CN1634139A - Injectio of brain protein hydrolysate and its preparing process - Google Patents
Injectio of brain protein hydrolysate and its preparing process Download PDFInfo
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- CN1634139A CN1634139A CNA2004100439392A CN200410043939A CN1634139A CN 1634139 A CN1634139 A CN 1634139A CN A2004100439392 A CNA2004100439392 A CN A2004100439392A CN 200410043939 A CN200410043939 A CN 200410043939A CN 1634139 A CN1634139 A CN 1634139A
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- protein hydrolysate
- brain protein
- preparation technology
- hydrolysate injection
- brain
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Abstract
Disclosed is an injection of brain protein hydrolysate and its preparing process wherein the injection comprises amino acid 337-1376, polypeptides 65.9-201.25, osmoregulation agent 0-100, the amino acid and polypeptides are prepared from the brain tissue of healthy mammal through ester removing, enzyme hydrolysis, hyperfiltration, and chromatography refining.
Description
Technical field: the present invention relates to a kind of brain protein hydrolysate injection and preparation technology thereof.
Background technology: brain protein hydrolysate injection system is a raw material with the health mammal brain, through enzyme hydrolysis refining and aseptic aqueous solution.Card such as dull-witted, absent minded and dysmnesia after clinical complete and dysfunction, the apoplexy in order to treatment cerebrovascular decompensation, craniocerebral injury, olivopontocerebellar atrophy, cerebral function.And can cooperate oxygen therapy or respirator assisted respiartion, in the clinical treatment chronic respiratory failure, improve patient's psychoneurosis shape, shorten and all to be better than giving merely oxygen therapy or respirator assisted respiartion aspect the course of treatment and the therapeutic effect, but its auxiliary treatment children's cerebral hypoplasia, organic syndrome and serious brain infect disease and the endogenous depression that disordered brain function, cerebral concussion or the contusion of secondary cause in addition, and epilepsy is had the support effect.Brain protein hydrolysate injection is a kind of medicine of effectively preventing cerebrovascular disease, be subjected to very much numerous doctors and patient's welcome, along with being on the rise of China's aging, aging population will reach 2.8 hundred million in 2005, account for 18.46% of total population, the sickness rate of cerebrovascular disease also will increase, and sickness rate reaches 2%～2.5% at present, its mortality rate accounts for 40% of general mortality rate, so its clinical practice has very wide prospect.
Cerebrolysin Vial solution main component is aminoacid, polypeptide, peptide matters easily aggregates into macromolecule in preservation, though the prolongation of holding time, polymer build-up, thereby cause that the anaphylaxis incidence rate also increases in the clinical practice, generally after medication, allergic symptoms such as erythra, fever, hypotension occur 5,6 days the time, so polymer substance causes that the problem of untoward reaction has had a strong impact on the clinical practice of medicine.Brain protein hydrolysate injection of the present invention, its drug level are lower than more than 10 times of Cerebrolysin Vial solution in the past, thereby reduced the incidence rate of polyreaction, and the safety that has improved medicine has solved the problem that polymer substance influences drug quality.
Summary of the invention: it is simple to the purpose of this invention is to provide a kind of preparation technology, easy to use, easily brain protein hydrolysate injection and the preparation technology thereof who stores.
The object of the present invention is achieved like this:
Brain protein hydrolysate injection and preparation technology thereof, its composition comprises: aminoacid, polypeptide and osmotic pressure regulator, described aminoacid, polypeptide are to go ester, enzyme hydrolysis, ultrafiltration, chromatography to make with extra care and make through cerebral tissue from the health mammal cerebral tissue, its parts by weight are aminoacid 337～1376, polypeptide 65.9～201.25, osmotic pressure regulator 0～100, the relative molecular cut off of polypeptides matter is 3000～10000 dalton, pH value is 5.0～8.5, show bluish violet with the ninhydrin solution reaction solution, character is little yellow or light yellow clear liquid.
Above-mentioned brain protein hydrolysate injection, described osmotic pressure regulator can be glucose, sodium chloride, mannitol, xylitol.
The preparation technology of above-mentioned brain protein hydrolysate injection, this preparation technology comprise that cerebral tissue goes ester, enzyme hydrolysis, ultrafiltration and chromatography refining.
