Preparation method of starch-derived maltodextrin for nephropathy

A maltodextrin and starch technology, applied in the field of medicine, can solve the problems of low starch branched chain content, high process control difficulty, extremely high process control requirements and the like

Active Publication Date: 2022-04-12
青岛力腾医药科技有限公司
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Problems solved by technology

[0002]Since the peritoneal dialysis therapy began to be applied clinically in the 1970s, it was soon discovered that there were significant defects in products using glucose as an osmotic pressure regulator:( 1) The molecular weight of glucose is small, it is easy to pass through the peritoneal epithelial cell barrier, and cannot maintain the dialysis effect for a long time; (2) The stability of glucose needs to be maintained under acidic conditions, and the lower pH level will cause peritoneal epithelial cells Stimulation then leads to its apoptosis; (3) Glucose will produce a large number of glucose degradation products (GDPs) under sterile conditions, such as formaldehyde, acetaldehyde, 3-deoxyglucosone, etc., and these degradation products will also lead to peritoneal cells. (4) Glucose forms negative ultrafiltration during dialysis, and entering the human body will cause blood sugar to rise, especially for diabetic nephropathy patients with serious consequences
[0010] The disadvantages of this process are: (1) high production cost: this process does not control the degradation of α-D-1,6-glucosidic bonds in the process, The degree of branching cannot be reduced, so the requirements for the starting material are high. The starch branching content used in the starting material should be low to meet the requirements. Usually, amylose (low branching content) should be used to meet the process. requirements, and according to the current domestic market conditions, the price of amylose is more than ten times that of ordinary cornstarch, which will greatly increase the production cost of the product. Products with qualified molecular weight and distribution can be obtained (such as Figure 4 ), the level of branching will be higher than 10% (such as Figure 5)
(2) The difficulty of process control is high: due to the precise control of the process of enzymatic hydrolysis, a product with qualified molecular weight and branching degree can be obtained (when the branching degree is qualified, the degree of starch hydrolysis is not enough, and the molecular weight is high; when the molecular weight is qualified, because the starch The degree of hydrolysis is deep, and the degree of branching is very easy to be higher than 10%), and when commercial production is carried out, the molecular weight of corn starch will vary between different sources and batches of the same source, and when the hydrolysis process freezes and solidifies , this difference in the molecular weight of the starting material will in turn lead to product failure
From the data, the pure acid hydrolysis process can obtain the required product, but through further analysis, we find that any acid hydrolysis process has the following problems: (1) molecular weight distribution defects: according to the results of repeated tests The results showed that there was no difference between acid hydrolysis in attacking α-D-1,6-glycosidic bonds and α-D-1,4-glycosidic bonds, but the hydrolysis mode of α-D-1,4-glycosidic bonds was more inclined Because of the hydrolysis from the middle segment of a single glucan molecule, rather than randomly hydrolyzing the α-D-1,4-glucosidic bonds in the molecular fragments in disorder, our repeated research results support this conclusion, and the mechanism of action is assumed to be Since starch molecules are glucans linked by α-D-1,4-glucosidic bonds, in the long chain formed by the helical structure, the hydrolysis steric hindrance of the middle segment is the least, so it is also the easiest to be attacked by various acid molecules. fracture
Under this process condition, the molecular weight distribution of the produced product tends to concentrate towards the median value of molecular weight, that is, its dispersion is low, even if it barely meets the molecular weight of the target product and its distribution range, it is also consistent with the molecular weight of the target product in each segment. There are obvious differences in the products of Baxter Medical Company. According to the theory of Chandra D. Mistry et al. that "the direction of penetration depends on the product of the solute reflection coefficient and its molar concentration", this difference in molecular weight distribution will lead to The speed and durability of post-ultrafiltration performance are different from those of the original product, which in turn affects its clinical efficacy
(2) The "retrogradation" phenomenon leads to poor stability: due to the indiscriminate degradation of α-D-1,6-glucosidic bonds and α-D-1,4-glycosidic bonds in the starch by acid hydrolysis, the proportion of polymers is different. The high α-D-1,6-glycosidic bond is significantly reduced. From the test results, it can be seen that when the molecular weight of the acid hydrolyzate is hydrolyzed to the target area, the branching degree level is significantly lower than that of the original research product, which is about 6 %, while the original products are basically around 8%-9%
However, in CN 106755199A, the hydrolysis temperature of pullulanase is relatively low, the degree of starch liquefaction is not high, and it is difficult to give full play to the debranching effect of pullulanase, so it is relatively difficult to obtain a qualified product with a branching degree, and the requirements for process control are extremely high. high
However, this process requires the use of α-amylase to hydrolyze corn starch to the range of molecular weight that is basically qualified, because α-amylase is non-selective to the attack on α-D-1,4-glucosidic bonds in the entire starch chain, resulting in A large number of small molecular dextran fragments appear, and the yield of the finished product is low, only about 10%, which greatly increases the production cost of the product and increases the burden on dialysis patients (such as Figure 10, Figure 11)
And compared with α-amylase, isoamylase and pullulan amylase are relatively easier to inactivate, need to add supplements many times during the production process, and their price is much higher than α-amylase, these factors lead to The production cost of this process condition is relatively high (such as Figure 12, Figure 13)

