CN102078291A - Method for preparing iron sorbitex injection - Google Patents
Method for preparing iron sorbitex injection Download PDFInfo
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- CN102078291A CN102078291A CN2009101752480A CN200910175248A CN102078291A CN 102078291 A CN102078291 A CN 102078291A CN 2009101752480 A CN2009101752480 A CN 2009101752480A CN 200910175248 A CN200910175248 A CN 200910175248A CN 102078291 A CN102078291 A CN 102078291A
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- iron sorbitex
- sorbitol
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Abstract
The invention discloses a method for preparing iron sorbitex injection. The method comprises the following steps of: (a) adding components of ferric trichloride, sodium bicarbonate, sorbitex and citric acid into pure water respectively to obtain corresponding aqueous solution; (b) weighing ferric trichloride aqueous solution and sodium bicarbonate aqueous solution and mixing, heating to the temperature of between 75 and 85 DEG C, and fully stirring to obtain mixed solution; (c) heating the mixed solution to 100 DEG C, adding sorbitex solution and citric acid solution in turn, and reacting to generate iron sorbitex mother liquor; (d) roughly filtering the mother liquor and performing membrane filtration to prepare iron sorbitex solution; and (e) adding 100g of iron sorbitex solution and 80g of medicinal sorbitex into every 1,000ml of injection water, uniformly stirring, performing carbon adsorption and decarburization, filtering, filling and sealing. By the method, the problem brought by adopting a dextrin auxiliary material is solved, a process is simplified, the production benefit is improved, and the production cost is reduced.
Description
Technical field:
The present invention relates to the preparation method of pharmaceutical preparation, specifically the preparation method of iron sorbitex inj.
Background technology:
Iron Sorbitex belongs to anti-anemic drug, contains 50mg ferrum in common every 2ml injection.Iron sorbitex inj is mainly used in prevention and treats various unsuitable oral chalybeate persons, as ulcerative colitis; Or the invalid iron deficiency anemia of oral medication; Or need correct anemia situation person rapidly.
Iron sorbitex inj is the sterilization colloid solution of sorbitol ferric citrate.The method for preparing at present iron sorbitex inj generally is first ferric chloride and sodium hydroxide or sodium carbonate reaction generation pulpous state intermediate product, slurry is mixed in proportion with sorbitol, refining dextrin, sodium citrate, natrium carbonicum calcinatum again, 100 ℃ of water-baths 1 hour, under high pressure, 120 ℃ of conditions, reacted 2 hours again, make the Iron Sorbitex mother solution.This mother solution cooling back reuse ethanol, methanol carry out refinement treatment (to remove the micromolecule complex), and drying is made Iron Sorbitex again, according to being routinely added to water for injection, makes injection.This method has the following disadvantages: (1) in preparation Iron Sorbitex mother solution process, its response speed shakiness, course of reaction are difficult to control, and the Iron Sorbitex yield is low.(2) prepared injection poor stability usually has precipitate to produce in the medicine effect phase.(3) need in process of production to make with extra care with ethanol, methanol, so complex manufacturing, the cycle is long, manufacturing cost is high, and poor stability, environment are unfriendly.For addressing this problem problem, the inventor once adopted dialysis process that the Iron Sorbitex mother solution is handled, but needed a large amount of drinking waters to exchange in the dialysis procedure, and because the exchange velocity between the ion is slower, had had a strong impact on speed of production.
Summary of the invention:
The preparation method that the purpose of this invention is to provide a kind of new iron sorbitex inj is to overcome the weak point of said method.
The object of the present invention is achieved like this:
The preparation method of iron sorbitex inj provided by the present invention may further comprise the steps:
(a) component with ferric chloride, sodium bicarbonate, sorbitol, citric acid adds pure water respectively, makes corresponding aqueous solution; Wherein the weight part ratio of each component is 3 parts of ferric chlorides, 2 parts of sodium bicarbonate, and 1 part of sorbitol, citric acid are 0.5% of gross weight.
