Method for preparing vitamin B1 hydrochloride

Abstract

The invention relates to the technical field of pharmacy, and discloses a method for preparing vitamin B1 hydrochloride. The method comprises the following steps: (1) carrying out ion exchange on a vitamin B1 sulfate aqueous solution through a chlorine type anion exchange resin column with a neutral pH value to obtain a sulfate radical type anion exchange resin column, and concentrating and crystallizing the obtained first column passing liquid to obtain a vitamin B1 hydrochloride finished product; (2) carrying out regeneration treatment on the chlorate I aqueous solution through the persulfate anion exchange resin column to obtain a regenerated chlorine anion exchange resin column and a second column passing solution; the regenerated chlorine type anion exchange resin column is returned to be used in the step (1); (3) mixing the second column passing solution with chlorate II, precipitating and filtering to remove sulfate radicals to obtain filtrate, and concentrating the filtrate to obtain a concentrated solution; the concentrated solution returns to the step (2) to participate in regeneration treatment. The method is high in safety, environment-friendly and simple in step, and the product yield is larger than or equal to 97%.

Description

Technical Field

[0001] The invention relates to the field of pharmaceutical technology, and in particular to a method for preparing vitamin B1 hydrochloride. Background Art

[0002] Vitamin B1 hydrochloride is B1 sulfate hydrochloride, chemical name is 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-5-(β-hydroxyethyl)-4-methylthiazole chloride hydrochloride, structural formula is The existing pharmaceutical industry generally uses the difference in solubility between vitamin B1 nitrate and vitamin B1 sulfate in water to add excess ammonium nitrate to the vitamin B1 sulfate aqueous solution to precipitate vitamin B1 nitrate, and then put the vitamin B1 nitrate into an excess of hydrogen chloride methanol solution to precipitate vitamin B1 hydrochloride B1. Excess ammonium nitrate is used in this process. The aqueous solution must be distilled to recover the excess ammonium nitrate. There is a risk of explosion when ammonium nitrate is heated. Even if alkali is added to convert ammonium nitrate into other nitrates, it may still explode when heated. The safety risk is relatively large and it is not easy to recover. Excess hydrogen chloride methanol solution is used in this process. It is difficult to recover the hydrogen chloride methanol solution containing nitric acid. The hydrogen chloride methanol solution needs to be prepared and stored under low temperature conditions. There is a risk of hydrogen chloride gas leakage, which pollutes the environment. Therefore, this process has major defects in safety and environmental protection, and there are more nitrate residues in the finished vitamin B1 hydrochloride produced by this process route, causing quality problems.

[0003] In addition, CN1459449A discloses a method for preparing vitamin B1 hydrochloride from thiol B1 sulfate, wherein barium chloride is added to a vitamin B1 sulfate aqueous solution to react and remove sulfate radicals, and the barium sulfate is precipitated and filtered out. In this method, the toxicity of barium chloride is too high, which is not conducive to implementation in industrial production. In addition, when ammonium bicarbonate is used to remove excess barium chloride, the ammonium chloride generated is difficult to remove, and it is difficult to completely remove the toxic barium ions. Therefore, this method is difficult to implement industrial production.

[0004] CN104817551A discloses a method for preparing vitamin B1 hydrochloride, wherein calcium chloride is added to a vitamin B1 sulfate aqueous solution to remove sulfate, and calcium sulfate is precipitated and filtered out. Although this method uses calcium chloride instead of highly toxic barium chloride, the residual amount of sulfate is too high, and the residual amount of sulfate in the vitamin B1 hydrochloride prepared by concentrated crystallization exceeds the Chinese Pharmacopoeia standard. In addition, excessive calcium chloride causes the ash content of the prepared vitamin B1 hydrochloride to exceed the Chinese Pharmacopoeia standard. Even if the step of removing excess calcium chloride with ammonium bicarbonate is added, and multiple crystallizations are performed, the ash content still exceeds the standard. This method is difficult to achieve industrial production.

[0005] CN104031038A discloses a method for preparing vitamin B1 hydrochloride using thiol thiamine, wherein an acidic cationic resin is used to adsorb vitamin B1 sulfate, the resin is then washed with water to remove sulfate, and then hydrochloric acid is used to desorb vitamin B1 hydrochloride. This method requires the use of high-concentration excess hydrochloric acid to desorb B1 adsorbed on the cationic resin. During the distillation and concentration process under high-concentration strong acid conditions, equipment that is resistant to high-temperature strong acid and high chloride ion corrosion is required, and the amount of distilled water is large.

[0006] CN102952126A discloses a method for synthesizing vitamin B1 hydrochloride, wherein an ion exchange resin is used to treat a vitamin B1 sulfate aqueous solution to remove sulfate, and then the vitamin B1 hydrochloride is prepared by concentration and crystallization, wherein a hydroxide-type basic ion exchange resin is used. In this method, since B1 degrades under alkaline conditions, although acid is pre-mixed in the vitamin B1 sulfate aqueous solution, it is difficult to ensure that B1 is always protected by acid during ion exchange with a hydroxide-type basic anion resin, and B1 will decompose when it is locally alkaline. In addition, if too much pre-mixed acid is used, it will affect the adsorption of sulfate ions, causing the sulfate content in the obtained vitamin B1 hydrochloride to exceed the Chinese Pharmacopoeia standard.

