CN102210704A - Process for removing pyrogen from polypeptide donkey-hide gelatin dextran - Google Patents
Process for removing pyrogen from polypeptide donkey-hide gelatin dextran Download PDFInfo
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- CN102210704A CN102210704A CN2011101484056A CN201110148405A CN102210704A CN 102210704 A CN102210704 A CN 102210704A CN 2011101484056 A CN2011101484056 A CN 2011101484056A CN 201110148405 A CN201110148405 A CN 201110148405A CN 102210704 A CN102210704 A CN 102210704A
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- active carbon
- corii asini
- colla corii
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- plasma substitute
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Abstract
The invention relates to a process for removing pyrogen from polypeptide donkey-hide gelatin dextran, belonging to the technical field of medicine. The process for removing pyrogen from polypeptide donkey-hide gelatin dextran is characterized in that granular activated carbon processed by deoxysodium cholate is used for removing pyrogen. After being processed by deoxysodium cholate, the activated carbon has good affinity with pyrogen; and meanwhile, because pyrogen is in full contact with the activated carbon, the pyrogen is thoroughly removed, and the filtration rate is high, thus the process is suitable for large-scale production of polypeptide donkey-hide gelatin dextran.
Description
Technical field
The present invention relates to a peptide species Colla Corii Asini plasma substitute depyrogenation technology, belong to medical technical field.
Background technology
As everyone knows, blood plasma is the liquid part of blood circulation, is a kind of serum albumin, inorganic salts, electrolyte, glucose and fibrinogenic aqueous solution of containing.At ordinary times particularly the wartime when human body severe loss of blood occurs because of various reasons, all need replenish blood plasma, use human serum/blood plasma and blood products and become not fool proof with some disease such as hepatitis, acquired immune deficiency syndrome (AIDS) etc. by blood-borne.Add human body blood source and be restricted, price is expensive again, and oneself can not satisfy a large amount of needs with blood therefore to depend merely on human body blood source.Exploitation and the plasma substitute of developing non-blood of human body have become the problem that scientific and technological circle and medical circle are extremely paid close attention to and paid attention to.
Current in clinical medicine, the plasma substitute of widespread usage is dextran, hetastarch and gelatine plasma substitutes.The untoward reaction of dextran clinical practice is more, as pseudoagglutination, acceleration erythrocyte sedimentation rate, the inhibition phagocytic function system of anaphylaxis, acute renal failure, cumulative action, bleeding tendency, cross matching experiment.The biological effect of hetastarch depends on its mean molecule quantity and the substitution value of ethoxy, dilatation intensity than the hetastarch of low relative molecular mass is little, it is longer to accumulate the phase than the hetastarch of high molecular weight in internal organs, erythrocyte aggregation is increased, bleeding time prolongs, the low hetastarch that replaces in blood circulation easily by the hydrolysis of hemodiastase institute, retention time is shorter in circulation, and high replacement hetastarch can body accumulation take place because of overstand and clotting mechanism is impaired.And the complicated process of preparation of this class plasma substitute, process conditions control is difficult, the few and price height of finished product output, and its composition does not participate in the internal metabolism process based on low-molecular-weight, no nutritive value.Studies show that, gelatine plasma substitutes has best blood compatibility, even heavy dose of infusion also influences clotting mechanism and fibrinolytic system hardly, symptoms of allergic is also slight than plasma protein or dextran in clinical practice, is preferred plasma substitute.Can there be 3 kinds for the gelatine plasma substitutes of clinical use, i.e. oxypolygelatin, urea connection gelatin, succinyl gelatin.Oxypolygelatin is used for clinical in nineteen fifty-one, but the anaphylaxis incidence rate is higher, and once report is used back generation anaphylactic shock death cases, and is also influential to erythrocyte sedimentation rate and blood group evaluation, now few using.Urea connection gelatin makes and is answering owing to calcium ion concentration in its solution is too high
Gelatin phenomenon appears with middle meeting.Succinyl gelatin is the colloid solution that is formed through succinylation by bovine collagen, and the skin rashes reaction is more, and along with the appearance and the whole world of bovine spongiform encephalopathy are spread, the reuse Os Bovis seu Bubali does not prepare gelatin.Seek new collagen protein the source, explore new technology, prepare that blood plasma substitute is extremely urgent safely and effectively.
