Method for recycling ranitidine hydrochloride kettle residues

Abstract

The invention relates to the technical field of waste treatment, and provides a method for recycling ranitidine hydrochloride kettle residues. The method comprises the following steps: dissolving ranitidine hydrochloride kettle residues in liquid caustic soda, decolorizing the obtained kettle residue solution, filtering, adjusting the pH value of the obtained filtrate to 11-12, adding sodium chloride until the filtrate is saturated, and extracting the obtained saturated solution with an extracting agent to obtain a water phase; the method comprises the following steps: adding a ranitidine solution into a water phase, distilling the water phase, sequentially carrying out first cooling crystallization and filtration to obtain a ranitidine crude product, dissolving the ranitidine crude product in water, and carrying out decoloration, filtration and cooling crystallization to obtain a ranitidine qualified product. According to the method provided by the invention, ranitidine in kettle residues can be effectively recycled, and resource waste is avoided; meanwhile, secondary pollution cannot be caused in the recovery process, harmful hazardous waste cannot be generated, the environmental protection property is good, and the problem that kettle residues are difficult to treat in the ranitidine hydrochloride production process is effectively solved.

Description

Technical Field

[0001] The invention relates to the technical field of waste treatment, and in particular to a method for recycling ranitidine hydrochloride kettle residue. Background Art

[0002] Ranitidine hydrochloride is a second-generation H2-receptor antagonist that can effectively inhibit gastric acid secretion caused by the stimulation of histamine, pentagastrin and carbachol, reduce the activity of gastric acid and gastric enzymes, and is mainly used for the treatment of excessive gastric acid and heartburn. It has the advantages of good efficacy, lasting action and low side effects.

[0003] At present, ranitidine hydrochloride is usually obtained by reacting ranitidine base and hydrochloric acid in ethanol. The ranitidine hydrochloride ethanol reaction liquid is distilled, concentrated, cooled and centrifuged to obtain ranitidine hydrochloride solid. The reaction liquid after centrifugation is concentrated to recover ethanol, and the ranitidine hydrochloride kettle residue is obtained after concentration. The production of 1 ton of ranitidine hydrochloride product will produce 20 to 30 kg of concentrated hazardous waste kettle residue, and the ranitidine hydrochloride content in the mixture is 94 to 97%.

[0004] Ranitidine hydrochloride still residue is currently mainly treated by incineration. Incineration is the direct burning of still residue, which will produce dioxins, which need to be completely decomposed at around 1100°C, resulting in high treatment costs and energy consumption. In addition, still residue contains ranitidine hydrochloride, and direct incineration will cause a large amount of resource waste.

[0005] Therefore, there is an urgent need to develop a method for treating ranitidine hydrochloride residue that can realize resource utilization of by-products and does not cause secondary pollution. Summary of the invention

[0006] In view of this, the present invention provides a method for recycling ranitidine hydrochloride still residue. The method provided by the present invention can effectively recycle the raw materials in the ranitidine hydrochloride still residue, avoiding waste of resources, and at the same time, no harmful waste is generated during the recycling process, and the method has good environmental protection.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] A method for recycling ranitidine hydrochloride kettle residue comprises the following steps:

[0009] Dissolving the ranitidine hydrochloride still residue in liquid alkali, mixing the still residue solution obtained with activated carbon for first decolorization, then filtering, adjusting the pH value of the obtained filtrate to 11-12, then adding sodium chloride to saturation, extracting the obtained saturated solution with an extractant to obtain an aqueous phase;

[0010] After distilling water from the aqueous phase, performing first cooling crystallization and filtering in sequence to obtain a crude ranitidine product;

[0011] The crude ranitidine product is dissolved in water, the obtained crude product solution is mixed with activated carbon for a second decolorization, filtered, and the obtained filtrate is subjected to a second cooling crystallization and then filtered to obtain a qualified ranitidine product.

[0012] Preferably, the mass fraction of ranitidine hydrochloride in the ranitidine hydrochloride still residue is 94-97%.

