CN106632721A - Glucose polymer, and preparation method and applications thereof - Google Patents
Glucose polymer, and preparation method and applications thereof Download PDFInfo
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- CN106632721A CN106632721A CN201510736347.7A CN201510736347A CN106632721A CN 106632721 A CN106632721 A CN 106632721A CN 201510736347 A CN201510736347 A CN 201510736347A CN 106632721 A CN106632721 A CN 106632721A
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Abstract
The invention provides a glucose polymer, and a preparation method and applications thereof. The weight average molecular weight of the glucose polymer ranges from 20000 to 45000 daltons, and polydispersity index ranges from 2.4 to 3.0. According to the preparation method, preparation technology of the glucose polymer is improved greatly via controlling on hydrolysis and ultrafiltration conditions, equipment cost is reduced effectively, and an adopted peritoneal dialysis solution is high in substance removing rate, so that peritoneal dialysis effect is improved effectively.
Description
Technical field
The present invention relates to field of medicaments, and in particular to glucose polymer, Preparation Method And The Use.
Background technology
Used as the last common stage of all types development of renal disease, ESRD (ESRD) is the disease for seriously threatening human health.Due to being limited by kidney source, high expense and rejection etc. affect, kidney transplant treatment ESRD is not still universal, peritoneal dialysis (abdomen is saturating), particularly continuous ambulatory peritoneal dialysis, it is a kind of method of effectively treatment ESRD, nearly all patient ERSD is adapted to, the prefered method that kidney trouble replaces treatment is recommended as by the saturating expert of authoritative abdomen.
At present the bleeding agent of peritoneal dialysis liquid conventional use of in the world is mainly glucose, amino acid, Icodextrin etc., their features are different, wherein Icodextrin is a kind of novel dialytic liquid with starch-polysaccharides as bleeding agent, it is preferable peritoneal dialysis solution generally acknowledged at present, it is developed earliest by ATTELION companies of the U.S., and FDA approvals were obtained in 2002 by hundred special medical companies, illustrate in the package insert that FDA is announced：Icodextrin peritoneal dialysis solution is the peritoneal dialysis solution comprising colloid Icodextrin, and Icodextrin is a kind of water miscible glucose polymer, and weight-average molecular weight is 13000～19000 dalton, and quantity-mean molecule quantity is 5000～6500 dalton.At present external production technology is with maltodextrin solution as initiation material, with the milipore filter ultrafiltration of molecular cut off 45000, then with the milipore filter ultrafiltration of molecular cut off 1638；Add activated carbon to process, be spray-dried to obtain finished product.
This area remains a need for preparation technology simpler, the more preferable peritoneal dialysis solution of dialysis-effect.
The content of the invention
The present inventor Jing is constantly studied, it is found that a class novel grape glycopolymers, there is higher material clearance rate by its obtained peritoneal dialysis solution, and by hydrolysis and the control of ultra-filtration conditions, the preparation technology of the glucose polymer is greatly optimized, the present invention is to find based on more than and complete.
A first aspect of the present invention provides a kind of glucose polymer, and its weight average molecular weight is 20,000～45,000 dalton, and polydispersity coefficient is 2.4～3.0.
In one embodiment of the invention, the number-average molecular weight of the glucose polymer is 5,400～11,400.
In a preferred embodiment of the invention, the weight average molecular weight of the glucose polymer is 24,000～30,000, and polydispersity coefficient is 2.4～2.8.
A second aspect of the present invention provides a kind of dialysis solution, and it includes the glucose polymer described in any one of first aspect present invention.
In one embodiment of the invention, wherein the concentration of the glucose polymer is 7～15%w/v, for example, for example, 7～12%w/v, 7～10%w/v.
In one embodiment of the invention, wherein the concentration of the glucose polymer is 7～8.5%w/v.
In one embodiment of the invention, the dislysate also contains electrolyte, buffer or combination.
In one embodiment of the invention, wherein the electrolyte is the material that can be ionized in the dialysis solution, such as sodium salt, calcium salt, magnesium salts, sylvite, lactate or its any combination.
In one embodiment of the invention, wherein the buffer is selected from carbonate, citrate, acetate, amino acid or its any combination.