(b) take by weighing ferric chloride aqueous solutions and sodium bicarbonate aqueous solution mix after, be warming up to 75 ℃～85 ℃, fully stir, make mixed liquor;
(c) above-mentioned mixed liquor is warming up to 100 ℃, adds sorbitol solution and citric acid solution successively, insulated and stirred 30～50 minutes, reaction generates the Iron Sorbitex mother solution;
(d) will be the membrane filtration of 3500～4500 molecular weight by the aperture again after the above-mentioned mother solution coarse filtration, making iron-holder be the Iron Sorbitex solution of 25mg/mL;
(e) according to every 1000ml water for injection, add above-mentioned Iron Sorbitex solution 100g, medicinal sorbitol 80g stirs evenly, and adds 0.1～0.5% activated carbon adsorption, takes off charcoal, filters, and fill is sealed.
For the further quality that improves iron sorbitex inj, and be convenient to storage, transportation, can after the fill of above-mentioned d step operation, carry out lyophilizing injection.
The preferred steps of its freeze-dry process is:
(a) pre-freeze: iron sorbitex inj is cooled to-5 ℃～-8 ℃, freezing 40～60 minutes earlier); And then be cooled to-40 ℃～-55 ℃, freezing 40～60 minutes;
(b) sublimation drying: be evacuated to 10～15 handkerchiefs in the casing, products temperature risen to-25～-30 ℃, be incubated 6～8 hours; Again products temperature is risen to-23～-27 ℃, be incubated 8～10 hours;
(c) dry again: as goods to be warming up to 38～40 ℃ gradually, to be incubated 1～2 hour.
The present invention innovates part and is: a, the synthetic first step of Iron Sorbitex select ferric chloride and sodium bicarbonate to react, and reaction is more relaxed, and better controls reaction speed is convenient to operation, thereby has been saved the time.B, will be in the Iron Sorbitex building-up process adopt reverse osmosis handle in synthetic Iron Sorbitex mother solution, both avoided the problem that adopts the dextrin adjuvant to be brought, simplify technology again, improved productivity effect, reduced production cost.
Following principal agent of the optional usefulness of its technical recipe of iron sorbitex inj of the present invention and adjuvant:
Iron Sorbitex in every 1000ml water for injection (by the ferrum amount 25%) 100g, medicinal sorbitol 80g.Also can add adjuvants such as tween 80, benzyl alcohol in the injection.
The preparation specification of iron sorbitex inj of the present invention is that 50mg/2ml/ props up.
The iron sorbitex inj that the inventive method is made, all same as the prior art with clinical indication and usage and dosage.
The made iron sorbitex inj of the inventive method is not seen toxic reaction through acute, sub-acute toxicity experiment.
The specific embodiment:
Following examples are used for that the present invention is described in further detail.
Embodiment 1:
(a) component with ferric chloride, sodium bicarbonate, sorbitol, citric acid adds an amount of pure water respectively, makes corresponding aqueous solution; Wherein the weight part ratio of each component is ferric chloride 3kg, sodium bicarbonate 2kg, sorbitol 1kg, citric acid 0.03kg.
(b) take by weighing ferric chloride aqueous solutions and sodium bicarbonate aqueous solution mix after, be warming up to 75 ℃, fully stir, make mixed liquor;
(c) above-mentioned mixed liquor is warming up to 100 ℃, adds sorbitol solution and citric acid solution successively, insulated and stirred 50 minutes, reaction generates the Iron Sorbitex mother solution;
(d) will be the membrane filtration of 3500 molecular weight again by the aperture after the above-mentioned mother solution coarse filtration; Making iron-holder is the Iron Sorbitex solution of 25mg/ml;
(e) according to every 1000ml water for injection, add above-mentioned Iron Sorbitex solution 100g, medicinal sorbitol 80g stirs evenly, and adds 0.1% activated carbon adsorption, takes off charcoal, filters, and fill is sealed.