[0013] Preferably, the source of the ranitidine hydrochloride still residue comprises: distilling, concentrating, cooling and centrifuging the ranitidine hydrochloride ethanol reaction liquid to obtain ranitidine hydrochloride solid and centrifuge liquid; concentrating the centrifuge liquid to recover ethanol, and the remaining concentrate is the ranitidine hydrochloride still residue.

[0014] Preferably, the concentration of the liquid caustic soda is 4 to 8 wt %.

[0015] Preferably, the mass ratio of the ranitidine hydrochloride still residue to the liquid caustic soda is 1:(2-3); and the temperature for dissolving the ranitidine hydrochloride still residue is 50-60°C.

[0016] Preferably, the extractant is chloroform and / or carbon tetrachloride, the number of extractions is 3 times, the extraction temperature is 45-60° C.; the mass ratio of the ranitidine hydrochloride still residue to the extractant used for a single extraction is 1:(0.5-1).

[0017] Preferably, the mass of the water distilled from the distilled water is 30-40% of the total water in the water phase.

[0018] Preferably, the temperature at which the crude ranitidine is dissolved is 50-60°C.

[0019] Preferably, the temperature of the first cooling crystallization and the second cooling crystallization are independently 0 to 7° C., and the time is independently 1 to 3 hours.

[0020] Preferably, the temperature of the first decolorization and the second decolorization are independently 55-60° C., and the time is independently 1-2 hours.

[0021] The present invention provides a method for recycling ranitidine hydrochloride kettle residue, comprising the following steps: dissolving the ranitidine hydrochloride kettle residue in liquid alkali, mixing the obtained kettle residue solution with activated carbon for first decolorization, then filtering, adjusting the pH value of the obtained filtrate to 11-12, then adding sodium chloride to saturation, extracting the obtained saturated liquid with an extractant to obtain an aqueous phase; after distilling the aqueous phase, successively performing first cooling crystallization and filtering to obtain a crude ranitidine product; dissolving the crude ranitidine product in water, mixing the obtained crude solution with activated carbon for second decolorization, filtering, and filtering the obtained filtrate after second cooling crystallization to obtain a qualified ranitidine product. The method provided by the present invention can realize the effective recovery of ranitidine in the kettle residue, and the recovered ranitidine can be used as a raw material for preparing ranitidine hydrochloride, avoiding waste of resources; at the same time, the method provided by the present invention has no secondary pollution, does not generate harmful and hazardous waste, has good environmental protection, and effectively solves the problem that the kettle residue in the production process of ranitidine hydrochloride is difficult to handle. The results of the embodiment show that the HPLC content of ranitidine recovered by the present invention is above 99%, the water content is ≤17%, and the transmittance is ≥90%, which meets the standards of ranitidine. DETAILED DESCRIPTION

[0022] The present invention provides a method for recycling ranitidine hydrochloride still residue, comprising the following steps:

[0023] Dissolving the ranitidine hydrochloride still residue in liquid alkali, mixing the still residue solution obtained with activated carbon for first decolorization, then filtering, adjusting the pH value of the obtained filtrate to 11-12, then adding sodium chloride to saturation, extracting the obtained saturated solution with an extractant to obtain an aqueous phase;

[0024] After distilling water from the aqueous phase, performing first cooling crystallization and filtering in sequence to obtain a crude ranitidine product;

[0025] The crude ranitidine product is dissolved in water, the obtained crude product solution is mixed with activated carbon for a second decolorization, filtered, and the obtained filtrate is subjected to a second cooling crystallization and then filtered to obtain a qualified ranitidine product.

[0026] The method comprises dissolving ranitidine hydrochloride still residue in liquid alkali, mixing the still residue solution obtained with activated carbon for first decolorization, filtering, adjusting the pH value of the obtained filtrate to 11-12, then adding sodium chloride to saturation, extracting the obtained saturated liquid with an extractant, and obtaining an aqueous phase. In the present invention, the ranitidine hydrochloride still residue is specifically the ranitidine hydrochloride ethanol concentrated still residue; the source of the ranitidine hydrochloride still residue includes: the ranitidine hydrochloride ethanol reaction liquid is distilled, concentrated, cooled and centrifuged to obtain ranitidine hydrochloride solid and centrifuge liquid; the centrifuge liquid is concentrated to recover ethanol, and the remaining concentrate is the ranitidine hydrochloride still residue; the mass fraction of ranitidine hydrochloride in the ranitidine hydrochloride still residue is preferably 94-97%; the concentration of the liquid alkali is 4-8wt%, preferably 5-6wt%, and the liquid alkali is a sodium hydroxide aqueous solution; the mass ratio of the ranitidine hydrochloride still residue to the liquid alkali is preferably 1:(2-3), more preferably 1:(2-2.5); the temperature for dissolving the ranitidine hydrochloride still residue is preferably 50-60°C, more preferably 55°C.

