CN102302768A - Method for preparing brain protein hydrolysate oral liquid - Google Patents

Abstract

The invention provides a method for preparing brain protein hydrolysate oral liquid. In the method, the optimum enzyme hydrolysis temperature is controlled by a constant-temperature automatic control system, and separation efficiency is improved by adopting a low-temperature continuous centrifugal separation technology. The method has the beneficial effects of reducing separation time, increasing yield, integrally lowering cost of the brain protein hydrolysate oral liquid and improving production efficiency so as to realize standardization, automatization and controllability, and stabilize and control quality.

Description

A kind of method for preparing the Cerebrolysin Vial oral liquid

Technical field

The invention belongs to chemical medicine field, is a kind of new technology for preparing chemical drugs.

Background technology

The Cerebrolysin Vial oral liquid is the product that ten thousand logical Pharmaceuticaies are produced, and is used for diseases such as congenital cerebral dysgenesis, central nervous system infection, alzheimer disease, craniocerebral trauma sequela, cerebrovascular trauma sequela.Its preparation method adopts the new technology of the up-to-date research and development of company.Former method is following:

Healthy Medulla sus domestica → thaw → removal of impurity → mix homogeneously → grinding → acetone defat → purified water dilution → adjust pH → mixing (enzyme) → hydrolysis → supernatant → adjust pH neutrality → deactivation → supernatant → sucking filtration separation → ultrafiltration → fill → sterilization → decals → packing → check → warehouse-in

Summary of the invention

The present invention has mainly provided a kind of new method for preparing the Cerebrolysin Vial oral liquid, and its positive beneficial effect is, and the one, reduced separation time; The 2nd, increased yield.Reduce the cost of Cerebrolysin Vial oral liquid on the whole, improved production efficiency.

Instance

Prescription:

Get refrigerated pig brain tissue and carry out nature at normal temperatures and thaw to there not being the piece of freezing basically, the pig brain tissue that will thaw takes advantage of cold and rejects bone chips, oils and fats, muscle, connective tissue, sludged blood and other impurity immediately; Clean pig brain tissue after will thawing immediately adds the purified water of 0.5 times of amount, puts and grinds to form even and fine colloid solution in the colloid mill; Then, put in the clean rustless steel container, pig brain tissue and acetone mixed solution were left standstill 0.6～1.1 hour, cerebral tissue liquid is fully separated with acetone soln; After mixed liquor leaves standstill end, draw upper strata acetone soln and emulsion layer, supply to reclaim acetone (recovery method is with reclaiming ethanol), lower floor's cerebral tissue liquid pours in the dilution trap, adds 2.5 times of amount purified water stirring and evenly mixings, dilutes; The pepsin (calculating by every gram 3800 units) of getting pig brain tissue 1% amount is earlier with the purified water immersion of 5 times of amounts 0.6～1.1 hour; (compound method: get concentrated hydrochloric acid (AR) 54ml, rare to 100ml with purified water, mixing promptly gets with 20% (W/V) hydrochloric acid solution will to dilute back pig brain tissue solution.) adjusting pH value 2.2～2.7 (measuring with accurate examination PH paper); Pepsin after soaking is joined in the pig brain tissue's solution after the dilution mix homogeneously; Enzymolysis groove bath temperature is heated to 47 ℃ ± 0.5 ℃ in advance; Regulate the constant temperature automatic control system; Keep the outer bath temperature of enzymolysis groove at 47 ℃ ± 0.5 ℃; Enzymolysis time: 15～17 hours (picking up counting when temperature reaches requirement); Whenever fully stirred once at a distance from 10 minutes during beginning; After 3～5 hours, whenever fully stirred once, accomplish until enzymolysis at a distance from 30 minutes; Measure the pH value of medicinal liquid when stirring, and medicinal liquid is remained within the scope of pH value=2.5～3, when pH value rises, regulate with 20% (W/V) hydrochloric acid solution; With the Medulla sus domestica hydrolyzed solution behind the enzymolysis, under the static condition, isolate supernatant with the method for siphon, be transferred in the preparing tank; Medicinal liquid in the preparing tank is transferred PH=7.0～7.5 with 20% sodium hydroxide solution; Above-mentioned solution is heated to rapidly boils, keep boiling; Add buffer agent after the deactivation while hot, sodium hydrogen phosphate, sodium dihydrogen phosphate, stirring and dissolving; To add the medicinal liquid behind the buffer agent, put clean rustless steel container internal cooling to room temperature; Medicinal liquid after the deactivation carries out lock out operation with the constant-temperature temperature-control centrifuge, the temperature and the centrifuge speed of adjustment centrifuge, and solution is clear and bright to centrifugal back; Above-mentioned ultra micro liquid used earlier indicate the isolated molecule amount and filter as the doughnut microfilter of 100K, uses then to indicate the isolated molecule amount and filter as the doughnut microfilter of 10K, filtrating is packed freezing keeping in the container closure of cleaning, weighs; Add purified water, sodium benzoate, mixing, fill, packing promptly gets.

