Inactivation treatment method and device for tegafur production wastewater

Abstract

The invention discloses an inactivation treatment method and device for tegafur production wastewater, and belongs to the field of pharmaceutical chemicals. The inactivation treatment method comprises the following steps: mixing tegafur production wastewater with alkali, carrying out inactivation treatment under the condition of introducing ozone, then detecting that the tegafur production wastewater is lower than a detection limit through liquid chromatography, and neutralizing with acid liquor to obtain an inactivated water body. The inactivation treatment device comprises an inactivation unit with a cavity for accommodating a solution, and ozone generation equipment communicated with a gas inlet of the inactivation unit, the liquid chromatography detection equipment is communicated with a solution outlet of the inactivation unit; and the solution outlet of the inactivation unit is used for discharging a solution neutralized by the detected acid liquor. According to the method, the synergistic inactivation treatment of alkali and ozone is mainly adopted, so that the inactivation effect on tegafur and degradation products thereof is improved. The invention provides an effective treatment method for inactivation of tegafur, and is beneficial to reducing the pollution of tegafur raw material medicine or preparation production residues to the environment.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical chemistry, and particularly to a method and device for inactivating the production wastewater of tegafur. Background Art

[0002] Tegafur (the structural formula is as follows, which is a derivative of fluorouracil) is used as an antitumor drug and is mainly used for the treatment of diseases such as gastric cancer, colon cancer, rectal cancer, pancreatic cancer, breast cancer, and liver cancer in clinical practice;

[0003]

[0004] Tegafur can be obtained by condensing 5-fluorouracil and 2-acetoxytetrahydrofuran; another production method is to use 5-fluorouracil, hexamethyldisilazane, and trimethylchlorosilane as starting materials to synthesize tegafur. Both tegafur and its degradation product 5-fluorouracil have certain toxicity, and traditional sewage treatment methods are difficult to completely remove such substances in the production wastewater, resulting in their ultimate entry into the environment and having an adverse impact on the ecology. Summary of the Invention

[0005] In view of this, the present invention provides a method and device for inactivating the production wastewater of tegafur. The technology of the present invention can inactivate tegafur and the degradation product 5-fluorouracil, ensuring that the wastewater after the production of tegafur has less pollution to the environment.

[0006] The present invention provides a method for inactivating the production wastewater of tegafur, which includes the following steps:

[0007] Mix the production wastewater of tegafur with an alkali, and perform inactivation treatment under the condition of introducing ozone. Then, detect by liquid chromatography and if it is below the detection limit, neutralize with an acid solution to obtain the inactivated water body.

[0008] In some embodiments of the present invention, the content of tegafur in the production wastewater of tegafur is above 20 μg / mL; the alkali is sodium hydroxide, and its weight is 20-40% of the weight of the production wastewater of tegafur.

[0009] In some embodiments of the present invention, the inactivation treatment includes: after mixing, introduce steam to raise the temperature to above 80 °C, keep warm and stir for 7-8 hours; then introduce ozone at normal temperature for auxiliary inactivation; the ozone flow rate is 200-300 g / h, and the introduction time is more than 4 hours.

[0010] In some embodiments of the present invention, the content of tegafur in the production wastewater of tegafur is 0.01-20 μg / mL; the alkali is sodium hydroxide, and its weight is 3-6% of the weight of the production wastewater of tegafur.

[0011] In some embodiments of the present invention, during the inactivation treatment process, an alkali is added to the tegafur production wastewater, and it is kept warm at 40 - 60 °C, while ozone is introduced synchronously and stirred for more than 4 hours, and the ozone flow rate is 200 - 300 g / h.

[0012] In some embodiments of the present invention, the liquid chromatography detection uses a C18 chromatographic column, with methanol - acetonitrile - water as the mobile phase; the acid solution is neutralized to neutral.