Polypeptide Colla Corii Asini plasma substitute belongs to gelatin class plasma substitute, the effect of its expanding blood volume, microcirculation improvement is outstanding, and have and promote regeneration of erythrocytes, promote the advantage that impaired hepatocyte recovers, to become ideal blood plasma product of new generation, can be widely used in replenishing under the various situations such as war wound, wound, burn, operation blood volume, keep blood pressure, not only market is considerable, and has bigger social meaning.
Pyrogen system can pyrogenicity the corpse and the metabolite thereof of microorganism, i.e. a kind of endotoxin of antibacterial.Antibacterial, mycete, virus all can produce pyrogen.The main characteristic of pyrogen is a thermostability, and its complex for being made up of phospholipid, lipopolysaccharide and protein is present between the cell and solid film of antibacterial.Lipopolysaccharide is endotoxic main component, the pyrogen activity that tool is very strong.The pyrogen molecular weight is about 10 * 105.The injection that injects human body contains the pyrogen amount and reaches 1 μ g/kg and just can cause untoward reaction, exothermic reaction occurs after injecting 1 hour usually, human body produced feel cold, shiver, generate heat, perspire, feel sick, symptom such as vomiting, sometimes body temperature can rise to more than 40 ℃, severe patient even stupor, collapse, as untimely rescue, but threat to life.This phenomenon is called " pyrogen reaction ".
The method of removing pyrogen from injections generally is that active carbon powder boils absorption method or ultrafiltration at present, yet the polypeptide Colla Corii Asini contains a large amount of macromole gelatin polypeptide, water-soluble back viscosity is bigger, the adsorption efficiency that active carbon powder boils the absorption method pyrogen is not high, and after boiling, it is very slow to filter decarbonization rate, has a strong impact on production efficiency; Ultrafiltration is removed active carbon, and then the loss of macromole gelatin polypeptide is more, influences the quality of product.Polypeptide Colla Corii Asini plasma substitute demands developing new depyrogenation technology urgently.
Summary of the invention
The purpose of this invention is to provide a kind of Colla Corii Asini of polypeptide safely and efficiently plasma substitute depyrogenation its preparation process.
At the foregoing invention purpose, the invention provides following technical scheme:
One peptide species Colla Corii Asini plasma substitute depyrogenation technology is characterized in that the granular active carbon removal pyrogen that adopts sodium deoxycholate to handle.
The granular active carbon that described sodium deoxycholate was handled, its processing method is characterised in that: active carbon and sodium deoxycholate were boiled in water 0.5～2 hour, and the consumption of sodium deoxycholate is 0.001%～1% of an active carbon weight, is preferably 0.1%.
The granular active carbon that described sodium deoxycholate was handled, the mean diameter that it is characterized in that granular active carbon is preferably 2 millimeters between 1 millimeter-5 millimeters.
Described polypeptide Colla Corii Asini plasma substitute depyrogenation technology is characterized in that comprising: with the pillar of polypeptide Colla Corii Asini solution by the granular active carbon loading sodium deoxycholate and handled.
The pillar of the granular active carbon that described filling sodium deoxycholate was handled, the height of its filling compares greater than 10 with diameter.
Described polypeptide Colla Corii Asini, the preparation method of its polypeptide Colla Corii Asini is: select that health, anosis donkey are cleaned, slaughter for use, peeling, unhairing, degrease, 2% soaking in sodium carbonate solution 5 minutes, clean up, decocting and concentrating and isolated by filtration, top layer little fat and bottom precipitation thing, further concentrate drying becomes virgin rubber, the virgin rubber thin up, centrifugal, it is refining with cation exchange resin to get supernatant, filters and removes impurity, vacuum drying, promptly.