Method used

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  • Preparation method of starch-derived maltodextrin for nephropathy
  • Preparation method of starch-derived maltodextrin for nephropathy
  • Preparation method of starch-derived maltodextrin for nephropathy

Examples

Experimental program
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Effect test

Embodiment 1

[0075] (1) Add cornstarch to purified water at 30°C to make the concentration reach 25wt%, stir and mix well, keep stirring all the time, add hydrochloric acid in an amount of 0.36mmol per gram of dry starch, turn on the temperature rise, and lower the temperature of the reaction solution Raise to 85°C, control the heating time between 0.5-1.5h, keep the temperature at 85°C±2°C, and react for 1h, add sodium hydroxide solution to adjust the pH to 6.5, terminate the acid hydrolysis reaction, obtain acid hydrolyzate, and measure the molecular weight : Number average molecular weight Mn6371, weight average molecular weight Mw32240 (such as Figure 14 );

[0076] (2) Heat the hydrolysis solution in (1) above to 95°C, add α-amylase in an amount of 50 U per gram of dry starch, keep the temperature at 95°C±5°C, stir for 40 minutes, and add a certain amount of dilute Adjust the pH to 2.0 with hydrochloric acid, keep it for 15 minutes to rapidly inactivate the enzyme, add a certain amo...

Embodiment 2

[0082] (1) Add cornstarch to purified water at 30°C to make the concentration reach 25wt%, stir and mix well, keep stirring all the time, add hydrochloric acid, the dosage is 0.36mmol per gram of dry starch, turn on the temperature rise, and raise the temperature of the reaction solution To 80°C, control the heating time between 30-80min, keep the temperature at 80°C±2°C, and react for 40min, add sodium hydroxide solution to adjust the pH to 6.5, stop the acid hydrolysis reaction, and obtain the acid hydrolyzate, measure the molecular weight: number Average molecular weight Mn8917, weight average molecular weight Mw55850 (such as Figure 18 );

[0083] (2) Heat the hydrolysis solution in (1) above to 95°C, add α-amylase, the dosage is 50U per gram of dry starch, keep the temperature at 95°C±5°C, stir for 60min, add a certain amount of dilute Adjust the pH to 2.5 with hydrochloric acid, keep for 10 minutes to rapidly inactivate the enzyme, then add a certain amount of dilute s...

Embodiment 3

[0089] (1) Add cornstarch to purified water at 40°C to make the concentration reach 20wt%, stir and mix well, keep stirring all the time, add α-amylase, the dosage is 45U per gram of dry starch, turn on the temperature rise, and lower the temperature of the reaction solution Raise to 100°C, control the heating time between 40-50min, monitor the dynamic viscosity during the reaction, measure the dynamic viscosity value between 5-20mPa·s, add citric acid to adjust the pH to 2.5, and the dosage is 0.9% of the volume of the reaction solution ( w / V), keep 20min to make enzyme inactivation, get enzyme hydrolyzate, measure molecular weight, number average molecular weight Mn 8122, weight average molecular weight Mw100900 (such as Figure 22 ).

[0090] (2) Reduce the temperature of the above (1) enzyme hydrolyzate to 75°C, add hydrochloric acid, the dosage is 0.2mmol per gram of dry starch, keep the temperature at 75±2°C, monitor the dynamic viscosity during the reaction process, and...

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Abstract

The invention provides a preparation method of starch-derived maltodextrin for nephropathy. The preparation method comprises the following steps: (1) hydrolyzing starch by adopting the combination of acid hydrolysis and enzyme hydrolysis; (2) adding activated carbon into hydrolysate after hydrolysis, stirring and filtering, and collecting to obtain filtrate; (3) enabling the filtrate to pass through an ultrafiltration membrane, and performing molecular weight screening to obtain ultrafiltrate; and (4) carrying out ion resin adsorption treatment and decarburization on the ultrafiltrate, and carrying out spray drying to obtain solid powder maltodextrin. The invention provides the preparation method of the starch-derived maltodextrin for nephropathy, the production process is stable, the yield is high, the quality is good, the defects of the existing similar target glucan preparation process are overcome, and the industrial production of the maltodextrin is realized.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of starch-derived maltodextrin for nephropathy. Background technique [0002] Since the clinical application of peritoneal dialysis therapy in the 1970s, it has been found that there are significant defects in products using glucose as an osmotic pressure regulator: (1) glucose has a small molecular weight and is easy to pass through the peritoneal epithelial cell barrier, The dialysis effect cannot be maintained for a long time; (2) The stability of glucose needs to be maintained under acidic conditions, and the lower pH level will stimulate the peritoneal epithelial cells and lead to their apoptosis; (3) Glucose is sterilized Conditions will produce a large amount of glucose degradation products (GDPs), such as formaldehyde, acetaldehyde, 3-deoxyglucosone, etc., and these degradation products will also cause damage to peritoneal cells; (4) gluc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B30/18
Inventor 王文彦孙健
Owner 青岛力腾医药科技有限公司
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