[0027] In the present invention, the mass ratio of the ranitidine hydrochloride residue to the activated carbon in the first decolorization process is preferably 50:1, the temperature of the first decolorization is preferably 50-60°C, the time is preferably 1-2h, and more preferably 1h; in a specific embodiment of the present invention, it is preferred to first add the ranitidine hydrochloride residue to liquid alkali, raise the temperature to 50-60°C to dissolve the ranitidine hydrochloride residue, then maintain the temperature, add activated carbon, and perform the first decolorization under stirring conditions.

[0028] After the first decolorization is completed, the present invention filters the decolorization system, adjusts the pH value of the obtained filtrate to 11-12, then adds sodium chloride to saturation, and extracts the obtained saturated liquid with an extractant to obtain an aqueous phase. In the present invention, the reagent used to adjust the pH value of the filtrate is preferably hydrochloric acid, and the mass fraction of the hydrochloric acid is preferably 30%; the present invention adds sodium chloride to the filtrate after the pH value is adjusted to saturation, which can reduce the solubility of the extractant in water.

[0029] In the present invention, the extractant is preferably chloroform and / or carbon tetrachloride, more preferably chloroform, carbon tetrachloride or a chloroform-carbon tetrachloride mixed solvent, the mass ratio of chloroform to carbon tetrachloride in the chloroform-carbon tetrachloride mixed solvent is preferably 3:7; the number of extractions is preferably 3 times, the extraction temperature is preferably 40-60°C, more preferably 45-55°C, and further preferably 50°C; the mass ratio of the ranitidine hydrochloride kettle residue and the extractant used for a single extraction is preferably 1:(0.5-1). After extraction, the aqueous phase and the organic phase are obtained by standing and separating the liquids, the aqueous phase is subsequently treated, and the organic phase is concentrated to recover the extractant.

[0030] After obtaining the aqueous phase, the present invention sequentially performs first cooling crystallization and filtration after distilling the aqueous phase to obtain a crude ranitidine product. In the present invention, the mass of the water distilled from the distillation is preferably 30-40% of the total water in the aqueous phase, and the temperature of the distillation is preferably 50-60°C, more preferably 55°C; the temperature of the first cooling crystallization is preferably 0-7°C, more preferably 5°C, and the time is preferably 1-3h, more preferably 2h; in a specific embodiment of the present invention, the water is preferably distilled from the aqueous phase at 55°C, then cooled to 0-7°C under stirring conditions, filtered after keeping warm for 1-3h, and the filter cake is washed with ice water to obtain a crude ranitidine product.

[0031] After obtaining the crude ranitidine, the present invention dissolves the crude ranitidine in water, mixes the obtained crude solution with activated carbon for a second decolorization, filters, and filters the obtained filtrate after a second cooling crystallization to obtain a qualified ranitidine. In the present invention, the temperature at which the crude ranitidine is dissolved is preferably 50-60°C, more preferably 55°C, and the mass ratio of the crude ranitidine to water is preferably 1:(1-4.5); the mass ratio of the crude ranitidine to the second decolorization activated carbon is preferably 1:(0.01-0.02); the temperature of the second decolorization is preferably 50-60°C, the time is preferably 1-2h, more preferably 1h; the second decolorization is preferably carried out under stirring; the temperature of the second cooling crystallization is preferably 0-7°C, more preferably 5°C, the time is preferably 1-3h, more preferably 2h; in a specific embodiment of the present invention, it is preferred to filter after the second decolorization is completed, cool the filtrate to 0-7°C, keep warm for 1-3h, and then filter again to obtain a qualified ranitidine.

