grade male SD rat, body weight 150～180g, be purchased from Chongqing rise prosperous Bill's laboratory animal sell company limited, animal Credit number SCXK (changes), 2012-0006.

1.1.2 medicine and reagent

1.1.2.1 the Chinese medicine preparation of the present invention: provided (hereinafter referred to as TNTL) by Braun Guizhou Pharmaceutical Enterprise Group Co, Cheng Renlin Bed dosage is 0.045g/kg, and rat dose,equivalent and people are scaled 7 times of people's clinical dosages.Face the used time by the content (brown powder) of Chinese medicine preparation Taking-up pure water is prepared.During test, rat TNTL low dose group is 0.63g/kg (two times of clinical dosage), and high dose group is that (four times are faced 1.26g/kg Bed dosage).

1.1.2.2 streptozotocin (Streptozotocin STZ), Beijing wins Alto and reaches Science and Technology Ltd., lot number: 040M1367.

1.1.2.3 rat insulin test kit: Manufactured by Mercodia AB, Sylveniusgatan 8A, SE-754 50 Uppsala, Sweden.Lot number: 20518, used time by specification operates.

1.1.2.4 rat C peptide reagent box: upper sea blue base Science and Technology Ltd., lot number: 20130617.Used time by specification operates.

1.1.2.5 metformin: for Tian An board Dimethyldiguanide hydrochloride enteric solubility tablet, adult's clinical dosage is 0.03g/kg every day, is scaled rat equivalent 0.21g/kg。

1.1.2.6 normal diet, be purchased from Chongqing rise prosperous Bill's laboratory animal sell company limited.

1.1.2.7 high-sugar-fat-diet makes: white sugar, Adeps Sus domestica, egg are all purchased from supermarket, and egg boils only uses egg yolk, and normal diet is broken into powder. Feed formula: containing normal diet 35g (Chongqing Teng Xin Bill's laboratory animal sells company limited), Adeps Sus domestica 15g, white sand in every 100g high lipid food Sugar 25g, egg yolk 25g, feeding animals 20 days.

1.2 animal packet and medications

Give TNTL the most in advance the impact of type Ⅱdiabetes mellitus rat is tested: rat is divided into 3 groups, respectively normal group, model group, TNTL Group.Normal group gives normal diet, model group and TNTL group high-sugar-fat-diet and feeds, and TNTL group gavage every day gives in the present invention simultaneously Medicine preparation (0.63g/kg, 1 times/day), after 20 days, model group and TNTL group lumbar injection STZ (face the used time to prepare with citrate buffer, PH value 4.2,30mg/kg, completed injection in 30 minutes), manufacture diabetes model, filter out modeling successful rat normal diet and feed 12 days (TNTL group is omnidistance to be administered 32 days).

1.2.2TNTL the impact on type 2 diabetes mellitus rat is tested: rat is divided into 5 groups, and normal group, model group, metformin group, TNTL are low Dosage group, TNTL high dose group.Normal group gives normal diet, other 4 groups of high-sugar-fat-diets feed 20 days after modeling (ibid), modeling Successfully rat uses normal diet nursing instead, and the most each group starts to be administered, 2 times/d, each 1 time of upper and lower noon.Metformin group ig 0.21g/kg, TNTL low dosage ig 0.63g/kg, (two times of clinical dosages), TNTL high dose ig 1.26g/kg (four times of clinical dosages).Omnidistance administration 27 days.

1.2.3TNTL impact on type 2 diabetes mellitus rat and normal rat test is used in combination with Western medicine: rat is divided into 4 groups, normal group, model Group, metformin+TNTL low dose group, normal+TNTL high dose group.Normal group and normal+TNTL high dose group give normal diet, mould Type group, metformin+TNTL low dose group high lipid food feed modeling (ibid) after 20 days, and the screening successful rat of modeling is used normal diet instead and feeds Supporting, the most each group starts to be administered, 2 times/d, each 1 time of upper and lower noon.Metformin+TNTL low dose group first gives metformin 27 days (ig, 0.21g/kg), Then TNTL low dosage (ig, 0.63g/kg, two times of clinical dosage) is changed into 21 days.Normally+TNTL high dose group to TNTL high dose (ig, 1.26g/kg, four times of clinical dosages) 21 days.

1.3 detection methods and instrument

1.3.1 insulin, C peptide all detect by ELISA method, detecting instrument Biotek Synergy 2 fluorescence microplate reader, and Biotek company of the U.S. produces Product.

1.3.2 blood-sugar detecting instrument and reagent paper: Roche Products of the U.S., ACCU-CHEK Pertorma.

After 1.4 check pathological section rat limosis 16 hours, sacrificed by decapitation, take pancreas and be placed in neutral formalin liquid fixing preservation, do pathology detection. This detection completes in Pathology Deparment of No. 2 Affiliated Hospital of Guiyang College of Traditional Chinese Medicine.Atrophy degree after being damaged according to pancreas is divided into normal and atrophy, By often organizing atrophy and normal number of elements carries out statistics (card side) inspection and processes.

1.5 statistical method: use SPSS17.0 statistical software, measurement data withExpressing, enumeration data, with percentage expression, is measured after group Data compares with T inspection, and enumeration data compares with X 2 test.

2. result

2.1 give the TNTL impact on type Ⅱdiabetes mellitus rat in advance

2.1.1 carbohydrate tolerance: rat limosis is after 16 hours, gives glucose solution (gavage, 20g/100mL, 3mL/ are only), measure rat empty stomach, 1h, 2h, 3h blood glucose value, the results are shown in Table 20, Fig. 4:

The impact on type 2 diabetes mellitus rat carbohydrate tolerance of the Chinese medicine preparation of the present invention given in advance by table 20

Note: compare with normal group, * p < 0.05, * * p < 0.01；Compare with model group,^#P < 0.05,^##p<0.01

From table 20, Fig. 4, the blood glucose value of TNTL group 3h is significantly lower than model group (P < 0.05), and other two time points also have reduction.

2.1.2 pancreatic tissue check pathological section

Pathology detection result is pointed out, and substantially alleviates to the damage of TNTL group relatively model group Pancreas pathology in advance.Be shown in Table 21, Fig. 5-Fig. 7:

Chinese medicine preparation impact (the unit: only) on type 2 diabetes mellitus pancreas in rat of the present invention given in advance by table 21

Note: compare with normal group, * p < 0.05；Compare with model group,^#p<0.05

The 2.2TNTL impact on type 2 diabetes mellitus rat

2.2.1 body weight

TNTL can significantly improve the body weight that diabetes rat reduces, and the results are shown in Table 22, Fig. 8:

The impact on type 2 diabetes mellitus rat body weight of the Chinese medicine preparation of table 22 present invention

Note: compare with normal group,^*P < 0.05,^**p<0.01；Compare with model group,^#P < 0.05,^##p<0.01

2.2.2 carbohydrate tolerance

After rat limosis 16 hours, give glucose solution (gavage, 20g/100mL, 3mL/ only), use Roche blood glucose meter measure empty stomach, 1h, 2h, 3h blood glucose value.The results are shown in Table 23, Fig. 9:

The impact on type 2 diabetes mellitus rat carbohydrate tolerance of the Chinese medicine preparation of table 23 present invention

Note: compare with normal group,^*P < 0.05,^**p<0.01；Compare with model group, #p < 0.05, ##p < 0.01

From table 23, Fig. 9, the fasting glucose of each group rat is not significantly different from, and the blood glucose value of TNTL low dosage and each time point of high dose is equal Less than model group, difference significance (p < 0.01), but the most variant with normal group.Chinese medicine TNTL low dose group is high with Chinese medicine TNTL There was no significant difference between dosage group.

2.2.3 insulin and C peptide

After rat limosis 16 hours, take blood centrifuging and taking supernatant, use rat insulin ELISA kit (Mercodia), rat C peptide ELISA Test kit (BluGene), the OD value at detection 450nm wavelength, the results are shown in Table 24:

The Chinese medicine preparation of table 24 present invention is on type 2 diabetes mellitus rat limosis insulin, the impact of C peptide

Note: compare with normal group,^*P < 0.05,^**p<0.01；Compare with model group,^#P < 0.05,^##p<0.01

Shown in table 24, the insulin of model group is substantially less than normal group, and TNTL high and low dose group insulin relatively model group has increase trend, but Still significantly lower than normal group.C peptide result shows, model group decreases, and TNTL high and low dose group relatively model group has and slightly increases trend.

2.2.4 Pancreas pathology inspection

Gather pancreas and be placed in neutral formalin liquid fixing preservation, check pathological section, the results are shown in Table 25, Figure 10-Figure 14:

The Chinese medicine preparation of the table 25 present invention impact (unit: only) on type 2 diabetes mellitus pancreas

Note: compare with normal group,^*p<0.05；Compare with model group, #p < 0.05

2.3 TNTL and metformin are used in combination the impact on type 2 diabetes mellitus rat

2.3.1 carbohydrate tolerance:

After rat limosis 16 hours, give glucose solution (gavage, 20g/100mL, 3mL/ are only), measure the empty stomach of rat, 1h, 2h, 3h Blood glucose value.The results are shown in Table 26, Figure 15:

The impact on type 2 diabetes mellitus rat carbohydrate tolerance of table 26 drug combination

Note: compare with normal group,^*P < 0.05,^**p<0.01；Compare with model group, #p < 0.05, ##p < 0.01

From table 26, Figure 15, metformin+TNTL low dose group fasting glucose is substantially less than model group, normal+TNTL high dose group with Normal group carbohydrate tolerance value does not has difference, illustrates that blood glucose level normal is not affected by this TNTL.

2.3.2 Pancreas pathology inspection

Gather pancreas and be placed in neutral formalin liquid fixing preservation, do pathology detection, the results are shown in Table 27, Figure 16-Figure 19:

The table 27 drug combination impact (unit: only) on pancreas in rat check pathological section

Note: compare with normal group,^*p<0.05

This first 3 groups of test compares, and result metformin+TNTL low dose group has certain protective role to rat Langerhans islet, but does not has statistics to anticipate Justice.Normally+TNTL high dose group compares with normal group, does not has diversity between two groups, and normal pancreas in rat is not affected by the TNTL of high dose.

