CN104490766A - Allicin solution and production method thereof - Google Patents

Abstract

The invention relates to the technical field of allicine, and relates to an allicin solution and a production method thereof. The allicin solution is prepared through the following method: step 1, preparing oxygen-removed injection water with the oxygen content less than 2 ppm; and step 2 and step 3. The allicin solution, an allicin injection and an allicin contrast sample are produced through current pharmaceutical technologies such as alliinase catalyzing alliin lysis for biosynthesis of allicin, microfiltration and ultrafiltration for purifying allicin, cycled extraction and molecular distillation for realizing liquid-liquid separation, physical sterilization and argon-filling precharging and the like. Air is effectively isolated, the temperature for biologically synthesizing allicin is reduced, allicin decomposition is avoided, and allicin biosynthesis conditions are mild, the yield is high, quality is excellent, and the production process is simple and efficient. Also, a low-temperature air-isolation allicin production apparatus is especially applicable to separation of heat-sensitive easily-oxidized substances, and is capable of effectively keeping the physical properties of natural substances.

Description

Allicin solution and production method thereof

Technical field

the present invention relates to allicin technical field, is a kind of allicin solution and production method thereof.

Background technology

the medicine food dual purpose plant that allium Bulbus Allii (Allium Sativum L.) is with a long history, different regions, the world, different nationalities is generally acknowledged.The records such as China classical Chinese medicine works " Newly Revised Canon of Materia Medica " (Tang), Compendium of Material Medica (bright): Bulbus Allii has " logical the five internal organs, reach all keys, cold removing wets, evil of avoiding evil spirits " etc. function.Uygur's medical science is thought: Bulbus Allii folk prescription or compatibility go thickness sputum matter, are used for the treatment of the various diseases such as qi and blood stagnation, apoplexy, hemiplegia, convulsions.

research confirms, the A.Longicuspis of Central Asia is the most original Bulbus Allii, and other garlic cultivars are all differentiated by it.Therefore the Central Asia (comprising Xinjiang) is the original producton location of Bulbus Allii, is that Bulbus Allii is evolved and multifarious metropolis.

recent studies proves, the major diseases such as garlic active ingredient is the most common to the present age, mortality rate is the highest cardiovascular and cerebrovascular disease, infectious disease and tumor have the prophylactic-therapeutic effect determined, therefore becomes the study hotspot of developed country medicine scholar.In order to prevent and treat cardiovascular and cerebrovascular vessel and infectious critical illness, the garlic preparation new drug that clinical needs are efficient and safe.Therefore, the developed countries such as U.S., moral, Israel, France drop into a large amount of financial resources and material resources, are adopting various modern pharmaceutical new technique, are managing to capture difficulty, research and development " the efficient novel formulation of Bulbus Allii ".But be still in development at present, there is no " the efficient novel formulation of Bulbus Allii " product both at home and abroad and release.

garlic bulb is cut or when pulverizing, the allinase (Alliinase, EC 4.4.1.4) be in Cell vacuoles meets with the alliin (alliin, S-allyl-L-cysteine sulfoxide) be present in Garlic cell matter.There is enzymatic and split conjunction reaction in the two, generating allicin (Allicin).

alliin (Alliin, CAS:556-27-24): chemical name: SACS (S-Allyl-L-cysteine sulfoxide), MW:177.2, mp:163 DEG C-165 DEG C, [α] _d =+60 ^o , white filament crystal.Being present in Bulbus Allii bulbil with odorless form, is original in Bulbus Allii unicorn bud and that content is the highest sulfur-containing amino acid.Because kind, home environment and cultivation technique are different, alliin content has very big-difference (between 0.30-2.50%).

allinase (Alliinase, EC 4.4.1.4, CAS:9031-77-0): have another name called alliin lyase, Alkylcysteine sulfoxide lyase (S-allyl-L-cysteine sulfoxide lyase).Belong to dimer glycoprotein, two molecular weight subunits are 51.5 KDa.The domain combined by N-terminal domains, P5P and C-terminal domains form, and crystallization is in yellow, and odorless, isoelectric pH: 4.9, to responsive to temperature.(EC 4.4.1.4 is the coding of international EC to allinase.First digit 4 represents that this enzyme belongs to the fourth-largest class (lyase); Second digit 4 represents genus the 4th subclass (Alkylcysteine sulfoxide lyase); Third digit 1 represents genus first group, and fourth digit 4 represents the sequence number finding this enzyme)

allicin (Allicin, CAS:539-86-6): have another name called allicin, chemical name: GIUCOSinoate (allyl 2-propenethiosulfinate, Diallyl thiosulfinate), MW:162.3, BP:25 DEG C (decomposition), is slightly soluble in water.That the primary product closing substrate alliin is split in allinase catalysis. be the most important bioactive nucleus of Bulbus Allii.But the physicochemical property of allicin is unstable, easily decomposes under room temperature, in air.A kind of compound of stable in physicochemical property is had: Diallytrisin in catabolite.

the mutual relation of alliin, allicin and garlicin as shown in Figure 3.

garlicin (Allitridum, CAS:2050-87-5): another name: Diallytrisin, trisulfides two propylene (Allisatin, Allitridum, Diallyl trisulfide).C ₆ h ₁₀ s ₃ =178.34, be a kind of industrial chemicals originally, as plasticizer and chemosynthesis intermediate.Shanghai Lang Yijiang etc. finds a small amount of Diallytrisin in 1975 from the chromatography of gases analysis of steam distillation Oleum Bulbus Allii." allicin " is named as " garlicin " by the national drug standards " WS-10001-(HD-0050)-2002 ".After this large amount of synthetic of domestic beginning, and make several formulations, supply clinical." Diallytrisin " is called " garlicin ".People being takeed for " effective ingredient that garlicin is Bulbus Allii ", " garlicin can extract from fresh Bulbus Allii ", is a kind of misleading or association.

" garlicin " is all chemosynthesis product at present.Yellow flammable liquid.There is moderate toxicity: acute toxicity: Mouse oral LD ₅₀ =100 mg/Kg, quiet note LD ₅₀ =70mg/kg, Oral Administration in Rats LD ₅₀ =265mg/kg.Heavy dose can cause poisoning and neuropathy.

not containing garlicin in fresh Bulbus Allii, it is the one in the multiple catabolite of allicin.Although experiment display, Bulbus Allii have many-sided drug effect, because the chemical constitution (material base) of allicin and garlicin is different.Garlicin can not the drug effect of On behalf of plant Bulbus Allii main component alliin and allicin.

the chemical constitution of alliin, allicin and garlicin compares sees shown in Fig. 4, Fig. 5 and Fig. 6.

allinase catalysis is split conjunction alliin and is produced the quantitative relation formula of allicin as shown in Figure 7.

the U.S. and European Union's pharmacopeia confirm that the principle active component of Bulbus Allii (Alliium sativum L.) is: allinase (Alliinase, EC 4.4.1.4) catalysis split close substrate " alliin (Alliin) ", the allicin (Allicin) of generation.

the physicochemical property of allicin is unstable, to responsive to temperature (during higher than 25 DEG C, allicin will decompose gradually), at normal temperatures, unstable in air, therefore traditional distillation technology (rely on boiling-point difference, obtain different material in the different temperatures period) can not be adopted.And split the reaction of closing alliin generation allicin due to allinase catalysis to carry out in aqueous phase, the dissolubility of fat-soluble allicin in water is about 5 ‰, therefore need to implement the operations such as extraction, concentrated, purification, if adopt general extracting operation, if unavoidable air enters affect product quality adopts classics rectification mode to extract, before ether arrives boiling point, allicin, at 25 DEG C, namely starts to decompose.So just, make to extract from plant or synthetic allicin very difficult, cause the garlic preparation gone on the market at present to remain the very low crude preparation by using of active constituent content all over the world.