[0007] The above process route has the problems of poor environmental performance, safety risks, difficulty in ensuring the quality of vitamin B1 hydrochloride or unsatisfactory product yield. Summary of the invention

[0008] Aiming at the problem that the existing process for preparing vitamin B1 hydrochloride is difficult to take into account safety, environmental protection, product quality and high product yield, the present invention provides a method for preparing vitamin B1 hydrochloride.

[0009] To achieve the above object, the present invention provides a method for preparing vitamin B1 hydrochloride, the method comprising:

[0010] (1) subjecting a vitamin B1 sulfate aqueous solution to ion exchange with a perchloride-type anion exchange resin column to obtain a sulfate-type anion exchange resin column and a first column liquid containing vitamin B1 hydrochloride; concentrating and crystallizing the first column liquid to obtain a finished product of vitamin B1 hydrochloride;

[0011] (2) passing the aqueous solution of chloride salt I through the sulfate anion exchange resin column for regeneration treatment to obtain a regenerated chloride anion exchange resin column and a second column liquid containing sulfate; the regenerated chloride anion exchange resin column is used to participate in the ion exchange in step (1);

[0012] (3) mixing the second column liquid with chloride salt II, removing sulfate by precipitation filtration to obtain a filtrate, and concentrating the filtrate to obtain a concentrated solution; the concentrated solution is returned to step (2) to participate in the regeneration process;

[0013] The pH value of the chloride-type anion exchange resin column is neutral.

[0014] The process for preparing vitamin B1 hydrochloride provided by the present invention has high safety, and the quality of the prepared vitamin B1 hydrochloride meets the requirements of the "Pharmacopoeia of the People's Republic of China (Part II 2020 Edition)" (hereinafter referred to as the Chinese Pharmacopoeia, which has formulated quality standards for vitamin B1 hydrochloride in the first part of the variety text). In this method, resin and regeneration salt are recycled, the product yield is ≥97%, the process steps are simple, and it is environmentally friendly. DETAILED DESCRIPTION

[0015] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0016] The present invention provides a method for preparing vitamin B1 hydrochloride, the method comprising:

[0017] (1) subjecting a vitamin B1 sulfate aqueous solution to ion exchange with a perchloride-type anion exchange resin column to obtain a sulfate-type anion exchange resin column and a first column liquid containing vitamin B1 hydrochloride; concentrating and crystallizing the first column liquid to obtain a finished product of vitamin B1 hydrochloride;

[0018] (2) passing the aqueous solution of chloride salt I through the sulfate anion exchange resin column for regeneration treatment to obtain a regenerated chloride anion exchange resin column and a second column liquid containing sulfate; the regenerated chloride anion exchange resin column is used to participate in the ion exchange in step (1);

[0019] (3) mixing the second column liquid with chloride salt II, removing sulfate by precipitation filtration to obtain a filtrate, and concentrating the filtrate to obtain a concentrated solution; the concentrated solution is returned to step (2) to participate in the regeneration process;

[0020] The pH value of the chloride-type anion exchange resin column is neutral.

[0021] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (1), a vitamin B1 sulfate aqueous solution is passed through a chloride-type anion exchange resin column, so that sulfate ions in the vitamin B1 sulfate are adsorbed on the resin column and undergo ion exchange with chloride ions to be directly converted into vitamin B1 hydrochloride. After the ion exchange, the chloride-type anion exchange resin column is converted into a sulfate-type anion exchange resin column, and then the first column liquid containing vitamin B1 hydrochloride is concentrated and crystallized in sequence to obtain the product vitamin B1 hydrochloride.

[0022] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (1), the concentration of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution is ≤32wt%, which is beneficial for the vitamin B1 sulfate aqueous solution to obtain a better ion exchange effect between sulfate and chloride ions in the perchlorinated anion exchange resin column process, and can reduce the amount of distilled water in the subsequent column liquid concentration process.

[0023] In the present invention, the pH value of the chloride-type anion exchange resin column is neutral, which means that after the chloride-type anion exchange resin column is washed and desalted with water, the pH value of the final water in the column washing water is in the range of 6.8-7.0. The chloride-type anion exchange resin with neutral pH value used in the present invention can release chloride ions while adsorbing sulfate ions, so that the column liquid can be concentrated and crystallized to obtain vitamin B1 hydrochloride of qualified quality, and the problem of unqualified purity of the prepared vitamin B1 hydrochloride caused by the destruction of vitamin B1 by alkali can be avoided.

