CN118184529A - Preparation method of low-chloride mesalazine - Google Patents
Preparation method of low-chloride mesalazine Download PDFInfo
- Publication number
- CN118184529A CN118184529A CN202410308965.0A CN202410308965A CN118184529A CN 118184529 A CN118184529 A CN 118184529A CN 202410308965 A CN202410308965 A CN 202410308965A CN 118184529 A CN118184529 A CN 118184529A
- Authority
- CN
- China
- Prior art keywords
- mesalazine
- acid
- mesalamine
- solution
- chloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 title claims abstract description 118
- 229960004963 mesalazine Drugs 0.000 title claims abstract description 116
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 56
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 34
- 239000002253 acid Substances 0.000 claims abstract description 26
- 101001015517 Betula pendula Germin-like protein 1 Proteins 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 23
- 239000000047 product Substances 0.000 claims abstract description 23
- 238000002156 mixing Methods 0.000 claims abstract description 19
- 238000001816 cooling Methods 0.000 claims abstract description 14
- 238000002425 crystallisation Methods 0.000 claims abstract description 13
- 230000008025 crystallization Effects 0.000 claims abstract description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000008213 purified water Substances 0.000 claims description 17
- 239000000706 filtrate Substances 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 235000011054 acetic acid Nutrition 0.000 claims description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 235000011007 phosphoric acid Nutrition 0.000 claims description 3
- 239000012043 crude product Substances 0.000 abstract description 12
- 230000001105 regulatory effect Effects 0.000 abstract description 5
- 238000006386 neutralization reaction Methods 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 4
- 239000003513 alkali Substances 0.000 abstract description 3
- 238000006073 displacement reaction Methods 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 50
- 238000011282 treatment Methods 0.000 description 24
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000003918 potentiometric titration Methods 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 238000007065 Kolbe-Schmitt synthesis reaction Methods 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- -1 amino, hydroxyl Chemical group 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 230000002884 effect on inflammation Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000008237 rinsing water Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of chemical medicines, and particularly relates to a method for preparing mesalazine with low chloride. Firstly, mixing an acid and a decolored mesalazine crude product solution, and then, adjusting the pH value of a system to 2.5-3.0 by using sodium hydroxide, and then, cooling; in the process of regulating the pH value of a system, sodium hydroxide is firstly subjected to neutralization reaction with acid to produce salt, and then the salt is subjected to displacement reaction with mesalamine hydrochloride to remove chloride in a mesalamine crude product; the preparation method provided by the invention avoids direct contact between strong acid and strong alkali, thereby reducing a large amount of packed chloride of the product during crystallization and improving the purity of the product. Meanwhile, the invention uses less concentrated hydrochloric acid to dissolve the mesalamine Qin Cupin, introduces less chloride ions into the system, and is beneficial to purification.
Description
Technical Field
The invention belongs to the technical field of chemical medicines, and particularly relates to a method for preparing mesalazine with low chloride.
Background
The mesalazine is mainly used for maintenance treatment of light and medium ulcerative colitis, and has remarkable inhibition effect on inflammation of intestinal walls. In addition, the mesalazine structure contains three active reactive groups of amino, hydroxyl and carboxyl, so that various reactions can be carried out, and the mesalazine structure can be used for preparing various active dyes with excellent quality in the field of dye industry.
There are many reports on the synthesis method of mesalazine at present, such as a nitro reduction method, an aniline synthesis method, a Kolbe-Schmitt synthesis method and the like, but more chloride remains in mesalazine prepared according to the existing preparation method, so that the purity of mesalazine is reduced to affect the performance of mesalazine. The existing report of a purification method for a mesalazine crude product mainly comprises the following patents: EP3044203 discloses a process for the production of mesalazine having a bulk density of greater than or equal to 0.30g/mL, which is substantially solvent free: the mesalamine is dissolved in aqueous hydrochloric acid to obtain acidic mesalamine hydrochloride solution with the pH value less than 2.0, and then the mesalamine hydrochloride solution is added into the aqueous solution of a buffer system of acetic acid and sodium acetate, the pH value is 3.5-4.5, so as to improve the pH value of the solution and promote the mesalamine crystallization with the bulk density greater than or equal to 0.30 g/mL. IN376069 discloses that inorganic acid is added into alkaline solution of mesalazine, the temperature range is 25-65 ℃, active carbon is added into the acidic solution of mesalazine, decolorization is carried out, filtrate is obtained by filtering, and then alkaline water solution is added, and the pH value is adjusted to be 2.5-5.0. Crystallizing and separating to obtain mesalazine. Wo2015036920A1 discloses a crystallization process for preparing high tightness using acetic acid and sodium acetate buffer systems. Wo2023144678 discloses a process for purifying 5-aminosalicylic acid (mesalazine), preparing an aqueous solution or suspension of 5-aminosalicylic acid, optionally adding at least one solvent, adding a base, adjusting the pH to 6-9, adding an acid to the solution obtained until the pH is 3.2-5.2, preferably between 4.3-4.6, and then precipitating mesalazine.
