CN1939341A - Brain protein hydrolyte freeze-drying preparation for injection and its making method - Google Patents
Brain protein hydrolyte freeze-drying preparation for injection and its making method Download PDFInfo
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- CN1939341A CN1939341A CNA2006101508929A CN200610150892A CN1939341A CN 1939341 A CN1939341 A CN 1939341A CN A2006101508929 A CNA2006101508929 A CN A2006101508929A CN 200610150892 A CN200610150892 A CN 200610150892A CN 1939341 A CN1939341 A CN 1939341A
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- 239000007924 injection Substances 0.000 title claims abstract description 33
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- 238000004108 freeze drying Methods 0.000 title description 2
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 abstract description 6
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Abstract
A freeze-dried powder injection of brain protein's hydrolyzate for treating insomnia, headache, hypomnesia, dizziness, the sequelae of cerebral trauma, cerebrovascular disease and encephalitis, etc is prepared from the hydrolyzate of brain protein and the auxiliary chosen from mannitol, sorbitol and dextran. Its preparing process is also disclosed.
Description
Technical field: the present invention relates to curative, be specially and be used to improve symptoms such as insomnia, headache, hypomnesis, dizziness and agitation, promote rehabilitation medication brain protein hydrolysate for injection lyophilized preparation of cerebral trauma sequela, sequal of cerebrovascular diseases, encephalitis sequela, acute cerebral infarction and acute brain wound and preparation method thereof.
Technical background: Cerebrolysin Vial is that the fresh brain with health pig forms through defat, enzyme hydrolysis, drying.Contain free amino acid and molecular weight mixture at small-molecular peptides below 10000 etc.Can act on nervus centralis in many ways; regulate and improve neuronic metabolism; promote the formation of synapse, induce neuronic differentiation, and further neuroprotective cell is in the infringement that is subjected to various but blood and neurotoxin; can pass through blood brain barrier; promote the synthetic of brain internal protein, influence respiratory chain, have the protective capability of anti-hypoxia; improve the metabolism of brain self-energy, other hormone systems of activated adenyl cyclase and catalysis.Improve neurotransmitter, peptide hormone and coenzyme precursors.
Mainly contain dosage forms such as tablet, injection, freeze-dried powder on the market now, the rehabilitation that be widely used in improving symptoms such as insomnia, headache, hypomnesis, dizziness and agitation clinically, promotes cerebral trauma sequela, sequal of cerebrovascular diseases, encephalitis sequela, acute cerebral infarction and acute brain wound.
Summary of the invention: the object of the present invention is to provide a kind of rehabilitation brain protein hydrolysate for injection lyophilized preparation of lyophilized formulations and preparation method thereof that is widely used in improving symptoms such as insomnia, headache, hypomnesis, dizziness and agitation, promotion cerebral trauma sequela, sequal of cerebrovascular diseases, encephalitis sequela, acute cerebral infarction and acute brain wound clinically.The object of the present invention is achieved like this: it comprises principal agent Cerebrolysin Vial, adjuvant.A, principal agent are Cerebrolysin Vial, preparation brain protein hydrolysate for injection lyophilized preparation; B, principal agent are Cerebrolysin Vial, add in adjuvant mannitol, sorbitol, the low molecular dextran any, preparation brain protein hydrolysate for injection lyophilized preparation.The present invention is measurement unit with the bottle, and every bottle contains total nitrogen 12～120mg, and the weight ratio of total nitrogen and free amino acid is 6: 35, and promptly every bottle contains free amino acid 70～700mg, and every bottle contains adjuvant is 0～400mg;
1, pretreatment
Putting into stainless steel cask after freezing Medulla sus domestica cleaned twice with purified water thaws naturally;