[0032] In the present invention, the HPLC content of the qualified ranitidine product is ≥99%, the water content is ≤20wt%, and the transmittance is ≥90%.

[0033] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] The mass fraction of ranitidine hydrochloride in the ethanol concentration kettle residue of ranitidine hydrochloride used in the examples was 94.1%.

[0035] Example 1

[0036] Take 100g of the residue from the concentrated ethanol kettle of ranitidine hydrochloride, add it to 200g of 8% liquid alkali, heat it to 60°C, add 2g of activated carbon after dissolution, stir and decolorize at 60°C for 1h, and then filter. Add 30% hydrochloric acid to the filtrate to adjust the pH to 11.3. After the pH of the filtrate is adjusted, add sodium chloride until the filtrate is saturated, then add chloroform at 50°C, stir and extract 3 times, using 50g of chloroform each time, and obtain 294.3g of aqueous phase after separation.

[0037] The aqueous phase obtained from the previous separation was put into a four-necked bottle, the kettle temperature was controlled at 55°C to evaporate 83.7g of water, then the mixture was cooled to 5°C with stirring and kept warm for 2h, filtered, and the filter cake was washed with 100g of ice water to obtain 57.3g of crude ranitidine.

[0038] Add 190g of pure water to the crude ranitidine, stir and heat to 55°C to completely dissolve, add 1g of activated carbon, stir to decolorize for 1h, and then filter. Cool the filtrate to 5°C and keep it warm for 2h, filter, and obtain 43.2g of ranitidine. After testing, HPLC content is 99.12%, water content is 16.9%, and transmittance is 92%, which meets the ranitidine standard.

[0039] Example 2

[0040] Take 100g of the residue from the concentrated ethanol kettle of ranitidine hydrochloride, add it to 300g of liquid alkali with a mass fraction of 4%, heat it to 50°C, add 2g of activated carbon after dissolution, stir and decolorize at 50°C for 1h, and then filter. Add 30% hydrochloric acid to the filtrate to adjust the pH to 11.9. After the pH of the filtrate is adjusted, add sodium chloride until the filtrate is saturated, then add chloroform at 50°C and stir and extract 3 times, using 50g of chloroform each time, and obtain 393.6g of aqueous phase after separation.

[0041] The aqueous phase obtained from the previous separation was put into a four-necked bottle, and the kettle temperature was controlled at 55°C to evaporate 108.3g of water. The mixture was then cooled to 5°C with stirring and kept warm for 2h. The filter cake was washed with 100g of ice water to obtain 51.7g of crude ranitidine.

[0042] Add 217g of pure water to the crude ranitidine, stir and heat to 55°C to completely dissolve, add 1g of activated carbon, stir and decolorize for 1h, and then filter. Cool the filtrate to 5°C and keep it warm for 2h, then filter to obtain 40.54g of ranitidine. HPLC content is 99.21%, water content is 17.0%, and transmittance is 93%, which meets the ranitidine standard.

[0043] Example 3

[0044] Take 100g of the residue from the concentrated ethanol kettle of ranitidine hydrochloride, add it to 250g of liquid alkali with a mass fraction of 6%, heat it to 55°C, add 2g of activated carbon after dissolution, stir and decolorize at 55°C for 1h, and then filter. Add 30% hydrochloric acid to the filtrate to adjust the pH to 11.5. After the pH of the filtrate is adjusted, add sodium chloride until the filtrate is saturated, then add 50g of chloroform at 50°C, stir and extract 3 times, and obtain 345.1g of aqueous phase after separation.

[0045] The aqueous phase obtained from the previous separation was put into a four-necked bottle, the kettle temperature was controlled at 55°C to evaporate 129.7g of water, then the mixture was cooled to 5°C with stirring and kept warm for 2h, filtered, and the filter cake was washed with 100g of ice water to obtain 58.7g of crude ranitidine.