Although the existing method can purify mesalamine to a certain extent, the treated product still contains more chloride (the chloride content is more than 300 ppm).
Disclosure of Invention
In view of the above, the invention provides a method for preparing mesalazine with low chloride, and the method provided by the invention can be used for purifying mesalazine crude product to effectively remove chloride in mesalazine crude product and greatly improve the purity of mesalazine.
In order to solve the technical problems, the invention provides a method for preparing mesalazine with low chloride, which comprises the following steps:
Mixing mesalamine Qin Cupin, purified water and concentrated hydrochloric acid solution to obtain mesalamine Qin Cupin solution; the mass concentration of the concentrated hydrochloric acid solution is 28-36%, and the molar ratio of the hydrogen chloride to the mesalamine Qin Cupin in the concentrated hydrochloric acid solution is 1.05-1.2:1;
Mixing the mesalamine Qin Cupin solution with activated carbon, decoloring and filtering to obtain filtrate;
and (3) mixing the filtrate with acid, then dropwise adding sodium hydroxide solution, controlling the pH value to be 2.5-3.0, and then cooling and crystallizing to obtain the mesalazine refined product.
Preferably, the acid comprises formic acid, acetic acid, phosphoric acid or benzoic acid.
Preferably, the mass ratio of the acid to the purified water is 0.1-5:100.
Preferably, the mass concentration of the sodium hydroxide solution is 5-30%.
Preferably, the dropping rate is 80-100 mL/h.
Preferably, the temperature of the dripping is 60-70 ℃.
Preferably, the mixing of mesalamine Qin Cupin, purified water and concentrated hydrochloric acid solution is performed under stirring at a temperature of 60 to 70 ℃.
Preferably, the mass ratio of the purified water to the crude mesalazine product is 18-22:1.
Preferably, the temperature of the cooling crystallization is 5-15 ℃ and the time is 2-4 h.
Preferably, the mass ratio of the active carbon to the mesalazine crude product is 2.4-2.6:100.
The invention provides a method for preparing low-chloride mesalazine, which comprises the following steps: mixing mesalamine Qin Cupin, purified water and concentrated hydrochloric acid solution to obtain mesalamine Qin Cupin solution; the mass concentration of the concentrated hydrochloric acid solution is 28-36%, and the molar ratio of the hydrogen chloride to the mesalamine Qin Cupin in the concentrated hydrochloric acid solution is 1.05-1.2:1; mixing the mesalamine Qin Cupin solution with activated carbon, decoloring and filtering to obtain filtrate; and (3) mixing the filtrate with acid, then dropwise adding sodium hydroxide solution, controlling the pH value to be 2.5-3.0, and then cooling and crystallizing to obtain the mesalazine refined product. Firstly, mixing an acid and a decolored mesalazine crude product solution, and then, cooling by utilizing a pH value of a sodium hydroxide regulating system; in the process of regulating the pH value of a system, sodium hydroxide is firstly subjected to neutralization reaction with acid to produce salt, and then the salt is subjected to displacement reaction with mesalamine hydrochloride to remove chloride in a mesalamine crude product; the preparation method provided by the invention avoids direct contact between strong acid and strong alkali, thereby reducing a large amount of packed chloride of the product during crystallization and improving the purity of the product. Meanwhile, the invention uses less concentrated hydrochloric acid solution to dissolve the crude mesalamine product, introduces less chloride ions into the system, and is beneficial to purification.
Drawings
FIG. 1 is a schematic flow chart of a chemical reaction occurring during the process of adjusting the pH value of a system by using sodium hydroxide solution by taking acid as an example of acetic acid;
FIG. 2 is an HPLC plot of mesalazine after treatment of example 1;
FIG. 3 is a potentiometric chloride profile of mesalazine after treatment of example 1;
FIG. 4 is an HPLC plot of mesalazine after treatment of example 2;
FIG. 5 is a potentiometric chloride profile of mesalazine after treatment of example 2;
FIG. 6 is an HPLC plot of mesalazine after treatment of example 3;
FIG. 7 is a potentiometric chloride profile of mesalazine after treatment of example 3;
FIG. 8 is an HPLC plot of mesalazine after treatment of example 4;
fig. 9 is a potentiometric chloride content profile of mesalazine after treatment of example 4;
Fig. 10 is an HPLC profile of mesalazine after treatment of comparative example 1;
fig. 11 is a potentiometric chloride content profile of mesalazine after treatment of comparative example 1.
