CN102250261B

CN102250261B - New method for producing iron dextran

Info

Publication number: CN102250261B
Application number: CN 201010576160
Authority: CN
Inventors: 邓涛; 周忠亮
Original assignee: TIANJIN HUAIREN PHARMACEUTICAL CO Ltd
Current assignee: TIANJIN HUAIREN PHARMACEUTICAL CO Ltd
Priority date: 2010-12-07
Filing date: 2010-12-07
Publication date: 2013-02-20
Anticipated expiration: 2030-12-07
Also published as: CN102250261A

Abstract

The invention is a new method for producing iron dextran, which mainly comprises four steps: 1. performing hydrolysis with hydrochloric acid in a high-temperature condition to turn dextran into required low-molecular dextran; 2. performing oxidation by a hydrogen peroxide stepwise oxidation method, and preserving a certain temperature to obtain dextran with a proper structure during complexation;3. preparing iron dextran with a controlled temperature and a controlled speed by a method of dropwise adding acid and alkali simultaneously with a uniform speed, and performing high-temperature aging to make the product more stable; 4. performing filtration and ceramic membrane ultrafiltration of the finished product for salt removal and concentration. In step 1, the hydrolysis method adopts hydrochloric acid high-temperature hydrolysis instead of traditional complicated bacterial fermentation, which saves a lot of time and cost. In step 2, a traditional potassium cyanide method is substituted so as to reduce the toxicity and improve environmental pollution. In step 3, many cumbersome intermediate links in a traditional synthetic process are reduced; a lot of investment cost and production cost are saved; and the product quality and yield are increased. In step 4, a traditional alcohol precipitation process is substituted; both the product quality is improved and the working hour andcost are saved; and a product with good quality is provided for the prevention of iron deficiency anemia.

Description

Produce the method for Iron Dextran

Technical field the present invention relates to a kind of polysaccharide derivatives Iron Dextran and production method.

Background technology is present, and hypoferric anemia (IDA) is global distribution, and is particularly outstanding with developing country, and women, infant and children are high risk population of IDA, in China and some developing country's morbiditys up to more than 30%.As the clinical first-selected medication of mending iron and enriching blood, mending chalybeates with other, to compare good effect, rapid-action, degree of absorbing height, acute toxic reaction low by both at home and abroad for Iron Dextran.

At present, the synthetic method of Iron Dextran is different, but the ubiquity quality is not bery stable, output is not high yet, and production difficulty is higher, toxicity is large, the problem of environmental pollution.

Summary of the invention the present invention is a kind of novel method that generates Iron Dextran, mainly divides for four steps:

1 usefulness hydrochloric acid is hydrolyzed in the situation of high temperature, dextran is become the low molecular dextran that needs.

2 adopt the method for hydrogen peroxide step-by-step oxidation to carry out oxidation, keep certain temperature, the dextran of appropriate configuration when obtaining complexing.

3 methods that adopt soda acid at the uniform velocity to drip simultaneously, temperature control control speed preparation Iron Dextran makes product more stable by high temperature ageing.

4 the finished product are concentrated by filtration and ceramic membrane ultrafitration desalination.

The bacterium that 1 one-step hydrolysis method adopts the hydrochloric acid pyrohydrolysis to replace traditional complexity is fermented a large amount of time and the cost of saving.Thereby 2 steps replaced traditional potassium cyanide method to reduce toxicity has improved environmental pollution.Reduce in traditional building-up process that many complicated middle-chains have been saved a large amount of costs of investment and production cost has improved quality product and output 3 steps, 4 steps replaced traditional alcohol precipitation process, saved man-hour and cost when improving the quality of products, the product of high-quality is provided for the prevention hypoferric anemia.

Embodiment

1 usefulness hydrochloric acid is hydrolyzed in the situation of high temperature, dextran is become the low molecular dextran that needs

To be molecular weight add 90～103 ℃ hot purified water at the 18000-35000 dextran to its method, in, insulated and stirred is to fully dissolving, and at the 90-103 ℃ of hydrochloric acid hydrolysis with 7mol/L about 30 minutes, neutralization obtains the lower molecular weight dextran that needs.

2 adopt the method for hydrogen peroxide step-by-step oxidation to carry out oxidation, keep certain temperature, the dextran of appropriate configuration when obtaining complexing

Go on foot in the lower molecular weight dextran solution of the 30%-35% that obtains 1, adding concentration is 30% superoxol, maintain the temperature at 63-70 ℃, after 25 minutes, again add the superoxol with isoconcentration and volume, oxidation is 25 minutes again, and oxidation is complete, in the oxidising process pH value of system is adjusted the maintenance system and keeps the pH value about 8.