Summary of the invention

the invention provides a kind of allicin solution and production method thereof, overcome the deficiency of above-mentioned prior art, it can effectively solve, and to adopt traditional distillation technology and abstraction technique from plant, extract allicin very difficult, makes the allicin preparation existed at present be the problem of the crude preparation by using that active constituent content is very low.

one of technical scheme of the present invention is realized by following measures: a kind of allicin solution, and it obtains as follows: the first step, prepares the deoxidation water for injection that oxygen content is less than 2ppm; Second step, according to deoxidation water for injection: allinase: the mass ratio of alliin is that deoxidation water for injection, allinase and alliin mix by the ratio of 57:1:1 to 57:3:1 at temperature is 25 DEG C, the pH value controlling solution is 6.5 to 7.0, be stirred to split under 30rmp to 100rmp stir speed (S.S.) and close reaction and complete and obtain reactant liquor, then reacting liquid temperature is down to 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion; 3rd step; first by the visible precipitate thing of reactant liquor in micro-filtration removing reactant liquor; then reactant liquor is obtained allicin solution after the macromolecular substances in ultrafiltration apparatus removing mixed solution; all the time the temperature of reactant liquor is remained on 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion.

here is the further optimization and/or improvements to one of foregoing invention technical scheme:

above-mentioned process further by allicin solution obtains allicin injection liquid: the concentration first measuring allicin solution, then according to the concentration of required allicin injection, the deoxidation water for injection of aequum is added in allicin solution, allicin injection is obtained after mix homogeneously, the pH value controlling allicin solution is 6.5 to 7.0, allicin injection is sent in injection filling apparatus threading prefilled syringe needle tubing and obtain allicin injection liquid, in this operating process, remain that the temperature of allicin solution and allicin injection is 0 DEG C to 4 DEG C, and operating process all the time with argon carry out positive pressure protection all the time with air exclusion, or/and, allicin solution is processed further and obtains allicin reference substance: with ether, iterative cycles extraction is carried out to allicin solution, after having extracted, get ether layer and carry out molecular distillation, molecular distillation condition: control sample introduction flow velocity is 2 ml/min to 10 ml/min, scraper velocity is 40 r/min to 70 r/min, chilling temperature is 5 DEG C to-15 DEG C, vacuum is 0.08 torr to 1 torr, obtains the flaxen allicin thick semisolid of grease-like and allicin standard reference material after molecular distillation completes.

two of technical scheme of the present invention is realized by following measures: a kind of production method of allicin solution, and it carries out in the steps below: the first step, prepares the deoxidation water for injection that oxygen content is less than 2ppm; Second step, according to deoxidation water for injection: allinase: the mass ratio of alliin is that deoxidation water for injection, allinase and alliin mix by the ratio of 57:1:1 to 57:3:1 at temperature is 25 DEG C, the pH value controlling solution is 6.5 to 7.0, be stirred to split under 30rmp to 100rmp stir speed (S.S.) and close reaction and complete and obtain reactant liquor, then reacting liquid temperature is down to 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion; 3rd step; first by the visible precipitate thing of reactant liquor in micro-filtration removing reactant liquor; then reactant liquor is obtained allicin solution after the macromolecular substances in ultrafiltration apparatus removing mixed solution; all the time the temperature of reactant liquor is remained on 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion.

here is the further optimization and/or improvements to foregoing invention technical scheme two:

above-mentioned process further by allicin solution obtains allicin injection liquid: the concentration first measuring allicin solution, then according to the concentration of required allicin injection, the deoxidation water for injection of aequum is added in allicin solution, allicin injection is obtained after mix homogeneously, the pH value controlling allicin solution is 6.5 to 7.0, allicin injection is sent in injection filling apparatus threading prefilled syringe needle tubing and obtain allicin injection liquid, in this operating process, remain that the temperature of allicin solution and allicin injection is 0 DEG C to 4 DEG C, and operating process all the time with argon carry out positive pressure protection all the time with air exclusion, or/and, allicin solution is processed further and obtains allicin reference substance: with ether, iterative cycles extraction is carried out to allicin solution, after having extracted, get ether layer and carry out molecular distillation, molecular distillation condition: control sample introduction flow velocity is 2 ml/min to 10 ml/min, scraper velocity is 40 r/min to 70 r/min, chilling temperature is 5 DEG C to-15 DEG C, vacuum is 0.08 torr to 1 torr, obtains the flaxen allicin thick semisolid of grease-like and allicin standard reference material after molecular distillation completes.

the production method of above-mentioned allicin solution also comprises low temperature and completely cuts off air allicin process units, and this low temperature completely cuts off air allicin process units and comprises retort, the first cryogenic sterile tank, the second cryogenic sterile tank, micro-filtration, ultrafiltration apparatus, cycling extraction device, injection filling apparatus, molecular distillation apparatus and deoxidation water pot, retort, first cryogenic sterile tank, agitating device is installed with respectively, retort in second cryogenic sterile tank and deoxidation water pot, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration, ultrafiltration apparatus, all there is cooling jacket the outside of cycling extraction device, bottom retort discharging opening and retaining between side of micro-filtration be installed with the first feed-stock pipeline, micro-filtration be installed with the second feed-stock pipeline through between side and the charging aperture of the first cryogenic sterile tank, discharging opening and the retaining between side of ultrafiltration apparatus of the first cryogenic sterile tank are installed with the 3rd feed-stock pipeline, ultrafiltration apparatus be installed with the 4th feed-stock pipeline through between side and the charging aperture of the second cryogenic sterile tank, the discharging opening of the second cryogenic sterile tank and be installed with injection fill pipeline and cycling extraction feeding line between injection filling apparatus and cycling extraction device respectively, distillation feeding line is installed with between cycling extraction device and molecular distillation apparatus, molecular distillation apparatus is installed with out sample pipeline, the upper end of deoxidation water pot is installed with to be taken over into water, the bottom of deoxidation water pot is installed with outfall sewer, outfall sewer and retort, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration retain side, ultrafiltration apparatus retain side, be installed with water inlet pipe respectively between cycling extraction device and molecular distillation apparatus, micro-filtration be installed with cleaning discharge nozzle respectively through on side, deoxidation water pot through side and ultrafiltration apparatus, retort, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration retain side, ultrafiltration apparatus retain side, injection filling apparatus, cycling extraction device and molecular distillation apparatus are respectively arranged with argon adapter, deoxidation water pot, retort, first cryogenic sterile tank, the inner of the argon adapter of the second cryogenic sterile tank and cycling extraction device lays respectively at deoxidation water pot, retort, first cryogenic sterile tank, the bottom of the second cryogenic sterile tank and cycling extraction device, at deoxidation water pot, retort, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration through side, ultrafiltration apparatus through side, injection filling apparatus, the upper end of cycling extraction device and molecular distillation apparatus is respectively arranged with emptying adapter, upper end and the retaining between side of ultrafiltration apparatus of the first cryogenic sterile tank are installed with trapped fluid pipeloop, first feed-stock pipeline is installed with peristaltic pump, the 3rd feed-stock pipeline is installed with reciprocating pump.

above-mentioned cycling extraction device comprises cycling extraction tank and cycling extraction peristaltic pump, the external stability of cycling extraction tank is provided with cooling jacket, in cycling extraction tank, agitating device is installed, connection tube is installed with in the upper end of cycling extraction tank, lower connection tube is installed with in the lower end of cycling extraction tank, be arranged in top inner chamber and lower lumen that the upper connection tube of cycling extraction tank inside and lower connection tube are vertically arranged on cycling extraction tank respectively, cycling extraction peristaltic pump is installed with between upper connection tube in cycling extraction tank outside and lower connection tube, the upper end of the lower end and lower connection tube that are positioned at the upper connection tube of cycling extraction tank inside is installed with sintered glass funnel respectively, cycling extraction feeding line is installed with between the discharging opening of the second cryogenic sterile tank and the upper end of cycling extraction tank, lower connection tube is installed with circulation control valve, lower connection tube between circulation control valve to cycling extraction tank lower end is installed with distillation feeding line, water inlet pipe is installed with between outfall sewer and cycling extraction tank, distillation feeding line is installed with oil plant control valve, the upper end of cycling extraction tank is respectively arranged with oil phase adapter, argon adapter and emptying adapter, the inner of the argon adapter of cycling extraction tank is positioned at the bottom of the inner chamber of cycling extraction tank, oil phase adapter is installed with oil phase control valve.

above-mentioned low temperature completely cuts off air allicin process units and also comprises the first refrigerant tank, second refrigerant tank, the liquid outlet of the first refrigerant tank respectively with retort, first cryogenic sterile tank, the cooling jacket of the second cryogenic sterile tank and micro-filtration is chained together by the first coolant pipeline, the first coolant liquid back pipe line is installed with between the cooling jacket of micro-filtration and the inlet of the first refrigerant tank, the second coolant pipeline is installed with between the inlet of the liquid outlet of the second refrigerant tank and the cooling jacket of ultrafiltration apparatus, the second coolant liquid back pipe line is installed with between the liquid outlet of ultrafiltration apparatus external refrigeration chuck and the inlet of the second refrigerant tank, the first coolant pipeline of liquid outlet respectively and between retort of the first refrigerant tank, the first coolant pipeline between retort and the first cryogenic sterile tank, the first coolant pipeline between first cryogenic sterile tank and the second cryogenic sterile tank, the first coolant pipeline between second cryogenic sterile tank and micro-filtration, first coolant liquid back pipe line, second coolant pipeline and the second coolant liquid back pipe line are installed with control valve respectively, or, this low temperature completely cuts off air allicin process units and also comprises the first refrigerant tank, second refrigerant tank, the liquid outlet of the first refrigerant tank is installed with coolant fluid house steward, the inlet of the first refrigerant tank is installed with coolant and returns liquid house steward, coolant fluid house steward and retort, first cryogenic sterile tank, second cryogenic sterile tank, coolant feed liquor arm is installed with respectively between the cooling jacket import of micro-filtration and cycling extraction tank, retort, first cryogenic sterile tank, second cryogenic sterile tank, the cooling jacket outlet of micro-filtration and cycling extraction tank and coolant return and are installed with coolant respectively between liquid house steward and return liquid arm, the second coolant pipeline is installed with between the inlet of the liquid outlet of the second refrigerant tank and the cooling jacket of ultrafiltration apparatus, the second coolant liquid back pipe line is installed with between the liquid outlet of ultrafiltration apparatus external refrigeration chuck and the inlet of the second refrigerant tank, every bar coolant feed liquor arm and every bar coolant liquid back pipe line are installed with control valve respectively, second coolant pipeline and the second coolant liquid back pipe line are installed with control valve respectively, or/and, deoxidation water pot, retort, the first cryogenic sterile tank, the second cryogenic sterile tank and cycling extraction tank are installed with temperature monitoring respectively.

