CN102703547B - Method for producing glucose bulk drug for injection by using rice - Google Patents

Abstract

The invention provides a method for producing a glucose bulk drug for injection by using rice. The method comprises the following steps of: soaking and defibrination, size mixing, liquefaction and slag removal, saccharification, primary decoloration and filtration, secondary decoloration and filtration, ion exchange, concentration and refining, primary crystallization, primary centrifugation, sugar solution, sugar concentration and decoloration, secondary sugar boiling and crystallization, secondary centrifugation, drying, packaging and the like. The method has the following advantages: (1), a two-time crystallization process is adopted, the quality is high, and a filtration speed is quick; (2), the problem that a raw material for producing an injection glucose in the south does not existis solved by using the rice as the raw material, and the blank of the production of a crystalline glucose in the south is filled; (3), the crystalline glucose produced by using the rice as the raw material has low-irritability in absorption property and is high in biological value; and (4), a breeding fermentation problem in a production procedure is solved successfully, the sugar concentration and the filtration are added, the quality of a finished product is greatly improved, and the clarity and the filtration speed of the product are guaranteed. The continuous feed and the continuous discharge can be carried out; the crystallization and fermentation contamination is stopped; the quality can be guaranteed; and the continuous production is guaranteed.

Description

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 made edible glucose, did not also make 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 starch small grain size determines the gelatinization point of 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, and it is very difficult to make 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

At 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 the rice washing is clean, 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 that grinds is added 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 α-Dian Fenmei 400-500ml in the weight of the dry-matter per ton of Rice ﹠ peanut milk the inside adds α-Dian Fenmei 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 ℃, enter that pressurize was kept jar pressurize 5 minutes and after temperature drops to 95 ℃, enter continuous liquefaction streamline column, 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 ℃; Enter the transfer jar by gas-liquid separator then, cool to 90-100 ℃ by 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 be cooled to 58-62 ℃ and deliver to saccharifying tank, with the salt acid for adjusting pH value to 4.0-4.4, by 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), a decolorization filtering, secondary decolourization filters: after bleacher receives sugar material in the saccharifying tank, regulating the pH value with hydrochloric acid or soda ash is 4.4-4.8, temperature control is 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, filter with plate filter, filtrate 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, just secondary decolourization filters and adopts airtight filter to filter, filtrate is as clear as crystal, no foreign matter, the visible impurity of no naked eyes can be delivered in the preceding basin of ion-exchange and carry out ion-exchange;

(6), ion-exchange: adopt sun-male-female ion-exchange pattern, by regulating positive post and control ion-exchange flow, make the feed liquid quality reach following requirement: water white transparency, free from extraneous odour; Transparence 〉=95%; Specific conductivity≤30 μ s/ ㎝; PH value 3.8-4.4; Check no calcium salt, molysite≤15ppm;

(7), concentrated refining: after the ion-exchange, with the falling film type quadruple effect evaporator liquid glucose being concentrated to concentration is 71%-72%, deliver in three bleachers and add gac stirring decolouring 30 minutes, filter with the closed filter, totally do not have foreign matter, no carbon granules, form and aspect≤1# to filtrate, deliver to the preceding transfer jar of crystallization;

(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 standby, after liquid glucose is cooled to 45-50 ℃ with plate-type heat exchanger in the transfer jar, be fed to for the first time 30% of crystallizer volume, as no crystal seed, add the finished product glucose powder by 4% of the dry matter weight in the liquid glucose that enters in jar, keep 45 ℃ of temperature and keep 12 hours growing the grains, after crystal seed is cultivated, send into liquid glucose for the second time crystallizer is filled; It is crystal seed that the sugar of crystallizer volume 30 ﹪ is stayed in continuous production 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), molten sugar: the centrifugal tide sugar that goes out is delivered to molten sugar bowl with stirring cage, and the adding distil water dissolving 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, the decolouring churning time is more than 30 minutes, filter 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 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, the quality height, filtration velocity is fast, and every 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 in sale;

3. be the crystalline dextrose absorbent properties hypoallergenic that raw material production goes out with rice, the biological value height;

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 to produce continuously.

