CN104402706A - Preparation method of high-purity calcium citrate - Google Patents
Preparation method of high-purity calcium citrate Download PDFInfo
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- CN104402706A CN104402706A CN201410664345.7A CN201410664345A CN104402706A CN 104402706 A CN104402706 A CN 104402706A CN 201410664345 A CN201410664345 A CN 201410664345A CN 104402706 A CN104402706 A CN 104402706A
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- preparation
- tricalcium dicitrate
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- high purity
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- 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
Abstract
The invention discloses a preparation method of high-purity calcium citrate. The preparation method comprises the steps that firstly, citric acid is reacted with alkali, so as to produce sodium citrate (II) or potassium citrate (III); secondly, the produce sodium citrate (II) or the potassium citrate (III) is reacted with calcium chloride, so as to produce the high-purity calcium citrate. The preparation method has the advantages that the cost is reduced, and the yield of calcium citrate is improved.
Description
Technical field
The present invention relates to technical field of medicine, particularly relate to a kind of preparation method of high purity Tricalcium dicitrate.
Background technology
Osteoporosis (osteoporosis) is a kind of systemic osteopathy, it is characterized in that bone amount declines and the microtexture of bone destroys, the fragility showing as bone increases, and the danger of thus fracturing greatly increases, even also easily fracture in slight wound or atraumatic situation.Osteoporosis is a kind of multifactor caused chronic disease.Before fracture occurs, usually without Special Clinical Manifestation.This sick women, more than the male sex, is common in postmenopausal women and the elderly.Along with the increase of China's elderly population, developing osteoporosis rate is in ascendant trend, is all a health problem merited attention in China and even the whole world.
Absorb appropriate calcareous be very important to preventing osteoporosis, particularly for women.Young masculinity and femininity all to need that 1000mg's is calcareous every day, and after 50 years old, this demand raises as 1200mg every day.
Tricalcium dicitrate has the advantage that disintegration rate is fast, bioavailability is high, untoward reaction is few, has a good application prospect in the prevention and therapy of osteoporosis.Tricalcium dicitrate abroad particularly the Western European countries be widely used in medicine and food service industry, become desirable and replenish the calcium and one of the medicine for the treatment of osteoporosis, Tricalcium dicitrate also records by " American Pharmacopeia " 22 editions.
Tricalcium dicitrate disintegration rate is fast, and the disintegration rate of calcium agent obviously will affect it and absorb, and non-disintegration part excretes with ight soil.Tricalcium dicitrate has oral absorption not by the advantage that pH and antacid affect.Tricalcium dicitrate bioavailability is high, the different calcium agent of identical element calcium, and the bioavailability of Tricalcium dicitrate is higher than calcium carbonate by 27.2%, and curative effect is not less than calcium carbonate, with food with then high by 21.6% when taking.
Tricalcium dicitrate untoward reaction is little, take the danger that Tricalcium dicitrate does not increase lithangiuria formation, the general calcium agent of long-term taking, blood calcium and urine calcium concn can be caused to raise, urinary tract calcium oxalate crystal, lithogenous risk must be increased, for calculus patient or there is the patient of calculus medical history just even more serious.Tricalcium dicitrate has stronger complexing action to calcium, when increasing Citric Acid concentration, can binding free ca ions and displacement caoxalate, calcium phosphate salt etc., and form complex compound soluble in water, suppress caoxalate over-saturation state crystallization and form calculus.Research proves that Tricalcium dicitrate can increase the concentration of urine free citric acid, reduces calcium/Citric Acid ratio, significantly suppresses the formation of lithangiuria, and its effect suppressing lithangiuria to be formed is linearly relevant to the concentration of Citric Acid.
