CN106632721B - Glucose polymer, preparation method and application thereof - Google Patents
Glucose polymer, preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a glucose polymer, a preparation method and application thereof. Specifically, the weight average molecular weight of the glucose polymer is 20,000-45,000 daltons, and the polydispersity is 2.4-3.0. According to the invention, through the control of hydrolysis and ultrafiltration conditions, the preparation process of the glucose polymer is greatly optimized, the equipment cost is effectively saved, and the peritoneal dialysis solution has better material clearance rate, so that the peritoneal dialysis effect is greatly improved.
Description
Technical Field
The invention relates to the field of medicines, in particular to a glucose polymer, a preparation method and application thereof.
Background
End-stage renal disease (ESRD), the last common stage of the development of all types of renal disease, is a disease that is a serious threat to human health. Because of the limitation of kidney source, high cost, rejection reaction and the like, the end-stage renal disease of kidney transplantation therapy is not common, and peritoneal dialysis (peritoneal dialysis), in particular to continuous ambulatory peritoneal dialysis, is a method for effectively treating the end-stage renal disease, is suitable for almost all ERSD patients, and is recommended by an authoritative peritoneal dialysis specialist as a first choice method for replacing the renal disease.
The currently internationally and conventionally used permeability agents for peritoneal dialysis are mainly glucose, amino acid, icodextrin and the like, which have different characteristics, wherein icodextrin is a novel dialysate taking starch polysaccharide as a permeability agent, is a better peritoneal dialysate which is recognized at present, is firstly developed by ATTELION company in the United states, and is approved by FDA in 2002 by Baite medical company, and is set forth in a medicine specification published by FDA: the icodextrin peritoneal dialysis solution is a peritoneal dialysis solution containing colloidal icodextrin, wherein the icodextrin is a water-soluble glucose polymer, the weight-average molecular weight is 13000-19000 daltons, and the number-average molecular weight is 5000-6500 daltons. The existing foreign production process is that maltodextrin solution is used as an initial raw material, ultrafiltration is carried out by an ultrafiltration membrane with the cut-off molecular weight of 45000, and ultrafiltration is carried out by an ultrafiltration membrane with the cut-off molecular weight of 1638; adding active carbon for treatment, and spray drying to obtain the final product.
There is still a need in the art for peritoneal dialysis solutions that are simpler in preparation process and more effective in dialysis.
Disclosure of Invention
The inventors of the present invention have continuously studied and found a novel glucose polymer, and a peritoneal dialysis solution prepared from the glucose polymer has a high material removal rate, and the preparation process of the glucose polymer is greatly optimized through controlling hydrolysis and ultrafiltration conditions.
In a first aspect, the present invention provides a glucose polymer having a weight average molecular weight of 20,000 to 45,000 daltons and a polydispersity of 2.4 to 3.0.
In one embodiment of the present invention, the glucose polymer has a number average molecular weight of 5,400 to 11,400.
In a preferred embodiment of the present invention, the weight average molecular weight of the glucose polymer is 24,000 to 30,000, and the polydispersity is 2.4 to 2.8.
In a second aspect, the present invention provides a dialysis solution comprising a glucose polymer according to any one of the first aspect of the present invention.
In one embodiment of the present invention, wherein the concentration of the glucose polymer is 7 to 15% w/v, such as 7 to 12% w/v, such as 7 to 10% w/v.
In one embodiment of the invention, wherein the concentration of the glucose polymer is 7 to 8.5% w/v.
In one embodiment of the invention, the dialysate also contains electrolytes, buffers, or a combination of both.
In one embodiment of the present invention, wherein the electrolyte is a substance capable of ionization in the dialysis solution, such as a sodium salt, a calcium salt, a magnesium salt, a potassium salt, a lactate salt, or any combination thereof.
In one embodiment of the present invention, wherein the buffer is selected from carbonate, citrate, acetate, amino acid, or any combination thereof.
A third aspect of the present invention provides a method for producing the glucose polymer according to any one of the first aspect of the present invention, comprising the steps of:
(1) hydrolyzing starch under an acidic condition, and adjusting the pH of a reaction solution to be neutral when the weight average molecular weight of a product is within the range of 15,000-40,000 to obtain a hydrolysate;
(2) performing ultrafiltration on the hydrolysate obtained in the step (1) to obtain an ultrafiltration product with the weight-average molecular weight of 20,000-45,000 and the polydispersity of 2.4-3.0;
(3) and (3) drying the ultrafiltration product obtained in the step (2) to obtain the glucose polymer.