Embodiment 2:
(a) ferric chloride, sodium bicarbonate, sorbitol, citric acid are added pure water respectively, make corresponding aqueous solution;
(b) take by weighing ferric chloride aqueous solutions and sodium bicarbonate aqueous solution mix after, be warming up to 80 ℃, fully stir, make mixed liquor;
(c) above-mentioned mixed liquor is warming up to 100 ℃, adds sorbitol solution and citric acid solution successively, insulated and stirred 30 minutes, reaction generates the Iron Sorbitex mother solution;
(d) will be the membrane filtration of 4500 molecular weight again by the aperture after the above-mentioned mother solution coarse filtration; The detection iron content is 25mg/ml;
(e) according to every 1000ml water for injection, add above-mentioned Iron Sorbitex solution 100g, medicinal sorbitol 80g stirs evenly, add 0.1-0.5% activated carbon adsorption, take off charcoal, filter, fill is sealed.
Embodiment 3:
(a) ferric chloride, sodium bicarbonate, sorbitol, citric acid are added pure water respectively, make corresponding aqueous solution;
(b) take by weighing ferric chloride aqueous solutions and sodium bicarbonate aqueous solution mix after, be warming up to 85 ℃, fully stir, make mixed liquor;
(c) above-mentioned mixed liquor is warming up to 100 ℃, adds sorbitol solution and citric acid solution successively, insulated and stirred 40 minutes, reaction generates the Iron Sorbitex mother solution;
(d) will be the membrane filtration of 4000 molecular weight again by the aperture after the above-mentioned mother solution coarse filtration; The detection iron content is 25mg/ml;
(e) according to every 1000ml water for injection, add above-mentioned Iron Sorbitex solution 100g, medicinal sorbitol 80g stirs evenly, add 0.1-0.5% activated carbon adsorption, take off charcoal, filter fill;
(f) with said products lyophilizing in accordance with the following methods, make lyophilized formulations:
Pre-freeze: goods are cooled to-8 ℃, freezing 40 minutes earlier; And then be cooled to-55 ℃, freezing 40 minutes;
Sublimation drying: be evacuated to 10～15 handkerchiefs in the casing, products temperature risen to-25 ℃, be incubated 8 hours; Again products temperature is risen to-27 ℃, be incubated 8 hours;
(g) dry again: as goods to be warming up to 40 ℃ gradually, to be incubated 1 hour.
Embodiment 4:
(a) ferric chloride, sodium bicarbonate, sorbitol, citric acid are added pure water respectively, make corresponding aqueous solution;
(b) take by weighing ferric chloride aqueous solutions and sodium bicarbonate aqueous solution mix after, be warming up to 85 ℃, fully stir, make mixed liquor;
(c) above-mentioned mixed liquor is warming up to 100 ℃, adds sorbitol solution and citric acid solution successively, insulated and stirred 40 minutes, reaction generates the Iron Sorbitex mother solution;
(d) will be the membrane filtration of 4000 molecular weight again by the aperture after the above-mentioned mother solution coarse filtration; The detection iron content is 25mg/ml;
(e) according to every 1000ml water for injection, add above-mentioned Iron Sorbitex solution 100g, medicinal sorbitol 80g stirs evenly, and adds 0.1～0.5% activated carbon adsorption, takes off charcoal, filters fill;
(f) with said products lyophilizing in accordance with the following methods, make lyophilized formulations:
Pre-freeze: goods are cooled to-5 ℃, freezing 60 minutes earlier; And then be cooled to-40 ℃, freezing 60 minutes;
Sublimation drying: be evacuated to 10 handkerchiefs in the casing, products temperature risen to-30 ℃, be incubated 8 hours; Again products temperature is risen to-23 ℃, be incubated 10 hours;
(g) dry again: as goods to be warming up to 38 ℃ gradually, to be incubated 2 hours.
Comparative Examples 1
(a) the abundant stirring reaction pulpous state intermediate product in 100 ℃ aqueous solution with ferric chloride and sodium hydroxide;
(b) above-mentioned slurry and sorbitol, refining dextrin, sodium citrate are mixed in proportion, 100 ℃ of water-baths 1 hour, the Iron Sorbitex mother solution was made in reaction 2 hours under high pressure, 120 ℃ of conditions again;
(c) with after this mother solution cooling, reuse ethanol, methanol carry out refinement treatment (to remove the micromolecule complex), and drying is made Iron Sorbitex again, according to being routinely added to water for injection, makes iron sorbitex inj.
