CN104511008B - A kind of Cerebrolysin Vial preparation method - Google Patents
A kind of Cerebrolysin Vial preparation method Download PDFInfo
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Abstract
The invention belongs to pharmaceutical technology field, and the invention provides a kind of preparation method of Cerebrolysin Vial, including the step of Feedstock treating, papain hydrolysis, complex enzyme for hydrolyzing, regulation pH, sterilizing and nanofiltration.Preparation method of the present invention is simple, is easy to industrialized production；Brain protein powder peptide content height is prepared by this method, vigor is high.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of preparation method of Cerebrolysin Vial.
Background technology
Cerebrolysin Vial class medicine is in recent years using one of most biochemical drugs.At home and abroad Related Research Domain and city
Occupy critical role on.Cerebrolysin Vial is living as the one kind of health, fresh animal cerebral tissue through multienzyme enzymolysis and extraction
Property brain polypeptides matter, containing a variety of human brains must the important member such as amino acid and cephalin, lecithin, peptides nerve growth factor
Element, nervous centralis, regulation and the metabolism for improving neuron can be acted in many ways, promotes the formation of cynapse, inducing neural
The differentiation of member, and further protect nerve cell from the infringement of various ischemics and neurotoxin.It can by blood-brain barrier,
Promote the synthesis of intracerebral protein, influence respiratory chain, the protective capability with anti anoxia, improve intracerebral energetic supersession, activate gland
Other Hormone systems of thuja acid cyclisation enzymatic, there is provided neurotransmitter, peptide hormone and coenzyme precursors.At present, clinically mainly adopt
Injection is made with Cerebrolysin Vial, for treat dull-witted and brain disorder, atelencephalia, encephalatrophy, neurasthenia,
Combined external head injuries, central nervous system infection, meningitis, senile dementia, depression, mental disease or cerebrovascular metabolism disorder
Etc. a variety of diseases, while it can effectively strengthen ability of learning and memory
CN200410022091.5 discloses a kind of preparation method of Cerebrolysin Vial, and the invention uses stomach by priority
The method that protease, trypsase are digested prepares Cerebrolysin Vial, this method complex procedures, and to adjust acid-base property,
The problems such as being likely to occur protein denaturation.
The content of the invention
For these reasons, applicant obtains a kind of method in research process：This method uses papain water
The step of solution, complex enzyme for hydrolyzing, regulation pH value and nanofiltration are combined, especially with a certain proportion of complex enzyme, obtains brain egg
White hydrolysate, the Cerebrolysin Vial, there is the advantages of peptide and total nitrogen content are high, and vigor numerical value is high, and pharmacological activity is stronger.
Specifically, the invention provides：
A kind of preparation method of Cerebrolysin Vial, this method comprise the following steps：
A) Feedstock treating：Fresh or freezen protective pig brain is removed to the coating and blood vessel on surface, with 0.5 after being cut into small pieces
~5% sodium hydroxide solution soaks 12~48 hours, takes out and cleans, drains away the water, standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 5000-10000U/g substrates from plant
The papain of extraction, stirring, digest 4-6 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digest 5-10 hours；
D) sterilize：After being 6-7 by step c) products therefroms regulation pH, 80-85 DEG C, enzyme deactivation 8-12min are warming up to, is cooled down
Activated carbon is added after to room temperature, is filtered after stirring 2-5 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 100~1000Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme is the bacterialprotease from bacillus amyloliquefaciens, the bacterioprotein from bacillus licheniformis
The mixture of enzyme composition.
The enzyme activity of the bacterialprotease from bacillus amyloliquefaciens is 400,000 U/ grams.
The enzyme activity of the bacterialprotease from bacillus licheniformis is 100,000 U/ grams.
Bacterialprotease from bacillus amyloliquefaciens, the bacterialprotease from bacillus licheniformis in the complex enzyme
Weight ratio is (0.5~3)：(1~5).
Bacterialprotease from bacillus amyloliquefaciens, the bacterialprotease from bacillus licheniformis in the complex enzyme
Weight ratio preferably 1：2.
The Cerebrolysin Vial that preparation method described above obtains is that raw material is prepared into oral formulations or ejection preparation.