Detailed Description
The invention provides a method for preparing mesalazine with low chloride, which comprises the following steps:
Mixing mesalamine Qin Cupin, purified water and concentrated hydrochloric acid solution to obtain mesalamine Qin Cupin solution; the mass concentration of the concentrated hydrochloric acid solution is 28-36%, and the molar ratio of the hydrogen chloride to the mesalamine Qin Cupin in the concentrated hydrochloric acid solution is 1.05-1.2:1;
Mixing the mesalamine Qin Cupin solution with activated carbon, decoloring and filtering to obtain filtrate;
and (3) mixing the filtrate with acid, then dropwise adding sodium hydroxide solution, controlling the pH value to be 2.5-3.0, and then cooling and crystallizing to obtain the mesalazine refined product.
The invention mixes mesalazine Qin Cupin, purified water and concentrated hydrochloric acid solution to obtain mesalazine crude product solution. In the invention, the purity of the mesalazine crude product is preferably 98-99%. In the invention, the mass ratio of the purified water to the crude mesalazine product is preferably 18-22:1, more preferably 20:1. In the invention, the mass concentration of the concentrated hydrochloric acid solution is 28-36%, preferably 30-32%; the molar ratio of the hydrogen chloride to the mesalamine Qin Cupin in the concentrated hydrochloric acid solution is 1.05-1.2:1, preferably 1.05-1.1:1.
In the present invention, the mixing of mesalamine Qin Cupin, purified water and concentrated hydrochloric acid solution is preferably performed under stirring conditions, the temperature of which is preferably 60 to 70 ℃, more preferably 63 to 68 ℃. The invention has no special requirements on the rotation speed and time of stirring, and only needs to be capable of completely clarifying the solution by dissolving.
After the mesalamine Qin Cupin solution is obtained, the mesalamine crude product solution is mixed with active carbon, decolorized and filtered to obtain filtrate. In the invention, the mass ratio of the active carbon to the crude mesalazine product is preferably 2.4-2.6:100, more preferably 2.5:100. In the present invention, the decoloring is preferably carried out with stirring, and the decoloring time is preferably 25 to 35 minutes, more preferably 30 minutes. The invention has special requirements on the filtration, and can be realized by adopting a conventional mode in the field.
After the filtrate is obtained, the filtrate is mixed with acid, then sodium hydroxide solution is dripped, the pH value is controlled to be 2.5-3.0, and cooling crystallization is carried out, so that the mesalazine essence is obtained. In the present invention, the acid preferably includes formic acid, acetic acid, phosphoric acid or benzoic acid, more preferably acetic acid or phosphoric acid. In the invention, the acid can react with sodium hydroxide to form a buffer system, so that the problem of chloride encapsulation is prevented when more chloride ions are subjected to neutralization reaction between HCl and NaOH. In the present invention, the mass ratio of the acid to the purified water is preferably 0.1 to 5:100, more preferably 0.1 to 1:100, still more preferably 0.25 to 0.4:100. The invention has no special requirement on the mixing of the filtrate and the acid, and the filtrate and the acid can be uniformly mixed.
In the present invention, the mass concentration of the sodium hydroxide solution is preferably 5 to 30%, more preferably 10 to 20%. In the present invention, the rate of the dropping is preferably 80 to 100mL/h, more preferably 80 to 90mL/h. In the present invention, the temperature of the dropping is preferably 60 to 70 ℃, more preferably 65 to 68 ℃. In the present invention, the pH of the system after dropping sodium hydroxide solution is 2.5 to 3.0, preferably 2.6 to 2.8. The amount of the sodium hydroxide solution used in the present invention is not particularly limited as long as the desired pH value can be achieved.
Fig. 1 is a schematic flow chart of chemical reaction in the process of adjusting the pH of a system by using sodium hydroxide solution, taking acid as acetic acid as an example, specifically: firstly, acetic acid and sodium hydroxide are subjected to neutralization reaction to generate sodium acetate, and the sodium acetate and mesalazine hydrochloride are subjected to displacement reaction to generate mesalazine; in the reaction process, direct contact between strong acid (HCl in mesalazine hydrochloride) and strong base (sodium hydroxide) is avoided, and the reaction rate is reduced, so that the situation that the crystallization product wraps up the chloride in a large amount due to too fast crystallization is avoided, and the purity of the crystallization product is improved.