Tricalcium dicitrate gastrointestinal side effect is few, and because Tricalcium dicitrate can not produce CO2 at gi tract, the incidence of the untoward reactions such as therefore constipation, abdominal distension and maldigestion is low, is suitable for Aged Patients with Osteoporosis life-time service.Take the patient of citrated compound, its blood aluminium level and the excretion of urine aluminium there is no considerable change.Result shows that the patient of normal renal function gives citrated compound long-term treatment and aluminium element in body can not be caused seriously to accumulate and poisoning.
Tricalcium dicitrate is as calsium supplement treatment and preventing osteoporosis disease, it has the advantage that disintegration rate is fast, bioavailability is high, untoward reaction is little, for the person (as achlorhydria, calculus patient) that is not suitable for Maalox Antacid or the person (as senile constipation patient) that can not tolerate calcium carbonate, there is obvious superiority.
The synthetic route of Tricalcium dicitrate is in the market as follows:
The defect that the method exists is that calcium carbonate solubleness in water is very poor, and can not form homogeneous phase, generated reactive gas, wayward, reaction effect is also undesirable, and the impurity in calcium carbonate and Citric Acid cannot be removed.
Summary of the invention
Technical problem to be solved by this invention there are provided a kind of high purity Tricalcium dicitrate preparation method, the productive rate of its Tricalcium dicitrate that can obviously improve and quality.
The technical solution used in the present invention is as follows: a kind of preparation method of high purity Tricalcium dicitrate, and it comprises following step:
1. Citric Acid becomes Sodium Citrate (II) or Potassium Citrate (III) with alkali reaction.
2. Sodium Citrate (II) or Potassium Citrate (III) are obtained by reacting Tricalcium dicitrate with calcium chloride.
Step 1. or step temperature of reaction be 2.-50 ~ 150 DEG C.
Step 1., step 2. in solvent be water.
Step 1. in alkali be one or several in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, sodium-acetate, Potassium ethanoate.
The step 1. middle consumption of Compound I and the equivalence ratio of alkali consumption is 1:3.2.
2. step is reacted and is, Compound II per or compound III and calcium chloride carry out ion exchange reaction; Wherein, temperature of reaction is-50 ~ 150 DEG C; Solvent is water; The consumption of compound and the equivalence ratio of alkali consumption are 1:3.2.
1. step can adopt the method for the oxidizing reaction of this area routine and condition to carry out, preferred following condition: step temperature of reaction is 1. preferably be-15 ~ 150 DEG C, and better is 15 ~ 30 DEG C; Reaction times preferably with detection reaction completely till, be generally 0.5 ~ 22h, that better is 0.5 ~ 3h.Described solvent is water; The consumption of solvent is 1 ~ 20 times of Compound I, and better is 5 ~ 10 times (ratio is herein volume mass ratio).
2. step can adopt calcium chloride to carry out permutoid reaction, preferred following condition: Compound II per or III and calcium chloride carry out permutoid reaction, and the temperature of reaction is preferably 20 ~ 150 DEG C, and better is 30 ~ 70 DEG C; The time of reaction is preferably (till complete with detection reaction), is generally 2 ~ 24h, preferably 3 ~ 5h.Described solvent is water; 1 ~ 20 times of the consumption of solvent to be the consumption of calcium chloride agent be Compound I, better is 5 ~ 10 times (ratios are herein volume mass than).
Namely each optimum condition in preparation method of the present invention arbitrary combination can obtain each preferred embodiment of the present invention.
The reagent that the present invention is used and raw material are all commercially.
Positive progressive effect of the present invention there are provided a kind of preparation method of Tricalcium dicitrate, and the purity of its Tricalcium dicitrate that can obviously improve, productive rate, simplify the operation.
Embodiment
Further illustrate the present invention by embodiment below, but the present invention is not limited.
Embodiment 1: a kind of preparation method of Tricalcium dicitrate.