In a particular embodiment of the invention, said ultrafiltration in step (2) refers to hydrolysates with a molecular weight cut-off higher than 5,000.
In one embodiment of the present invention, the ultrafiltration in step (2) is carried out to obtain an ultrafiltration product having a weight average molecular weight of 24,000 to 30,000 and a polydispersity of 2.4 to 2.8.
In one embodiment of the invention, the method is characterized by one or more of the following:
1) the starch in the step (1) is corn starch;
2) the concentration of starch in the hydrolysis reaction in the step (1) is 0.1-0.5% w/v;
3) adding concentrated hydrochloric acid in the hydrolysis reaction in the step (1), preferably, the ratio of starch to concentrated hydrochloric acid is (40-60): 1(Kg/L, preferably (45-50): 1);
4) the hydrolysis temperature in the step (1) is 80-100 ℃, preferably 85-95 ℃, and more preferably 90-95 ℃;
5) the method also comprises a step of decoloring the hydrolysate before the step (2), preferably decoloring by using activated carbon for sugar; more preferably, the decolorization is carried out at 35-50 ℃, preferably 40-45 ℃;
6) the method further comprises the step of sterilizing, or removing insoluble impurities, before subjecting the hydrolysate obtained in step (1) to ultrafiltration, for example by filtration, preferably with a filter having a pore size of 0.1 to 0.5 μm, for example 0.2 μm;
7) the ultrafiltration in the step (2) refers to hydrolysate with molecular weight cutoff larger than 5000;
8) performing ultrafiltration for 1-3 times in the step (2);
9) before the drying in the step (3), refining the ultrafiltration product by a microporous filter membrane, preferably a microporous filter membrane with the pore diameter of 0.1-0.2 μm, for example 0.1 μm;
10) the purification of item 9) is carried out under heating (refluxing) conditions;
11) the refining of the 9) item also comprises the step of preserving the temperature of the system at 70-90 ℃, preferably 75-85 ℃;
12) drying the product in the step (3) by adopting a spray drying mode, preferably, the spray drying condition is as follows: the air inlet temperature is 180-190 ℃, the air outlet temperature is 100-110 ℃, and the rotation frequency of the material pump is 0-50 Hz.
A fourth aspect of the present invention provides a method for preparing a dialysis solution according to any one of the second aspects of the present invention, comprising the steps of:
the dialysis solution is prepared by formulating a prescribed amount of the glucose polymer according to any one of the first aspect of the present invention into an aqueous solution having a concentration of 7-15% w/v.
In one embodiment of the invention, the dialysis solution is prepared by formulating a prescribed amount of the glucose polymer according to any one of the first aspect of the invention as an aqueous solution having a concentration of 7 to 12% w/v (e.g., 7 to 10% w/v, e.g., 7 to 8.5% w/v).
In a specific embodiment of the present invention, it further comprises a step of decolorizing the aqueous solution, preferably the decolorizing is performed at 60-80 ℃ (e.g. 70 ℃), preferably the decolorizing is performed with 0.1-10% (w/v) activated carbon, e.g. 0.1-1% (w/v), e.g. 0.6% (w/v).
In a specific embodiment of the present invention, wherein the water is water for injection.
Another aspect of the invention provides the use of a glucose polymer according to any one of the first aspect of the invention in the preparation of a dialysate for the treatment of renal disease.
In one embodiment of the invention, wherein the kidney disease comprises renal insufficiency (e.g., acute or chronic renal insufficiency), renal failure, uremia, or end stage renal disease.
A further aspect of the invention provides the use of a dialysis solution according to any of the second aspects of the invention in the manufacture of a medicament for the treatment of renal disease.
In one embodiment of the invention, wherein the kidney disease comprises renal insufficiency (e.g., acute or chronic renal insufficiency), renal failure, uremia, or end stage renal disease.
Detailed Description
The term "glucose polymer" as used in the present invention is a homogeneous polysaccharide of glucose polymerized from glucose, and the molecular formula of which can be represented by (C)6H10O5)nWherein n is greater than 10.