Bacterialprotease of the present invention from bacillus amyloliquefaciens, the bacterioprotein from bacillus licheniformis
Enzyme, papain are purchased from Shanghai Baofeng biochemistry Co., Ltd.
The present invention has the advantages that compared with prior art：
1st, ensure to realize the hydrolysis of raw material to the full extent using the technique of two steps of papain and complex enzyme enzymolysis；
2nd, with activated carbon deodorization, suction-operated and the filtrating aid function of activated carbon is made full use of, improves product content, simultaneously
Shorten the process time；
3rd, UF membrane is carried out using NF membrane, effectively eliminates small molecular weight impurity, while also feed liquid is concentrated, greatly
Width reduces the energy consumption of spray-drying process；
4th, preparation method of the present invention is simple, is easy to industrialized production；
5th, brain protein powder peptide content height is prepared by this method, vigor is high.
Embodiment
Below by way of the description of embodiment, the invention will be further described, but this is not the limit to the present invention
System, those skilled in the art according to the present invention basic thought, various modifications may be made or improve, but without departing from this
The basic thought of invention, within the scope of the present invention.
The following experiments of the present invention are the conclusive checking tests of progress in multiple creative experimental basis.
The animal pharmacodynamics test of experimental example 1
Trial drug：Commercially available compound cerebroprotin hydrolysate piece (being purchased from Dalian Bel pharmaceutcal corporation, Ltd), the present invention are implemented
Sample made from example 5, the solution of required concentration is made into distilled water, it is for oral administration
Use.
1) to the influence of mouse hypobaric hypoxia state
18-21g mouse 150 are taken, male and female half and half, are randomly divided into 3 groups, the drug dose gastric infusion as shown in table 1,30
After minute, three groups of operations are put into vacuum storehouse simultaneously, closed, decompression vacuum pumping, when control group mice is dead up to more than half
When, continue observation 30 minutes after ventilation, record the death toll of each group animal.
It the results are shown in Table 1.
The mouse hypoxia endurance test of table 1 is studied
From the result of table 1, sample produced by the present invention is significantly improved to the hypobaric hypoxia state of mouse.
2) to the influence of cerebral hypoxia
Underage mouse 150 is taken, is randomly divided into 3 groups, the drug dose gastric infusion as shown in table 2, after 40 minutes, tail
It is injected intravenously the KCN decoctions (1.8mg/kg) of normal saline, timing after injection, to exhaling after measure animal injection
Inhale the life span stopped.
It the results are shown in Table 2.
Influence of the table 2 to cerebral hypoxia
As a result show：It is injected intravenously with the KCN of absolute lethal dose, commercially available group and group of the embodiment of the present invention all highly significants
The time-to-live of animal is extended, shows that the present invention has the function that to improve animal central nervous systems anaerobic condition；The present invention
Group has had significant extension animal survival time compared with commercially available group, shows that the present invention lacks to improving animal central nervous systems
The effect of oxygen condition is better than commercially available product.
Peptide content determination test in the Cerebrolysin Vial of experimental example 2
1st, trial drug
Take the sample prepared by embodiment 3, embodiment 5, embodiment 8 and CN200410022091.5 methods.
2nd, the method for determining the Cerebrolysin Vial content (in terms of ammonia nitrogen) in Cerebrolysin Vial
Take sample appropriate (being approximately equivalent to peptide 50mg), it is accurately weighed, put in digest tube, add hydrochloric acid (to make test sample complete in right amount
It is complete to submerge and no more than 2/3 volume of container), nitrogen charging sealing, put 110 DEG C and hydrolyze 20 hours, let cool, break seal, hydrolyzate is complete
Amount is transferred in evaporating dish, and water-bath is evaporated to dryness, and is added water to dissolve residue and is diluted to suitable concentration, is surveyed as total amino acid
Surely need testing solution is used；Separately take this product appropriate, be diluted with water to suitable concentration, it is molten as free amine group acidity test test sample
Liquid, it is measured with amino-acid analyzer.Corresponding amino acid reference substance (see the table below) is separately taken,
Suitable concn is made in accurately weighed and dilution, as reference substance solution, is measured in the same method.By external standard method or with suitable
Amino acid is marked with each amino acid content of calculated by peak area to be interior (except tryptophan).Subtracted with total amino acid content after hydrolysis free
Amino acid content is peptide content.