Beneficial effect of the present invention mainly is:
The affinity that active carbon is handled back and pyrogen through sodium deoxycholate is good, because pyrogen fully contacts with active carbon, and pyrogen is removed thoroughly, the rate of filtration is fast, is suitable for the large-scale production of polypeptide Colla Corii Asini plasma substitute simultaneously.
The specific embodiment
Below in conjunction with example the present invention is described in further detail, but scope of the present invention is not subjected to any restriction of these examples.
Embodiment 1
Select for use healthy, anosis donkey is cleaned, slaughter, peeling, unhairing, degrease, 2% soaking in sodium carbonate solution 5 minutes cleans up, decocting and concentrating and isolated by filtration, top layer little fat and bottom precipitation thing, further concentrate drying becomes virgin rubber, the virgin rubber thin up, centrifugal, it is refining with cation exchange resin to get supernatant, filters and removes impurity, vacuum drying, packing promptly gets the polypeptide Colla Corii Asini.
Polypeptide Colla Corii Asini 250g, sodium chloride 70g, escherichia coli culture fluid are dissolved in the 20L water for injection, make and contain a certain amount of bacterial endotoxin, transfer pH value 6.5, standby.
Get the polypeptide Colla Corii Asini solution of the above-mentioned pollution of 10L, add the 50g active carbon powder and boil 1h, 0.45 micron membrane filtration of 100 millimeters of diameters filtered 76 minutes consuming time under the 0.2Mpa pressure, detect the endotoxin in the filtrate, calculate endotoxin removal rate (the results are shown in Table 1).
Get the polypeptide Colla Corii Asini solution of the above-mentioned pollution of 10L; pillar (height of filling is 18 with the diameter ratio) by 50g granular active carbon (mean diameter is 2 millimeters) filling; natural filtration; filtered 16 minutes consuming time; 0.2Mpa 0.45 micron membrane filtration of 100 millimeters of diameters under the pressure; filtered 7 minutes consuming time, and detected the endotoxin in the filtrate, calculate endotoxin removal rate (the results are shown in Table 1).
50g granular active carbon (mean diameter is 2 millimeters) and 50mg sodium deoxycholate were boiled in water 1 hour; get granular active carbon and fill pillar (height of filling is 18 with the diameter ratio); natural filtration; filtered 15 minutes consuming time; 0.2Mpa 0.45 micron membrane filtration of 100 millimeters of diameters under the pressure; filtered 5 minutes consuming time, and detected the endotoxin in the filtrate, calculate endotoxin removal rate (the results are shown in Table 1).
The endotoxin removal rate of table 1 different process polypeptide Colla Corii Asini
| Technology | Endotoxin removal rate (%) |
| The active carbon powder boiling method | 76.3 |
| Granular active carbon is crossed the post method | 91.1 |
| The granular active carbon that sodium deoxycholate was handled is crossed the post method | 99.8 |
Embodiment 2
Select for use healthy, anosis donkey is cleaned, slaughter, peeling, unhairing, degrease, 2% soaking in sodium carbonate solution 5 minutes cleans up, decocting and concentrating and isolated by filtration, top layer little fat and bottom precipitation thing, further concentrate drying becomes virgin rubber, the virgin rubber thin up, centrifugal, it is refining with cation exchange resin to get supernatant, filters and removes impurity, vacuum drying, packing promptly gets the polypeptide Colla Corii Asini, and the mean molecule quantity of polypeptide Colla Corii Asini is 15800.