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 the rice washing is clean, 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 that grinds is added 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 α-Dian Fenmei 400-500ml in the weight of the dry-matter per ton of Rice ﹠ peanut milk the inside adds α-Dian Fenmei 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 ℃, enter that pressurize was kept jar pressurize 5 minutes and after temperature drops to 95 ℃, enter continuous liquefaction streamline column, 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 ℃; Enter the transfer jar by gas-liquid separator then, cool to 90-100 ℃ by 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 be cooled to 58-62 ℃ and deliver to saccharifying tank, with the salt acid for adjusting pH value to 4.0-4.4, by 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), a decolorization filtering, secondary decolourization filters: after bleacher receives sugar material in the saccharifying tank, regulating the pH value with hydrochloric acid or soda ash is 4.4-4.8, temperature control is 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, filter with plate filter, filtrate 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, just secondary decolourization filters and adopts airtight filter to filter, filtrate is as clear as crystal, no foreign matter, the visible impurity of no naked eyes can be delivered in the preceding basin of ion-exchange and carry out ion-exchange;

(6), ion-exchange: adopt sun-male-female ion-exchange pattern, by regulating positive post and control ion-exchange flow, make the feed liquid quality reach following requirement: water white transparency, free from extraneous odour; Transparence 〉=95%; Specific conductivity≤30 μ s/ ㎝; PH value 3.8-4.4; Check no calcium salt, molysite≤15ppm;

(7), concentrated refining: after the ion-exchange, with the falling film type quadruple effect evaporator liquid glucose being concentrated to concentration is 71%-72%, deliver in three bleachers and add gac stirring decolouring 30 minutes, filter with the closed filter, totally do not have foreign matter, no carbon granules, form and aspect≤1# to filtrate, deliver to the preceding transfer jar of crystallization;

(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 standby, after liquid glucose is cooled to 45-50 ℃ with plate-type heat exchanger in the transfer jar, be fed to for the first time 30% of crystallizer volume, as no crystal seed, add the finished product glucose powder by 4% of the dry matter weight in the liquid glucose that enters in jar, keep 45 ℃ of temperature and keep 12 hours growing the grains, after crystal seed is cultivated, send into liquid glucose for the second time crystallizer is filled; It is crystal seed that the sugar of crystallizer volume 30 ﹪ is stayed in continuous production 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), molten sugar: the centrifugal tide sugar that goes out is delivered to molten sugar bowl with stirring cage, and the adding distil water dissolving 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, the decolouring churning time is more than 30 minutes, filter 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 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 processing method makes, as 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

Claims (1)

1. a method of producing the glucose for injection bulk drug with rice is characterized in that, comprises the steps:

(1), soak defibrination: after the rice washing is clean, 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 that grinds is added 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 α-Dian Fenmei 400-500ml in the weight of the dry-matter per ton of Rice ﹠ peanut milk the inside adds α-Dian Fenmei 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 ℃, enter that pressurize was kept jar pressurize 5 minutes and after temperature drops to 95 ℃, enter continuous liquefaction streamline column, 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 ℃; Enter the transfer jar by gas-liquid separator then, cool to 90-100 ℃ by 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 be cooled to 58-62 ℃ and deliver to saccharifying tank, with the salt acid for adjusting pH value to 4.0-4.4, by 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), a decolorization filtering, secondary decolourization filters: after bleacher receives sugar material in the saccharifying tank, regulating the pH value with hydrochloric acid or soda ash is 4.4-4.8, temperature control is 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, filter with plate filter, filtrate 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, just secondary decolourization filters and adopts airtight filter to filter, filtrate is as clear as crystal, no foreign matter, the visible impurity of no naked eyes can be delivered in the preceding basin of ion-exchange and carry out ion-exchange;

(6), ion-exchange: adopt sun-male-female ion-exchange pattern, by regulating positive post and control ion-exchange flow, make the feed liquid quality reach following requirement: water white transparency, free from extraneous odour; Transparence 〉=95%; Specific conductivity≤30 μ s/ ㎝; PH value 3.8-4.4; Check no calcium salt, molysite≤15ppm;

(7), concentrated refining: after the ion-exchange, with the falling film type quadruple effect evaporator liquid glucose being concentrated to concentration is 71%-72%, deliver in three bleachers and add gac stirring decolouring 30 minutes, filter with the closed filter, totally do not have foreign matter, no carbon granules, form and aspect≤1# to filtrate, deliver to the preceding transfer jar of crystallization;

(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 standby, after liquid glucose is cooled to 45-50 ℃ with plate-type heat exchanger in the transfer jar, be fed to for the first time 30% of crystallizer volume, as no crystal seed, add the finished product glucose powder by 4% of the dry matter weight in the liquid glucose that enters in jar, keep 45 ℃ of temperature and keep 12 hours growing the grains, after crystal seed is cultivated, send into liquid glucose for the second time crystallizer is filled; It is crystal seed that the sugar of crystallizer volume 30 ﹪ is stayed in continuous production 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), molten sugar: the centrifugal tide sugar that goes out is delivered to molten sugar bowl with stirring cage, and the adding distil water dissolving 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, the decolouring churning time is more than 30 minutes, filter 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 polyethylene bag, and outer is multiple film woven bag, and every bag of net weight is 25kg.