CN105131135B - The industrialized preparing process of Icodextrin - Google Patents
The industrialized preparing process of Icodextrin Download PDFInfo
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- CN105131135B CN105131135B CN201510595537.1A CN201510595537A CN105131135B CN 105131135 B CN105131135 B CN 105131135B CN 201510595537 A CN201510595537 A CN 201510595537A CN 105131135 B CN105131135 B CN 105131135B
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Abstract
The present invention provides a kind of industrialized preparing process of Icodextrin, it includes the following steps：A. a concentration of 0.3 1.5% acid solution is prepared；B. the acid solution for taking 1000 parts by weight is added with stirring 400 450 parts by weight Corn starch, and hydrolysis temperature is 90~95 DEG C, after 1 2h of hydrolysis, adjusts pH to 57, obtains hydrolysate；C. the step b hydrolysates prepared are cooled to 55 60 DEG C, 12 13.5 parts by weight of activated carbon is added, decolourized 0.5 1 hours, filtered after decoloration；D. to filtrate prepared by step c carry out ultrafiltration, it is dry to get.The method of the present invention preparation process is easy, production cost is low, and the good product quality of preparation is suitable for the industrialized production of Icodextrin.
Description
Technical field
The present invention relates to a kind of industrialized preparing process of Icodextrin, belong to drug field.
Background technology
Icodextrin is starch derivatives by α (1-4) and less than the water-soluble grape of 10% α (1-6) glucosides key connection
Glycopolymers, weight-average molecular weight are 13000-19000 dalton, and quantity-average molecular weight is 5000-6500 dalton.
Icodextrin is the main active in Icodextrin peritoneal dialysis solution, is used for the treatment of end-stage renal disease.Icodextrin abdomen
Since film dialyzate lists, although the whole world has had more than 45 19000 national multidigit patients and has been indebted to it, wherein Europe is each
The patient that country is more up to one third uses one bag of Icodextrin peritoneal dialysis solution daily, but China's peritoneal dialysis at present makes
It is also very low (about 10%) with rate, preparation price, production equipment, the feasibility of technique and the continuity of this and peritoneal dialysis solution
It is related.
Currently, the domestic report about the preparation process of Icodextrin bulk pharmaceutical chemicals is few, application number：
201310453098.1；Denomination of invention：Icodextrin and preparation method thereof discloses a kind of preparation method of Icodextrin, packet
Include following step：A. after configuring cereal starch and water to mixed solution, acid is added and forms reaction solution, be 70-93 DEG C in temperature
Under the conditions of, reaction is hydrolyzed, reaction is neutralized to pH7 with aqueous slkali, hydrolysis is terminated, obtains product 1, the reaction time is
0.5-4h；B. molecular weight screening is carried out to product 1, obtains product 2；C. to product 2 be dried solidification to get.The preparation method
Obtained hydrolysate molecular vibrational temperature is wider, both needed with small molecular cut off (5000Da) when molecular weight of product screening
Ultrafiltration membrane need to use big molecular cut off (100KDa) ultrafiltration membrane again, increase production cost and the product that is prepared by this method not
Through removal of impurities, quality defect is not suitable for the industrialized production of Icodextrin.
Invention content
The technical solution of the present invention is to provide a kind of industrialized preparing process of Icodextrin.
The present invention provides a kind of industrialized preparing process of Icodextrin, include the following steps：
A. the acid solution that concentration of hydrochloric acid is 0.3-1.5% is prepared；
B. the acid solution for taking 1000 parts by weight, is added with stirring 400-450 parts by weight Corn starch, and hydrolysis temperature is 90~
95 DEG C, after hydrolysis 1-2, pH to 5-7 is adjusted, hydrolysate is obtained；
C. hydrolysate prepared by b step is cooled to 55-60 DEG C, 12-13.5 parts by weight of activated carbon is added, decolourize 0.5-
It 1 hour, is filtered after decoloration；
D. to filtrate prepared by step c carry out ultrafiltration, it is dry to get.
Preferably, the acid solutions that prepared by a steps are 0.9%；
It is 90~95 DEG C that the acid solution of 1000 parts by weight, the cornstarch of 450 parts by weight, hydrolysis temperature are taken in b step, water
After solution reaction 1.2h, pH to 5-7 is adjusted；
Hydrolysate prepared by b step is cooled to 60 DEG C, and 13.5 parts by weight of activated carbon are added, and decolourizes 1 hour.
Wherein, the acid described in a steps is hydrochloric acid.
Wherein, the aqueous slkali that b step adjusts pH is NaOH solution.
Wherein, a concentration of 10%v/v~30%v/v of the NaOH solution.
Wherein, the filtrate in step c carries out ultrafiltration using the ultrafiltration membrane of 1000Da.
Wherein, the drying means filtrate in step c used for constant pressure and dry, be dried under reduced pressure, be freeze-dried or spray
It is dry.
Preferably, the drying means is spray drying.