[0024] According to the present invention, the chlorine-type anion exchange resin refers to an anion exchange resin adsorbed with chloride ions, and the chlorine-type anion exchange resin column using such anion exchange resin can adsorb other anions other than chloride ions and release chloride ions of equal charge in the process of ion exchange through the salt solution column. In the method for preparing vitamin B1 hydrochloride, all known chlorine-type anion exchange resins that meet the above definition can be used, and their source channels can be homemade or commercially available. For example, the chlorine-type resins that can be used include but are not limited to D301 resin, D315 resin, 717 resin, D318 resin, LX-67 resin produced by Xi'an Lanxiao Science and Technology New Materials Co., Ltd., LX-6703 resin, LX-300C resin, ZG-640 resin produced by Zhejiang Zhengguang Industrial Co., Ltd., ZG-312 resin, IRC-45 resin produced by Amberlite, IRA-93 resin, AD-41 resin produced by Wofatit, etc.

[0025] In the present invention, in step (1), the chloride-type anion exchange resin column can be loaded and cleaned by the following process before the first use, including: loading the resin column with the chloride-type anion exchange resin, and then sequentially washing the column with water, washing the column with ethanol, and washing the column with water again to obtain the chloride-type anion exchange resin column.

[0026] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (1), the perchlorinated anion exchange resin column is operated at 10-60°C, preferably at 25-35°C.

[0027] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (1), the ratio of the total exchange capacity of the chloride-type anion exchange resin in the chloride-type anion exchange resin column to the amount of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution is ≥2.4, preferably (2.4-10):1.

[0028] In the present invention, the total exchange capacity of the chloride-type anion exchange resin = total exchange capacity (unit: mmol / g, the total exchange capacity is indicated on the product instructions of the commercially available resin) × the weight (unit: g) of the chloride-type anion exchange resin used to fill the resin column.

[0029] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (1), the time for the vitamin B1 sulfate aqueous solution to pass through the chloride-type anion exchange resin column is ≥30 min, preferably 30-120 min, which is conducive to sufficient ion exchange and complete adsorption of sulfate.

[0030] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (1), the concentration and crystallization are not particularly limited and can be carried out in a manner known in the art.

[0031] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (2), the sulfate-type anion exchange resin column is regenerated using chloride I to convert the sulfate-type anion exchange resin into a chloride-type anion exchange resin to obtain a regenerated chloride-type anion exchange resin column, and simultaneously obtain a second column liquid containing sulfate.

[0032] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (2), the chloride salt I is used in the form of a chloride salt I aqueous solution (regeneration salt solution). Preferably, the ratio of the amount of chloride ions in the chloride salt I to the amount of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution in step (1) is ≥10, preferably (12-30):1, and the concentration of chloride ions in the chloride salt I aqueous solution is ≥8wt%, which is conducive to obtaining a better regeneration effect.

[0033] According to the present invention, preferably, the concentration of chloride ions in the aqueous solution of chloride salt I is 8-27 wt%.

[0034] According to the present invention, the chloride salt I can be selected from at least one of sodium chloride, potassium chloride, ammonium chloride, ferric chloride, ferrous chloride, magnesium chloride, aluminum chloride and lithium chloride.

[0035] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (2), in the regeneration treatment, the persulfate type anion exchange resin column is carried out at 10-60°C, preferably at 35-45°C, which is conducive to obtaining excellent regeneration effect and preventing salt precipitation in the regeneration salt solution from clogging the resin column during the regeneration process.

[0036] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (2), the time for the chloride salt I aqueous solution to pass through the sulfate anion exchange resin column is ≥30 min, preferably 30-120 min, which is conducive to the full regeneration of the resin.

[0037] According to the present invention, the regenerated chloride-type anion exchange resin column can be reused to carry out the ion exchange described in step (1) with the vitamin B1 sulfate aqueous solution to prepare vitamin B1 hydrochloride.

[0038] According to a preferred embodiment of the present invention, in step (2), the process of regenerating the sulfate anion exchange resin column comprises: first passing water through the column, then passing a chloride salt I aqueous solution through the column, and finally passing water through the column again for cleaning to obtain a regenerated chloride anion exchange resin column.

[0039] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (2), when the sulfate content in the final section of the second column liquid is less than 0.2 wt %, the regeneration process can be considered completed.

[0040] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (3), the second column liquid is mixed with a specific chloride salt II to cause a precipitation reaction, and the free sulfate in the second column liquid is converted into a precipitate, and then the precipitate is separated by filtration to achieve the removal of the sulfate.

[0041] According to the present invention, in step (3), the chloride salt II can be selected from barium chloride and / or calcium chloride. From the perspective of safety, the chloride salt II is preferably calcium chloride.

[0042] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (3), preferably, the amount of the chloride salt II is such that, after precipitation and filtration, the concentration of sulfate in the filtrate is ≤0.15wt%, and the cations (e.g., Ba) from the chloride salt II in the filtrate are 2+ and / or Ca 2+ ) concentration ≤0.1wt%.

[0043] According to the present invention, in the method for preparing vitamin B1 hydrochloride, in step (3), the concentration of chloride ions in the concentrated solution is ≥ 8wt%, preferably 8-27wt%. The concentrated solution can be returned to the sulfate anion exchange resin column in step (2) to achieve regeneration of the sulfate anion exchange resin.

[0044] According to the present invention, in the method for preparing vitamin B1 hydrochloride, the quality of the obtained product meets the requirements of the Chinese Pharmacopoeia for the ignition residue and sulfate of vitamin B1 hydrochloride, with the specific indicators being ignition residue ≤0.1wt%, sulfate ≤0.01wt%, and the purity requirement being the sum of impurity peaks in the high performance liquid chromatogram <0.5%.