A third aspect of the present invention provides the preparation method of the glucose polymer described in any one of first aspect present invention, and it is comprised the following steps：
(1) starch is hydrolyzed in acid condition, when product weight average molecular weight is 15,000～40, when in the range of 000, reactant liquor pH is adjusted to neutrality, obtain hydrolyzate；
(2) step (1) gained hydrolyzate is carried out into ultrafiltration, obtains weight average molecular weight for 20,000～45,000, the ultrafiltration product that polydispersity coefficient is 2.4～3.0；
(3) the ultrafiltration product that drying steps (2) are obtained, obtains final product the glucose polymer.
In one embodiment of the invention, ultrafiltration described in step (2) refers to hydrolysate of the molecular cut off more than 5,000.
In one embodiment of the invention, ultrafiltration obtains weight average molecular weight for 24,000～30,000, the ultrafiltration product that polydispersity coefficient is 2.4～2.8 in step (2).
In one embodiment of the invention, methods described is characterised by following one or more：
1) starch described in step (1) is cornstarch；
2) concentration of starch is 0.1～0.5%w/v in the hydrolysis of step (1)；
3) concentrated hydrochloric acid is added in the hydrolysis of step (1), it is preferable that the ratio of starch and concentrated hydrochloric acid is (40～60)：1 (Kg/L, preferably (45～50)：1)；
4) hydrolysis temperature is 80～100 DEG C, preferably 85～95 DEG C, more preferably 90～95 DEG C in step (1)；
5) methods described also includes, the step of decolourizing to the hydrolyzate before step (2), it is preferable that decolourized using craboraffin；It is highly preferred that the decolouring is carried out at 35～50 DEG C, preferably 40～45 DEG C；
6) methods described also includes, the step of the degerming or insoluble impurity of removing before carrying out ultrafiltration to step (1) gained hydrolyzate, for example by filtration sterilization or the insoluble impurity of removing, preferably, the aperture of filter membrane used is filtered at 0.1-0.5 μm, such as 0.2 μm；
7) ultrafiltration described in step (2) refers to hydrolysate of the molecular cut off more than 5000；
8) ultrafiltration carries out 1～3 time described in step (2)；
9) also include that miillpore filter is crossed to the ultrafiltration product carries out refined step before step (3) drying, preferred aperture is 0.1～0.2 μm of miillpore filter, such as 0.1 μm；
10) the 9) described the refining of item carry out under the conditions of heating (backflow)；
11) the 9) item it is described it is refined after also include to system the step of being incubated for 70～90 DEG C, it is preferable that in 75～85 DEG C of insulations；
12) in step (3) using being dried to product by the way of spray drying, it is preferable that the condition of the spray drying is：180～190 DEG C of EAT, 100～110 DEG C of leaving air temp expects pump 0～50Hz of rotational frequency.
A fourth aspect of the present invention provides the preparation method of the dialysis solution described in any one of second aspect present invention, and it is comprised the following steps：
Glucose polymer described in any one of first aspect present invention of recipe quantity is configured to into the aqueous solution that concentration is 7～15%w/v, the dialysis solution is obtained final product.
In one embodiment of the invention, glucose polymer described in any one of first aspect present invention of recipe quantity is configured to into the aqueous solution that concentration is 7～12%w/v (such as 7～10%w/v, such as 7～8.5%w/v), the dialysis solution is obtained final product.
In one embodiment of the invention, it to the aqueous solution also comprising the step of decolouring, preferably, the decolouring is carried out at 60-80 DEG C (such as 70 DEG C), preferably, decolourized using the activated carbon of 0.1～10% (w/v), such as 0.1～1% (w/v), such as 0.6% (w/v).
In one embodiment of the invention, wherein the water is water for injection.
Purposes of the glucose polymer described in another aspect of the present invention offer any one of first aspect present invention in the dislysate for preparing treatment ephrosis.
In one embodiment of the invention, wherein the ephrosis includes renal insufficiency (such as acute or chronic renal insufficiency), kidney failure, uremia or ESRD.
Purposes of the dialysis solution described in another aspect of the invention offer any one of second aspect present invention in the medicine for preparing treatment ephrosis.