Wherein, the feeding temperature of spray drying is 80-90 DEG C, and leaving air temp is 80-110 DEG C, inlet air temperature 195-225
℃。
Preferably, the leaving air temp is 90-100 DEG C, and inlet air temperature is 205-215 DEG C.
With patent (application number：201310453098.1) method is compared, and the improvement of the method for the present invention and advantage are following
Several points：
1. the method for the present invention first prepares the acid solution of low concentration, then adds cornstarch, cornstarch is enable uniformly to hydrolyze,
So that hydrolysate molecular weight is more concentrated, is conducive to hydrolysate molecular weight and screens.
2. the method for the present invention increases hydrolysis temperature, the hydrolysis degree of raw material macromolecular substances is made to improve, reaction time contracting
Short, hydrolysate molecular weight obtained is more concentrated, and only need to carry out ultrafiltration with small molecular cut off (1000Da) ultrafiltration membrane, is conducive to production
The screening of object molecular weight simplifies processing step in the case where ensureing product quality and significantly reduces production cost.
3. the present invention selects activated carbon to carry out decolorization to hydrolyzate, the absorbance of product is not significantly lower than after decoloration
The product of decoloration can remove the impurity that external or raw material itself is brought through activated carbon decolorizing, substantially increase the quality of product.
The method of the present invention but produces unexpected technology by carrying out small improvement to each step in patented method
Effect not only shortens technique and takes, significantly reduces production cost, but also obtained the product of better quality, particularly suitable
In the industrialized production of Icodextrin, have very important significance to the development and application of Icodextrin at home.
Description of the drawings
Fig. 1 synthesizes the process route chart of Icodextrin.
Fig. 2 synthesizes the reaction equation of Icodextrin.
Below by way of specific implementation mode, the present invention is described in further detail, but is not intended to limit the present invention, ability
The various changes and replacement that field technique personnel make according to the present invention should all belong to this hair without departing from the spirit of the present invention
Bright scope of the appended claims.
Specific implementation mode
The preparation of 1 Icodextrin of the present invention of embodiment
A. the acid solution that concentration of hydrochloric acid is 0.6% is prepared；
B. the acid solution for taking 1000 parts by weight is added with stirring 400 parts by weight Corn starch, and hydrolysis temperature is 90 DEG C, water
After solution reaction 2h, pH to 6 is adjusted, hydrolysate is obtained；
C. hydrolysate prepared by b step is cooled to 55 DEG C, 12 parts by weight of activated carbon is added, decolourized 0.5 hour, decoloration
After filter；
D. to filtrate prepared by step c carry out ultrafiltration, it is dry to get.
Gained molecular weight analyte (MW) is 1.68 ten thousand Da, water content 3.86%.
The preparation of 2 Icodextrin of the present invention of embodiment
A. the acid solution that concentration of hydrochloric acid is 0.9% is prepared；
B. the acid solution for taking 1000 parts by weight, is added with stirring 450 parts by weight Corn starch, and hydrolysis temperature is 90~95
DEG C, when the Ping Shi viscosimeters that reaction solution is 0.6mm with capillary inner diameter measure the delivery time in 2min, adjust pH to 5.5 eventually
Sealing solution obtains hydrolysate, hydrolysis time 1.2h
C. hydrolysate prepared by b step is cooled to 55-60 DEG C, 13.5 parts by weight of activated carbon is added, decolourized 1 hour,
It is filtered after decoloration；
D. to filtrate prepared by step c carry out ultrafiltration, it is dry to get.
Gained molecular weight analyte (MW) is 1.46 ten thousand Da, water content 3.94%.
The preparation of 3 Icodextrin of the present invention of embodiment
A. the acid solution that concentration of hydrochloric acid is 1.2% is prepared；
B. the acid solution for taking 1000 parts by weight is added with stirring 450 parts by weight Corn starch, and hydrolysis temperature is 95 DEG C, water
After solution reaction 1.0h, pH to 5.5 is adjusted, hydrolysate is obtained；
C. hydrolysate prepared by b step is cooled to 55 DEG C, 13.5 parts by weight of activated carbon is added, decolourized 1 hour, decoloration
After filter；
D. to filtrate prepared by step c carry out ultrafiltration, it is dry to get.
Gained molecular weight analyte (MW) is 1.38 ten thousand Da, water content 3.86%.
Beneficial effects of the present invention are proved below by way of specific experiment.
1 preparation method Decolorant Test of the present invention of experimental example
1. experimental method
Liquid is prepared according to step a in embodiment 1, is divided into two groups, every group 3 parts.
It is separately added into activated carbon decolorizing in one group of liquid, is filtered after decoloration；Another group of liquid is not added with activated carbon.By two groups of medicines
Liquid carries out absorbance detection respectively.
2. experimental result is shown in Table 1.
Table 1
3. experiment conclusion
Experimental data shows that the absorbance of liquid is significantly lower than the liquid of no bleaching after activated carbon decolorizing, shows through work
Property carbon decoloring can reduce the impurity in liquid, improve the quality of liquid.