Total nitrogen takes this product about 10mg, accurately weighed, determines (two annex VII D second of Chinese Pharmacopoeia version in 2010 in accordance with the law
Method).
It the results are shown in Table 3.
The peptide content determination test of table 3 investigates result
Conclusion (of pressure testing)：Stability test result shows that peptide content is significantly higher than in Cerebrolysin Vial prepared by the present invention
The Cerebrolysin Vial of comparative example.
3rd, vitality test is tested
The sample that sample is prepared by embodiment 3, embodiment 5, embodiment 8 and CN200410022091.5 methods.
Determination method takes this product appropriate, and being dissolved in water and diluting is made solution of every 1ml containing about total nitrogen 6mg, aseptic filtration, takes
Filtrate is in right amount plus the solution that nitrogen content in every 1ml is 60 μ g is made in 10% calf serum nutrient solution, is determined according to vitality test method, knot
Fruit is shown in Table 4.
Vitality test method, to increased logarithmic phase, is used with the PC12 cells in the generation of 10% calf serum nutrient solution culture 3~8
0.25% trypsase-Calcium Disodium Versenate digestive juice digestion, adds 10% calf serum nutrient solution to be diluted in every 1ml and contains
(0.8~1.2) × 105 cell, by above-mentioned cell suspension in 96 porocyte culture plates bed board, per the μ l of hole 100, with
The μ l of 10% calf serum nutrient solution 100 put 37 DEG C, cultivated in 5% carbon dioxide saturation vapour incubator as blank control group
24 hours.Test sample group, the μ l of need testing solution 100 are added per hole, normal cell group, damaging cells group, blank control group are per hole
Respectively plus the μ l of 10% calf serum nutrient solution 100, every group sets 3 multiple holes.37 DEG C is put, 5% carbon dioxide saturation vapour culture
Cultivated 24 hours in case.Test sample group, damaging cells group are separately added into the μ l of 0.5mmol/L hydrogenperoxide steam generators 50, and remaining hole adds
Enter the μ l of 10% calf serum nutrient solution 50, put 37 DEG C, cultivated 48 hours in 5% carbon dioxide saturation vapour incubator.Terminate training
Support first 4 hours and take out culture plate, suck nutrient solution, 0.01mol/L phosphate buffers (pH7.3) are added per hole and are washed once, so
Add the μ l of 100 μ l and MTT solution of above-mentioned phosphate buffer (pH7.3) 20 in every hole again afterwards, continue to cultivate.Culture terminates
Afterwards, nutrient solution is suctioned out, the μ l of dimethyl sulfoxide (DMSO) 100 are added per hole, are shaken up, after placing 5 minutes, with 550 nm on ELIASA
Wavelength at determine its absorbance A value respectively.
Repair rate %=(Ag-As)/(Az-As) × 100%
Ag is test sample group mean light absorbency-blank control group mean light absorbency in formula；
As is damaging cells group mean light absorbency-blank control group mean light absorbency；
Az is normal cell group mean light absorbency-blank control group mean light absorbency.
Result is investigated in the experiment of the vitality test of table 4
Conclusion (of pressure testing)：Vitality test experimental result shows that Cerebrolysin Vial repair rate prepared by the present invention is significantly higher than
Comparative example.Show that Cerebrolysin Vial activity prepared by this method is better than comparative example.
Embodiment
Embodiment 1
A) Feedstock treating：The pig brain of fresh preservation is removed to the coating and blood vessel on surface, with 0.5% hydrogen-oxygen after being cut into small pieces
Change sodium solution to soak 48 hours, take out and clean, drain away the water, it is standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 10000U/g substrates from plant extract
Papain, stirring, digest 4 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 5 hours；
D) sterilize：After being 6 by step c) products therefroms regulation pH, 85 DEG C, enzyme deactivation 8min are warming up to, is added after being cooled to room temperature
Enter activated carbon, stirring is filtered after 4.8 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 600Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity be
100000 U/ grams from bacillus licheniformis bacterialprotease composition.
Embodiment 2
A) Feedstock treating：The pig brain of fresh preservation is removed to the coating and blood vessel on surface, with 1% hydroxide after being cut into small pieces
Sodium solution soaks 36 hours, takes out and cleans, drains away the water, standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 5000U/g substrates from plant extract
Papain, stirring, digest 6 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 6 hours；
D) sterilize：After being 6.5 by step c) products therefroms regulation pH, 80 DEG C are warming up to, enzyme deactivation 12min, is cooled to room temperature
After add activated carbon, stirring is filtered after 3.8 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 400Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity 10
Ten thousand U/ grams from bacillus licheniformis bacterialprotease composition.