In one embodiment of the invention, wherein the ephrosis includes renal insufficiency (such as acute or chronic renal insufficiency), kidney failure, uremia or ESRD.
Detailed description of the invention
Term " glucose polymer " used is a kind of homogeneity polysaccharide by glucose polymerisation in the present invention, and its molecular formula is represented by (C6H10O5)n, wherein n values are more than 10.
Term used herein " dialysis " includes haemodialysis and peritoneal dialysis, and in embodiments of the invention it refers mainly to peritoneal dialysis, and it is a kind of a kind of dialysis of peritonaeum by the use of human body itself as dialysis membrane.Exchanging for solute and moisture is carried out by pouring into the dislysate in abdominal cavity and the plasma fraction in the capillary of peritonaeum opposite side, the metabolite and excessive moisture of internal retention is removed, while by material necessary to dislysate supplement body.
Term used herein " polydispersity coefficient (polydispersity, PDI) " is alternatively referred to as molecular weight distribution index, non-uniform index, decentralization etc..It is defined as Mw/Mn (wherein Mw, Mn attach most importance to respectively, number-average molecular weight), for weighing the width of molecular weight distribution.
In the present invention, glucose polymer its role is to maintain water and noxious material through the osmotic gradient needed for Peritoneal Transport to dialysis solution as the bleeding agent in dislysate.
Also containing electrolyte and buffer salt in heretofore described dislysate.The electrolyte is the material that can be ionized in the dislysate, including sylvite, sodium salt, calcium salt, magnesium salts, lactate, etc. or its combination.Specifically, such as sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium lactate, sodium acid carbonate etc. or its combination.The buffer salt can be bicarbonate, lactate, acetonate, acetate, citrate, amino acid, peptide, intermediate of Krebs circulations etc. or its combination.
Heretofore described dislysate can be allocated in a specific way with suitable for peritoneal dialysis therapy.Dialysis solution can be used as the single dialysis solution in single container or as two or more dialysis part in two Room or multichamber vessel.Dialysis solution can be sterilized using any suitable sterilization technology, such as autoclave, steam, ultraviolet, high pressure, filtration or combinations thereof.
The preparation method of the dislysate to glucose polymer of the present invention and containing the glucose polymer is described in detail below.
Glucose polymer of the present invention is mainly prepared through several steps as shown in Figure 1：
[1] hydrolyze：Weight average molecular weight is obtained 15 by controlling the ratio of raw material and acid, hydrolysis temperature during Starch Hydrolysis, 000～40, in the range of 000 (preferably, weight average molecular weight is 20, and 000～25, hydrolysate 000).In a preferred embodiment of the invention, the ratio of starch and concentrated hydrochloric acid is (40～60)：1(Kg/L).In the more preferred of the present invention, the ratio of starch and concentrated hydrochloric acid is (45～50)：1(Kg/L).Hydrolysis temperature should be controlled at 80～100 DEG C, preferably 85～95 DEG C, more preferably 90～95 DEG C.
[2] decolourize：This step is preferred embodiment, also can be carried out before the drying step after hydrolyzing.Decolouring scheme can refer to state of the art, and this present invention is not particularly limited.It is preferred that being decolourized at 35～50 DEG C using craboraffin, more preferably carry out at 40～45 DEG C, such as 40 DEG C.
[3] ultrafiltration：This step be in order to screen out hydrolytic process in produce small molecule product.To improve ultrafiltration efficiency, reduction instrument strain, while removing the bacterium in system and insoluble impurities, first system can be crossed into miillpore filter before ultrafiltration is carried out carries out refined filtration, it is preferred to use 0.2～0.5 μm of miillpore filter.Filtrate after refined filtration reuses the milipore filter of molecular cut off 5,000 and carries out ultrafiltration, weight average molecular weight 20,000～45, when 000 (preferably, weight average molecular weight is 24, and 000～30, when 000) be considered as qualified, the ultrafiltration can be carried out 1～3 time, until obtaining qualified products till.
[4] it is dried：The drying of glucose polymer can refer to textbook or common sense in the field and carry out, present invention preferably employs the mode being spray-dried, specific drying condition can be：180～190 DEG C of EAT, 100～110 DEG C of leaving air temp expects pump 0～50Hz of rotational frequency.To ensure product quality, the product of the present invention can further be refined before it is dried, refined scheme can be：First product is crossed into 0.1～0.2 μm of miillpore filter, heating (backflow) 10～20 minutes, then 70～90 DEG C of insulations, preferably in 75～85 DEG C of insulations.
The preparation method of dislysate of the present invention is：
Glucose polymer described in any one of first aspect present invention of recipe quantity is configured to into the aqueous solution that concentration is 7～15%w/v, the dialysis solution is obtained final product.
In one embodiment of the invention, glucose polymer described in any one of first aspect present invention of recipe quantity is configured to into the aqueous solution that concentration is 7～12%w/v (such as 7～10%w/v, such as 7～8.5%w/v), the dialysis solution is obtained final product.
In one embodiment of the invention, it to the aqueous solution also comprising the step of decolouring, preferably, the decolouring is carried out at 60-80 DEG C (such as 70 DEG C), preferably, decolourized using the activated carbon of 0.1～10% (w/v), such as 0.1～1% (w/v), such as 0.6% (w/v).
In one embodiment of the invention, it to the aqueous solution also comprising the step of decolouring, preferably, the decolouring is carried out at 60-80 DEG C (such as 70 DEG C), preferably, decolourized using the activated carbon of 0.1～10% (w/v), such as 0.1～1% (w/v), such as 0.6% (w/v).
In one embodiment of the invention, wherein the water is water for injection.
Heretofore described ephrosis refers mainly to deteriorate the chronic kidney disease of progress, mainly including renal insufficiency (such as acute or chronic renal insufficiency), kidney failure, uremia or ESRD.
Wherein described kidney failure is that various chronic renal diseases develop into a kind of pathological state that the renal function that the later stage causes partly or completely is lost.Acute renal failure and chronic renal failure can be divided into.Main clinical manifestation is：Oliguresis or anuria, low-gravity urine, urine sodium height, blood urine, albuminuria, cylindruria, water intoxication, potassemia, metabolic acidosis, azotemia etc..Uremia (or ESRD) is developed into when chronic renal failure enters whole latter stage.
Term " treatment " used refers to therapeutic treatment and preventive measure in the present invention, its objective is to prevent or delay (mitigation) targeted morbid state or illness.If experimenter is dialysed using dislysate of the present invention, one or more ephrosis indication of the experimenter and Symptoms go out observable and/or detectable reduction or improvement, then the ephrosis of experimenter successfully " is treated ".It is also understood that the prevention of described morbid state or illness or treatment not only include fully prevent or treat, also including not up to fully preventing or treat, but realize the related result of some biology or medical science.For example postpone, prevent, slowing down development or the progress of the state of an illness.
Dislysate of the present invention can be used for intermittent peritoneal dialysis (IPD), continue Non-staying in bed peritoneal dialysis (CAPD), automated peritoneal dialysis (APD) and persistent loop formula peritoneal dialysis (CCPD).The using method of dislysate should be carried out with reference to different dialysis modes or physician guidance.
The beneficial effect of the invention
The present invention is by hydrolysis and the control of ultra-filtration conditions so that the preparation technology of glucose polymer optimizes significantly, is effectively saved equipment cost, and thus obtained peritoneal dialysis solution has more preferable material clearance rate, substantially increases the effect of peritoneal dialysis.
Description of the drawings
Fig. 1 is the preparation process of the glucose polymer in one embodiment of the invention.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, it will be appreciated by those skilled in the art that the following example is merely to illustrate the present invention, and be should not be taken as limiting the scope of the invention.Unreceipted actual conditions person in embodiment, the condition advised according to normal condition or manufacturer is carried out.Agents useful for same or the unreceipted production firm person of instrument, be can pass through city available from conventional products.
Weight average molecular weight is with reference to high effective liquid chromatography for measuring (Chinese Pharmacopoeia two D of annex V of version in 2010).
Chromatographic condition and system suitability：With polysaccharide determination special gel post, it is combined using multi-angle laser light scattering detector and differential refraction detector, (18.7g sodium acetates and 34.5mL glacial acetic acid with acetate buffer as mobile phase, plus twice water dissolves and be diluted to 5L), flow velocity is 0.5ml/min, 30 DEG C of column temperature, 35 DEG C of detection temperature.
