CN102218080B - High-speed filtration preparation process of polypeptide donkey-skin gelatin plasma substitutes - Google Patents
High-speed filtration preparation process of polypeptide donkey-skin gelatin plasma substitutes Download PDFInfo
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- CN102218080B CN102218080B CN2011101484075A CN201110148407A CN102218080B CN 102218080 B CN102218080 B CN 102218080B CN 2011101484075 A CN2011101484075 A CN 2011101484075A CN 201110148407 A CN201110148407 A CN 201110148407A CN 102218080 B CN102218080 B CN 102218080B
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- polypeptide
- corii asini
- colla corii
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- porous titanium
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Abstract
The invention combines the polypeptide donkey-skin gelatins with different weight-average molecular weights and then adds tryptophan into the combined polypeptide donkey-skin gelatins to prepare the plasma substitutes containing gelatin molecules with different molecular weights. The process has the advantages that: smaller molecules can easily pass through renal glomerulus, which contributes to diuretics at the early stage of introduction; bigger molecules are left in the blood vessels, and the dilatation effect is prolonged; and the increase of the tryptophan can stimulate the synthesis of albumins so as to replenish the plasma proteins in huge loss.
Description
Technical field
The present invention relates to a peptide species Colla Corii Asini plasma substitute high-rate fitration preparation 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, 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, like 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 in internal organs, to accumulate the phase than the hetastarch of high molecular weight; Erythrocyte aggregation is increased, and the bleeding time prolongs, and low substituted hetastarch is prone in blood circulation by the hydrolysis of hemodiastase institute; RT 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 type plasma substitute, process conditions control is difficult, and finished product output is few and price is high, and its composition is main with low-molecular-weight, does not participate in the internal metabolism process, no nutritive value.Research shows; 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 supply the gelatine plasma substitutes of clinical use to have 3 kinds, promptly oxypolygelatin, urea join 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, few at present using.Urea joins gelatin owing to calcium ion concentration in its solution is too high, makes and is answering
With in gelatin phenomenon can appear.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 has the advantage that promotes regeneration of erythrocytes, promotes impaired hepatocyte recovery, will become ideal blood plasma product of new generation; Can be widely used in replenishing under the various situation such as war wound, wound, burn, operation blood volume; Keep blood pressure, not only market is considerable, and has bigger social meaning.
Contain a large amount of macromole gelatin polypeptide in the polypeptide Colla Corii Asini plasma substitute; Water-soluble back viscosity is bigger; The rate of filtration is very slow, has a strong impact on production efficiency, and because the rate of filtration is slow; In filtering process, be secondary polluted easily, so polypeptide Colla Corii Asini plasma substitute demands developing high-rate fitration preparation technology urgently.
Summary of the invention
The purpose of this invention is to provide a peptide species Colla Corii Asini plasma substitute high-rate fitration preparation technology.
To the foregoing invention purpose, the present invention provides following technical scheme:
One peptide species Colla Corii Asini plasma substitute high-rate fitration preparation technology, its characteristic comprises:
(1) in polypeptide Colla Corii Asini solution, add leucine, leucic consumption is the 0.01%-1% of polypeptide Colla Corii Asini weight, is preferably 0.1%.
(2) adopt POROUS TITANIUM rod and microporous filter membrane combination to filter, the temperature of polypeptide Colla Corii Asini solution remained on 60 ℃-80 ℃ when the POROUS TITANIUM rod filtered.
Described POROUS TITANIUM rod and microporous filter membrane combination are filtered, and it is characterized in that the specification of POROUS TITANIUM rod is 0.45 micron, and the specification of microporous filter membrane is 0.45 micron.
Described POROUS TITANIUM rod and microporous filter membrane combination are filtered, and it is characterized in that at first carrying out the titanium rod and filter, and carry out filtering with microporous membrane then.
Described polypeptide Colla Corii Asini plasma substitute high-rate fitration preparation technology is characterized in that comprising: polypeptide Colla Corii Asini, leucine etc. are dissolved in an amount of water for injection, add active carbon and boil; The POROUS TITANIUM rod filters; The temperature of polypeptide Colla Corii Asini solution remains on 60 ℃-80 ℃ during filtration, and filtrating adds the injection water to ormal weight, 0.45 micron filtering with microporous membrane; Packing, pressure sterilizing.
Described polypeptide Colla Corii Asini, the method for preparing of its polypeptide Colla Corii Asini is: select that health, anosis donkey are cleaned, slaughter for use, peeling, QUMAO, 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; Filter and remove impurity, vacuum drying promptly gets.
Beneficial effect of the present invention mainly is:
After in polypeptide Colla Corii Asini solution, adding leucine, the viscosity of polypeptide Colla Corii Asini solution can descend significantly; Polypeptide Colla Corii Asini plasma substitute adopts POROUS TITANIUM rod and microporous filter membrane combination to filter; When POROUS TITANIUM rod is filtering filtering most microgranules; And the temperature of polypeptide Colla Corii Asini solution remained on 60 ℃-80 ℃ when the POROUS TITANIUM rod filtered; Solution viscosity is little, and the rate of filtration is fast, the also unsuitable breeding of microorganism; When adopting microporous filter membrane again, removed when filtering owing to most microgranules titanium rod in front, the rate of filtration increases substantially.Filter method provided by the invention, the rate of filtration is fast, is suitable for the large-scale production of polypeptide Colla Corii Asini plasma substitute.
The specific embodiment
Below in conjunction with instance the present invention is done further explain, but scope of the present invention does not receive any restriction of these instances.
Embodiment 1
Select for use healthy, anosis donkey is cleaned, slaughter, peeling, QUMAO, degrease, 2% soaking in sodium carbonate solution 5 minutes cleans up, decocting and concentrating and isolated by filtration; Remove 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.
With polypeptide Colla Corii Asini 250g, sodium chloride 70g, be dissolved in the 20L water for injection; Transfer pH value 6.5, add the 30g active carbon powder and boiled 30 minutes, 0.45 micron filtering with microporous membrane of 150 millimeters of diameters under the 0.2Mpa pressure under the room temperature; Investigate filtration time, the result filtered 157 minutes consuming time.
With polypeptide Colla Corii Asini 250g, sodium chloride 70g, be dissolved in the 20L water for injection; Transfer pH value 6.5, add the 30g active carbon powder and boiled 30 minutes, 0.45 micron POROUS TITANIUM rod of 150 millimeters of diameters filters under the 0.2Mpa pressure; The temperature of polypeptide Colla Corii Asini solution remained on 60 ℃ when the POROUS TITANIUM rod filtered; Investigate filtration time, the titanium rod filtered 29 minutes consuming time as a result, then 0.45 micron filtering with microporous membrane of 150 millimeters of diameters under the 0.2Mpa pressure under the room temperature; Investigate filtration time, filtering with microporous membrane is 7 minutes consuming time as a result.
Polypeptide Colla Corii Asini 250g, sodium chloride 70g, leucine 0.25g are dissolved in the 20L water for injection; Transfer pH value 6.5, add the 30g active carbon powder and boiled 30 minutes, 0.45 micron POROUS TITANIUM rod of 150 millimeters of diameters filters under the 0.2Mpa pressure; The temperature of polypeptide Colla Corii Asini solution remained on 60 ℃ when the POROUS TITANIUM rod filtered; Investigate filtration time, the titanium rod filtered 8 minutes consuming time as a result, then 0.45 micron filtering with microporous membrane of 150 millimeters of diameters under the 0.2Mpa pressure under the room temperature; Investigate filtration time, filtering with microporous membrane is 5 minutes consuming time as a result.
Embodiment 2
Select for use healthy, anosis donkey is cleaned, slaughter, peeling, QUMAO, degrease, 2% soaking in sodium carbonate solution 5 minutes cleans up, decocting and concentrating and isolated by filtration; Remove top layer little fat and bottom precipitation thing, further concentrate drying becomes virgin rubber, and the virgin rubber thin up is 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, leucine 0.25g are dissolved in the 20L water for injection, transfer pH value 6.5, add the 30g active carbon powder and boiled 30 minutes; 0.2Mpa 0.45 micron of 150 millimeters of diameters POROUS TITANIUM rod filters under the pressure, the temperature of polypeptide Colla Corii Asini solution remained on 60 ℃ when the POROUS TITANIUM rod filtered, and transferred pH value 7.4; Then 0.45 micron filtering with microporous membrane of 150 millimeters of diameters under the 0.2Mpa pressure under the room temperature; Packing, filtrating divide in the infusion bottle of the 250mL that packs into, 115 ℃ of pressure sterilizings 45 minutes; The inspection mean molecule quantity, the result is 15600.