Embodiment 3
A) Feedstock treating：The pig brain of freezen protective is removed to the coating and blood vessel on surface, with 1.5% hydrogen-oxygen after being cut into small pieces
Change sodium solution to soak 30 hours, take out and clean, drain away the water, it is standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 5000U/g substrates from plant extract
Papain, stirring, digest 6 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 6.5 hours；
D) sterilize：After being 7 by step c) products therefroms regulation pH, 85 DEG C, enzyme deactivation 8min are warming up to, is added after being cooled to room temperature
Enter activated carbon, stirring is filtered after 2.8 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 200Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity 10
Ten thousand U/ grams from bacillus licheniformis bacterialprotease composition.
Embodiment 4
A) Feedstock treating：The pig brain of freezen protective is removed to the coating and blood vessel on surface, with 2% hydroxide after being cut into small pieces
Sodium solution soaks 28 hours, takes out and cleans, drains away the water, standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 6000U/g substrates from plant extract
Papain, stirring, digest 5.3 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 7 hours；
D) sterilize：After being 7 by step c) products therefroms regulation pH, 84 DEG C, enzyme deactivation 9min are warming up to, is added after being cooled to room temperature
Enter activated carbon, stirring is filtered after 2 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 100Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity 10
Ten thousand U/ grams from bacillus licheniformis bacterialprotease composition.
Embodiment 5
A) Feedstock treating：The pig brain of freezen protective is removed to the coating and blood vessel on surface, with 2.5% hydrogen-oxygen after being cut into small pieces
Change sodium solution to soak 24 hours, take out and clean, drain away the water, it is standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 7000U/g substrates from plant extract
Papain, stirring, digest 4.8 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 7.5 hours；
D) sterilize：After being 6 by step c) products therefroms regulation pH, 83 DEG C are warming up to, enzyme deactivation 10min, after being cooled to room temperature
Activated carbon is added, stirring is filtered after 3 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 500Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity 10
Ten thousand U/ grams from bacillus licheniformis bacterialprotease composition.
Embodiment 6
A) Feedstock treating：The pig brain of fresh preservation is removed to the coating and blood vessel on surface, with 3% hydroxide after being cut into small pieces
Sodium solution soaks 20 hours, takes out and cleans, drains away the water, standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 8000U/g substrates from plant extract
Papain, stirring, digest 5 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 8 hours；
D) sterilize：After being 6.5 by step c) products therefroms regulation pH, 82 DEG C are warming up to, enzyme deactivation 11min, is cooled to room temperature
After add activated carbon, stirring is filtered after 4 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 800Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity 10
Ten thousand U/ grams from bacillus licheniformis bacterialprotease composition.
Embodiment 7
A) Feedstock treating：The pig brain of fresh preservation is removed to the coating and blood vessel on surface, with 4% hydroxide after being cut into small pieces
Sodium solution soaks 16 hours, takes out and cleans, drains away the water, standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 9000U/g substrates from plant extract
Papain, stirring, digest 4.5 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 9 hours；
D) sterilize：After being 6 by step c) products therefroms regulation pH, 81 DEG C are warming up to, enzyme deactivation 12min, after being cooled to room temperature
Activated carbon is added, stirring is filtered after 4.5 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 900Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity 10
Ten thousand U/ grams from bacillus licheniformis bacterialprotease composition.
Embodiment 8
A) Feedstock treating：The pig brain of freezen protective is removed to the coating and blood vessel on surface, with 5% hydroxide after being cut into small pieces
Sodium solution soaks 12 hours, takes out and cleans, drains away the water, standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 10000U/g substrates from plant extract
Papain, stirring, digest 4 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in step b) products therefroms, stirred, digested 10 hours；
D) sterilize：After being 7 by step c) products therefroms regulation pH, 80 DEG C are warming up to, enzyme deactivation 12min, after being cooled to room temperature
Activated carbon is added, stirring is filtered after 5 hours, obtains filtrate；
E) concentrate：Filtrate obtained by step d) is subjected to ultrafiltration with 1000Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial.