Conclusion:

This experiment male SD rat, feeds the classical way adding half amount streptozotocin partial destruction B cell, successfully structure with high calorie Build type 2 diabetes mellitus rat model.

The study find that, the method being either administered with the method being administered in advance or conventional therapy, the most individually dosed method or and diformazan The method of biguanide administering drug combinations, either observes with carbohydrate tolerance or observes with conventional blood sugar, and TNTL all can substantially reduce type 2 diabetes mellitus rat serum Sugar (P value all < 0.05), shows the TNTL obvious blood sugar reducing function of tool.

This research also finds, after TNTL acts on type 2 diabetes mellitus rat, while blood glucose substantially reduces, its fasting insulin and C peptide there is no Substantially change, point out this blood sugar reducing function mechanism to be not necessarily B cell and promote to secrete effect, may be relevant with improving the factors such as insulin resistant (IR).

This research observes the change of the Pancreas Disease Neo-Confucianism after TNTL effect, finds that its atrophy number is significantly lower than the model group without TNTL effect (P < 0.05), shows that TNTL has a certain degree of islets of langerhans protective effect to type 2 diabetes mellitus rat.

TNTL is acted on normal SD rats by this research, and it is found that the blood glucose of normal SD rats is unchanged before and after TNTL effect, its Pancreas also without pathological change, show TNTL to normal rat without blood sugar influence, its islets of langerhans is also had no significant effect.This result is pointed out the most further The blood sugar reducing function of TNTL is not likely to be mainly by promoting what B cell excreting insulin realized.

Experimental example 7: acute toxicity test

1.1 medicine

The Chinese medicine preparation of the present invention, is provided by Braun Guizhou Pharmaceutical Enterprise Group Co, lot number: 20130106.Face used time distilled water The suspension oral gavage being configured to desired concn is administered.

1.2 animal

Kunming mouse, male and female half and half, body weight 20 ± 2g, Military Medical Univ No.3, P.L.A's Experimental Animal Center provide, the quality certification number: SCXK (Chongqing) 2012-0003.

1.3 feedstuff

Feedstuff is full-valence pellet feed, above-mentioned unit provide.

1.4 zoopery places

Guiyang College of Traditional Chinese Medicine's pharmacological toxicology laboratory ventilation is good, and sanitation and hygiene, temperature, humidity all reach new drug pharmacological research requirement.

1.5 key instrument

ALC-210.3 type electronic balance, upper current chart level instruments and meters company limited.

1.6 statistical procedures

The poor opposite sex between data acquisition group, withRepresent, carry out t inspection.

2 experimental techniques and result

2.1 prerun tests

With the Chinese medicine preparation aqueous solution of the present invention of Cmax 23%, gavage of 0.3ml/10g body weight gives mice, observes 7 days.Result: Have no animal dead, show to measure its LD₅₀, therefore measure the maximum dosage-feeding of the Chinese medicine preparation of the present invention.

2.2 formal test

Take Kunming mouse 40, be randomly divided into the Chinese medicine preparation group of blank group, the present invention, often group 20, male and female half and half.Prohibit before experiment Water 12h be can't help by food, and the Chinese medicine preparation group gavage of the present invention gives the Chinese medicine preparation aqueous solution 0.3ml/10g body weight of the present invention of mice 23%, one Secondary, is equivalent to 13.8g/kg body weight, for 400 times of clinic plan dosage 0.0345g/kg body weight；Blank group is with same amount of normal saline Gavage, a twice-daily.Continuous Observation 14d after administration, record animal has body weight change before and after non-toxic reaction and experiment, not produce death Dosage is maximum dosage-feeding.

Result: after the Chinese medicine preparation aqueous solution 13.8g/kg of the Kunming mouse gavage present invention, grows healthy, and fleshiness is glossy by Mao Mi, Eyes secretions bright and flexible, N/R, crissum is clean, ingests normal, and extremity are healthy and strong, and spontaneous activity is normal, and in the observation period, body weight is gradually Increase, compare no significant difference with blank group.Animal dead and toxicity is had no in 14d.At the end of experiment, naked eyes become celestial and have no obvious disease Reason changes.Experimental result is shown in Table 28:

The Chinese medicine preparation of table 28 present invention on the impact of Mouse Weight (g) (N=10)

Note: the Chinese medicine preparation group of the present invention is female female with blank group compares P > 0.05；The Chinese medicine preparation group of the present invention is male with blank group Male compare P > 0.05.

Conclusion: the Chinese medicine preparation of the Kunming mouse gavage present invention, with Cmax 0.23g/ml, is administered volume 0.3ml/10g body weight, one day two Secondary administration, is equivalent to 13.8g/kg body weight, for 400 times of clinic plan dosage.Root " it is generally acknowledged that mice is the most according to the weight according to the literature It is the safest that big dosis tolerata is equivalent to people's consumption more than 100 times ", it is therefore contemplated that the Chinese medicine preparation of the present invention is the least to the acute toxicity of animal, Safety, it is provided that clinic trial；Additionally, inventor has also carried out long term toxicity test to the Chinese medicine preparation of the present invention, result of the test also indicates that this The Chinese medicine preparation toxicity of invention is less, and Clinical practice is safer.

Experimental example 8 long term toxicity test

1. purpose

Observe larger dose, long period, give rat continuously and repeat the Chinese medicine preparation 12 weeks of the gavage present invention, 24 weeks and drug withdrawal 4 weeks to rat Produced toxic reaction, the order of severity and the symptom first occurred；The target organ observing toxic reaction recovers and development, determines nontoxic reactant Amount, provides foundation for drafting people's safe dose.

2. experiment material

2.1 medicine

The Chinese medicine preparation of the present invention, is provided by Braun Guizhou Pharmaceutical Enterprise Group Co, lot number: 20130106.Function cures mainly: yin nourishing Promote blood circulation, promoting the production of body fluid to quench thirst, clearing away heat-fire.For the diabetes caused by deficiency of both QI and YIN, disease see thirst and liking drink, polyphagia, polyuria, become thin, breathe hard, weary Power, sleep poor, lumbago, feverish sensation in the palms and soles；Type 2 diabetes mellitus is shown in above-mentioned patient.Dosage form: capsule.Usage and dosage: oral, 3 times on the one, one Secondary 3-4 grain；Bfore meals.Specification: every seed lac capsule weight 0.3g, is equivalent to crude drug amount 1.73g.Adult's body weight calculates according to 60kg, then clinical plan Determining Coming-of-Age Day consumption is 0.0345g/kg body weight, is equivalent to 0.19895g crude drug amount/kg body weight.

Face the used time with distilled water be configured to desired concn suspension oral gavage be administered.

2.2 animal

SD rat, male and female half and half, 120, body weight 100g ± 20g, Military Medical Univ No.3, P.L.A's Experimental Animal Center provide, The quality certification number: SCXK (Chongqing) 2012-0003.

2.3 key instrument

JY601 type electronic balance, upper current chart level instruments and meters company limited；OLYMPUS BH-2 microscope, Japan；The full-automatic blood of SC-970 Cytoanalyze, Bei Ken company of Switzerland；Hitachi's 7170A automatic clinical chemistry analyzer, Kodak of the U.S.；HPIAS-1000 high-definition color picture and text Pathological analysis system, light microscopic.

2.4 experimental data statistics

Experimental data withRepresent, t inspection between organizing.

3 experimental techniques

3.1 experiment condition

Not every 5 group supports of cage of the equal unisexuality of rat before and after administration, feed with full-valence pellet feed, freely drink water, room temperature 20 DEG C～23 DEG C, humidity 55%～65%.First adapt to environment before administration, observe 7 days rat general status, change without exception, then start to be grouped administration and test.

3.2 packet and dosage

SD rat 120, male and female half and half, it is randomly divided into 4 groups, often group 30, high, medium and low three respectively as the Chinese medicine preparation of the present invention Dosage group and blank group.Administration group dosage is respectively 2.07g, 1.035g, 0.5175g/kg body weight, administration concentration is respectively 20.7%, 10.35%, 5.175%, it is said preparation and drafts clinical Coming-of-Age Day with 60 times of dosage 0.0345g/kg body weight, 30 times, 15 times.Administration volume is 10ml/kg Body weight.

3.3 route of administration and method

Because the Chinese medicine preparation clinical administration approach of the present invention is oral administration, so the equal gastric infusion of each treated animal.During 8-10 in morning every day, gavage is given Once, be administered volume is 10ml/kg body weight to medicine, continuous 24 weeks；Observe animal general status every day, record weekly each treated animal body weight and food-intake Once, increase change according to the weight of animals, adjust dosage.

3.4 the test period

Testing total cycle is 28 weeks, and first 24 weeks is administration time, drug withdrawal in latter 4 weeks, observes animal different time whether toxic reaction respectively.It is administered Phase, respectively at be administered 12 weeks, 24 weeks time, after last administration, fasting can't help water 12 hours, and often group takes 10 animals (male and female half and half) and weighs Rear femoral vein takes blood, measures animal blood cytology, blood biochemical analysis, puts to death animal simultaneously and carries out system and become celestial, and observing each organs and tissues of animal has After hyperemia, enlargement, the ANOMALOUS VARIATIONS such as hemorrhage, then take each Mus main organs and weigh respectively, after calculating organ coefficient and other organs and tissues specimen son Thin immersion 10% formaldehyde such as peripheral adipose tissue of peeling off are fixed, and carry out Pathomorphologic and check.Withdrawal time, remaining animal drug withdrawal routine raises 4 In week, carrying out general status observation, every journal body weight and food-intake every day, fasting be can't help drinking 12 hours execution animals, detects above-mentioned indices.

4 check project

4.1 overview

Observe every day the mode of appearance sign of each treated animal, behavioral activity, hair luster, take food, drink water, stool etc.；Find intoxicated animals Isolate immediately, primary part observation；Find dead or moribund animals, postmortem at once.Claiming weekly the weight of animals, adjust dosage accordingly, record is each simultaneously Treated animal feed consumption.