2, homogenate
Add purified water by 1: 1～3 and stir 5～30min, colloid mill homogenate twice, fineness 20 μ m, fineness 10 μ m for the second time for the first time;
3, primary enzymolysis
Homogenate is put in the hydrolytic decomposition pot, transfers pH value 3.0～6.0 with HCl, is heated to 30～50 ℃, presses raw material weight and adds 1～10% gastric enzyme enzymolysis, and enzymolysis was heated to 80～100 ℃ of 15～30min after 12～18 hours, cooled to 30～50 ℃;
4, secondary enzymolysis
Transfer pH value 7.0～9.5 with NaOH, press raw material weight and add 1～10% pancreatin, 30～50 ℃ of hydrolysis temperatures, 1～6 hour post-heating to 80～100 ℃ 15～30min of enzymolysis, filter cloth filters when cooling to 30～50 ℃, gets coarse filtration liquid, take by weighing weight, calculated yield;
5, fine straining
Coarse filtration liquid is put in the jacketed pan by filtrate weight 0.1～1% and is added after medicinal carbon is heated to 80～100 ℃ of stirring and adsorbing 15～30min, when cooling to 25～35 ℃, with 0.45 μ m filtering with microporous membrane carbon removal, reuse 0.22 μ m filtering with microporous membrane, get fine straining liquid, take by weighing weight, calculated yield;
6, ultrafiltration
Fine straining liquid is transferred pH value 6.0～8.0, and 20～25 ℃ of fluid temperature are with 3000～10000 dalton's ultrafilter ultrafiltration, pressure 0.05～0.1MPa.Ultrafiltrate is packed in the pyrogen-free Plastic Drum, sampling censorship, refrigerated storage;
7, freeze-dry process
(1), take by weighing the adjuvant of recipe quantity, add the injection water, stir and make dissolving, add needle-use activated carbon by 0.05～1% of solution amount, 80～100 ℃ are stirred 15～35min, it is clear and bright to be filtered to solution, standby;
(2), get the Cerebrolysin Vial extracting solution of recipe quantity, mix with above-mentioned solution, add the injection water to 80～90% of solution total amount, transfer pH to 6.0～8.0, after-teeming is penetrated water to full dose;
(3), cross microporous filter membrane, mensuration content;
(4), fill is in glass tube vial;
(5), sample that fill is good inserts in the freezer dryer, is cooled to-50～-20 ℃ earlier, is incubated 1～6 hour, evacuation then, and by 1～2 ℃ of/hour intensification, after temperature reaches-5 ℃, be warming up to 45 ℃ by 5～10 ℃/hour is incubated 2～3 hours, the moulding plug.
(6), Zha Gai, quality inspection, the vanning.
The invention has the advantages that: (1) this product is a lyophilized formulations, its characteristics are good stability, avoided brain protein injection liquid in long preservation and long-distance transport process, the easy generation polymerization affected by environment of polypeptides matter and influence the phenomenon of product quality, thereby reduced the probability of the formation of polymer substance, reduced anaphylactoid generation in the clinical course simultaneously.
Sample was placed 24 months under the condition of 25 ℃ of temperature, relative humidity 60%, respectively at sampling in the 0th, 3,6,9,12,18,24 month, test according to quality standard draft specifies project approach, main character, acid-base value, other materials, index of refraction, protein, loss on drying, clarity, bacterial endotoxin, pyrogen, the assay of investigating this product, and with 0 month numeric ratio, the results are shown in Table 1,2.The quality of each sample was compared no significant change with 0 month.(2) pharmacological action of this product, drug effect, usage and dosage all are equal to brain protein injection liquid, and have no side effect.(3) kind of adjuvant just is not confined to dextran among the present invention, has increased mannitol, sorbitol again, and producing greatly for industry has increased selectivity.(4) the present invention has broken through the limitation that the amount of adjuvant is frozen shape to this product, can not add adjuvant, adopts Cerebrolysin Vial to carry out lyophilization by the freeze-dry process of novelty, obtains freezing the good this product of shape, greatly reduces production cost simultaneously.