The preparation technology of above-mentioned brain protein hydrolysate injection: described cerebral tissue goes the ester condition, and at 30 ℃～60 ℃ following vacuum dryings, the ester cerebral tissue is removed in preparation with acetone.
The preparation technology of above-mentioned brain protein hydrolysate injection, described enzyme hydrolysis condition: sour enzymolysis pH value is 1.5～3.0, alkali enzymolysis pH value is 5.5～8.5; Time is 3～24 hours; Temperature is 30 ℃～55 ℃.Described enzyme can be: pepsin, carase, pancreatin, pancreas slurry.
The preparation technology of above-mentioned brain protein hydrolysate injection, described ultrafiltration condition: with relative molecular cut off is 3000～10000 daltonian membrane ultrafiltration.
The preparation technology of above-mentioned brain protein hydrolysate injection, in the described chromatography subtractive process: the gel chromatography condition is as follows: gel model: SephadexG-10, G-15, G-25, G-50, G-75, G-100, G-150, G-200harmacia); Column type: diameter 3～64cm, high 60～1200cm; The gel loading height is 52～1040cm; Eluent: 0.05M～0.5M phosphate buffer (pH6.5～8.0); Operating room temperature: 3～20 ℃.
The preparation of above-mentioned brain protein hydrolysate injection, getting Cerebrolysin Vial solution, to add the aminoacid parts by weight that water for injection makes mixed liquor be 337～1376, the polypeptide parts by weight are 65.9～201.25, adjust pH to 5.0～8.5 are mixed, are filtered and make brain protein hydrolysate injection with dense osmotic pressure regulator solution then.
Packing specification of the present invention is 100ml, 150ml, 200ml, 250ml.
[usage and dosage] intravenous drip, a 100ml～250ml suitable slowly instils, 1 time on the one or follow the doctor's advice.
The invention has the advantages that:
1. brain protein hydrolysate injection of the present invention is to add dense osmotic pressure regulator solution in Cerebrolysin Vial solution, through mixing, filtration is made, it has overcome Cerebrolysin Vial solution and has easily caused clinical anaphylactoid defective, its drug level is compared with solution concentration and is descended 10 times, thereby descended the polymer production rate, so in storing process, reduced the generation that medicine is separated out, thereby reduced harm to patient, and brain protein hydrolysate injection need not dilution in use, not only made things convenient for but also reduced the pollution that may cause in the preparation, so clinical application is comparatively safe, is numerous doctors, the patient provides medicine safely and effectively.
2. because brain protein hydrolysate injection contains tens seed amino acids and polypeptide, be the peculiar peptidergic nerve nutritional drugs of a kind of brain.Can act on nervus centralis in many ways, regulate and improve neuronic metabolism, promote the formation of synapse, induce neuronic differentiation, and further the neuroprotective cell is avoided the infringement of various ischemias and neurotoxin.The present invention can pass through blood brain barrier, promotes the synthetic of brain internal protein, influences respiratory chain, has anoxybiotic protective capability, improves the metabolism of brain self-energy.Other hormone systems of activated adenyl cyclase and catalysis.Neurotransmitter, peptide hormone and coenzyme precursors are provided.Be used for craniocerebral trauma and cerebrovascular disease (cerebral blood supply insufficiency, cerebral infarction) sequela and concentrate the doing well,improving of obstacle with hypomnesis and attention.
3. the present invention compares with Cerebrolysin Vial solution, and this product has reduced the generation that medicine is separated out in the process of storage, and good stability has reduced the anaphylaxis incidence rate, has guaranteed patient's drug safety.
4. the preparation technology of this product is simple, advanced, easily operation.
Description of drawings: accompanying drawing 1 is technology path of the present invention and process chart.
The specific embodiment of the present invention:
Embodiment 1:
(1) preparation of defat brain powder
Get fresh mammiferous brain, homogenate.Add acetone under stirring, isolate precipitate.Precipitate acetone cyclic washing, sucking filtration is used the ether washing precipitate, and sucking filtration, precipitate are at room temperature flung to ether, then at 30 ℃ of following vacuum dryings, get degrease brain powder.