above-mentioned low temperature completely cuts off air allicin process units and also comprises argon bottle, argon bottle is installed with gas transmission main, gas transmission main and each argon are installed with gas transmission arm between taking over respectively, gas transmission main near argon bottle outlet fixedly mounts limited valve, effusion meter and depurator respectively, every bar gas transmission arm is all installed with control valve.

the port of export of the argon adapter in above-mentioned deoxidation water pot is installed with allotter.

above-mentioned every bar water inlet pipe is installed with control valve, the first feed-stock pipeline between retort and peristaltic pump is installed with control valve, second feed-stock pipeline is installed with control valve, the 3rd feed-stock pipeline between the first cryogenic sterile tank and reciprocating pump is installed with control valve, injection fill pipeline and cycling extraction feeding line are installed with control valve respectively; Or/and the microfiltration scope that micro-filtration adopts is 0.1 μm to 1.0 μm, the ultrafiltration range that ultrafiltration apparatus adopts is 500D to 5000D; Or/and, retort, the first cryogenic sterile tank and the second cryogenic sterile tank are installed with pH monitor respectively.

the present invention is by " allinase catalysis alliin splits and closes biosynthesis allicin ", " microfiltration and ultrafiltration purification allicin ", the modern pharmaceutical new technique such as " cycling extraction and molecular distillation realize Liquid liquid Separation " and " physics is degerming to be pre-installed with argon filling " produces allicin solution, allicin injection liquid and allicin reference substance, effectively isolated air, reduce the temperature of biosynthesis allicin, allicin is avoided to decompose, make the mild condition of biosynthesis allicin, productive rate is high, Functionality, quality and appealing design, production process simple and effective, and low temperature of the present invention completely cuts off the suitable especially thermal sensitivity of air allicin process units, the separation of readily oxidizable substance, the physical property of effective maintenance natural materials.

Accompanying drawing explanation

accompanying drawing 1 is the process structure schematic diagram of preferred embodiment.

accompanying drawing 2 is the structural representation of cycling extraction device in the present invention.

accompanying drawing 3 is the mutual relation figure of alliin, allicin and garlicin in the present invention.

accompanying drawing 4 is alliin chemical structural drawing in the present invention.

accompanying drawing 5 is allicin chemical structural drawing in the present invention.

accompanying drawing 6 is garlicin chemical structural drawing in the present invention.

accompanying drawing 7 is that in the present invention, the quantitative relation formula figure closing alliin generation allicin is split in allinase catalysis.

coding in accompanying drawing is respectively: 1 is retort, 2 is the first cryogenic sterile tank, 3 is the second cryogenic sterile tank, 4 is deoxidation water pot, 5 is agitating device, 6 is micro-filtration, 7 is ultrafiltration apparatus, 8 is cycling extraction device, 9 is the first feed-stock pipeline, 10 is the second feed-stock pipeline, 11 is the 3rd feed-stock pipeline, 12 is the 4th feed-stock pipeline, 13 is injection filling apparatus, 14 is injection fill pipeline, 15 is cycling extraction feeding line, 16 is molecular distillation apparatus, 17 is distillation feeding line, 18 for going out sample pipeline, 19 is depurator, 20 is water inlet adapter, 21 is outfall sewer, 22 is water inlet pipe, 23 is cleaning discharge nozzle, 24 is argon adapter, 25 is emptying adapter, 26 is trapped fluid pipeloop, 27 is peristaltic pump, 28 is reciprocating pump, 29 is cycling extraction tank, 30 is cycling extraction peristaltic pump, 31 is upper connection tube, 32 is lower connection tube, 33 is sintered glass funnel, 34 is circulation control valve, 35 is oil phase control valve, 36 is oil plant control valve, 37 is oil phase adapter, 38 is the first refrigerant tank, 39 is the first coolant pipeline, 40 is the first coolant liquid back pipe line, 41 is the second refrigerant tank, 42 is the second coolant pipeline, 43 is the second coolant liquid back pipe line, 44 is argon bottle, 45 is gas transmission main, 46 is gas transmission arm, 47 is pressure limiting valve, 48 is effusion meter.

Detailed description of the invention

the present invention by the restriction of following embodiment, can not determine concrete embodiment according to technical scheme of the present invention and practical situation.Unless stated otherwise, the % in the present invention is mass percent; Unless stated otherwise, preparation process is carried out under room temperature, atmospheric pressure state; Unless stated otherwise, the reagent adopted in the present invention, method and apparatus are the art conventional reagent, method and apparatus; Unless stated otherwise, in the present invention, agents useful for same is commercial; Unless stated otherwise, the water in the present invention is deionized water; Unless stated otherwise, the solution in the present invention is the aqueous solution that solvent is water, and such as, if illustrate, hydrochloric acid solution is aqueous hydrochloric acid solution.

in the present invention, for convenience of description, the description of the relative position relation of each parts is all be described according to the Butut mode of Figure of description 1, as: the position relationship of upper and lower, left and right etc. determines according to the Butut direction of Figure of description.

below in conjunction with embodiment and accompanying drawing, the invention will be further described:

embodiment 1, this allicin solution obtains by following preparation method: the first step, prepares the deoxidation water for injection that oxygen content is less than 2ppm; Second step, according to deoxidation water for injection: allinase: the mass ratio of alliin is that deoxidation water for injection, allinase and alliin mix by the ratio of 57:1:1 to 57:3:1 at temperature is 25 DEG C, the pH value controlling solution is 6.5 to 7.0, be stirred to split under 30rmp to 100rmp stir speed (S.S.) and close reaction and complete and obtain reactant liquor, then reacting liquid temperature is down to 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion; 3rd step; first by the visible precipitate thing of reactant liquor in micro-filtration removing reactant liquor; then reactant liquor is obtained allicin solution after the macromolecular substances in ultrafiltration apparatus removing mixed solution; all the time the temperature of reactant liquor is remained on 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion.

embodiment 2, preferred as enforcement 1, allicin solution is processed further and obtains allicin injection liquid: the concentration first measuring allicin solution, then according to the concentration of required allicin injection, the deoxidation water for injection of aequum is added in allicin solution, allicin injection is obtained after mix homogeneously, the pH value controlling allicin solution is 6.5 to 7.0, allicin injection is sent in injection filling apparatus threading prefilled syringe needle tubing and obtain allicin injection liquid, in this operating process, remain that the temperature of allicin solution and allicin injection is 0 DEG C to 4 DEG C, and operating process all the time with argon carry out positive pressure protection all the time with air exclusion.

embodiment 3, preferred as enforcement 1, allicin solution is processed further and obtains allicin reference substance: with ether, iterative cycles extraction is carried out to allicin solution, after having extracted, get ether layer and carry out molecular distillation, molecular distillation condition: control sample introduction flow velocity is 2 ml/min to 10 ml/min, scraper velocity is 40 r/min to 70 r/min, chilling temperature is 5 DEG C to-15 DEG C, vacuum is 0.08 torr to 1 torr, obtains the flaxen allicin thick semisolid of grease-like and allicin standard reference material after molecular distillation completes.