[0045] The process for preparing vitamin B1 hydrochloride provided by the present invention abandons the current process of converting vitamin B1 nitrate into vitamin B1 hydrochloride, eliminates the generation of waste salt in the crystallization process of producing vitamin B1 nitrate, avoids nitrate residue in the product, and also eliminates the process of preparing hydrogen chloride methanol solution in the current process, avoiding the generation of waste acid. The preparation method of the present invention has excellent safety and environmental protection, the quality of the prepared vitamin B1 hydrochloride meets the requirements of the Chinese Pharmacopoeia, the ignition residue content in the product is less than 0.1wt%, the resin and the regeneration salt are recycled in the method, and the product yield is ≥97%.

[0046] The present invention will be described in detail below by way of examples. In the following preparation examples and embodiments, unless otherwise specified, all materials used are common commercially available products.

[0047] Chloride anion exchange resin column (denoted as A1): 700 g of commercially available D315 chloride anion exchange resin (wet) (total mass exchange capacity (wet) is 2.9 mmol / g) was loaded to obtain a resin column (total exchange capacity is 2.030 mol), and the following steps (A) to (C) were performed in sequence:

[0048] (A) 2250 g of water was passed through the resin column for 15 min;

[0049] (B) 1200 g of ethanol was passed through the resin column for 100 min;

[0050] (C) 2250 g of water was passed through the resin column for 15 min;

[0051] After the resin was cleaned, the pH value of the final water in the column cleaning water in step (C) was measured to be 6.9, and a chloride-type anion exchange resin column was obtained.

[0052] Chloride anion exchange resin column (denoted as A2): 800 g of commercially available D318 chloride anion exchange resin (wet) (total mass exchange capacity (wet) 2.8 mmol / g) was loaded to obtain a resin column (total exchange capacity 2.240 mol), and the following steps (A) to (C) were performed in sequence:

[0053] (A) 2500 g of water was passed through the resin column for 15 min;

[0054] (B) 1500 g of ethanol was passed through the resin column for 100 min;

[0055] (C) 2500 g of water was passed through the resin column for 15 min;

[0056] After the resin was cleaned, the pH value of the final water in the column cleaning water in step (C) was measured to be 6.9, and a chloride-type anion exchange resin column was obtained.

[0057] Product yield = (weight of crystallized vitamin B1 hydrochloride × purity of vitamin B1 hydrochloride (wt%) / 337.29) / (weight of vitamin B1 sulfate aqueous solution entering chloride-type anion exchange resin column × content of vitamin B1 sulfate in vitamin B1 sulfate aqueous solution (wt%) / 362.29) × 100%;

[0058] Among them, 337.29 is the molecular weight of vitamin B1 hydrochloride, and 362.29 is the molecular weight of vitamin B1 sulfate;

[0059] The purity of vitamin B1 hydrochloride and the content of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution were both determined by the external standard content using the high performance liquid chromatography method specified in the Chinese Pharmacopoeia.

[0060] Example 1

[0061] In this embodiment, the chloride anion exchange resin column A1 is used.

[0062] (1) 1000 g of a vitamin B1 sulfate aqueous solution (sulfate concentration of 8.1 wt%, vitamin B1 sulfate concentration of 30.3 wt%, vitamin B1 sulfate of 0.836 mol) was passed through a chlorine-type anion exchange resin column (the ratio of the total exchange capacity of the chlorine-type anion exchange resin in the chlorine-type anion exchange resin column to the amount of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution was 2.43:1), the column temperature was 30°C, the column time was 40 min, and the first column liquid was obtained. Different sections of the first column liquid were cut to determine the sulfate content. The results are shown in Table 1 below.

[0063] Table 1

[0064] First column liquid Sulfate / wt% 0-200g 0.001 200-910g 0.001 910-1000g 0.002

[0065] The first column liquid is concentrated and crystallized to obtain a vitamin B1 hydrochloride product;

[0066] The water-washed resin column is used to recover the vitamin B1 sulfate set for the next batch of vitamin B1 sulfate aqueous solution perchloride type anion exchange resin column. After the water washing, the resin column is a sulfate anion exchange resin column to be regenerated;

[0067] (2) regenerating the sulfate anion exchange resin column by passing 3500 g of a 23.0 wt% sodium chloride aqueous solution (chloride ion concentration of 14.0 wt%, 13.802 mol of chloride ion in total, and a molar ratio of chloride ion to vitamin B1 sulfate in step (1) of 16.5:1) through the column at a temperature of 40° C. for 35 min (the sulfate content in the final stage of the obtained second column liquid was <0.2 wt%), and the sulfate anion exchange resin column was converted into a regenerated chloride anion exchange resin column, and the second column liquid was collected; then, 4000 g of water was used to pass the column for desalination, and the water-washed salt in the previous stage was collected and incorporated into the second column liquid;

[0068] The obtained regenerated chloride-type anion exchange resin column is used to continue to participate in ion exchange in step (1);

[0069] (3) 94.0 g (0.847 mol) of calcium chloride was added to the second column liquid, and the mixture was stirred to allow sulfate to be fully converted into calcium sulfate precipitate. The calcium sulfate was then filtered out, and the filter cake was washed with water, and the filtrate was concentrated to 3486 g. The calcium sulfate was removed by secondary filtration to obtain 3484 g of secondary filtrate (sulfate concentration: 0.08 wt %, calcium ion concentration: 0.03 wt %, chloride ion concentration: 14.0 wt %). A 23.0 wt % sodium chloride aqueous solution was then added to 3500 g. The resulting solution was returned to the persulfate anion exchange resin column in step (2) to regenerate the sulfate anion exchange resin.