The term "dialysis" as used herein includes hemodialysis and peritoneal dialysis, which in the embodiments of the present invention mainly refers to peritoneal dialysis, which is a form of dialysis that utilizes the human body's own peritoneum as a dialysis membrane. The dialysate filled into the abdominal cavity exchanges solute and moisture with the plasma components in the capillary vessel on the other side of the peritoneal cavity, thereby removing the metabolites and excessive moisture retained in the body, and simultaneously supplementing the substances necessary for the body through the dialysate.
The term "Polydispersity (PDI)" used in the present invention may also be referred to as molecular weight distribution coefficient, non-uniformity index, degree of dispersion, and the like. It is defined as Mw/Mn (where Mw, Mn are weight average, number average molecular weight, respectively) and is used to measure the width of the molecular weight distribution.
In the present invention, the glucose polymer acts as an osmotic agent in the dialysis solution, and its role is to maintain the osmotic gradient required for the transport of water and toxic substances across the peritoneal membrane into the dialysis solution.
The dialysate of the present invention also contains electrolytes and buffer salts. The electrolyte is a substance capable of ionization in the dialysate, including potassium salts, sodium salts, calcium salts, magnesium salts, lactate salts, and the like, or combinations thereof. Specifically, for example, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium lactate, sodium bicarbonate, or the like, or a combination thereof. The buffer salt may be bicarbonate, lactate, pyruvate, acetate, citrate, amino acids, peptides, intermediates of the Krebs cycle, and the like, or combinations thereof.
The dialysate described in the present invention can be formulated in a specific manner to be suitable for peritoneal dialysis therapy. The dialysis solution can be used as a single dialysis solution in a single container or as two or more dialysis parts in a two or more chambered container. The dialysis solution can be sterilized using any suitable sterilization technique, such as autoclave, steam, ultraviolet, high pressure, filtration, or combinations thereof.
The glucose polymer and the method for preparing a dialysate containing the glucose polymer according to the present invention will be described in detail below.
The glucose polymer is mainly prepared by the following steps as shown in figure 1:
[1] hydrolysis: the hydrolysis product with the weight-average molecular weight of 15,000-40,000 (preferably 20,000-25,000) can be obtained by controlling the ratio of the raw material to the acid and the hydrolysis temperature during the hydrolysis of the starch. In a preferred embodiment of the invention, the ratio of starch to concentrated hydrochloric acid is (40-60): 1 (Kg/L). In a more preferred embodiment of the invention, the ratio of starch to concentrated hydrochloric acid is (45-50): 1 (Kg/L). The hydrolysis temperature should be controlled at 80-100 deg.C, preferably 85-95 deg.C, and more preferably 90-95 deg.C.
[2] And (3) decoloring: this step is a preferred embodiment and can be carried out either after the hydrolysis or before the drying step. The decolorization scheme is referred to the prior art, and the present invention is not particularly limited. The decolorization is preferably carried out with activated carbon for sugar at 35 to 50 ℃, more preferably at 40 to 45 ℃, for example 40 ℃.
[3] And (3) ultrafiltration: this step is to screen out small molecule products produced during the hydrolysis process. In order to improve the ultrafiltration efficiency, reduce the strain of the instrument and remove bacteria and insoluble impurities in the system, the system is subjected to fine filtration by a microporous filter membrane before ultrafiltration, and the microporous filter membrane with the diameter of 0.2-0.5 mu m is preferably adopted. And (3) performing ultrafiltration on the filtrate after the fine filtration by using an ultrafiltration membrane with the molecular weight cutoff of 5,000, wherein the filtrate is qualified when the weight average molecular weight is 20,000-45,000 (preferably, when the weight average molecular weight is 24,000-30,000), and the ultrafiltration can be performed for 1-3 times until a qualified product is obtained.
[4] And (3) drying: the drying of the glucose polymers can be carried out by referring to textbooks or common knowledge in the art, the spray drying mode is preferably adopted in the invention, and the specific drying conditions can be as follows: the air inlet temperature is 180-190 ℃, the air outlet temperature is 100-110 ℃, and the rotation frequency of the material pump is 0-50 Hz. In order to ensure the product quality, the product of the invention can be further refined before drying, and the refining scheme can be as follows: firstly, the product is filtered through a 0.1-0.2 mu m microporous filter membrane, heated (refluxed) for 10-20 minutes, and then kept at 70-90 ℃, preferably 75-85 ℃.
The preparation method of the dialysate comprises the following steps:
the dialysis solution is prepared by formulating a prescribed amount of the glucose polymer according to any one of the first aspect of the present invention into an aqueous solution having a concentration of 7-15% w/v.