Claims (2)
1. a peptide species Colla Corii Asini plasma substitute high-rate fitration preparation technology, its characteristic comprises:
(1) in polypeptide Colla Corii Asini solution, add leucine, leucic consumption is the 0.01%-1% of polypeptide Colla Corii Asini weight;
(2) adopt POROUS TITANIUM rod and microporous filter membrane combination to filter, the temperature of polypeptide Colla Corii Asini solution remained on 60 ℃-80 ℃ when the POROUS TITANIUM rod filtered; Wherein at first carry out the titanium rod in the step (2) and filter, carry out filtering with microporous membrane then; The specification of POROUS TITANIUM rod is 0.45 micron, and the specification of microporous filter membrane is 0.45 micron.
2. polypeptide Colla Corii Asini plasma substitute high-rate fitration preparation technology according to claim 1 is characterized in that comprising:
Polypeptide Colla Corii Asini 250g, sodium chloride 70g, leucine 0.25g are dissolved in the 20L water for injection; Transfer pH value 6.5, add the 30g active carbon powder and boiled 30 minutes, 0.45 micron POROUS TITANIUM rod of 150 millimeters of diameters filters under the 0.2Mpa pressure; The temperature of polypeptide Colla Corii Asini solution remained on 60 ℃ when the POROUS TITANIUM rod filtered; Investigate filtration time, the titanium rod filtered 8 minutes consuming time as a result, then 0.45 micron filtering with microporous membrane of 150 millimeters of diameters under the 0.2Mpa pressure under the room temperature; Investigate filtration time, filtering with microporous membrane is 5 minutes consuming time as a result;
Or polypeptide Colla Corii Asini 250g, sodium chloride 70g, leucine 0.25g be dissolved in the 20L water for injection, transfer pH value 6.5, add the 30g active carbon powder and boiled 30 minutes; 0.2Mpa 0.45 micron of 150 millimeters of diameters POROUS TITANIUM rod filters under the pressure, the temperature of polypeptide Colla Corii Asini solution remained on 60 ℃ when the POROUS TITANIUM rod filtered, and transferred pH value 7.4; Then 0.45 micron filtering with microporous membrane of 150 millimeters of diameters under the 0.2Mpa pressure under the room temperature; Packing, filtrating divide in the infusion bottle of the 250mL that packs into, 115 ℃ of pressure sterilizings 45 minutes; The inspection mean molecule quantity, the result is 15600.
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| CN2011101484075A CN102218080B (en) | 2011-06-03 | 2011-06-03 | High-speed filtration preparation process of polypeptide donkey-skin gelatin plasma substitutes |
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| CN2011101484075A CN102218080B (en) | 2011-06-03 | 2011-06-03 | High-speed filtration preparation process of polypeptide donkey-skin gelatin plasma substitutes |
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| CN102218080B true CN102218080B (en) | 2012-06-27 |
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| CN102988989B (en) * | 2012-12-20 | 2014-04-23 | 江苏久吾高科技股份有限公司 | Refining and extracting method of dextran by membrane separation |
| CN113209137A (en) * | 2021-02-19 | 2021-08-06 | 林岳云 | Donkey-hide gelatin plasma substitute and preparation method thereof |
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| CN1055111A (en) * | 1990-03-24 | 1991-10-09 | 中国人民解放军空军石家庄医院 | Ass-hide glue plasma substitute and preparation method thereof |
| CN101190236A (en) * | 2006-11-30 | 2008-06-04 | 溧阳市宏兴生物工程有限公司 | Donkey hide gelatin injection plasma substitutes and preparation method thereof |
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