CN117088770A - Method for separating and purifying ferrous gluconate - Google Patents
Method for separating and purifying ferrous gluconate Download PDFInfo
- Publication number
- CN117088770A CN117088770A CN202311053744.5A CN202311053744A CN117088770A CN 117088770 A CN117088770 A CN 117088770A CN 202311053744 A CN202311053744 A CN 202311053744A CN 117088770 A CN117088770 A CN 117088770A
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- CN
- China
- Prior art keywords
- ferrous gluconate
- separating
- purifying
- lactone
- delta
- 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.)
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- 239000004222 ferrous gluconate Substances 0.000 title claims abstract description 55
- 229960001645 ferrous gluconate Drugs 0.000 title claims abstract description 55
- 235000013924 ferrous gluconate Nutrition 0.000 title claims abstract description 55
- VRIVJOXICYMTAG-IYEMJOQQSA-L iron(ii) gluconate Chemical compound [Fe+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O VRIVJOXICYMTAG-IYEMJOQQSA-L 0.000 title claims abstract description 55
- 238000000034 method Methods 0.000 title claims abstract description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 74
- 239000007787 solid Substances 0.000 claims abstract description 28
- 238000001914 filtration Methods 0.000 claims abstract description 24
- 238000001035 drying Methods 0.000 claims abstract description 22
- 239000012043 crude product Substances 0.000 claims abstract description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 15
- 239000000706 filtrate Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000008213 purified water Substances 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000001291 vacuum drying Methods 0.000 claims description 8
- 239000002994 raw material Substances 0.000 claims description 5
- 238000010009 beating Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000011534 incubation Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims 3
- 239000012045 crude solution Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 description 11
- 238000004821 distillation Methods 0.000 description 7
- 238000004537 pulping Methods 0.000 description 6
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000007806 chemical reaction intermediate Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000004042 decolorization Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Crystallography & Structural Chemistry (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for separating and purifying ferrous gluconate, which comprises the steps of pouring a ferrous gluconate crude product solution into ethanol, separating out solids, filtering and drying to obtain ferrous gluconate. Compared with the prior art, the method has the advantages of milder reaction conditions, simpler step operation, shorter time consumption and lower production cost, and solves the defects of complicated process flow, complicated operation and long time consumption in the prior art.
Description
Technical Field
The invention relates to a method for separating and purifying bulk drugs, in particular to a method for separating and purifying ferrous gluconate.
Background
The currently common purification method for ferrous gluconate is recrystallization in water. CN202010600056.6 discloses a method for obtaining ferrous gluconate meeting pharmacopoeia standards through the steps of hydrolysis of glucose-delta-lactone as raw material, direct reaction of acid and iron powder, further decolorization, filtration, concentration, crystallization, centrifugation, crushing, drying and the like, wherein the purification step uses a method of recrystallization in water, and the purification process flow in the method is complex, the operation is complex, and the time is as long as 20 hours.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a method for separating and purifying ferrous gluconate, which can obtain a ferrous gluconate bulk drug with high purity and high yield.
Specifically, a method for separating and purifying ferrous gluconate is provided, wherein a ferrous gluconate crude product solution is poured into ethanol, solids are separated out, and the ferrous gluconate is obtained after filtration and drying. The invention separates the ferrous gluconate from other impurities by utilizing the solubility difference that the target product ferrous gluconate is indissolvable in ethanol and the raw material glucose-delta-lactone and the reaction intermediate such as gluconic acid are soluble in ethanol.
The ethanol solution is 3-12 times of the volume of the raw material glucose-delta-lactone for generating ferrous gluconate by reaction. Ethanol solution 75-100% volume fraction
Pouring the ferrous gluconate crude product solution into ethanol and standing for 1-2 h.
In the drying, a vacuum drying oven is adopted, the drying temperature is 80-95 ℃, the pressure is 100-1000 mbar, and the drying time is 8-20 h. Preferably, the drying temperature is 90℃and the pressure is 500mbar and the drying time is 16h.
The preparation of the ferrous gluconate crude product comprises the following steps: placing glucose-delta-lactone and purified water in a reactor, heating to 90 ℃, stirring to dissolve and hydrolyze the glucose-delta-lactone and the purified water into acid, adding excessive reduced iron powder, reacting for 1.5-3.5 h at a constant temperature, filtering, and taking filtrate to obtain the glucose-delta-lactone.
Purified water is 1.5 to 6 times, preferably 3 times, the mass of the glucose-delta-lactone.
The incubation time is preferably 2h.
Further, the invention also comprises a beating step, namely adding ethanol into the solid obtained by filtering, beating, filtering and drying the solid.