embodiment 4, as shown in accompanying drawing 1,2, the production method of this allicin solution also comprises low temperature and completely cuts off air allicin process units, and this low temperature completely cuts off air allicin process units and comprises retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3, micro-filtration 6, ultrafiltration apparatus 7, cycling extraction device 8, injection filling apparatus 13, molecular distillation apparatus 16 and deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, agitating device 5 is installed with respectively, retort 1 in second cryogenic sterile tank 3 and deoxidation water pot 4, first cryogenic sterile tank 2, second cryogenic sterile tank 3, micro-filtration 6, ultrafiltration apparatus 7, all there is cooling jacket the outside of cycling extraction device 8, bottom retort 1 discharging opening and retaining between side of micro-filtration 6 be installed with the first feed-stock pipeline 9, micro-filtration 6 be installed with the second feed-stock pipeline 10 through between side and the charging aperture of the first cryogenic sterile tank 2, discharging opening and the retaining between side of ultrafiltration apparatus 7 of the first cryogenic sterile tank 2 are installed with the 3rd feed-stock pipeline 11, ultrafiltration apparatus 7 be installed with the 4th feed-stock pipeline 12 through between side and the charging aperture of the second cryogenic sterile tank 3, the discharging opening of the second cryogenic sterile tank 3 and be installed with injection fill pipeline 14 and cycling extraction feeding line 15 between injection filling apparatus 13 and cycling extraction device 8 respectively, distillation feeding line 17 is installed with between cycling extraction device 8 and molecular distillation apparatus 16, molecular distillation apparatus 16 is installed with out sample pipeline 18, the upper end of deoxidation water pot 4 is installed with into water adapter 20, the bottom of deoxidation water pot 4 is installed with outfall sewer 21, outfall sewer 21 and retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3, micro-filtration 6 retain side, ultrafiltration apparatus 7 retain side, be installed with water inlet pipe 22 respectively between cycling extraction device 8 and molecular distillation apparatus 16, micro-filtration 6 through side and ultrafiltration apparatus 7 through side being installed with respectively cleaning discharge nozzle 23, deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3, micro-filtration 6 retain side, ultrafiltration apparatus 7 retain side, injection filling apparatus 13, cycling extraction device 8 and molecular distillation apparatus 16 are respectively arranged with argon adapter 24, deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, the inner of the argon adapter 24 of the second cryogenic sterile tank 3 and cycling extraction device 8 lays respectively at deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, the bottom of the second cryogenic sterile tank 3 and cycling extraction device 8, at deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3, micro-filtration 6 through side, ultrafiltration apparatus 7 through side, injection filling apparatus 13, the upper end of cycling extraction device 8 and molecular distillation apparatus 16 is respectively arranged with emptying adapter 25, upper end and the retaining between side of ultrafiltration apparatus 7 of the first cryogenic sterile tank 2 are installed with trapped fluid pipeloop 26, first feed-stock pipeline 9 is installed with peristaltic pump 27, the 3rd feed-stock pipeline 11 is installed with reciprocating pump 28.In cycling extraction device 8 and molecular distillation apparatus 16, pass into deoxidation water for injection one by water inlet pipe 22 to be used to catch up with most air, and be used to clean flushing device, cleaning discharge nozzle 23 for this low temperature is completely cut off to air allicin process units and comprehensively cleans and aseptic process time exhaustjet water; Trapped fluid after ultrafiltration apparatus process and the temperature of permeate all remain on 0 DEG C to 4 DEG C.

embodiment 5, preferred as above-described embodiment 4, as accompanying drawing 1, shown in 2, cycling extraction device comprises cycling extraction tank 29 and cycling extraction peristaltic pump 30, the external stability of cycling extraction tank 29 is provided with cooling jacket, agitating device 5 is installed in cycling extraction tank 29, connection tube 31 is installed with in the upper end of cycling extraction tank 29, lower connection tube 32 is installed with in the lower end of cycling extraction tank 29, be arranged in top inner chamber and lower lumen that the upper connection tube 31 of cycling extraction tank 29 inside and lower connection tube 32 are vertically arranged on cycling extraction tank 29 respectively, cycling extraction peristaltic pump 30 is installed with between upper connection tube 31 in cycling extraction tank 29 outside and lower connection tube 32, the upper end of the lower end and lower connection tube 32 that are positioned at the upper connection tube 31 of cycling extraction tank 29 inside is installed with sintered glass funnel 33 respectively, cycling extraction feeding line 15 is installed with between the discharging opening of the second cryogenic sterile tank 2 and the upper end of cycling extraction tank 29, lower connection tube 32 is installed with circulation control valve 34, lower connection tube 32 between circulation control valve 34 to cycling extraction tank 29 lower end is installed with distillation feeding line 17, water inlet pipe 22 is installed with between outfall sewer 21 and cycling extraction tank 29, distillation feeding line 17 is installed with oil plant control valve 36, the upper end of cycling extraction tank 29 is respectively arranged with oil phase adapter 37, argon adapter 24 and emptying adapter 25, the inner of the argon adapter 24 of cycling extraction tank 29 is positioned at the bottom of the inner chamber of cycling extraction tank 29, oil phase adapter 37 is installed with oil phase control valve 35.The distillation other end of feeding line 15 and the import of molecular distillation apparatus 16 are fixedly installed togather, allicin solution is sent in cycling extraction tank 29 by cycling extraction feeding line 15, ether is added by oil phase adapter 37, and make the sintered glass funnel 3 of the sintered glass funnel 33 of connection tube 31 lower end and lower connection tube 32 upper end be immersed in ether layer and water layer respectively, then cycling extraction peristaltic pump 30 is started, by ether iterative cycles in cycling extraction tank 29, and the mixing speed of controlled circulation extractor 29 is 100r/min, the circulation rate of ether is 30ml/min to 60ml/min, the allicin in the allicin solution of water layer is made fully to enter ether layer, then the ether after having extracted allicin is sent into molecular distillation apparatus 16 carry out molecular distillation by being distilled feeding line 17, this cycling extraction device adopts argon to completely cut off air, and the cold water passing into 0 DEG C to 4 DEG C in cooling jacket all the time circulates, adopt ether cold cycle extraction allicin from aqueous solution, ether cycling extraction technology, cycling extraction tank is protected by argon gas positive pressure, isolated air, and is placed in the water-bath of 0 DEG C to 4 DEG C, extraction process is in low temperature state all the time, prevents allicin ingress of air and the too high allicin that causes of temperature decomposes, sintered glass funnel 33 is No. three sintered glass funnels, selects No. three sintered filter funnels can fine precipitate thing in easier removing solution.

embodiment 6, preferred as embodiment 5, as accompanying drawing 1, shown in 2, comprise the first refrigerant tank 38, second refrigerant tank 41, the liquid outlet of the first refrigerant tank 38 respectively with retort 1, first cryogenic sterile tank 2, the cooling jacket of the second cryogenic sterile tank 3 and micro-filtration 6 is chained together by the first coolant pipeline 39, the first coolant liquid back pipe line 40 is installed with between the cooling jacket of micro-filtration 6 and the inlet of the first refrigerant tank 38, the second coolant pipeline 42 is installed with between the inlet of the liquid outlet of the second refrigerant tank 41 and the cooling jacket of ultrafiltration apparatus 7, the second coolant liquid back pipe line 43 is installed with between the liquid outlet of ultrafiltration apparatus 7 external refrigeration chuck and the inlet of the second refrigerant tank 41, the first coolant pipeline 39 of liquid outlet respectively and between retort 1 of the first refrigerant tank 38, the first coolant pipeline 39 between retort 1 and the first cryogenic sterile tank 2, the first coolant pipeline 39 between first cryogenic sterile tank 2 and the second cryogenic sterile tank 3, the first coolant pipeline 39 between second cryogenic sterile tank 3 and micro-filtration 6, first coolant liquid back pipe line 40, second coolant pipeline 42 and the second coolant liquid back pipe line 43 are installed with control valve respectively, or/and, deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3 and cycling extraction tank 8 are installed with temperature monitoring respectively.This connected mode is by the first refrigerant tank 38, retort 1, first cryogenic sterile tank 2, connect between second cryogenic sterile tank 3 and micro-filtration 6, temperature monitoring can monitor deoxidation water pot 4 at any time, retort 1, first cryogenic sterile tank 2, the temperature of solution in second cryogenic sterile tank 3 and cycling extraction tank 8, make deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, in second cryogenic sterile tank 3 and cycling extraction tank 8, the temperature of solution remains in rational scope, stored in 0 DEG C of coolant in first refrigerant tank 38, as frozen water, stored in-200 DEG C of coolant in second refrigerant tank 41, as propylene glycol.

embodiment 7, preferred as embodiment 6, also comprise the first refrigerant tank 38, second refrigerant tank 41, the liquid outlet of the first refrigerant tank 38 is installed with coolant fluid house steward, the inlet of the first refrigerant tank 38 is installed with coolant and returns liquid house steward, coolant fluid house steward and retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3, coolant feed liquor arm is installed with respectively between the cooling jacket import of micro-filtration 7 and cycling extraction tank 8, retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3, the cooling jacket outlet of micro-filtration 6 and cycling extraction tank 8 and coolant return and are installed with coolant respectively between liquid house steward and return liquid arm, the second coolant pipeline 42 is installed with between the inlet of the liquid outlet of the second refrigerant tank 41 and the cooling jacket of ultrafiltration apparatus 7, the second coolant liquid back pipe line 43 is installed with between the liquid outlet of ultrafiltration apparatus 7 external refrigeration chuck and the inlet of the second refrigerant tank 41, every bar coolant feed liquor arm and every bar coolant liquid back pipe line are installed with control valve respectively, second coolant pipeline 43 and the second coolant liquid back pipe line 43 are installed with control valve respectively, or/and, deoxidation water pot 4, retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3 and cycling extraction tank 8 are installed with temperature monitoring respectively.This connected mode is by the first refrigerant tank 38, retort 1, first cryogenic sterile tank 2, second cryogenic sterile tank 3, carries out parallel connection between micro-filtration 6 and cycling extraction tank 8.