The specific embodiment: a, principal agent are Cerebrolysin Vial, preparation brain protein hydrolysate for injection lyophilized preparation; B, principal agent are Cerebrolysin Vial, add in adjuvant mannitol, sorbitol, the low molecular dextran any, preparation brain protein hydrolysate for injection lyophilized preparation.The present invention is measurement unit with the bottle, and every bottle contains total nitrogen 12～120mg, and total nitrogen is 6: 35 with the amount ratio of free amino acid, and promptly every bottle contains free amino acid 70～700mg, and every bottle contains adjuvant is 0～400mg;
1, pretreatment
Putting into stainless steel cask after freezing Medulla sus domestica cleaned twice with purified water thaws naturally;
2, homogenate
Add purified water by 1: 1～3 and stir 5～30min, colloid mill homogenate twice, fineness 20 μ m, fineness 10 μ m for the second time for the first time;
3, primary enzymolysis
Homogenate is put in the hydrolytic decomposition pot, transfers pH value 3.0～6.0 with HCl, is heated to 30～50 ℃, presses raw material weight and adds 1～10% gastric enzyme enzymolysis, and enzymolysis was heated to 80～100 ℃ of 15～30min after 12～18 hours, cooled to 30～50 ℃;
4, secondary enzymolysis
Transfer pH value 7.0～9.5 with NaOH, press raw material weight and add 1～10% pancreatin, 30～50 ℃ of hydrolysis temperatures, 1～6 hour post-heating to 80～100 ℃ 15～30min of enzymolysis, filter cloth filters when cooling to 30～50 ℃, gets coarse filtration liquid, take by weighing weight, calculated yield;
5, fine straining
Coarse filtration liquid is put in the jacketed pan by filtrate weight 0.1～1% and is added after medicinal carbon is heated to 80～100 ℃ of stirring and adsorbing 15～30min, when cooling to 25～35 ℃, with 0.45 μ m filtering with microporous membrane carbon removal, reuse 0.22 μ m filtering with microporous membrane, get fine straining liquid, take by weighing weight, calculated yield;
6, ultrafiltration
Fine straining liquid is transferred pH value 6.0～8.0, and 20～25 ℃ of fluid temperature are with 3000～10000 dalton's ultrafilter ultrafiltration, pressure 0.05～0.1MPa.Ultrafiltrate is packed in the pyrogen-free Plastic Drum, sampling censorship, refrigerated storage;
7, freeze-dry process
(1), take by weighing the adjuvant of recipe quantity, add the injection water, stir and make dissolving, add needle-use activated carbon by 0.05～1% of solution amount, 80～100 ℃ are stirred 15～35min, it is clear and bright to be filtered to solution, standby;
(2), get the Cerebrolysin Vial extracting solution of recipe quantity, mix with above-mentioned solution, add the injection water to 80～90% of solution total amount, transfer pH to 6.0～8.0, after-teeming is penetrated water to full dose;
(3), cross microporous filter membrane, mensuration content;
(4), fill is in glass tube vial;
(5), sample that fill is good inserts in the freezer dryer, is cooled to-50～-20 ℃ earlier, is incubated 1～6 hour, evacuation then, and by 1～2 ℃ of/hour intensification, after temperature reaches-5 ℃, be warming up to 45 ℃ by 5～10 ℃/hour is incubated 2～3 hours, the moulding plug.
(6), Zha Gai, quality inspection, the vanning.
Embodiment 1
Putting into stainless steel cask after freezing Medulla sus domestica cleaned twice with purified water thaws naturally.Added purified water by 1: 1 and stir 5min, colloid mill homogenate twice, fineness 20 μ m, fineness 10 μ m for the second time for the first time.Homogenate is put in the hydrolytic decomposition pot, transfers pH value 3.0 with 8mol/LHCl, is heated to 30 ℃, adds 1% gastric enzyme enzymolysis by raw material weight, and enzymolysis was heated to 80 ℃ of 30min after 18 hours, cooled to 50 ℃.Transfer pH value 7.0 with 6mol/LNaOH, add 1% pancreatin by raw material weight, 30 ℃ of hydrolysis temperatures, 6 hours post-heating to 80 ℃ 30min of enzymolysis, filter cloth filters when cooling to 30 ℃, gets coarse filtration liquid, takes by weighing weight, calculated yield.Coarse filtration liquid is put in the jacketed pan by filtrate weight 0.1% and is added after medicinal carbon is heated to 100 ℃ of stirring and adsorbing 30min, when cooling to 25 ℃, with 0.45 μ m filtering with microporous membrane carbon removal, reuse 0.22 μ m filtering with microporous membrane, get fine straining liquid, take by weighing weight, calculated yield.Fine straining liquid is transferred pH value 8.0, and 25 ℃ of fluid temperature are with 10000 dalton's ultrafilter ultrafiltration, pressure 0.05～0.1MPa.Ultrafiltrate is packed in the pyrogen-free Plastic Drum, sampling censorship, refrigerated storage.