In the present invention, the temperature of the cooling crystallization is preferably 5 to 15 ℃, more preferably 8 to 12 ℃; the cooling crystallization time is preferably 2 to 4 hours, more preferably 2 to 3 hours.
The cooling crystallization in the present invention preferably further comprises: and carrying out solid-liquid separation on the cooled and crystallized system, and sequentially washing and drying the solid obtained by the solid-liquid separation to obtain the mesalazine refined product. In the present invention, the solid-liquid separation is preferably filtration. In the present invention, the water for washing is preferably purified water; the water washing is preferably rinsing, and the mass of the rinsing water is preferably 90 to 110g, more preferably 100g. The present invention has no special requirement for the drying, as long as the solvent on the solid surface can be removed.
In the present invention, the residual amount of chloride in the fine mesalazine product is preferably 200ppm or less, more preferably 89 to 152ppm.
The technical solutions provided by the present invention are described in detail below in conjunction with examples for further illustrating the present invention, but they should not be construed as limiting the scope of the present invention.
Example 1
800G of purified water, 40g (0.261 mol) of crude mesalazine product and 34.92g (0.287 mol) of concentrated hydrochloric acid solution with the mass concentration of 30% are stirred and mixed to be dissolved at 60 ℃ to obtain mesalazine Qin Cupin solution;
Mixing the mesalazine crude product solution with 1g of active carbon, stirring and decoloring for 30min, and then thermally filtering to obtain filtrate;
Adding 3.2g of acetic acid into the filtrate, dropwise adding 10% sodium hydroxide solution at the dropwise adding rate of 85mL/h at 60 ℃, regulating the pH value of the system to 2.8, cooling to 10 ℃, cooling and crystallizing for 3h, filtering, leaching the solid obtained by filtering with 100g of purified water, and drying to obtain the mesalamine refined product.
Example 2
Crude mesalazine was treated as in example 1, except that 3.2g of acetic acid was replaced with 2.5g of formic acid, and the sodium hydroxide solution having a mass concentration of 10% was replaced with a sodium hydroxide solution having a mass concentration of 5%.
Example 3
Crude mesalazine was treated as in example 1, except that 3.2g of acetic acid was replaced with 3g of phosphoric acid.
Example 4
Crude mesalazine was treated as in example 1, except that 3.2g of acetic acid was replaced with 2g of benzoic acid.
Comparative example 1
Crude mesalazine was treated as in example 1, except that no acid was added (3.2 g of acetic acid addition was omitted);
the equation of the reaction of the coarse mesalazine product and mesalazine hydrochloride with sodium hydroxide by using the concentrated hydrochloric acid solution is shown as the formula 1:
The yields of mesalazine after the treatment in examples 1 to 4 and comparative example 1 were calculated, and the results thereof are shown in table 1; the purity of mesalazine after the treatment in examples 1 to 4 and comparative example 1 was measured by High Performance Liquid Chromatography (HPLC), and the results are shown in table 1; the chloride content of mesalazine after the treatments of examples 1 to 4 and comparative example 1 was measured by potentiometric titration and visual colorimetry, and the results are shown in table 1.
Table 1 characterization parameters of refined mesalazine products after treatment in examples 1 to 4 and comparative example 1
Fig. 2 is an HPLC profile of mesalazine after treatment of example 1, and fig. 3 is a potentiometric titration chloride content profile of mesalazine after treatment of example 1; fig. 4 is an HPLC profile of mesalazine after treatment of example 2, and fig. 5 is a potentiometric titration chloride content profile of mesalazine after treatment of example 2; fig. 6 is an HPLC profile of mesalazine after treatment of example 3, and fig. 7 is a potentiometric titration chloride content profile of mesalazine after treatment of example 3; fig. 8 is an HPLC profile of mesalazine after treatment of example 4, and fig. 9 is a potentiometric titration chloride content profile of mesalazine after treatment of example 4; fig. 10 is an HPLC profile of mesalazine after treatment of comparative example 1, and fig. 11 is a potentiometric titration chloride content profile of mesalazine after treatment of comparative example 1.
As can be seen by combining Table 1 with FIGS. 2-11, the chloride content in mesalazine treated according to the method provided by the invention is lower than 200 ppm. In comparative example 1, the pH is directly regulated by sodium hydroxide solution, the strong acid and the strong alkali are in quick contact reaction, the product precipitation speed is too high, the precipitated product is caused to instantly wrap chloride, and the residual amount of the chloride in mesalazine is improved.
Although the foregoing embodiments have been described in some, but not all, embodiments of the invention, it should be understood that other embodiments may be devised in accordance with the present embodiments without departing from the spirit and scope of the invention.