4.2 detection projects

4.2.1 blood cytology Index for examination

Leukocyte (WBC), neutrophilic granulocyte sum (#NEUT), lymphocyte absolute value (#LYMPH), monocyte count (MONO#), Acidophil number (#EOS), basophilic leukocyte number (#BASO), Erythrocyte hemoglobin distribution width (RDW), neutrophilic granulocyte percentage ratio (%NEUT), Cent lymphocytes (%LYMPH), mononuclear cell percentage ratio (%MONO), acidophil percentage ratio (%EOS), basophilic leukocyte percentage ratio (%BASO), erythrocyte (RBC), hemoglobin (HGB), packed cell volume (HCT), mean corpuscular volume (MCV) (MCV), erythrocyte Average hemoglobin amount (MCH), mean corpuscular hemoglobin (MCHC), platelet (PLT), Mean Platelet Volume (MPV).

4.2.2 blood biochemical analysis Index for examination

Potassium (K), sodium (Na), chlorine (CL), glucose (GLU), triglyceride (TG), T-CHOL (CHOL), blood urea nitrogen (BUN), Creatinine (CREA), glutamate pyruvate transaminase (ALT), glutamic oxaloacetic transaminase, GOT (AST), alkali phosphatase (AKP), creatine kinase (CK), total protein (TP), albumin (ALB), globulin (GLB), total bilirubin (TBIL).

4.2.3 major organs tissue specimen

The heart, liver, spleen, lung, kidney, adrenal gland, thymus, brain, uterus, ovary, testis, epididymis, weigh respectively, calculates acropetal coefficient； Then at the heart, liver, spleen, lung, kidney, adrenal gland, thymus, cerebral tissue, thyroid, hypophysis, trachea, esophagus, stomach, intestinal, bladder, pancreas, Draw materials and carry out paraffin embedding in the same position of the internal organs such as lymph node, optic nerve, section, and HE dyes；Put observation by light microscope and with blank group Carry out internal organs pathological tissue to compare.First comparison check high dose group and blank treated animal tissue morphology pathological change, middle dosage group and low dose group Animal organ's tissue specimen 10% formaldehyde is fixed for future reference.

4.2.4 pathological examination

Carry out corpse analysis, and main organ and tissue are fixed with 10% formaldehyde, preserved.When the analysis of each dosage treated animal corpse does not finds obvious pathological changes only Carry out high dose group and the histopathological examination of blank treated animal.As found, pathological changes centering again, low dose group animal check accordingly.

4.3 index observing times

Every day all laboratory animals of complete observation general status, animal activity behavior, stool, outward appearance sign, the feedstuff consumption of a week； Weigh weekly once；Be administered 12 weeks, after 24 weeks last medicines 12 hours and drug withdrawal within 4 weeks, recover the end of term, respectively carry out the most above-mentioned project and check comprehensively.

5 experimental results

The Chinese medicine preparation of 5.1 present invention is on rat ordinary circumstance and the impact of feed

In successive administration 12 weeks, 24 weeks and drug withdrawal 4 weeks, each administration group is compared with blank group, observes animal activity, behavior, drink Food, stool, hair luster etc., 4 treated animal situations are similar, show no obvious abnormalities change.Rat food ration also no significant difference within the same time. The results are shown in Table 29, table 30:

During the Chinese medicine preparation successive administration of table 29 present invention 12 weeks, 24 weeks and drug withdrawal 4 weeks Impact on female rats Zhou Pingjun food-intake (g)

Note: different time points, each administration group compares with blank group, P > 0.05.

During the Chinese medicine preparation successive administration of table 30 present invention 12 weeks, 24 weeks and drug withdrawal 4 weeks Impact on male rat Zhou Pingjun food-intake (g)

Note: different time points, each administration group compares with blank group, P > 0.05.

Result shows, consumption of each treated animal week appetite is all in being gradually increased trend, and each administration group compares with blank group, no significant difference, P ＞ 0.05. Show the continuous gastric infusion of rat 12 weeks, 24 weeks and drug withdrawal 4 weeks, has no significant effect male and female rat chow week consumption.

5.2 the impact that the Chinese medicine preparation of the present invention is on rat body weight

Body weight after rat successive administration different time is compared by the high, medium and low Three doses of Chinese medicine preparation of the present invention with blank group, and it is poor Different without significant change, the results are shown in Table 31, table 32.

During the long-term successive administration of Chinese medicine preparation of table 31 present invention 12 weeks, 24 weeks and drug withdrawal 4 weeks Impact on female rats body weight (g)

Note: each administration group compares with blank group, P > 0.05；Within 0 week, it is medicine early stage, n=15；1-12 week is the administration phase 1, n=15；13-24 week is The administration phase 2, n=10；25-28 week is withdrawal time, n=5.

During the long-term successive administration of Chinese medicine preparation of table 32 present invention 12 weeks, 24 weeks and drug withdrawal 4 weeks Impact on male rat body weight (g)

Note: each administration group compares with blank group, P > 0.05；Within 0 week, it is medicine early stage, n=15；1-12 week is the administration phase 1, n=15；13-24 week is The administration phase 2, n=10；25-28 week is withdrawal time, n=5.

Result shows, in the observation period, each group male and female rat body weight is all gradually increased, and growth promoter is good；Each administration group with time period blank Group is compared, each time point body weight no significant difference compared with blank group, P ＞ 0.05.Show the continuous gastric infusion of rat 12 weeks, 24 weeks and stop Medicine 4 weeks, affects without overt toxicity male and female rat body weight.

Rat blood cytology is affected by the Chinese medicine preparation of 5.3 present invention

The Chinese medicine preparation of the present invention is administered 12 weeks, 24 weeks and drug withdrawal 4 weeks to rat oral gavage, and each treated animal hematological indices testing result is shown in Table 33～35.

The impact on rat blood cytology's index in 12 weeks of the Chinese medicine preparation successive administration of table 33 present invention (N=10)

Note: be respectively administered treated animal blood cytology indices numerical value respectively with blank group corresponding index numeric ratio relatively, P > 0.05.

The impact on rat blood cytology's index in 24 weeks of the Chinese medicine preparation successive administration of table 34 present invention (N=10)

Note: be respectively administered treated animal blood cytology indices numerical value respectively with blank group corresponding index numeric ratio relatively, P > 0.05.

The Chinese medicine preparation drug withdrawal of table 35 present invention impact on rat blood cytology's index in 4 weeks (N=10)

Note: be respectively administered treated animal blood cytology indices numerical value respectively with blank group corresponding index numeric ratio relatively, P > 0.05.

Result shows, the Chinese medicine preparation high, medium and low Three doses successive administration of the present invention 12 weeks, 24 weeks and drug withdrawal 4 weeks, the blood to rat Cell is showed no appreciable impact, through statistical procedures, P ＞ 0.05.It is therefore contemplated that the Chinese medicine preparation larger dose of the present invention, long period (24 Week) it is administered and drug withdrawal 4 weeks, to the hemopoietic function of rat without significant toxic effect.

The Chinese medicine preparation of 5.4 present invention is on the biochemical impact of rat blood

The Chinese medicine preparation of the present invention is administered 12 weeks, 24 weeks and drug withdrawal 4 weeks to rat oral gavage, and each treated animal blood biochemical analysis Indexs measure result is shown in Table 36, table 37, table 38.

The impact on rat blood biochemical indexes in 12 weeks of the Chinese medicine preparation successive administration of table 36 present invention (N=10)

Note: be respectively administered treated animal blood cytology indices numerical value respectively with blank group corresponding index numeric ratio relatively, P > 0.05.

The impact on rat blood biochemical indexes in 24 weeks of the Chinese medicine preparation successive administration of table 37 present invention (N=10)

Note: be respectively administered treated animal blood cytology indices numerical value respectively with blank group corresponding index numeric ratio relatively, P > 0.05.

The Chinese medicine preparation drug withdrawal of table 38 present invention impact on rat blood biochemical indexes in 4 weeks (N=10)

Note: be respectively administered treated animal blood cytology indices numerical value respectively with blank group corresponding index numeric ratio relatively, P > 0.05.

Result shows, the Chinese medicine preparation high, medium and low Three doses successive administration of the present invention 12 weeks, 24 weeks and drug withdrawal 4 weeks, the blood to rat Liquid biochemical indicator is showed no appreciable impact, and every biochemical indicator numerical value such as the liver function of rat and renal function is respectively compared with blank group respective value Relatively, notable difference, P ＞ 0.05 are had no；Therefore show that the Chinese medicine preparation larger dose successive administration 12 weeks of the present invention, 24 weeks and drug withdrawal 4 weeks are to rat The index such as liver function, renal function is all without notable toxic action.

The impact on rat major organs index of the Chinese medicine preparation of 5.5 present invention

The Chinese medicine preparation of the present invention is administered 12 weeks, 24 weeks and drug withdrawal 4 weeks to rat oral gavage, system obduction: brain, heart, liver, The form of the internal organs such as spleen, lungs, kidney, adrenal gland, thymus, thyroid, stomach, intestinal, testis, epididymis, prostate, uterus, ovary, Size, color all do not find macroscopic change.Each treated animal main organs index testing result is shown in Table 39, table 40, table 41, table 42, table 43, table 44.

The impact on female rats main organs index (g/100g) in 12 weeks of the Chinese medicine preparation successive administration of table 39 present invention (N=5)

Note: each treated animal each organ index value exponential quantity corresponding to blank group respectively that be administered compares, P > 0.05.

The impact on female rats main organs index (g/100g) in 24 weeks of the Chinese medicine preparation successive administration of table 40 present invention (N=5)

Note: each treated animal each organ index value exponential quantity corresponding to blank group respectively that be administered compares, P > 0.05.

The Chinese medicine preparation drug withdrawal of table 41 present invention impact on female rats main organs index (g/100g) in 4 weeks (N=5)

Note: each treated animal each organ index value exponential quantity corresponding to blank group respectively that be administered compares, P > 0.05.

The impact on male rat main organs index (g/100g) in 12 weeks of the Chinese medicine preparation successive administration of table 42 present invention (N=5)

Note: each treated animal each organ index value exponential quantity corresponding to blank group respectively that be administered compares, P > 0.05.

The impact on male rat main organs index (g/100g) in 24 weeks of the Chinese medicine preparation successive administration of table 43 present invention (N=5)

Note: each treated animal each organ index value exponential quantity corresponding to blank group respectively that be administered compares, P > 0.05.

The Chinese medicine preparation drug withdrawal of table 44 present invention impact on male rat main organs index (g/100g) in 4 weeks (N=5)

Note: each treated animal each organ index value exponential quantity corresponding to blank group respectively that be administered compares, P > 0.05.

Result shows, the Chinese medicine preparation high, medium and low Three doses successive administration of the present invention 12 weeks, 24 weeks and drug withdrawal 4 weeks, main to rat Organs and tissues has no obvious toxic effect, each administration every organ index of group rat compared with blank group all without significant difference, P ＞ 0.05；Therefore Show that the Chinese medicine preparation larger dose successive administration 12 weeks of the present invention, 24 weeks and 4 weeks organs and tissues each to rat of drug withdrawal are without notable toxic action.

The impact on rat important organ histoorgan pathomorphism of the Chinese medicine preparation of 5.6 present invention

Chinese medicine preparation successive administration 12 weeks, 24 weeks to the present invention, and the drug withdrawal high, medium and low Three doses group of 4 weeks and blank group three Batch, kills and takes rat and solution cuts the heart of each group of rat, liver, spleen, lung, kidney, adrenal gland, thymus, brain, uterus, ovary, testis, attached Testis, prostate, thyroid, trachea, esophagus, stomach, aorta, duodenum, colon, bladder, pancreas, lymph node, optic nerve, ischium The histoorgans such as nerve, draw materials in same area, fix by 10% formalin.By big to Chinese medicine preparation high dose group and the blank group of the present invention Mus organ specimens carries out tissue slice, carries out pathological examination, and remaining specimen retains with standby.Result: through two treated animal organ specimens are checked, Various organ-tissue structures are normal, and cell dyeing is uniform, without substantially changing.Owing to the Chinese medicine preparation high dose group animal of the present invention is checked Organ-tissue does not occurs that medicine causes pathological change, therefore dosage group in the Chinese medicine preparation of the present invention and low dose group are not carried out organ-tissue section.Tested Organ-tissue form section photo and pathological section report are attached.

Pathological observation result shows, the histiocyte of each administration all multi viscera of group rat is harmless, morphology is pointed out this medicine to each organs and tissues without Toxic action.

6. conclusion

Rat chronic toxicity test result shows, with Chinese medicine preparation 2.07g/kg, 1.035g/kg, 0.5175g/kg of the present invention, is equivalent to clinical adult 60 times of daily dose 0.0345g/kg body weight, 30 times, 15 times, once a day, continuous 12 weeks, 24 weeks rat oral gavages be administered and drug withdrawal 4 weeks, Compare with blank group；Each dosed administration general state (mode of appearance, activity, stool shape etc.) to rat, growth promoter (body weight Increase), hemopoietic function (hematological examination), Liver and kidney function (blood biochemical analysis), vitals ponderal index, all find no obvious poison Property effect；Prove through pathological examination, the Chinese medicine preparation high dose group of the present invention and blank group comparative observation, to the rat heart, liver, spleen, lung, Kidney, adrenal gland, thymus, brain, uterus, ovary, testis, epididymis, prostate, thyroid, trachea, esophagus, stomach, aorta, 12 The histoorgans such as duodenum 12, colon, bladder, pancreas, lymph node, optic nerve, sciatic nerve all do not find that obvious toxic damages changes.Due to this There is not obvious pathological change in the Chinese medicine preparation each histoorgan of high dose group animal of invention, therefore to dosage group, low dosage in the Chinese medicine preparation of the present invention Group does not carries out organ-tissue section detection, and its Saving specimen is standby.So it is believed that larger dose, long period be orally administered to the Chinese medicine of the present invention The toxicity of preparation is relatively low, Clinical practice safety.

The experimentation of the tablet being made up of the Chinese medicine preparation for the treatment of diabetes:

It is attractive in appearance that this product Film coated tablets has tablet, indicates apparent, is difficult to emit imitative, and volume is less, is more easy to swallow, the advantage being convenient for carrying, metering Advantage more accurately.Under conditions of not changing former extraction process, drying process and route of administration, it is studied by spy, increases this product the most sugary Film coated tablet, the dosage form making up the peaceful removing obstruction from collaterals pill of sugar clinically is blank, preferably serves patient.

Study on extraction is tested:

For making the composition of prescription Chinese crude drug extract as far as possible, with paste-forming rate as inspection target, process of preparing Chinese medicine length, the amount of water to medical material, soak time, Decocting time, decoction number of times are investigated respectively, and its result is as follows:

(1) process of preparing Chinese medicine length of the prescription Chinese crude drug impact on paste-forming rate

Herba Plantaginis, Herba Agrimoniae are concocted into different length, and the decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, with 10 times Medical material is infiltrated 30 minutes by amount water, decocts 2 times, each 2 hours, filters, merging filtrate, concentrate, carry out paste-forming rate mensuration, the results are shown in Table 51:

The impact on paste-forming rate of the table 51 medicinal material processing length

From table 51: the paste-forming rate of medicinal material coarse powder is the highest, but after medicinal material coarse powder is extracted, medicinal liquid is difficult to filter, and during experiment, the method for machinery used drains Medicinal residues, are not suitable for big commercial production；And the paste-forming rate that cuts into 1.0cm section is close with it, therefore Herba Plantaginis, Herba Agrimoniae are cut into 1.0cm section and enter Row extraction is preferred.

(2) soak time impact on paste-forming rate

Herba Plantaginis, Herba Agrimoniae are concocted into 1.0cm section, and the decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, uses 10 times amount Medical material is infiltrated different time by water, then with a sieve, water filtration is fallen, weighs the weight of medical material, and (weight in wet base deducts dry weight divided by medicine to carry out hydroscopicity Material dry weight is hydroscopicity) measure, the results are shown in Table shown in 52:

The different soak time impact on paste-forming rate of table 52

As seen from the above table, medical material infiltrated after 30 minutes, and water absorption rate almost no longer increases, and from the consideration that saves time and cost, was preferred infiltrating 30 minutes.

(3) impact on paste-forming rate of different amount of water, decocting time and the extraction times

Herba Plantaginis, Herba Agrimoniae are concocted into 1.0cm section, and the decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, with different Amount of water, soaks 30 minutes, extracts with different decocting times and extraction time, filters, filtrate, concentrates, and carries out paste-forming rate mensuration, specifically with Scheme in table 5 below 3 is investigated, and result of the test is as shown in table 54:

The extraction scheme that table 53 is different

The different extraction scheme impact on extractum yield of table 54

From table 53, table 54: prescription medicinal material extract 2 times, adding 8 times amount water soaking 30 minutes for the first time, decoct 2 hours, second time adds 6 times amount water After decocting 1 hour, extractum yield almost no longer increases, and from saving the energy and time cost consideration, concocts into 1.0cm section with Herba Plantaginis, Herba Agrimoniae, The decoction pieces of Flos Lonicerae and the section Luo Qu that dies young directly feeds intake, and weighs recipe quantity medical material, decocts 2 times, is infiltrated 30 minutes by medical material with 8 times amount water for the first time, pan-fried Boil 2 hours；Second time 6 times amount soak by water 1 hour, filtration, the technique of merging filtrate is preferred.

Described paste-forming rate measures method particularly includes: takes and is concentrated into the clear paste that relative density is 1.2～1.3 (mensuration temperature 60 Cs), and transfer is also It is settled in 1000ml volumetric flask, shakes up；Precision measures 20ml, is respectively placed in the evaporating dish of constant weight, and water-bath volatilizes, and residue is in 105 DEG C It is dried 3 hours, takes out, put in exsiccator and place 30 minutes, weigh, calculate.

Experimental example 3: filter, concentrate and drying process research

3.1 filtering technique researchs:

Crude extract test uses (the 300 mesh filter cloth) method of filtration to carry out, in conjunction with producing appointed condition, has investigated with centrifuge and plate-and-frame filtration Two schemes:

Centrifugation protocol: take crude extract machine 3000/min by centrifugation and be centrifuged 1 minute, 2 minutes, 3 minutes, 5 minutes, observation centrifugal effect, be centrifuged 2 points Time more than clock, it is good that supernatant substantially becomes cleer and peaceful precipitate and separate.

Plate-and-frame filtration scheme: take crude extract through 5 pieces, 8 pieces, 10 pieces of filter plate, take filtrate machine 3000/min by centrifugation and be centrifuged 2 minutes, sees Examine precipitation number, find crude extract after 10 pieces of filter plate, almost without precipitation.

Save time from simplicity, preferable through the scheme of 10 pieces of filter plate with crude extract from the point of view of saving the energy.

3.2 concentration technology researchs:

In conjunction with industrial process conditions, there are uncovered Dumpage type interlayer steamer and triple effect concentrating under reduced pressure equipment,

For preventing effective ingredient for a long time by heat damage, triple effect concentrating under reduced pressure equipment is used to concentrate.The filtrate reduced in volume merged becomes relative density It is the clear paste of 1.2～1.3, measures temperature 60 C.

Concentrating under reduced pressure condition: temperature is 65～75 DEG C, vacuum is 0.04～0.06Mpa, and temperature and vacuum exceed upper limit extracting solution meeting bumping, The longest less than lower limit.

3.3 drying process researchs: combine industrial process conditions, have constant pressure and dry and decompression drying equipment, for making the production cycle shorten, select decompression It is dried.