Take by weighing the mannitol of 20g, add the injection water, stir and make dissolving, add needle-use activated carbon by 0.05% of solution amount, 80 ℃ are stirred 15min, and it is clear and bright to be filtered to solution, standby.Get Cerebrolysin Vial extracting solution 1009ml, mix with above-mentioned solution, add the injection water to 90% of solution total amount, transfer pH to 8.0, after-teeming is penetrated water to full dose.Cross microporous filter membrane, measure content.Fill is in glass tube vial.The sample that fill is good is inserted in the freezer dryer, is cooled to-50 ℃ earlier, is incubated 1 hour, evacuation then, and, after temperature reaches-5 ℃, be warming up to 45 ℃ by 10 ℃/hour by 1～2 ℃ of/hour intensification, be incubated 3 hours, the moulding plug.Zha Gai, quality inspection, vanning.
Embodiment 2
The Cerebrolysin Vial extracting method is with embodiment 1.
Take by weighing the mannitol of 400g, add the injection water, stir and make dissolving, add needle-use activated carbon by 1% of solution amount, 100 ℃ are stirred 35min, and it is clear and bright to be filtered to solution, standby.Get Cerebrolysin Vial extracting solution 10013ml, mix with above-mentioned solution, add the injection water to 80% of solution total amount, transfer pH to 6.0, after-teeming is penetrated water to full dose.Cross microporous filter membrane, measure content.Fill is in glass tube vial.The sample that fill is good is inserted in the freezer dryer, is cooled to-20 ℃ earlier, is incubated 6 hours, evacuation then, and, after temperature reaches-5 ℃, be warming up to 45 ℃ by 5 ℃/hour by 1～2 ℃ of/hour intensification, be incubated 2 hours, the moulding plug.Zha Gai, quality inspection, vanning.
Embodiment 3
The Cerebrolysin Vial extracting method is with embodiment 1.
Take by weighing the sorbitol of 50g, add the injection water, stir and make dissolving, add needle-use activated carbon by 0.05% of solution amount, 80 ℃ are stirred 15min, and it is clear and bright to be filtered to solution, standby.Get Cerebrolysin Vial extracting solution 995ml, mix with above-mentioned solution, add the injection water to 90% of solution total amount, transfer pH to 8.0, after-teeming is penetrated water to full dose.Cross microporous filter membrane, measure content.Fill is in glass tube vial.The sample that fill is good is inserted in the freezer dryer, is cooled to-50 ℃ earlier, is incubated 1 hour, evacuation then, and, after temperature reaches-5 ℃, be warming up to 45 ℃ by 10 ℃/hour by 1～2 ℃ of/hour intensification, be incubated 3 hours, the moulding plug.Zha Gai, quality inspection, vanning.
Embodiment 4
The Cerebrolysin Vial extracting method is with embodiment 1.
Take by weighing the sorbitol of 400g, add the injection water, stir and make dissolving, add needle-use activated carbon by 1% of solution amount, 100 ℃ are stirred 35min, and it is clear and bright to be filtered to solution, standby.Get Cerebrolysin Vial extracting solution 9987ml, mix with above-mentioned solution, add the injection water to 80% of solution total amount, transfer pH to 6.0, after-teeming is penetrated water to full dose.Cross microporous filter membrane, measure content.Fill is in glass tube vial.The sample that fill is good is inserted in the freezer dryer, is cooled to-20 ℃ earlier, is incubated 6 hours, evacuation then, and, after temperature reaches-5 ℃, be warming up to 45 ℃ by 5 ℃/hour by 1～2 ℃ of/hour intensification, be incubated 2 hours, the moulding plug.Zha Gai, quality inspection, vanning.
Embodiment 5
The Cerebrolysin Vial extracting method is with embodiment 1.