Further, the invention also comprises a step of recovering ethanol, in particular, the ethanol can be recovered by a distillation method.
The invention has the technical effects that:
the invention separates the ferrous gluconate from other impurities by utilizing the solubility difference that the target product ferrous gluconate is indissolvable in ethanol and the raw material glucose-delta-lactone and the reaction intermediate such as gluconic acid are soluble in ethanol. In the process, a plurality of purification steps such as decoloration, filtration, concentration, centrifugation and the like in the current common method are omitted, and only 2 purification steps such as ethanol crystallization, filtration and drying are needed, so that the consumption of about 10 hours is reduced. The obtained ferrous gluconate has high yield of more than 80%, high purity of more than 97%, ferrous gluconate meeting pharmacopoeia standards, and the used ethanol can be recovered, so that the material cost is reduced.
Detailed Description
The technical scheme of the present invention will be described in further detail below with reference to the specific embodiments, but the present invention is not limited thereto.
Example 1
Purified water, 3 times the weight of glucose-delta-lactone, was added to the reactor, warmed to 90 ℃, stirred to dissolve and hydrolyze to acid. Adding 0.25 times of reduced iron powder into the solution, and reacting for 1.5h at a constant temperature.
Filtering to remove residual iron powder, and obtaining filtrate which is the ferrous gluconate crude product solution. The filtrate was added to a 95% volume fraction ethanol solution of 6 times the mass of glucose-delta-lactone, allowed to stand for 2 hours, and the solid was precipitated, filtered through 10 μm filter paper with suction, and collected. Pulping with ethanol for 0.33 hr, filtering, and drying the solid in vacuum drying oven at 90deg.C and 500mbar for 16 hr to obtain ferrous gluconate solid. The preparation took 19.83 hours altogether. The ethanol solution used in the purification process can be recovered after distillation treatment and reused.
The product yield is 85% and the ferrous gluconate content is 97%.
Example 2
Purified water, 1.5 times the weight of glucose-delta-lactone, was added to the reactor, warmed to 90 ℃, stirred to dissolve and hydrolyze to acid. Adding 0.25 times of reduced iron powder into the solution, and reacting for 2h under heat preservation.
Filtering to remove residual iron powder, and obtaining filtrate which is the ferrous gluconate crude product solution. The filtrate was added to a 95% volume fraction ethanol solution 3 times the mass of glucose-delta-lactone, allowed to stand for 1.5 hours, solids were precipitated, filtered through 10 μm filter paper, and the solids were collected. Pulping with ethanol for 0.33 hr, filtering, and drying the solid in vacuum drying oven at 90deg.C and 500mbar for 16 hr to obtain ferrous gluconate solid. The preparation took 19.83 hours altogether. The ethanol solution used in the purification process can be recovered after distillation treatment and reused.
The product yield is 87%, and the content of ferrous gluconate is 101%.
Example 3
Purified water, 6 times the weight of glucose-delta-lactone, was added to the reactor, warmed to 90 ℃, stirred to dissolve and hydrolyze to acid. Adding 0.25 times of reduced iron powder into the solution, and reacting for 2.5h at a constant temperature.
Filtering to remove residual iron powder, and obtaining filtrate which is the ferrous gluconate crude product solution. The filtrate was added to a 95% volume fraction ethanol solution of 12 times the mass of glucose-delta-lactone, allowed to stand for 1h, solids were precipitated, filtered through 10 μm filter paper, and the solids were collected. Pulping with ethanol for 0.33 hr, filtering, and drying the solid in vacuum drying oven at 90deg.C and 500mbar for 16 hr to obtain ferrous gluconate solid. The preparation took 19.83 hours altogether. The ethanol solution used in the purification process can be recovered after distillation treatment and reused.
The product yield is 86%, and the content of ferrous gluconate is 98%.
Example 4
Purified water, 6 times the weight of glucose-delta-lactone, was added to the reactor, warmed to 90 ℃, stirred to dissolve and hydrolyze to acid. Adding 0.25 times of reduced iron powder into the solution, and reacting for 3h under heat preservation.
Filtering to remove residual iron powder, and obtaining filtrate which is the ferrous gluconate crude product solution. The filtrate was added to a 75% volume fraction ethanol solution of 12 times the mass of glucose-delta-lactone, allowed to stand for 2 hours, and the solid was precipitated, filtered through 10 μm filter paper with suction, and collected. Pulping with ethanol for 0.33 hr, filtering, and drying the solid in vacuum drying oven at 90deg.C and 500mbar for 16 hr to obtain ferrous gluconate solid. The preparation takes 21.33h in total. The ethanol solution used in the purification process can be recovered after distillation treatment and reused.
