CN112409505A - Production method for controlling stability of weight average molecular weight and distribution coefficient of iron dextran - Google Patents
Production method for controlling stability of weight average molecular weight and distribution coefficient of iron dextran Download PDFInfo
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- CN112409505A CN112409505A CN202011298006.3A CN202011298006A CN112409505A CN 112409505 A CN112409505 A CN 112409505A CN 202011298006 A CN202011298006 A CN 202011298006A CN 112409505 A CN112409505 A CN 112409505A
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- dextran
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- molecular weight
- iron
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0021—Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/12—Powdering or granulating
- C08J3/122—Pulverisation by spraying
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/02—Dextran; Derivatives thereof
Abstract
The invention discloses a production method for controlling the stability of weight average molecular weight and distribution coefficient of iron dextran, which comprises the following steps: s01, hydrolysis of dextran: dextran is hydrolyzed under acidic condition, and molecular weight is reduced; s02, complexing: reacting ferric trichloride with sodium hydroxide to produce ferric hydroxide, and complexing the ferric hydroxide with dextran to produce iron dextran; s03, nanofiltration: removing salt, heavy metal and free iron impurities in the complexing solution by adopting an ultrafiltration process, and concentrating the complexing solution; s04, spray drying: and adding the qualified solution after ultrafiltration into spray drying equipment, and spray drying to obtain powder. The invention produces the iron dextran with stable weight average molecular weight and distribution coefficient, and accurately controls the weight average molecular weight (Mw) of the iron dextran raw material and the preparation to be about 6000, so that the inherent quality and the clinical treatment effect of the iron dextran are improved.
Description
The technical field is as follows:
the invention relates to the technical field of iron dextran preparation, in particular to a method for controlling the stability of the weight average molecular weight and the distribution coefficient of iron dextran.
Background art:
the iron dextran is a common antiangiogenic drug, is a complex of iron hydroxide and dextran with the weight average relative molecular mass of 5000-7500, and contains not less than 25.0% of iron. The iron dextran injection is the most widely used iron supplementing injection for preventing and treating piglet iron deficiency anemia at present. The quality standard of the first edition of Chinese veterinary pharmacopoeia 2015 requires that the weight-average molecular weight (Mw) of iron dextran raw materials and preparations is 5000-7500. At present, most domestic veterinary drug enterprises are difficult to produce iron dextran injection products meeting the national standard, the weight average molecular weight (Mw) of iron dextran injections sold in domestic markets basically exceeds more than 10000 and does not meet the national standard requirements, and the iron dextran injection products are traced to the fact that the weight average molecular weight and the distribution coefficient of iron dextran raw materials are high and do not meet the national standard requirements.
The weight average molecular weight (Mw) is controlled to be 5000-7500 accurately, the iron supplement effect is important, the product quality of the iron dextran injection is directly influenced, the molecular weight is not favorable for the absorption of an organism after intramuscular injection to medicines, and piglet stress is large during injection, so that black necrotic lesions or lumps are formed at the injection part to influence the carcass quality of pigs.
Although the polysaccharide dextran is produced by the enzyme method, the polysaccharide dextran is degraded by the acidolysis method, which results in high production cost and difficult obtainment of the ultra-micro dextran with narrow molecular weight distribution. The relative molecular mass and the relative molecular mass distribution of the dextran before and after hydrolysis are determined, and the results show that the weight-average relative molecular mass of most samples after hydrolysis is reduced, the distribution width is narrowed, and the determination of the relative molecular mass and the relative molecular mass distribution of the dextran after hydrolysis is not enough to control the product quality.
The invention content is as follows:
the invention aims to at least solve the technical problems and provides a production method for controlling the weight average molecular weight and the distribution coefficient stability of the iron dextran.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for controlling the stability of the weight average molecular weight and the distribution coefficient of iron dextran comprises the following steps:
s01, hydrolysis of dextran: adding 260kg of purified water into a reaction kettle with the volume of 1000L, heating to 100 ℃, adding 100kg of dextran with the molecular weight of 20000, heating and stirring for 30 minutes for dissolving, and keeping the kettle temperature at 100 ℃; dissolving dextran, adding 6L hydrochloric acid, hydrolyzing, heating, and stirring for 15 min; adding about 8L of 50% sodium hydroxide solution into the hydrolyzed dextran solution in the kettle for neutralization, quickly adjusting the pH value to 7-8, stopping hydrolysis of the dextran, stirring, naturally cooling to 80 ℃, supplementing evaporated water, and keeping the temperature of 80 ℃ for 30 minutes;
s02, complexing: naturally cooling the neutralized solution to 65 ℃, and adding 185kg of 65 mass percent ferric trichloride solution; after the feeding is finished, keeping the temperature at 60 ℃ and stirring for 30 minutes; then adding 110kg of 50% sodium hydroxide solution, controlling the whole feeding time to be 6 hours, keeping the temperature to be 95-100 ℃ in the feeding process, and maintaining the temperature to be 95-100 ℃ for 1 hour after the feeding is finished so as to ensure that the iron hydroxide and the dextran are tightly complexed;
s03, nanofiltration: removing salt, heavy metal and free iron impurities in the complexing solution by adopting an ultrafiltration process, and concentrating the complexing solution;
s04, spray drying: and adding the qualified solution after ultrafiltration into spray drying equipment, and spray drying to obtain powder.