[0070] In this embodiment, the resin column and the regenerated salt solution are recycled, and the vitamin B1 hydrochloride product obtained by the first column liquid has a sulfate content of <0.01wt%, an ignition residue content of 0.05wt%, and other test results such as purity meet the Chinese Pharmacopoeia standards, and the product yield is 99.1%.

[0071] Example 2

[0072] In this embodiment, the chloride anion exchange resin column A1 is used.

[0073] (1) 1500 g of a vitamin B1 sulfate aqueous solution (sulfate concentration of 5.4 wt%, vitamin B1 sulfate concentration of 20.2 wt%, vitamin B1 sulfate of 0.836 mol) was passed through a chlorine-type anion exchange resin column (the ratio of the total exchange capacity of the chlorine-type anion exchange resin in the chlorine-type anion exchange resin column to the amount of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution was 2.43:1), the column temperature was 33° C., the column time was 60 min, and the first column liquid was obtained. Different sections of the first column liquid were cut to determine the sulfate content. The results are shown in Table 2 below.

[0074] Table 2

[0075] First column liquid Sulfate / wt% 0-1350g 0.001 1350-1500g 0.002

[0076] The first column liquid is concentrated and crystallized to obtain a vitamin B1 hydrochloride product;

[0077] The water-washed resin column is used to recover the vitamin B1 sulfate and apply the next batch of vitamin B1 sulfate aqueous solution perchloride type anion exchange resin column. After the water washing, the resin column is a sulfate anion exchange resin column to be regenerated;

[0078] (2) The sulfate anion exchange resin column is regenerated by passing 3200 g of a 23.0 wt% ammonium chloride aqueous solution (chloride ion concentration is 15.3 wt%, chloride ions are 13.757 mol in total, and the molar ratio of chloride ions to vitamin B1 sulfate in step (1) is 16.5:1) through the column at a temperature of 40° C. for 45 min (the sulfate content in the final stage of the second column liquid is <0.2 wt%). The sulfate anion exchange resin column is converted into a regenerated chloride anion exchange resin column, and the second column liquid is collected; then, 4000 g of water is passed through the column for desalination, and the salt from the front stage of the water wash is collected and incorporated into the second column liquid;

[0079] The obtained regenerated chloride-type anion exchange resin column is used to continue to participate in ion exchange in step (1);

[0080] (3) 95.0 g (0.856 mol) of calcium chloride was added to the second column liquid, and the mixture was stirred to allow sulfate to be fully converted into calcium sulfate precipitate. The calcium sulfate was then filtered out, and the filter cake was washed with water, and the filtrate was concentrated to 3186 g. The calcium sulfate was removed by secondary filtration to obtain 3185 g of secondary filtrate (sulfate concentration of 0.15 wt%, calcium ion concentration of 0.06 wt%, chloride ion concentration of 15.3 wt%). A 23.0 wt% aqueous solution of ammonium chloride was then added to 3200 g. The resulting solution was returned to the persulfate anion exchange resin column in step (2) to regenerate the sulfate anion exchange resin.

[0081] In this embodiment, the resin column and the regenerated salt solution are recycled, and the vitamin B1 hydrochloride product obtained by the first column liquid has a sulfate content of <0.01wt%, an ignition residue content of 0.06wt%, and other test results such as purity meet the Chinese Pharmacopoeia standards, and the product yield is 98.7%.

[0082] Example 3

[0083] In this embodiment, the chloride anion exchange resin column A1 is used.

[0084] (1) 1200 g of a vitamin B1 sulfate aqueous solution (sulfate concentration of 6.8 wt %, vitamin B1 sulfate concentration of 25.3 wt %, vitamin B1 sulfate of 0.836 mol) was passed through a chlorine-type anion exchange resin column (the ratio of the total exchange capacity of the chlorine-type anion exchange resin in the chlorine-type anion exchange resin column to the amount of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution was 2.43:1), the column temperature was 26° C., the column time was 35 min, and the first column liquid was obtained. Different sections of the first column liquid were cut to determine the sulfate content. The results are shown in Table 3 below.

