CN113045409A - Crystallization method of calcium gluconate for injection - Google Patents
Crystallization method of calcium gluconate for injection Download PDFInfo
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- CN113045409A CN113045409A CN202110319196.0A CN202110319196A CN113045409A CN 113045409 A CN113045409 A CN 113045409A CN 202110319196 A CN202110319196 A CN 202110319196A CN 113045409 A CN113045409 A CN 113045409A
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- CN
- China
- Prior art keywords
- calcium carbonate
- calcium gluconate
- calcium
- drying
- hours
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- 229960004494 calcium gluconate Drugs 0.000 title claims abstract description 25
- 239000004227 calcium gluconate Substances 0.000 title claims abstract description 25
- 235000013927 calcium gluconate Nutrition 0.000 title claims abstract description 25
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 title claims abstract description 25
- 238000002425 crystallisation Methods 0.000 title claims abstract description 16
- 238000002347 injection Methods 0.000 title claims abstract description 8
- 239000007924 injection Substances 0.000 title claims abstract description 8
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 30
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 9
- 239000000706 filtrate Substances 0.000 claims abstract description 9
- 239000000047 product Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000013078 crystal Substances 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 238000004537 pulping Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 4
- 239000008187 granular material Substances 0.000 claims abstract description 3
- 238000004042 decolorization Methods 0.000 claims description 8
- 235000012209 glucono delta-lactone Nutrition 0.000 claims description 4
- 229960003681 gluconolactone Drugs 0.000 claims description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 3
- 239000000182 glucono-delta-lactone Substances 0.000 claims description 3
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 2
- 239000000174 gluconic acid Substances 0.000 claims description 2
- 235000012208 gluconic acid Nutrition 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 238000006911 enzymatic reaction Methods 0.000 abstract 1
- 229940090044 injection Drugs 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 3
- 206010006956 Calcium deficiency Diseases 0.000 description 2
- 208000003217 Tetany Diseases 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 208000005223 Alkalosis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229910001339 C alloy Inorganic materials 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 208000013558 Developmental Bone disease Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010016818 Fluorosis Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 206010072610 Skeletal dysplasia Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002340 alkalosis Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940070006 calcium gluconate injection Drugs 0.000 description 1
- 229940040682 calcium gluconate monohydrate Drugs 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- XLNFVCRGJZBQGX-XRDLMGPZSA-L calcium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;hydrate Chemical compound O.[Ca+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 XLNFVCRGJZBQGX-XRDLMGPZSA-L 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000004042 dental fluorosis Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 238000003756 stirring 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
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a crystallization method of calcium gluconate for injection, which comprises the steps of firstly pulping calcium carbonate, dissolving gluconic acid-delta lactone in water, adding activated carbon for decoloring, filtering after decoloring, pouring filtrate into the pulped calcium carbonate, reacting the filtrate with the pulped calcium carbonate, and adding the activated carbon for decoloring after reacting for 1 hour; filtering to obtain calcium gluconate solution; standing, cooling and crystallizing, adding seed crystal after reaching a certain temperature, and continuously crystallizing for 20 hours. Centrifuging, finishing granules and drying to obtain the finished product of the calcium gluconate. The method is simple to operate, the used solvent is only water, the environmental pollution is reduced, and the problem of solution residue in the product is avoided; meanwhile, an enzymatic method and an expensive catalyst are not adopted, so that the cost is reduced, and the labor force is reduced.
Description
Technical Field
The invention belongs to the technical field of medicine production, and particularly relates to a crystallization method of calcium gluconate.
Background
Calcium gluconate monohydrate with molecular formula of Ca (C)6H11O7)2.H2O, the structural formula is shown as I. The product is white crystalA powder of a neutral or particulate nature, the aqueous solution being neutral (pH about 6-7). It is mainly used as calcium fortifier, nutrient, buffering agent, solidifying agent and chelating agent of food. It can also be used for preventing and treating calcium deficiency, such as osteoporosis, tetany, bone dysplasia, rickets, and calcium supplement for children, pregnant and lactating women, menopausal women, and the elderly. The calcium gluconate injection is used for treating tetany disease caused by calcium deficiency, acute hypercalcemia, alkalosis and parathyroid hypofunction; allergic diseases; relief of magnesium poisoning; relief of fluorosis, etc.
At present, the domestic production methods of calcium gluconate comprise an enzymolysis method, a fermentation method and the like. The calcium gluconate needs to be concentrated during crystallization, and the obtained calcium gluconate has the problems of poor clarity, low content and the like.
In patent CN108611378A, a method for continuous cooling and rapid crystallization is disclosed, in which oxidase and catalase are used, which are easily contaminated to breed bacteria, resulting in failure of reaction. And the continuous stirring in the crystallization process can lead the crystallization to be too fine and not easy to be centrifuged.
Patent CN110452111A mentions another crystallization method of calcium gluconate, the first production process adopts palladium carbon alloy as catalyst, which increases the cost, and in addition, the alcohol solvent is added into the calcium gluconate filtrate, and the problem of solvent residue exists in the generated calcium gluconate.
In order to solve the problems, the invention provides a calcium gluconate crystallization method.
Disclosure of Invention
The invention provides a crystallization method of injection calcium gluconate, which comprises the following steps: firstly, pulping calcium carbonate, dissolving glucono-delta lactone in water and adding activated carbon for decolorization; filtering after the decolorization is finished, pouring the filtrate into the calcium carbonate which is being pulped, reacting the filtrate and the calcium carbonate, and adding activated carbon for decolorization after reacting for 1 hour; filtering to obtain calcium gluconate solution; standing, cooling and crystallizing, and adding seed crystals after reaching a certain temperature; and continuously crystallizing for 20 hours, centrifuging, finishing granules and drying to obtain a finished product of the calcium gluconate.