Further, the hydrochloric acid is a hydrochloric acid solution with the mass ratio of 1:1 to water.
Further, after the complexation is finished, sampling, measuring the pH value to be 6-7, and standing for more than 12 hours.
Further, in the nanofiltration step, the ultrafiltration process comprises adding the complexed solution into ultrafiltration equipment, wherein the ultrafiltration equipment comprises a nanofiltration membrane, the ultrafiltration equipment pressurizes the complexed solution, and the complexed solution passes through the nanofiltration membrane and filters the salt, heavy metal and free iron impurities in the solution to obtain the ultrafiltered and concentrated complexed solution.
Further, in the spray drying step, the complexing liquid is input from the top of the drying tower, sprayed into atomized liquid drops through an atomizer, dried into powder through hot air dried in the tower, and accumulated at the bottom of the tower to form powder.
The working principle of the invention is as follows: dextran is hydrolyzed under acidic condition, and molecular weight is reduced; reacting ferric trichloride with sodium hydroxide to produce ferric hydroxide, and complexing the ferric hydroxide with dextran to produce iron dextran; then, ultrafiltration and spray drying are carried out.
The production method for controlling the weight average molecular weight and the distribution coefficient stability of the iron dextran has the following beneficial effects: by adopting the scheme, the iron dextran with stable weight average molecular weight and distribution coefficient is produced, the weight average molecular weight (Mw) of the iron dextran raw material and the weight average molecular weight (Mw) of the preparation are accurately controlled to be about 6000, so that the inherent quality and the clinical treatment effect of the iron dextran raw material and the preparation are improved, and the iron dextran raw material and the preparation are safe, effective and controllable in quality.
The specific implementation mode is as follows:
it should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The technical solutions in the embodiments of the present invention will be described clearly and completely below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that all the directional indications in the embodiments of the present invention are only used to explain the relative position relationship between the components in a specific posture-the motion situation, etc., and if the specific posture is changed, the directional indication is changed accordingly, and the connection may be a direct connection or an indirect connection.
Example 1:
a method for controlling the stability of the weight average molecular weight and the distribution coefficient of iron dextran comprises the following steps:
s01, hydrolysis of dextran: adding 260kg of purified water into a reaction kettle with the volume of 1000L, heating to 100 ℃, adding 100kg of dextran with the molecular weight of 20000, heating and stirring for 30 minutes for dissolving, and keeping the kettle temperature at 100 ℃; adding 6L of hydrochloric acid after the dextran is dissolved, wherein the hydrochloric acid adopts a hydrochloric acid solution with the mass ratio of 1:1 to water, and hydrolyzing, heating and stirring for 15 minutes; adding about 8L of 50% sodium hydroxide solution into the hydrolyzed dextran solution in the kettle for neutralization, quickly adjusting the pH value to 7, stopping the hydrolysis of the dextran, stirring, naturally cooling to 80 ℃, supplementing evaporated water, and keeping the temperature of 80 ℃ for 30 minutes;
s02, complexing: naturally cooling the neutralized solution to 65 ℃, and adding 185kg of 65 mass percent ferric trichloride solution; after the feeding is finished, keeping the temperature at 60 ℃ and stirring for 30 minutes; then adding 110kg of 50% sodium hydroxide solution, controlling the whole feeding time to be 6 hours, keeping the temperature at 95 ℃ in the feeding process, and maintaining the temperature at 100 ℃ for 1 hour after the feeding is finished so as to ensure that the iron hydroxide and the dextran are tightly complexed; after the complexation is finished, sampling, measuring the pH value to be between 6, and standing for more than 12 hours;
s03, nanofiltration: removing salt, heavy metal and free iron impurities in the complexing solution by adopting an ultrafiltration process, and concentrating the complexing solution; the ultrafiltration process comprises the steps of adding the complex solution into ultrafiltration equipment, wherein the ultrafiltration equipment comprises a nanofiltration membrane, the ultrafiltration equipment pressurizes the complex solution, and the complex solution passes through the nanofiltration membrane and filters salt, heavy metal and free iron impurities in the solution to obtain an ultrafiltration and concentrated complex solution;
s04, spray drying: adding the solution qualified by ultrafiltration into a spray drying tower, inputting the complexing solution from the top of the drying tower, spraying the complexing solution into vaporous liquid drops through an atomizer, drying the liquid drops into powder after passing through hot air dried in the tower, and accumulating the powder at the bottom of the tower to form powder, thus preparing the iron dextran powder.