In 1000ml there-necked flask, add 30g Citric Acid (143mmol) and 500ml water, add 20.7g sodium hydroxide (518mmol), at 20 DEG C, stir 1h, suction filtration, filtrate is liquor sodii citratis (II).Measure 27.8g calcium chloride (250mmol), be dissolved in 200ml water.Added in there-necked flask by calcium chloride solution in batches, stir 3h, separate out white solid gradually, suction filtration, solid washing, suction filtration 2 times, at 45 DEG C of dry 2h, obtain solid 33.5g, yield 95.7%, quality meets standards of pharmacopoeia.
Embodiment 2: a kind of preparation method of Tricalcium dicitrate.
In 1000ml there-necked flask, add 30g Citric Acid (143mmol) and 500ml water, add 28.49g sodium hydroxide (518mmol), at 20 DEG C, stir 1h, suction filtration, filtrate is liquor kalii citratis (III).Measure 27.8g calcium chloride (250mmol), be dissolved in 200ml water.Added in there-necked flask by calcium chloride solution in batches, stir 4h, separate out white solid gradually, suction filtration, solid washing, suction filtration 2 times, at 45 DEG C of dry 2h, obtain solid 33.1g, yield 94.5%, quality meets standards of pharmacopoeia.
Embodiment 3: a kind of preparation method of Tricalcium dicitrate.
In 1000ml there-necked flask, add 30g Citric Acid (143mmol) and 500ml water, add 43.5g sodium bicarbonate (518mmol), at 20 DEG C, stir 2h, suction filtration, filtrate is liquor sodii citratis (II).Measure 27.8g calcium chloride (250mmol), be dissolved in 200ml water.Added in there-necked flask by calcium chloride solution in batches, stir 3h, separate out white solid gradually, suction filtration, solid washing, suction filtration 2 times, at 45 DEG C of dry 2h, obtain solid 32.3g, yield 92.3%, quality meets standards of pharmacopoeia.
Embodiment 4: a kind of preparation method of Tricalcium dicitrate.
In 1000ml there-necked flask, add 30g Citric Acid (143mmol) and 500ml water, add 35.7g salt of wormwood (25.9mmol), at 20 DEG C, stir 2h, suction filtration, filtrate is liquor kalii citratis (III).Measure 27.8g calcium chloride (250mmol), be dissolved in 200ml water.Added in there-necked flask by calcium chloride solution in batches, stir 3h, separate out white solid gradually, suction filtration, solid washing, suction filtration 2 times, at 45 DEG C of dry 2h, obtain solid 33.6g, yield 96%, quality meets standards of pharmacopoeia.
Embodiment 5: a kind of preparation method of Tricalcium dicitrate.
In 1000ml there-necked flask, add 30g Citric Acid (143mmol) and 500ml water, add 42.5g sodium-acetate (518mmol), at 20 DEG C, stir 2h, suction filtration, filtrate is liquor sodii citratis (II).Measure 27.8g calcium chloride (250mmol), be dissolved in 200ml water.Added in there-necked flask by calcium chloride solution in batches, stir 3h, separate out white solid gradually, suction filtration, solid washing, suction filtration 2 times, at 45 DEG C of dry 2h, obtain solid 32.1g, yield 91.7%, quality meets standards of pharmacopoeia.
More than describe embodiments of the present invention in detail, but this example just lifted for the ease of understanding, should not be considered to be limitation of the scope of the invention.Equally, any person of ordinary skill in the field all according to the description of technical scheme of the present invention and preferred embodiment thereof, can make various possible equivalent change or replacement, but all these change or replace the protection domain that all should belong to the claims in the present invention.
Claims (6)
1. a preparation method for high purity Tricalcium dicitrate, it comprises following step:
1. Citric Acid becomes Sodium Citrate (II) or Potassium Citrate (III) with alkali reaction,
2. Sodium Citrate (II) or Potassium Citrate (III) are obtained by reacting Tricalcium dicitrate with calcium chloride,
2. the preparation method of a kind of high purity Tricalcium dicitrate as claimed in claim 1, is characterized in that: step 1. or step temperature of reaction be 2.-50 ~ 100 DEG C.