Drying condition:

Using temperature is 65～75 DEG C, and vacuum is 0.07～0.09Mpa to carry out drying under reduced pressure.Temperature and vacuum is too high can bubble outside spilling dish, Pollute exsiccator, waste material.

Experimental example 4: preparations shaping technical study

4.1 supplementary product kinds and consumption select

1., the screening of disintegrating agent kind

According to the screening of preliminary experiment, in the case of this prescription medicated powder and auxiliary material proportion are constant, drug extract powder is directly added into different disintegrating agent, mixed Even, tabletting, with disintegration time as inspection target, measure its disintegration.

The mensuration of disintegration: carry out by Film coated tablets inspection requirements under " Chinese Pharmacopoeia " annex Ⅻ A inspection technique disintegration item in 2010.Record Completely disintegration time, the results are shown in Table 54-1:

Table 54-1 disintegrating agent kind the selection result

Therefore: the disintegration time with carboxymethyl starch sodium and microcrystalline Cellulose is shorter, therefore selects carboxymethyl starch sodium and microcrystalline Cellulose to combine and answer It is used as disintegrating agent.

2. the screening of suspending agent

After this product disintegrate, i.e. form thick suspension, therefore suspending agent need not be added.

3. the screening of filler

It was found that, apply multiple high-quality disintegrating agent, hardness is little, disintegrate is the most not ideal, because drug extract powder viscosity, moisture absorption are the strongest, And conventional disintegrating agent has hygroscopicity more, extract powder moisture absorption strengthens, and viscosity increases and makes tablet difficulty disintegrate.Therefore a kind of adjuvant should be selected to fill Agent is to reduce the hygroscopicity of extract powder and to increase the seeping of hydrone, it is simple to pelletizes and reduces the consumption of disintegrating agent.Experiment is with carboxymethyl starch sodium Combining with microcrystalline Cellulose and make disintegrating agent, extract powder and adjuvant are the ratio addition same amount of filler of variety classes of 21, mixing, tabletting, With disintegration time as inspection target, the results are shown in Table 54-2:

Table 54-2: filler kind the selection result

Result shows, when pregelatinized Starch is filler, tablet disintegration times is short, and hardness is relatively preferable, therefore selects pregelatinized Starch to do filler.

4. the screening of binding agent

Carboxymethylstach sodium, microcrystalline Cellulose and pregelatinized Starch is added in drug extract powder, although when the slice, thin piece hardness of compacting gained and disintegrate Limit is all fine, but outward appearance is the brightest and the cleanest, and mealiness is very big, therefore considers to select binding agent to improve this situation, and experiment accounts for 2 parts with extract powder, carboxylic first Starch Sodium, microcrystalline Cellulose and pregelatinized Starch three's equivalent add, and account for 1 part altogether, with the binding agent of variety classes different amounts, pelletize, tabletting, With disintegration time, hardness, outward appearance as inspection target, the results are shown in Table 54-3:

Table 54-3 binding agent kind the selection result

Result shows, with consumption be inventory 55% starch slurry (concentration is for 12%) be binding agent time, tablet disintegration times is short, and hardness is relatively Good, smooth appearance.

5. the screening of lubricant

After making granule with starch slurry, during tabletting, its mobility is not fine, through preliminary experiment, draws and compares by silicon dioxide and magnesium stearate Example is that 1:1 cooperation makees lubricant most preferably, accounts for 2 parts with extract powder, and carboxymethylstach sodium, microcrystalline Cellulose and pregelatinized Starch three's equivalent add, altogether Account for 1 part, be binding agent with the starch slurry (concentration is 12%) of inventory 55%, pelletize, tabletting, with compressibility as inspection target, the results are shown in Table 54-5:

Table 54-5 lubricant and the screening experiment of consumption

Wherein (silicon dioxide: the magnesium stearate) 1:1 with admixture doses 0.16% makees lubricant compressibility is optimal.

6. the screening of disintegrating agent, filler loading

The determination of index:

Mobility of particle: use the method measuring angle of repose to measure the mobility of granule.Angle of repose:

$\mathrm{\&alpha;}=\mathrm{arctg}\frac{h}{r}$

α value is the least shows that the mobility of granule is the best.

Grain graininess: the best according to production practices grain graininess the most oarse-grained compressibility between 20-60 mesh.Measured 20 mesh sieves only 60 mesh The particle weight of sieve, and calculated weight percentage ratio.

The evaluation of outward appearance: observing the integrity of slice, thin piece, with or without sliver, bright and clean degree, if sticking, color and luster is the most uniform.

Tablet weight variation: by " Chinese Pharmacopoeia 2005 version one (under annex I D tablet item) measures.

Hardness: measure the hardness of slice, thin piece with tablet hardness tester.

Disintegration: by " Chinese Pharmacopoeia 2005 version one (under annex I D tablet item) measures.

The evaluation of index:

Compressibility is the best: refer to α angle of repose less than 45 degree, grain graininess 20-60 mesh percentage by weight more than 70%, slice, thin piece complete appearance, bright and clean, Tablet weight variation meets regulation.Slice, thin piece hardness is more than 5Kg；

Compressibility is preferable: refer to angle of repose α more than 45 degree be less than 50 degree, grain graininess 20-60 mesh percentage by weight between 60%～70%, slice, thin piece Complete appearance, bright and clean, tablet weight variation meets regulation.Slice, thin piece hardness is between 4Kg～5Kg；

Compressibility is general: refer to angle of repose α more than 50 degree be less than 55 degree, grain graininess 20-60 mesh percentage by weight between 50%～60%, slice, thin piece Complete appearance, but fineness is poor, and tablet weight variation meets regulation, and slice, thin piece hardness is more than 3～4Kg；

Poor compressibility: referring to that angle of repose, α was less than 60 degree more than 55 degree, grain graininess 20-60 mesh percentage by weight is less than 50% more than 40%, slice, thin piece Outward appearance is sufficiently complete.Tablet weight variation is big, and slice, thin piece hardness is less than 3Kg；

Compressibility is poor: referring to that angle of repose, α was more than 60 degree, grain graininess 20-60 mesh percentage by weight is less than 40%, and slice, thin piece outward appearance is sufficiently complete.Sheet Heavily differing greatly, slice, thin piece hardness is less than 3Kg；

After the kind determining adjuvant, in order to ensure quality, and making its quality the most excellent, the consumption tackling various adjuvant screens.Use The method of orthogonal experiment, determines the varying level of each factor according to the result of preliminary experiment, is shown in Table 54-6:

The foundation of table 54-6 overall merit experiment water product

According to L₉(3⁴) experiment, medicated powder (going out based on dry cream rate 20.30% by medicinal material extract) is added the auxiliary materials and mixing of proper proportion, with the shallow lake of inventory 55% Slurry (concentration is 12%) is binding agent, pelletizes, and adds the lubricant of preferable amount, tabletting, with compressibility as inspection target, is evaluated.Just Hand over experimental result: be shown in Table 54-7:

Table 54-7 Orthogonal experiment results

X1, X2, X3 are respectively 3 result averages of varying level under each factor.

Table 54-8 orthogonal design analysis of variance table:

*P<0.05

From table 54-8, it is that C > A > B, i.e. microcrystalline Cellulose have spongiform porous according to the order of numeral the most each the least factor impact Tubular structure, during pressurized, its loose structure is become linear arrangement from disorderly and unsystematic, makes hydrone be easily accessible inside tablet, assists disintegrate, and crystallite is fine The addition of dimension element is on experimental result impact maximum；Carboxymethylstach sodium has good hydrophilic, water absorption and dilatancy, the volume of expansion own 200～ 300 times, disintegrate excellent result, improve the compressibility of slice, thin piece, the hardness of the slice, thin piece pressed increases, and the situation of mealiness does not occur in smooth appearance. Best prescription composition A₂B₂C₂, i.e. carboxymethylstach sodium accounts for medicated powder amount 1.67%, and pregelatinized Starch accounts for the 2.9% of medicated powder amount, and microcrystalline Cellulose is medicated powder amount 15.67%, other right amount of auxiliary materials.

4.2 Particle physical properties researchs

1. character: this product granule is that brown is to sepia, feeble QI, bitter in the mouth.

2. bulk density: weigh constant weight conforming particle, loads in 10ml graduated cylinder, falls for several times (control condition as far as possible is consistent) with certain altitude, Make degree of tightness appropriateness, obtain bulk density with weight divided by volume, the results are shown in Table 54-9.

Table 54-9 granular pile density measurement result

3. the mensuration of angle of repose: take conforming particle and flow down and in cone shape through funnel, measure its angle of repose, the results are shown in Table 54-10.

Table 54-10 granule angle of repose

The angle of repose of granule is less than 45.0 °, has good mobility, is suitable for the requirement of tabletting.

4. the critical relative humidity of granule measures

The relative humidity table of table 54-11 different solutions

Table 54-12 critical relative humidity determination data

Being tried to achieve by sucting wet curve, critical relative humidity is about 58%.In conjunction with producing, should be by relative humidity control when beating powder, mixing, fill and store System is below 55%, to reduce moisture to pharmaceutical properties and the impact of stability.

4.3 tablet forming technique researchs

4.3.1 the selection of pellet moisture

Pellet moisture affects sheet protonatomic mass, and the granule plasticity that water content is suitable is big, and the hardness of the tablet being pressed into is preferable, and granule is overly wet, the most easily sends out Raw sticking.By test, the moisture Control in granule is when 4.0～5.5%, and hardness is preferable, unilateral bright and clean, and degree of fragmentation is preferable, and qualification rate is higher.

4.3.2 hardness is at various pressures, and the slice, thin piece hardness prepared is very big on the impact of disintegration time, and along with the increase of sheet hardness, disintegration time subtracts Slowly.By to the slice, thin piece outward appearance prepared under different hardness and disintegration time result, being shown in Table 54-13

Outward appearance under table 54-13 different hardness and disintegration time

As can be seen here, when hardness is 3～4kg, disintegration time is within 40 minutes, and surface is glossy, it is thus determined that hardness is 3～4kg.

