CN109400722A - A method of for removing peptide glycan in glucidtemns - Google Patents
A method of for removing peptide glycan in glucidtemns Download PDFInfo
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- CN109400722A CN109400722A CN201811347344.4A CN201811347344A CN109400722A CN 109400722 A CN109400722 A CN 109400722A CN 201811347344 A CN201811347344 A CN 201811347344A CN 109400722 A CN109400722 A CN 109400722A
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- glucidtemns
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 42
- 150000004676 glycans Chemical class 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 38
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 45
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000003756 stirring Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000000243 solution Substances 0.000 claims abstract description 10
- 239000012265 solid product Substances 0.000 claims abstract description 8
- 238000001179 sorption measurement Methods 0.000 claims abstract description 8
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- 230000003750 conditioning effect Effects 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 238000004321 preservation Methods 0.000 claims abstract description 4
- 229920002177 Icodextrin Polymers 0.000 claims description 19
- 229940016836 icodextrin Drugs 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 9
- 239000003610 charcoal Substances 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 238000012545 processing Methods 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 abstract description 11
- 108010013639 Peptidoglycan Proteins 0.000 abstract description 11
- 239000007787 solid Substances 0.000 abstract description 9
- 210000002381 plasma Anatomy 0.000 abstract description 4
- 241000255789 Bombyx mori Species 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000007788 liquid Substances 0.000 description 21
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 8
- 239000008103 glucose Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 238000001694 spray drying Methods 0.000 description 6
- 238000000108 ultra-filtration Methods 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 230000003292 diminished effect Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000002203 pretreatment Methods 0.000 description 5
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- 230000008901 benefit Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 239000000385 dialysis solution Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
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- 239000010839 body fluid Substances 0.000 description 2
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- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
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- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 231100000719 pollutant Toxicity 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000009738 saturating Methods 0.000 description 2
- 102000005575 Cellulases Human genes 0.000 description 1
- 108010084185 Cellulases Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 206010071648 Noninfectious peritonitis Diseases 0.000 description 1
- 206010034665 Peritoneal fibrosis Diseases 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
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- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
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- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000002016 colloidosmotic effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- -1 heavy metal ion Chemical compound 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000001455 metallic ions Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B30/00—Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
- C08B30/12—Degraded, destructured or non-chemically modified starch, e.g. mechanically, enzymatically or by irradiation; Bleaching of starch
- C08B30/18—Dextrin, e.g. yellow canari, white dextrin, amylodextrin or maltodextrin; Methods of depolymerisation, e.g. by irradiation or mechanically
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- Chemical & Material Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Peptides Or Proteins (AREA)
Abstract
The present invention provides a kind of method for removing peptide glycan in glucidtemns, its main feature is that: include the following steps: that (1) active carbon is scattered in 5 times or more water, hydrochloric acid conditioning solution pH is added between 1.0 ~ 3.0, is heated to 60 DEG C or more, 0.5 ~ 2h of stirring is filtered to dry；(2) processed active carbon is put into glucidtemns, is heated to 90 DEG C or more, 0.5 ~ 1h of stirring heat preservation；(3) then glucidtemns aqueous solution is obtained, glucidtemns is spray-dried by filtering, obtain solid product.It is lower than 2ng/g with the solid peptidoglycan content that silkworm blood plasma reagent detects.Cost of the invention is extremely low, and using a small amount of active carbon, a small amount of hydrochloric acid can greatly improve the adsorption efficiency of active carbon, and compared to other methods are used, cost is very little.
Description
Technical field
The invention belongs to medicinal chemicals to synthesize field, specifically a kind of for removing peptide glycan in glucidtemns
Method.
