A kind of method of producing the glucose for injection bulk drug with rice
Technical field
The invention belongs to the medical medicine production technical field, particularly relate to a kind of method of producing the glucose for injection bulk drug with rice.
Background technology
Used glucose for injection adopts the W-Gum preparation, and Japan prepares glucose for injection with cassava.Starch rice was only processed edible glucose, did not also process the report of glucose for injection at present.It is few to contain albumen in the corn starch liquid, and the starch particle diameter is big.Reach 7.0~10.0% and rice contains albumen, the little and starch of starch particle diameter becomes reticulated structure closely with protein binding.The gelatinization point of starch small grain size decision starch influences the liquefaction of starch.The corn starch pasting temperature is low, liquefaction easily, and the Starch rice particle diameter is little, gelatinization point is higher, reaches 85 ℃, and tight with protein binding, is difficult for liquefaction.DE reaches more than 98% behind the W-Gum liquefying-saccharifying, and is difficult to thoroughly after the Starch rice liquefaction, saccharification, and impurity is many, processes very difficulty of glucose for injection.Therefore, use rice to prepare the technical barrier that the glucose for injection medicine is present medical preparation field.
Summary of the invention
To the problems referred to above, the purpose of this invention is to provide a kind of method of producing the glucose for injection bulk drug with rice.
A kind of method with rice production glucose for injection bulk drug of the present invention comprises the steps:
(1), soak defibrination: after rice washing totally, be soaked in water 2-4 hour, with the emery wheel mill, the defibrination fineness is more than 60 orders then;
(2), size mixing: the Rice & peanut milk to grinding adds water; Regulating concentration is 17-19Be °; With soda ash or hydrochloric acid the pH value of Rice & peanut milk is adjusted to 5.6-5.8; The ratio that adds high temperature resistant AMS 400-500ml in the weight of the dry-matter per ton of Rice & peanut milk the inside adds AMS in Rice & peanut milk, stirs and send into the transfer jar that liquefies after 30 minutes;
(3), slag is taken off in liquefaction: the Rice & peanut milk that enters into liquefaction transfer jar is delivered to high-pressure injector with the liquefaction squirt pump and is once sprayed; The feed temperature that ejects is 105-110 ℃; Get into that pressurize was kept jar pressurize 5 minutes and after temperature drops to 95 ℃; Get into liquefaction streamline column continuously, the control laminar flow time is 90-120 minute; Then, the feed liquid behind the laminar flow is carried out the DE value detect, be 15%-20% when detecting DE value, and after iodine examination reaction is brown or iodine liquid true qualities, carry out second spraying with high-pressure injector again, the feed temperature that ejects is 125-130 ℃; Get into the transfer jar through gas-liquid separator then, cool to 90-100 ℃ through the spiral coil cooling tube water flowing after, adopt plate filter to filter and take off slag;
(4), saccharification: feed liquid behind the slag is taken off in liquefaction is cooled to 58-62 ℃ and delivers to saccharifying tank, with the salt acid for adjusting pH value to 4.0-4.4, through concentration and the volume of measuring every jar of feed liquid; Calculate the weight of dry-matter in every jar of feed liquid; Add the 700ml compounded saccharifying enzyme by dry-matter per ton, saccharification 40-60 hour, after content >=96% that detects glucose in the qualified and feed liquid of dextrin reaction; Be warming up to 80-85 ℃ with injector, the enzyme discharging of going out; If the dextrin reaction is defective, should adds saccharifying enzyme or prolong saccharification time, to the discharging of the qualified ability of dextrin reaction;
(5), decolorization filtering, a secondary decolourization filter: after one time bleacher receives the sugar material in the saccharifying tank, use hydrochloric acid or soda ash to regulate the pH value and be 4.4-4.8, temperature is controlled at 80-90 ℃; The ratio that adds 3 ㎏ craboraffins in dry-matter per ton in the sugar material adds craboraffin in the sugar material; Stirred 30 minutes, and filtered with plate filter, filtrating is back to as clear as crystal can sending into and carries out the secondary decolourization filtration in the secondary decolourization jar; Method is with a decolorization filtering; Be that secondary decolourization filters the airtight filter filtration of employing, as clear as crystal, the no foreign matter of filtrating, the visible impurity of no naked eyes can be delivered in the preceding basin of IX and carry out IX;
(6), IX: adopt sun-male-female IX pattern,, make the feed liquid quality reach following requirement: water white transparency, free from extraneous odour through regulating positive post and control IX flow; Transparence>=95%; Specific conductivity≤30 μ s/ ㎝; PH value 3.8-4.4; Check no calcium salt, molysite≤15ppm;