Technology comparative illustration before and after improving:

1, former process using Artificial Control hydrolysis temperature has adopted constant temperature automatic controlling system enzyme hydrolysis optimum temperature, thereby has reached standardization, automatization, controlledization after the improvement, make stable and controllable for quality.Experiment contrast index is following:

2, former technology is used the sucking filtration separation method, has selected for use low temperature continuous centrifugal isolation technics to improve separation efficiency after the improvement, and medicinal liquid clarity is improved greatly, and yield increases.Low temperature continuous centrifugal isolation technics is the emerging separation that is used for genetic fragment, the deposition of pheron and the separation and preparation technology of recovery and other biological product.Its advanced technology degree reaches leading domestic.Experiment contrast index is following:

Claims (1)

1. method for preparing the Cerebrolysin Vial oral liquid, its raw material and method for preparing are following:

1) raw material:

2) method for preparing:

Get refrigerated pig brain tissue and carry out nature at normal temperatures and thaw to there not being the piece of freezing basically, the pig brain tissue that will thaw takes advantage of cold and rejects bone chips, oils and fats, muscle, connective tissue, sludged blood and other impurity immediately; Clean pig brain tissue after will thawing immediately adds the purified water of 0.5 times of amount, puts and grinds to form even and fine colloid solution in the colloid mill; Then, put in the clean rustless steel container, pig brain tissue and acetone mixed solution were left standstill 0.6～1.1 hour, cerebral tissue liquid is fully separated with acetone soln; After mixed liquor leaves standstill end, draw upper strata acetone soln and emulsion layer, supply to reclaim acetone (recovery method is with reclaiming ethanol), lower floor's cerebral tissue liquid pours in the dilution trap, adds 2.5 times of amount purified water stirring and evenly mixings, dilutes; The pepsin (calculating by every gram 3800 units) of getting pig brain tissue 1% amount is earlier with the purified water immersion of 5 times of amounts 0.6～1.1 hour; (compound method: get concentrated hydrochloric acid (AR) 54ml, rare to 100ml with purified water, mixing promptly gets with 20% (W/V) hydrochloric acid solution will to dilute back pig brain tissue solution.) adjusting pH value 2.2～2.7 (measuring with accurate examination PH paper); Pepsin after soaking is joined in the pig brain tissue's solution after the dilution mix homogeneously; Enzymolysis groove bath temperature is heated to 47 ℃ ± 0.5 ℃ in advance; Regulate the constant temperature automatic control system; Keep the outer bath temperature of enzymolysis groove at 47 ℃ ± 0.5 ℃; Enzymolysis time: 15～17 hours (picking up counting when temperature reaches requirement); Whenever fully stirred once at a distance from 10 minutes during beginning; After 3～5 hours, whenever fully stirred once, accomplish until enzymolysis at a distance from 30 minutes; Measure the pH value of medicinal liquid when stirring, and medicinal liquid is remained within the scope of pH value=2.5～3, when pH value rises, regulate with 20% (W/V) hydrochloric acid solution; With the Medulla sus domestica hydrolyzed solution behind the enzymolysis, under the static condition, isolate supernatant with the method for siphon, be transferred in the preparing tank; Medicinal liquid in the preparing tank is transferred PH=7.0～7.5 with 20% sodium hydroxide solution; Above-mentioned solution is heated to rapidly boils, keep boiling; Add buffer agent after the deactivation while hot, sodium hydrogen phosphate, sodium dihydrogen phosphate, stirring and dissolving; To add the medicinal liquid behind the buffer agent, put clean rustless steel container internal cooling to room temperature; Medicinal liquid after the deactivation carries out lock out operation with the constant-temperature temperature-control centrifuge, the temperature and the centrifuge speed of adjustment centrifuge, and solution is clear and bright to centrifugal back; Above-mentioned ultra micro liquid used earlier indicate the isolated molecule amount and filter as the doughnut microfilter of 100K, uses then to indicate the isolated molecule amount and filter as the doughnut microfilter of 10K, filtrating is packed freezing keeping in the container closure of cleaning, weighs; Add purified water, sodium benzoate, mixing, fill, packing promptly gets.