CN102250261A - New method for producing iron dextran - Google Patents

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 and cost are saved; and a product with good quality is provided for the prevention of iron deficiency anemia.

Description

Produce the novel method of 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 mending the clinical first-selected medication that iron is enriched 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 difference of Iron Dextran, but the ubiquity quality is not really stable, output is not high yet, and the production difficulty is higher, toxicity is big, environmental pollution problems.

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 under the pyritous situation, 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 concentrate 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, man-hour and cost have been saved when improving the quality of products, for the prevention hypoferric anemia provides the fine product.

Embodiment

1 usefulness hydrochloric acid is hydrolyzed under the pyritous situation, 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 dissolving fully, 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, add superoxol once more with isoconcentration and volume, reoxidation 25 minutes, oxidation finishes, and 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, controlled 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, left standstill then 24 hours, and be cooled to 15-20 ℃ and get final product.By filtering and the ceramic membrane ultrafitration desalination concentrates, 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, help 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 to concentrate, and 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 dissolving fully, adds 4ml hydrochloric acid, encloses container, and condensing reflux, and be incubated 90～103 ℃.Hydrolysis adds sodium hydroxide solution rapidly 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 being 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, and by filtering and the ceramic membrane ultrafitration desalination concentrates, disinfection finally sprays and driedly becomes powder to obtain product.

Claims (1)

1. novel method of producing Iron Dextran, its concrete feature has the following aspects:

1 pyrohydrolysis dextran saves time and obtains the lower molecular weight dextran of needs fast.Molecular weight is at the dextran of 18000-35000, 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 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, add superoxol once more with isoconcentration and volume, reoxidation 25 minutes, oxidation finishes, and in the oxidising process pH value of system is adjusted the maintenance system and keeps the pH value about 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 simultaneously with 50 ℃ concentration, add oxalic acid in the dropping process as initiation, controlled 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, left standstill then 24 hours, and be cooled to 15-20 ℃ and get final product.By filtering and the ceramic membrane ultrafitration desalination concentrates, disinfection through strict quality control, finally sprays and driedly becomes powder to obtain product.

Through above step synthetic product, meet the Chinese Pharmacopoeia regulation, and dissolution rate is preferably arranged, do not absorb other indexs such as iron and have outstanding performance yet.