In one embodiment of the invention, the dialysis solution is prepared by formulating a prescribed amount of the glucose polymer according to any one of the first aspect of the invention as an aqueous solution having a concentration of 7 to 12% w/v (e.g., 7 to 10% w/v, e.g., 7 to 8.5% w/v).
In a specific embodiment of the present invention, it further comprises a step of decolorizing the aqueous solution, preferably the decolorizing is performed at 60-80 ℃ (e.g. 70 ℃), preferably the decolorizing is performed with 0.1-10% (w/v) activated carbon, e.g. 0.1-1% (w/v), e.g. 0.6% (w/v).
In a specific embodiment of the present invention, wherein the water is water for injection.
The renal disease in the present invention mainly refers to chronic renal disease with advanced deterioration, and mainly includes renal insufficiency (such as acute or chronic renal insufficiency), renal failure, uremia or end stage renal disease.
Among them, renal insufficiency is caused by various causes, and glomeruli are seriously damaged, causing clinical syndrome of disorder of the body in excreting metabolic waste and regulating water electrolyte, acid-base balance, etc. It is classified into acute renal insufficiency and chronic renal insufficiency. The main clinical manifestations are: creatinine and urea nitrogen increase, anemia, fatigue, weakness, weight loss, mental confusion, nocturia, edema, malignant hypertension, emesis, and skin pruritus.
Wherein the renal failure is a pathological state in which various chronic kidney diseases progress to a later stage causing partial or complete loss of renal function. It can be classified into acute renal failure and chronic renal failure. The main clinical manifestations are: oliguria or anuria, low specific gravity urine, high urine sodium, hematuria, proteinuria, cylindruria, water poisoning, hyperkalemia, metabolic acidosis, azotemia, etc. Uremia (or end stage renal disease) develops when chronic renal failure enters the end stage.
The term "treatment" as used herein refers to both therapeutic treatment and prophylactic measures, the purpose of which is to prevent or delay (lessen) the disease state or condition in question. A subject is successfully "treated" for kidney disease if the subject is dialyzed against a dialysate of the invention in which one or more of the indications and symptoms of kidney disease exhibit an observable and/or detectable decrease or improvement. It is also understood that the prevention or treatment of a disease state or condition as described includes not only complete prevention or treatment, but also less than complete prevention or treatment, but also achievement of some biologically or medically relevant result. Such as delaying, arresting, slowing the progression or progression of the condition.
The dialysate of the invention can be used for Intermittent Peritoneal Dialysis (IPD), Continuous Ambulatory Peritoneal Dialysis (CAPD), Automated Peritoneal Dialysis (APD) and Continuous Cycling Peritoneal Dialysis (CCPD). The method of use of the dialysate should be performed in conjunction with different dialysis modes or physician guidance.
Advantageous effects of the invention
According to the invention, through the control of hydrolysis and ultrafiltration conditions, the preparation process of the glucose polymer is greatly optimized, the equipment cost is effectively saved, and the prepared peritoneal dialysis solution has better material clearance rate, so that the peritoneal dialysis effect is greatly improved.
Drawings
FIG. 1 is a process for preparing the glucose polymer in one embodiment of the present invention.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
The weight average molecular weight is determined by high performance liquid chromatography (appendix V D of the second part of the pharmacopoeia 2010 edition).
Chromatographic conditions and system suitability test: a gel column special for polysaccharide determination is used, a multi-angle laser light scattering detector and a refractive index detector are combined, acetate buffer solution is used as a mobile phase (18.7g of sodium acetate and 34.5mL of glacial acetic acid are added with water for dissolving twice and are diluted to 5L), the flow rate is 0.5mL/min, the column temperature is 30 ℃, and the detection temperature is 35 ℃.
Example 1
1. Hydrolysis:
a. 1000L of purified water is added into the hydrolysis kettle, the stirring is started, and 250kg of corn starch is added.
b. Adding 5.1L concentrated hydrochloric acid, heating to about 85 deg.C, adjusting the opening degree of steam valve to slowly raise the temperature to 90 deg.C, and maintaining at 90-95 deg.C.
c. After 3 hours of incubation the temperature was recorded and sampled and the weight average molecular weight of the sample was determined by HPLC to be 20930 daltons.
d. Adding sodium hydroxide solution into the hydrolysis kettle, adjusting the pH value to be neutral, and cooling to about 40 ℃.