Background technique
Peritoneal dialysis (PD) be using the peritonaeum of patient as semi-permeable membrane, to intraperitoneal injection peritoneal dialysis liquid, by blood plasma with
Solute concentration gradient between peritoneal dialysis liquid is removed under normal circumstances as caused by nitrogen metabolism and kidney excretion with osmotic gradient
Noxious material, and help to adjust body fluid, electrolyte and the acid-base balance in body, whole end stage renal is treated as a kind of
The method of sick (end stage renal disease, ESRD) patient, it is easy to operate since its house is treated, reduce haematogenous
Transmission, the special advantages such as protection residual renal function, has been widely used in recent years.
Using glucose as bleeding agent, glucose has many advantages, such as to be easy acquirement as bleeding agent, cheap.But it is traditional
Peritoneal dialysis solution is many in high sugar, high glucose catabolite (GDPs), high-glycosylation dead end product (AGEs) and low ph value etc.
Aspect can have an adverse effect to patient, can lead to peritoneal fibrosiss after long-time use and ultrafiltration volume is reduced, be the saturating patient of abdomen
The main reason for exiting PD treatment.In addition, glucose molecule size is small, glucose is transported by rapidly peritonaeum, thus about 2
Into injections in 4 hours, lead to the loss of loss and the ultrafiltration of osmotic gradient.Therefore, glucose is not a kind of ideal infiltration
Agent needs other bleeding agents and comes instead.
Glucose polymer is macromolecular polymeric body, and molecular volume is big, directly can not pass through peritoneal wall via diffusion
Capilary is absorbed by body in into peritonaeum, therefore, in generating high colloid osmotic pressure in cavum peritoneale, to maintain the indwelling phase de-
Water and efficiency is cleaned up, meanwhile, multinomial clinical benefit is also provided: promoting the long ultrafiltration effect of patients undergoing peritoneal dialysis, improves peritoneal dialysis
Patient body fluid balance；The carbohydrate that the every Nikkei peritoneal dialysis solution of patient absorbs is reduced, patients with lipid's disease risks are reduced；Delay patient
The forfeiture of ultrafiltration efficiency extends the saturating age of patients undergoing peritoneal dialysis.
This kind of glucose polymer is all the shallow lake for obtaining specified molecular weight by sour water solution or enzymatic hydrolysis by starch
Powder hydrolysate, such as Icodextrin.However it is used for the preparation of peritoneal dialysis, microbial contamination wants strict control.But it uses
In the starting material cornstarch etc. for preparing these glucidtemns, microbial contamination is to be unable to control, often containing a large amount of
Bacterial endotoxin and peptide glycan.Endotoxin is the cell wall constituent of a variety of Gram-negative bacterias, by what is released after cellular lysate
Toxin.And peptide glycan is primarily present in the cell wall of gram-positive bacteria, existing document proves, peptide glycan may be to cause nothing
One of the main reason for bacterium property peritonitis.Therefore is had to for peritoneal dialysis class pharmaceutical preparation containing for strict control peptide glycan
Amount.The areas such as Europe, the U.S., Japan have begun working on the content for formulating peptide glycan in the preparations such as injection, peritoneal dialysis solution
Limit.
The main method of peptide glycan has enzyme edman degradation Edman, ultrafiltration, absorption method etc. at present.
Enzyme edman degradation Edman: being by the way that active enzyme component is added into the solution containing bulk pharmaceutical chemicals, such as Chinese patent (publication number
CN103228678B the rill wall that gram- bacteria is decomposed using lysozyme and laminarinase mentioned in), reaches degradation peptide
The effect of glycan.But for drug, these degrading enzymes inherently pollutant, it is subsequent will also for remove these pollutants and
Effort.
Ultrafiltration: being to realize endotoxic removal by the retention of different molecular weight.Such method can only be suitble to product point
Son amount is larger with endotoxin difference, and glucidtemns such as Icodextrin molecular weight ranges are between 2K ~ 80K, this and peptide glycan
Molecular weight be overlapped, therefore such method can not as glucidtemns removal peptide glycan conventional method.
Absorption method includes physical absorption and electrically absorption.Since peptide glycan is negatively charged, reached by ion exchange resin
To the effect of absorption, Baxter company describes such method in its patent WO2009/117302.But such method absorption
Peptide glycan amount it is limited, can not be met the requirements completely greatly increasing the amount of ion exchange resin.This is mainly due to peptide is poly-
It is electrically weaker since molecule is larger although sugar is negatively charged, cause peptide glycan not adsorbed completely.
The conventional method of physical absorption is activated carbon adsorption, generallys use activated carbon adsorption in bulk pharmaceutical chemicals and preparation terminal
The problem of mode carries out the endotoxic control of product, does not pay close attention to peptide glycan also due to the country, the less decoloration for carrying out peptide glycan are ground
Study carefully.
It when carrying out decoloration related experiment to glucidtemns, finds when the dosage of active carbon reaches the 30% of product, material
Peptidoglycan content in liquid is still higher, and conversion solid still reaches 20ng/g or more.
Document points out that the aseptic peritonitis that hundred special Icodextrin peritoneal dialysis solutions were abnormal at 2002 or so leads to
Product recall and later period research are crossed, is ultimately determined to and peptidoglycan content is higher direct correlation.Then which reports using work
Property charcoal absorption with enzyme degradation integrated processes, achieve the purpose that reduce peptidoglycan content.
Already described above, for pharmaceutical preparation, enzyme is inherently used as impurity to need studied limitation, and therefore, we attempt excellent
Change the method for activated carbon adsorption, the easier content for achieving the purpose that reduce peptide glycan.Hundred spies are in its Icodextrin preparation
The ideal peptidoglycan content required in patent is 7.9ng/ml, and being scaled Icodextrin solid is about 100ng/g.
Therefore, a kind of method for removing peptide glycan in glucidtemns how is designed, by the excellent of conventional method
Change, above-mentioned peptidoglycan content is made to reach 2ng/g or less.This is this field technical problem urgently to be resolved.
Summary of the invention
The present invention in order to solve the problems existing in the prior art, provides a kind of for removing the side of peptide glycan in glucidtemns
Method, by the method for the present invention treated solid product, peptidoglycan content reaches 2ng/g or less.
The purpose of the present invention is what is be achieved through the following technical solutions: a kind of for removing peptide glycan in glucidtemns
Method, it is characterised in that, include the following steps:
(1) active carbon is scattered in 5 times or more water, be added hydrochloric acid conditioning solution pH between 1.0 ~ 3.0, be heated to 60 DEG C with
On, 0.5 ~ 2h of stirring is filtered to dry；
(2) processed active carbon is put into glucidtemns, is heated to 90 DEG C or more, stirring 0.5 ~ 1h of heat preservation passes through work
Property charcoal discharge the hydrogen chloride that adsorbs during processing, so that pH value of solution is reached 3.0 ~ 4.0, with this condition, activity can be enhanced
The adsorption capacity of charcoal, and be unlikely to keep molecular weight product not because the reduction of acidity causes the secondary hydrolysis of glucidtemns
Become；
(3) then glucidtemns aqueous solution is obtained, glucidtemns is spray-dried by filtering, obtain solid product.
Improvement to above-mentioned technical proposal: the glucidtemns of the step (2) is Icodextrin.
Further improvement to above-mentioned technical proposal: in the step (1), the pH is 2.0, mixing time 1h；
Further improvement to above-mentioned technical proposal: in the step (2), stirring soaking time is 1h, and the pH is 3.5.
The present invention has the following advantages that compared with prior art and good effect:
1, the method for provided removal peptide glycan of the invention, implementation condition requirement is low, need to only heat reaction kettle and centrifugation
The filter plants such as machine, almost all of production line can all carry out, easy to operate, low to personnel requirement, easy to promote and utilize.
Peptidoglycan content in the solid product of the method for the present invention acquisition, which is detected, with silkworm blood plasma reagent is lower than 2ng/g.
2, cost of the invention is extremely low, and using a small amount of active carbon, a small amount of hydrochloric acid can greatly improve the suction of active carbon
Attached efficiency, compared to other methods are used, cost is very little.
3, by detection discovery, a large amount of metal ions are contained in active carbon, if magnesium ion reaches 100ug/g or more, aluminium from
Son reaches 50ug/g or more, and there are also zinc ion, including heavy metal ion, and the present invention is by the pretreatment of active carbon, not only greatly
Improve the adsorption activity of active carbon greatly, and eliminate the above-mentioned metal ion etc. for including in active carbon, make its with feed liquid
Contact process in, the almost release of non-metallic ion.
Specific embodiment
The present invention is a kind of for removing the embodiment of the method for peptide glycan in glucidtemns, includes the following steps:
(1) active carbon is scattered in 5 times or more water, be added hydrochloric acid conditioning solution pH between 1.0 ~ 3.0, be heated to 60 DEG C with
On, 0.5 ~ 2h of stirring is filtered to dry；
(2) processed active carbon is put into glucidtemns, is heated to 90 DEG C or more, stirring 0.5 ~ 1h of heat preservation passes through work
Property charcoal discharge the hydrogen chloride that adsorbs during processing, so that pH value of solution is reached 3.0 ~ 4.0, with this condition, activity can be enhanced
The adsorption capacity of charcoal, and be unlikely to keep molecular weight product not because the reduction of acidity causes the secondary hydrolysis of glucidtemns
Become；
(3) then glucidtemns aqueous solution is obtained, glucidtemns is spray-dried by filtering, obtain solid product.
The glucidtemns of above-mentioned steps (2) is Icodextrin or hydroxyethyl starch.
The following are the present invention is a kind of for removing several specific embodiments of the method for peptide glycan in glucidtemns:
The present invention is a kind of for removing the embodiment 1 of the method for peptide glycan in glucidtemns:
Purified water 30L, active carbon 3kg are added in 50L reaction kettle, salt acid for adjusting pH is added to 1.5, opens heating, is heated to 60
DEG C, insulated and stirred 1h.It is filtered under diminished pressure, obtains Pre-Treatment of Activated charcoal.
Pretreated active carbon is added in Icodextrin feed liquid (about 1200L feed liquid Icodextrin containing 200kg), is heated to
It 90 DEG C or more, is filtered after keeping the temperature 0.5h, feed liquid spray drying, it is 1.25ng/g that solid, which detects peptide glycan,.
The present invention is a kind of for removing the embodiment 2 of the method for peptide glycan in glucidtemns:
Purified water 30L, active carbon 3kg are added in 50L reaction kettle, salt acid for adjusting pH is added to 1.0, opens heating, is heated to 60
DEG C, insulated and stirred 1h.It is filtered under diminished pressure, obtains Pre-Treatment of Activated charcoal.
Pretreated active carbon is added in Icodextrin feed liquid (about 1200L feed liquid Icodextrin containing 200kg), is heated to
It 90 DEG C, is filtered after keeping the temperature 0.5h, feed liquid spray drying, it is 0.88ng/g that solid, which detects peptide glycan,.
The present invention is a kind of for removing the embodiment 3 of the method for peptide glycan in glucidtemns:
Purified water 30L, active carbon 3kg are added in 50L reaction kettle, salt acid for adjusting pH is added to 3.0, opens heating, is heated to 60
DEG C, insulated and stirred 1h.It is filtered under diminished pressure, obtains Pre-Treatment of Activated charcoal.
Pretreated active carbon is added in Icodextrin feed liquid (about 1200L feed liquid Icodextrin containing 200kg), is heated to
It 90 DEG C, is filtered after keeping the temperature 0.5h, feed liquid spray drying, it is 1.76ng/g that solid, which detects peptide glycan,.
The present invention is a kind of for removing the embodiment 4 of the method for peptide glycan in glucidtemns:
Purified water 15L, active carbon 3kg are added in 50L reaction kettle, salt acid for adjusting pH is added to 1.5, opens heating, is heated to 60
DEG C, insulated and stirred 1h.It is filtered under diminished pressure, obtains Pre-Treatment of Activated charcoal.
Pretreated active carbon is added in Icodextrin feed liquid (about 1200L feed liquid Icodextrin containing 200kg), is heated to
It 90 DEG C, is filtered after keeping the temperature 0.5h, feed liquid spray drying, it is 1.49ng/g that solid, which detects peptide glycan,.
The present invention is a kind of for removing the embodiment 5 of the method for peptide glycan in glucidtemns:
Purified water 15L, active carbon 3kg are added in 50L reaction kettle, salt acid for adjusting pH is added to 1.5, opens heating, is heated to 60
DEG C, insulated and stirred 1h.It is filtered under diminished pressure, obtains Pre-Treatment of Activated charcoal.
Pretreated active carbon was added in Icodextrin feed liquid (about 1200L contains 200kg), 90 DEG C is heated to, keeps the temperature 2h
After filter, feed liquid spray drying, solid detect peptide glycan be 1.21ng/g.
2ng/g is below with peptidoglycan content in silkworm blood plasma reagent detection above embodiments 1-5 solid product obtained.
And the comparison example without the pretreated active carbon removal peptide glycan of the method for the present invention is as follows:
To addition active carbon 25kg, 90 DEG C of insulated and stirred 1h in Icodextrin feed liquid (about 1200L feed liquid Icodextrin containing 90kg)
Afterwards, it filters, feed liquid spray drying obtains solid, is 97.3ng/g, significantly larger than the method for the present invention institute through detection peptidoglycan content
Peptidoglycan content in the solid product of acquisition.
Certainly, above description is not the limitation to invention, and the present invention is also not limited to the example above, the art
Those of ordinary skill, the variations, modifications, additions or substitutions made within the essential scope of the present invention also should belong to of the invention
Protection scope.
Claims (5)
1. a kind of method for removing peptide glycan in glucidtemns, it is characterised in that, include the following steps:
(1) active carbon is scattered in 5 times or more water, be added hydrochloric acid conditioning solution pH between 1.0 ~ 3.0, be heated to 60 DEG C with
On, 0.5 ~ 2h of stirring is filtered to dry；
(2) processed active carbon is put into glucidtemns, is heated to 90 DEG C or more, stirring 0.5 ~ 1h of heat preservation passes through work
Property charcoal discharge the hydrogen chloride that adsorbs during processing, so that pH value of solution is reached 3.0 ~ 4.0, with this condition, activity can be enhanced
The adsorption capacity of charcoal, and be unlikely to keep molecular weight product not because the reduction of acidity causes the secondary hydrolysis of glucidtemns
Become；
(3) then glucidtemns aqueous solution is obtained, glucidtemns is spray-dried by filtering, obtain solid product.
2. the method described in accordance with the claim 1 for removing peptide glycan in glucidtemns, which is characterized in that the step
(2) glucidtemns is Icodextrin.
3. the method according to claim 1 or 2 for removing peptide glycan in glucidtemns, which is characterized in that described
In step (1), the pH is 2.0, mixing time 1h.
4. the method according to claim 1 or 2 for removing peptide glycan in glucidtemns, which is characterized in that described
In step (2), stirring soaking time is 1h, and the pH is 3.5.
5. the method described in accordance with the claim 3 for removing peptide glycan in glucidtemns, which is characterized in that the step
(2) in, stirring soaking time is 1h, and the pH is 3.5.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811347344.4A CN109400722A (en) | 2018-11-13 | 2018-11-13 | A method of for removing peptide glycan in glucidtemns |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201811347344.4A CN109400722A (en) | 2018-11-13 | 2018-11-13 | A method of for removing peptide glycan in glucidtemns |
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| CN109400722A true CN109400722A (en) | 2019-03-01 |
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