CN104829745A - Iron dextran and preparation method thereof - Google Patents
Iron dextran and preparation method thereof Download PDFInfo
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Abstract
The invention provides a preparation method of iron dextran. In the provided preparation method, after the complexing liquid is obtained, the pH of the complexing liquid is adjusted so as to greatly improve the dissolving property of iron dextran, while during the process, intermediates, which has a molecular weight of about 180000 to 200000, and accounts for 5 to 8% of the total weight of the final product, are generated, a great amount of ions absorbs on the intermediates, because the molecular weight of the intermediates is similar to that of iron dextran, the iron dextran and intermediates cannot be separated easily through ultrafiltration, thus the ion content of the final product is high, and the iron content is influenced in some degree, so a treatment is carried out before the ultrafiltration so as to remove the intermediates. The iron content of the prepared iron dextran is much higher than the national standard (25%), and can reach 40% or more. The solubility of iron dextran in cold water can reach 4g/100g (cold water) or more, moreover, the contents of ions such as sodium iron, chlorine iron, and the like are greatly reduced, and the purity of iron dextran is higher.
Description
Technical field
The present invention relates to a kind of anti-anemic and preparation method thereof, particularly a kind of Iron Dextran and preparation method thereof.
Background technology
Iron Dextran is also called Iron-Dextrin Complex, in Vandyke brown, and can through hot pressing and the sterilizing of the method for filtration; Being one of important derivatives of lower molecular weight dextran, is the dextran of weight-average molecular weight 5000 ~ 7500 and the complex compound of ironic hydroxide.Wherein iron ion is effective active composition, can be used for treating hypoferric anemia, supplements the chalybeate lacked in patient body, accelerates the synthesis of oxyphorase, also can make and organize iron deficiency and iron enzyme activity to reduce relevant symptom to be improved.
The method preparing Iron Dextran mainly adopts Dextran 20 to be hydrolyzed, then with iron trichloride carry out complex reaction obtain.Certain traditional technology preparing Iron Dextran is as follows:
(1) 150-160kg purified water is put into retort, control pressure is 0.05-0.15MPa, is heated with stirring to 75-85 DEG C, then adds the Dextran 20 of 60kg Hubei Yuancheng Saichuang Technology Co., Ltd. production, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 3-5 of 5.4mol/L, continue to boil 1-2 hour, be then cooled to 35-40 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 6-7, be heated to 65-75 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 80-90kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 10-11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.05-0.15MPa, solution is heated to boiling, boil 1-2 hour, be then cooled to 35-40 DEG C, obtain complex liquid;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.1-0.2 MPa, flow velocity is 1-3m/s, temperature is 50-60 DEG C, filter sizes is 0.45 μm, filter membrane material is aluminum oxide; The filtrate obtained is carried out ultrafiltration, and ultra-filtration membrane material is polysulfones, and its working pressure is 0.1-0.3 MPa, temperature 30-40 DEG C; By the filtrate that obtains in 20-30 DEG C, working pressure is that 0.6-0.8 MPa carries out nanofiltration, and filter membrane rubs the NF-1812 rolling nanofiltration membrane that fast science equipment company limited produces in Shanghai; Then carry out spraying dry, its inlet temperature is 180-190 DEG C, and temperature out is 80-90 DEG C, and after dry, rewinding is packed and be get final product.
The solubility property of Iron Dextran in cold water adopting above-mentioned traditional technology to obtain is very poor, and iron level only has 25-30%.
The present invention has carried out a pH regulator process respectively at the end of complex reaction He before ultrafiltration, its solubility property in cold water is improved greatly, and solubleness reaches more than 4g/100 cold water, and iron level reaches more than 40%, far above 25% of 2010 editions States Pharmacopoeia specifications, and Na
+, Cl
-the content of plasma impurity is lower, and purity is higher.
Summary of the invention
The object of the invention is to solve the problem that the solubleness of Iron Dextran in cold water is less and iron level is on the low side, for improving it at the solubility property in cold water, improve iron level, the present invention takes following technique means at the end of complex reaction:
Technique means 1: regulate complex liquid pH to 5.3-5.8 with the hydrochloric acid soln of 5.4mol/L, leaves standstill 1-3 hour, then regulates pH to 9.4-9.8 with 10mol/L sodium hydroxide solution.