2. And (3) decoloring:
a. sealing the pot mouth of the decoloring kettle, vacuumizing the decoloring kettle to be below-0.08 Mpa, sucking the feed liquid in the hydrolysis kettle to the decoloring kettle, adding about 100L of water for injection after the suction is finished, brushing the pot, and starting stirring.
b. And starting a heating system to heat the feed liquid to 40 ℃, and adding 3kg of sugar activated carbon. Keeping the temperature at 40 plus or minus 2 ℃ for one hour.
c. Decarbonizing the feed liquid by a plate-and-frame filter, conveying the feed liquid into an ultrafiltration storage tank, wherein the pressure of the plate-and-frame filter is less than 0.2MPa, adding about 100L of injection water before the filtration is finished, brushing the tank, and stopping pumping after the filtration is finished.
3. Fine filtering:
installing a 0.2-micron microporous filter membrane on a plate-frame filter, filtering the feed liquid in an ultrafiltration storage tank to an ultrafiltration tank, wherein the pressure of the plate-frame is less than 0.2MPa, adding about 100L of injection water before the filtration is finished, brushing the tank, and stopping the pump after the filtration is finished.
4. And (3) ultrafiltration:
adding purified water into the ultrafiltration tank to 1500L, starting a pump, performing ultrafiltration, intercepting hydrolysate with molecular weight larger than 5,000, adding purified water to 1500L when 500L of feed liquid is ultrafiltered in the ultrafiltration tank, performing ultrafiltration for the third time, stopping the machine, and finishing the ultrafiltration after the molecular weight is qualified by HPLC (the weight average molecular weight is 26700 Dalton and the number average molecular weight is 9830 Dalton).
5. Refining:
a. installing a 0.1-micron microporous filter membrane on a plate-and-frame filter, starting a refined feed liquid pump, refluxing for 10-20 minutes, then conveying the feed liquid to a liquid storage tank, adding about 60L of water for injection before the feed liquid is filtered, and stopping the pump after the filtering is finished.
b. Starting a liquid storage tank for stirring, heating the feed liquid to 75 ℃, and preserving heat at 75-85 ℃.
6. Spray drying:
the air inlet temperature (180-190 ℃) and the air outlet temperature (100-110 ℃) and the rotation frequency (0-50 HZ) of the material pump. And opening the bin wall vibrator and receiving materials every half hour. Thus, a novel glucose polymer (weight average molecular weight 26700, number average molecular weight 9830, dispersion coefficient 2.6) was obtained.
The following glucose polymers were synthesized (same procedure as in example 1 except for hydrolysis and ultrafiltration):
EXAMPLE 2 preparation of dextran Polymer peritoneal dialysis solution
Adding 80% of fresh water for injection into a concentration preparation container, adding a glucose polymer according to the prescription amount, stirring, adding 0.6% (W/V) of activated carbon after dissolution, keeping the temperature at 70 ℃, stirring, adsorbing, decarburizing and filtering. Transferring the medicinal liquid to a diluting preparation tank, cooling, adding water for injection to desired volume, starting the medicinal liquid pump, and bottling.
Prescription: each 100ml of dialysate contains 7-8.5 g of dextran, 535mg of sodium chloride, 448mg of sodium lactate, 25.7mg of calcium chloride and 5.08mg of magnesium chloride.
Electrolyte content per liter: sodium 132mEq/L, calcium 3.5mEq/L, magnesium 0.5mEq/L, chlorine 96mEq/L and lactate 40 mEq/L.
Example 3 biological experiments
1. Material
Animal(s) production
40 New Zealand white rabbits are half female and half male, and the weight is about 1.5-2 kg.
Dialysate to be tested
7% -24k glucose polymer;
7% -30k glucose polymer;
7% -45k glucose polymer;
8.5% -24k glucose polymer;
8.5% -30k glucose polymer;
8.5% -45k glucose polymer;
7.5% of icodextrin produced by Baite medical Co (Cat. No.: S14G01064, M)w＝13000～19000)。
2. Method of producing a composite material
56 healthy New Zealand white rabbits were selected, half female and half male, weighing approximately 1.5-2 kg. And (5) feeding the chicken with normal diet and drinking water, and performing adaptive feeding for one week. Anaesthetizing, placing an abdominal penetrating tube in the abdominal cavity, and resting for 7-10 days after the operation until the wound is completely healed. Complete randomization into 7 groups of 8 animals each. Namely, a baite 7.5% icodextrin dialysis set (denoted as extra), a glucose polymer dialysis set with a dispersion coefficient of 7% -24k (denoted as sample 1), a glucose polymer dialysis set with a dispersion coefficient of 7% -30k (denoted as sample 2), a glucose polymer dialysis set with a dispersion coefficient of 7% -45k (denoted as sample 3), a glucose polymer dialysis set with a dispersion coefficient of 8.5% -24k (denoted as sample 4), a glucose polymer dialysis set with a dispersion coefficient of 8.5% -30k (denoted as sample 5), and a glucose polymer dialysis set with a dispersion coefficient of 8.5% -45k (denoted as sample 6). Then, a peritoneal dialysis treatment test was performed for one week in the course of treatment, and peritoneal dialysis was performed once a day by injecting each group of peritoneal dialysis solution at 30 ml/kg. At the end of the dialysis for 240min, blood and dialysate effluent samples were collected. And respectively detecting the concentration of creatinine and urea nitrogen in the blood plasma and the dialysis effluent at 240min, and measuring the total volume of the dialysis effluent. The ratio of concentration of creatinine, urea nitrogen and plasma (D/P) was calculated for the dialysis effluent.
Creatinine and urea nitrogen clearance rates were selected primarily in this experiment to reflect the dialysis treatment effect of glucose polymer dialysate. In this experiment, the creatinine and urea nitrogen clearance was calculated as follows:
clearance rate (total volume ml of peritoneal dialysis effluent solution x ratio of dialysate to plasma concentration D/P) ÷ 240min
The creatinine and urea nitrogen clearance results for each group after 240min dialysis treatment are shown in the following table:
| urea nitrogen clearance (ml/min) | Creatinine clearance (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 No. 4 | 0.792±0.120 | 0.821±0.120 |
| Sample No. 5 | 0.780±0.126 | 0.802±0.119 |
| Sample No. 6 | 0.714±0.119 | 0.737±0.126 |
| Extraneal | 0.588±0.080 | 0.598±0.068 |
The above data are presented as mean ± SD. The results show that the creatinine and urea nitrogen clearance of each glucose polymer group is higher than that of an Extraneal control group (p is less than 0.05), wherein the glucose polymer with 24-30k and a dispersion coefficient of 2.5 has better drug effect. The animal experiment results show that the novel glucose polymer peritoneal dialysis fluid prepared by the method is superior to the Extraneal sold in Baite foreign countries at present in the aspect of substance removal pharmacodynamics.
Although specific embodiments of the invention have been described in detail, those skilled in the art will appreciate. Various modifications and substitutions of those details may be made in light of the overall teachings of the disclosure, and such changes are intended to be within the scope of the present invention. The full scope of the invention is given by the appended claims and any equivalents thereof.
Claims (20)
1. A dialysis solution comprising one or more of glucose polymers having the following weight average molecular weight and polydispersity index:
the weight average molecular weight is 24,000 daltons, and the polydispersity is 2.5;
the weight average molecular weight is 30,000 daltons, and the polydispersity is 2.7; and the combination of (a) and (b),
the weight average molecular weight was 45,000 daltons, with a polydispersity of 2.8;
and the concentration of the glucose polymer is 7-8.5% w/v.
2. The dialysis solution of claim 1, further comprising an electrolyte, a buffer, or a combination of both.
3. The dialysis solution of claim 2, wherein the electrolyte is selected from the group consisting of sodium salts, calcium salts, magnesium salts, lactate salts, and any combination thereof.
4. The dialysis solution of claim 2, wherein the buffer is selected from the group consisting of a carbonate, a citrate, an acetate, an amino acid, or any combination thereof.
5. A method for preparing a dialysis solution as claimed in claim 1, comprising the steps of:
formulating a prescribed amount of the glucose polymer defined in claim 1 into an aqueous solution having a concentration of 7-8.5% w/v to obtain said dialysis solution; wherein the glucose polymer is prepared by the following method:
(1) hydrolyzing starch under an acidic condition, and adjusting the pH of a reaction solution to be neutral when the weight average molecular weight of a product is within the range of 15,000-40,000 to obtain a hydrolysate;
(2) performing ultrafiltration on the hydrolysate obtained in the step (1) to obtain an ultrafiltration product with the following weight average molecular weight and polydispersion coefficient:
the weight average molecular weight is 24,000 daltons, and the polydispersity is 2.5;
the weight average molecular weight is 30,000 daltons, and the polydispersity is 2.7; or the like, or, alternatively,
the weight average molecular weight was 45,000 daltons, with a polydispersity of 2.8;
(3) and (3) drying the ultrafiltration product obtained in the step (2) to obtain the glucose polymer.