[0013] The present invention provides an inactivation treatment device for tegafur production wastewater, comprising:

[0014] An inactivation unit having a cavity for accommodating a solution, the inactivation unit having a solution inlet for introducing tegafur production wastewater, an alkali, and an acid solution; the inactivation unit having a gas inlet and a solution outlet;

[0015] An ozone generation device communicated with the gas inlet of the inactivation unit;

[0016] A liquid chromatography detection device communicated with the solution outlet of the inactivation unit, and the solution outlet of the inactivation unit is used to discharge the solution after the acid solution is neutralized in the detection.

[0017] In some embodiments of the present invention, the inactivation treatment device further comprises a corrosion - resistant high - temperature treatment unit having an inlet and an outlet, and the corrosion - resistant high - temperature treatment unit has a steam heating control device and a stirring device;

[0018] The inlet of the corrosion - resistant high - temperature treatment unit is used to introduce high - concentration tegafur production wastewater and an alkali, and the outlet is used to discharge the solution after high - temperature treatment; the corrosion - resistant high - temperature treatment unit is connected to the solution inlet of the inactivation unit via the outlet.

[0019] In some embodiments of the present invention, the inactivation unit further has a steam heating control device.

[0020] In some embodiments of the present invention, a stirring device is provided in the cavity of the inactivation unit; the liquid chromatography detection device includes a C18 chromatographic column.

[0021] Currently, there are no relevant reports on effectively inactivating tegafur in tegafur production wastewater. The inactivation treatment method for tegafur production wastewater provided by the present invention is a technology for quickly inactivating tegafur, including: mixing tegafur production wastewater with an alkali, performing inactivation treatment under the condition of introducing ozone, then detecting by liquid chromatography to be below the detection limit, neutralizing with an acid solution, and discharging the water body. The present invention mainly uses the synergistic inactivation treatment of an alkali and ozone to improve the inactivation effect on tegafur and its degradation products. The present invention provides an effective treatment method for inactivating tegafur, which is beneficial to reducing the environmental pollution caused by the residues in the production of tegafur raw materials or preparations. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention, and thus should not be regarded as limiting the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.

[0023] Figure 1 Mechanism reactions involved in the inactivation treatment in some embodiments of the present invention;

[0024] Figure 2 Schematic diagram of the inactivation treatment process device for low-concentration tegafur wastewater in some embodiments of the present invention;

[0025] Figure 3 Schematic diagram of the inactivation treatment process device for high-concentration tegafur wastewater in some embodiments of the present invention;

[0026] Figure 4 Chromatogram of the mixed control solution in an embodiment of the present invention;

[0027] Figure 5 Chromatogram of the high-concentration inactivation solution in an embodiment of the present invention;

[0028] Figure 6 Chromatogram of the low-concentration inactivation solution in an embodiment of the present invention. Specific embodiments

[0029] In order to further understand the present invention below, the preferred implementation schemes of the present invention will be described in combination with embodiments. However, it should be understood that these descriptions are only for further explaining the features and advantages of the present invention, rather than limiting the claims of the present invention.

[0030] In traditional sewage treatment processes, wastewater is generally classified and collected according to the types of pollutants, concentrations, and pretreatment methods in the wastewater, and pretreated separately. For example, high-salt wastewater is desalted and then enters the sewage treatment system; high-phosphorus wastewater should be collected separately and pretreated for phosphorus removal; acidic or alkaline wastewater is preferably collected separately, quantitatively mixed, and neutralized for pretreatment; wastewater containing first-class pollutants such as heavy metals should be collected in the workshop, pretreated to meet the workshop discharge standards, and then mixed with other wastewater; biological engineering pharmaceutical process wastewater in contact with viruses and active bacteria should be sterilized and inactivated before being mixed with other wastewater, and preferably treated using a "two-stage biochemical - disinfection" combined process; high-concentration kettle residues and mother liquors in the process of genetic engineering drugs should be disposed of as hazardous waste to prevent these waste liquids from entering the sewage treatment system.

[0031] During the production of tegafur, wastewater containing tegafur with different concentrations is generated from different sources. For example, high-concentration tegafur solutions are stored in equipment that comes into direct contact with the drug, while low-concentration tegafur wastewater mainly consists of cleaning waste liquids from utilities, clean clothing, and other utensils or process components that have minimal contact with the drug. However, there have been no relevant reports on the effective inactivation of tegafur in wastewater.

[0032] The present invention provides a method for inactivating tegafur production wastewater, comprising the following steps:

[0033] Mix the tegafur production wastewater with an alkali, and perform inactivation treatment under the condition of introducing ozone. Then, detect by liquid chromatography to be below the detection limit, and neutralize with an acid solution to obtain the inactivated water body.

[0034] The tegafur inactivation method and process established by the present invention can solve the problem of inactivating residual raw materials in tegafur preparations, and reduce the environmental pollution caused by raw materials and degradation products.

[0035] In some embodiments of the present invention, for high-concentration tegafur production wastewater, the content (concentration) of tegafur in the tegafur production wastewater is above 20 μg / mL, for example, its concentration is 30 - 1000 μg / mL, or between 100 - 900 μg / mL.

[0036] In the embodiments of the present invention, high-concentration tegafur production wastewater can be first inactivated at high temperature in an alkaline environment: preferably pump it into a stainless steel tank, add an alkali such as sodium hydroxide, mainly use solid sodium hydroxide, and other alkalis are not suitable for use due to operation or high price. The weight of the alkali is preferably 20 - 40% of the weight of the tegafur production wastewater, and further stir to dissolve and mix; introduce steam, heat up to above 80°C, preferably 80 - 100°C, and further 80 - 85°C, and keep warm and stir for 7 - 8 hours.

[0037] After the heat preservation is completed, in the embodiments of the present invention, ozone is introduced at room temperature for auxiliary inactivation. The concentrations of tegafur and 5-fluorouracil are detected by liquid chromatography. After reaching the discharge standard, it is preferably neutralized to neutral with an acid solution, and then the inactivated water body can be discharged.

[0038] Among them, the flow rate of the ozone (O3) can be 200 - 300 g / h, preferably 230 g / h, 240 g / h, 250 g / h, 260 g / h, etc.; the introduction time is more than 4 hours, preferably 5 - 8 hours, and further 6 - 7 hours, which can achieve a better effect of auxiliary ozone inactivation at room temperature. The liquid chromatography detection preferably uses a C18 chromatographic column with methanol - acetonitrile - water as the mobile phase; after detecting that the inactivation is complete, it is preferably neutralized to neutral with a hydrochloric acid solution (the neutral generally refers to a pH range of 6.5 - 7.5).

[0039] Some other embodiments of the present invention are directed to low-concentration tegafur production wastewater, wherein the tegafur content in the low-concentration tegafur production wastewater is 0.01 - 20 μg / mL, further 0.1 - 18 μg / mL, or 1 - 15 μg / mL, for example, between 5 - 8 μg / mL and 10 - 13 μg / mL.

[0040] In specific embodiments of the present invention, the low-concentration tegafur production wastewater can be pumped into an inactivation treatment container, and an alkali (the alkali can be sodium hydroxide, and its weight is 3 - 6% of the weight of the tegafur production wastewater) is added. Preferably, it is stirred and dissolved evenly, and kept warm at 40 - 60°C (preferably kept warm at 50 - 55°C), and ozone is simultaneously introduced (the flow rate can be 200 - 300 g / h, preferably 210 - 250 g / h), and the reaction is carried out with stirring and keeping warm for more than 4 hours, further 4 - 8 hours.

[0041] The inactivation treatment mechanism of some specific embodiments of the present invention includes Figure 1 The reaction process shown. Tegafur in the wastewater or waste liquid decomposes into tetrahydrofuran and 5-fluoropyrimidine in the presence of sodium hydroxide (NaOH) at a temperature of 80°C. 5-Fluoropyrimidine undergoes a ring-opening reaction under NaOH and 80°C to form HOOC-NH-CH=CF-CONH2, which further decomposes under the action of ozone. In addition, tegafur and 5-fluoropyrimidine can be ring-opened by the action of ozone respectively.

[0042] In the embodiments of the present invention, the concentrations of tegafur and 5-fluoropyrimidine are detected by the same liquid chromatography. After reaching the discharge standard (not exceeding 1 μg / ml), it is preferably neutralized to neutral with hydrochloric acid, and then the inactivated treated water body can be discharged, and its inactivation effect is better.

[0043] Correspondingly, the present invention provides an inactivation treatment device for tegafur production wastewater, including:

[0044] An inactivation unit having a cavity for accommodating a solution. The inactivation unit has a solution inlet for introducing tegafur production wastewater, an alkali, and an acid solution; the inactivation unit has a gas inlet and a solution outlet;

[0045] An ozone generation device communicated with the gas inlet of the inactivation unit;

[0046] A liquid chromatography detection device communicated with the solution outlet of the inactivation unit. The solution outlet of the inactivation unit is used to discharge the solution neutralized by the acid solution after detection.

[0047] For the inactivation treatment process device involved in some embodiments of the present invention, see Figure 2 , where 11 is the inactivation unit and 12 is the ozone generation device, Figure 2The liquid chromatography detection device is not shown. The inactivation unit 11 is hermetically arranged, having a cavity and a solution inlet, and can accommodate the low-concentration tegafur production wastewater pumped in from the solution inlet. Moreover, the alkali can also enter it from the solution inlet. The inactivation unit 11 can be made of plastic, and preferably has a stirring device located in the center in its cavity. The inactivation unit 11 can be a tank-shaped inactivation treatment container, and its solution inlet is generally arranged at the upper part of the container.

[0048] In an embodiment of the present invention, the inactivation unit 11 also has a steam heating control device, which can adjust the temperature of the inactivation unit to 40 - 60 °C by introducing pure steam and keep good heat preservation. Moreover, the inactivation unit 11 has a gas inlet, which is located at the upper part of the container and is connected to the ozone generation device 12. The ozone generated by the ozone generation device 12 enters the cavity of the inactivation unit 11 through the gas inlet and performs inactivation treatment synchronously with the introduced alkali. As a preference, the ozone generation device 12 is equipped with a flow meter to precisely control the flow rate, such as controlling it to be 200 - 300 g / h, etc.

[0049] In the embodiment of the present invention, the solution in the treatment process of the inactivation unit 11 is detected by a liquid chromatography detection device. The liquid chromatography detection device includes a C18 chromatographic column, and the mobile phase is methanol - acetonitrile - water (volume ratio 10:5:85). When the contents of tegafur and 5-fluorouracil are detected to reach the discharge standard, that is, the inactivation is complete, then in the embodiment of the present invention, hydrochloric acid solution can be introduced from the hydrochloric acid storage tank through the gas inlet, neutralized to neutral, and then discharged to the sewage treatment station for centralized treatment.

[0050] In addition, for the inactivation treatment process device involved in some embodiments of the present invention, refer to Figure 3 , where 21 is a corrosion-resistant high-temperature treatment unit, 22 is an inactivation unit, and 23 is an ozone generation device. Figure 3 The liquid chromatography detection device is not shown either.

[0051] Among them, the corrosion-resistant high-temperature treatment unit 21 has an inlet and an outlet. The high-concentration tegafur production wastewater and alkali enter the interior from the inlet respectively or simultaneously; the outlet is used to discharge the solution after high-temperature treatment. The corrosion-resistant high-temperature treatment unit 21 is specifically a hermetically sealed tank-shaped container resistant to acid and alkali corrosion (such as a stainless steel tank), having a steam heating control device and a stirring device, and their functions are basically the same as those of the devices described above. For example, the steam heating control device can adjust the temperature of the corrosion-resistant high-temperature treatment unit to 80 - 90 °C, etc. by introducing pure steam and keep good heat preservation.

[0052] The structure of the inactivation unit 22 is similar to that described above, and its solution inlet is connected to the outlet of the corrosion-resistant high-temperature treatment unit 21. The inactivation unit 22 can be an inactivation tank, and the waste liquid after high-temperature inactivation is preferably pumped into it, and ozone is introduced under stirring for continuous inactivation. The ozone generation device 23 generates ozone and is preferably equipped with a flow meter.

[0053] In an embodiment of the present invention, a liquid chromatography detection device is used to detect the solution in the inactivation unit 22 during the treatment process. The liquid chromatography detection device includes a C18 chromatographic column, and methanol-acetonitrile-water (volume ratio 10:5:85) is used as the mobile phase. When the contents of tegafur and 5-fluorouracil are detected to reach the discharge standard, that is, the inactivation is complete, then in the embodiment of the present invention, hydrochloric acid solution can be introduced from the hydrochloric acid storage tank through the gas inlet, neutralized to neutrality, and discharged.

[0054] For the production wastewater with complex composition and properties, the water body after the above inactivation treatment can be used as raw water and further treated through a sewage treatment station, including: collecting tank ~ regulating tank ~ aerobic [aeration 1], anoxic tank [aeration 2] [aeration 3] ~ sedimentation tank [return 1] ~ sedimentation tank [return 2] ~ discharge.

[0055] The embodiment of the present invention mainly adopts the synergistic inactivation treatment of alkali and ozone, and also combines the control of process conditions such as temperature and pH, which can improve the inactivation effect on tegafur and its degradation products, and is conducive to reducing the environmental pollution caused by the residues in the production of tegafur raw materials or preparations.

[0056] To better illustrate the present invention, further examples are given below through embodiments. In the embodiments, all the original reagents and materials can be obtained commercially, and the experimental methods without specific experimental conditions indicated are conventional methods and conditions well-known in the art.

[0057] Example 1

[0058] As Figure 2 shown, 400 L of low-concentration tegafur waste liquid (tegafur content 12.69 μg / ml) is pumped into a plastic inactivation tank from the solution inlet. 21 kg of sodium hydroxide is added, and after stirring and dissolving, pure steam is used to heat the inactivation tank to an internal temperature of 50 - 55 °C. Ozone (250 g / h) is introduced under stirring, and inactivation continues for 7 hours. The contents of tegafur and 5-fluorouracil are detected at this time and reach the discharge standard. Hydrochloric acid is added to neutralize to pH neutral, and then it is discharged to the sewage treatment station for centralized treatment.

[0059] Example 2

[0060] After the production of tegafur preparations is completed, 200 L of high-concentration tegafur waste liquid (tegafur content 864.9 μg / ml) is pumped into a stainless-steel inactivation tank from the inlet. 50 kg of sodium hydroxide is added, and after stirring and dissolving, pure steam is used to heat the inactivation tank to an internal temperature of 80 - 85 °C and keep it warm for 8 hours. The waste liquid after high-temperature inactivation is pumped into the inactivation tank, and ozone (250 g / h) is introduced under stirring, and inactivation continues for 7 hours. The contents of tegafur and 5-fluorouracil are detected at this time and reach the discharge standard. Hydrochloric acid is added to adjust the pH to neutral and then discharged; for the schematic diagram of the device process, see Figure 3 .

[0061] The detection method and results are as follows; the detection spectrum includes: Figure 4 It is the liquid chromatography map of the mixed control. Figure 5 It is the chromatogram of the high-concentration inactivated solution (corresponding to Example 2). Figure 6 It is the chromatogram of the low-concentration inactivated solution (corresponding to Example 1).

[0062] Table 1 Conditions of the liquid chromatography detection method in the embodiments of the present invention

[0063]

[0064] Table 2 Inactivation monitoring of the embodiments of the present invention

[0065]

[0066] Comparative Example 1

[0067] Take the high-concentration tegafur-containing wastewater (the same as in Example 2), and inactivate it with sodium hydroxide at high temperature in the same way (without ozone) for 8 hours. Detect the contents of tegafur and fluorouracil, and the results are 53.2 and 1.2 μg / ml respectively.

[0068] Comparative Example 2

[0069] Take the high-concentration tegafur-containing wastewater (the same as in Example 2), and inactivate it with ozone in the same way (without sodium hydroxide) for 8 hours. Detect the contents of tegafur and fluorouracil, and the results are 152.6 and 5.2 μg / ml respectively.

[0070] As can be seen from the above examples, the embodiments of the present invention mainly adopt the synergistic inactivation treatment of alkali and ozone to improve the inactivation effect on tegafur and its degradation products. The present invention provides an effective treatment method for the inactivation of tegafur, which is conducive to reducing the environmental pollution caused by the residues in the production of tegafur raw materials or preparations.

[0071] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principle and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for inactivating the production wastewater of tegafur, characterized in that, It includes the following steps: Mix the tegafur production wastewater with alkali, carry out inactivation treatment under the condition of introducing ozone, then detect by liquid chromatography and the result is below the detection limit, and neutralize with acid solution to obtain the inactivated water body.

2. The inactivation treatment method according to claim 1, wherein The content of tegafur in the tegafur production wastewater is above 20 μg / mL; the alkali is sodium hydroxide, and its weight is 20 - 40% of the weight of the tegafur production wastewater.

3. The inactivation treatment method according to claim 2, wherein The inactivation treatment includes: after mixing, heat with steam to above 80°C and keep warm and stir for 7 - 8 hours; then introduce ozone at normal temperature for auxiliary inactivation; the ozone flow rate is 200 - 300 g / h, and the introduction time is more than 4 hours.

4. The inactivation treatment method according to claim 1, characterized in that, The content of tegafur in the tegafur production wastewater is 0.01 - 20 μg / mL; the alkali is sodium hydroxide, and its weight is 3 - 6% of the weight of the tegafur production wastewater.

5. The inactivation treatment method according to claim 4, wherein, During the inactivation treatment process, the alkali is added to the tegafur production wastewater, kept warm at 40 - 60°C, ozone is introduced synchronously and stirred for more than 4 hours, and the ozone flow rate is 200 - 300 g / h.

6. The inactivation treatment method according to any one of claims 1-5, characterized in that, The liquid chromatography detection uses a C18 chromatographic column, with methanol - acetonitrile - water as the mobile phase; the acid solution is neutralized to neutral.

7. An inactivation treatment device for tegafur production wastewater, characterized in that, It includes: An inactivation unit with a cavity for accommodating the solution, the inactivation unit has a solution inlet for introducing tegafur production wastewater, alkali and acid solution; the inactivation unit has a gas inlet and a solution outlet; An ozone generating device communicated with the gas inlet of the inactivation unit; A liquid chromatography detection device communicated with the solution outlet of the inactivation unit, and the solution outlet of the inactivation unit is used to discharge the solution after acid neutralization of the detection.

8. The inactivation treatment device according to claim 6, characterized in that, The inactivation treatment device further includes a corrosion - resistant high - temperature treatment unit with an inlet and an outlet, and the corrosion - resistant high - temperature treatment unit has a steam heating control device and a stirring device; The inlet of the corrosion - resistant high - temperature treatment unit is used to introduce high - concentration tegafur production wastewater and alkali, and the outlet is used to export the solution after high - temperature treatment; the corrosion - resistant high - temperature treatment unit is connected to the solution inlet of the inactivation unit via the outlet.

9. The inactivation treatment device according to claim 6, characterized in that The inactivation unit also has a steam heating control device.

10. The inactivation treatment device according to any one of claims 7-9, characterized in that, A stirring device is provided in the cavity of the inactivation unit; the liquid chromatography detection device includes a C18 chromatographic column.

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