3 methods that adopt soda acid at the uniform velocity to drip simultaneously, temperature control control speed preparation Iron Dextran makes product more stable by high temperature ageing

The liquor ferri trichloridi that at first prepares 40-50%, under 35-40 ℃ temperature, stir and be that 40% sodium hydroxide solution splashes in the dextran solution simultaneously with 50 ℃ concentration, add oxalic acid in the dropping process as initiation, the control temperature is between 40-66 ℃ in the dropping process, reacted 3-4 hour, the final pH value of regulating product with sodium hydroxide is 8-9, begins to heat up to remain on 95-105 ℃, at sustained reaction 1-1.5 hour, then left standstill 24 hours, and be cooled to 15-20 ℃ and get final product.By filter and the ceramic membrane ultrafitration desalination concentrated, disinfection through strict quality control, finally sprays and driedly becomes powder to obtain product.

The invention has the advantages that:

1 adopts hydrolysis method to obtain low molecular dextran, and equipment cost is low, operation is few, processing condition are easily controlled, and production cost, personnel also reduce man-hour greatly.

2 adopt hydrogen peroxide to replace traditional potassium cyanide as oxygenant, have reduced toxicity, are conducive to environment protection and personnel's labour protection.

After 3 reactions finish, make quality product more stable by high temperature ageing.

4 adopt the ceramic membrane ultrafitration desalination concentrated, make the end product quality index more stable.

Embodiment 1

1 gets the 1000ml Erlenmeyer flask, adds the 120g dextran, injects about 300ml to boil purified water, stirs and be incubated 90～103 ℃ to fully dissolving, adds 4ml hydrochloric acid, encloses container, and condensing reflux, and be incubated 90～103 ℃.Hydrolysis adds rapidly sodium hydroxide solution and neutralizes after finishing, and regulates pH value and is not more than 9.

2 in 1 low molecular dextran that obtains of step gradation add the 4ml hydrogen peroxide and carry out oxidation, keep in the still feed temperature 63-70 ℃.Oxidization time was controlled at about 1 hour.

3 drip 40% liquor ferri trichloridi (in iron 30g) and 40% sodium hydroxide solution 75ml in 2 feed liquids that obtain of step, and the oxalic acid 2.5ml for preparing of adding.Keep 40-66 ℃ of temperature in the kettle until be added dropwise to complete.Regulate material liquid PH value 8-9.Insulation is 1-1.5 hour after being warming up to 95-105 ℃, end of synthesis.

4 left standstill 24 hours, by filter and the ceramic membrane ultrafitration desalination concentrated, disinfection finally sprays and driedly becomes powder to obtain product.

Claims

1. method of producing Iron Dextran, its specific features has the following aspects:

1 pyrohydrolysis dextran saves time and obtains fast the lower molecular weight dextran that needs, and molecular weight is at the dextran of 18000-35000,90-103 ℃ with the hydrochloric acid hydrolysis of 7mol/L 30 minutes, neutralization obtains the lower molecular weight dextran that needs

2 adopt hydrogen peroxide method oxidation dextran, in the lower molecular weight dextran solution of 30%-35%, adding concentration is 30% superoxol, maintain the temperature at 63-70 ℃, after 25 minutes, again add the superoxol with isoconcentration and volume, oxidation is 25 minutes again, oxidation is complete, in the oxidising process pH value of system is adjusted the maintenance system and keeps the pH value 8

The synthetic preparation of 3 Iron Dextrans

The liquor ferri trichloridi that at first prepares 40-50%, under 35-40 ℃ temperature, stir and be that 40% sodium hydroxide solution splashes in the dextran solution with the liquor ferri trichloridi that has prepared simultaneously with 50 ℃ concentration, add oxalic acid in the dropping process as initiation, the control temperature is between 40-66 ℃ in the dropping process, reacted 3-4 hour, the final pH value of regulating product with sodium hydroxide is 8-9, begins to heat up to remain on 95-105 ℃, sustained reaction 1-1.5 hour, then left standstill 24 hours, be cooled to 15-20 ℃ and get final product, concentrated by filtration and ceramic membrane ultrafitration desalination, disinfection, through strict quality control, finally spray and driedly become powder to obtain product.