6. The method of claim 5, characterized by one or more of the following:
1) the starch in the step (1) is corn starch;
2) the concentration of starch in the hydrolysis reaction in the step (1) is 0.1-0.5% w/v;
3) adding concentrated hydrochloric acid into the hydrolysis reaction in the step (1) for hydrolysis, wherein the ratio of starch to concentrated hydrochloric acid is (40-60): 1 (Kg/L);
4) the hydrolysis temperature in the step (1) is 80-100 ℃;
5) before the step (2), the step of decoloring the hydrolysate is further included;
6) the method also comprises the step of sterilizing or insoluble impurities before the hydrolysate obtained in the step (1) is subjected to ultrafiltration;
7) the ultrafiltration in the step (2) refers to hydrolysate with molecular weight cutoff larger than 5000;
8) performing ultrafiltration for 1-3 times in the step (2);
9) before the drying in the step (3), refining the ultrafiltration product by passing through a microporous filter membrane with the aperture of 0.1-0.2 μm;
10) and (4) drying the product in the step (3) in a spray drying mode.
7. The method of claim 6, wherein in item 3), the ratio of starch to concentrated hydrochloric acid is (45-50): 1.
8. the process of claim 6, item 4), wherein the hydrolysis temperature is 85 to 95 ℃.
9. The process of claim 6, item 4), wherein the hydrolysis temperature is 90 to 95 ℃.
10. The method according to claim 6, item 5), wherein the sugar is decolorized with activated carbon, and the decolorization is performed at 35 to 50 ℃.
11. The process of claim 10, wherein the decolorization is performed at 40 to 45 ℃.
12. The method of claim 6, item 6), wherein the sterilization or insoluble impurities are removed by filtration through a microfiltration membrane having a pore size of 0.1 to 0.5 μm.
13. The method of claim 12, wherein the pore size of the microfiltration membrane is 0.2 μm.
14. The process of claim 6, wherein the refining of item 9) is carried out under heating or reflux conditions.
15. The method of claim 6, wherein the refining of item 9) further comprises the step of maintaining the temperature of the system at 70 to 90 ℃.
16. The method of claim 6, wherein the refining of item 9) further comprises the step of maintaining the temperature of the system at 75 to 85 ℃.
17. The method of claim 6, item 10), wherein the spray drying conditions are: the air inlet temperature is 180-190 ℃, the air outlet temperature is 100-110 ℃, and the rotation frequency of the material pump is 0-50 Hz.
18. Use of the dialysis solution of any one of claims 1 to 4 in the manufacture of a medicament for the treatment of renal disease.
19. The use according to claim 18, wherein the renal disease is acute or chronic renal insufficiency or uremia.
20. The use of claim 18, wherein the renal disease is renal failure or end stage renal disease.
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| CN101445565A (en) * | 2008-12-24 | 2009-06-03 | 江南大学 | Separation and purification method for Dunaliella salina polysaccharide |
| CN101932719A (en) * | 2007-04-26 | 2010-12-29 | 株式会社林原生物化学研究所 | Side chain alpha-glucan and generate its alpha-glucosyl transferring enzyme and their manufacture method and purposes |
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| CN103467608B (en) * | 2013-09-27 | 2015-08-26 | 华仁药业股份有限公司 | Icodextrin and preparation method thereof |
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| CN101932719A (en) * | 2007-04-26 | 2010-12-29 | 株式会社林原生物化学研究所 | Side chain alpha-glucan and generate its alpha-glucosyl transferring enzyme and their manufacture method and purposes |
| CN101445565A (en) * | 2008-12-24 | 2009-06-03 | 江南大学 | Separation and purification method for Dunaliella salina polysaccharide |
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| "不同相对分子质量葡萄糖聚合物腹膜透析液对健康新西兰兔透析作用比较";李继仁等;《中国血液净化》;20161012;第15卷(第10期);第559-562页 * |
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