embodiment 8, preferred as embodiment 7, as shown in accompanying drawing 1,2, this low temperature completely cuts off air allicin process units and also comprises argon bottle 44, argon bottle 44 is installed with gas transmission main 45, be installed with gas transmission arm 46 respectively between gas transmission main 45 and each argon adapter 24, the gas transmission main 45 exported fixedly mount limited valve 47, effusion meter 48 and depurator 19 respectively, every bar gas transmission arm 46 is all installed with control valve near argon bottle 44.Argon used is high-purity medical argon.

embodiment 9, preferred as embodiment 4 to embodiment 8, the port of export of the argon adapter 24 in deoxidation water pot 4 is installed with allotter.When argon enters deoxidation water pot 4, through allotter, make argon be vaporificly enter in deoxidation water pot 4, be convenient to argon like this evenly the water being dispersed in deoxidation water pot 4 in.

embodiment 10, preferred as embodiment 4 to embodiment 9, as shown in accompanying drawing 1,2, every bar water inlet pipe 22 is installed with control valve, the first feed-stock pipeline 9 between retort 1 and peristaltic pump 27 is installed with control valve, second feed-stock pipeline 10 is installed with control valve, the 3rd feed-stock pipeline 11 between the first cryogenic sterile tank 2 and reciprocating pump 28 is installed with control valve, injection fill pipeline 14 and cycling extraction feeding line 15 are installed with control valve respectively; Or/and the microfiltration scope that micro-filtration adopts is 0.1 μm to 1.0 μm, the ultrafiltration range that ultrafiltration apparatus adopts is 500D to 5000D; Or/and, retort 1, first cryogenic sterile tank 2 and the second cryogenic sterile tank 3 are installed with pH monitor respectively.PH monitor can monitor the pH value of solution in retort 1, first cryogenic sterile tank 2 and the second cryogenic sterile tank 3 at any time, and the pH of solution in retort 1, first cryogenic sterile tank 2 and the second cryogenic sterile tank 3 is remained in rational scope.

embodiment 11, preferred as above-described embodiment, the using method that this low temperature completely cuts off air allicin process units is carried out in the steps below:

the first step, deviate from the air in water for injection: air allicin process units is completely cut off to this low temperature and comprehensively cleans and aseptic process, in deoxidation water pot 4, the water for injection of 0 DEG C to 25 DEG C is added by water inlet adapter 20, in deoxidation water pot 4, high-purity medical argon is injected by the argon adapter 24 of deoxidation water pot 4, and the agitating device 5 opened in deoxidation water pot 4, the flow controlling to enter the argon of deoxidation water pot 4 is 120ml/min to 240ml/min, continue in deoxidation water pot 4, pass into argon and be less than 2ppm to the oxygen content in water for injection, obtain deoxidation water for injection, to this low temperature completely cut off air allicin process units comprehensively clean and aseptic process time, first individual equipment can be filled deoxidation water for injection, then pass into argon, exhaustjet water, and ensure to continue to be full of argon in each equipment, isolated air,

second step, conjunction alliin is split in allinase catalysis, biosynthesis allicin: continue to pass into argon and carry out positive pressure protection in retort 1, deoxidation water for injection enters retort 1 through outfall sewer 21 and exit branch 22, connect 25 pipes by emptying and drop into powdery Bulbus Allii enzyme in retort 1, open the agitating device in retort 1, be stirred to without visible precipitate thing, in retort, powdery alliin is dropped into again through emptying adapter 25, the pH value of the solution now controlled in retort 1 is 6.5 to 7.0, continue to be stirred to split and close reaction and complete and obtain reactant liquor, then in the cooling jacket of retort 1, pass into 0 DEG C to 4 DEG C refrigerant circulation lower the temperature, reacting liquid temperature is down to 0 DEG C to 4 DEG C,

3rd step, micro-filtration is except visible precipitate thing: pass in the first cryogenic sterile tank 2 and continue to pass into argon and carry out positive pressure protection, in the cooling jacket of micro-filtration 6 and the first cryogenic sterile tank 2, pass into 0 DEG C to 4 DEG C refrigerant circulation the temperature of the solution entered in micro-filtration 6 and the first cryogenic sterile tank 2 is down to 0 DEG C to 4 DEG C, start peristaltic pump 27, open the control valve on the first feed-stock pipeline 9, reactant liquor is sent into micro-filtration 6, in the cooling jacket of micro-filtration 6, pass into 0 DEG C to 4 DEG C refrigerant circulation to lower the temperature simultaneously, after micro-filtration 6, the reactant liquor through micro-filtration 6 is delivered to the first cryogenic sterile tank 2, the pH value controlling the reactant liquor in the first cryogenic sterile tank 2 is 6.5 to 7.0, start the agitating device 8 of the first cryogenic sterile tank 2 simultaneously and in the cooling jacket of the first cryogenic sterile tank 2, pass into 0 DEG C to 4 DEG C refrigerant circulation lower the temperature, remain that the temperature of reactant liquor is at 0 DEG C to 4 DEG C,

4th step, ultrafiltration apparatus is except macromolecular substances: pass in the second cryogenic sterile tank 3 and continue to pass into argon and carry out positive pressure protection, in the cooling jacket of the second cryogenic sterile tank 3, pass into 0 DEG C to 4 DEG C refrigerant circulation the temperature of the solution entered in the second cryogenic sterile tank 3 is down to 0 DEG C to 4 DEG C, in the cooling jacket of ultrafiltration apparatus 7, pass into-20 DEG C to-30 DEG C coolant circulate, start reciprocating pump 28, open the control valve on the 3rd feed-stock pipeline 11, reactant liquor in first cryogenic sterile tank 2 sends into ultrafiltration apparatus 7 through reciprocating pump 28, after ultrafiltration apparatus 7, the reactant liquor through ultrafiltration apparatus 7 is delivered to the second cryogenic sterile tank 3, the pH value controlling the reactant liquor in the second cryogenic sterile tank 3 is 6.5 to 7.0, the liquid be retained down through ultrafiltration apparatus 7 sends in the first cryogenic sterile tank 2 filtration continuing to participate in ultrafiltration apparatus 7 by trapped fluid pipeloop 26, start the agitating device 5 in the second cryogenic sterile tank 3 simultaneously, in the second cryogenic sterile tank 3, add deoxidation water for injection obtain allicin solution, in the cooling jacket of the second cryogenic sterile tank, pass into 0 DEG C to 4 DEG C refrigerant circulation lower the temperature, make the temperature of allicin solution remain on 0 DEG C to 4 DEG C, in the cooling jacket of ultrafiltration apparatus, pass into-20 DEG C to-30 DEG C refrigerant circulations lower the temperature, because the heat production of ultra-filtration process is higher, with the refrigerant circulation refrigeration of-20 DEG C to-30 DEG C in the cooling jacket of ultrafiltration apparatus, allicin is avoided to decompose, ensure through the permeate of ultrafiltration apparatus simultaneously and sent ultrafiltration apparatus by the trapped fluid that ultrafiltration apparatus is retained down, temperature remains on 0 DEG C to 4 DEG C, the amount adding deoxidation water for injection in the second cryogenic sterile tank allicin injection concentration according to demand and determining, the concentration of the allicin solution obtained can be analyzed by the emptying adapter sampling on the second cryogenic sterile tank,

5th step, the preparation of allicin standard reference material or allicin injection: the preparation of allicin standard reference material: add ether by oil phase adapter 37 in cycling extraction tank 29, 0 DEG C of refrigerant circulation is passed in the cooling jacket of cycling extraction tank 29, and pass in cycling extraction tank 29 and continue to pass into argon and carry out positive pressure protection, open the control valve on cycling extraction feeding line 15, allicin solution in second cryogenic sterile tank 3 is sent in cycling extraction tank 29 through cycling extraction feeding line 15, agitating device 5 in ON cycle extractor 29, and start cycling extraction peristaltic pump 30, the mixing speed of controlled circulation extractor 29 is 80r/min to 120r/min, the circulation rate of ether is 30ml/min to 60ml/min, by ether iterative cycles in cycling extraction tank 29, the allicin in allicin solution is made fully to enter ether layer, then the ether after extraction allicin is sent into molecular distillation apparatus 16 and carried out deviating from ether by distilling feeding line 17 and namely obtain the flaxen allicin thick semisolid of grease-like and allicin standard reference material, the preparation of allicin injection: open the control valve on injection fill pipeline 14, puts into the allicin solution feeding injection filling apparatus 13 regulating concentration in the brown prefilled syringe needle tubing of 5ml and obtains allicin injection liquid.Prefilled syringe needle tubing in injection filling apparatus 13 was first full of argon before injection allicin solution, and injection filling apparatus 13 is the syringe filling and sealing machine of existing known technology, specifically can with reference to the syringe filling and sealing machine of sky above Hubei and Hunan science and technology; Completely cut off allicin injection that air allicin process units obtains for being light yellow clear liquid according to low temperature of the present invention, the content of allicin is 3mg/ml to 8mg/ml.