[0046] Add 260g of pure water to the crude ranitidine, stir and heat to 55°C to completely dissolve, add 1g of activated carbon, stir to decolorize for 1h, and then filter. Cool the filtrate to 5°C and keep it warm for 2h, filter to obtain 39.75g of ranitidine. HPLC content is 99.09%, water content is 16.9%, and transmittance is 92%, which meets the ranitidine standard.

[0047] Example 4

[0048] Take 100g of the residue from the concentrated kettle of ranitidine hydrochloride ethanol, add it to 250g of 6% liquid alkali, heat it to 60°C, add 2g of activated carbon after dissolution, stir and decolorize at 50°C for 1h, and then filter. Add 30% hydrochloric acid to the filtrate to adjust the pH to 11.5. After the pH of the filtrate is adjusted, add sodium chloride until the filtrate is saturated, then add a mixed extractant at 50°C and stir and extract twice, using 70g of carbon tetrachloride and 30g of chloroform each time, and obtain 343.2g of aqueous phase after separation.

[0049] The aqueous phase obtained from the separation in the previous step was put into a four-necked bottle, and the kettle temperature was controlled at 55°C to evaporate 104.9g of water. The mixture was then cooled to 5°C with stirring and kept warm for 2h. The filter cake was washed with 100g of ice water to obtain 56.4g of crude ranitidine.

[0050] Add 217g of pure water to the crude ranitidine, stir and heat to 55°C to completely dissolve, add 1g of activated carbon, stir to decolorize for 1h, and then filter. Cool the filtrate to 5°C and keep it warm for 2h, filter, and obtain 40.54g of ranitidine. HPLC content is 99.13%, water content is 16.8%, and transmittance is 90%, which meets the ranitidine standard.

[0051] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for recycling ranitidine hydrochloride still residue, characterized in that: The following steps are involved: Dissolving the ranitidine hydrochloride still residue in liquid alkali, mixing the still residue solution obtained with activated carbon for first decolorization, then filtering, adjusting the pH value of the obtained filtrate to 11-12, then adding sodium chloride to saturation, extracting the obtained saturated solution with an extractant to obtain an aqueous phase; After distilling water from the aqueous phase, performing first cooling crystallization and filtering in sequence to obtain a crude ranitidine product; The crude ranitidine product is dissolved in water, the obtained crude product solution is mixed with activated carbon for a second decolorization, filtered, and the obtained filtrate is subjected to a second cooling crystallization and then filtered to obtain a qualified ranitidine product.

2. The recycling method according to claim 1, characterized in that: The mass fraction of ranitidine hydrochloride in the ranitidine hydrochloride kettle residue is 94-97%.

3. The recycling method according to claim 1, characterized in that: The source of the ranitidine hydrochloride still residue includes: distilling, concentrating, cooling and centrifuging the ranitidine hydrochloride ethanol reaction liquid to obtain ranitidine hydrochloride solid and centrifuge liquid; concentrating the centrifuge liquid to recover ethanol, and the remaining concentrate is the ranitidine hydrochloride still residue.

4. The recycling method according to claim 1, characterized in that: The concentration of the liquid caustic soda is 4-8wt%.

5. The recycling method according to claim 1 or 4, characterized in that: The mass ratio of the ranitidine hydrochloride still residue to the liquid caustic soda is 1:(2-3); the temperature at which the ranitidine hydrochloride still residue is dissolved is 50-60°C.

6. The recycling method according to claim 1, characterized in that: The extractant is chloroform and / or carbon tetrachloride, the number of extractions is 3, the extraction temperature is 40-60° C.; the mass ratio of the ranitidine hydrochloride kettle residue to the extractant used for a single extraction is 1:(0.5-1).

7. The recycling method according to claim 1, characterized in that: The mass of the water distilled out of the distilled water is 30-40% of the total water in the water phase.

8. The recycling method according to claim 1, characterized in that: The temperature at which the crude ranitidine is dissolved is 50-60°C.

9. The recycling method according to claim 1, characterized in that: The temperatures of the first cooling crystallization and the second cooling crystallization are independently 0 to 7° C., and the times are independently 1 to 3 hours.

10. The recycling method according to claim 1, characterized in that: The temperature of the first decolorization and the second decolorization are independently 55-60° C., and the time is independently 1-2 hours.