4.3.3 tabletting

According to the studies above result, making granule, be dried, mixing, regulation tablet weight is 0.39g, and hardness is 3～4kg, is pressed into 1000 elements Sheet.

4.4 film coating technical studies

4.4.1 the selection of film coating pre-mix dose consumption

Take the purified water of 4.93kg, form vortex with stirring slurry stirring, weigh film coating pre-mix dose 1.01kg and join vortex sidewall and be configured to Concentration is the Coating Solution of 17%, continuously stirred 45 minutes, crosses 60～80 mesh sieves stand-by.Take this product element sheet (lot number: 20120901, average sheet It is heavily 0.3915g) 19.57kg, about 50000, puts in high-efficiency coating machine, is warming up to 40～60 DEG C.With spray gun, Coating Solution is sprayed into rotation In the high-efficiency coating machine turned, controlling rotating speed is 5～20rpm, and sheet bed tempertaure requires at 38～45 DEG C, compressed air 0.4～0.5Mpa, until will bag Clothing material has sprayed.Turn off hot blast, rotating speed is down to≤5.After slice, thin piece cools down, turn off air draft.Detection outward appearance, moisture≤4%.Respectively at coating Solution spray is removed 2.30kg, 2.50kg, 3.00kg, 3.45kg, 4.60kg, 5.25kg and is sprayed onto when Coating Solution is finished and respectively takes out sample 20 Sheet, is designated as sample 1, sample 2, sample 3, sample 4, sample 5, sample 6, sample 7 respectively, freeze-day with constant temperature 8 hours when putting 50 DEG C of baking oven, Now taking 4, each sample, recording moisture with fast tester for water content is 3.5%.It is carried out remaining sample outward appearance and disintegration examines Examining, result see table 54-14.

Outward appearance under table 54-14 different amounts film coating pre-mix dose and disintegration time

From result in upper table, 50000 this product element sheets, spraying into Coating Solution 4.60kg that concentration is 17% and to the bag having sprayed experiment Sample after clothing solution, outward appearance and disintegration all meet the requirements.In conjunction with factors such as production costs, choose the Coating Solution 4.60 that spray concentration is 17% Kg is optimal, containing 17% film coating pre-mix dose, i.e. 782.8g in 4.60kg Coating Solution, is converted into recipe quantity 1000 and calculates, thin film Coating pre-mixing agent consumption should be 15.66g.

4.4.2 art for coating

Take appropriate water, form vortex with stirring slurry stirring, weigh and film coating pre-mix dose is joined vortex sidewall be configured to the bag that concentration is 17% Clothing solution, continuously stirred 45 minutes, crosses 60-80 mesh sieve stand-by.Element sheet is put in high-efficiency coating machine, is warming up to 40-60 DEG C.Will bag with spray gun Clothing solution sprays in the high-efficiency coating machine of rotation, and control rotating speed is 5-20rpm, and sheet bed tempertaure requires at 38-45 DEG C, compressed air 0.4-0.5Mpa, Until coating material has been sprayed.Turn off hot blast, rotating speed is down to≤5.After slice, thin piece cools down, turn off air draft.Detection outward appearance, moisture≤4%, increase Weigh 4.0%.

Experimental example 5: scale up test is tested

The extraction process that preferably goes out according to the present invention, filter, concentrate and drying process, preparations shaping technique, carry out the engineer testing of pilot-scale, Feeding intake three batches altogether, carry out by 100 times of recipe quantities, three batches of pilot products detection data are shown in Table 56-1, table 56-2:

Tri-batches of pilot plant test data of table 56-1

Tri-batches of pilot sample assays of table 56-2

Through the checking of three batch scale up test, result shows: the technique of the peaceful removing obstruction from collaterals pill of sugar is rational, feasible.

Compared with prior art, the Chinese medicine preparation blood sugar lowering of the treatment diabetes that the present invention is made up of Miao Ethnomedicine secret recipe is notable, has more preferable therapeutic effect. This prescription derives from folk remedy, and the use history of existing more than 50 year, is the prescription summed up by clinical practice, have consolidate yin nourishing, change turbid Promote blood circulation, effect of promoting the production of body fluid to quench thirst, particularly with the diabetes caused by deficiency of both QI and YIN and complication, there is obvious blood sugar reducing function, and this blood sugar reducing function It is not entirely dependent on promotion B cell secretion；It addition, the Chinese medicine preparation of the present invention has a certain degree of islets of langerhans protective effect to type 2 diabetes mellitus, Insulin resistant can be improved；It does not have blood sugar reducing function to normal SD rats；Additionally, the Chinese medicine preparation quality safety of the present invention is reliable, do not find not Good reaction and toxic and side effects.Additionally, the tablet that the present invention makes, only disintegration time are shorter, hardness is relatively preferable, appearance is bright and clean, compressibility is good, Bulk density is good, reduce moisture to the advantage such as pharmaceutical properties and good stability.

Accompanying drawing explanation

Fig. 1 is the preparation technology flow chart that the present invention treats the Chinese medicine preparation of diabetes；

Tu2Shi section dies young the preparation technology flow chart of Luo Qu；

Fig. 3 is that critical relative humidity measures curve chart；

Fig. 4 is rat limosis after 16 hours, gives glucose solution (gavage, 20g/100mL, 3mL/ are only), measure the empty stomach of rat, 1h, 2h, 3h blood glucose value result curve；

Fig. 5 is that normal group is to type Ⅱdiabetes mellitus pancreas in rat pathological change schematic diagram；

Fig. 6 is that model group is to type Ⅱdiabetes mellitus pancreas in rat pathological change schematic diagram；

Fig. 7 is that model group is to type Ⅱdiabetes mellitus pancreas in rat pathological change schematic diagram；

Fig. 8 is that the Chinese medicine preparation of the present invention affects schematic diagram to type Ⅱdiabetes mellitus rat body weight；

Fig. 9 is that the Chinese medicine preparation of the present invention affects schematic diagram to type 2 diabetes mellitus rat carbohydrate tolerance；

Figure 10 is the section schematic diagram of normal rats pancreas；

Figure 11 is the section schematic diagram of model group diabetic rat pancreas；

Figure 12 is that metformin group affects schematic diagram to the section of diabetic rat pancreas；

Figure 13 is that TNTL low dose group affects schematic diagram to the section of diabetic rat pancreas；

Figure 14 is that TNTL high dose group affects schematic diagram to the section of diabetic rat pancreas；

Figure 15 is that drug combination affects schematic diagram to type 2 diabetes mellitus rat carbohydrate tolerance；

Figure 16 is the pancreas schematic diagram of normal rats；

Figure 17 is the pancreas schematic diagram of model group rats；

Figure 18 is that metformin+TNTL low dose group drug combination affects schematic diagram to pancreas in rat；

Figure 19 is that normal+TNTL high dose group affects schematic diagram to pancreas in rat；

Figure 20 is that critical relative humidity measures curve.

Detailed description of the invention

Embodiment 1:

Section dies young the preparation method of Luo Qu: the mixture fresh for medical material Fructus Trichosanthis 2g, fresh Caulis Spatholobi 2g and fresh Herba Sedi 1g formed takes through squeezing After juice, the dry fine powder of medicinal residues mixes with flour 2g, wheat bran 1g again, adds medicine juice and water and stirs evenly and make soft material, steams thoroughly, to keep temperature be 22 DEG C, Humidity is 50%, adds bent essence fermentation 25 days, takes out, dry, pulverize, to obtain final product.Described fresh Fructus Trichosanthis can also be Semen Trichosanthis, Pericarpium Trichosanthis With one or more in Radix Trichosanthis.

The preparation method of capsule for the treatment of diabetes: the section of weighing dies young Luo Qu 480g, Herba Plantaginis 350g, Herba Agrimoniae 335g and Flos Lonicerae 335g, will Herba Plantaginis and Herba Agrimoniae cut into 1.0cm section, add 8 times amount water, soak 30 minutes, decoct 2 hours, filter, take filtrate standby；Medicinal residues add 6 Times amount soak by water 1 hour, filters, merges twice filtrate, filters, is condensed into the clear paste that relative density is 1.2 of 60 DEG C, in temperature 65 DEG C, true Under conditions of reciprocal of duty cycle 0.1Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, granulate, add 1.13g silicon dioxide, mixing, load capsule, i.e. make Obtain capsule.Instructions of taking: in terms of crude drug powder, 3g/ time, daily 3 times, daily crude drug powder meter 9-12g, bfore meals；With capsule Meter: owing to medical material inventory is 1500g, paste-forming rate is 20.3%, thus calculates dry cream about 304.5g, adjuvant silica 1 .13g again, amounts to 305.63g, makes 1000, every weight 0.3056g, and i.e. every is equivalent to raw medicinal herbs 1.5g, and average every is heavily 0.30g, and therefore design is every time Take 2-3 grain (0.30 dry cream/grain), three times a day, suitable with daily 9-12g crude drug powder, bfore meals.

Character: this product is hard capsule, content should be brown to tan powder, bitter in the mouth.

Embodiment 2:

Section dies young the preparation method of Luo Qu: the mixture fresh for medical material Fructus Trichosanthis 2g, fresh Caulis Spatholobi 2g and fresh Herba Sedi 1g formed takes through squeezing After juice, the dry fine powder of medicinal residues mixes with flour 2g, wheat bran 1g again, adds medicine juice and stirs evenly and makes soft material, steams thoroughly, and to keep temperature be 26 DEG C, wet Degree is 65%, adds bent essence fermentation 30 days, takes out, dry, pulverize, and Ji get section dies young Luo Qu.

The preparation method of tablet for the treatment of diabetes: the section of weighing dies young Luo Qu 400g, Herba Plantaginis 300g, Herba Agrimoniae 400g and Flos Lonicerae 400g, by car Front grass and Herba Agrimoniae cut into 1.0cm section, add 10 times amount water, soak 120 minutes, decoct 2 hours, filter, take filtrate standby；Medicinal residues add 10 times amount soak by water 2 hours, filter, merge twice filtrate, filter, be condensed into the clear paste that relative density is 1.3 of 60 DEG C, in temperature 75 DEG C, Under conditions of vacuum 0.1Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, add the corresponding adjuvant of tablet, obtain 1000, tablet.The side of taking Method: three times a day, each 2, every weight 0.15g, bfore meals.