Example 2:
a method for controlling the stability of the weight average molecular weight and the distribution coefficient of iron dextran comprises the following steps:
s01, hydrolysis of dextran: adding 260kg of purified water into a reaction kettle with the volume of 1000L, heating to 100 ℃, adding 100kg of dextran with the molecular weight of 20000, heating and stirring for 30 minutes for dissolving, and keeping the kettle temperature at 100 ℃; adding 6L of hydrochloric acid after the dextran is dissolved, wherein the hydrochloric acid adopts a hydrochloric acid solution with the mass ratio of 1:1 to water, and hydrolyzing, heating and stirring for 15 minutes; adding about 8L of 50% sodium hydroxide solution into the hydrolyzed dextran solution in the kettle for neutralization, quickly adjusting the pH value to 8, stopping the hydrolysis of the dextran, stirring, naturally cooling to 80 ℃, supplementing evaporated water, and keeping the temperature of 80 ℃ for 30 minutes;
s02, complexing: naturally cooling the neutralized solution to 65 ℃, and adding 185kg of 65 mass percent ferric trichloride solution; after the feeding is finished, keeping the temperature at 60 ℃ and stirring for 30 minutes; then adding 110kg of 50% sodium hydroxide solution, controlling the whole feeding time to be 6 hours, keeping the temperature at 100 ℃ in the feeding process, and maintaining the temperature at 95 ℃ for 1 hour after the feeding is finished so as to ensure that the iron hydroxide and the dextran are tightly complexed; after the complexation is finished, sampling, measuring the pH value to be 7, and standing for more than 12 hours;
s03, nanofiltration: removing salt, heavy metal and free iron impurities in the complexing solution by adopting an ultrafiltration process, and concentrating the complexing solution; the ultrafiltration process comprises the steps of adding the complex solution into ultrafiltration equipment, wherein the ultrafiltration equipment comprises a nanofiltration membrane, the ultrafiltration equipment pressurizes the complex solution, and the complex solution passes through the nanofiltration membrane and filters salt, heavy metal and free iron impurities in the solution to obtain an ultrafiltration and concentrated complex solution;
s04, spray drying: adding the solution qualified by ultrafiltration into a spray drying tower, inputting the complexing solution from the top of the drying tower, spraying the complexing solution into vaporous liquid drops through an atomizer, drying the liquid drops into powder after passing through hot air dried in the tower, and accumulating the powder at the bottom of the tower to form powder, thus preparing the iron dextran powder.
The foregoing shows and describes the general principles, essential features, and inventive features of this invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is to be protected by the following claims and their equivalents.
Claims (5)
1. A method for controlling the stability of the weight average molecular weight and the distribution coefficient of iron dextran is characterized in that: the method comprises the following steps:
s01, hydrolysis of dextran: adding 260kg of purified water into a reaction kettle with the volume of 1000L, heating to 100 ℃, adding 100kg of dextran with the molecular weight of 20000, heating and stirring for 30 minutes for dissolving, and keeping the kettle temperature at 100 ℃; dissolving dextran, adding 6L hydrochloric acid, hydrolyzing, heating, and stirring for 15 min; adding about 8L of 50% sodium hydroxide solution into the hydrolyzed dextran solution in the kettle for neutralization, quickly adjusting the pH value to 7-8, stopping hydrolysis of the dextran, stirring, naturally cooling to 80 ℃, supplementing evaporated water, and keeping the temperature of 80 ℃ for 30 minutes;
s02, complexing: naturally cooling the neutralized solution to 65 ℃, and adding 185kg of 65 mass percent ferric trichloride solution; after the feeding is finished, keeping the temperature at 60 ℃ and stirring for 30 minutes; then adding 110kg of 50% sodium hydroxide solution, controlling the whole feeding time to be 6 hours, keeping the temperature to be 95-100 ℃ in the feeding process, and maintaining the temperature to be 95-100 ℃ for 1 hour after the feeding is finished so as to ensure that the iron hydroxide and the dextran are tightly complexed;
s03, nanofiltration: removing salt, heavy metal and free iron impurities in the complexing solution by adopting an ultrafiltration process, and concentrating the complexing solution;
s04, spray drying: and adding the qualified solution after ultrafiltration into spray drying equipment, and spray drying to obtain powder.