Embodiment 1
1. hydrolyze：
A, add purified water 1000L in hydrolysis kettle, open stirring, add cornstarch 250kg.
B, addition 5.1L concentrated hydrochloric acids, are warmed up to 85 DEG C or so, adjust steam valve open degree, make temperature be slowly increased to 90 DEG C, 90 DEG C of -95 DEG C of insulations.
C, insulation are recorded after 3 hours and temperature and sampled, and the weight average molecular weight of HPLC determination samples is 20930 dalton.
D, sodium hydroxide solution is added into hydrolysis kettle, adjust pH to neutrality, be cooled to about 40 DEG C.
2. decolourize：
A, sealing decolouring kettle tank mouth, decolouring kettle is evacuated to below -0.08Mpa, and feed liquid in hydrolysis kettle is drawn to into decolouring kettle, and suction is finished, plus water for injection about 100L brush tanks, opens stirring.
B, unlatching heating system heat up to feed liquid, are warming up to 40 DEG C, add 3kg craboraffins.40 ± 2 DEG C of insulations, one hour.
C, by the de- charcoal of feed liquid Jing plate filter, be delivered in ultrafiltration storage tank, sheet frame pressure<0.2MPa, before filtration terminates, plus water for injection about 100L brush tanks, filter and finish termination of pumping.
3. refined filtration：
0.2 μm of miillpore filter is arranged on plate filter, the feed liquid of ultrafiltration storage tank is filtered to ultrafiltration tank, sheet frame pressure<0.2MPa, before filtration terminates, plus water for injection about 100L brush tanks, filter and finish termination of pumping.
4. ultrafiltration：
Add purified water in ultrafiltration tank to about 1500L; start pump; start ultrafiltration, hydrolysate of the molecular cut off more than 5,000; when falling 500L feed liquids per ultrafiltration in ultrafiltration tank; again plus purified water is to 1500L, shut down after ultrafiltration the 3rd time, (weight average molecular weight is 26700 dalton after HPLC detection molecules amounts are qualified; number-average molecular weight is 9830 dalton), ultrafiltration is finished.
5. refine：
A, 0.1 μm of miillpore filter is arranged on plate filter, starts refined feed pump, flowed back 10-20 minutes, then feed liquid is delivered to into receiver, feed liquid is filtered before terminating, plus water for injection about 60L, and filtration terminates, termination of pumping.
B, unlatching receiver stirring, heat up to feed liquid, 75 DEG C are warming up to, in 75 DEG C～85 DEG C insulations.
6. it is spray-dried：
EAT (180 DEG C～190 DEG C) and leaving air temp (100 DEG C～110 DEG C) and material pump rotational frequency (0～50HZ).Hopper wall vibrator, a rewinding are opened per half an hour.(weight average molecular weight is 26700, and number-average molecular weight is 9830, and 2.6) coefficient of dispersion is to obtain new glucose polymer.
The present invention has also synthesized following glucose polymer (in addition to hydrolysis and ultrafiltration, remaining step is with embodiment 1)：
The preparation of the dextran polymer peritoneal dialysis solution of embodiment 2
80% fresh water for injection is added in dense dispensing container, adds the glucose polymer of recipe quantity, stirring that 0.6% (W/V) activated carbon, 70 DEG C of insulated and stirred absorption, decarbonization filtering are added after dissolving.Transfer liquid adds water for injection to be settled to full dose to dilute preparing tank, after cooling, opens spray pump, filling.
Prescription：Per 100ml dislysate 7～8.5g containing glucan, sodium chloride 535mg, sodium lactate 448mg, calcium chloride 25.7mg and magnesium chloride 5.08mg.
Per liter contains electrolyte：Sodium 132mEq/L, calcium 3.5mEq/L, magnesium 0.5mEq/L, chlorine 96mEq/L and lactate 40mEq/L.
The biological experiment of embodiment 3
1. material
Animal
NZw 40, male and female half and half, body weight about 1.5～2kg.
Dislysate to be measured
7%-24k glucose polymers；
7%-30k glucose polymers；
7%-45k glucose polymers；
8.5%-24k glucose polymers；
8.5%-30k glucose polymers；
8.5%-45k glucose polymers；
7.5% hundred special medical company produces Icodextrin (article No.：S14G01064, Mw=13000～19000).
2. method
Select the NZw 56 of health, male and female half and half, body weight about 1.5-2kg.Normal diet, drinking-water are given, adaptability is raised one week.Anaesthetized, abdomen is inserted in abdominal cavity and is managed thoroughly, Post operation rest 7-10 days is complete to wound healing.Completely random is divided into 7 groups, per group of 8 animals.I.e. hundred special 7.5% Icodextrin dialysis groups (being designated as Extraneal), the 7%-24k coefficients of dispersion are 2.5 glucose polymer dialysis group (being designated as sample 1), the 7%-30k coefficients of dispersion are 2.5 glucose polymer dialysis group (being designated as sample 2), the 7%-45k coefficients of dispersion are 3.0 glucose polymer dialysis group (being designated as sample 3), the 8.5%-24k coefficients of dispersion are 2.5 glucose polymer dialysis group (being designated as sample 4), the 8.5%-30k coefficients of dispersion are 2.5 glucose polymer dialysis group (being designated as sample 5), the 8.5%-45k coefficients of dispersion are 3.0 glucose polymer dialysis group (being designated as sample 6).Then the saturating therapeutic test of one-week abdomen is carried out, an abdomen is carried out daily and is treated thoroughly, every time each group peritoneal dialysis liquid of injection 30ml/kg.In dialysis 240min at the end of, collect blood and dialysis efflux sample.When detecting 240min respectively, creatinine, the concentration of urea nitrogen in blood plasma and dialysis efflux, and measure dialysis efflux cumulative volume.Calculate the concentration proportion (D/P) in dialysis efflux creatinine, urea nitrogen and blood plasma.
It is main in this experiment to select creatinine and urea nitrogen clearance to react the dialysis treatment effect of glucose polymer dislysate.In this experiment, the computing formula of creatinine and urea nitrogen clearance is as follows：
Clearance rate=(the saturating efflux cumulative volume ml × dislysate of abdomen and PC ratio D/P) ÷ 240min
Through the dialysis treatment of 240min, its creatinine and urea nitrogen clearance result see the table below each group：
| Urea nitrogen clearance (ml/min) | CrCl (ml/min) | |
| Sample 1 | 0.786±0.122 | 0.802±0.146 |
| Sample 2 | 0.773±0.125 | 0.787±0.134 |
| Sample 3 | 0.689±0.102 | 0.698±0.112 |
| Sample 4 | 0.792±0.120 | 0.821±0.120 |
| Sample 5 | 0.780±0.126 | 0.802±0.119 |
| Sample 6 | 0.714±0.119 | 0.737±0.126 |
| Extraneal | 0.588±0.080 | 0.598±0.068 |
Above each group of data is with the presentation of mean value ± SD forms.As a result show, the creatinine and urea nitrogen clearance of each glucose polymer group are above Extraneal control group (p<0.05), wherein 24-30k, the coefficient of dispersion be 2.5 glucose polymer drug effect it is more excellent.Above results of animal is pointed out, the Extraneal of the novel grape glycopolymers peritoneal dialysis liquid that we prepare external listing special better than current hundred in terms of material removes pharmacodynamics.
Although the specific embodiment of the present invention has obtained detailed description, it will be understood to those of skill in the art that.According to disclosed all teachings, various modifications and replacement can be carried out to those details, these change within protection scope of the present invention.The four corner of the present invention is given by claims and its any equivalent.
Claims (16)
1. a kind of glucose polymer, its weight average molecular weight is 20,000～45,000 dalton,
Polydispersity coefficient is 2.4～3.0.
2. the glucose polymer of claim 1, its weight average molecular weight is 24,000～30,000,
Polydispersity coefficient is 2.4～2.8.
3. a kind of dialysis solution, it includes the glucose polymer described in claim 1 or 2.
4. the dialysis solution of claim 3, wherein the concentration of the glucose polymer be 7～
15%w/v, for example, 7～12%w/v, for example, 7～10%w/v.
5. the dialysis solution of claim 3, wherein the concentration of the glucose polymer be 7～
8.5%w/v.