(7), concentrated refining: after the IX; Use the falling film type quadruple effect evaporator that liquid glucose is concentrated to concentration and be 71%-72%; Deliver in three bleachers and add gac stirring decolouring 30 minutes; Filter with the closed filter,, deliver to the preceding transfer jar of crystallization to the clean no foreign matter of filtrating, no carbon granules, form and aspect≤1#;
(8), primary crystallization:
Charging: before the charging, thoroughly clean crystallizer, and to crystallizer with the steam high-temperature sterilization after 30-50 minute; Naturally cooling is subsequent use, after liquid glucose is cooled to 45-50 ℃ with plate-type heat exchanger in the transfer jar, is fed to 30% of crystallizer volume for the first time; Jar is interior as no crystal seed, and 4% adding finished product glucose powder by the dry matter weight in the liquid glucose that gets into keeps 45 ℃ of temperature and keeps 12 hours growing the grains; Crystal seed is sent into liquid glucose for the second time crystallizer is filled after cultivating well; It is crystal seed that continuous production stays the sugar of crystallizer volume 30 ﹪ at every turn;
Crystallization: after the crystallizer liquid glucose is filled, begin to stir 0.6 rev/min of rotating speed; Stir more than 4 hours, crystallization time 48-60 hour, press the crystallization curve cooling; The crystallization crystal that finally obtains is sticking to be stirred, it is obvious to pinch granular sensation with hand, cool the temperature to 27 ℃ after, can discharging;
(9), once centrifugal: before the primary crystallization discharging; Earlier stir cage, whizzer distribution trough, whizzer special column, affination waterpipe, whizzer hopper with the discharging of sterile distilled water wash clean; Begin centrifugally then, obtain the tide sugar that moisture content in the crystal is lower than crystal weight 14% after centrifugal;
(10), dissolve sugar: the tide sugar that will be centrifugal goes out is delivered to molten sugar bowl with stirring cage, and adding distil water dissolves, and obtains the dense sugar of concentration 72-73% after the dissolving, and adjusting pH value is 4.0-4.2, delivers to bleacher again;
(11), dense sugar decolouring: add activated carbon decolorizing by 2% of glucose weight in the dense sugar during decolouring; Bleaching temperature 80-85 ℃; Decolouring pH value is: 4.0-4.2, and the decolouring churning time is more than 30 minutes, filters with plate filter again; Totally do not have foreign matter, no carbon granules until dense sugar, deliver to crystallization transfer jar;
(12), secondary cane sugar boiling and crystal: the dense sugar after will decolouring is delivered to the high temperature boiling pan, and vacuum tightness is 0.011-0.02Mpa, boils sugared temperature 70-80 ℃, and pH value: 3.5-4.5 boiled sugar time 2-3 hour;
(13), secondary centrifuging: working method is with once centrifugal, centrifugal after, the moisture content in the damp sugar≤5%;
(14), oven dry: adopt fluidised bed drying, hot blast temperature 90-95 ℃, cold wind temperature≤24 ℃, discharging Icing Sugar temperature≤27 ℃, moisture content in the Icing Sugar≤1% gets final product;
(15), packing: in 100,000 grades of control areas, adopt device of full automatic packaging, packing bag is two-layer, and internal layer is a polyethylene bag, and outer is multiple film woven bag, and every bag of net weight is 25kg.
The present invention has following advantage:
1. adopt crystallization processes twice, quality is high, and filtration velocity is fast, and each item quality index all is higher than 2010 editions " Chinese pharmacopoeia quality standards;
2. be that raw material solves the problem that south (no W-Gum production line) production injectable dextrose monohydrate does not have raw material with the rice, filled up the blank that southern crystalline dextrose is produced, product has regional superiority on selling;
3. the crystalline dextrose absorbent properties hypoallergenic that uses rice to go out as raw material production, biological value is high;
4. adopt Ye Huamei of new generation and saccharifying enzyme, significantly improved saccharification purity, adopt alkaline soak, high-temperature injection and high temperature cane sugar boiling and crystal successfully to solve breeding fermentation problem in the production process.Increase dense sugar and filter, improved final product quality greatly, guaranteed the clarity of product, filtration velocity is made into and loses liquid and improved lamp inspection qualification rate.Adopt twice injection, twice enzyme-added, effectively controlled liquefaction DE value, guaranteed that liquefaction iodine examination reaction is qualified, and the reaction of saccharification dextrin is qualified.Adopt the novel vertical crystallizer, can continuously feeding, discharging continuously stops and finishes the microbiological contamination of trichite ferment, can ensure the quality of products, and guarantees continuous production.