Comparative Examples 2
(a) the abundant stirring reaction pulpous state intermediate product in 100 ℃ aqueous solution with ferric chloride and sodium carbonate;
(b) above-mentioned slurry and sorbitol, refining dextrin, sodium citrate are mixed in proportion, 100 ℃ of water-baths 1 hour, the Iron Sorbitex mother solution was made in reaction 2 hours under high pressure, 120 ℃ of conditions again;
(c) above-mentioned mother solution is filtered, filtrate add pure water dialyse to clarity up to standard after, add water for injection, be about 25mg/mL to iron-holder, fill, seal, promptly get iron sorbitex inj.
Embodiment 5
The contrast test of the inventive method and prior art processes.
By above-mentioned test data as seen, the inventive method process cycle weak point, low cost of manufacture and product stability are good.
Claims (3)
1. the preparation method of an iron sorbitex inj is characterized in that it may further comprise the steps:
(a) component with ferric chloride, sodium bicarbonate, sorbitol, citric acid adds pure water respectively, makes corresponding aqueous solution; Wherein the weight part ratio of each component is 3 parts of ferric chlorides, 2 parts of sodium bicarbonate, and 1 part of sorbitol, citric acid are 0.5% of gross weight.
(b) take by weighing ferric chloride aqueous solutions and sodium bicarbonate aqueous solution mix after, be warming up to 75 ℃～85 ℃, fully stir, make mixed liquor;
(c) above-mentioned mixed liquor is warming up to 100 ℃, adds sorbitol solution and citric acid solution successively, insulated and stirred 30～50 minutes, reaction generates the Iron Sorbitex mother solution;
(d) will be the membrane filtration of 3500～4500 molecular weight by the aperture again after the above-mentioned mother solution coarse filtration, making iron-holder be the Iron Sorbitex solution of 25mg/mL;
(e) according to every 1000ml water for injection, add above-mentioned Iron Sorbitex solution 100g, medicinal sorbitol 80g stirs evenly, and adds 0.1～0.5% activated carbon adsorption, takes off charcoal, filters, and fill is sealed.
2. the preparation method of iron sorbitex inj according to claim 1, it is characterized in that described d step operation fill after, injection is carried out lyophilizing.
3. the preparation method of iron sorbitex inj according to claim 2 is characterized in that described freeze-dry process is:
(a) pre-freeze: iron sorbitex inj is cooled to-5 ℃～-8 ℃, freezing 40～60 minutes earlier; And then be cooled to-40 ℃～-55 ℃, freezing 40～60 minutes;
(b) sublimation drying: be evacuated to 10～15 handkerchiefs in the casing, products temperature risen to-25～-30 ℃, be incubated 6～8 hours; Again products temperature is risen to-23～-27 ℃, be incubated 8～10 hours;
(c) dry again: as goods to be warming up to 38～40 ℃ gradually, to be incubated 1～2 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101752480A CN102078291B (en) | 2009-11-26 | 2009-11-26 | Method for preparing iron sorbitex injection |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101752480A CN102078291B (en) | 2009-11-26 | 2009-11-26 | Method for preparing iron sorbitex injection |
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| CN102078291A true CN102078291A (en) | 2011-06-01 |
| CN102078291B CN102078291B (en) | 2012-05-16 |
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| CN1087518A (en) * | 1992-03-25 | 1994-06-08 | 中国农业科学院饲料研究所 | Poultry are used the prescription and the technology of hemopoietin injection |
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Owner name: HUABEI PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: NORTH CHINA PHARMACEUTICAL GROUP PREPARATION CO., LTD. Effective date: 20121101 |
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Effective date of registration: 20121101 Address after: 050015 Heping East Road, Hebei, Shijiazhuang, No. 388 Patentee after: NORTH CHINA PHARMACEUTICAL Co.,Ltd. Address before: 050015 No. 135 North sports street, Hebei, Shijiazhuang Patentee before: NORTH CHINA PHARMACEUTICAL GROUP PREPARATION Co.,Ltd. |
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Granted publication date: 20120516 Termination date: 20211126 |