[0085] Table 3

[0086] First column liquid Sulfate / wt% 0-1100g 0.002 1100-1200g 0.004

[0087] The first column liquid is concentrated and crystallized to obtain a vitamin B1 hydrochloride product;

[0088] The water-washed resin column is used to recover the vitamin B1 sulfate set for the next batch of vitamin B1 sulfate aqueous solution perchloride type anion exchange resin column. After the water washing, the resin column is a sulfate anion exchange resin column to be regenerated;

[0089] (2) regenerating the sulfate anion exchange resin column by passing 2800 g of a 30.0 wt% ferrous chloride aqueous solution (chloride ion concentration of 16.8 wt%, 13.251 mol of chloride ion in total, and a molar ratio of chloride ion to vitamin B1 sulfate in step (1) of 15.9:1) through the column at a temperature of 50° C. for 40 min (the sulfate content in the final stage of the obtained second column liquid was <0.2 wt%), and the sulfate anion exchange resin column was converted into a regenerated chloride anion exchange resin column, and the second column liquid was collected; then, the column was desalted by passing 4000 g of water, and the water-washed salt in the previous stage was collected and incorporated into the second column liquid;

[0090] The obtained regenerated chloride-type anion exchange resin column is used to continue to participate in ion exchange in step (1);

[0091] (3) 94.0 g (0.847 mol) of calcium chloride was added to the second column liquid, and the mixture was stirred to allow sulfate to be fully converted into calcium sulfate precipitate. The calcium sulfate was then filtered out, and the filter cake was washed with water, and the filtrate was concentrated to 2775 g. The calcium sulfate was removed by secondary filtration to obtain 2774 g of secondary filtrate (sulfate concentration of 0.05 wt%, calcium ion concentration of 0.02 wt%, chloride ion concentration of 16.8 wt%). A 30.0 wt% ferrous chloride aqueous solution was then added to 2800 g. The resulting solution was returned to the persulfate anion exchange resin column in step (2) to regenerate the sulfate anion exchange resin.

[0092] In this embodiment, the resin column and the regenerated salt solution are recycled to obtain a vitamin B1 hydrochloride product with a sulfate content of <0.01wt%, a residue on ignition content of 0.05wt%, purity and other test results that meet the Chinese Pharmacopoeia standards, and a product yield of 97.3%.

[0093] Example 4

[0094] In this embodiment, the chloride anion exchange resin column A1 is used.

[0095] (1) 1200 g of a vitamin B1 sulfate aqueous solution (sulfate concentration of 6.8 wt %, vitamin B1 sulfate concentration of 25.3 wt %, vitamin B1 sulfate of 0.836 mol) was passed through a chlorine-type anion exchange resin column (the ratio of the total exchange capacity of the chlorine-type anion exchange resin in the chlorine-type anion exchange resin column to the amount of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution was 2.43:1), the column temperature was 20° C., the column time was 60 min, and the first column liquid was obtained. Different sections of the first column liquid were cut to determine the sulfate content. The results are shown in Table 4 below.

[0096] Table 4

[0097] First column liquid Sulfate / wt% 0-1100g 0.001 1100-1200g 0.001

[0098] The first column liquid is concentrated and crystallized to obtain a vitamin B1 hydrochloride product;

[0099] The water-washed resin column is used to recover the vitamin B1 sulfate set for the next batch of vitamin B1 sulfate aqueous solution perchloride type anion exchange resin column. After the water washing, the resin column is a sulfate anion exchange resin column to be regenerated;

[0100] (2) regenerating the sulfate anion exchange resin column by passing it through the column with 6200 g of a 16.7 wt % potassium chloride aqueous solution (chloride ion concentration is 8.0 wt %, chloride ions are 13.972 mol in total, and the molar ratio of chloride ions to vitamin B1 sulfate in step (1) is 16.7:1) at a temperature of 50° C. for 60 min (the sulfate content in the final stage of the second column liquid is <0.2 wt %). The sulfate anion exchange resin column is converted into a regenerated chloride anion exchange resin column, and the second column liquid is collected; then, passing it through the column with 4000 g of water for desalting, collecting the salt from the front stage of the washing and incorporating it into the second column liquid;

[0101] The obtained regenerated chloride-type anion exchange resin column is used to continue to participate in ion exchange in step (1);

[0102] (3) 175.0 g (0.840 mol) of barium chloride was added to the second column liquid, and the mixture was stirred to allow sulfate to be fully converted into barium sulfate precipitate. The barium sulfate was then filtered out, and the filter cake was washed with water, and the filtrate was concentrated to 6118 g. The barium sulfate was removed by secondary filtration to obtain 6117 g of secondary filtrate (sulfate concentration: 0.001 wt %, barium ion concentration: 0.05 wt %, chloride ion concentration: 8.0 wt %). A 16.7 wt % potassium chloride aqueous solution was then added to 6200 g. The resulting solution was returned to the persulfate anion exchange resin column in step (2) to regenerate the sulfate anion exchange resin.

[0103] In this embodiment, the resin column and the regenerated salt solution are recycled to obtain a vitamin B1 hydrochloride product with a sulfate content of <0.01wt%, a residue on ignition content of 0.04wt%, purity and other test results that meet the Chinese Pharmacopoeia standards, and a product yield of 97.1%.

[0104] Example 5

[0105] In this embodiment, the chloride anion exchange resin column A2 is used.