The present invention also aims to solve macromole impurity that Iron Dextran middle-molecular-weihydroxyethyl is 18-20 ten thousand and the higher problem of ionic impurity, the present invention takes following technique means before ultrafiltration for this reason:
Technique means 2: the hydrochloric acid soln solution regulator solution pH to 7.5-7.9 adding 5.4mol/L in the iron dextran solutions after micro-filtration process again, stirs after 20-30 minute and leaves standstill 2-5 hour again.
Technique means 2 and ultrafiltration means conbined usage solve macromole impurity that Iron Dextran middle-molecular-weihydroxyethyl is 18-20 ten thousand and the higher problem of ionic impurity.
The invention reside in the preparation method providing a kind of Iron Dextran, the Iron Dextran adopting present method to obtain has the advantage that solubility property is good, iron level is high.The present invention is achieved through the following technical solutions:
(1) 150-160kg purified water is put into retort, control pressure is 0.05-0.15MPa, is heated with stirring to 75-85 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 3-5 of 5.4mol/L, continue to boil 1-2 hour, be then cooled to 35-40 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 6-7, be heated to 65-75 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 80-90kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 10-11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.05-0.15MPa, solution is heated to boiling, boil 1-2 hour, be then cooled to 35-40 DEG C, obtain complex liquid; Adopt technique means 1 to process again, namely regulate complex liquid pH to 5.3-5.8 with the hydrochloric acid soln of 5.4mol/L, leave standstill 1-3 hour, then regulate pH to 9.4-9.8 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.1-0.2 MPa, flow velocity is 1-3m/s, temperature is 50-60 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide, cellulose acetate or aluminum oxide; Technique means 2 is adopted to process the filtrate obtained, namely in the iron dextran solutions after micro-filtration process, add the hydrochloric acid soln solution regulator solution pH to 7.5-7.9 of 5.4mol/L again, stir after leaving standstill 2-5 hour again after 20-30 minute and carry out ultrafiltration again, ultra-filtration membrane material is polyethersulfone, polyvinylidene difluoride (PVDF) or polysulfones, its working pressure is 0.1-0.3 MPa, temperature 30-40 DEG C; By the filtrate that obtains in 20-30 DEG C, working pressure is that 0.6-0.8 MPa carries out nanofiltration, rubs the NF-1812 rolling nanofiltration membrane that fast science equipment company limited produces in the NF270 polyamide composite film that the GE Nano filtering composite membrane of filter membrane to be model is DK8040F, LG-DOW company produce or Shanghai; Then carry out spraying dry, its inlet temperature is 180-190 DEG C, and temperature out is 80-90 DEG C, and after dry, rewinding is packed and be get final product.
Dextran 20 of the present invention refers to the Dextran 10 of molecular-weight average 10,000-2 ten thousand, is provided by Hubei Yuancheng Saichuang Technology Co., Ltd..
The present invention processes it by technique means 1 again after obtained complex liquid in step (2), final obtained Iron Dextran solubility property is greatly improved, iron level improves, but this treatment process creates the intermediate that the molecular weight accounting for end product weight 5-8 % is about 18-20 ten thousand, and this intermediate is adsorbed with a large amount of Na
+, Cl
-plasma, because of its molecular weight and Iron Dextran relatively, be difficult to be removed by the method for ultrafiltration, cause the Na in product
+, Cl
-plasma content is higher, affects the purity of Iron Dextran, and have impact on iron level to a certain extent.Therefore ultrafiltration is front in step (3) processes it by technique means 2 iron dextran solutions that micro-filtration is crossed again, and eliminates the intermediate impurities that molecular weight is about 18-20 ten thousand, makes the Na in product
+, Cl
-plasma content reduces greatly, improves product purity and iron level.
In the Iron Dextran that the present invention obtains, iron level is far above 25% of national standard, can reach more than 40%; Solubility property in cold water is good, and solubleness can reach more than 4g/100g cold water; And Na
+, Cl
-isoionic content reduces greatly, and the purity of product is higher.
