阅读说明：本技术 一种高品质磺胺多辛的精制方法 (Refining method of high-quality sulfadoxine ) 是由 蔡中文 宋小莉 谢晓芹 于 2020-12-22 设计创作，主要内容包括：本发明公开一种高品质磺胺多辛的精制方法。本发明采用食品级氢氧化钙作为磺胺多辛的成盐剂,磺胺多辛钙盐水溶液经脱色处理后用分析纯冰醋酸的纯化水溶液分2次调pH值分级结晶从而得到高品质磺胺多辛。采用食品级氢氧化钙作为成盐剂精制的磺胺多辛金属元素残留低,分2次调pH分级结晶得到的高品质磺胺多辛外观为白色、溶液色浅。(The invention discloses a refining method of high-quality sulfadoxine. The invention adopts food-grade calcium hydroxide as a salt forming agent of sulfadoxine, and after decoloration treatment, the sulfadoxine calcium salt aqueous solution is subjected to pH value graded crystallization by 2 times by using a purified aqueous solution of analytically pure glacial acetic acid, thereby obtaining the high-quality sulfadoxine. Food-grade calcium hydroxide is adopted as a salt forming agent, so that metal element residues of refined sulfadoxine are low, and high-quality sulfadoxine obtained by adjusting pH for fractional crystallization for 2 times is white in appearance and light in solution color.)

1. A refining method of high-quality sulfadoxine comprises the following steps:

(1) adding crude sulfadoxine into purified water while stirring, and heating to 55-65 ℃;

(2) adding food-grade calcium hydroxide to adjust the pH value to be alkaline;

(3) adding active carbon, heating to 65-70 deg.c and decolorizing for 30 min;

(4) removing the activated carbon;

(5) dripping a purified water solution with the mass concentration of dilute analytical pure glacial acetic acid into the filtrate at the temperature of between 55 and 65 ℃ while stirring, accurately adjusting the pH value to be alkalescent, and separating out yellow sulfadoxine;

(6) dropwise adding a purified water solution of analytically pure glacial acetic acid into the filtrate obtained in the previous step at the temperature of 55-65 ℃ while stirring, adjusting the pH to be slightly acidic, and separating out white sulfadoxine;

(7) and separating and drying the sulfadoxine in the previous step to obtain high-quality sulfadoxine.

2. The preparation method according to claim 1, wherein the food grade calcium hydroxide is added in the step (2) to adjust the pH value to be alkaline, and the pH value is 10.0-10.5.

3. The method according to claim 1, wherein the filtrate obtained in the step (5) is added dropwise with a purified aqueous solution of dilute analytical pure glacial acetic acid at a temperature of 55 ℃ to 65 ℃ to adjust the pH to be weakly alkaline with accuracy, wherein the purified aqueous solution of analytical pure glacial acetic acid has a mass concentration of 10%.

4. The process according to claim 1, wherein the filtrate obtained in the step (5) is added to a purified aqueous solution of analytically pure glacial acetic acid to adjust the pH to a slightly alkaline pH of 8.0.

5. The method according to claim 1, wherein the filtrate obtained in the previous step of step (6) is added dropwise with a purified aqueous solution of analytically pure glacial acetic acid at a temperature of 55 ℃ to 65 ℃ to adjust the pH to be slightly acidic, wherein the purified aqueous solution of analytically pure glacial acetic acid has a mass concentration of 15%.

6. The method according to claim 1, wherein the filtrate obtained in the previous step of step (6) is added with a purified aqueous solution of analytically pure glacial acetic acid to adjust the pH to a slightly acidic pH value of 5.1-5.4.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a refining method of sulfadoxine.

Background

Sulfadoxine is also known as sulfadoxine, with the english name: sulfadoxine, chemical name: 4- (p-Aminobenzenesulfonylamino) -5, 6-dimethoxydoxine, CAS registry number: 2447-57-6, the chemical formula is as follows:

sulfadoxine belongs to sulfanilamide antibacterial drugs. Sulfadoxine has the characteristics of long curative effect and low toxicity, can treat common inflammations such as upper respiratory tract infection pangolin, bacillary dysentery enteritis, skin infection and the like, has certain curative effect on pulmonary tuberculosis lymphoid tuberculosis and the like by being matched with other medicines, and can also treat malaria. Sulfadoxine has been included in The 5 th edition of The International Pharmacopoeia (IntPh, The International Pharmacopeia) authored by The world health organization. CN103910685A describes a conventional refining method of sulfadoxine, but the product obtained by the conventional refining method hardly reaches the standard of white or milk white crystalline powder and the solution color is not darker than standard solution Yw 3.

Based on the ICH (International harmonization international requirements for drug registration technology) series guiding principles, the quality control of the raw material drug as the active ingredient of the drug is very critical. The invention selects food-grade calcium hydroxide as a salt forming agent to prepare sulfadoxine calcium refined sulfadoxine, after decoloring treatment, the sulfadoxine calcium salt water solution is subjected to pH value grade crystallization by 2 times of pH value adjustment by using a purified water solution of analytically pure glacial acetic acid, so that high-quality sulfadoxine is obtained, the quality of the used raw materials is controllable, and the quality of a sulfadoxine product is better ensured.

Standard for food-grade calcium hydroxide (GB 25572-2010)

The purified water is required to meet the regulations of 2020 edition of Chinese pharmacopoeia.

The preparation process of the crude sulfadoxine refers to the national pharmaceutical administration, national process compilation of bulk drugs, P172-175.

Disclosure of Invention

The invention provides a refining method of high-quality sulfadoxine. A refining method of high-quality sulfadoxine comprises the following steps:

(1) adding crude sulfadoxine into purified water while stirring, and heating to 55-65 ℃;

(2) adding food-grade calcium hydroxide to adjust the pH value to be alkaline;

(3) adding active carbon, heating to 70-65 deg.c and decolorizing for 30 min;

(4) removing the activated carbon;

(5) dripping a purified water solution with the mass concentration of dilute analytical pure glacial acetic acid into the filtrate at the temperature of between 55 and 65 ℃ while stirring, accurately adjusting the pH value to be alkalescent, and separating out yellow sulfadoxine;

(6) dropwise adding a purified water solution of analytically pure glacial acetic acid into the filtrate obtained in the previous step at the temperature of 55-65 ℃ while stirring, adjusting the pH to be slightly acidic, and separating out white sulfadoxine;

(7) and separating and drying the sulfadoxine in the previous step to obtain high-quality sulfadoxine.

Wherein the food-grade calcium hydroxide is added in the step (2) to adjust the pH value to be alkaline, and the pH value is 10.0-10.5.

Wherein the filtrate obtained in the step (5) is dripped with a purified aqueous solution of diluted analytical pure glacial acetic acid with the mass concentration to be adjusted to be alkalescent accurately at the temperature of 55-65 ℃, and the purified aqueous solution of analytical pure glacial acetic acid with the mass concentration of 10%.

Wherein the filtrate obtained in the step (5) is added with a purified aqueous solution of analytically pure glacial acetic acid to accurately adjust the pH value to be alkalescent, and the pH value is 8.0.

Wherein the filtrate obtained in the last step of the step (6) is dripped into purified water solution of analytically pure glacial acetic acid at the temperature of 55-65 ℃ to adjust the pH value to be slightly acidic, and the mass concentration of the purified water solution of analytically pure glacial acetic acid is 15%.

And (3) adding a purified water solution of analytically pure glacial acetic acid into the filtrate obtained in the last step of the step (6) to adjust the pH value to be slightly acidic, wherein the pH value is 5.1-5.4.

Wherein the technology of the step (7) is a conventional separation and drying means.

The technical scheme of the invention is that food-grade calcium hydroxide is adopted, the calcium hydroxide has good quality, carries less metal ions except calcium ions, has controllable quality, so that the obtained sulfadoxine carries less and controllable metal ions, a small amount of sulfadoxine with poor appearance and solubility is removed by using dilute glacial acetic acid purified water solution at the pH value of 8, and then the high-quality sulfadoxine is obtained by acidification.

Detailed Description

The technical solutions of the present invention are further described below with specific examples, which may enable those skilled in the art to better understand the present invention, but the scope of the present invention is not limited thereto.

Example 1 purification of high-quality sulfadoxine

Adding 500g of purified water, starting stirring, adding 50.0g of crude sulfadoxine, and heating to 55-65 ℃;

adjusting the pH value to 10.0-10.5 by using food-grade calcium hydroxide, completely dissolving, and repeatedly measuring the pH value after 15 minutes until the pH value is unchanged;

adding 5g of active carbon, and decoloring for 30 minutes at 65-70 ℃;

filtering while the mixture is hot, washing the carbon residue with 15g of purified water, and transferring the filtrate into a crystallization bottle;

dropwise adding a purified water solution of analytical pure glacial acetic acid with the mass concentration of 10% into the filtrate at the temperature of 55-65 ℃ while stirring, accurately adjusting the pH to 8.0, and separating out yellow sulfadoxine;

dropwise adding a purified water solution of analytically pure glacial acetic acid into the filtrate obtained in the previous step at the temperature of 55-65 ℃ while stirring, adjusting the pH to 5.1-5.4, and separating out white sulfadoxine;

separating and drying the sulfadoxine in the previous step to obtain high-quality sulfadoxine, and obtaining 42.5-45.0 g of high-quality sulfadoxine finished product; the weight yield is 85.0-90.0%, the purity of HPLC normalization method is 99.8%, the residue on ignition is 0.05%, and the heavy metal: less than 10ppm, white or milky crystalline powder in appearance, and solution color not darker than standard solution Yw 3.

The invention has been described in detail, including the preferred embodiments thereof; it will be appreciated that those skilled in the art, on consideration of the present disclosure, may make modifications and/or improvements within the spirit and scope of the present invention as defined by the appended claims, which modifications and enhancements are also considered to fall within the scope of the present invention.