[0106] (1) 1000 g of a vitamin B1 sulfate aqueous solution (sulfate concentration of 8.1 wt%, vitamin B1 sulfate concentration of 30.3 wt%, vitamin B1 sulfate of 0.836 mol) was passed through a chlorine-type anion exchange resin column (the ratio of the total exchange capacity of the chlorine-type anion exchange resin in the chlorine-type anion exchange resin column to the amount of vitamin B1 sulfate in the vitamin B1 sulfate aqueous solution was 2.43:1), the column temperature was 30°C, the column time was 40 min, and the first column liquid was obtained. Different sections of the first column liquid were cut to determine the sulfate content. The results are shown in Table 5 below.

[0107] Table 5

[0108] First column liquid Sulfate / wt% 0-200g 0.001 200-910g 0.001 910-1000g 0.002

[0109] The first column liquid is concentrated and crystallized to obtain a vitamin B1 hydrochloride product;

[0110] The water-washed resin column is used to recover the vitamin B1 sulfate set for the next batch of vitamin B1 sulfate aqueous solution perchloride type anion exchange resin column. After the water washing, the resin column is a sulfate anion exchange resin column to be regenerated;

[0111] (2) regenerating the sulfate anion exchange resin column by passing 3500 g of a 23.0 wt% sodium chloride aqueous solution (chloride ion concentration of 14.0 wt%, 13.802 mol of chloride ion in total, and a molar ratio of chloride ion to vitamin B1 sulfate in step (1) of 16.5:1) through the column at a temperature of 40° C. for 35 min (the sulfate content in the final stage of the obtained second column liquid was <0.2 wt%), and the sulfate anion exchange resin column was converted into a regenerated chloride anion exchange resin column, and the second column liquid was collected; then, 4000 g of water was used to pass the column for desalination, and the water-washed salt in the previous stage was collected and incorporated into the second column liquid;

[0112] The obtained regenerated chloride-type anion exchange resin column is used to continue to participate in ion exchange in step (1);

[0113] (3) 94.0 g (0.847 mol) of calcium chloride was added to the second column liquid, and the mixture was stirred to allow sulfate to be fully converted into calcium sulfate precipitate. The calcium sulfate was then filtered out, and the filter cake was washed with water, and the filtrate was concentrated to 3486 g. The calcium sulfate was removed by secondary filtration to obtain 3484 g of secondary filtrate (sulfate concentration: 0.08 wt %, calcium ion concentration: 0.03 wt %, chloride ion concentration: 14.0 wt %). A 23.0 wt % sodium chloride aqueous solution was then added to 3500 g. The resulting solution was returned to the persulfate anion exchange resin column in step (2) to regenerate the sulfate anion exchange resin.

[0114] In this embodiment, by recycling the resin column and the regenerated salt solution, the vitamin B1 hydrochloride product obtained by the first column liquid has a sulfate content of <0.01wt%, an ignition residue content of 0.05wt%, and other test results such as purity meet the Chinese Pharmacopoeia standards, and the product yield is 99.0%.

[0115] Comparative Example 1

[0116] (1) Same as step (1) in Example 1;

[0117] (2) regenerating the sulfate anion exchange resin column obtained in step (1) above by passing 10,000 g of 11.5 wt % sodium chloride aqueous solution (chloride ion concentration of 7.0 wt %) through the column at a temperature of 40° C. and a flow rate of 4000 mL / h until the sulfate content in the obtained second column liquid is less than 0.2 wt %, and the sulfate anion exchange resin column is converted into a regenerated chloride anion exchange resin column, and the second column liquid is collected; then, passing 4000 mL of water through the column for desalination at a flow rate of 200 mL / min, and collecting the salt from the front stage of the water wash and incorporating it into the second column liquid;

[0118] The obtained regenerated chloride-type anion exchange resin column is used to continue to participate in ion exchange in step (1);

[0119] (3) Collect 10500 g of the second column liquid (sulfate concentration of 0.26 wt %, chloride concentration of 6.4 wt %), add 33.8 g of 92 wt % calcium chloride, stir to allow sulfate to be fully converted into calcium sulfate precipitate, then filter to remove calcium sulfate, wash the filter cake with water, concentrate the filtrate, filter again to remove calcium sulfate, and obtain 9600 g of secondary filtrate (sulfate concentration of 0.05 wt %, calcium ion concentration of 0.02 wt %, chloride ion concentration of 7.0 wt %), then add 11.5 wt % sodium chloride aqueous solution to 10000 g, and return the resulting solution to the persulfate type anion exchange resin column in step (2) for regeneration of the sulfate type anion exchange resin.

[0120] In this comparative example, the resin column and the regenerated salt solution were recycled, and the conversion of the sulfate-type anion exchange resin column into the regenerated chloride-type anion exchange resin column was not complete. The obtained vitamin B1 hydrochloride product had a sulfate content of 0.16wt% and an ignition residue content of 0.13wt%, which did not meet the Chinese Pharmacopoeia standards. Other test results such as purity met the Chinese Pharmacopoeia standards, and the product yield was 70.2%.