Embodiment 3:

Section dies young the preparation method of Luo Qu: the mixture fresh for medical material Fructus Trichosanthis 2g, fresh Caulis Spatholobi 2g and fresh Herba Sedi 1g formed takes through squeezing After juice, the dry fine powder of medicinal residues mixes with flour 2g, wheat bran 1g again, adds medicine juice and stirs evenly and makes soft material, steams thoroughly, and to keep temperature be 18 DEG C, wet Degree is 45%, adds bent essence fermentation 20 days, takes out, dry, pulverize, and Ji get section dies young Luo Qu.

The preparation method of granule for the treatment of diabetes: the section of weighing dies young Luo Qu 500g, Herba Plantaginis 400g, Herba Agrimoniae 300g and Flos Lonicerae 300g, will Herba Plantaginis and Herba Agrimoniae cut into 1.0cm section, add 6 times amount water, soak 90 minutes, decoct 1 hour, filter, take filtrate standby；Medicinal residues add 8 Times amount soak by water 1 hour, filters, merges twice filtrate, filters, is condensed into the clear paste that relative density is 1.2 of 60 DEG C, in temperature 55 DEG C, true Under conditions of reciprocal of duty cycle 0.08Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, add the corresponding adjuvant of granule, obtain granule 1000.Clothes By method: three times a day, each 2, every weight 0.15g, bfore meals.

Embodiment 4:

The preparation method of drop pill for the treatment of diabetes: weigh the section of preparation in embodiment 1 die young Luo Qu 550g, Herba Plantaginis 350g, Herba Agrimoniae 300g and Flos Lonicerae 300g, cuts into 1.0cm section by Herba Plantaginis and Herba Agrimoniae, adds 10 times amount water, soaks 120 minutes, decocts 2 hours, filters, takes Filtrate is standby；Medicinal residues add 10 times amount soak by water 2 hours, filter, merge twice filtrate, filter, and the relative density being condensed into 60 DEG C is 1.3 Clear paste, becomes dry cream by clear paste drying under reduced pressure under conditions of temperature 75 DEG C, vacuum 0.1Mpa；Pulverize, add the corresponding adjuvant of drop pill, to obtain final product Drop pill.Instructions of taking: three times a day, each 2-3 grain, every weight 0.3g, bfore meals.

Embodiment 5: a kind of tablet treating diabetes:

Prescription:

Section dies young Luo Qu 400g Herba Plantaginis 300g Herba Agrimoniae 400g Flos Lonicerae 400g

Make 1000 preparation unit

Wherein, the described section Luo Qu that dies young is Miao ethnic group's conventional crude drugs, the fresh Fructus Trichosanthis of Guizhou genuine medicinal materials and fresh Exocarpium Benincasae mix with the weight ratio of 9:1 Glutinous rice flour carries out carrying out zymolysis through song system through song system and forms.

Specifically, the described section Luo Qu that dies young is prepared from by the following method: the fresh Fructus Trichosanthis of weighting raw materials and fresh Exocarpium Benincasae, squeezes extracting juice, Standby；Medicinal residues are dried, it is ground into fine powder, by this medicinal residues fine powder according to medicinal residues fine powder: the weight proportion of glutinous rice flour=9:1 mixes with glutinous rice flour, Adding medicine juice, add water to stir evenly simultaneously and make soft material, steam thoroughly, to keep temperature be 18～26 DEG C, humidity is 45%～65%, add bent essence fermentation 16～ In 30 days (summer 16～25, winter 20～30, spring and autumn 16～30), take out, pulverize, be dried, to obtain final product.

Preparation method: weigh the recipe quantity section Luo Qu that dies young and (carried out zymolysis through song system formed by fresh Fructus Trichosanthis Herb and fresh Caulis Spatholobi, Herba Sedi.)、 Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, add 8 times amount water, soaks 30 minutes, decocts 2 hours, filters, and medicinal residues add 6 times amount soak by water 1 hour, filters, Merging filtrate, is concentrated into the clear paste that relative density is 1.2～1.3 (mensuration temperature 60 Cs), 65～75 DEG C of drying under reduced pressure.Dried cream powder is broken, crosses 100 mesh Sieve, adds carboxymethyl starch sodium, pregelatinized Starch and microcrystalline Cellulose, pelletizes, and takes out wet granular and is dried in 65～75 DEG C, and dry granule is whole with No. two sieves After Li, add mix lubricant uniformly, tabletting, film coating, obtain tablet.Instructions of taking: oral.3-4 sheet, 3 times on the one；After meal Take or follow the doctor's advice.Every tablet weight 0.4g

The invention discloses a kind of Chinese medicine preparation treating diabetes and preparation method thereof, described preparation method includes: calculates by weight, weighs section Die young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, add 6～10 times amount water, soak 30～120 minutes, decoct 1～2 hour, filter, take filtrate standby With；Medicinal residues add 6～10 times amount soak by water 1～2 hours, filter；Merge twice filtrate, filter, concentrate, dry, pulverize, add adjuvant, system Become corresponding Chinese medicine preparation, to obtain final product.

Embodiment 6: the preparation method of a kind of tablet treating diabetes:

Active component prescription:

Section dies young Luo Qu 480g Herba Plantaginis 350g Herba Agrimoniae 335g Flos Lonicerae 335g

Weigh section to die young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, Herba Plantaginis and Herba Agrimoniae are cut into 1.0cm section, adds 8 times amount water, soak 30 points Clock, decocts 2 hours, filters, takes filtrate standby；Medicinal residues add 6 times amount soak by water 1 hour, filter, merge twice filtrate, filter, are condensed into 60 DEG C the clear paste that relative density is 1.2, under conditions of temperature 65 DEG C, vacuum 0.1Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, granulate, mistake 100 mesh sieves, add the carboxymethylstach sodium of dry cream gross weight 1.67%, the pregelatinized Starch of 2.9%, the microcrystalline Cellulose of 15.67%, with inventory 55%, And the starch slurry that concentration is 12% is that binding agent is pelletized, takes out wet granular and be dried in 65～75 DEG C, after dry granule sieves granulate with No. two, admixture doses It is uniform that the silicon dioxide of the 1:1 of 0.16% and magnesium stearate make mix lubricant, is pressed into 1000, film coating, and every tablet weight 0.4g to obtain final product.Take Method: oral, a 3-4 sheet, 3 times on the one；One after each meal or follow the doctor's advice.

Embodiment 7: the detection method of the tablet for the treatment of diabetes:

(1) taking this product and remove coating, grind to form fine powder, weigh 1.3g, the methanol adding 10ml filters for ultrasonic 30 minutes, takes filtrate 5ml, adds A small amount of magnesium powder, drips 12～14 concentrated hydrochloric acid, and water-bath 1～2 minutes, solution becomes reddish violet.

(2) taking this product and remove coating, grind to form fine powder, weigh 3.8g, add 95% ethanol 50ml, reflux, extract, 2 hours, filter, filtrate concentrates To 5ml, as need testing solution.Separately take luteoloside reference substance, add methanol and make every 1ml solution containing 0.4mg, as reference substance solution. Test according to thin layer chromatography (one annex VI B of " Chinese Pharmacopoeia " version in 2010), draw need testing solution 3.5 μ l, reference substance solution 1 μ l, point Other point is on same silica gel G plate, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, take out, dry, spray with 5% aluminum chloride ethanol solution, 105 DEG C are heated 10 minutes, let cool, put and inspect under uviol lamp (365nm).In test sample chromatograph, with compare On product chromatograph relevant position, the fluorescence speckle of aobvious same color.

(3) taking this product and remove coating, grind to form fine powder, weigh 2.6g, add 95% ethanol 50ml, reflux, extract, 2 hours, filter, filtrate concentrates To 10ml, as need testing solution.Separately take Big Semen Plantaginis glycosides reference substance, add 60% methanol and make every 1ml solution containing 0.1mg, as reference substance Solution.Test according to thin layer chromatography (one annex VI B of " Chinese Pharmacopoeia " version in 2010), draw need testing solution 2 μ l, reference substance solution 2 μ l, Put respectively on same polyamide film, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, open up away from for 5cm, Take out, heat 10 minutes at 60 DEG C, put and inspect under uviol lamp (365nm).In test sample chromatograph, on position corresponding with reference substance chromatograph, The fluorescence speckle of aobvious same color.

(4) taking this product and remove coating, grind to form fine powder, weigh 2.6g, add methanol 30ml, reflux, extract, 3 hours, filter, filtrate is concentrated into 10ml, As need testing solution.Separately take 3,5-Dicaffeoylquinic acid reference substance, add methanol and make every 1ml solution containing 0.4mg, as reference substance solution.According to thin layer Chromatography (" Chinese Pharmacopoeia " 2010 editions one annex VI B) is tested, and draws need testing solution 2 μ l, reference substance solution 1 μ l, puts respectively in same On one polyamide film, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, open up away from for 5cm, take out, 60 DEG C heating 10 minutes, put and inspect under uviol lamp (365nm).In test sample chromatograph, with on reference substance chromatograph relevant position, show same color Fluorescence speckle.

Claims (17)

1. the Chinese medicine preparation treating diabetes, it is characterised in that calculate by weight, its active component is prepared from by following crude drug:

Section dies young Luo Qu 400～300～400 parts of Herba Agrimoniaes of 550 portions of Herba Plantaginiss 300～400 parts of Flos Lonicerae 300～400 parts.

The Chinese medicine preparation for the treatment of diabetes the most according to claim 1, it is characterised in that calculate by weight, it prepared by following crude drug and Become:

Section dies young 480 portions of Herba Plantaginiss of Luo Qu, 335 parts of Flos Lonicerae of 350 parts of Herba Agrimoniaes 335 parts.