Polypeptide Colla Corii Asini 250g, sodium chloride 70g, escherichia coli culture fluid are dissolved in the 20L water for injection; make and contain 1EU endotoxin/ml; transfer pH value 6.5; the pillar (height of filling is 16 with the diameter ratio) that the granular active carbon of handling by the 100g sodium deoxycholate (mean diameter is 2 millimeters) is filled; natural filtration; filtrate is regulated pH7.0-7.5; 0.2Mpa 0.45 micron membrane filtration of 100 millimeters of diameters under the pressure; filtrate is divided in the infusion bottle of the 250mL that packs into; 115 ℃ of pressure sterilizings 45 minutes are checked weight average molecular weight and endotoxin content (the results are shown in Table 2).
The molecular weight and the endotoxin content measurement result of table 2 polypeptide Colla Corii Asini plasma substitute
| Molecular weight | Endotoxin content (EU/ml) |
| 15800 | Do not detect |
Claims (8)
1. a peptide species Colla Corii Asini plasma substitute depyrogenation technology is characterized in that the granular active carbon removal pyrogen that adopts sodium deoxycholate to handle.
2. a peptide species Colla Corii Asini plasma substitute depyrogenation technology according to claim 1; the preparation method that it is characterized in that the granular active carbon that described sodium deoxycholate was handled: active carbon and sodium deoxycholate boiled in water 0.5～2 hour, and the consumption of sodium deoxycholate is an active carbon weight 0.001%～1%.
3. a peptide species Colla Corii Asini plasma substitute depyrogenation technology according to claim 2 is characterized in that the consumption of sodium deoxycholate is 0.1% for active carbon weight.
4. a peptide species Colla Corii Asini plasma substitute depyrogenation technology according to claim 1, the mean diameter that it is characterized in that described granular active carbon is 1 millimeter-5 millimeters.
5. a peptide species Colla Corii Asini plasma substitute depyrogenation technology according to claim 4, the mean diameter that it is characterized in that described granular active carbon is 2 millimeters.
6. polypeptide Colla Corii Asini plasma substitute depyrogenation technology according to claim 1 is characterized in that comprising: with the pillar of polypeptide Colla Corii Asini solution by the granular active carbon loading sodium deoxycholate and handled.
7. polypeptide Colla Corii Asini plasma substitute depyrogenation technology according to claim 6 is characterized in that the pillar of the granular active carbon that described filling sodium deoxycholate was handled, and the height of its filling and diameter are than greater than 10.
8. polypeptide Colla Corii Asini plasma substitute depyrogenation technology according to claim 1, the preparation method that it is characterized in that described polypeptide Colla Corii Asini is: select that health, anosis donkey are cleaned, slaughter for use, peeling, unhairing, degrease, 2% soaking in sodium carbonate solution 5 minutes, clean up, decocting and concentrating and isolated by filtration, top layer little fat and bottom precipitation thing, further concentrate drying becomes virgin rubber, the virgin rubber thin up, centrifugal, it is refining with cation exchange resin to get supernatant, filters and removes impurity, vacuum drying, promptly.
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| CN2011101484056A CN102210704A (en) | 2011-06-03 | 2011-06-03 | Process for removing pyrogen from polypeptide donkey-hide gelatin dextran |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771914A (en) * | 2005-10-25 | 2006-05-17 | 江苏正大天晴药业股份有限公司 | Freeze dried polyene lecithin powder for injection and its prepn |
| CN101185657A (en) * | 2007-09-05 | 2008-05-28 | 中国人民解放军北京军区白求恩国际和平医院256临床部 | Production process and device for donkey-hide gelatin plasma substitutes |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771914A (en) * | 2005-10-25 | 2006-05-17 | 江苏正大天晴药业股份有限公司 | Freeze dried polyene lecithin powder for injection and its prepn |
| CN101185657A (en) * | 2007-09-05 | 2008-05-28 | 中国人民解放军北京军区白求恩国际和平医院256临床部 | Production process and device for donkey-hide gelatin plasma substitutes |
Non-Patent Citations (1)
| Title |
|---|
| 《科学技术与工程》 20081001 陈孝云等 活性炭表面化学改性及应用研究进展 5463-5467 1-8 第8卷, 第19期 * |
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Application publication date: 20111012 |