low temperature of the present invention completely cuts off air allicin process units and is installed on sterile workshop, ambient temperature is 0 DEG C to 4 DEG C, local cleanliness factor A level, each parts connecting tube and valve have biological safety and are easy to purification, provide reliable guarantee for producing allicin safely and efficiently.

it is isolated air that the present invention produces one of feature of the method for allicin solution, deoxidation water for injection used in course of reaction, oxygen content in water and nitrogen content are very low, low temperature is adopted to completely cut off the air allicin process units method passing into argon, the dissolved oxygen that may exist in replacing water and nitrogen; Argon (Ar, argon), colourless, tasteless noble gas, molecular weight: 39.94, in normal conditions, density is 1.784kg/m ³ , boiling point is-185.7 DEG C, than density of nitrogen 1.25 kg/m ³ high 1.4 times, use argon-degassed to be more conducive to removing, covering and isolated air, reach the object of protection allicin, eliminate allicin because there is the impact of air on stability.

it is low temperature that the present invention produces two of the feature of the method for allicin solution, this technique is closed alliin biosynthesis allicin and is adopted except 25 DEG C except allinase splits, microfiltration, ultrafiltration, extraction, the technical process such as degerming, all carry out under 0 DEG C to 4 DEG C condition, because the heat production of ultra-filtration process is higher, with the refrigerant circulation refrigeration of-20 DEG C to-30 DEG C in the cooling jacket of ultrafiltration apparatus 7, allicin is avoided to decompose.

it is prepare allicin injection liquid to have employed molecular distillation technique and cycling extraction technology that the present invention produces three of the feature of the method for allicin solution, allicin is obtained from ether extraction liquid, when extract along molecular distillation apparatus 13 cartridge heater 15 DEG C to 20 DEG C flowing time, gently, weight molecule effusion liquid level, enter gas phase displacement different, ether molecule first arrives cold plate (-25 DEG C to-30 DEG C) and is discharged, and allicin is discharged along mixed liquor, repeated multiple times operation, reach the object of isolation and identification

and adopt low temperature of the present invention to completely cut off air allicin process units and produce allicin solution and allicin injection liquid and allicin standard reference material, in device, between all devices and pipeline, connection sealing is good, continuous input argon (maintenance malleation) and refrigerant circulation refrigeration, have the effect of better isolated air and maintenance low temperature.

operative temperature that air allicin process units carries out producing is low, vacuum is high (zero load≤1Pa), heated time short (in second), separation efficiency are high to adopt low temperature of the present invention to completely cut off, the separation of suitable especially thermal sensitivity, readily oxidizable substance, keeps the physical property of natural materials.

the present invention, by the modern pharmaceutical new technique such as " allinase catalysis alliin split close biosynthesis allicin ", " microfiltration+ultrafiltration purification allicin ", " cycling extraction+molecular distillation realizes liquid-liquid separation " and " physics degerming+argon filling prepackage ", solves key equipment and Technology that biosynthesis produces the staple product such as allicin standard reference material and injection.Allinase splits and closes substrate alliin, the mild condition of biosynthesis allicin, productive rate is high, Functionality, quality and appealing design, when adopting low temperature of the present invention to completely cut off air allicin process units production allicin injection liquid and allicin reference substance, because this device connects all sealings, and aseptic process was carried out before production, argon is adopted to carry out isolated air conservation in production process, ensure that the sealed, sterile of production process, overall process ensures that the temperature of material is 0 DEG C to 4 DEG C simultaneously, this ensure that allicin is avoided because ingress of air oxidation Decomposition, avoid the decomposition of the too high allicin of temperature, so just can ensure production process allicin almost without decomposition, condition has been prepared for researching and developing serial allicin preparation.

the present invention relates to Combination application various modern new and high technology:

1, conjunction technology is split in enzyme catalysis: with the metastable alliin of physicochemical property and allinase, under mild conditions " biosynthesis " allicin.Output, purity and production cost are much better than chemical synthesis.

2, microfiltration+hyperfiltration technique purified garlic Capsaicin technology: residual a large amount of allinase in biosynthesis reactant liquor, is a kind of biological foreign preteins, must removes.Adopt the microfiltration+hyperfiltration technique of channelization both can keep the low temperature of 0 DEG C to 4 DEG C, ensure closed sterile soft, improve production efficiency, because adopt low temperature of the present invention to completely cut off air allicin process units can carry out continuous seepage simultaneously.

3, cycling extraction+molecular distillation technique: adopt conventional fractional distillation and distillation technology, decomposition cannot obtain by allicin, the present invention adopts ether cold cycle extraction allicin from aqueous solution, ether cycling extraction technology, cycling extraction tank 29 is protected by argon gas positive pressure, isolated air, and be placed in the water-bath of 0 DEG C to 4 DEG C, extraction process is in low temperature state all the time, then the diethyl ether solution molecular distillation new technique in modern age of allicin, when far below when both boiling points be separated obtain allicin, molecular distillation does not rely on the separation principle of boiling-point difference, when mixing material flows along heating cylinder, gently, weight molecule effusion liquid level, enter gas phase, due to varying in weight of different molecular, displacement is different.Thus light molecule first arrives cold plate is discharged, and weight molecule does not reach cold plate, discharges along mixed liquor.Reach the object of separating substances.Low (the temperature of heating plate: 15 DEG C to 20 DEG C of this law operative temperature.Cold plate temperature :-25 DEG C to-30 DEG C), vacuum high (zero load≤1Pa), heated time short (in second), separation efficiency be high, the separation of suitable especially thermal sensitivity, readily oxidizable substance, keep the physical property of natural materials, by the difference of the molecular tools according to allicin and ether, realize liquid-liquid separation.It does not rely on boiling-point difference to be separated.

4, physics degerming+the pre-packing technique of argon filling: it is canned that conventional ampoule or cillin bottle fill nitrogen, is unfavorable for isolated air and high temperature, adopt microfiltration physics degerming+the pre-packing technique of argon filling, thoroughly completely cut off air and taken leave of high temperature.

5, the above-mentioned various modern new and high technology of Combination application, successfully prepares and produces allicin standard reference material and allicin injection liquid.

the present invention is adopted to produce allicin, by " allinase catalysis alliin splits and closes biosynthesis allicin ", " microfiltration and ultrafiltration purification allicin ", the modern pharmaceutical new technique such as " cycling extraction and molecular distillation realize Liquid liquid Separation " and " physics is degerming to be pre-installed with argon filling ", effectively isolated air, reduce the temperature of biosynthesis allicin, allicin is avoided to decompose, make the mild condition of biosynthesis allicin, productive rate is high, Functionality, quality and appealing design, and low temperature of the present invention completely cuts off the suitable especially thermal sensitivity of air allicin process units, the separation of readily oxidizable substance, the physical property of effective maintenance natural materials.

it is isolated air that the present invention produces one of feature of the method for allicin solution, deoxidation water for injection used in course of reaction, and oxygen content and nitrogen content are very low, adopts the method passing into argon, the dissolved oxygen that may exist in replacing water and nitrogen; Argon (Ar, argon), colourless, tasteless noble gas, molecular weight: 39.94, in normal conditions, density is 1.784kg/m ³ , boiling point is-185.7 DEG C, than density of nitrogen 1.25 kg/m ³ high 1.4 times, use argon-degassed to be more conducive to removing, covering and isolated air, reach the object of protection allicin, eliminate allicin because there is the impact of air on stability.

it is low temperature that the present invention produces two of the feature of the method for allicin solution, this technique is closed alliin biosynthesis allicin and is adopted except 25 DEG C except allinase splits, microfiltration, extraction, the technical process such as degerming, all carry out under 0 DEG C to 4 DEG C condition, because the heat production of ultra-filtration process is higher, with the refrigerant circulation refrigeration of-20 DEG C to-30 DEG C in the interlayer of ultrafiltration apparatus, allicin is avoided to decompose.