The Chinese medicine preparation for the treatment of diabetes the most according to claim 1 and 2, it is characterised in that described section dies young Luo Qu, calculates by weight, By the fresh Fructus Trichosanthis of medical material 2 parts, fresh Caulis Spatholobi 2 parts and 1 part of mixture formed of fresh Herba Sedi after squeezing extracting juice, the dry fine powder of medicinal residues Mix with flour 2 parts, 1 part of wheat bran again, add medicine juice, carry out zymolysis through song system and form.

The Chinese medicine preparation for the treatment of diabetes the most according to claim 3, it is characterised in that the dry fine powder of described medicinal residues and flour and wheat bran Mixture, adds medicine juice and stirs evenly and makes soft material, steams thoroughly, and to keep temperature be 18～26 DEG C, humidity is 45%～65%, adds bent essence fermentation 20 days ～30 days, taking out, dry, pulverize, Ji get section dies young Luo Qu.

The Chinese medicine preparation for the treatment of diabetes the most according to claim 1 and 2, it is characterised in that described section die young Luo Qu by the fresh Fructus Trichosanthis of medical material, Fresh Exocarpium Benincasae, Herba Sedi mix with the weight ratio of 2:2:1, through squeezing, are dried, pulverize and obtain fine powder, then with this fine powder, flour and wheat bran with 5:2:1 carries out zymolysis through song system and forms.

The Chinese medicine preparation for the treatment of diabetes the most according to claim 5, it is characterised in that Luo Qu dies young by the fresh Fructus Trichosanthis of medical material, fresh in described section Exocarpium Benincasae, Herba Sedi mix with the weight ratio of 2:2:1；After drying, it is ground into fine powder, then with this fine powder: flour: the weight of wheat bran=5:2:1 Amount proportioning mixing, adds medicine juice, adds water to stir evenly simultaneously and make soft material, steam thoroughly, and to keep temperature be 18～26 DEG C, humidity is 45%～65%, adds Bent essence fermentation 20～30 days, takes out, dry, pulverize, to obtain final product.

7. a kind of preparation method of the Chinese medicine preparation of the arbitrary described treatment diabetes of claim 1-6, it is characterised in that calculate by weight, weigh section Die young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, add 6～10 times amount water, soak 30～120 minutes, decoct 1～2 hour, filter, take filter Liquid is standby；Medicinal residues add 6～10 times amount soak by water 1～2 hours, filter；Merge twice filtrate, filter, concentrate, dry, pulverize, add auxiliary Material, makes corresponding Chinese medicine preparation, to obtain final product.

The preparation method of the Chinese medicine preparation for the treatment of diabetes the most according to claim 7, it is characterised in that calculate by weight, the section of weighing dies young sieve Song, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, cut into 1.0cm section by Herba Plantaginis and Herba Agrimoniae, adds 8 times amount water, soaks 30 minutes, decocts 2 Hour, filter, take filtrate standby；Medicinal residues add 6 times amount soak by water 1 hour, filter, merge twice filtrate, filter, and are condensed into 60 DEG C relative Density is the clear paste of 1.2～1.3, under conditions of temperature 55～75 DEG C, vacuum 0.08～0.1Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, Add adjuvant, make corresponding Chinese medicine preparation, to obtain final product.

The preparation method of the Chinese medicine preparation for the treatment of diabetes the most according to claim 8, it is characterised in that calculate by weight, the section of weighing dies young sieve Song, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, cut into 1.0cm section by Herba Plantaginis and Herba Agrimoniae, adds 8 times amount water, soaks 30 minutes, decocts 2 Hour, filter, take filtrate standby；Medicinal residues add 6 times amount soak by water 1 hour, filter, merge twice filtrate, filter, and are condensed into 60 DEG C relative Density is the clear paste of 1.2, under conditions of temperature 65 DEG C, vacuum 0.1Mpa, clear paste drying under reduced pressure is become dry cream；Pulverize, granulate, add dry The silicon dioxide of the 0.37% of cream gross weight, mixing, load capsule, obtain capsule.

10. the tablet prepared according to Chinese medicine preparation described in claim 1-6, it is characterised in that also include filler, disintegrating agent, binding agent and lubricant.

11. tablets prepared according to Chinese medicine preparation described in claim 1-6, it is characterised in that include the filler of active component weight 1%-5%, activity The disintegrating agent of Ingredients Weight 10%-20%, inventory 40-60% and concentration are binding agent and the inventory 0.1-0.5% lubricant of 10-15%.

12. tablets prepared according to Chinese medicine preparation described in claim 11, it is characterised in that described filler is pregelatinized Starch, described disintegrate Agent be carboxymethyl starch or/and microcrystalline Cellulose, described binding agent is starch slurry, and described lubricant is silicon dioxide or/and magnesium stearate.

13. tablets prepared according to Chinese medicine preparation described in claim 12, it is characterised in that described disintegrating agent includes that 1-3 part carboxymethyl forms sediment by weight Powder and 10-20 part microcrystalline Cellulose；Described lubricant includes 1-5 part silicon dioxide and 1-5 part magnesium stearate by weight.

14. according to Chinese medicine preparation described in claim 13 prepare tablets, it is characterised in that include active component weight 1.67% carboxymethyl starch sodium, The pregelatinized Starch of active component weight 2.9%, the microcrystalline Cellulose of active component weight 15.67%, inventory 55% and concentration are the starch of 12% Slurry, the silicon dioxide of inventory 0.16% and magnesium stearate, wherein silicon dioxide: the weight ratio of magnesium stearate is 1:1.

15. according to the preparation method of the tablet described in any one of claim 10-14, it is characterised in that: the section of taking dies young Luo Qu, Herba Plantaginis, Herba Agrimoniae and mountain Flos Lonicerae four taste, soaks 30 minutes, decocts twice, 2 hours for the first time, 1 hour for the second time, collecting decoction, filters, and concentrates, and is dried Become dry cream；Pulverize, cross 100 mesh sieves, add carboxymethyl starch sodium, pregelatinized Starch and microcrystalline Cellulose, pelletize, be dried, granulate, add lubrication Agent mix homogeneously, tabletted, film coating, to obtain final product.

The preparation method of 16. tablets according to claim 15, it is characterised in that: the section of weighing dies young Luo Qu, Herba Plantaginis, Herba Agrimoniae and Flos Lonicerae, Herba Plantaginis and Herba Agrimoniae are cut into 1.0cm section, adds 8 times amount water, soak 30 minutes, decoct 2 hours, filter, take filtrate standby；Medicinal residues Add 6 times amount soak by water 1 hour, filter, merge twice filtrate, filter, be condensed into the clear paste that relative density is 1.2 of 60 DEG C, in temperature 65 DEG C, clear paste drying under reduced pressure is become dry cream under conditions of vacuum 0.1Mpa；Pulverize, granulate, cross 100 mesh sieves, add dry cream gross weight 1.67% Carboxymethylstach sodium, the pregelatinized Starch of 2.9%, the microcrystalline Cellulose of 15.67%, with inventory 55% and starch slurry that concentration is 12% be bonding Agent pelletize, take out wet granular in 65～75 DEG C be dried, dry granule with No. two sieve granulate after, the silicon dioxide of the 1:1 of admixture doses 0.16% with It is uniform that magnesium stearate makees mix lubricant, tabletting, and film coating to obtain final product.

17. according to the detection method of the tablet described in claim 10-16, it is characterised in that: (1) takes this product and removes coating, grinds to form fine powder, weighs 1.3g, The methanol adding 10ml filters for ultrasonic 30 minutes, takes filtrate 5ml, adds a small amount of magnesium powder, drips 12～14 concentrated hydrochloric acid, water-bath 1～2 points Clock, solution becomes reddish violet.

(2) taking this product and remove coating, grind to form fine powder, weigh 3.8g, add 95% ethanol 50ml, reflux, extract, 2 hours, filter, filtrate concentrates To 5ml, as need testing solution.Separately take luteoloside reference substance, add methanol and make every 1ml solution containing 0.4mg, as reference substance solution. Test according to thin layer chromatography (one annex VI B of " Chinese Pharmacopoeia " version in 2010), draw need testing solution 3.5 μ l, reference substance solution 1 μ l, point Other point is on same silica gel G plate, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, take out, dry, spray with 5% aluminum chloride ethanol solution, 105 DEG C are heated 10 minutes, let cool, put and inspect under uviol lamp (365nm).In test sample chromatograph, with compare On product chromatograph relevant position, the fluorescence speckle of aobvious same color.

(3) taking this product and remove coating, grind to form fine powder, weigh 2.6g, add 95% ethanol 50ml, reflux, extract, 2 hours, filter, filtrate concentrates To 10ml, as need testing solution.Separately take Big Semen Plantaginis glycosides reference substance, add 60% methanol and make every 1ml solution containing 0.1mg, as reference substance Solution.Test according to thin layer chromatography (one annex VI B of " Chinese Pharmacopoeia " version in 2010), draw need testing solution 2 μ l, reference substance solution 2 μ l, Put respectively on same polyamide film, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, open up away from for 5cm, Take out, heat 10 minutes at 60 DEG C, put and inspect under uviol lamp (365nm).In test sample chromatograph, on position corresponding with reference substance chromatograph, The fluorescence speckle of aobvious same color.

(4) taking this product and remove coating, grind to form fine powder, weigh 2.6g, add methanol 30ml, reflux, extract, 3 hours, filter, filtrate is concentrated into 10ml, As need testing solution.Separately take 3,5-Dicaffeoylquinic acid reference substance, add methanol and make every 1ml solution containing 0.4mg, as reference substance solution.According to thin layer Chromatography (" Chinese Pharmacopoeia " 2010 editions one annex VI B) is tested, and draws need testing solution 2 μ l, reference substance solution 1 μ l, puts respectively in same On one polyamide film, with ethyl acetate-acetone-formic acid-water (7:3:1:1.2) as developing solvent, launch, open up away from for 5cm, take out, 60 DEG C heating 10 minutes, put and inspect under uviol lamp (365nm).In test sample chromatograph, with on reference substance chromatograph relevant position, show same color Fluorescence speckle.