6. the dialysis solution of claim 5, it is also containing electrolyte, buffer or the group of the two
Close.
7. the dialysis solution of claim 6, wherein the electrolyte is in the dialysis solution
The material that can be ionized, such as sodium salt, calcium salt, magnesium salts, lactate or its any combination.
8. the dialysis solution of claim 6, wherein the buffer is selected from carbonate, citric acid
Salt, acetate, amino acid or its any combination.
9. the preparation method of the glucose polymer described in any one of claim 1-3, it includes
Following steps：
(1) starch is hydrolyzed in acid condition, when product weight average molecular weight is 15,000～
When in the range of 40,000, reactant liquor pH is adjusted to neutrality, obtain hydrolyzate；
(2) step (1) gained hydrolyzate is carried out into ultrafiltration, obtain weight average molecular weight for 20,000～
45,000th, polydispersity coefficient is 2.4～3.0 ultrafiltration product；
(3) the ultrafiltration product that drying steps (2) are obtained, obtains final product the glucose polymer.
10. the method for claim 9, ultrafiltration wherein in step (2) obtains weight average molecular weight and is
24,000～30,000, polydispersity coefficient is 2.4～2.8 ultrafiltration product.
11. the method for claim 9, it is characterised in that one or more below：
1) starch described in step (1) is cornstarch；
2) concentration of starch is 0.1～0.5%w/v in the hydrolysis of step (1)；
3) concentrated hydrochloric acid is added to be hydrolyzed in the hydrolysis of step (1), it is preferable that starch
It is (40～60) with the ratio of concentrated hydrochloric acid：1 (Kg/L, preferably (45～50)：1)；
4) hydrolysis temperature is 80～100 DEG C in step (1), preferably 85～95 DEG C, more excellent
Select 90～95 DEG C；
5) the step of decolourizing to the hydrolyzate is also included before step (2), it is preferable that
Decolourized using craboraffin, it is highly preferred that the decolouring is carried out at 35～50 DEG C,
It is preferred that 40～45 DEG C；
6) methods described also includes, degerming before ultrafiltration is carried out to step (1) gained hydrolyzate,
Or the step of insoluble impurity, such as filtration sterilization or insoluble impurity, it is preferable that filter filter used
The aperture of film at 0.1-0.5 μm, such as 0.2 μm；
7) ultrafiltration described in step (2) refers to hydrolysate of the molecular cut off more than 5000；
8) ultrafiltration carries out 1～3 time described in step (2)；
9) also include that crossing miillpore filter to the ultrafiltration product enters before step (3) drying
The refined step of row, preferred aperture is 0.1～0.2 μm of miillpore filter, such as 0.1 μm；
10) the 9) described the refining of item carry out under the conditions of heating (backflow)；
11) the 9) item it is described it is refined after also include to system the step of being incubated for 70～90 DEG C,
Preferably, in 75～85 DEG C of insulations；
12) in step (3) product is dried by the way of being spray-dried, it is preferable that
The condition of the spray drying is：180～190 DEG C of EAT, leaving air temp 100～110
DEG C, expect pump 0～50Hz of rotational frequency.
The preparation method of the dialysis solution described in 12. any one of claim 3～8, it include with
Lower step：
By the glucose polymer described in the claim 1 or 2 of recipe quantity be configured to concentration for 7～
15%w/v (for example, 7～12%w/v, for example, 7～10%w/v, for example, 7～8.5%
W/v the aqueous solution), obtains final product the dialysis solution.
Glucose polymer described in 13. claims 1 or 2 is preparing the dialysis for the treatment of ephrosis
Purposes in liquid.
The purposes of 14. claims 13, wherein the ephrosis includes that renal insufficiency is (such as acute
Or chronic renal insufficiency), kidney failure, uremia or ESRD.
Dialysis solution described in 15. any one of claim 3～8 is preparing the medicine for the treatment of ephrosis
In purposes.
The purposes of 16. claims 15, wherein the ephrosis includes that renal insufficiency is (such as anxious
Property or chronic renal insufficiency), kidney failure, uremia or ESRD.
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| CN109400722A (en) * | 2018-11-13 | 2019-03-01 | 华仁药业股份有限公司 | A method of for removing peptide glycan in glucidtemns |
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