it is prepare allicin injection liquid to have employed molecular distillation technique and cycling extraction technology that the present invention produces three of the feature of the method for allicin solution, allicin is obtained from ether extraction liquid, when extract flows along cartridge heater 15 DEG C to 20 DEG C, gently, weight molecule effusion liquid level, the displacement entering gas phase is different, ether molecule first arrives cold plate (-25 DEG C to-30 DEG C) and is discharged, and allicin is discharged along mixed liquor, repeated multiple times operation, reach the object of isolation and identification, the inventive method operative temperature is low, vacuum high (zero load≤1Pa), heated time short (in second), separation efficiency is high, suitable especially thermal sensitivity, the separation of readily oxidizable substance, keep the physical property of natural materials.

and adopt low temperature to completely cut off air allicin process units and produce allicin solution and allicin injection liquid and allicin standard reference material, in device, between all devices and official road, connection sealing is good, continuous input argon (maintenance malleation) and refrigerant circulation refrigeration, have the effect of better isolated air and maintenance low temperature.

the present invention, by the modern pharmaceutical new technique such as " allinase catalysis alliin split close biosynthesis allicin ", " microfiltration+ultrafiltration purification allicin ", " cycling extraction+molecular distillation realizes liquid-liquid separation " and " physics degerming+argon filling prepackage ", solves key equipment and Technology that biosynthesis produces the staple product such as allicin standard reference material and injection.Allinase splits and closes substrate alliin, the mild condition of biosynthesis allicin, productive rate is high, Functionality, quality and appealing design, when adopting low temperature of the present invention to completely cut off air allicin process units production allicin injection liquid and allicin reference substance, because this device connects all sealings, and aseptic process was carried out before production, argon is adopted to carry out isolated air conservation in production process, ensure that the sealed, sterile of production process, overall process ensures that the temperature of material is 0 DEG C to 4 DEG C simultaneously, this avoid allicin because ingress of air and/or the too high oxidation Decomposition caused of ambient temperature, so just can ensure production process allicin almost without decomposition, condition has been prepared for researching and developing serial allicin preparation.

" allinase/alliin biosynthesis allicin and the low temperature preparing allicin injection completely cut off air allicin process units and production Technology ".Relate to Combination application various modern new and high technology:

1, conjunction technology is split in enzyme catalysis: with the metastable alliin of physicochemical property and allinase, under mild conditions " biosynthesis " allicin.Output, purity and production cost are much better than chemical synthesis.

2, microfiltration+hyperfiltration technique purified garlic Capsaicin technology: residual a large amount of allinase in biosynthesis reactant liquor, is a kind of biological foreign preteins, must removes.Adopt the microfiltration+hyperfiltration technique of channelization both can keep the low temperature of 0 DEG C to 4 DEG C, ensure closed sterile soft, improve production efficiency, because adopt low temperature of the present invention to completely cut off air allicin process units can carry out continuous seepage simultaneously.

3, cycling extraction+molecular distillation technique: adopt conventional fractional distillation and distillation technology, decomposition cannot obtain by allicin.The present invention adopts ether cold cycle extraction allicin from aqueous solution, ether cycling extraction technology, cycling extraction tank 29 is protected by argon gas positive pressure, isolated air, and be placed in the water-bath of 0 DEG C to 4 DEG C, extraction process is in low temperature state all the time, then the diethyl ether solution molecular distillation new technique in modern age of allicin, when far below when both boiling points be separated obtain allicin, molecular distillation does not rely on the separation principle of boiling-point difference, when mixing material flows along heating cylinder, gently, weight molecule effusion liquid level, enter gas phase, due to varying in weight of different molecular, displacement is different, thus light molecule first arrives cold plate is discharged, and weight molecule does not reach cold plate, discharge along mixed liquor, reach the object of separating substances.Low (the temperature of heating plate: 15 DEG C to 20 DEG C of this law operative temperature.Cold plate temperature :-25 DEG C to-30 DEG C), vacuum high (zero load≤1Pa), heated time short (in second), separation efficiency be high, the separation of suitable especially thermal sensitivity, readily oxidizable substance, keeps the physical property of natural materials.By the difference of the molecular tools according to allicin and ether, realizing liquid--liquid is separated, and it does not rely on boiling-point difference to be separated.

4, physics degerming+the pre-packing technique of argon filling: it is canned that conventional peace heavy rain or cillin bottle fill nitrogen, is unfavorable for isolated air and high temperature.Adopt microfiltration physics degerming+the pre-packing technique of argon filling, thoroughly completely cut off air and taken leave of high temperature.

5, the above-mentioned various modern new and high technology of Combination application, successfully prepare and produce allicin standard reference material and allicin injection liquid, allicin injection that air allicin process units obtains is completely cut off for being yellow clear liquid according to low temperature of the present invention, the content of allicin is 3mg/ml to 8mg/ml, completely cuts off according to low temperature of the present invention allicin standard reference material purity>=90% that air allicin process units obtains.

the present invention is by " allinase catalysis alliin splits and closes biosynthesis allicin ", " microfiltration and ultrafiltration purification allicin ", the modern pharmaceutical new technique such as " cycling extraction and molecular distillation realize Liquid liquid Separation " and " physics is degerming to be pre-installed with argon filling " produces allicin solution, allicin injection liquid and allicin reference substance, effectively isolated air, reduce the temperature of biosynthesis allicin, allicin is avoided to decompose, make the mild condition of biosynthesis allicin, productive rate is high, Functionality, quality and appealing design, production process simple and effective, and low temperature of the present invention completely cuts off the suitable especially thermal sensitivity of air allicin process units, the separation of readily oxidizable substance, the physical property of effective maintenance natural materials.

above technical characteristic constitutes embodiments of the invention, and it has stronger adaptability and implementation result, can increase and decrease non-essential technical characteristic according to actual needs, meet the demand of different situations.

Claims (10)

1. an allicin solution, is characterized in that obtaining as follows: the first step, prepares the deoxidation water for injection that oxygen content is less than 2ppm; Second step, according to deoxidation water for injection: allinase: the mass ratio of alliin is that deoxidation water for injection, allinase and alliin mix by the ratio of 57:1:1 to 57:3:1 at temperature is 25 DEG C, the pH value controlling solution is 6.5 to 7.0, be stirred to split under 30rmp to 100rmp stir speed (S.S.) and close reaction and complete and obtain reactant liquor, then reacting liquid temperature is down to 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion; 3rd step; first by the visible precipitate thing of reactant liquor in micro-filtration removing reactant liquor; then reactant liquor is obtained allicin solution after the macromolecular substances in ultrafiltration apparatus removing mixed solution; all the time the temperature of reactant liquor is remained on 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion.

2. allicin solution according to claim 1, it is characterized in that allicin solution to process further to obtain allicin injection liquid: the concentration first measuring allicin solution, then according to the concentration of required allicin injection, the deoxidation water for injection of aequum is added in allicin solution, allicin injection is obtained after mix homogeneously, the pH value controlling allicin solution is 6.5 to 7.0, allicin injection is sent in injection filling apparatus threading prefilled syringe needle tubing and obtain allicin injection liquid, in this operating process, remain that the temperature of allicin solution and allicin injection is 0 DEG C to 4 DEG C, and operating process all the time with argon carry out positive pressure protection all the time with air exclusion, or/and, allicin solution is processed further and obtains allicin reference substance: with ether, iterative cycles extraction is carried out to allicin solution, after having extracted, get ether layer and carry out molecular distillation, molecular distillation condition: control sample introduction flow velocity is 2 ml/min to 10 ml/min, scraper velocity is 40 r/min to 70 r/min, chilling temperature is 5 DEG C to-15 DEG C, vacuum is 0.08 torr to 1 torr, obtains the flaxen allicin thick semisolid of grease-like and allicin standard reference material after molecular distillation completes.

3. a production method for allicin solution, is characterized in that carrying out in the steps below: the first step, prepares the deoxidation water for injection that oxygen content is less than 2ppm; Second step, according to deoxidation water for injection: allinase: the mass ratio of alliin is that deoxidation water for injection, allinase and alliin mix by the ratio of 57:1:1 to 57:3:1 at temperature is 25 DEG C, the pH value controlling solution is 6.5 to 7.0, be stirred to split under 30rmp to 100rmp stir speed (S.S.) and close reaction and complete and obtain reactant liquor, then reacting liquid temperature is down to 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion; 3rd step; first by the visible precipitate thing of reactant liquor in micro-filtration removing reactant liquor; then reactant liquor is obtained allicin solution after the macromolecular substances in ultrafiltration apparatus removing mixed solution; all the time the temperature of reactant liquor is remained on 0 DEG C to 4 DEG C, this step operating process argon carry out positive pressure protection all the time with air exclusion.