2. The method for controlling the stability of the weight average molecular weight and the distribution coefficient of the iron dextran of claim 1, wherein: the hydrochloric acid adopts a hydrochloric acid solution with the mass ratio of 1:1 to water.
3. The method for controlling the stability of the weight average molecular weight and the distribution coefficient of the iron dextran of claim 1, wherein: after complexing, sampling after complexing, measuring the pH value to be 6-7, and standing for more than 12 hours.
4. The method for controlling the stability of the weight average molecular weight and the distribution coefficient of the iron dextran of claim 1, wherein: in the nanofiltration step, the ultrafiltration process comprises the step of adding the complexed solution into ultrafiltration equipment, wherein the ultrafiltration equipment comprises a nanofiltration membrane, the ultrafiltration equipment pressurizes the complexed solution, and the complexed solution passes through the nanofiltration membrane and filters the salt, heavy metal and free iron impurities in the solution to obtain the ultrafiltered and concentrated complexed solution.
5. The method for controlling the stability of the weight average molecular weight and the distribution coefficient of the iron dextran of claim 1, wherein: in the spray drying step, the complexing liquid is input from the top of a drying tower, sprayed into atomized liquid drops through an atomizer, dried into powder through hot air dried in the tower, and accumulated at the bottom of the tower to form the powder.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113087818A (en) * | 2021-05-18 | 2021-07-09 | 华科营养与生物技术(深圳)有限公司 | Dextran sulfate sodium salt or potassium salt and production method thereof |
| CN113480678A (en) * | 2021-08-06 | 2021-10-08 | 江西华太药业有限公司 | Iron dextran synthesizing method and its dispersing tablet |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044571A (en) * | 2011-10-13 | 2013-04-17 | 天津中敖生物科技有限公司 | Iron dextran bulk drug and preparation method thereof |
| CN104031170A (en) * | 2014-05-22 | 2014-09-10 | 海纳阳光（北京）医药控股有限公司 | Iron dextran raw material for human intravenous injection and preparation method thereof |
| CN106543294A (en) * | 2015-09-18 | 2017-03-29 | 瑞普（天津）生物药业有限公司 | A kind of preparation method of iron-dextrin |
| CN107049933A (en) * | 2017-02-28 | 2017-08-18 | 广西壮族自治区化工研究院 | A kind of weight average molecular weight is the preparation method of 3,000 24000 iron dextran injection |
| CN107400178A (en) * | 2017-08-29 | 2017-11-28 | 湖北龙翔药业科技股份有限公司 | A kind of preparation method of iron-dextrin |
-
2020
- 2020-11-18 CN CN202011298006.3A patent/CN112409505A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044571A (en) * | 2011-10-13 | 2013-04-17 | 天津中敖生物科技有限公司 | Iron dextran bulk drug and preparation method thereof |
| CN104031170A (en) * | 2014-05-22 | 2014-09-10 | 海纳阳光（北京）医药控股有限公司 | Iron dextran raw material for human intravenous injection and preparation method thereof |
| CN106543294A (en) * | 2015-09-18 | 2017-03-29 | 瑞普（天津）生物药业有限公司 | A kind of preparation method of iron-dextrin |
| CN107049933A (en) * | 2017-02-28 | 2017-08-18 | 广西壮族自治区化工研究院 | A kind of weight average molecular weight is the preparation method of 3,000 24000 iron dextran injection |
| CN107400178A (en) * | 2017-08-29 | 2017-11-28 | 湖北龙翔药业科技股份有限公司 | A kind of preparation method of iron-dextrin |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113087818A (en) * | 2021-05-18 | 2021-07-09 | 华科营养与生物技术(深圳)有限公司 | Dextran sulfate sodium salt or potassium salt and production method thereof |
| CN113480678A (en) * | 2021-08-06 | 2021-10-08 | 江西华太药业有限公司 | Iron dextran synthesizing method and its dispersing tablet |
| CN113480678B (en) * | 2021-08-06 | 2022-03-25 | 江西华太药业有限公司 | Iron dextran synthesizing method and its dispersing tablet |
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Application publication date: 20210226 |