Specific embodiment
Embodiment 1: a kind of preparation method of Iron Dextran, comprises the steps:
(1) 155kg purified water is put into retort, control pressure is 0.10 MPa, is heated with stirring to 80 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 4 of 5.4mol/L, continue to boil 1.5 hours, be then cooled to 38 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 6, be heated to 70 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 85kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.10MPa, solution is heated to boiling, boil 1.5 hours, be then cooled to 38 DEG C, obtain complex liquid; Adopt technique means 1 to process again, namely regulate complex liquid pH to 5.6 with the hydrochloric acid soln of 5.4mol/L, leave standstill 2 hours, then regulate pH to 9.6 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.15MPa, flow velocity is 2m/s, temperature is 55 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide; Technique means 2 is adopted to process the filtrate obtained, namely in the iron dextran solutions after micro-filtration process, add the hydrochloric acid soln solution regulator solution pH to 7.7 of 5.4mol/L again, to stir after 25 minutes to leave standstill again and carry out ultrafiltration again after 3.5 hours, ultra-filtration membrane material is polyethersulfone, its working pressure is 0.2 MPa, temperature 35 DEG C; By the filtrate that obtains in 25 DEG C, working pressure is that 0.7 MPa carries out nanofiltration, the GE Nano filtering composite membrane of filter membrane to be model be DK8040F; Then carry out spraying dry, its inlet temperature is 185 DEG C, and temperature out is 85 DEG C, and after dry, rewinding is packed and be get final product.
Embodiment 2: a kind of preparation method of Iron Dextran, comprises the steps:
(1) 150kg purified water is put into retort, control pressure is 0.05MPa, is heated with stirring to 75 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 3 of 5.4mol/L, continue to boil 1 hour, be then cooled to 35 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 6, be heated to 65 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 80kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 10 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.05MPa, solution is heated to boiling, boil 1 hour, be then cooled to 35 DEG C, obtain complex liquid; Adopt technique means 1 to process again, namely regulate complex liquid pH to 5.3 with the hydrochloric acid soln of 5.4mol/L, leave standstill 1 hour, then regulate pH to 9.4 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.1MPa, flow velocity is 1m/s, temperature is 50 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide; Technique means 2 is adopted to process the filtrate obtained, namely in the iron dextran solutions after micro-filtration process, add the hydrochloric acid soln solution regulator solution pH to 7.5 of 5.4mol/L again, to stir after 20 minutes to leave standstill again and carry out ultrafiltration again after 2 hours, ultra-filtration membrane material is polyethersulfone, its working pressure is 0.1MPa, temperature 30 DEG C; By the filtrate that obtains in 20 DEG C, working pressure is that 0.6 MPa carries out nanofiltration, the GE Nano filtering composite membrane of filter membrane to be model be DK8040F; Then carry out spraying dry, its inlet temperature is 180 DEG C, and temperature out is 80 DEG C, and after dry, rewinding is packed and be get final product.
Embodiment 3: a kind of preparation method of Iron Dextran, comprises the steps:
(1) 160kg purified water is put into retort, control pressure is 0.15MPa, is heated with stirring to 85 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 5 of 5.4mol/L, continue to boil 2 hours, be then cooled to 40 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 7, be heated to 75 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 90kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.15MPa, solution is heated to boiling, boil 2 hours, be then cooled to 40 DEG C, obtain complex liquid; Adopt technique means 1 to process again, namely regulate complex liquid pH to 5.8 with the hydrochloric acid soln of 5.4mol/L, leave standstill 3 hours, then regulate pH to 9.8 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.2 MPa, flow velocity is 3m/s, temperature is 60 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide; Technique means 2 is adopted to process the filtrate obtained, namely in the iron dextran solutions after micro-filtration process, add the hydrochloric acid soln solution regulator solution pH to 7.9 of 5.4mol/L again, to stir after 30 minutes to leave standstill again and carry out ultrafiltration again after 5 hours, ultra-filtration membrane material is polyethersulfone, its working pressure is 0.3 MPa, temperature 40 DEG C; By the filtrate that obtains in 30 DEG C, working pressure is that 0.8 MPa carries out nanofiltration, the GE Nano filtering composite membrane of filter membrane to be model be DK8040F; Then carry out spraying dry, its inlet temperature is 190 DEG C, and temperature out is 90 DEG C, and after dry, rewinding is packed and be get final product.