4. the production method of allicin solution according to claim 3, it is characterized in that allicin solution to process further to obtain allicin injection liquid: the concentration first measuring allicin solution, then according to the concentration of required allicin injection, the deoxidation water for injection of aequum is added in allicin solution, allicin injection is obtained after mix homogeneously, the pH value controlling allicin solution is 6.5 to 7.0, allicin injection is sent in injection filling apparatus threading prefilled syringe needle tubing and obtain allicin injection liquid, in this operating process, remain that the temperature of allicin solution and allicin injection is 0 DEG C to 4 DEG C, and operating process all the time with argon carry out positive pressure protection all the time with air exclusion, or/and, allicin solution is processed further and obtains allicin reference substance: with ether, iterative cycles extraction is carried out to allicin solution, after having extracted, get ether layer and carry out molecular distillation, molecular distillation condition: control sample introduction flow velocity is 2 ml/min to 10 ml/min, scraper velocity is 40 r/min to 70 r/min, chilling temperature is 5 DEG C to-15 DEG C, vacuum is 0.08 torr to 1 torr, obtains the flaxen allicin thick semisolid of grease-like and allicin standard reference material after molecular distillation completes.

5. the production method of allicin solution according to claim 4, characterized by further comprising low temperature and completely cut off air allicin process units, this low temperature completely cuts off air allicin process units and comprises retort, the first cryogenic sterile tank, the second cryogenic sterile tank, micro-filtration, ultrafiltration apparatus, cycling extraction device, injection filling apparatus, molecular distillation apparatus and deoxidation water pot, retort, first cryogenic sterile tank, agitating device is installed with respectively, retort in second cryogenic sterile tank and deoxidation water pot, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration, ultrafiltration apparatus, all there is cooling jacket the outside of cycling extraction device, bottom retort discharging opening and retaining between side of micro-filtration be installed with the first feed-stock pipeline, micro-filtration be installed with the second feed-stock pipeline through between side and the charging aperture of the first cryogenic sterile tank, discharging opening and the retaining between side of ultrafiltration apparatus of the first cryogenic sterile tank are installed with the 3rd feed-stock pipeline, ultrafiltration apparatus be installed with the 4th feed-stock pipeline through between side and the charging aperture of the second cryogenic sterile tank, the discharging opening of the second cryogenic sterile tank and be installed with injection fill pipeline and cycling extraction feeding line between injection filling apparatus and cycling extraction device respectively, distillation feeding line is installed with between cycling extraction device and molecular distillation apparatus, molecular distillation apparatus is installed with out sample pipeline, the upper end of deoxidation water pot is installed with to be taken over into water, the bottom of deoxidation water pot is installed with outfall sewer, outfall sewer and retort, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration retain side, ultrafiltration apparatus retain side, be installed with water inlet pipe respectively between cycling extraction device and molecular distillation apparatus, micro-filtration be installed with cleaning discharge nozzle respectively through on side, deoxidation water pot through side and ultrafiltration apparatus, retort, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration retain side, ultrafiltration apparatus retain side, injection filling apparatus, cycling extraction device and molecular distillation apparatus are respectively arranged with argon adapter, deoxidation water pot, retort, first cryogenic sterile tank, the inner of the argon adapter of the second cryogenic sterile tank and cycling extraction device lays respectively at deoxidation water pot, retort, first cryogenic sterile tank, the bottom of the second cryogenic sterile tank and cycling extraction device, at deoxidation water pot, retort, first cryogenic sterile tank, second cryogenic sterile tank, micro-filtration through side, ultrafiltration apparatus through side, injection filling apparatus, the upper end of cycling extraction device and molecular distillation apparatus is respectively arranged with emptying adapter, upper end and the retaining between side of ultrafiltration apparatus of the first cryogenic sterile tank are installed with trapped fluid pipeloop, first feed-stock pipeline is installed with peristaltic pump, the 3rd feed-stock pipeline is installed with reciprocating pump.

6. the production method of allicin solution according to claim 5, it is characterized in that cycling extraction device comprises cycling extraction tank and cycling extraction peristaltic pump, the external stability of cycling extraction tank is provided with cooling jacket, in cycling extraction tank, agitating device is installed, connection tube is installed with in the upper end of cycling extraction tank, lower connection tube is installed with in the lower end of cycling extraction tank, be arranged in top inner chamber and lower lumen that the upper connection tube of cycling extraction tank inside and lower connection tube are vertically arranged on cycling extraction tank respectively, cycling extraction peristaltic pump is installed with between upper connection tube in cycling extraction tank outside and lower connection tube, the upper end of the lower end and lower connection tube that are positioned at the upper connection tube of cycling extraction tank inside is installed with sintered glass funnel respectively, cycling extraction feeding line is installed with between the discharging opening of the second cryogenic sterile tank and the upper end of cycling extraction tank, lower connection tube is installed with circulation control valve, lower connection tube between circulation control valve to cycling extraction tank lower end is installed with distillation feeding line, water inlet pipe is installed with between outfall sewer and cycling extraction tank, distillation feeding line is installed with oil plant control valve, the upper end of cycling extraction tank is respectively arranged with oil phase adapter, argon adapter and emptying adapter, the inner of the argon adapter of cycling extraction tank is positioned at the bottom of the inner chamber of cycling extraction tank, oil phase adapter is installed with oil phase control valve.

7. the production method of allicin solution according to claim 6, characterized by further comprising the first refrigerant tank, second refrigerant tank, the liquid outlet of the first refrigerant tank respectively with retort, first cryogenic sterile tank, the cooling jacket of the second cryogenic sterile tank and micro-filtration is chained together by the first coolant pipeline, the first coolant liquid back pipe line is installed with between the cooling jacket of micro-filtration and the inlet of the first refrigerant tank, the second coolant pipeline is installed with between the inlet of the liquid outlet of the second refrigerant tank and the cooling jacket of ultrafiltration apparatus, the second coolant liquid back pipe line is installed with between the liquid outlet of ultrafiltration apparatus external refrigeration chuck and the inlet of the second refrigerant tank, the first coolant pipeline of liquid outlet respectively and between retort of the first refrigerant tank, the first coolant pipeline between retort and the first cryogenic sterile tank, the first coolant pipeline between first cryogenic sterile tank and the second cryogenic sterile tank, the first coolant pipeline between second cryogenic sterile tank and micro-filtration, first coolant liquid back pipe line, second coolant pipeline and the second coolant liquid back pipe line are installed with control valve respectively, or, also comprise the first refrigerant tank, second refrigerant tank, the liquid outlet of the first refrigerant tank is installed with coolant fluid house steward, the inlet of the first refrigerant tank is installed with coolant and returns liquid house steward, coolant fluid house steward and retort, first cryogenic sterile tank, second cryogenic sterile tank, coolant feed liquor arm is installed with respectively between the cooling jacket import of micro-filtration and cycling extraction tank, retort, first cryogenic sterile tank, second cryogenic sterile tank, the cooling jacket outlet of micro-filtration and cycling extraction tank and coolant return and are installed with coolant respectively between liquid house steward and return liquid arm, the second coolant pipeline is installed with between the inlet of the liquid outlet of the second refrigerant tank and the cooling jacket of ultrafiltration apparatus, the second coolant liquid back pipe line is installed with between the liquid outlet of ultrafiltration apparatus external refrigeration chuck and the inlet of the second refrigerant tank, every bar coolant feed liquor arm and every bar coolant liquid back pipe line are installed with control valve respectively, second coolant pipeline and the second coolant liquid back pipe line are installed with control valve respectively, or/and, deoxidation water pot, retort, the first cryogenic sterile tank, the second cryogenic sterile tank and cycling extraction tank are installed with temperature monitoring respectively.

8. the production method of allicin solution according to claim 7, characterized by further comprising argon bottle, argon bottle is installed with gas transmission main, gas transmission main and each argon are installed with gas transmission arm between taking over respectively, gas transmission main near argon bottle outlet fixedly mounts limited valve, effusion meter and depurator respectively, every bar gas transmission arm is all installed with control valve.

9. the production method of the allicin solution according to claim 5 or 6 or 7 or 8, is characterized in that the port of export of the argon adapter in deoxidation water pot is installed with allotter.

10. the production method of the allicin solution according to claim 5 or 6 or 7 or 8 or 9, it is characterized in that every bar water inlet pipe is installed with control valve, the first feed-stock pipeline between retort and peristaltic pump is installed with control valve, second feed-stock pipeline is installed with control valve, the 3rd feed-stock pipeline between the first cryogenic sterile tank and reciprocating pump is installed with control valve, injection fill pipeline and cycling extraction feeding line are installed with control valve respectively; Or/and the microfiltration scope that micro-filtration adopts is 0.1 μm to 1.0 μm, the ultrafiltration range that ultrafiltration apparatus adopts is 500D to 5000D; Or/and, retort, the first cryogenic sterile tank and the second cryogenic sterile tank are installed with pH monitor respectively.