3. the preparation method of a kind of high purity Tricalcium dicitrate as claimed in claim 1, is characterized in that: step 1., step 2. in solvent be water.
4. the preparation method of a kind of high purity Tricalcium dicitrate as claimed in claim 1, is characterized in that: step 1. in alkali be one or several in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, sodium-acetate, Potassium ethanoate.
5. the preparation method of a kind of high purity Tricalcium dicitrate as claimed in claim 1, is characterized in that: the step 1. middle consumption of Compound I and the equivalence ratio of alkali consumption is 1:3.2.
6. the preparation method of a kind of high purity Tricalcium dicitrate as claimed in claim 1, is characterized in that: 2. step is reacted and be, Compound II per or compound III and calcium chloride carry out ion exchange reaction; Wherein, temperature of reaction is-50 ~ 150 DEG C; Solvent is water; The consumption of Compound II per or compound III and the equivalence ratio of calcium chloride consumption are 1:3.2.
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| CN201410664345.7A CN104402706A (en) | 2014-11-19 | 2014-11-19 | Preparation method of high-purity calcium citrate |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106278870A (en) * | 2016-08-03 | 2017-01-04 | 广东先导稀材股份有限公司 | A kind of preparation method of bismuth potassium citrate |
| CN107011156A (en) * | 2017-05-04 | 2017-08-04 | 江苏润普食品科技股份有限公司 | A kind of method of utilization citric acid and liquid potassium hydroxide synthesizing citric acid potassium |
| CN108218694A (en) * | 2018-01-30 | 2018-06-29 | 日照金禾博源生化有限公司 | A kind of preparation method of ultra-fine calcium citrate |
| CN111909032A (en) * | 2020-08-07 | 2020-11-10 | 日照金禾博源生化有限公司 | Treatment method of unqualified sodium citrate mother liquor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101607892A (en) * | 2009-08-07 | 2009-12-23 | 湖南尔康制药有限公司 | The production method of Sodium Citrate |
| CN102334690A (en) * | 2010-07-27 | 2012-02-01 | 河北农业大学 | Method for preparing calcium citrate with oyster shells and fan shells |
| CN102921036A (en) * | 2012-10-11 | 2013-02-13 | 海南医学院 | Method for preparing marine environment-friendly calcium citrate hard tissue repair material |
-
2014
- 2014-11-19 CN CN201410664345.7A patent/CN104402706A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101607892A (en) * | 2009-08-07 | 2009-12-23 | 湖南尔康制药有限公司 | The production method of Sodium Citrate |
| CN102334690A (en) * | 2010-07-27 | 2012-02-01 | 河北农业大学 | Method for preparing calcium citrate with oyster shells and fan shells |
| CN102921036A (en) * | 2012-10-11 | 2013-02-13 | 海南医学院 | Method for preparing marine environment-friendly calcium citrate hard tissue repair material |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106278870A (en) * | 2016-08-03 | 2017-01-04 | 广东先导稀材股份有限公司 | A kind of preparation method of bismuth potassium citrate |
| CN107011156A (en) * | 2017-05-04 | 2017-08-04 | 江苏润普食品科技股份有限公司 | A kind of method of utilization citric acid and liquid potassium hydroxide synthesizing citric acid potassium |
| CN108218694A (en) * | 2018-01-30 | 2018-06-29 | 日照金禾博源生化有限公司 | A kind of preparation method of ultra-fine calcium citrate |
| CN108218694B (en) * | 2018-01-30 | 2020-12-25 | 日照金禾博源生化有限公司 | Preparation method of superfine calcium citrate |
| CN111909032A (en) * | 2020-08-07 | 2020-11-10 | 日照金禾博源生化有限公司 | Treatment method of unqualified sodium citrate mother liquor |
| CN111909032B (en) * | 2020-08-07 | 2023-04-14 | 日照金禾博源生化有限公司 | Treatment method of unqualified sodium citrate mother liquor |
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Application publication date: 20150311 |