Take by weighing the low molecular dextran of 70g, add the injection water, stir and make dissolving, add needle-use activated carbon by 0.05% of solution amount, 80 ℃ are stirred 15min, and it is clear and bright to be filtered to solution, standby.Get Cerebrolysin Vial extracting solution 989ml, mix with above-mentioned solution, add the injection water to 90% of solution total amount, transfer pH to 8.0, after-teeming is penetrated water to full dose.Cross microporous filter membrane, measure content.Fill is in glass tube vial.The sample that fill is good is inserted in the freezer dryer, is cooled to-50 ℃ earlier, is incubated 1 hour, evacuation then, and, after temperature reaches-5 ℃, be warming up to 45 ℃ by 10 ℃/hour by 1～2 ℃ of/hour intensification, be incubated 3 hours, the moulding plug.Zha Gai, quality inspection, vanning.
Embodiment 6
The Cerebrolysin Vial extracting method is with embodiment 1.
Take by weighing the low molecular dextran of 320g, add the injection water, stir and make dissolving, add needle-use activated carbon by 1% of solution amount, 100 ℃ are stirred 35min, and it is clear and bright to be filtered to solution, standby.Get Cerebrolysin Vial extracting solution 9996ml, mix with above-mentioned solution, add the injection water to 80% of solution total amount, transfer pH to 6.0, after-teeming is penetrated water to full dose.Cross microporous filter membrane, measure content.Fill is in glass tube vial.The sample that fill is good is inserted in the freezer dryer, is cooled to-20 ℃ earlier, is incubated 6 hours, evacuation then, and, after temperature reaches-5 ℃, be warming up to 45 ℃ by 5 ℃/hour by 1～2 ℃ of/hour intensification, be incubated 2 hours, the moulding plug.Zha Gai, quality inspection, vanning.
Embodiment 7
The Cerebrolysin Vial extracting method is with embodiment 1.
Get Cerebrolysin Vial extracting solution 9989ml, add the injection water to 80% of solution total amount, transfer pH to 6.5, after-teeming is penetrated water to full dose.Cross microporous filter membrane, measure content.Fill is in glass tube vial.The sample that fill is good is inserted in the freezer dryer, is cooled to-20 ℃ earlier, is incubated 6 hours, evacuation then, and, after temperature reaches-5 ℃, be warming up to 45 ℃ by 5 ℃/hour by 1～2 ℃ of/hour intensification, be incubated 2 hours, the moulding plug.Zha Gai, quality inspection, vanning.
Embodiment 8
Putting into stainless steel cask after freezing Medulla sus domestica cleaned twice with purified water thaws naturally.Added purified water by 1: 3 and stir 30min, colloid mill homogenate twice, fineness 20 μ m, fineness 10 μ m for the second time for the first time.Homogenate is put in the hydrolytic decomposition pot, transfers pH value 6.0 with 10mol/LHCl, is heated to 50 ℃, adds 10% gastric enzyme enzymolysis by raw material weight, and enzymolysis was heated to 100 ℃ of 15min after 12 hours, cooled to 30 ℃.Transfer pH value 9.5 with 8mol/LNaOH, add 10% pancreatin by raw material weight, 50 ℃ of hydrolysis temperatures, 1 hour post-heating to 100 ℃ 15min of enzymolysis, filter cloth filters when cooling to 50 ℃, gets coarse filtration liquid, takes by weighing weight, calculated yield.Coarse filtration liquid is put in the jacketed pan by filtrate weight 1% and is added after medicinal carbon is heated to 80 ℃ of stirring and adsorbing 15min, when cooling to 35 ℃, with 0.45 μ m filtering with microporous membrane carbon removal, reuse 0.22 μ m filtering with microporous membrane, get fine straining liquid, take by weighing weight, calculated yield.Fine straining liquid is transferred pH value 6.0, and 20 ℃ of fluid temperature are with 3000 dalton's ultrafilter ultrafiltration, pressure 0.05～0.1MPa.Ultrafiltrate is packed in the pyrogen-free Plastic Drum, sampling censorship, refrigerated storage.