Embodiment
Following embodiment can illustrate in greater detail the present invention, but does not limit the present invention in any form.
Embodiment 1: this drops into 100 tons in rice.
(1), soak defibrination: after rice washing totally, be soaked in water 2-4 hour, with the emery wheel mill, the defibrination fineness is more than 60 orders then;
(2), size mixing: the Rice & peanut milk to grinding adds water; Regulating concentration is 17-19Be °; With soda ash or hydrochloric acid the pH value of Rice & peanut milk is adjusted to 5.6-5.8; The ratio that adds high temperature resistant AMS 400-500ml in the weight of the dry-matter per ton of Rice & peanut milk the inside adds AMS in Rice & peanut milk, stirs and send into the transfer jar that liquefies after 30 minutes;
(3), slag is taken off in liquefaction: the Rice & peanut milk that enters into liquefaction transfer jar is delivered to high-pressure injector with the liquefaction squirt pump and is once sprayed; The feed temperature that ejects is 105-110 ℃; Get into that pressurize was kept jar pressurize 5 minutes and after temperature drops to 95 ℃; Get into liquefaction streamline column continuously, the control laminar flow time is 90-120 minute; Then, the feed liquid behind the laminar flow is carried out the DE value detect, be 15%-20% when detecting DE value, and after iodine examination reaction is brown or iodine liquid true qualities, carry out second spraying with high-pressure injector again, the feed temperature that ejects is 125-130 ℃; Get into the transfer jar through gas-liquid separator then, cool to 90-100 ℃ through the spiral coil cooling tube water flowing after, adopt plate filter to filter and take off slag;
(4), saccharification: feed liquid behind the slag is taken off in liquefaction is cooled to 58-62 ℃ and delivers to saccharifying tank, with the salt acid for adjusting pH value to 4.0-4.4, through concentration and the volume of measuring every jar of feed liquid; Calculate the weight of dry-matter in every jar of feed liquid; Add the 700ml compounded saccharifying enzyme by dry-matter per ton, saccharification 40-60 hour, after content >=96% that detects glucose in the qualified and feed liquid of dextrin reaction; Be warming up to 80-85 ℃ with injector, the enzyme discharging of going out; If the dextrin reaction is defective, should adds saccharifying enzyme or prolong saccharification time, to the discharging of the qualified ability of dextrin reaction;
(5), decolorization filtering, a secondary decolourization filter: after one time bleacher receives the sugar material in the saccharifying tank, use hydrochloric acid or soda ash to regulate the pH value and be 4.4-4.8, temperature is controlled at 80-90 ℃; The ratio that adds 3 ㎏ craboraffins in dry-matter per ton in the sugar material adds craboraffin in the sugar material; Stirred 30 minutes, and filtered with plate filter, filtrating is back to as clear as crystal can sending into and carries out the secondary decolourization filtration in the secondary decolourization jar; Method is with a decolorization filtering; Be that secondary decolourization filters the airtight filter filtration of employing, as clear as crystal, the no foreign matter of filtrating, the visible impurity of no naked eyes can be delivered in the preceding basin of IX and carry out IX;
(6), IX: adopt sun-male-female IX pattern,, make the feed liquid quality reach following requirement: water white transparency, free from extraneous odour through regulating positive post and control IX flow; Transparence>=95%; Specific conductivity≤30 μ s/ ㎝; PH value 3.8-4.4; Check no calcium salt, molysite≤15ppm;
(7), concentrated refining: after the IX; Use the falling film type quadruple effect evaporator that liquid glucose is concentrated to concentration and be 71%-72%; Deliver in three bleachers and add gac stirring decolouring 30 minutes; Filter with the closed filter,, deliver to the preceding transfer jar of crystallization to the clean no foreign matter of filtrating, no carbon granules, form and aspect≤1#;
(8), primary crystallization:
Charging: before the charging, thoroughly clean crystallizer, and to crystallizer with the steam high-temperature sterilization after 30-50 minute; Naturally cooling is subsequent use, after liquid glucose is cooled to 45-50 ℃ with plate-type heat exchanger in the transfer jar, is fed to 30% of crystallizer volume for the first time; Jar is interior as no crystal seed, and 4% adding finished product glucose powder by the dry matter weight in the liquid glucose that gets into keeps 45 ℃ of temperature and keeps 12 hours growing the grains; Crystal seed is sent into liquid glucose for the second time crystallizer is filled after cultivating well; It is crystal seed that continuous production stays the sugar of crystallizer volume 30 ﹪ at every turn;
Crystallization: after the crystallizer liquid glucose is filled, begin to stir 0.6 rev/min of rotating speed; Stir more than 4 hours, crystallization time 48-60 hour, press the crystallization curve cooling; The crystallization crystal that finally obtains is sticking to be stirred, it is obvious to pinch granular sensation with hand, cool the temperature to 27 ℃ after, can discharging;
(9), once centrifugal: before the primary crystallization discharging; Earlier stir cage, whizzer distribution trough, whizzer special column, affination waterpipe, whizzer hopper with the discharging of sterile distilled water wash clean; Begin centrifugally then, obtain the tide sugar that moisture content in the crystal is lower than crystal weight 14% after centrifugal;
(10), dissolve sugar: the tide sugar that will be centrifugal goes out is delivered to molten sugar bowl with stirring cage, and adding distil water dissolves, and obtains the dense sugar of concentration 72-73% after the dissolving, and adjusting pH value is 4.0-4.2, delivers to bleacher again;
(11), dense sugar decolouring: add activated carbon decolorizing by 2% of glucose weight in the dense sugar during decolouring; Bleaching temperature 80-85 ℃; Decolouring pH value is: 4.0-4.2, and the decolouring churning time is more than 30 minutes, filters with plate filter again; Totally do not have foreign matter, no carbon granules until dense sugar, deliver to crystallization transfer jar;
(12), secondary cane sugar boiling and crystal: the dense sugar after will decolouring is delivered to the high temperature boiling pan, and vacuum tightness is 0.011-0.02Mpa, boils sugared temperature 70-80 ℃, and pH value: 3.5-4.5 boiled sugar time 2-3 hour;
(13), secondary centrifuging: working method is with once centrifugal, centrifugal after, the moisture content in the damp sugar≤5%;
(14), oven dry: adopt fluidised bed drying, hot blast temperature 90-95 ℃, cold wind temperature≤24 ℃, discharging Icing Sugar temperature≤27 ℃, moisture content in the Icing Sugar≤1% gets final product;
(15), packing: in 100,000 grades of control areas, adopt device of full automatic packaging, packing bag is two-layer, and internal layer is a polyethylene bag, and outer is multiple film woven bag, and every bag of net weight is 25kg.
This actual production result: throw 100 tons of rice amounts, produce 65 tons of Icing Sugar, produce 30 tons in mother liquor (50% concentration), 10 tons in production feedstuff protein powder, the Icing Sugar quality is by " second injectable dextrose monohydrate bulk drug of Chinese pharmacopoeia detection method detects.
Use the examining report of the glucose for injection that this process method makes, like following table:
Test item |
2010 editions " Chinese Pharmacopoeia standard " |
Detected result |
Proterties |
It is sweet that colourless or white crystalline powder does not have stink |
Qualified |
Differentiate |
Should be up to specification |
Qualified |
Specific optical rotation |
+52.6°- +53.2° |
Qualified (+53.1 °) |
Acidity |
Should be up to specification |
Qualified |
The clarity of solution and color |
Should be up to specification |
Qualified (1#) |
The clarity of ethanolic soln |
Should be up to specification |
Qualified |
Muriate |
≤100ppm |
Qualified (<=30ppm) |
Vitriol |
≤0.01% |
Qualified |
Sulphite and Zulkovsky starch |
Should be up to specification |
Qualified |
Weight loss on drying |
≤1.0% |
Qualified (0.5%) |
Residue on ignition |
≤0.1% |
Qualified (0.02%) |
Protein |
Should be up to specification |
Qualified |
Barium salt |
Should be up to specification |
Qualified |
Calcium salt |
≤0.01% |
Qualified |
Molysite |
≤0.001% |
Qualified |
Heavy metal |
≤5ppm |
Qualified (1ppm) |
Arsenic salt |
≤0.0001% |
Qualified |
Microbial limit detects |
Should be up to specification |
Qualified |