Embodiment 4: a kind of preparation method of Iron Dextran, comprises the steps:
(1) 130kg purified water is put into retort, control pressure is 0.03MPa, is heated with stirring to 70 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 2 of 5.4mol/L, continue to boil 0.5 hour, be then cooled to 30 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 5, be heated to 60 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 70kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 9 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.03MPa, solution is heated to boiling, boil 0.5 hour, be then cooled to 30 DEG C, obtain complex liquid; Adopt technique means 1 to process again, namely regulate complex liquid pH to 5.0 with the hydrochloric acid soln of 5.4mol/L, leave standstill 0.5 hour, then regulate pH to 8.9 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.05MPa, flow velocity is 0.5m/s, temperature is 40 DEG C, filter sizes is 0.45 μm, filter membrane material is cellulose acetate; Technique means 2 is adopted to process the filtrate obtained, namely in the iron dextran solutions after micro-filtration process, add the hydrochloric acid soln solution regulator solution pH to 7.1 of 5.4mol/L again, to stir after 15 minutes to leave standstill again and carry out ultrafiltration again after 1 hour, ultra-filtration membrane material is polyvinylidene difluoride (PVDF), its working pressure is 0.05 MPa, temperature 25 DEG C; By the filtrate that obtains in 15 DEG C, working pressure is that 0.5MPa carries out nanofiltration, and filter membrane is the NF270 polyamide composite film that LG-DOW company produces; Then carry out spraying dry, its inlet temperature is 170 DEG C, and temperature out is 70 DEG C, and after dry, rewinding is packed and be get final product.
Embodiment 5: a kind of preparation method of Iron Dextran, comprises the steps:
(1) 170kg purified water is put into retort, control pressure is 0.20MPa, is heated with stirring to 95 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 6 of 5.4mol/L, continue to boil 3 hours, be then cooled to 50 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 8, be heated to 80 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 100kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 12 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.20 MPa, solution is heated to boiling, boil 3 hours, be then cooled to 50 DEG C, obtain complex liquid; Adopt technique means 1 to process again, namely regulate complex liquid pH to 6.0 with the hydrochloric acid soln of 5.4mol/L, leave standstill 4 hours, then regulate pH to 10.1 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.3 MPa, flow velocity is 4m/s, temperature is 70 DEG C, filter sizes is 0.45 μm, filter membrane material is aluminum oxide; Technique means 2 is adopted to process the filtrate obtained, namely in the iron dextran solutions after micro-filtration process, add the hydrochloric acid soln solution regulator solution pH to 8.2 of 5.4mol/L again, to stir after 40 minutes to leave standstill again and carry out ultrafiltration again after 6 hours, ultra-filtration membrane material is polysulfones, its working pressure is 0.4MPa, temperature 45 C; By the filtrate that obtains in 40 DEG C, working pressure is that 0.9 MPa carries out nanofiltration, and filter membrane is rub the NF-1812 rolling nanofiltration membrane that fast science equipment company limited produces in Shanghai; Then carry out spraying dry, its inlet temperature is 200 DEG C, and temperature out is 100 DEG C, and after dry, rewinding is packed and be get final product.
Embodiment 6: a kind of preparation method of Iron Dextran, comprises the steps:
Step (1) is with embodiment 1.
(2) take after 38.9kg iron trichloride 85kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.10MPa, solution is heated to boiling, boil 1.5 hours, be then cooled to 38 DEG C, obtain complex liquid;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.15MPa, flow velocity is 2m/s, temperature is 55 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide; The filtrate obtained is carried out ultrafiltration, and ultra-filtration membrane material is polyethersulfone, and its working pressure is 0.2 MPa, temperature 35 DEG C; By the filtrate that obtains in 25 DEG C, working pressure is that 0.7 MPa carries out nanofiltration, the GE Nano filtering composite membrane of filter membrane to be model be DK8040F; Then carry out spraying dry, its inlet temperature is 185 DEG C, and temperature out is 85 DEG C, and after dry, rewinding is packed and be get final product.
What embodiment 6 adopted is the conventional preparation techniques of Iron Dextran, and the solubility property of obtained Iron Dextran in cold water is very poor, and iron level only has 25-30%, but can meet the basic purposes of medicine.
Embodiment 7: a kind of preparation method of Iron Dextran, comprises the steps:
Step (1) and step (2) are with embodiment 1.
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.15MPa, flow velocity is 2m/s, temperature is 55 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide; The filtrate obtained is carried out ultrafiltration, and ultra-filtration membrane material is polyethersulfone, and its working pressure is 0.2 MPa, temperature 35 DEG C; By the filtrate that obtains in 25 DEG C, working pressure is that 0.7 MPa carries out nanofiltration, the GE Nano filtering composite membrane of filter membrane to be model be DK8040F; Then carry out spraying dry, its inlet temperature is 185 DEG C, and temperature out is 85 DEG C, and after dry, rewinding is packed and be get final product.