Embodiment 9
Putting into stainless steel cask after freezing Medulla sus domestica cleaned twice with purified water thaws naturally.Added purified water by 1: 2.5 and stir 20min, colloid mill homogenate twice, fineness 20 μ m, fineness 10 μ m for the second time for the first time.Homogenate is put in the hydrolytic decomposition pot, transfers pH value 4.0 with 8mol/LHCl, is heated to 40 ℃, adds 2% gastric enzyme enzymolysis by raw material weight, and enzymolysis was heated to 95 ℃ of 25min after 15 hours, cooled to 35 ℃.Transfer pH value 7.8 with 7mol/LNaOH, add 3% pancreatin by raw material weight, 35 ℃ of hydrolysis temperatures, 3 hours post-heating to 85 ℃ 20min of enzymolysis, filter cloth filters when cooling to 40 ℃, gets coarse filtration liquid, takes by weighing weight, calculated yield.Coarse filtration liquid is put in the jacketed pan by filtrate weight 0.5% and is added after medicinal carbon is heated to 100 ℃ of stirring and adsorbing 30min, when cooling to 35 ℃, with 0.45 μ m filtering with microporous membrane carbon removal, reuse 0.22 μ m filtering with microporous membrane, get fine straining liquid, take by weighing weight, calculated yield.Fine straining liquid is transferred pH value 7.5, and 23 ℃ of fluid temperature are with 6000 dalton's ultrafilter ultrafiltration, pressure 0.05～0.1MPa.Ultrafiltrate is packed in the pyrogen-free Plastic Drum, sampling censorship, refrigerated storage.
Table 1, brain protein hydrolysate for injection long-term stable experiment result
| Lot number | Time (moon) | Character | Acid-base value | Other materials (%) | Index of refraction | Protein | Clarity | Loss on drying (%) | Bacterial endotoxin | Pyrogen | Total amino acid content (mg) | Total nitrogen content (mg) | Aseptic |
| 021112 | 0 3 6 9 12 18 24 | The little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of little yellow blocks of solid | 7.24 7.26 7.25 7.28 7.27 7.27 7.27 | 0 0 0.80 4.01 2.54 5.24 5.18 | 1.3413 1.3422 1.3422 1.3415 1.3423 1.3419 1.3421 | Up to specification up to specification up to specification | Up to specification up to specification up to specification | 0.41 0.25 0.40 0.69 0.44 0.54 0.52 | Up to specification up to specification up to specification | Up to specification up to specification up to specification | 304.3 336.1 355.9 334.6 332.9 320.0 318.2 | 63.94 61.52 61.55 61.47 61.20 61.45 60.97 | Up to specification-----up to specification |
| 021114 | 0 3 6 9 12 18 24 | The little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of little yellow blocks of solid | 7.27 7.28 7.27 7.30 7.29 7.29 7.28 | 0 0 0.63 3.90 1.73 5.07 5.18 | 1.3418 1.3422 1.3418 1.3418 1.3420 1.3418 1.3419 | Up to specification up to specification up to specification | Up to specification up to specification up to specification | 0.53 0.91 0.22 0.48 0.41 0.49 0.48 | Up to specification up to specification up to specification | Up to specification up to specification up to specification | 327.3 332.3 356.9 335.7 336.3 322.2 324.5 | 62.92 61.45 61.34 60.96 61.82 61.53 60.43 | Up to specification-----up to specification |