In the crystallization method of the calcium gluconate for injection, the calcium carbonate adopts medicinal grade, and the pulping solvent is water; the time is more than 30 minutes.
The gluconic acid-delta lactone decoloration temperature is 50-60 ℃, and the time is 30 minutes.
The reaction temperature of the calcium carbonate and the gluconic acid is 50-60 ℃.
The second decolorization time was 30 minutes.
According to the crystallization method of the calcium gluconate for the injection, the crystal seed amount is 0.01 percent of the weight ratio of gluconic acid-delta lactone at 45 ℃.
The crystallization method of the injection calcium gluconate is characterized in that the drying is carried out for 16 hours at room temperature, then for 24 hours at 30-35 ℃, and finally for 8 hours at 50-55 ℃.
The invention aims to provide a crystallization method of calcium gluconate, which solves the problems of complex operation in the production process, poor clarity of the obtained finished product and the like.
The method has the advantages of simple operation, avoidance of distillation and concentration processes, labor force reduction, avoidance of the problem of solvent residue in the product due to the fact that the used solvent is only water, and reduction of environmental pollution.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Example 1
Adding 18.3g of calcium carbonate and 50mL of water into a 500mL four-mouth bottle, and pulping at room temperature; and adding 50g of gluconolactone, 150mL of water and 1.5g of activated carbon into another 250mL four-mouth bottle, heating to 50 ℃, keeping the temperature at 50-60 ℃ for decoloring for 30 minutes, performing suction filtration, pouring the filtrate into pulped calcium carbonate, heating to 50 ℃, keeping the temperature at 50-60 ℃ for reacting for 1 hour, adding 1.5g of activated carbon, decoloring for 30 minutes, performing suction filtration to obtain calcium gluconate filtrate, adding seed crystals at 45 ℃, standing at room temperature for crystallizing for 20 hours, performing suction filtration to obtain a wet calcium gluconate product, and drying to obtain 47.2g of finished product, wherein the yield is 75%.
The above description is only for the purpose of creating a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can substitute or change the technical solution and the inventive concept of the present invention within the technical scope of the present invention.
Claims (7)
1. A crystallization method of injection calcium gluconate is characterized by comprising the following steps: firstly, pulping calcium carbonate, dissolving glucono-delta lactone in water and adding activated carbon for decolorization; filtering after the decolorization is finished, pouring the filtrate into the calcium carbonate which is being pulped, reacting the filtrate and the calcium carbonate, and adding activated carbon for decolorization after reacting for 1 hour; filtering to obtain calcium gluconate solution; standing, cooling and crystallizing, and adding seed crystals after reaching a certain temperature; and continuously crystallizing for 20 hours, centrifuging, finishing granules and drying to obtain a finished product of the calcium gluconate.
2. The method of claim 1, wherein the calcium carbonate is pharmaceutical grade, and the pulping solvent is water; the time is more than 30 minutes.
3. The method of claim 1, wherein the temperature for decoloring gluconic acid-delta lactone is 50-60 ℃ and the time is 30 minutes.
4. The method of claim 1, wherein the reaction temperature of calcium carbonate and gluconic acid is 50-60 ℃.
5. The method of claim 1, wherein the second decolorization time is 30 minutes.
6. The method of claim 1, wherein the crystal is added at 45 ℃ in an amount of 0.01% by weight of glucono-delta lactone.
7. The method of claim 1, wherein the drying is performed by drying at room temperature for 16 hours, drying at 30-35 ℃ for 24 hours, and drying at 50-55 ℃ for 8 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110319196.0A CN113045409A (en) | 2021-03-25 | 2021-03-25 | Crystallization method of calcium gluconate for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110319196.0A CN113045409A (en) | 2021-03-25 | 2021-03-25 | Crystallization method of calcium gluconate for injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113045409A true CN113045409A (en) | 2021-06-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110319196.0A Pending CN113045409A (en) | 2021-03-25 | 2021-03-25 | Crystallization method of calcium gluconate for injection |
Country Status (1)
| Country | Link |
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| CN (1) | CN113045409A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115154415A (en) * | 2022-08-04 | 2022-10-11 | 山东新华制药股份有限公司 | Preparation method of calcium gluconate injection |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101607952A (en) * | 2009-07-14 | 2009-12-23 | 浙江天益食品添加剂有限公司 | A kind of preparation method of maltonic acid-delta-lactone |
| CN109608328A (en) * | 2019-01-15 | 2019-04-12 | 山东新华制药股份有限公司 | A kind of preparation method of injection calcium gluconate |
| CN111875490A (en) * | 2020-08-10 | 2020-11-03 | 连云港瑞邦药业有限公司 | Preparation method of calcium gluconate |
-
2021
- 2021-03-25 CN CN202110319196.0A patent/CN113045409A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101607952A (en) * | 2009-07-14 | 2009-12-23 | 浙江天益食品添加剂有限公司 | A kind of preparation method of maltonic acid-delta-lactone |
| CN109608328A (en) * | 2019-01-15 | 2019-04-12 | 山东新华制药股份有限公司 | A kind of preparation method of injection calcium gluconate |
| CN111875490A (en) * | 2020-08-10 | 2020-11-03 | 连云港瑞邦药业有限公司 | Preparation method of calcium gluconate |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115154415A (en) * | 2022-08-04 | 2022-10-11 | 山东新华制药股份有限公司 | Preparation method of calcium gluconate injection |
| CN115154415B (en) * | 2022-08-04 | 2024-03-08 | 山东新华制药股份有限公司 | Preparation method of calcium gluconate injection |
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| PB01 | Publication | ||
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| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210629 |
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| RJ01 | Rejection of invention patent application after publication |