Embodiment 8:
According to publication number a kind of novel method of producing Iron Dextran disclosed in the Chinese patent of CN102250261A, its embodiment is as follows:
(1) 1000ml Erlenmeyer flask is got, add 120g dextran, inject about 300ml and boil purified water, stir and be incubated 90-103 DEG C to dissolving completely, adding 4ml hydrochloric acid, encloses container, condensing reflux, and be incubated 90-103 DEG C, after hydrolysis terminates, add rapidly sodium hydroxide solution to neutralize, adjust ph is not more than 9;
(2) in the low molecular dextran obtained to step (1), gradation adds 4ml hydrogen peroxide and is oxidized, and keep feed temperature 63-70 DEG C in still, oxidization time controls at 1 hours.
(3) drip 40% liquor ferri trichloridi (in iron 30g) and 40% sodium hydroxide solution 75ml in the feed liquid obtained to step (2), and add the oxalic acid 2.5ml prepared.Keep temperature in the kettle 40-66 DEG C until be added dropwise to complete.1-1.5 hour is incubated, end of synthesis after regulating material liquid pH value 8-9. to be warming up to 95-105 DEG C.
(4) leave standstill 24 hours, by filter and ceramic membrane ultrafitration desalination concentrates, sterilization and disinfection, final spray dry become powder obtain product.
Test example 1: the assay of iron in Iron Dextran
The Iron Dextran that Example 1-8 is obtained is respectively about 0.3g, accurately weighed, puts in tool plug Erlenmeyer flask, add water 34ml and sulfuric acid 2ml, is heated to solution and shows orange-yellow, cooling, drip potassium permanganate test solution, just show pink to solution and continued for 5 seconds, adding hydrochloric acid 30ml and potassiumiodide test solution 30ml, close plug, leave standstill 3 minutes, add water 50ml, with Sulfothiorine titrating solution (0.1mol/L) titration, during to nearly terminal, add starch indicating liquid 2ml, continue to be titrated to blue disappearance.Every 1ml Sulfothiorine titrating solution (0.1mol/L) is equivalent to the Fe of 5.585mg.Record the amount of Sulfothiorine titrating solution used, and calculate the content of iron in Iron Dextran.Test-results is in table 1.
The content of iron in table 1 Iron Dextran
Test example 2: the solubility test of Iron Dextran
The obtained Iron Dextran of excessive embodiment 1-8 is added respectively and constant temperature stirs 30 minutes at 15 DEG C in 200ml water, leave standstill after 3 hours, with 0.45 μm of millipore filtration membrane filtration, after being diluted to suitable concentration, adopt ultraviolet-visible spectrophotometer analytical concentration, until analytical results repeats for continuous three times, with standard curve control, the solubleness at 15 DEG C can be obtained.Test-results is in table 2.
The solubleness of table 2 Iron Dextran
Test example 3:
The Iron Dextran that embodiment 1-8 is obtained is got 10g to be respectively dissolved in ml distilled water, and measure its specific conductivity with conductivitimeter after stirring, test-results is in table 3.
The each experimental group conductivity value of table 3
In the product that in table 1, embodiment 1-3 obtains, in Iron Dextran, the content of iron all reaches more than 40%, and embodiment 7 reaches 37.1%, far above product obtained in embodiment 4-6 and embodiment 8; The solubleness of product in cold water obtained in embodiment 1-3 and embodiment 7 in table 2 is all greater than 4g, far above product obtained in embodiment 4-6 and embodiment 8; In table 3, the specific conductivity of the product that embodiment 1-3 obtains all is less than 2 μ s/cm, and is less than embodiment 4-6 and the obtained product of embodiment 8, and the conductivity value of the obtained product of embodiment 7 is far away higher than the product that embodiment 1-3 is obtained, reaches 24 μ s/cm; This shows, the iron level of the Iron Dextran adopting technical solution of the present invention to obtain in embodiment 1-3 and be water-solublely all better than other embodiments, wherein embodiment 1 best results; Embodiment 7 only have employed technique means 1 and processes, water-soluble more satisfactory, iron level is also higher, but be the macromole intermediate impurities of 18-20 ten thousand containing a large amount of ionic impurities and molecular weight in end product, cause specific conductivity higher, have impact on the purity of product, make its iron level also lower than product obtained in embodiment 1-3.