| 021116 | 0 3 6 9 12 18 24 | The little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of the little yellow blocks of solid of little yellow blocks of solid | 7.25 7.26 7.26 7.29 7.27 7.28 7.27 | 0 0 3.90 3.92 0.29 5.14 5.22 | 1.3423 1.3419 1.3418 1.3416 1.3417 1.3420 1.3417 | Up to specification up to specification up to specification | Up to specification up to specification up to specification | 0.50 0.49 0.64 0.26 0.59 0.52 0.59 | Up to specification up to specification up to specification | Up to specification up to specification up to specification | 329.0 315.9 357.9 338.1 336.5 312.3 326.5 | 63.34 62.22 60.97 61.81 61.58 60.90 60.61 | Up to specification-----up to specification |
Table 2, brain protein hydrolysate for injection long-term stable experiment amino acid content measurement result
| Lot number | Time (moon) | Free aminoacid content (mg) | |||||||||||||||
| ASP | GLU | SER | GLY | HIS | ARG | THR | ALA | PRO | VAL | MET | ILE | LEU | PHE | TRP | LYS | ||
| 021112 | 0 3 6 9 12 18 24 | 26.9 26.5 26.9 25.9 27.8 28.7 25.9 | 34.3 37.3 44.1 44.3 46.5 37.9 35.1 | 2.5 2.4 3.7 3.4 3.2 2.3 2.4 | 14.1 14.5 15.8 15.7 15.3 13.6 13.3 | 12.0 12.8 14.7 14.0 12.9 12.6 12.7 | 8.5 7.1 8.1 4.5 3.7 8.7 9.6 | 2.8 3.1 3.9 3.4 3.1 2.9 2.6 | 27.6 28.7 28.9 26.7 26.3 27.8 29.0 | 18.4 19.1 20.1 22.8 21.9 18.9 18.7 | 17.6 18.8 20.6 19.9 19.7 17.4 17.5 | 4.8 4.8 6.4 4.7 4.7 4.9 4.8 | 18.2 18.5 21.5 19.4 19.1 19.4 19.2 | 52.2 57.6 61.7 53.3 52.9 52.9 51.1 | 18.8 20.8 18.7 20.2 20.0 19.7 19.8 | 5.0 5.0 4.5 4.8 4.7 4.1 4.2 | 48.4 59.1 56.1 51.7 51.2 48.0 52.4 |
| 021114 | 0 3 6 9 12 18 24 | 26.7 26.3 27.0 26.4 26.6 26.3 26.6 | 34.6 33.6 44.2 45.0 45.2 34.4 36.5 | 2.6 2.6 3.8 3.5 3.2 3.5 2.4 | 14.2 14.4 16.0 15.7 15.6 13.9 13.4 | 11.5 12.6 14.4 14.0 12.9 12.7 12.7 | 7.1 7.1 8.3 4.6 6.7 8.7 9.1 | 2.6 3.1 3.5 3.4 3.1 3.2 2.6 | 27.6 28.7 29.2 26.7 26.6 27.9 28.1 | 19.3 19.0 20.3 22.7 22.2 19.1 20.7 | 18.0 18.8 20.7 19.9 19.9 20.1 18.4 | 4.6 4.8 6.4 4.6 4.7 4.9 5.0 | 18.2 18.5 21.6 19.3 19.3 18.0 20.5 | 54.7 57.6 62.0 53.3 53.5 51.5 51.4 | 20.0 20.8 18.8 20.2 20.2 21.8 20.8 | 5.3 5.1 4.4 4.8 4.7 4.7 4.6 | 60.3 59.5 56.2 51.7 51.8 51.6 51.6 |
| 021116 | 0 3 6 9 12 18 24 | 26.7 26.6 27.7 28.0 26.9 27.2 26.6 | 34.7 35.6 45.0 46.8 45.4 34.2 36.7 | 2.6 3.3 3.8 3.5 3.1 3.4 2.8 | 14.3 12.4 15.8 15.6 15.5 13.8 13.4 | 11.6 11.4 14.8 13.9 12.9 11.8 12.9 | 7.1 4.6 8.2 4.5 6.6 6.8 7.9 | 2.7 2.4 3.5 3.4 3.1 2.1 2.3 | 27.5 24.8 29.1 26.7 26.6 27.7 24.9 | 19.3 19.8 20.1 22.8 22.2 17.7 18.6 | 18.0 17.8 20.7 19.8 19.9 17.6 21.2 | 4.6 4.2 6.4 4.8 4.7 4.9 5.3 | 18.2 20.7 21.6 19.2 19.3 17.1 20.5 | 54.7 53.9 61.9 53.1 53.5 53.7 51.2 | 20.0 17.3 18.5 20.0 20.2 20.6 21.0 | 5.4 4.5 4.8 4.7 4.8 4.4 4.4 | 60.3 56.4 56.1 51.4 51.8 49.3 56.8 |
Claims (7)
1, pretreatment
Putting into stainless steel cask after freezing Medulla sus domestica cleaned twice with purified water thaws naturally;
2, homogenate
Add purified water by 1: 1～3 and stir 5～30min, colloid mill homogenate twice, fineness 20 μ m, fineness 10 μ m for the second time for the first time;
3, primary enzymolysis
Homogenate is put in the hydrolytic decomposition pot, transfers pH value 3.0～6.0 with HCl, is heated to 30～50 ℃, presses raw material weight and adds 1～10% gastric enzyme enzymolysis, and enzymolysis was heated to 80～100 ℃ of 15～30min after 12～18 hours, cooled to 30～50 ℃;
4, secondary enzymolysis
Transfer pH value 7.0～9.5 with NaOH, press raw material weight and add 1～10% pancreatin, 30～50 ℃ of hydrolysis temperatures, 1～6 hour post-heating to 80～100 ℃ 15～30min of enzymolysis, filter cloth filters when cooling to 30～50 ℃, gets coarse filtration liquid, take by weighing weight, calculated yield;
