CN110437349A

CN110437349A - A kind of novel postcibal diarrhea of heparin sodium, enzymatic hydrolysis, elution process

Info

Publication number: CN110437349A
Application number: CN201810411757.8A
Authority: CN
Inventors: 鲁保存
Original assignee: Shandong Hengrui Meat Product Co Ltd
Current assignee: Shandong Hengrui Meat Product Co Ltd
Priority date: 2018-05-02
Filing date: 2018-05-02
Publication date: 2019-11-12

Abstract

The invention discloses a kind of novel postcibal diarrhea of heparin sodium, enzymatic hydrolysis, elution process, including postcibal diarrhea, enzymatic hydrolysis, five big process of absorption, elution and precipitating, it is characterized in that, in the postcibal diarrhea process, the mucus scraped out of casing is collected when carrying out striking to hair intestines breaks its intestines skin and casing, again casing inside is carried out pouring water flushing after the separation of intestines skin simultaneously and collect flushing liquor, by the mucus and flushing liquor as the intestinal mucosa liquid in the enzymatic hydrolysis process；Three-level elution is carried out to the resin filtered out from the absorption process using salt water in the elution procedure.The novel postcibal diarrhea of heparin sodium of the present invention, enzymatic hydrolysis improve existing postcibal diarrhea, enzymatic hydrolysis, elution procedure method in elution process, it can be improved the working efficiency of heparin production, the heparin compositions in hair intestines are more fully extracted, the productivity effect of better heparin sodium is obtained.

Description

A kind of novel postcibal diarrhea of heparin sodium, enzymatic hydrolysis, elution process

Technical field

The present invention relates to heparin process for producing sodium field, it is specifically related to a kind of novel postcibal diarrhea of heparin sodium, enzymatic hydrolysis, elution side Method.

Background technique

Heparin sodium is a kind of mucopolysaccharide sulfuric acid ester anticoagulant, is the sulfuric acid amino by extracting in the intestinal mucosa of pig or ox The sodium salt of glucan belongs to mucopolysaccharide substance, and the compound that molecular structure hitherto known in the world is most complicated, short Can not be artificial synthesized in phase, separation can only be extracted from the mucous membrane of small intestine of the livestocks such as pig or ox at present.Recent study proves liver There are also effect for reducing blood fat for plain sodium, have very high medical value.

Heparin stoste obtained in mucous membrane of small intestine from live pig, due to containing the impurity such as a large amount of albumen, nucleic acid, microorganism, Physics and chemical extraction separation process need to be passed through, the complete heparin sodium crude of natural structure group could be obtained, so that liver be made Plain bulk pharmaceutical chemicals.In the novel postcibal diarrhea of existing heparin sodium of heparin first product, enzymatic hydrolysis, elution process, can generally it need by postcibal diarrhea, enzyme The process such as solution, absorption, elution and precipitating.

But the preparation method of existing heparin sodium first product has the following deficiencies: that 1, heparin sodium extraction efficiency is not high, substantially Every 1600-1700 root chitterlings could prepare the heparin sodium first product of one hundred million unit (referring to active matter prime number).2, more in each step Using manual operations, the degree of automation is low, causes labor efficiency low.

More particularly, currently, artificial postcibal diarrhea is generally used in postcibal diarrhea process, under efficiency is very low.In order to improve Efficiency, the invention of CN201388473Y was once disclosed a kind of archenteron-scrapping machine in the prior art, and structure includes rack, the bottom of rack Motor, retarder are installed, retarder is equipped with two output shafts and thong wheel or sprocket wheel, wherein in the upper design of rack There is left and right fulcrum bearing, active rubber roll, transition rubber roller and doctor roll are sequentially installed between two fulcrum bearings, and before three rollers are in High dip arrangement after low；Wherein active rubber roll and doctor roll respective one end axis Extension support seat installs belt pulley or chain on axis Wheel, by belt or chain respectively on reducer output shaft belt pulley or sprocket wheel be sequentially connected；The device is able to solve people Work postcibal diarrhea large labor intensity, production efficiency is low, the low problem of yield rate.But still it has the following defects.

1, the postcibal diarrhea mechanism of the device is mainly made of active rubber roll, transition rubber roller and doctor roll, and hair intestines are in scraper Carry out striking between roller and transition rubber roller, at the same hair intestines bypass transition rubber roller surface again after pass through transition rubber roller and active Gap between rubber rollers, the rotation between active rubber roll and transition rubber roller are drawn, the traction speed of such hair intestines Degree and striking speed can all be influenced by the velocity of rotation of transition rubber roller, cause to be difficult to grasp mao intestines draw between striking process Balance so that hair intestines are broken out or to be difficult to striking clean.Therefore device presence is difficult to adjust postcibal diarrhea speed and make The poor defect of postcibal diarrhea effect.

2, the device only can be realized a mao function for intestines striking, subsequent after processing at the beginning of cannot achieve mao intestines and striking Processing and etc., it is difficult to realize the flow line production of postcibal diarrhea technique, production efficiency is lower.

In enzymatic hydrolysis process, generally digested using enzymatic vessel.The patent of CN200920084667.9 is once disclosed one Kind enzymatic vessel, structure include tank body, and tank body upper end is equipped with driving motor, is connected with stirring rod on motor, stirring rod protrudes into In tank body, inner tank wall is equipped with heating coil, and the input end of heating coil and the heat source tube outside tank body connect, and tank body top is set There are feed inlet, peephole and an aproll ball, tank body lower end is equipped with tail gas mouth, and lower end is equipped with discharge gate, enzymatic vessel, on the stirring rod Equipped with paddle, can be sufficiently stirred.The enzymatic vessel of the invention has heat insulation effect good, and dissolution is abundant, the characteristics of pollution；But still So have the following defects.

1, it is only provided with a feed inlet in the enzymatic vessel, is unfavorable for the addition of some adjustments.

2, the enzymatic vessel stirring rod is directly connected to the motor, and stirring rod stress in stirring is larger, can generate very big rush It hits and vibrates, be easy to cause fracture.

3, the not set manhole cover of manhole, heat insulation effect is poor and liquid splashes out when being easy to cause stirring.

4, when digesting, the control parameters such as pH value and salinity need to detect and rule of thumb control manually by worker Operation, haves the defects that inefficiency and reliability difference empirically causes hydrolysis result to be difficult to ensure.

Elution procedure be the resin that heparin compositions are adsorbed in absorption process is eluted using sodium chloride solution so that Contain heparin sodium in eluent, and is separated eluent and resin by corresponding device.Publication number in the prior art The patent of CN202526939U discloses a kind of resin elution tank, and which employs following technical solutions: the elution tank is equipped with Feed opening, discharge hole, inlet opening, liquid outlet and temp probe, it is characterized in that the elution tank is Double-layer clamp nested structure, including Inner cylinder and heat exchange outer sleeve body, heat exchange outer sleeve body are hollow structure, and interior be equipped with leads warm medium, heat exchange outer sleeve body fitting packet It is wound on the lateral surface of inner cylinder, resin separating screen is equipped in the elution tank, resin separating screen is obliquely installed, lower One end and discharge hole be in sustained height.The elution functions of the equipments produced which solves existing heparin are simple, technique The problem of regulation trouble, equipment and materials easy fast erosion, but still have the following deficiencies:

1, primary using equipment elution resin, the extraction that will lead to heparin is insufficient, not only reduces heparin sodium crude Specific yield, also affect adsorption effect when resin reuses, reduce the production efficiency of heparin sodium, reduce production The economic benefit of heparin sodium.

2, resin is repeatedly eluted using the equipment, also needs to combine other tools that could complete (to be used as increased by one Save the container of eluent or resin), a large amount of artificial participations moreover, in operating process are also needed, so, are not only operated Cumbersome trouble, improved efficiency are unobvious, also will increase production cost.

In short, in the novel postcibal diarrhea of the heparin sodium of the prior art, enzymatic hydrolysis, elution process, in the postcibal diarrhea, enzymatic hydrolysis, elution work Sequence is operated using above-mentioned apparatus, there are the extraction of heparin is insufficient, the lower problem of heparin sodium production efficiency.

Summary of the invention

It is regarding to the issue above and insufficient, the technical problems to be solved by the present invention are: how to provide one kind can be improved liver Plain sodium extraction efficiency and the novel postcibal diarrhea of heparin sodium of productivity effect, enzymatic hydrolysis, elution process.

To solve the above-mentioned problems, present invention employs technical solutions below: a kind of novel postcibal diarrhea of heparin sodium, enzymatic hydrolysis, Elution process, including postcibal diarrhea, enzymatic hydrolysis, five big process of absorption, elution and precipitating, which is characterized in that in the postcibal diarrhea process, The mucus scraped out of casing is collected when carrying out striking to hair intestines breaks its intestines skin and casing, while after the separation of intestines skin Again casing inside is carried out pouring water flushing and collect flushing liquor, by the mucus and flushing liquor as in the enzymatic hydrolysis process Intestinal mucosa liquid；Three-level elution is carried out to the resin filtered out from the absorption process using salt water in the elution procedure, Wherein third level elution is using the salt water (after elution become eluent) newly prepared and the resin filtered out after the elution of the second level, Second level elution uses the resin filtered out after the eluent after third level elution and first order elution, and first order elution uses Eluent after the elution of the second level and the resin that is filtered out in the absorption process, eluent after first order elution into Enter the subsequent precipitation process.