(2) enzyme hydrolysis
1) takes by weighing degrease brain powder, get pepsin, with the dissolving of an amount of purified water, add again in the defat brain powder suspension respectively, add purified water, stir evenly, solution adjust pH to 1.5,30 ℃ of hydrolysis 4 hours.After hydrolysis finishes, centrifugal collection supernatant, supernatant adjust pH to 5.5.
2) take by weighing pancreatin, add in the above-mentioned supernatant after centrifugal, adjust pH to 5.5 again, 30 ℃ of hydrolysis 2 hours.
3) get hydrolyzed solution, centrifugal collection supernatant, white precipitate are centrifugal again after washing with purified water, collect supernatant, merge supernatant twice, with molecular cut off 3000 membrane ultrafiltration, collect ultrafiltrate.
(3) chromatography is refining: get ultrafiltrate, after the gel bed was used 0.5M phosphate buffer (pH6.5) balance, last sample carried out eluting with eluent, and flow speed control behind the eluting, begins to collect the bioactive peptide peak, as eluent I at the 3ml/ branch.Continue to use the eluent eluting, as eluent II.The eluent I, the eluent II that collect are evaporated to certain volume respectively, are heated to 50 ℃, 5 minutes, and cooling is filtered, and collects filtrate, gets Cerebrolysin Vial elaboration liquid I and Cerebrolysin Vial elaboration liquid II.
Described gel chromatography condition is as follows: gel model: SephadexG-10harmacia); Column type: diameter 3cm, high 60cm; The gel loading height is 52cm; Eluent: 0.5M phosphate buffer (pH6.5); Operating room temperature: 20 ℃.
(4) preparation of Cerebrolysin Vial solution
Cerebrolysin Vial elaboration liquid I mixes with Cerebrolysin Vial elaboration liquid II, and adding the aminoacid parts by weight that water for injection makes mixed liquor is 337, and the polypeptide parts by weight are 65.9, and adjust pH to 5.0 promptly gets Cerebrolysin Vial solution.
(5) preparation of brain protein hydrolysate injection: Cerebrolysin Vial solution is mixed, filters and make brain protein hydrolysate injection with dense osmotic pressure regulator solution.
Packing specification of the present invention is 100ml, 150ml, 200ml, 250ml.
[usage and dosage] intravenous drip, a 100ml～250ml suitable slowly instils, 1 time on the one or follow the doctor's advice.
Claims (8)
1. brain protein hydrolysate injection and preparation technology thereof, its composition comprises: aminoacid, polypeptide and osmotic pressure regulator, it is characterized in that: described aminoacid, polypeptide is to remove ester through cerebral tissue from the health mammal cerebral tissue, enzyme hydrolysis, ultrafiltration, chromatography is made with extra care and is made, its parts by weight are aminoacid 337～1376, polypeptide 65.9～201.25, osmotic pressure regulator 0～100, the relative molecular cut off of polypeptides matter is 3000～10000 dalton, pH value is 5.0～8.5, show bluish violet with the ninhydrin solution reaction solution, character is little yellow or light yellow clear liquid.
2. brain protein hydrolysate injection according to claim 1 is characterized in that: described osmotic pressure regulator can be glucose, sodium chloride, mannitol, xylitol.
3. the preparation technology of the described brain protein hydrolysate injection of claim 1 is characterized in that: this preparation technology comprises that cerebral tissue goes ester, enzyme hydrolysis, ultrafiltration and chromatography refining.
4. the preparation technology of brain protein hydrolysate injection according to claim 3, it is characterized in that: described cerebral tissue goes the ester process to comprise: at 30 ℃～60 ℃ following vacuum dryings, the ester cerebral tissue is removed in preparation with acetone.
5. the preparation technology of brain protein hydrolysate injection according to claim 3, it is characterized in that: described enzyme hydrolysis condition: sour enzymolysis pH value is 1.5～3.0, alkali enzymolysis pH value is 5.5～8.5; Time is 3～24 hours; Temperature is 30 ℃～55 ℃.Described enzyme can be: pepsin, carase, pancreatin, pancreas slurry.