The optimization experiment of 2 drying process with atomizing of the present invention of experimental example
1. experimental method
Prepare liquid Jing Guo ultrafiltration according to step c in embodiment 1, under the conditions of different leaving air temps, inlet air temperature into
Row spray drying, detects the appearance, loss on drying, clarity of solution of drying sample.
2. experimental result is shown in Table 2.
Table 2
3. experiment conclusion
Experimental data shows, spray drying condition is 90~100 DEG C of leaving air temp, when 205~215 DEG C of inlet air temperature, outside sample
Sight, loss on drying, clarity of solution are best, product it is best in quality, therefore select spray drying condition for leaving air temp 90~
100 DEG C, 205~215 DEG C of inlet air temperature.
Claims (7)
1. a kind of industrialized preparing process of Icodextrin, it is characterised in that：Include the following steps：
A. a concentration of 0.9% hydrochloric acid solution is prepared；
B. the acid solution for taking 1000 parts by weight is added with stirring 450 parts by weight Corn starch, and hydrolysis temperature is 90~95 DEG C, water
After solution reaction 1.2h, NaOH solution adjusts pH to 5.5, obtains hydrolysate；
C. hydrolysate prepared by b step is cooled to 55-60 DEG C, 12-13.5 parts by weight of activated carbon is added, decoloration 0.5-1 is small
When, after decoloration, filtrate carries out ultra-filtration filters using the ultrafiltration membrane of 1000Da；
D. to filtrate prepared by step c carry out ultrafiltration, it is dry to get.
2. according to the method described in claim 1, it is characterized in that：
Hydrolysate prepared by b step is cooled to 60 DEG C, and 13.5 parts by weight of activated carbon are added, and decolourizes 1 hour.
3. according to the method described in claim 1, it is characterized in that：A concentration of 10% ~ 30%v/v of the NaOH solution.
4. according to the method described in claim 1, it is characterized in that：The drying means used to the filtrate in step c is normal pressure
It dries, be dried under reduced pressure, be freeze-dried or be spray-dried.
5. according to the method described in claim 4, it is characterized in that：The drying means is spray drying.
6. according to the method described in claim 5, it is characterized in that：The feeding temperature of spray drying is 80-90 DEG C, leaving air temp
It it is 80-110 DEG C, inlet air temperature is 195-225 DEG C.
7. according to the method described in claim 6, it is characterized in that：The leaving air temp is 90-100 DEG C, and inlet air temperature is
205-215℃。
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106397616B (en) * | 2016-08-30 | 2019-10-18 | 华南理工大学 | A kind of preparation method of starch base Icodextrin used for peritoneal dialysate |
| CN107831227B (en) * | 2017-10-12 | 2022-01-28 | 青岛力腾医药科技有限公司 | Method for measuring glucan branch degree |
| 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 |
| CN109264812A (en) * | 2018-11-13 | 2019-01-25 | 华仁药业股份有限公司 | One kind is for removing endotoxic method in glucidtemns |
| CN110483649A (en) * | 2019-08-28 | 2019-11-22 | 西安乐析医疗科技有限公司 | A kind of preparation method of novel dextrin and its application in dialyzate |
| CN114316076B (en) * | 2020-09-29 | 2023-01-31 | 青岛力腾医药科技有限公司 | Preparation method of starch-derived maltodextrin for nephropathy |
| CN114605563B (en) * | 2022-04-08 | 2023-02-17 | 中国海洋大学 | Preparation method of icodextrin raw material medicine single enzyme system for peritoneal dialysis solution |
| CN117050201B (en) * | 2023-07-31 | 2024-06-21 | 武汉华科大生命科技股份有限公司 | Method for removing aluminum salt and magnesium salt in icodextrin bulk drug |
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| CN102617744A (en) * | 2012-04-07 | 2012-08-01 | 山东齐都药业有限公司 | Preparation method of narrow-distribution medium-molecular-weight hydroxyethyl starch |
| CN103467608A (en) * | 2013-09-27 | 2013-12-25 | 华仁药业股份有限公司 | Icodextrin and preparing method thereof |
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| US20090239819A1 (en) * | 2008-03-20 | 2009-09-24 | Run Wang | Peritoneal dialysis solution test method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102617744A (en) * | 2012-04-07 | 2012-08-01 | 山东齐都药业有限公司 | Preparation method of narrow-distribution medium-molecular-weight hydroxyethyl starch |
| CN103467608A (en) * | 2013-09-27 | 2013-12-25 | 华仁药业股份有限公司 | Icodextrin and preparing method thereof |
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| Title |
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| 玉米淀粉制取葡萄糖的研究;宋永生等;《济南大学学报》;19940215;第4卷(第1期);第83-86、95页 * |
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Address after: 620036 East District of Meishan Economic Development Zone, Sichuan Province Applicant after: Sichuan Bo Jia Pharmaceutical Co., Ltd. Address before: 611231 606 Chongzhou Road, Yang Ma Town, Chongzhou City, Chengdu, Sichuan Applicant before: CHENGDU BOJIA PHARMACEUTICAL CO., LTD. |
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