5, fine straining
Coarse filtration liquid is put in the jacketed pan by filtrate weight 0.1～1% and is added after medicinal carbon is heated to 80～100 ℃ of stirring and adsorbing 15～30min, when cooling to 25～35 ℃, with 0.45 μ m filtering with microporous membrane carbon removal, reuse 0.22 μ m filtering with microporous membrane, get fine straining liquid, take by weighing weight, calculated yield;
6, ultrafiltration
Fine straining liquid is transferred pH value 6.0～8.0, and 20～25 ℃ of fluid temperature are with 3000～10000 dalton's ultrafilter ultrafiltration, pressure 0.05～0.1MPa.Ultrafiltrate is packed in the pyrogen-free Plastic Drum, sampling censorship, refrigerated storage;
7, freeze-dry process
(1), take by weighing the adjuvant of recipe quantity, add the injection water, stir and make dissolving, add needle-use activated carbon by 0.05～1% of solution amount, 80～100 ℃ are stirred 15～35min, it is clear and bright to be filtered to solution, standby;
(2), get the Cerebrolysin Vial extracting solution of recipe quantity, mix with above-mentioned solution, add the injection water to 80～90% of solution total amount, transfer pH to 6.0～8.0, after-teeming is penetrated water to full dose;
(3), cross microporous filter membrane, mensuration content;
(4), fill is in glass tube vial;
(5), sample that fill is good inserts in the freezer dryer, is cooled to-50～-20 ℃ earlier, is incubated 1～6 hour, evacuation then, and by 1～2 ℃ of/hour intensification, after temperature reaches-5 ℃, be warming up to 45 ℃ by 5～10 ℃/hour is incubated 2～3 hours, the moulding plug;
(6), Zha Gai, quality inspection, the vanning.
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Cited By (5)
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| CN100525833C (en) * | 2007-09-21 | 2009-08-12 | 南京大学 | A method for forming dextran 40/polypeptide freeze dried powder injection solution |
| CN101637457B (en) * | 2009-09-01 | 2011-06-08 | 广州市隆赋药业有限公司 | Preparation method for cerebroprotein hydrolysate freeze-dried injection for injection |
| CN101371917B (en) * | 2007-08-20 | 2011-08-24 | 俞嘉林 | Brain protein hydrolysate sodium chloride injection |
| CN102166200A (en) * | 2011-04-12 | 2011-08-31 | 罗诚 | Freeze-drying composition containing cerebroprotein hydrolysates and preparation method of freeze-drying composition |
| CN101343317B (en) * | 2007-07-09 | 2012-01-04 | 锡林郭勒盟鑫泰生物制品有限责任公司 | Brain peptide, preparation and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101343317B (en) * | 2007-07-09 | 2012-01-04 | 锡林郭勒盟鑫泰生物制品有限责任公司 | Brain peptide, preparation and uses thereof |
| CN101371917B (en) * | 2007-08-20 | 2011-08-24 | 俞嘉林 | Brain protein hydrolysate sodium chloride injection |
| CN100525833C (en) * | 2007-09-21 | 2009-08-12 | 南京大学 | A method for forming dextran 40/polypeptide freeze dried powder injection solution |
| CN101637457B (en) * | 2009-09-01 | 2011-06-08 | 广州市隆赋药业有限公司 | Preparation method for cerebroprotein hydrolysate freeze-dried injection for injection |
| CN102166200A (en) * | 2011-04-12 | 2011-08-31 | 罗诚 | Freeze-drying composition containing cerebroprotein hydrolysates and preparation method of freeze-drying composition |
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