6. the preparation technology of brain protein hydrolysate injection according to claim 3 is characterized in that: in the described ultra-filtration process, be 3000～10000 daltonian membrane ultrafiltration with relative molecular cut off.
7. the preparation technology of brain protein hydrolysate injection according to claim 3, it is characterized in that: described chromatography purification condition: the gel chromatography condition is as follows: gel model: SephadexG-10, G-15, G-25, G-50, G-75, G-100, G-150, G-200harmacia); Column type: diameter 3～64cm, high 60～1200cm; The gel loading height is 52～1040cm; Eluent: 0.05M～0.5M phosphate buffer (pH6.5～8.0); Operating room temperature: 3～20 ℃.
8. the preparation of brain protein hydrolysate injection according to claim 3, it is characterized in that: getting Cerebrolysin Vial solution, to add the aminoacid parts by weight that water for injection makes mixed liquor be 337～1376, the polypeptide parts by weight are 65.9～201.25, adjust pH to 5.0～8.5 are mixed, are filtered and make brain protein hydrolysate injection with dense osmotic pressure regulator solution then.
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| CNB2004100439392A CN100386113C (en) | 2004-10-15 | 2004-10-15 | Injectio of brain protein hydrolysate and its preparing process |
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| CNB2004100439392A CN100386113C (en) | 2004-10-15 | 2004-10-15 | Injectio of brain protein hydrolysate and its preparing process |
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| CN1634139A true CN1634139A (en) | 2005-07-06 |
| CN100386113C CN100386113C (en) | 2008-05-07 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302768A (en) * | 2011-09-04 | 2012-01-04 | 潘首德 | Method for preparing brain protein hydrolysate oral liquid |
| CN102718857A (en) * | 2012-07-09 | 2012-10-10 | 河北智同医药控股集团有限公司 | Denatured protein powder and brain protein hydrolyzate prepared from same |
| CN103656607A (en) * | 2013-12-17 | 2014-03-26 | 弘美制药（中国）有限公司 | Cerebroprotein hydrolysate in piracetam and cerebroprotein hydrolysate tablets and preparation method of cerebroprotein hydrolysate |
| CN117143850A (en) * | 2023-09-27 | 2023-12-01 | 四川德博尔制药有限公司 | Pepsin preparation method for removing blood group A substances |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1048629C (en) * | 1993-04-10 | 2000-01-26 | 北京市西城区华新生化技术研究所 | Brain hormone production method |
| CN1087940C (en) * | 1994-04-26 | 2002-07-24 | 中国药品生物制品标准化研究中心 | Method for prepn. of cerebral proteolytic liquid-cerebral health injection |
| CN1129451C (en) * | 2001-11-24 | 2003-12-03 | 海南斯达制药有限公司 | Process for preparing injection liquid of brain protein hydrolyzate |
-
2004
- 2004-10-15 CN CNB2004100439392A patent/CN100386113C/en active Active
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302768A (en) * | 2011-09-04 | 2012-01-04 | 潘首德 | Method for preparing brain protein hydrolysate oral liquid |
| CN102718857A (en) * | 2012-07-09 | 2012-10-10 | 河北智同医药控股集团有限公司 | Denatured protein powder and brain protein hydrolyzate prepared from same |
| CN102718857B (en) * | 2012-07-09 | 2013-05-22 | 河北智同医药控股集团有限公司 | Denatured protein powder and brain protein hydrolyzate prepared from same |
| CN103656607A (en) * | 2013-12-17 | 2014-03-26 | 弘美制药（中国）有限公司 | Cerebroprotein hydrolysate in piracetam and cerebroprotein hydrolysate tablets and preparation method of cerebroprotein hydrolysate |
| CN103656607B (en) * | 2013-12-17 | 2015-05-20 | 弘美制药（中国）有限公司 | Cerebroprotein hydrolysate in piracetam and cerebroprotein hydrolysate tablets and preparation method of cerebroprotein hydrolysate |
| CN117143850A (en) * | 2023-09-27 | 2023-12-01 | 四川德博尔制药有限公司 | Pepsin preparation method for removing blood group A substances |
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| CN100386113C (en) | 2008-05-07 |
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