Claims (3)
1. a preparation method for Iron Dextran, is characterized in that:
(1) 155kg purified water is put into retort, control pressure is 0.10MPa, is heated with stirring to 80 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 4 of 5.4mol/L, continue to boil 1.5 hours, be then cooled to 38 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 6, be heated to 70 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 85kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.10MPa, solution is heated to boiling, boil 1.5 hours, be then cooled to 38 DEG C, obtain complex liquid;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.15MPa, flow velocity is 2m/s, temperature is 55 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide; The filtrate obtained is carried out ultrafiltration, and ultra-filtration membrane material is polyethersulfone, and its working pressure is 0.2 MPa, temperature 35 DEG C; By the filtrate that obtains in 25 DEG C, working pressure is that 0.7 MPa carries out nanofiltration, the GE Nano filtering composite membrane of filter membrane to be model be DK8040F; Then carry out spraying dry, its inlet temperature is 185 DEG C, and temperature out is 85 DEG C, and after dry, rewinding is packed and be get final product.
2. a preparation method for Iron Dextran, is characterized in that:
(1) 150-160kg purified water is put into retort, control pressure is 0.05-0.15MPa, is heated with stirring to 75-85 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 3-5 of 5.4mol/L, continue to boil 1-2 hour, be then cooled to 35-40 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 6-7, be heated to 65-75 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 80-90kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 10-11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.05-0.15MPa, solution is heated to boiling, boil 1-2 hour, be then cooled to 35-40 DEG C, obtain complex liquid; Then regulate complex liquid pH to 5.3-5.8 with the hydrochloric acid soln of 5.4mol/L, leave standstill 1-3 hour, then regulate pH to 9.4-9.8 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.1-0.2 MPa, flow velocity is 1-3m/s, temperature is 50-60 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide, cellulose acetate or aluminum oxide; The hydrochloric acid soln solution regulator solution pH to 7.5-7.9 of 5.4mol/L is added again in the iron dextran solutions after micro-filtration process, stir after leaving standstill 2-5 hour again after 20-30 minute and carry out ultrafiltration again, ultra-filtration membrane material is polyethersulfone, polyvinylidene difluoride (PVDF) or polysulfones, its working pressure is 0.1-0.3 MPa, temperature 30-40 DEG C; By the filtrate that obtains in 20-30 DEG C, working pressure is that 0.6-0.8 MPa carries out nanofiltration, rubs the NF-1812 rolling nanofiltration membrane that fast science equipment company limited produces in the NF270 polyamide composite film that the GE Nano filtering composite membrane of filter membrane to be model is DK8040F, LG-DOW company produce or Shanghai; Then carry out spraying dry, its inlet temperature is 180-190 DEG C, and temperature out is 80-90 DEG C, and after dry, rewinding is packed and be get final product.
3. the preparation method of a kind of Iron Dextran as claimed in claim 2, is characterized in that:
(1) 155kg purified water is put into retort, control pressure is 0.10MPa, is heated with stirring to 80 DEG C, then adds 60kg Dextran 20, boils to dissolving completely; Add the hydrochloric acid conditioning solution pH to 4 of 5.4mol/L, continue to boil 1.5 hours, be then cooled to 38 DEG C, add 10mol/L sodium hydroxide solution and regulate hydrolyzed solution pH to 6, be heated to 70 DEG C, after crossing 100 mesh sieves, obtain brown color clear solution;
(2) take after 38.9kg iron trichloride 85kg purified water is dissolved and add retort, add the Dextran 20 hydrolyzed solution prepared again, pH to 11 is regulated with 10mol/L sodium hydroxide solution, control pressure is 0.10MPa, solution is heated to boiling, boil 1.5 hours, be then cooled to 38 DEG C, obtain complex liquid; Then regulate complex liquid pH to 5.6 with the hydrochloric acid soln of 5.4mol/L, leave standstill 2 hours, then regulate pH to 9.6 with 10mol/L sodium hydroxide solution;
(3) solution that step (2) obtains is carried out micro-filtration, its operating pressure is 0.15MPa, flow velocity is 2m/s, temperature is 55 DEG C, filter sizes is 0.45 μm, filter membrane material is polymeric amide; The hydrochloric acid soln solution regulator solution pH to 7.7 of 5.4mol/L is added again in the iron dextran solutions after micro-filtration process, to stir after 25 minutes to leave standstill again and carry out ultrafiltration again after 3.5 hours, ultra-filtration membrane material is polyethersulfone, and its working pressure is 0.2 MPa, temperature 35 DEG C; By the filtrate that obtains in 25 DEG C, working pressure is that 0.7 MPa carries out nanofiltration, the GE Nano filtering composite membrane of filter membrane to be model be DK8040F; Then carry out spraying dry, its inlet temperature is 185 DEG C, and temperature out is 85 DEG C, and after dry, rewinding is packed and be get final product.
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