CN111268707A

CN111268707A - Preparation method of medicinal magnesium sulfate

Info

Publication number: CN111268707A
Application number: CN202010097948.9A
Authority: CN
Inventors: 赵思太; 任业明; 马新成; 邓玉晓; 张宁; 张宗磊; 冯光玲; 孔祥雨; 杨利; 崔新强; 刘文涛; 刘宜辉; 龚艳艳; 樊志萍; 孙晋瑞; 段崇刚
Original assignee: Shandong Academy of Pharmaceutical Sciences
Current assignee: Shandong Academy of Pharmaceutical Sciences
Priority date: 2020-02-18
Filing date: 2020-02-18
Publication date: 2020-06-12

Abstract

The invention discloses a preparation method of medicinal magnesium sulfate. The method takes magnesium oxide and sulfuric acid as raw materials, oxalic acid as an impurity removal reagent, magnesium sulfate is prepared through one-step reaction, and the content of calcium ions in the product meets the specification. The preparation method disclosed by the invention has the advantages of cheap and easily-obtained raw materials, mild reaction conditions, simplicity in operation, good reproducibility and high product yield and purity, and is suitable for industrial production requirements.

Description

Preparation method of medicinal magnesium sulfate

Technical Field

The invention belongs to the field of food and medicine, and particularly relates to a method for preparing pharmaceutical magnesium sulfate.

Background

Magnesium sulfate is commonly referred to as magnesium sulfate heptahydrate, also known as thiopicrin, bitter salt, epsomite. It can be widely applied to the fields of food, medicine and the like. In the food field, magnesium sulfate is used for producing products such as monosodium glutamate, yeast, salt and the like; can also be used as food additive as nutritional supplement. In the field of medicine, the magnesium sulfate can be clinically used for catharsis, detoxification, cholagogic treatment and cholecystitis and biliary colic treatment, and is used for preventing and treating digitalis toxic arrhythmia and other arrhythmia when being used as a supplement of magnesium ions in vivo; can be used for treating hyperlipidemia, congestive heart failure, angina pectoris, and myocardial infarction; can be used for sedation, anticonvulsant and lowering blood pressure; intravenous injection or intravenous drip can be used for treating biliary ascariasis, tetanus, preterm pregnancy, etc.

The quality standard of the industrial grade magnesium sulfate is that the magnesium sulfate is not less than 99.5 percent, the pH (5 w/v% solution) is between 5 and 9, the heavy metal is not more than 0.0008 percent, and the arsenic salt is not more than 0.0002 percent; calcium is not more than 0.05%. The medicinal magnesium sulfate is magnesium sulfate with quality index far higher than that of industrial grade magnesium sulfate, has wider application range than that of the industrial grade magnesium sulfate, and is used in the field of food and medicine. The Chinese pharmacopoeia (2015 second part) stipulates that the content of magnesium sulfate is not less than 99.5%, the content of chloride is not more than 0.01%, the content of iron salt is not more than 0.0015%, the content of calcium is not more than 0.02%, the content of heavy metal is not more than ten parts per million, and the content of arsenic salt is not more than 0.0002%.

Popivate (production of magnesium sulfate, 1986, p391-393) reported a classical process for the preparation of magnesium sulfate, namely the reaction of technical magnesium oxide (magnesite) with sulfuric acid, filtration, crystallization and isolation to obtain magnesium sulfate. In the process of preparing magnesium sulfate, most impurities such as chloride, iron ions, heavy metals, arsenic salt and the like are relatively easy to remove. And calcium and magnesium are homologous elements, physical and chemical properties are very similar, and in the purification process, impurity calcium salt is difficult to remove from a finished product, so that the calcium content in the product exceeds the standard.

The prior method for removing and modifying calcium reported in the literature comprises the following steps: chinese patent (CN101885498) adopts high-purity magnesium oxide to react with sulfuric acid, and the filtrate is concentrated to a certain relative density through pH adjustment, so as to control the purity of magnesium sulfate. Chinese patent (CN107935003) provides a method for preparing high-purity magnesium sulfate from magnesium sulfate waste, which mainly comprises the steps of roasting the magnesium sulfate waste at high temperature, hydrating, and then carrying out twice concentration and crystallization to prepare the high-purity magnesium sulfate. Chinese patent (CN103058235) obtains high purity magnesium sulfate by precipitating calcium ion as an impurity in magnesium sulfate with hydrofluoric acid. The method disclosed in the above patent document is complicated in preparation process and does not solve the problem of calcium impurity in magnesium sulfate. Chinese patent (CN103058235) uses hydrofluoric acid to precipitate calcium ions in magnesium sulfate as impurities to prepare high-purity magnesium sulfate, but hydrofluoric acid belongs to a high-corrosivity substance, has great corrosivity on metal equipment, enamel equipment, transmission pipelines and the like, and has potential safety hazards.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides the preparation method of the medicinal magnesium sulfate, which has the advantages of simple process and mild reaction conditions, and can effectively reduce the content of calcium ions in the magnesium sulfate to obtain a product meeting the specification of pharmacopoeia.

The invention adopts the following technical scheme:

adding deionized water and magnesium oxide in a certain proportion into a reaction kettle, stirring, slowly dropwise adding concentrated sulfuric acid to obtain a magnesium sulfate solution with the pH value of 5-6, heating to 50-80 ℃, adding oxalic acid and activated carbon in proportion, keeping the temperature, stirring, reacting for 0.5-2 hours, filtering while hot, cooling and crystallizing filtrate, centrifuging, and leaching with a small amount of deionized water to obtain medicinal magnesium sulfate.

In the technical scheme, the mass ratio of the magnesium oxide to the oxalic acid is 20-60: 1.

Compared with the prior art, the invention has the following advantages:

1) magnesium and calcium are elements of the same group, the physical and chemical properties are very similar, and calcium ions are difficult to remove. Calcium oxalate has very low solubility (6.7X 10)^-4g/100ml, 20 ℃ C.), which is three orders of magnitude lower than that of calcium sulfate (0.255g/100ml, 20 ℃) and magnesium oxalate (0.104g/100ml, 20 ℃). Therefore, after a certain amount of oxalic acid is added, calcium ions can react with the oxalic acid preferentially to generate insoluble calcium oxalate precipitate, and the insoluble calcium oxalate precipitate is removed by filtration to ensure that calcium in the final productThe ion content meets the specifications.

2) The invention relates to a preparation method of medicinal magnesium sulfate, wherein the used raw material industrial magnesium oxide does not need to have high-purity grade, and the content of the magnesium oxide in the raw material is higher than 90%.

3) The invention relates to a preparation method of medicinal magnesium sulfate, which has simple operation steps and mild reaction conditions and is particularly suitable for industrial scale production.

Detailed Description

The present invention will be described in further detail with reference to specific examples, but the scope of the present invention is not limited thereto, and any technique realized based on the above-described contents of the present invention falls within the scope of the present invention.

Example 1

Adding 50 liters of deionized water into a reaction kettle, starting stirring, adding 10 kilograms of industrial magnesium oxide, slowly dropwise adding concentrated sulfuric acid after the materials are uniformly stirred and dispersed, controlling the pH value of a reaction system to be 5-6, and stopping adding sulfuric acid. Heating the reaction to 70-80 ℃, adding 0.17 kg of oxalic acid and 0.1 kg of active carbon, stirring the mixture for reaction for 0.5-1 hour, filtering the mixture while the mixture is hot, transferring the filtrate into a crystallization tank, stirring the mixture for crystallization at the temperature of 20-30 ℃, centrifuging the mixture, leaching the mixture with a small amount of water, and drying the mixture to obtain the medicinal magnesium sulfate.

Example 2

Adding 100 liters of deionized water into a reaction kettle, starting stirring, adding 20 kilograms of industrial magnesium oxide, slowly dropwise adding concentrated sulfuric acid after the materials are uniformly stirred and dispersed, controlling the pH value of a reaction system to be 5-6, and stopping adding sulfuric acid. Heating the reaction kettle to 60-70 ℃, adding 0.6 kg of oxalic acid and 0.2 kg of active carbon, stirring and reacting for 1-2 hours, filtering while hot, transferring the filtrate into a crystallization tank, stirring and crystallizing at 20-30 ℃, centrifuging, leaching with a small amount of water, and drying to obtain the medicinal magnesium sulfate.

Example 3

Adding 100 liters of deionized water into a reaction kettle, starting stirring, adding 20 kilograms of industrial magnesium oxide, slowly dropwise adding concentrated sulfuric acid after the materials are uniformly stirred and dispersed, controlling the pH value of a reaction system to be 5-6, and stopping adding sulfuric acid. Heating the reaction kettle to 50-60 ℃, adding 0.9 kg of oxalic acid and 0.2 kg of active carbon, stirring and reacting for 1-2 hours, filtering while hot, transferring the filtrate into a crystallization tank, stirring and crystallizing at 20-30 ℃, centrifuging, leaching with a small amount of water, and drying to obtain the medicinal magnesium sulfate.

The result of the detection

The magnesium sulfate finished product of the embodiment of the invention is detected according to a detection method of magnesium sulfate in Chinese pharmacopoeia (2015 edition two).

The detection results are as follows:

Claims

1. the preparation method of medicinal magnesium sulfate is characterized in that oxalic acid is used as a calcium removal reagent, and comprises the following steps:

1) adding deionized water and magnesium oxide in a certain proportion into a reaction kettle, and dropwise adding concentrated sulfuric acid to obtain a magnesium sulfate reaction solution with the pH value of 5-6;

2) heating the magnesium sulfate reaction solution in the step 1) to 50-80 ℃, and adding oxalic acid and activated carbon in proportion;

3) keeping the reaction temperature of the step 2) at 50-80 ℃, and stirring for reaction for 0.5-2 hours;

4) cooling and crystallizing the filtrate obtained in the step 3), centrifuging, washing with water, and drying to obtain magnesium sulfate.

2. The method for preparing magnesium sulfate for pharmaceutical use as claimed in claim 1, wherein the mass ratio of magnesium oxide to oxalic acid is 20-60: 1.