The product yield is 83% and the ferrous gluconate content is 100%.
Example 5
Purified water, 6 times the weight of glucose-delta-lactone, was added to the reactor, warmed to 90 ℃, stirred to dissolve and hydrolyze to acid. Adding 0.25 times of reduced iron powder into the solution, and reacting for 3.5h at a constant temperature.
Filtering to remove residual iron powder, and obtaining filtrate which is the ferrous gluconate crude product solution. The filtrate was added to a 100% volume fraction ethanol solution of 10 times the mass of glucose-delta-lactone, allowed to stand for 1h, solids were precipitated, filtered through 10 μm filter paper, and the solids were collected. Pulping with ethanol for 0.33 hr, filtering, and drying the solid in vacuum drying oven at 90deg.C and 500mbar for 16 hr to obtain ferrous gluconate solid. The preparation took 20.83 hours altogether. The ethanol solution used in the purification process can be recovered after distillation treatment and reused.
The product yield is 84% and the ferrous gluconate content is 99%.
Example 6
Purified water, 6 times the weight of glucose-delta-lactone, was added to the reactor, warmed to 90 ℃, stirred to dissolve and hydrolyze to acid. Adding 0.25 times of reduced iron powder into the solution, and reacting for 3.5h at a constant temperature.
Filtering to remove residual iron powder, and obtaining filtrate which is the ferrous gluconate crude product solution. The filtrate was added to a 90% volume fraction ethanol solution of 8 times the mass of glucose-delta-lactone, allowed to stand for 2 hours, and the solid was precipitated, filtered through 10 μm filter paper with suction, and collected. Pulping with ethanol for 0.33 hr, filtering, and drying the solid in vacuum drying oven at 90deg.C and 500mbar for 16 hr to obtain ferrous gluconate solid. The preparation took 21.83 hours altogether. The ethanol solution used in the purification process can be recovered after distillation treatment and reused.
The product yield is 83% and the ferrous gluconate content is 100%.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
1. A method for separating and purifying ferrous gluconate is characterized in that a ferrous gluconate crude product solution is poured into ethanol, solids are separated out, and the ferrous gluconate is obtained after filtration and drying.
2. The method for separating and purifying ferrous gluconate according to claim 1, wherein the ethanol solution is used in an amount of 3-12 times by volume of the raw material glucose-delta-lactone that reacts to form ferrous gluconate.
3. The method for separating and purifying ferrous gluconate according to claim 1, wherein the volume fraction of the ethanol solution is 75-100%.
4. The method for separating and purifying ferrous gluconate according to claim 1, wherein the crude solution of ferrous gluconate in comfort mode is poured into ethanol and allowed to stand for 1-2 hours.
5. The method for separating and purifying ferrous gluconate according to claim 1, wherein a vacuum drying oven is used in the drying process, the drying temperature is 80-95 ℃, the pressure is 100-1000 mbar, and the drying time is 8-20 h.
6. The method for separating and purifying ferrous gluconate according to claim 5, wherein the drying is performed at 90 ℃ under a pressure of 500mbar for 16 hours.
7. The method for separating and purifying ferrous gluconate according to claim 1, wherein the preparation of the crude ferrous gluconate product is as follows: placing glucose-delta-lactone and purified water in a reactor, heating to 90 ℃, stirring to dissolve and hydrolyze the glucose-delta-lactone and the purified water into acid, adding excessive reduced iron powder, reacting for 1.5-3.5 h at a constant temperature, filtering, and taking filtrate to obtain the glucose-delta-lactone.
8. The method for separating and purifying ferrous gluconate according to claim 7, wherein the purified water is 1.5 to 6 times the mass of glucose-delta-lactone.
9. The method for separating and purifying ferrous gluconate according to claim 7, wherein the incubation time is preferably 2 hours.
10. The method for separating and purifying ferrous gluconate according to claim 1, further comprising a beating step of adding ethanol to the solid obtained by the filtration, beating, filtering, and drying the solid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311053744.5A CN117088770A (en) | 2023-08-21 | 2023-08-21 | Method for separating and purifying ferrous gluconate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311053744.5A CN117088770A (en) | 2023-08-21 | 2023-08-21 | Method for separating and purifying ferrous gluconate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117088770A true CN117088770A (en) | 2023-11-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311053744.5A Pending CN117088770A (en) | 2023-08-21 | 2023-08-21 | Method for separating and purifying ferrous gluconate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117088770A (en) |
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2023
- 2023-08-21 CN CN202311053744.5A patent/CN117088770A/en active Pending
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