Claims (10)
1. A method for preparing mesalazine with low chloride, comprising the following steps:
Mixing mesalamine Qin Cupin, purified water and concentrated hydrochloric acid solution to obtain mesalamine Qin Cupin solution; the mass concentration of the concentrated hydrochloric acid solution is 28-36%, and the molar ratio of the hydrogen chloride to the mesalamine Qin Cupin in the concentrated hydrochloric acid solution is 1.05-1.2:1;
Mixing the mesalamine Qin Cupin solution with activated carbon, decoloring and filtering to obtain filtrate;
and (3) mixing the filtrate with acid, then dropwise adding sodium hydroxide solution, controlling the pH value to be 2.5-3.0, and then cooling and crystallizing to obtain the mesalazine refined product.
2. The method of claim 1, wherein the acid comprises formic acid, acetic acid, phosphoric acid, or benzoic acid.
3. The preparation method according to claim 1 or 2, wherein the mass ratio of the acid to the purified water is 0.1 to 5:100.
4. The preparation method according to claim 1, wherein the mass concentration of the sodium hydroxide solution is 5-30%.
5. The method according to claim 1 or 4, wherein the dropping rate is 80 to 100mL/h.
6. The method according to claim 1 or 5, wherein the dropping temperature is 60 to 70 ℃.
7. The preparation method according to claim 1, wherein the mixing of mesalamine Qin Cupin, purified water and concentrated hydrochloric acid solution is performed under stirring conditions, the temperature of which is 60 to 70 ℃.
8. The preparation method according to claim 1 or 7, wherein the mass ratio of the purified water to the crude mesalazine is 18-22:1.
9. The method according to claim 1, wherein the cooling crystallization is carried out at a temperature of 5 to 15 ℃ for a time of 2 to 4 hours.
10. The preparation method according to claim 1, wherein the mass ratio of the active carbon to the crude mesalazine is 2.4-2.6:100.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410308965.0A CN118184529A (en) | 2024-03-19 | 2024-03-19 | Preparation method of low-chloride mesalazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410308965.0A CN118184529A (en) | 2024-03-19 | 2024-03-19 | Preparation method of low-chloride mesalazine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118184529A true CN118184529A (en) | 2024-06-14 |
Family
ID=91394063
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410308965.0A Pending CN118184529A (en) | 2024-03-19 | 2024-03-19 | Preparation method of low-chloride mesalazine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118184529A (en) |
-
2024
- 2024-03-19 CN CN202410308965.0A patent/CN118184529A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2046709B1 (en) | A process for producing succinic acid | |
| CN118184529A (en) | Preparation method of low-chloride mesalazine | |
| CN112552167B (en) | Preparation method of calcium gluconate | |
| CN107400069B (en) | Preparation method of lauroyl arginine ethyl ester hydrochloride | |
| CN114989055B (en) | Preparation method of N-acetyl-L-cysteine | |
| JP7430944B2 (en) | Method for producing acetylated sodium hyaluronate | |
| CN113336640B (en) | Method for reducing content of 1, 4-naphthalenedicarboxylic acid impurities | |
| CN113801031B (en) | Purification method of pregabalin | |
| CN108752230B (en) | Synthesis method of key intermediate of contrast agent iodixanol impurity E | |
| CN1294124A (en) | Process for preparing high-purity thiourea | |
| CN110713444A (en) | Preparation method of caprylyl hydroximic acid | |
| CN1076725C (en) | Process for preparing sodium lactate | |
| CN113979886B (en) | Protective amino acid with side chain being amide and preparation method thereof | |
| CN112375031B (en) | Preparation method of cilnidipine | |
| CN114560782B (en) | Preparation method of high-purity leucine | |
| CN112661727B (en) | Purification method of 7- (2, 2-trichloroethyl oxycarbonyl) taxol | |
| CN111302982B (en) | Preparation method of DL-p-methylsulfonyl phenyl serine ester | |
| CN112876440B (en) | Synthetic method of sodium dehydroacetate | |
| CN118324674A (en) | Method for removing tyrosine impurities in carbocisteine | |
| CN110857279B (en) | Preparation method of 2-acrylamide-2-methylpropanesulfonic acid | |
| CN117342960A (en) | Preparation method and application of pentetic acid | |
| CN115521221A (en) | Method for refining levodopa | |
| CN117700383A (en) | Method for improving quality and yield of 2-keto-L-gulonic acid conversion product | |
| CN118271214A (en) | Synthesis method of p-methylsulfonyl phenylserine ethyl ester | |
| CN118255669A (en) | Nitroanthraquinone purification method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination |