CN101003580A - Method for preparing polyferose - Google Patents
Method for preparing polyferose Download PDFInfo
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- CN101003580A CN101003580A CNA2006100072043A CN200610007204A CN101003580A CN 101003580 A CN101003580 A CN 101003580A CN A2006100072043 A CNA2006100072043 A CN A2006100072043A CN 200610007204 A CN200610007204 A CN 200610007204A CN 101003580 A CN101003580 A CN 101003580A
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- China
- Prior art keywords
- iron
- polyferose
- alkali lye
- water
- adds
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- 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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- 238000000034 method Methods 0.000 title claims abstract description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 58
- 229910052742 iron Inorganic materials 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003513 alkali Substances 0.000 claims abstract description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 10
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 10
- 239000006188 syrup Substances 0.000 claims abstract description 10
- 235000020357 syrup Nutrition 0.000 claims abstract description 10
- 238000001556 precipitation Methods 0.000 claims description 15
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 230000000694 effects Effects 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 230000002496 gastric effect Effects 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 150000004676 glycans Chemical class 0.000 abstract 2
- 229920001282 polysaccharide Polymers 0.000 abstract 2
- 239000005017 polysaccharide Substances 0.000 abstract 2
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 abstract 1
- 230000009469 supplementation Effects 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 208000007502 anemia Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 2
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- -1 iron ion Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229910001447 ferric ion Inorganic materials 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种以低聚糖浆、碱、高铁为原料制备多糖铁的工艺，该工艺在水铁质量比大于3.5以上操作，采用流加方式加入碱液，以乙醇为沉淀剂，用低速离心机分离纯化产品。多糖铁用于治疗缺铁性贫血，补铁效果好，生产成本低，对胃肠副作用极小。The invention discloses a process for preparing polysaccharide iron by using oligosaccharide syrup, alkali and high iron as raw materials. The process is operated when the mass ratio of water and iron is greater than 3.5, and the lye is added in a feeding mode, and ethanol is used as a precipitant. The centrifuge separates and purifies the product. The polysaccharide iron is used for treating iron-deficiency anemia, has good effect of iron supplementation, low production cost, and minimal gastrointestinal side effects.
Description
One, technical field
The present invention relates to ferric iron, oligose, alkali is the technology of raw material production Polyferose, belongs to technical field of medicine synthesis.
Two, background technology
Polyferose is oligose and ferric mixture, is used for the treatment of hypoferric anemia, and iron level is 40～46% in the Polyferose.Iron content height in the Polyferose, it is effective to mend iron, and production cost is low.Polyferose is with the complete absorption of molecular form, and do not contain the free iron ion in the Polyferose, so Polyferose is little to gastrointestinal side effect, do not have feel sick, side effects such as stomachache, diarrhoea.
The main method of controlling hypoferric anemia is to replenish the iron of capacity to body.The medicine of existing treatment hypoferric anemia mainly is that ferrous iron is mended chalybeate, and is very big to the stomach side effect, can cause nausea, suffers from abdominal pain, side effect such as diarrhoea, makes many patients be difficult to accept; Ferrous porphyrin is free from side effects to stomach, but its production cost height, price has exceeded numerous patients' ability to bear.That Polyferose is enriched blood is effective, to stomach have no side effect and production cost low, be a kind of chalybeate of mending preferably.
United States Patent (USP) (USP3821192) discloses a kind of preparation technology who produces Polyferose, adopts oligosaccharide syrup, alkali, high ferro to prepare Polyferose.In this preparation technology, do not mention water iron than parameter, still, water iron is than the important parameter that is the preparation Polyferose.This preparation technology does not mention the feed way of alkali lye, and still, the alkali lye feed way is significant to the preparation Polyferose.This preparation technology adopts supercentrifuge to carry out separation and purification of products, its rotating speed is 25000 rev/mins, and supercentrifuge costs an arm and a leg, and the price of supercentrifuge is more than 100 times of low speed centrifuge, and the processing power of supercentrifuge is less than 1/50 of low speed centrifuge.In fact, adopt low speed centrifuge can realize separating purpose.In addition, this process using methyl alcohol is precipitation agent, and still, the toxicity of methyl alcohol is bigger, should adopt the less precipitation agent of toxicity.So, be necessary to improve above-mentioned Polyferose preparation technology.
Three, summary of the invention
The invention discloses a kind of is the technology of the fast Polyferose of feedstock production with oligosaccharide syrup, alkali, high ferro, and this technology than greater than operation more than 3.5, adopts fed-batch mode reinforced at water iron, is precipitation agent with ethanol, with low speed centrifuge separation and purification Polyferose product.
The preparation method of Polyferose of the present invention mainly realizes by following steps: add oligosaccharide syrup, ferric chloride aqueous solutions in reactor, stir.In mixing solutions, slowly add alkali aqueous solution until generating Fe (OH) with fed-batch mode
3Precipitation, and the pH value of solution is still tart (pH＜7).Fully stir, and then make pH value of solution value to 11.5～13.5,, make solution temperature rise to 75～85 ℃ the reaction solution heating with fed-batch mode adding alkali lye.Keep temperature, stir about 15～30 minutes is until the Nu-Iron solution that forms homogeneous.This solution is cooled to room temperature, moves to setting tank, Nu-Iron is precipitated fully to the ethanol that wherein adds at least 50%.With whizzer centrifugation precipitation, the washing with alcohol precipitation with 50% 2 times will precipitate drying, promptly get the Polyferose product.
In above-mentioned complex reaction, water weight of iron ratio is an important parameter, directly influences the quality of Polyferose product.Water weight of iron ratio is defined as:
Water weight of iron ratio=total quality/weight of iron,
In the formula, the water of the water+ferric chloride aqueous solutions substitution of total water=oligosaccharide syrup substitution, quality; Iron is meant the iron trichloride quality.
Through repeatedly experiment, find to have only when water iron than greater than 3.5 the time, complex reaction could normally be carried out, and obtains qualified product, and yield is higher.This means that ferric ion and oligose carry out compound reaction time, iron concentration has material impact to complex reaction, if iron concentration is too high, then complex reaction can not normally be carried out, and can not get qualified Polyferose product.
The feed way of alkali lye also has material impact to the Polyferose complex reaction, and experiment shows, if with the disposable adding of alkali lye, then can not obtain qualified Polyferose product.Must adopt fed-batch mode to divide to add for 2 times alkali lye, wherein first add the alkali lye time should be greater than 30 minutes.
Experiment shows, in separation and purification of products, adopts rotating speed greater than 3500 rev/mins low speed centrifuge, can carry out the product separation purifying.
The more detailed implementation method of the present invention can be referring to embodiment.
Embodiment
Embodiment 1
Under the room temperature, add ferric chloride (FeCl36H2O) 360 grams in reactor, water 750 grams are dissolved into ferric chloride aqueous solutions.Adding reduction value DE is 71% oligosaccharide syrup 780 grams, and the sugar cube content of oligosaccharide syrup is 26.5%.Stir, add the aqueous sodium carbonate that concentration is 0.2 (W/W) continuously, uniformly, up to generating Fe (OH)
3Precipitation, this moment, solution still was acid.It is 35 minutes that the stream of sodium bicarbonate aqueous solution adds the time.Stir after 15 minutes, in 20 minutes, adding concentration uniformly continuously is the aqueous sodium hydroxide solution of 0.3 (W/W), is 11.6 up to the pH of solution value.Reactor is heated up, make reacting liquid temperature reach 81 ℃, keep after 20 minutes reaction solution being cooled to room temperature.Reaction solution is moved to setting tank, add the ethanol of 1.1 times of reaction solution volumes, make Polyferose product precipitation.With rotating speed is 4000 rev/mins centrifugal 15 minutes of whizzer, obtains the Polyferose precipitation.Washing with alcohol Polyferose precipitation with 50, centrifugal, obtain Polyferose.Wash once with method, oven dry promptly gets Polyferose product 144 grams again.Through check, the Polyferose quality product meets state quality standard.
Embodiment 2
Under 10 ℃, add 18 kilograms of ferric chloride (FeCl36H2O)s in reactor, 45 kilograms in water is dissolved into ferric chloride aqueous solutions.Add reduction value DE and be 39 kilograms of 69% oligosaccharide syrups, the sugar cube content of oligosaccharide syrup is 26.1%.Stir, add the aqueous sodium carbonate that concentration is 0.3 (W/W) continuously, uniformly, up to generating Fe (OH)
3Precipitation, this moment, solution still was acid.It is 45 minutes that the stream of sodium bicarbonate aqueous solution adds the time.Stir after 20 minutes, in 25 minutes, adding concentration uniformly continuously is the aqueous sodium hydroxide solution of 0.3 (W/W), is 11.6 up to the pH of solution value.Reactor is heated up, make reacting liquid temperature reach 78 ℃, keep after 20 minutes reaction solution being cooled to room temperature.Reaction solution is moved to setting tank, add the ethanol of 1.1 times of reaction solution volumes, make Polyferose product precipitation.With rotating speed is that 3500 rev/mins industrial centrifugal machine is centrifugal, obtains the Polyferose precipitation.Aqueous ethanolic solution washing Polyferose precipitation with 50, centrifugal, obtain Polyferose.Wash once with method, oven dry obtains 7.85 kilograms of Polyferose products again.Through check, the Polyferose quality product meets state quality standard.
Claims (4)
1. one kind prepares the method for Polyferose with oligose, iron trichloride, alkali lye, it is characterized in that (1) adopt bigger water weight of iron than operation; (2) alkali lye adds with fed-batch mode; (3) adopt low speed centrifuge to carry out the product separation purifying; (4) used precipitation agent is an ethanol.
2. the described bigger water weight of iron ratio of claim 1, the numerical value that it is characterized in that water weight of iron ratio is greater than 3.5.Water weight of iron ratio is meant total water/iron, the water of the water+ferric chloride aqueous solutions substitution of total water=oligosaccharide syrup substitution, quality; Iron is meant the iron trichloride quality.
3. the described alkali lye of claim 1 adds with fed-batch mode, it is characterized in that adopting fed-batch mode to divide 2 times and adds alkali lye, and alkali lye adds retort with even, successive mode, and the time of finishing alkali lye adding for the first time was greater than 30 minutes.
4. the low speed centrifuge described in the claim 1, the rotating speed that it is characterized in that whizzer is more than or equal to 3500 rev/mins.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100072043A CN101003580A (en) | 2006-01-20 | 2006-01-20 | Method for preparing polyferose |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100072043A CN101003580A (en) | 2006-01-20 | 2006-01-20 | Method for preparing polyferose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101003580A true CN101003580A (en) | 2007-07-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006100072043A Pending CN101003580A (en) | 2006-01-20 | 2006-01-20 | Method for preparing polyferose |
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| Country | Link |
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| CN (1) | CN101003580A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102086232A (en) * | 2010-12-15 | 2011-06-08 | 青岛市中心医院 | Method for preparing polyferose |
| CN102167752A (en) * | 2011-05-23 | 2011-08-31 | 华南理工大学 | Preparation method of water-soluble soybean polysaccharide ferrous coordination compound |
| CN102219864A (en) * | 2011-04-26 | 2011-10-19 | 华南理工大学 | Preparation method for water-soluble soybean polysaccharide trivalent ferric complex |
| CN102049035B (en) * | 2009-10-29 | 2012-03-28 | 青岛科技大学 | A kind of starch polysaccharide iron compound preparation |
| CN103626807A (en) * | 2013-11-20 | 2014-03-12 | 青岛国风药业股份有限公司 | Preparation method and mass detection method of polysaccharide-iron complex |
| CN103641875A (en) * | 2013-11-20 | 2014-03-19 | 青岛国风药业股份有限公司 | Preparation process and quality detection method of polysaccharide-iron complex |
| CN103864950A (en) * | 2014-03-21 | 2014-06-18 | 张忠山 | Preparation method and application of low-molecular porphyra haitanensis polyferose compound |
| CN111333745A (en) * | 2020-04-17 | 2020-06-26 | 内江师范学院 | Citrus peel polysaccharide iron (III) compound and preparation method thereof |
| CN112694511A (en) * | 2020-12-23 | 2021-04-23 | 福建呈睿医药科技有限公司 | Preparation method and quality control method of polysaccharide-iron complex and capsule preparation |
-
2006
- 2006-01-20 CN CNA2006100072043A patent/CN101003580A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102049035B (en) * | 2009-10-29 | 2012-03-28 | 青岛科技大学 | A kind of starch polysaccharide iron compound preparation |
| CN102086232A (en) * | 2010-12-15 | 2011-06-08 | 青岛市中心医院 | Method for preparing polyferose |
| CN102219864A (en) * | 2011-04-26 | 2011-10-19 | 华南理工大学 | Preparation method for water-soluble soybean polysaccharide trivalent ferric complex |
| CN102167752A (en) * | 2011-05-23 | 2011-08-31 | 华南理工大学 | Preparation method of water-soluble soybean polysaccharide ferrous coordination compound |
| CN102167752B (en) * | 2011-05-23 | 2012-08-08 | 华南理工大学 | Preparation method of water-soluble soybean polysaccharide ferrous coordination compound |
| CN103626807A (en) * | 2013-11-20 | 2014-03-12 | 青岛国风药业股份有限公司 | Preparation method and mass detection method of polysaccharide-iron complex |
| CN103641875A (en) * | 2013-11-20 | 2014-03-19 | 青岛国风药业股份有限公司 | Preparation process and quality detection method of polysaccharide-iron complex |
| CN103641875B (en) * | 2013-11-20 | 2017-10-24 | 上海医药集团青岛国风药业股份有限公司 | The preparation technology and its quality determining method of a kind of Nu-Iron |
| CN103864950A (en) * | 2014-03-21 | 2014-06-18 | 张忠山 | Preparation method and application of low-molecular porphyra haitanensis polyferose compound |
| CN103864950B (en) * | 2014-03-21 | 2016-08-17 | 湖州师范学院 | A kind of preparation method and applications of low molecule Porphyra haitanensis polysaccharide iron complexes |
| CN111333745A (en) * | 2020-04-17 | 2020-06-26 | 内江师范学院 | Citrus peel polysaccharide iron (III) compound and preparation method thereof |
| CN112694511A (en) * | 2020-12-23 | 2021-04-23 | 福建呈睿医药科技有限公司 | Preparation method and quality control method of polysaccharide-iron complex and capsule preparation |
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