[0121] Comparative Example 2

[0122] 700 g of commercially available D315 chloride-type anion exchange resin (total exchange capacity of the resin column is 2.030 mmol) was loaded to obtain a chloride-type anion exchange resin column.

[0123] The chloride-type anion exchange resin column is converted into a hydroxide-type alkaline ion exchange resin column: 2500 g of 4 wt% sodium hydroxide aqueous solution is passed through the chloride-type anion exchange resin column until the chloride ion content in the column alkaline solution is less than 0.1 wt%, and then 10000 g of water is passed through the column to remove the alkali until the pH value of the last section of the column water is 7.5, thereby obtaining a hydroxide-type alkaline ion exchange resin column;

[0124] Vitamin B1 sulfate aqueous solution column: 1000g of vitamin B1 sulfate aqueous solution (sulfate concentration of 8.1wt%, vitamin B1 sulfate concentration of 30.3wt%, vitamin B1 sulfate total 0.836mol) was added with 350g of 32wt% concentrated hydrochloric acid, and passed through the above-mentioned hydroxide-type basic anion exchange resin column. The column temperature was 15°C, and the column time of the vitamin B1 sulfate aqueous solution was 35min. The column liquid was obtained, and different sections were cut to determine the sulfate content. The results are shown in Table 6.

[0125] Table 6

[0126] Column liquid Sulfate / wt% 0-1400g 0.002 1400-1550g 0.014

[0127] 0-1400 g of the column liquid is intercepted for concentration and crystallization to obtain a vitamin B1 hydrochloride product;

[0128] The sulfate content of the prepared vitamin B1 hydrochloride product is less than 0.01wt%, the ignition residue content is 0.05wt%, the total impurity peaks in the chromatogram are 0.78%, and the purity does not meet the Chinese Pharmacopoeia standards. Other test results meet the Chinese Pharmacopoeia standards.

[0129] It can be seen from the above examples and comparative examples that the method for preparing vitamin B1 hydrochloride provided by the present invention is highly safe and environmentally friendly, and the quality of the obtained vitamin B1 hydrochloride meets the requirements of the Chinese Pharmacopoeia, the sulfate content in the product is less than 0.01wt%, and the ignition residue content is less than 0.1wt%. In this method, the resin and the regeneration salt are recycled, and the product yield can be ≥97%. In the comparative examples, the product yield is low or the product does not meet the standard.

[0130] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A method for preparing vitamin B1 hydrochloride, characterized in that: The method comprises: (1) subjecting a vitamin B1 sulfate aqueous solution to ion exchange with a perchloride-type anion exchange resin column to obtain a sulfate-type anion exchange resin column and a first column liquid containing vitamin B1 hydrochloride; concentrating and crystallizing the first column liquid to obtain a finished product of vitamin B1 hydrochloride; (2) passing the aqueous solution of chloride salt I through the sulfate anion exchange resin column for regeneration treatment to obtain a regenerated chloride anion exchange resin column and a second column liquid containing sulfate; the regenerated chloride anion exchange resin column is used to participate in the ion exchange in step (1); (3) mixing the second column liquid with chloride salt II, removing sulfate by precipitation filtration to obtain a filtrate, and concentrating the filtrate to obtain a concentrated solution; the concentrated solution is returned to step (2) to participate in the regeneration process; The pH value of the chloride-type anion exchange resin column is neutral.

2. The method according to claim 1, wherein: In step (1), the perchlorinated anion exchange resin column is carried out at 10-60°C, preferably at 25-35°C.

3. The method according to claim 1 or 2, wherein: In step (1), the ratio of the total exchange capacity of the chloride-type anion exchange resin to the amount of vitamin B1 sulfate is ≥2.4, preferably (2.4-10):

1.

4. The method according to any one of claims 1 to 3, wherein: In step (1), the time for the vitamin B1 sulfate aqueous solution to pass through the chloride-type anion exchange resin column is ≥30 min, preferably 30-120 min.

5. The method according to any one of claims 1 to 4, wherein: In step (2), the ratio of the amount of chloride ions in the chloride salt I to the amount of vitamin B1 sulfate is ≥10, preferably (12-30):1, and the concentration of chloride ions in the aqueous solution of the chloride salt I is ≥8wt%; Preferably, the concentration of chloride ions in the aqueous solution of chloride salt I is 8-27 wt%.

6. The method according to claim 5, wherein: The chloride salt I is selected from at least one of sodium chloride, potassium chloride, ammonium chloride, ferric chloride, ferrous chloride, magnesium chloride, aluminum chloride and lithium chloride.

7. The method according to any one of claims 1 to 6, wherein: In step (2), during the regeneration treatment, the persulfate anion exchange resin column is treated at 10-60°C, preferably at 35-45°C.

8. The method according to claim 1, wherein: In step (2), the time for the aqueous solution of chloride salt I to pass through the sulfate anion exchange resin column is ≥30 min, preferably 30-120 min.

9. The method according to any one of claims 1 to 8, wherein: In step (3), the chloride salt II is selected from barium chloride and / or calcium chloride, preferably calcium chloride.

10. The method according to any one of claims 1 to 9, wherein: In step (3), the concentration of chloride ions in the concentrated solution is ≥ 8wt%.