The novel postcibal diarrhea of heparin sodium of the present invention, enzymatic hydrolysis, elution process, by collecting and being carried out to hair intestines in postcibal diarrhea process The mucus that striking scrapes its intestines skin and casing out of casing when being broken, and casing inside is carried out again after the separation of intestines skin It pours water the flushing liquor of flushing, the loss rich in the mucus and flushing liquor that have heparin compositions in postcibal diarrhea process is greatly reduced, Using the mucus and flushing liquor as the intestinal mucosa liquid in enzymatic hydrolysis process, to increase the extraction efficiency of heparin sodium.In elution procedure (resin needs to make repeatedly while the middle resin progress three-level elution, sufficiently elution resin filtered out using salt water to absorption process With sufficiently after elution, next time is more preferable for adsorption effect when adsorbing), more heparin sodiums can be also extracted, unit raw material is increased Heparin sodium yield, promoted production heparin sodium productivity effect.

As an improvement, third level elution time is 1 hour, and the second level is washed when carrying out three-level elution in the elution procedure The de- time is 1.5 hours, and first order elution time is 3 hours.

In this way, the resin of third level elution is the resin stripped twice, and eluent therein is the salt newly prepared Water, therefore the least time is designed, a hour enough elutes effective component remaining in resin；The first order is fresh tree Rouge elution, and utilize and stripped eluent twice, therefore longest elution time is designed so that reaching post precipitation process Eluent in contain more active principles.According to the elution time of above-mentioned setting elution not at the same level, can not only play more preferable Elution effect, moreover it is possible to reduce unnecessary elution time, reduce elution energy consumption, the further production effect for increasing heparin sodium Benefit.

It is used as in the above method and specifically optimizes process, in the enzymatic hydrolysis process, digested using enzymatic vessel；It is first First, the intestinal mucosa liquid inlet valve on enzymatic vessel is opened；Then, intestinal mucosa liquid fresh obtained in postcibal diarrhea process is sent into enzymatic hydrolysis In tank, and intestinal mucosa liquid in enzymatic vessel is stirred；Meanwhile intestinal mucosa liquid in enzymatic vessel is heated, while viscous in intestines Alkali and salt is gradually added to convert the mixed liquid of synthesis in film liquid, when heating to 47~53 DEG C, alkali protease is added will be at mixed liquid enzymatic hydrolysis Reason is enzymolysis liquid, and controlled enzymatic hydrolysis liquid PH=8~9, salinity is 3~3.5 degree；Heat preservation 2~3 hours, then heats to 80 ± 5 DEG C, And keep the temperature no less than 30 minutes；Finally, stopping being stirred enzymolysis liquid in enzymatic vessel, enzymatic vessel baiting valve is opened by enzymolysis liquid It is put into filtering tank and is filtered (with 80~100 mesh filter screens)；In the absorption process, firstly, the enzymolysis liquid is sucked into adsorption tanks, The enzymolysis liquid is stirred, when the enzymolysis liquid is cooled to 55 DEG C~60 DEG C, heparin adsorption resin is added (AMBERLITEFPA98CL resin), insulated and stirred are adsorbed 8~10 hours；It, will be in the absorption process in the elution procedure The absorption resin is rinsed well, is put into elution tank and is eluted after being filtered dry, adds salt water (chlorine identical with weight resin Change sodium solution, salinity is 19~23 Baume degrees) synthesis mixing is converted, the mixing is heated to 55~60 DEG C, is eluted；It is described In precipitation process, using the eluent from elution procedure, add the alcohol of concentration 80%~90%, after mixing evenly, alcoholic strength Control precipitates 20~24 hours at 35~45 degree, extracts supernatant out, collects sediment and waits for being placed in dehydration barrel for 2~5 days, adds Enter concentration be 90%~95% alcohol, alcohol with and mixed sediment volume than be about 2:1, be dehydrated 1~2 hour, extraction supernatant It is dry to collect remaining heparin sodium for liquid.

In this way, being digested according to above-mentioned enzymatic hydrolysis process, the contaminant protein in intestinal mucosa liquid can sufficiently be digested, be protected Stay heparin compositions needed for it.The absorption process so that absorption resin more fully adsorb the heparin in enzymolysis liquid at Point.The resin for adsorbing heparin compositions described in the absorption process is eluted in the elution procedure, obtains eluent for precipitating Heparin sodium is extracted in process.Alcohol soaking flushing is used in the precipitation process twice, improves heparin sodium precision.

As an improvement, first obtaining the heparin sodium of flowering structure such as in the postcibal diarrhea process and processing postcibal diarrhea device, the heparin sodium The archenteron-scrapping machine that postcibal diarrhea device includes rack and is arranged on the rack is processed, the archenteron-scrapping machine includes being fixed on the rack the left and right sides Left and right fulcrum bearing, and the striking mechanism and traction mechanism that are horizontally installed in the fulcrum bearing of left and right, the striking mechanism includes simultaneously Arrange setting doctor roll and auxiliary rubber roller, which is characterized in that the traction mechanism in the archenteron-scrapping machine, including be set side by side one To traction roller, traction roller length direction is consistent with doctor roll length direction and is located at the front lower of doctor roll and auxiliary rubber roller gap Orientation is set, and a pair of of the tooth being intermeshed and for driving two traction roller relative rotation is provided on the end of a pair of of traction roller Wheel；

Further include position-limit mechanism in the archenteron-scrapping machine, the position-limit mechanism include laterally be erected in the fulcrum bearing of left and right and The support rod of position between traction mechanism and striking mechanism, forward upward is set side by side with several uniform intervals on support rod The limited post of distribution；

The doctor roll flip lid for being covered in doctor roll under it, the doctor roll flip lid are additionally provided in the archenteron-scrapping machine The both ends of front side edge are rotationally hinged in the fulcrum bearing of left and right；

The doctor roll renovates the observation window that upper face doctor roll top position is additionally provided with glass material；

The heparin sodium processing postcibal diarrhea device further includes the workbench of strip, and the archenteron-scrapping machine is located at workbench middle part Position,

Primary launder is provided on the table top of workbench rear end section start, primary launder Inner Front End position is each side set It is equipped with the water faucet for previous cleaning, rear end is provided with sewage outlet in primary launder；Between primary launder and archenteron-scrapping machine also Linking is provided with collecting tank, and there is one to be used to collect the mucous membrane pond for scraping intestinal mucosa for collecting tank rear end；It is located at postcibal diarrhea on workbench Machine front position is additionally provided with water flowing cleaning leak detection slot, is each provided at left and right sides of the water flowing cleaning leak detection slot Inner Front End position One water faucet for water flowing leak detection, water flowing clean rear end in leak detection slot and are additionally provided with leak detection liquid collecting pit；

One is provided with positioned at water faucet rear position in the primary launder and water flowing cleaning leak detection slot and loses leak hole, loses leakage Activity is linked with one and loses leaky bucket in hole；

Then it is operated according to following operating procedure:

Firstly, first the sundries such as the loose fat of hair intestines surface attachment are extractd in primary launder, and by the sundries of excision by losing Leak hole is directly discarded into leaky bucket；Hair intestines one end is subjected to flushing of pouring water to the water faucet for being used for previous cleaning is connected again, is rinsed Waste water by sewage outlet outlet；Hair intestines are passed on collecting tank after flushing, by hair intestines along workbench length on collecting tank Direction put and along workbench width direction laid out in parallel be more after upper machine postcibal diarrhea；

Then, in postcibal diarrhea, upper archenteron-scrapping machine, adjacent hair intestines spacing 15-25cm simultaneously lean on position-limit mechanism to Duo Genmao intestines side by side Limited post separates；Start archenteron-scrapping machine, hair intestines end is sent between the doctor roll and auxiliary rubber roller of striking mechanism and is passed through, then to Front lower place is sent between a pair of of traction roller of traction mechanism, and a pair of of traction roller is clamped mao intestines relative rotation offer tractive force and drawn automatically Dynamic hair intestines carry out striking in striking mechanism, scrape the mucous membrane liquid produced and flow to mucous membrane pond by collecting tank and regather；

Finally, the hair intestines after striking, which are sent forward to water flowing, cleans leak detection slot, manually the intestines skin that casing surface is adhered to is gone Fall and be put into specified basket, then remaining casing is cleaned using water faucet water flowing, loophole or broken is found when cleaning Casing need to be cut off, and the aqueous washed out regathers after being pooled to leak detection liquid collecting pit.

In this way, the heparin sodium processes postcibal diarrhea device, doctor roll and auxiliary rubber of the hair intestines from striking mechanism when work Passed through between roller, doctor roll and auxiliary rubber roller are driven by a motor rotation and carry out striking to hair intestines, then hair intestines from doctor roll and Auxiliary rubber roller gap extends downwardly after pulling out forward and is sandwiched between a pair of of traction roller, two traction roller nibbling in end gear Cooperation is driven by a motor relative rotation under, and the pulling for hair intestines provides traction.In this way, the rotation of traction roller and turning for doctor roll It is dynamic just respectively independent, it will not influence each other, the convenient respectively adjusting to hauling speed and striking speed reaches Best striking effect.When due to striking, usually several maos of intestines strikings together, after adding position-limit mechanism, in position-limit mechanism Support rod can separate each hair intestines, avoid phenomena such as contacting with each other between mao intestines and generate winding or blocking.In striking Doctor roll is covered, the liquid that can adhere to avoid hair intestines surface is splashed out in striking, while will be scraped when needing to clear up Rotor flip lid opens cleaning, can be convenient and cleans out the attachment of scraper roller surface.The doctor roll is renovated upper face and is scraped Rotor top position is additionally provided with the observation window of glass material, whether just to observe doctor roll work by observation window with can be convenient Often.

The postcibal diarrhea device is provided with workbench, and the pipelining of entire postcibal diarrhea technique may be implemented.Specifically, In When work, worker in primary launder first by hair intestines surface attachment loose fat extract, then by hair intestines one end dock upper hose faucet into Row is poured water flushings, washes off excrement and helminth, and when flushing finds that hair intestines have the place of damaged leak to cut off and ensure pre-feed Hair intestines length is greater than two meters, and the waste water of flushing is by sewage outlet outlet.Hair intestines are passed on collecting tank after flushing, in collecting tank On by hair intestines along workbench length direction put and along workbench width direction laid out in parallel be more after upper machine postcibal diarrhea, postcibal diarrhea When, upper machine, adjacent hair intestines spacing 15-25cm are simultaneously separated by the limited post of position-limit mechanism Duo Genmao intestines side by side, and starting is scraped when upper machine Hair intestines end is sent between the doctor roll and auxiliary rubber roller of striking mechanism and is passed through by intestines machine, and dragger is sent into lower section further along Between a pair of of traction roller of structure, two traction rollers clamp mao intestines relative rotation offer tractive force and pull hair intestines in striking mechanism automatically Upper carry out striking, scrapes the mucous membrane liquid produced and flow to mucous membrane pond by collecting tank and regather as heparin stoste.Hair intestines after striking Before send to water flowing clean leak detection slot, the intestines skin that casing surface is adhered to is removed by worker and is put into specified basket, then will be left Casing cleaned using water faucet water flowing, when cleaning discovery loophole or it is broken need to cut off, the aqueous washed out is pooled to leak detection It is regathered after liquid collecting pit as heparin stoste.In whole process, water consumption expends 6-7kg's according to a complete chitterlings Ratio is controlled.When working in this way, first extracing loose fat can enter after heparin stoste to avoid loose fat in subsequent enzymolysis processing It turns to oil liquid and floats on liquid level influence enzymatic hydrolysis operation；Discovery has the place of damaged leak to cut off when rinsing hair intestines, it can be ensured that scrapes That makes is smooth, avoids encountering damaged place in striking and blocking and shut down, hair intestines length ensures first along work when two meters and striking Platform length direction arranges on collecting tank, it can be ensured that striking more smoothly carries out, and improves striking efficiency, and when postcibal diarrhea is adjacent Hair intestines separate and keep spacing 15-25cm by the limited post of position-limit mechanism, can collide to avoid hair intestines adjacent in striking and and Cause wind or block, it is ensured that striking it is smooth；After striking, water flowing is hunted leak again, it is ensured that obtains complete casing with benefit It is processed in subsequent casing, while the cleaning aqueous of water flowing leak detection is collected as heparin stoste again, thus farthest extracts Heparin raw material in hair intestines, avoids waste, improves heparin sodium extraction efficiency.Water consumption control is a small intestine 6-7kg Ratio, can ensure to complete the demand of cleaning and the acquisition of heparin, and save and avoided wasting with water.

It can directly be discarded into leaky bucket in the waste that excision of hunting leak is cleaned in leak detection slot in primary launder and water flowing and collect again Middle processing, it is ensured that working site clean simultaneously saves the time, improves the working efficiency of assembly line.

As an improvement, first obtaining the heparin sodium of flowering structure such as in the enzymatic hydrolysis process and producing enzymolysis device, the heparin sodium Producing enzymolysis device includes enzymatic vessel, and the tank body top of the enzymatic vessel is provided with manhole, and lower end is provided with discharge port, enzymatic vessel On be additionally provided with agitating device and heating device, which is characterized in that the intestines being connected to tank inner chamber are additionally provided on the tank body Mucous membrane liquid inlet tube, alkali liquor pipe, salt water water inlet pipe and tap water inlet pipe；The heparin sodium production enzymolysis device further includes automatic Detecting and controlling system, the automatic detection and control system include the temperature for being used to detect temperature of charge being arranged in inner tank wall Sensor, the pH value detection sensor for detecting material pH value and the salinometer for detecting material salinity, the temperature Sensor, pH value detection sensor and salinometer are connected with a control centre and provide detection data, the automatic inspection for it Surveying control system further includes being separately positioned on the intestinal mucosa liquid inlet tube, alkali liquor pipe, salt water water inlet pipe and tap water inlet pipe On electric-controlled switch valve, the electric-controlled switch in the intestinal mucosa liquid inlet tube, alkali liquor pipe, salt water water inlet pipe and tap water inlet pipe Valve is respectively connected and is controlled by it with the control centre；

The heating device includes the heating coil along the coiling setting of enzymatic vessel inner tank wall, and heating coil has from upper end Extend the air inlet pipe of tank body, there is the escape pipe for extending tank body from lower end, be provided with electrical control steam valve in the air inlet pipe, The electrical control steam valve is connected and is controlled by it with the control centre；

The agitating device includes the stirring motor for being located at top of the tank, and the stirring being vertically provided in the middle part of tank inner chamber Axis installs support construction by agitating shaft between the stirring motor and the agitating shaft and is connected, the agitating shaft installation support Structure, including it is fixed on top of the tank and whole tubular fulcrum bearing upwards, there is a horizontally disposed branch in the middle part of fulcrum bearing Platform is supportted, the stirring motor is fixed at the top of fulcrum bearing and electric machine main shaft extends down into fulcrum bearing, in the middle part of the fulcrum bearing Supporting table on by bearing be rotatably mounted with a jackshaft, jackshaft upper end end and stirring motor output shaft lower end end It is docked by concave-convex fit structure and transmits torque in portion；The jackshaft lower end, which is closed on end position fixing sleeve and enclosed equipped with one, to be connected Steel bushing is connect, the agitating shaft upper end extends into fulcrum bearing and fixing sleeve is equipped with a lower connection steel corresponding with upper connection steel bushing Set, several connecting rods that annular is uniformly arranged between the upper connection steel bushing and lower connection steel bushing, connecting rod both ends pass through The upper connection steel bushing and lower connection steel bushing are simultaneously connected using nut, while going back ring between upper connection steel bushing and lower connection steel bushing Shape is evenly equipped with several helical springs, and the upper and lower ends of the helical spring are fixed on connection steel bushing and lower connection steel bushing respectively On；

Being circular layout on the upper connection steel bushing has several connection bolts, and the connection bolt front end is outside upper connection steel bushing Side horizontal penetrates in jackshaft the connection realized and connect steel bushing and jackshaft；

It is additionally provided with manhole cover structure on the tank body at manhole, the manhole cover structure includes along manhole to outside tank body It stretches the circle neck mouth convexed to form and surrounds the lid that cover type is mounted in neck mouth, lid upper surface is diametrically fixed It is provided with a mounting rod, one end of mounting rod and the free bearing being fixed in neck mouth are rotatably connected, and the other end of mounting rod prolongs It stretches out lid and is provided with the U-lag that a horizontal cross-section is in U-shape, can be rotatably set in corresponding neck mouth below U-lag One check lock lever, check lock lever outer end also lean on screw thread activity to be screwed with a handle, and check lock lever outer end can be pivoted upwardly into institute It states in U-lag and is locked at U-lag upper surface by rotating handles；

Then it is operated according to following operating procedure:

Firstly, feeding by the electric-controlled switch valve that control centre opens intestinal mucosa liquid inlet tube, intestines are poured into enzymatic vessel Mucous membrane liquid；

Secondly, the stirring motor of starting top of the tank, agitating shaft start to stir；At the same time, control centre is detected automatically The data of temperature sensor, pH value detection sensor and salinometer, and control electrical control steam valve respectively, automatically controlled on alkali liquor pipe opens The electric-controlled switch valve on valve and salt water water inlet pipe is closed, so that the temperature of enzymolysis liquid maintains 47~53 DEG C in tank, pH value maintains PH=8~9, salt angle value maintain 3~3.5 degree；

Finally, after axis to be mixed stirs 2.5 hours (can realize within 2 to 3 hours and be sufficiently stirred), control centre's control electricity Control steam valve will be warming up to 80 DEG C (within the scope of 80 ± 5 DEG C all preferably) in tank, and maintain no less than 30 minutes；Then, tank body is closed The stirring motor at top, agitating shaft stop stirring；It opens enzymatic vessel lower end and is provided with discharge port, enzymolysis liquid is delivered to filtering Tank.

In this way, being also provided with the intestinal mucosa being connected to tank inner chamber on tank body in the heparin sodium production enzymolysis device Liquid inlet tube, alkali liquor pipe, salt water water inlet pipe and tap water inlet pipe, in this way, pipe control can be leaned on to realize the charging of intestinal mucosa liquid, Facilitate realize lye addition and tap water addition to adjust pH value, facilitate realize salt water addition and tap water addition with Adjust salinity.Facilitate the addition of adjustment.Meanwhile in the present invention, it is also provided with automatic detection and control system, it is made to work When, each sensing detection device can be leaned on to detect each parameter situation, then will test after data are sent to control centre, control centre The control with addition of realization to each parameter of adjustment can be controlled, is made according to pre-set programs by the adjustment to each electric-controlled switch valve It meets production demand for control.Automated control operation is thereby realized, avoids manually detecting existing inefficiency, it can By degree difference and the defect of high labor cost, it ensure that enzymolysis process is under the working condition accurately controlled and carry out, ensure that enzyme Solve effect.

The heating device includes the heating coil along the coiling setting of enzymatic vessel inner tank wall, and heating coil has from upper end Extend the air inlet pipe of tank body, there is the escape pipe for extending tank body from lower end, be provided with electrical control steam valve in the air inlet pipe, The electrical control steam valve is connected and is controlled by it with the control centre.In this way, when production, can by air inlet pipe and an air outlet pipe and Steam production system is connected, and control steam, which enters to be added in coil pipe, realizes heating and heat preservation, by control centre according to temperature sensing The switch of the temperature data control electrical control steam valve of device detection, realizes the control of temperature.It is simple with structure, it is easy to implement, easily In control the advantages that.

In the work of enzymatic vessel agitating device, the stirring motor output shaft drives jackshaft to revolve by concave-convex fit structure Turn, jackshaft realizes the function of shaft coupling and bumper and absorbing shock, and specifically jackshaft lower end passes through upper connection steel bushing and lower connection The connecting rod and helical spring being arranged between steel bushing drive agitating shaft rotation, in this way, the elastic force of the helical spring of setting passes through Pull rod full curve when being driven spin load is converted to circumference to component, it is made to have higher turning shock loads buffering Ability achievees the effect that protect shaft coupling part, stirring rod is avoided to be broken because shock loading is larger, extends agitating device use Service life.Simultaneously wherein it is possible to connect the spacing of steel bushing and lower connection steel bushing in the nut adjustment for passing through adjusting connecting rod both ends From, adjusting of the realization to the deformation degree of helical spring, and then realize the fine tuning to device buffer capacity.

Being circular layout on the upper connection steel bushing has several connection bolts, and the connection bolt front end is outside upper connection steel bushing Side horizontal penetrates in jackshaft the connection realized and connect steel bushing and jackshaft.Steel bushing is connected in realization in this way, can be convenient Connection and disassembly between jackshaft.

It is additionally provided with manhole cover structure at manhole on the tank body, manhole cover can be leaned on conveniently and efficiently to realize beating for manhole Open and close, the foul smell generated when to avoid production overflows.Specifically, check lock lever is screwed in U-shaped upwards after manhole cover is closed Slot, then rotating handles are screwed and are close to U-lag upper surface, locking can be realized, when opening, only need reversely to revolve rotating handles It opens, then check lock lever is put down, i.e., openable manhole cover is very convenient quick.Wherein, the lid includes the side of a steel Circle, and the tempered glass being embedded in inside flange.In this way, can guarantee lid integral strength, and it is conducive to see by lid Examine tank interior situation.It further can also be in lid inside edge with neck mouth contact position one corresponding groove of setting and recessed It is embedded a circle elastic seal ring in slot, sealing can be easy to implement in this way, leaks to avoid foul smell when production.In addition, specific real Shi Shi can also be connected to one exhaust pipe of setting on tank body, to realize the outlet of production gas, while avoid the closing because of manhole cover It generates high pressure and influences to produce.

As an improvement, first obtaining the heparin sodium of flowering structure such as in the elution procedure and producing washing device, the heparin sodium Producing washing device includes elution tank, and each elution tank lower end is provided with drain pipe, sets in the drain pipe along cross-sectional direction It is equipped with strainer, is lower than the strainer on the drain pipe and is provided with the switch valve for controlling drain, also set higher than the strainer It is equipped with bypass discharge nozzle, the switch valve for controlling discharging is provided on the bypass discharge nozzle；The elution tank is at least two It is a and be concatenated into multilevel structure；In the multilevel structure, the drain pipe of next stage elution tank is same as above one by Drainage pipe The upper end of grade elution tank is connected, and the electric pump for drain is provided on the Drainage pipe；The bypass of upper level elution tank Discharge nozzle is connected by the upper end that discharge pipe elutes tank with next stage, and the electricity for discharging is provided on the discharge pipe Pump；

The multilevel structure is tertiary structure, and the tertiary structure includes first order elution tank, second level elution tank and the Three-level elutes tank；The drain pipe of the third level elution tank elutes the upper end phase of tank by Drainage pipe with the second level Even, the drain pipe of the second level elution tank is connected by the upper end that Drainage pipe elutes tank with the first order；It is described The bypass discharge nozzle that the first order elutes tank is connected by the upper end that discharge pipe elutes tank with the second level, and described second The bypass discharge nozzle of grade elution tank is connected by the upper end that discharge pipe elutes tank with the third level；

Rabbling mechanism is additionally provided on the elution tank；

The rabbling mechanism includes stirring motor and stirring rod, and the stirring motor setting is eluting tank upper end, described to stir It mixes bar to protrude into elution tank, the stirring motor is connected with the stirring rod；

It further include rack in the multilevel structure, the elution tank is mounted on the rack, and is also set up in the rack There is helper；

The elution tank upper end is provided with manhole；

The elution tank is additionally provided with heating mechanism；

Then it is operated according to following operating procedure:

Heparin sodium production washing device in present embodiment is in use, circulation executes following steps:

Step 1: at the same open the first order elution tank and the third level elution tank eluted.Wherein, the first order elutes tank The resin that resin is filtered out from the absorption process, eluent are eluted after tank elutes from the second level in last circulation and are filtered The eluent arrived；The tree that the resin of third level elution tank is obtained by filtration after elution tank elution in the second level in last circulation Rouge, salt water of the eluent from fresh addition；When elution, the first order elutes tank and elutes three hours, and the third level elutes tank elution 1 Hour.

Step 2: draining into the precipitation process for the eluent that first order elution tank elution filters out in step 1 and handle, The resin filtered out drains into second level elution tank；The eluent that third level elution tank elution filters out in step 1 is drained into second Grade elutes tank, collects and recycles after the resin outlet filtered out；

Step 3: opening second level elution tank and eluted, and elution time 1.5 hours, the elution that will filter out after elution Liquid drains into first order elution tank, and resin drains into third level elution tank, recycles since then；

In above three step, the elution tank opens stirring motor 14 to being stirred in tank in elution, stirring Meanwhile heating mechanism is opened, mixed liquor in tank body is heated to 55~60 DEG C.

In this way, the heparin sodium production washing device uses tertiary structure, it may make heparin sodium elution processes more excellent, i.e., together One batch de- resin to be washed can be eluted three times in the washing device, and the sodium chloride solution that the third level elutes in tank can also be with It is eluted in the washing device three times, so that sodium chloride solution can adequately extract the heparin compositions adsorbed in resin, And the higher eluent of heparin sodium content is obtained, meanwhile, the resin after being fully extracted heparin compositions can be produced in heparin sodium In utilize again, play better adsorption effect.In addition, the setting of tertiary structure, so that the present apparatus is easy to operate simple, also The time that the elution of heparin sodium can effectively be saved, improve production efficiency.Moreover, with the structure phase for being greater than three-level Than, additionally it is possible to obviously save energy consumption.

The rabbling mechanism being arranged on elution tank, avoids the low problem of artificial stirring efficiency, but also elution processes energy Enough stir more abundant.

It further include rack in the mechanism as the improvement of the multilevel structure, the elution tank is mounted on the rack, Helper is additionally provided in the rack.In this way, the setting of rack can the present apparatus can utilize longitudinal space, saving accounts for Ground area reduces costs.

Elution tank upper end be provided with manhole, by manhole can be more convenient add materials, can also very easily see Survey the condition of production in tank.

The elution tank is additionally provided with heating mechanism.In this way, can be arranged in tank body heating coil directly in tank body into Row heating.It can also be a cavity between the collet, be provided with heating coil in cavity by tank body as double layer jacket structure, Heating coil input end is connect with the heat source tube outside tank body, using the heating to tank body, indirectly to being heated in tank body Technical solution.Because elution process can reach preferably elution effect, the setting of heating structure at a suitable temperature Washing device of the invention can be helped, preferably elution effect is got.

In conclusion the novel postcibal diarrhea of heparin sodium of the present invention, enzymatic hydrolysis, elution process, compared with the existing technology compared with energy The working efficiency of heparin production, the more fully heparin compositions in extraction hair intestines are enough improved, the life of better heparin sodium is obtained Produce benefit.

Detailed description of the invention

Fig. 1 is the novel postcibal diarrhea of heparin sodium of the invention, enzymatic hydrolysis, the heparin sodium processing used in elution process in postcibal diarrhea process The structural schematic diagram of postcibal diarrhea device；

Fig. 2 is the top view of Fig. 1.

Fig. 3 is the structural schematic diagram of independent archenteron-scrapping machine part in Fig. 1；

Fig. 4 is the top view of Fig. 3.

Fig. 5 is the novel postcibal diarrhea of heparin sodium of the invention, enzymatic hydrolysis, digests the heparin sodium production used in process in elution process The structural schematic diagram of enzymolysis device；

Fig. 6 is the novel postcibal diarrhea of heparin sodium of the invention, enzymatic hydrolysis, digests the heparin sodium production used in process in elution process The A direction view of the agitating shaft installation support construction of enzymolysis device；

Fig. 7 is the partial enlarged view in Fig. 5；

Fig. 8 is the novel postcibal diarrhea of heparin sodium of the invention, enzymatic hydrolysis, the heparin sodium production used in elution process in elution procedure Washing device structural schematic diagram.

Specific embodiment

The present invention is described in further detail with specific implementation example with reference to the accompanying drawing.

Specific embodiment: as shown in Figures 1 to 8, a kind of novel postcibal diarrhea of heparin sodium, enzymatic hydrolysis, elution process, including scrape Intestines, enzymatic hydrolysis, five big process of absorption, elution and precipitating, in the postcibal diarrhea process, to hair intestines carry out striking make its intestines skin and The mucus scraped out of casing is collected when casing is broken, while flushing of pouring water is carried out to casing inside again after the separation of intestines skin And flushing liquor is collected, by the mucus and flushing liquor as the intestinal mucosa liquid in the enzymatic hydrolysis process；

Three-level elution is carried out to the resin filtered out from the absorption process using salt water in the elution procedure, wherein Third level elution is using the salt water (after elution become eluent) newly prepared and the resin filtered out after the elution of the second level, and second Grade elutes the resin for using and filtering out after the eluent after third level elution and first order elution, and first order elution, which uses, to be come from Eluent after the elution of the second level and the resin that is filtered out in the absorption process, after the eluent after first order elution enters Continue the precipitation process.

Wherein, when carrying out three-level elution in the elution procedure, third level elution time is 1 hour, when the second level elutes Between be 1.5 hours, first order elution time be 3 hours.

Wherein, it in the enzymatic hydrolysis process, is digested using enzymatic vessel；Firstly, open enzymatic vessel on intestinal mucosa liquid into Expect valve；Then, fresh intestinal mucosa liquid obtained in postcibal diarrhea process is sent into enzymatic vessel, and to intestinal mucosa liquid in enzymatic vessel into Row stirring；Meanwhile intestinal mucosa liquid in enzymatic vessel is heated, while gradually adding alkali and salt to convert synthesis in intestinal mucosa liquid and mixing Liquid, when heating to 47~53 DEG C, it is enzymolysis liquid, controlled enzymatic hydrolysis liquid PH=8 that alkali protease, which is added, by mixed liquid enzymolysis processing ~9, salinity is 3~3.5 degree；Heat preservation 2~3 hours then heats to 80 ± 5 DEG C, and keeps the temperature no less than 30 minutes；Finally, stopping Only enzymolysis liquid in enzymatic vessel is stirred, enzymolysis liquid is put into filtering tank by opening enzymatic vessel baiting valve to be filtered；

In the absorption process, firstly, the enzymolysis liquid is sucked adsorption tanks, the enzymolysis liquid is stirred, to institute When stating enzymolysis liquid and being cooled to 55 DEG C~60 DEG C, heparin adsorption resin is added, insulated and stirred is adsorbed 8~10 hours；

In the elution procedure, absorption resin described in the absorption process is rinsed well, elution tank is put into after being filtered dry It is inside eluted, adds salt water identical with weight resin and convert synthesis mixing, the mixing is heated to 55~60 DEG C, is carried out Elution；

In the precipitation process, using the eluent from elution procedure, add the alcohol of concentration 80%~90%, stirring is equal After even, alcoholic strength is controlled at 35~45 degree, is precipitated 20~24 hours, extracts supernatant out, is collected sediment and is waited for being placed on for 2~5 days In dehydration barrel, be added the alcohol that concentration is 90%~95%, alcohol with and mixed sediment volume than being about 2:1, be dehydrated 1~2 small When, it extracts supernatant out, it is dry to collect remaining heparin sodium.

Wherein, it in the postcibal diarrhea process, first obtains the heparin sodium of flowering structure such as and processes postcibal diarrhea device (as shown in Figure 1 to Figure 4), institute The archenteron-scrapping machine that heparin sodium processing postcibal diarrhea device includes rack 1 and is arranged in rack 1 is stated, the archenteron-scrapping machine includes being fixed on rack The left and right fulcrum bearing 2 of the left and right sides on 1, and the striking mechanism and traction mechanism that are horizontally installed in left and right fulcrum bearing 2, it is described to scrape Mechanism processed includes the doctor roll 3 and auxiliary rubber roller 4 being set side by side, the traction mechanism in the archenteron-scrapping machine, including is set side by side A pair of of traction roller 5,5 length direction of traction roller it is consistent with 3 length direction of doctor roll and be located at doctor roll 3 and auxiliary rubber roller 4 The front lower place position in gap is provided on the end of a pair of of traction roller 5 and is intermeshed and for driving two traction rollers 5 are opposite to revolve A pair of of the gear 6 turned；

Further include position-limit mechanism in the archenteron-scrapping machine, the position-limit mechanism include laterally be erected in left and right fulcrum bearing 2 and The support rod 7 of position between traction mechanism and striking mechanism, on support rod 7 forward upward be set side by side with it is several uniformly between Every the limited post 8 of distribution；

The doctor roll flip lid 19 for being covered in doctor roll 3 under it, the doctor roll are additionally provided in the archenteron-scrapping machine The both ends for renovating 19 front side edges are rotationally hinged in left and right fulcrum bearing 2；

3 top position of face doctor roll is additionally provided with the observation window 9 of glass material on the doctor roll flip lid 19；The liver Plain sodium processing postcibal diarrhea device further includes the workbench of strip, and the archenteron-scrapping machine is located at position among workbench, the workbench Be provided with primary launder 10 on the table top of rear end section start, be each provided at left and right sides of 10 Inner Front End position of primary launder one for just The water faucet 18 washed, rear end is provided with sewage outlet 11 in primary launder 10；Also it is connected between primary launder 10 and archenteron-scrapping machine and sets It is equipped with collecting tank 12, there is 12 rear end of collecting tank one to be used to collect the mucous membrane pond 13 for scraping intestinal mucosa；It is located at postcibal diarrhea on workbench Machine front position is additionally provided with water flowing cleaning leak detection slot 14, and the water flowing cleaning leak detection 14 Inner Front End position of slot is each side set It is equipped with a water faucet 20 for water flowing leak detection, rear end is additionally provided with leak detection liquid collecting pit in water flowing cleaning leak detection slot 14 15；

One, which is provided with, positioned at water faucet rear position in the primary launder 10 and water flowing cleaning leak detection slot 14 loses leak hole 16, it loses activity in leak hole 16 and is linked with one and lose leaky bucket 17；

Then it is operated according to following operating procedure:

Firstly, first extracing the sundries such as the loose fat of hair intestines surface attachment in primary launder 10, and the sundries of excision is passed through Leak hole 16 is lost directly to be discarded into leaky bucket 17；Hair intestines one end is subjected to punching of pouring water to the water faucet 18 for being used for previous cleaning is connected again It washes, the waste water of flushing is by 11 outlet of sewage outlet；Hair intestines are passed on collecting tank 12 after flushing, by hair intestines on collecting tank 12 Along workbench length direction put and along workbench width direction laid out in parallel be more after upper machine postcibal diarrhea；

Then, in postcibal diarrhea, upper archenteron-scrapping machine, adjacent hair intestines spacing 15-25cm simultaneously lean on position-limit mechanism to Duo Genmao intestines side by side Limited post 8 separates；Start archenteron-scrapping machine, hair intestines end be sent between the doctor roll 3 and auxiliary rubber roller 4 of striking mechanism and passed through, Lower section is sent between a pair of of traction roller 5 of traction mechanism further along, and a pair of of traction roller 5 clamps mao intestines and relatively rotates offer tractive force It is automatic that hair intestines is pulled to carry out striking in striking mechanism, it scrapes the mucous membrane liquid produced mucous membrane pond 13 is flow to by collecting tank 12 and receive again Collection；

Finally, the hair intestines after striking, which are sent forward to water flowing, cleans leak detection slot 14, the intestines skin for manually adhering to casing surface Remove and be put into specified basket and (be not drawn into figure), then remaining casing is cleaned using 20 water flowing of water faucet, when cleaning It was found that loophole or broken casing need to be cut off, the aqueous washed out regathers after being pooled to leak detection liquid collecting pit 15.

Wherein, in the enzymatic hydrolysis process, the heparin sodium production enzymolysis device such as flowering structure is first obtained (such as Fig. 5 to Fig. 7 institute Show), the heparin sodium production enzymolysis device includes enzymatic vessel 1 ', and the tank body top of the enzymatic vessel 1 ' is provided with manhole 2 ', under End is provided with discharge port 3 ', and enzymatic vessel 1 ' is above additionally provided with agitating device and heating device, is additionally provided on the tank body and tank Intestinal mucosa liquid inlet tube 4 ', alkali liquor pipe 5 ', salt water water inlet pipe 6 ' and the tap water inlet pipe 7 ' of intracoelomic cavity connection；The heparin sodium Producing enzymolysis device further includes automatic detection and control system, and the automatic detection and control system includes being arranged in inner tank wall For detecting the temperature sensor 11a ' of temperature of charge, the pH value detection sensor 11b ' for detecting material pH value and being used for Salinometer 11c ', the temperature sensor 11a ', pH value detection sensor 11b ' and the salinometer 11c ' for detecting material salinity are equal It is connected with a control centre 11d ' and provides detection data for it, the automatic detection and control system further includes being separately positioned on institute State the electric-controlled switch valve 11e ' in intestinal mucosa liquid inlet tube 4 ', alkali liquor pipe 5 ', salt water water inlet pipe 6 ' and tap water inlet pipe 7 ', institute The electric-controlled switch valve 11e ' stated in intestinal mucosa liquid inlet tube 4 ', alkali liquor pipe 5 ', salt water water inlet pipe 6 ' and tap water inlet pipe 7 ' is each It is connected and is controlled by it with the control centre 11d ' from equal；

The heating device includes the heating coil 8 ' along the coiling setting of 1 ' inner tank wall of enzymatic vessel, and heating coil 8 ' has Extend the air inlet pipe 9a ' of tank body from upper end, there is the escape pipe 9b ' for extending tank body from lower end, the air inlet pipe 9a ' above to set It is equipped with electrical control steam valve 10 ', the electrical control steam valve 10 ' is connected and is controlled by it with the control centre 11d '；

The agitating device includes the stirring motor 12 ' positioned at top of the tank, and is vertically provided in the middle part of tank inner chamber Agitating shaft 13 ' installs support construction 14 ' by agitating shaft between the stirring motor 12 ' and the agitating shaft 13 ' and is connected, institute Agitating shaft installation support construction 14 ' is stated, including is fixed on top of the tank and whole tubular fulcrum bearing 14a ', fulcrum bearing upwards The middle part 14a ' has a horizontally disposed supporting table 14b ', and the stirring motor 12 ' is fixed on the top fulcrum bearing 14a ' and motor Main shaft extends down into that fulcrum bearing 14a ' is interior, is rotatably mounted on the supporting table 14b ' at the middle part the fulcrum bearing 14a ' by bearing There is a jackshaft 14c ', the upper end jackshaft 14c ' end and 12 ' output shaft lower end of stirring motor pass through male-female engagement knot Structure 14d ' docking simultaneously transmits torque；The jackshaft 14c ' close on lower end end position fixing sleeve equipped with one circle on connect steel bushing 14e ', the 13 ' upper end of agitating shaft extend into that fulcrum bearing 14a ' is interior and fixing sleeve is equipped with one and upper connection steel bushing 14e ' correspondence Lower connection steel bushing 14f ', several connections for being uniformly arranged of annular between the upper connection steel bushing 14e ' and lower connection steel bushing 14f ' Pull rod 14h ', the both ends connecting rod 14h ' are passed through the upper connection steel bushing 14e ' and lower connection steel bushing 14f ' and are connected using nut It connects, while also annular is evenly equipped with several helical spring 14g ' between upper connection steel bushing 14e ' and lower connection steel bushing 14f ', it is described The upper and lower ends of helical spring 14g ' are fixed on respectively on connection steel bushing 14e ' and lower connection steel bushing 14f '；

The upper connection steel bushing 14e ', which is above circular layout, several connection bolt 14i ', the connection front end bolt 14i ' edge Upper connection steel bushing 14e ' lateral surface level penetrates in the interior realization of jackshaft 14c ' connection for connecting steel bushing 14e ' and jackshaft 14c '；

2 ' place of manhole is additionally provided with manhole cover structure on the tank body, and the manhole cover structure includes along manhole 2 ' to tank body Outside stretches the circle neck mouth 16 ' convexed to form and surrounds the lid 17 ' that cover type is mounted in neck mouth, 17 ' upper surface of lid It is diametrically fixedly installed a mounting rod 18 ', one end of mounting rod 18 ' and the free bearing being fixed in neck mouth 16 ' can turn Dynamic connection, the other end of mounting rod 18 ' extend lid 17 ' and are provided with the U-lag 19 ' that a horizontal cross-section is in U-shape, U-shaped A check lock lever 20 ' is can be rotatably set in the corresponding neck mouth in 19 ' lower section of slot, 20 ' outer end of check lock lever also leans on screw thread activity to revolve It is connected to a handle 21 ', it is interior and lock by rotating handles 21 ' that 20 ' outer end of check lock lever can be pivoted upwardly into the U-lag 19 ' Tightly in 19 ' upper surface of U-lag；

Then it is operated according to following operating procedure:

Firstly, passing through the electric-controlled switch valve 11e ' charging of control centre 11d ' opening intestinal mucosa liquid inlet tube 4 ', to enzymatic hydrolysis Tank 1 ' is interior to pour into intestinal mucosa liquid；

Secondly, the stirring motor 12 ' of starting top of the tank, agitating shaft 13 ' start to stir；At the same time, control centre The data of 11d ' automatic detection for temperature sensor 11a ', pH value detection sensor 11b ' and salinometer 11c ', and control electricity respectively The electric-controlled switch valve 11e ' on electric-controlled switch valve 11e ' and salt water water inlet pipe 6 ' on control steam valve 10 ', alkali liquor pipe 5 ', so that tank The temperature of interior enzymolysis liquid maintains 47~53 DEG C, pH value maintains PH=8~9, salt angle value maintains 3~3.5 degree；

Finally, control centre 11d ' control electrical control steam valve 10 will heat up in tank after axis 13 ' to be mixed stirs 2.5 hours To 80 DEG C, and maintain no less than 30 minutes；Then, the stirring motor 12 ' of top of the tank is closed, agitating shaft 13 ' stops stirring；It beats It opens 1 ' lower end of enzymatic vessel and is provided with discharge port 3 ', enzymolysis liquid is delivered to filtering tank (being not drawn into figure).

Wherein, it in the elution procedure, first obtains the heparin sodium of flowering structure such as and produces washing device (as shown in Figure 8), institute Stating heparin sodium production washing device includes elution tank 1 ", each elution tank 1 " lower end is provided with drain pipe 2 ", the drain pipe 2 " It is middle that cross-sectional direction is provided with strainer 3 ", the drain pipe 2 " being above lower than the strainer 3 " is provided with for controlling opening for drain Valve 4 is closed on ", be higher than the strainer 3 " being additionally provided with bypass discharge nozzle 5 ", the bypass discharge nozzle 5 " to be provided with for controlling out Material switch valve 6 "；The elution tank 1 " is at least two and is concatenated into multilevel structure；In the multilevel structure, next stage elution The drain pipe 2 " pass through Drainage pipe 7 " of tank is connected with the upper end that upper level elutes tank, the Drainage pipe 7 " on be provided with Electric pump 8 for drain "；The bypass discharge nozzle 5 " passing through discharge pipe 9 " that upper level elutes tank elutes tank with next stage Upper end is connected, the discharge pipe 9 " on be provided with electric pump 10 " for discharging；

The multilevel structure is tertiary structure, the tertiary structure include the first order elution tank 11 ", the second level elution tank 12 " and the third level elutes tank 13 "；Third level elution tank 13 " the drain pipe 2 " passes through Drainage pipe 7 " with described the Second level elutes tank 12 " upper end be connected, second level elution tank 12 " the drain pipe 2 " passes through Drainage pipe 7 " with described The first order elute tank 11 " upper end be connected；First order elution tank 11 " the bypass discharge nozzle 5 " passes through discharge pipe 9 " Elute tank 12 with the second level " upper end be connected, second level elution tank 12 " the bypass discharge nozzle 5 " passes through discharging The upper end of pipeline 9 " eluting tank 13 with the third level " is connected；

The elution tank 1 " on be additionally provided with rabbling mechanism；

The rabbling mechanism includes stirring motor 14 " and stirring rod 15 ", the stirring motor 14 " setting is in elution tank 1 " Upper end, the stirring rod 15 " protruding into elution tank 1 " is interior, stirring motor 14 " with the described stirring rod 15 " connection；

Further include rack 16 in the multilevel structure ", on the elution tank 1 " being mounted on the rack 16 ", the rack 16 " on be additionally provided with helper 17 "；

The elution tank 1 " upper end is provided with manhole 18 "；

The elution tank 1 " is additionally provided with heating mechanism (not drawing in figure)；

Then it is operated according to following operating procedure:

Step 1: while opening first order elution tank 11 " and the third level elutes tank 13 " and being eluted.Wherein, the first order is washed De- tank 11 " the resin that is filtered out from the absorption process of resin, eluent elute tank 12 in the second level in last circulation " The eluent being obtained by filtration after elution；Third level elution tank 13 " resin elute tank 12 in the second level in last circulation " is washed The resin being obtained by filtration after de-, salt water of the eluent from fresh addition；When elution, the first order elutes tank 11, and " elution is three small When, it is vacant that the third level elutes tank 13 " elution 1 hour (second level elutes tank 12 during this ").

Step 2: the first order in step 1 is eluted tank 11, and " eluent that elution filters out drains at the precipitation process Reason, the resin filtered out drain into second level elution tank 12 "；The third level in step 1 is eluted into tank 13 and " elutes the elution filtered out Liquid drains into second level elution tank 12 ", it collects after the resin outlet filtered out and recycles；

Step 3: it opens the second level and elutes tank 12 and " eluted, (first order elutes tank to elution time when elution within 1.5 hours 11 " and the third level elutes tank 13 " are vacant), the eluent that will filter out after elution drains into first order elution tank 11 ", resin drains into The third level elutes tank 13 ", it recycles since then；

In above three step, the elution tank, which opens stirring motor 14 in elution, " to being stirred in tank, to be stirred While, it opens heating mechanism (not drawn in figure), mixed liquor in tank body is heated to 55~60 DEG C.

Through testing, heparin sodium processing is carried out according to above-mentioned specific embodiment and is extracted, every 1500 chitterlings can be reached The heparin sodium first product of one hundred million unit (referring to active matter prime number) can be prepared, therefore compared to the prior art, it greatly improves Heparin sodium extraction efficiency.

Claims

1. a kind of novel postcibal diarrhea of heparin sodium, enzymatic hydrolysis, elution process, including postcibal diarrhea, enzymatic hydrolysis, five big processes of absorption, elution and precipitating Step, which is characterized in that in the postcibal diarrhea process, collect when carrying out striking to hair intestines breaks its intestines skin and casing from intestines The mucus scraped in clothing, while again casing inside carried out pouring water flushing after the separation of intestines skin and collecting flushing liquor, it will be described Mucus and flushing liquor are as the intestinal mucosa liquid in the enzymatic hydrolysis process；Using salt water to from described in the elution procedure The resin that absorption process filters out carries out three-level elution, and wherein third level elution is eluted using the salt water newly prepared and from the second level The resin filtered out afterwards, second level elution use the resin filtered out after the eluent after third level elution and first order elution, First order elution is washed using the eluent after the elution of the second level and the resin filtered out in the absorption process, the first order Eluent after de- enters the subsequent precipitation process.

2. the novel postcibal diarrhea of heparin sodium as described in claim 1, enzymatic hydrolysis, elution process, which is characterized in that in the elution procedure When carrying out three-level elution, third level elution time is 1 hour, and second level elution time is 1.5 hours, and first order elution time is 3 hours.

3. the novel postcibal diarrhea of heparin sodium as described in claim 1, enzymatic hydrolysis, elution process, which is characterized in that

In the enzymatic hydrolysis process, digested using enzymatic vessel；Firstly, opening the intestinal mucosa liquid inlet valve on enzymatic vessel；Then, Intestinal mucosa liquid fresh obtained in postcibal diarrhea process is sent into enzymatic vessel, and intestinal mucosa liquid in enzymatic vessel is stirred；Together When, intestinal mucosa liquid in enzymatic vessel is heated, while gradually adding alkali and salt to convert the mixed liquid of synthesis, heat temperature raising in intestinal mucosa liquid When to 47~53 DEG C, it is enzymolysis liquid, controlled enzymatic hydrolysis liquid PH=8~9, salinity 3 that alkali protease, which is added, by mixed liquid enzymolysis processing ~3.5 degree；Heat preservation 2~3 hours then heats to 80 ± 5 DEG C, and keeps the temperature no less than 30 minutes；Finally, stopping in enzymatic vessel Enzymolysis liquid is stirred, and enzymolysis liquid is put into filtering tank by opening enzymatic vessel baiting valve to be filtered；

In the absorption process, firstly, the enzymolysis liquid is sucked adsorption tanks, the enzymolysis liquid is stirred, to the enzyme When solution liquid is cooled to 55 DEG C~60 DEG C, heparin adsorption resin is added, insulated and stirred is adsorbed 8~10 hours；In the elution procedure, Absorption resin described in the absorption process is rinsed well, is put into elution tank and is eluted after being filtered dry, added and resin The identical salt water of weight converts synthesis mixing,

The salt water is sodium chloride solution, and salinity is 19~23 Baume degrees, and the mixing is heated to 55~60 DEG C, is washed It is de-；

In the precipitation process, using the eluent from elution procedure, adds the alcohol of concentration 80%~90%, stir evenly Afterwards, alcoholic strength control precipitates 20~24 hours at 35~45 degree, extracts supernatant out, and collection sediment waits for being placed on for 2~5 days de- In bucket, be added concentration be 90%~95% alcohol, alcohol with and mixed sediment volume than be about 2:1, dehydration 1~2 hour, It extracts supernatant out, it is dry to collect remaining heparin sodium.

4. the novel postcibal diarrhea of heparin sodium as claimed any one in claims 1 to 3, enzymatic hydrolysis, elution process, which is characterized in that institute It states in postcibal diarrhea process, first obtains the heparin sodium of flowering structure such as and process postcibal diarrhea device, the heparin sodium processing postcibal diarrhea device includes machine Frame (1) and the archenteron-scrapping machine being arranged on rack (1), the archenteron-scrapping machine include the left and right bearing for being fixed on the left and right sides in rack 1 Seat (2), and the striking mechanism and traction mechanism that are horizontally installed on left and right fulcrum bearing (2), the striking mechanism include setting side by side The doctor roll (3) and auxiliary rubber roller (4) set, which is characterized in that the traction mechanism in the archenteron-scrapping machine, including what is be set side by side A pair of of traction roller (5), traction roller (5) length direction is consistent with doctor roll (3) length direction and is located at doctor roll (3) and auxiliary rubber The front lower place position in rubber roller (4) gap is provided on the end of a pair of of traction roller (5) and is intermeshed and for driving two tractions A pair of of gear (6) of roller (5) relative rotation；

It further include position-limit mechanism in the archenteron-scrapping machine, the position-limit mechanism is erected on left and right fulcrum bearing (2) including transverse direction and position The support rod (7) of position between traction mechanism and striking mechanism, on support rod (7) forward upward be set side by side with it is several uniformly The limited post (8) being spaced apart；

The doctor roll flip lid (19) for being covered in doctor roll (3) under it, the doctor roll are additionally provided in the archenteron-scrapping machine The both ends of flip lid (19) front side edge are rotationally hinged on left and right fulcrum bearing (2)；

Face doctor roll (3) top position is additionally provided with the observation window (9) of glass material on the doctor roll flip lid (19)；

The heparin sodium processing postcibal diarrhea device further includes the workbench of strip, and the archenteron-scrapping machine is located at position among workbench, It is provided on the table top of the workbench rear end section start primary launder (10), primary launder (10) Inner Front End position is each side set It is equipped with the water faucet (18) for previous cleaning, primary launder (10) interior rear end is provided with sewage outlet (11)；Primary launder (10) also it is connected between archenteron-scrapping machine and is provided with collecting tank (12), there is one to be scraped intestinal mucosa for collecting for collecting tank (12) rear end Mucous membrane pond (13)；It is located at archenteron-scrapping machine front position on workbench and is additionally provided with water flowing cleaning leak detection slot (14), the water flowing is clear It washes at left and right sides of leak detection slot (14) Inner Front End position and is each provided with a water faucet (20) for water flowing leak detection, water flowing cleaning Leak detection slot (14) interior rear end is additionally provided with leak detection liquid collecting pit (15)；

One, which is provided with, positioned at water faucet rear position in the primary launder (10) and water flowing cleaning leak detection slot (14) loses leak hole (16), it loses leak hole (16) interior activity and is linked with one and lose leaky bucket (17)；

Then it is operated according to following operating procedure:

Firstly, first the sundries such as the loose fat of hair intestines surface attachment are extractd in primary launder (10), and by the sundries of excision by losing Leak hole (16) is directly discarded into leaky bucket (17)；Hair intestines one end is filled to the water faucet (18) for being used for previous cleaning is connected again Water rinses, and the waste water of flushing is by sewage outlet (11) outlet；Hair intestines are passed on collecting tank (12) after flushing, in collecting tank (12) on by hair intestines along workbench length direction put and along workbench width direction laid out in parallel be more after upper machine postcibal diarrhea；

Then, in postcibal diarrhea, Duo Genmao intestines go up archenteron-scrapping machine, adjacent hair intestines spacing 15-25cm and the limit for leaning on position-limit mechanism side by side Column (8) separates；Start archenteron-scrapping machine, hair intestines end is sent between the doctor roll (3) and auxiliary rubber roller (4) of striking mechanism and is worn It crosses, lower section is sent between a pair of of traction roller (5) of traction mechanism further along, and a pair of of traction roller (5) is clamped a mao intestines relative rotation and mentioned It pulls hair intestines to carry out striking in striking mechanism automatically for tractive force, scrapes the mucous membrane liquid produced and flow to mucous membrane by collecting tank (12) Pond (13) regathers；

Finally, the hair intestines after striking, which are sent forward to water flowing, cleans leak detection slot (14), manually the intestines skin that casing surface is adhered to is gone Fall and be put into specified basket, then remaining casing is cleaned using water faucet (20) water flowing, discovery loophole or broken when cleaning Broken casing need to be cut off, and the aqueous washed out regathers after being pooled to leak detection liquid collecting pit (15).