The complex enzyme by enzyme activity be 400,000 U/ grams the bacterialprotease from bacillus amyloliquefaciens, enzyme activity 10
Ten thousand U/ grams from bacillus licheniformis bacterialprotease composition.
Claims (1)
1. a kind of preparation method of Cerebrolysin Vial, it is characterised in that this method comprises the following steps：
A) Feedstock treating：Fresh or freezen protective pig brain is removed to the coating and blood vessel on surface, after being cut into small pieces with 0.5~
5% sodium hydroxide solution soaks 12~48 hours, takes out and cleans, drains away the water, standby；
B) enzyme hydrolysis：Add water in the reactor for hold pig brain, added in the ratio of 5000-10000U/g substrates from plant extract
Papain, stirring, digest 4-6 hours；
C) complex enzyme for hydrolyzing：Complex enzyme will be added in papain hydrolysis product, stirred, digest 5-10 hours；
D) sterilize：Complex enzyme for hydrolyzing is obtained into product regulation pH after 6-7, to be warming up to 80-85 DEG C, enzyme deactivation 8-12min, being cooled to
Activated carbon is added after room temperature, is filtered after stirring 2-5 hours, obtains filtrate；
E) concentrate：Filtrate is subjected to ultrafiltration with 100~1000Da NF membrane, collects trapped fluid；
F) trapped fluid of collection is spray-dried, obtains the Cerebrolysin Vial；
Wherein described complex enzyme is the bacterialprotease from bacillus amyloliquefaciens, the bacterioprotein from bacillus licheniformis
The mixture of enzyme composition；The enzyme activity of the wherein described bacterialprotease from bacillus amyloliquefaciens is 400,000 U/ grams；Wherein
The enzyme activity of the bacterialprotease from bacillus licheniformis is 100,000 U/ grams；Starch bud is self solved in wherein described complex enzyme
The bacterialprotease of spore bacillus, the bacterialprotease weight ratio from bacillus licheniformis are 1: 2.
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| CN105726575A (en) * | 2016-02-04 | 2016-07-06 | 魏建萍 | Granule used for syndromes after brain injuries and preparation method thereof |
| CN107303385B (en) * | 2016-04-15 | 2021-08-31 | 北京四环科宝制药有限公司 | Preparation method of cerebroprotein hydrolysate solution |
| CN113908174B (en) * | 2021-10-29 | 2022-06-24 | 北京四环制药有限公司 | Efficient and safe preparation method and application of cerebroprotein hydrolysate |
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| CN1589811A (en) * | 2003-08-07 | 2005-03-09 | 詹姆斯－安迪制药（通化）有限公司 | Medicinal composition, its preparation method and its use |
| CN102093440A (en) * | 2010-12-28 | 2011-06-15 | 山东新时代药业有限公司 | Coproduction process of pig brain protein hydrolysate and monosialoganglioside |
| CN102771620B (en) * | 2012-07-14 | 2015-01-14 | 临高泽世泰生物科技有限公司 | Method for producing hydrolyzed brain protein powder and cephalin by grease removal of supercritical carbon dioxide |
| CN103142991B (en) * | 2013-03-27 | 2015-01-21 | 山西普德药业股份有限公司 | Cerebroprotein hydrolysate and lyophilized powder thereof for injection |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1589811A (en) * | 2003-08-07 | 2005-03-09 | 詹姆斯－安迪制药（通化）有限公司 | Medicinal composition, its preparation method and its use |
| CN102093440A (en) * | 2010-12-28 | 2011-06-15 | 山东新时代药业有限公司 | Coproduction process of pig brain protein hydrolysate and monosialoganglioside |
| CN102771620B (en) * | 2012-07-14 | 2015-01-14 | 临高泽世泰生物科技有限公司 | Method for producing hydrolyzed brain protein powder and cephalin by grease removal of supercritical carbon dioxide |
| CN103142991B (en) * | 2013-03-27 | 2015-01-21 | 山西普德药业股份有限公司 | Cerebroprotein hydrolysate and lyophilized powder thereof for injection |
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