5. the novel postcibal diarrhea of heparin sodium as claimed any one in claims 1 to 3, enzymatic hydrolysis, elution process, which is characterized in that institute It states in enzymatic hydrolysis process, first obtains the heparin sodium of flowering structure such as and produce enzymolysis device, the heparin sodium production enzymolysis device includes enzyme It solves tank (1 '), the tank body top of the enzymatic vessel (1 ') is provided with manhole (2 '), and lower end is provided with discharge port (3 '), enzymatic vessel Agitating device and heating device are additionally provided on (1 '), which is characterized in that be additionally provided on the tank body and be connected to tank inner chamber Intestinal mucosa liquid inlet tube (4 '), alkali liquor pipe (5 '), salt water water inlet pipe (6 ') and tap water inlet pipe (7 ')；The heparin sodium is raw Producing enzymolysis device further includes automatic detection and control system, and the automatic detection and control system includes the use being arranged in inner tank wall In the temperature sensor (11a ') of detection temperature of charge, the pH value detection sensor (11b ') for detecting material pH value and use In the salinometer (11c ') of detection material salinity, the temperature sensor (11a '), pH value detection sensor (11b ') and salinity Count (11c ') and a control centre

(11d ') is connected and provides detection data for it, and the automatic detection and control system further includes being separately positioned on the intestines to glue Electric-controlled switch valve in film liquid inlet tube (4 '), alkali liquor pipe (5 '), salt water water inlet pipe (6 ') and tap water inlet pipe (7 ') (11e '), in the intestinal mucosa liquid inlet tube (4 '), alkali liquor pipe (5 '), salt water water inlet pipe (6 ') and tap water inlet pipe (7 ') Electric-controlled switch valve (11e ') is respectively connected and is controlled by it with the control centre (11d ')；

The heating device includes the heating coil (8 ') along the coiling setting of enzymatic vessel (1 ') inner tank wall, heating coil (8 ') tool There is the air inlet pipe (9a ') for extending tank body from upper end, there is the escape pipe (9b ') for extending tank body from lower end, the air inlet pipe Be provided with electrical control steam valve (10 ') on (9a '), the electrical control steam valve (10 ') be connected with the control centre (11d ') and by It is controlled；

The agitating device includes the stirring motor (12 ') positioned at top of the tank, and is vertically provided at stirring in the middle part of tank inner chamber It mixes axis (13 '), support construction (14 ') phase is installed by agitating shaft between the stirring motor (12 ') and the agitating shaft (13 ') Even, the agitating shaft installs support construction (14 '), including is fixed on top of the tank and whole tubular fulcrum bearing upwards (14a '), fulcrum bearing (14a ') middle part have a horizontally disposed supporting table (14b '), and the stirring motor (12 ') is fixed on branch It holds at the top of seat (14a ') and electric machine main shaft extends down into fulcrum bearing (14a '), the supporting table in the middle part of the fulcrum bearing (14a ') A jackshaft (14c '), the upper end end jackshaft (14c ') and stirring motor are rotatably mounted with by bearing on (14b ') (12 ') output shaft lower end is docked by concave-convex fit structure (14d ') and transmits torque；Jackshaft (14c ') lower end End position fixing sleeve is closed on equipped with steel bushing (14e ') is connected on a circle, and agitating shaft (13 ') upper end extends into fulcrum bearing In (14a ') and fixing sleeve is equipped with one and the corresponding lower connection steel bushing (14f ') of upper connection steel bushing (14e '), the upper connection steel Several connecting rods (14h ') that annular is uniformly arranged between set (14e ') and lower connection steel bushing (14f '), connecting rod (14h ') Both ends are passed through the upper connection steel bushing (14e ') and lower connection steel bushing (14f ') and are connected using nut, while in upper connection steel bushing Also annular is evenly equipped with several helical springs (14g '), the helical spring (14g ') between (14e ') and lower connection steel bushing (14f ') Upper and lower ends be fixed on respectively connection steel bushing (14e ') and lower connection steel bushing (14f ') on；

Being circular layout on the upper connection steel bushing (14e ') has several connection bolts (14i '), connection bolt (14i ') front end It is penetrated in jackshaft (14c ') along upper connection steel bushing (14e ') lateral surface level and realizes connection steel bushing (14e ') and jackshaft The connection of (14c ')；Manhole cover structure is additionally provided on the tank body at manhole (2 '), the manhole cover structure includes along manhole (2 ') to stretching circle neck mouth (16 ') convexed to form outside tank body and encirclement cover type is mounted on lid (17 ') in neck mouth, Lid (17 ') upper surface is diametrically fixedly installed a mounting rod (18 '), one end of mounting rod (18 ') and is fixed on neck A free bearing on mouth (16 ') is rotatably connected, and the other end of mounting rod (18 ') extends lid (17 ') and is provided with a water The U-lag (19 ') that plane section is in U-shape can be rotatably set a check lock lever in corresponding neck mouth below U-lag (19 ') (20 '), check lock lever (20 ') outer end also lean on screw thread activity to be screwed with a handle (21 '), and check lock lever (20 ') outer end can be upward It is rotated into the U-lag (19 ') and is locked at U-lag (19 ') upper surface by rotating handles (21 ')；

Then it is operated according to following operating procedure:

Firstly, electric-controlled switch valve (11e ') charging of intestinal mucosa liquid inlet tube (4 ') is opened by control centre (11d '), to enzyme Intestinal mucosa liquid is poured into solution tank (1 ')；

Secondly, the stirring motor (12 ') of starting top of the tank, agitating shaft (13 ') start to stir；At the same time, control centre The data of (11d ') automatic detection for temperature sensor (11a '), pH value detection sensor (11b ') and salinometer (11c '), and point It Kong Zhi not electrical control steam valve (10 '), automatically controlled on electric-controlled switch valve (11e ') and salt water water inlet pipe (6 ') on alkali liquor pipe (5 ') Switch valve (11e '), so that the temperature of enzymolysis liquid maintains 47~53 DEG C in tank, pH value maintains PH=8~9, salt angle value maintains At 3~3.5 degree；

Finally, control centre (11d ') control electrical control steam valve (10) will rise in tank after axis (13 ') to be mixed is stirred 2.5 hours Temperature maintains no less than 30 minutes to 80 DEG C；Then, the stirring motor (12 ') of top of the tank is closed, agitating shaft (13 ') stops Stirring；It opens enzymatic vessel (1 ') lower end and is provided with discharge port (3 '), enzymolysis liquid is delivered to filtering tank.

6. the novel postcibal diarrhea of heparin sodium as claimed any one in claims 1 to 3, enzymatic hydrolysis, elution process, which is characterized in that institute It states in elution procedure, first obtains the heparin sodium of flowering structure such as and produce washing device, the heparin sodium production washing device includes washing De- tank (1 "), each elution tank (1 ") lower end are provided with drain pipe (2 "), are arranged in the drain pipe (2 ") along cross-sectional direction Have strainer (3 "), the strainer (3 ") are provided with the switch valve (4 ") for controlling drain on the drain pipe (2 "), it is high It is additionally provided with bypass discharge nozzle (5 ") in the strainer (3 "), is provided on bypass discharge nozzle (5 ") for controlling discharging Switch valve (6 ")；The elution tank (1 ") is at least two and is concatenated into multilevel structure；In the multilevel structure, next stage elution The drain pipe (2 ") of tank is connected by the upper end that Drainage pipe (7 ") elute tank with upper level, on the Drainage pipe (7 ") It is provided with the electric pump (8 ") for drain；The bypass discharge nozzle (5 ") that upper level elutes tank passes through discharge pipe (9 ") under The upper end that level-one elutes tank is connected, and the electric pump (10 ") for discharging is provided on the discharge pipe (9 ")；

The multilevel structure is tertiary structure, and the tertiary structure includes first order elution tank (11 "), second level elution tank (12 ") and the third level elute tank (13 ")；The drain pipe (2 ") of third level elution tank (13 ") passes through Drainage pipe (7 ") are connected with the upper end of second level elution tank (12 "), and the drain pipe (2 ") of second level elution tank (12 ") is logical The upper end that Drainage pipe (7 ") is crossed with first order elution tank (11 ") is connected；The side of first order elution tank (11 ") Pass-out expects pipe (5 ") is connected by discharge pipe (9 ") with the upper end of second level elution tank (12 "), the second level elution The bypass discharge nozzle (5 ") of tank (12 ") is connected by discharge pipe (9 ") with the upper end of third level elution tank (13 ")；

Rabbling mechanism is additionally provided on the elution tank (1 ")；

The rabbling mechanism includes stirring motor (14 ") and stirring rod (15 "), and stirring motor (14 ") setting is in elution tank (1 ") upper end, the stirring rod (15 ") are protruded into elution tank (1 "), and the stirring motor (14 ") is the same as the stirring rod (15 ") Connection；

It further include rack (16 ") in the multilevel structure, the elution tank (1 ") is mounted on the rack (16 "), the machine Helper (17 ") are additionally provided on frame (16 ")；

Elution tank (the 1 ") upper end is provided with manhole (18 ")；

The elution tank (1 ") is additionally provided with heating mechanism；

Then it is operated according to following operating procedure:

Above-mentioned heparin sodium production washing device is in use, circulation executes following steps:

Step 1: at the same open the first order elution tank (11 ") and the third level elute tank (13 ") eluted；Wherein, the first order is washed The resin that the resin of de- tank (11 ") is filtered out from the absorption process, eluent elute tank in the second level in last circulation (12 ") eluent being obtained by filtration after eluting；The third level elutes resin second level elution in last circulation of tank (13 ") The resin being obtained by filtration after tank (12 ") elution, salt water of the eluent from fresh addition；When elution, the first order elutes tank (11 ") Three hours are eluted, the third level elutes tank (13 ") and elutes 1 hour；

Step 2: draining into the precipitation process for the eluent that first order elution tank (11 ") elution filters out in step 1 and handle, The resin filtered out drains into second level elution tank (12 ")；Third level elution tank (13 ") in step 1 is eluted into the elution filtered out Liquid drains into second level elution tank (12 "), collects and recycles after the resin outlet filtered out；

Step 3: opening second level elution tank (12 ") and eluted, and elution time 1.5 hours, the elution that will filter out after elution Liquid drains into first order elution tank (11 "), and resin drains into third level elution tank (13 "), recycles since then；

In above three step, the elution tank opens stirring motor (14 ") to being stirred in tank in elution, stirring Meanwhile heating mechanism is opened, mixed liquor in tank body is heated to 55~60 DEG C.