CN104341420B - A kind of method of extracting theophylline from theophylline mother liquor - Google Patents
A kind of method of extracting theophylline from theophylline mother liquor Download PDFInfo
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- CN104341420B CN104341420B CN201410610891.2A CN201410610891A CN104341420B CN 104341420 B CN104341420 B CN 104341420B CN 201410610891 A CN201410610891 A CN 201410610891A CN 104341420 B CN104341420 B CN 104341420B
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- theophylline
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
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- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a kind of method of extracting theophylline from theophylline mother liquor, comprise the following steps: the extraction of (1) theophylline: after theophylline mother liquor is filtered, add chloride solution; (2) enrichment of theophylline: by parahydroxyben-zaldehyde polymeric adsorbent column chromatography absorption for above-mentioned solution, wash-out after absorption, collect eluent, then reduced pressure concentration obtains medicinal extract; (3) purifying: by alumina column chromatography, then wash-out, collects eluent, then reduced pressure concentration by medicinal extract, and concentrate, through refrigeration, crystallization, filtration drying, obtains theophylline compounds. The present invention is by the lixiviate of acid chlorine salting liquid, the enrichment of parahydroxyben-zaldehyde polymeric adsorbent, alumina column chromatography, and four steps of crystallization can obtain the theophylline compounds of a large amount of high-quality. The mild condition of four steps, requires lowly, and manufacturing cycle is short; Technological process is simple, easy and simple to handle, low to the requirement of operating personnel's technical merit, is applicable to industrialization promotion.
Description
Technical field
The present invention relates to a kind of method of extracting theophylline from theophylline mother liquor, belong to technical field of organic chemistry.
Background technology
Theophylline is methyl purine compounds, is the important component in tealeaves, and it has the effect of the central nervous excitation of promotion, can also distend the blood vessels, and accelerates blood circulation, strengthens contraction of muscle ability, has effect of cardiac stimulant. Well diuretics of it or one, can strengthen renal function, and unobstructed urine, excretes toxin and refuse in kidney as early as possible, so tealeaves can prevent again kidney trouble and lithiasis. The effect of theophylline is mainly dissolved fat, and having helps digestion separates greasy effect. Drink tea and why can lose weight, and effect is more remarkable, reason also here.
It is reported that the discharge capacity of factory's theophylline mother liquor of producing 1000 tons of caffeines per year is 1.2 ten thousand tons, will cause serious waste if do not reclaimed. From molecular structure, theophylline is good hydrogen bond receptor, and carboxyl, phenolic hydroxyl group are good hydrogen-bond donors.
In addition, the extraction of highly purified theophylline, development of separation process, have great importance. Yet there are no the report of theophylline process of preparing in tealeaves.
Summary of the invention
The object of the invention is for the deficiencies in the prior art, a kind of extracting method of theophylline theophylline in mother solution compounds is provided, the preparation cost of the method is low, the cycle is short, product purity easy and simple to handle, that make is high.
For realizing the object of the invention, the technical scheme adopting is:
A method of extracting theophylline from theophylline mother liquor, comprises the following steps:
(1) extraction of theophylline: add chloride solution after theophylline mother liquor is filtered;
(2) enrichment of theophylline: by parahydroxyben-zaldehyde polymeric adsorbent column chromatography absorption for above-mentioned solution, wash-out after absorption, collect eluent, then reduced pressure concentration obtains medicinal extract;
(3) purifying: by alumina column chromatography, then wash-out, collects eluent, then reduced pressure concentration by medicinal extract, and concentrate, through refrigeration, crystallization, filtration drying, obtains theophylline compounds;
The making step of described parahydroxyben-zaldehyde polymeric adsorbent is as follows: styrene-divinylbenzene copolymer and chloromethylether are carried out to chloromethylation, add dichloroethanes, swelling 12-15h; Crosslinking agent P-hydroxybenzoic acid and ferric trichloride after adding under mechanical agitation, add hot reflux 2-3h, is cooled to room temperature and filters; Washing resin, Soxhlet extract dry after and get final product.
Further, in described (1) step, chloride solution mass fraction is the 3.0-5.0% aqueous solution, and pH value is adjusted to 2-4.
Further, the making step of described parahydroxyben-zaldehyde polymeric adsorbent is as follows: styrene-divinylbenzene copolymer and chloromethylether are carried out to chloromethylation, and introducing-CH2Cl active group, adds dichloroethanes, swelling 12-15h; Crosslinking agent P-hydroxybenzoic acid and ferric trichloride after adding under mechanical agitation, add hot reflux 2-3h under ultrasound condition, be cooled to room temperature and filter; With ethanol, hydrochloric acid, water, ethanol order washing resin, after Soxhlet is extracted and dried and get final product.
Further, in described (2) step, para hydroxybenzene urea formaldehyde volume and dry tealeaves part by weight are 1L-1.5L:1Kg.
Further, the wash-out in described (2) step is the water elution removal of impurities of first using 1.0BV, then uses the hydrophilic solvent wash-out of 2.5BV ~ 4.0BV, after wash-out at 60 DEG C of-75 DEG C of reduced pressure concentrations.
Further, in described (3) step, the weight ratio of medicinal extract and aluminium oxide is 1:(8 ~ 12).
Further, in described (3) step, wash-out is first to adopt 4.0BV ~ 6.0BV methylene chloride-methanol system wash-out, in methylene chloride-methanol system, the volume ratio of carrene and methyl alcohol is 9-7:1-3, then adopts 16.0BV-20.0BV methanol-eluted fractions, merges meoh eluate; Eluent carries out reduced pressure concentration, the 1/12-1/8 that the concentrate volume after concentrating is effluent volume in 45 DEG C ~ 60 DEG C.
Further, in described (3) step, concentrate is put under 4 DEG C of conditions of refrigerator and is placed 36h-48h, crystallization, and filtration drying, obtains purity and is greater than more than 80% theophylline compounds.
Further, while regulating chloride solution pH value, the acid adopting is one or more the mixture in hydrochloric acid, sulfuric acid, nitric acid; Villaumite in described step (1) is NaCl, KCl or CaCl2One or more mixture.
The relative prior art of the present invention has following advantage and effect:
One, para hydroxybenzene aldehyde polymeric adsorbent of the present invention aperture is abundant, and micropore, mesopore are more, more easily adsorb tea alkaloids.
Two, para hydroxybenzene aldehyde polymeric adsorbent adsorption rate of the present invention is high, absorption power is strong.
Three, the present invention is by the lixiviate of acid chlorine salting liquid, the enrichment of parahydroxyben-zaldehyde polymeric adsorbent, alumina column chromatography, and four steps of crystallization can obtain the theophylline compounds of a large amount of high-quality. The mild condition of four steps, requires lowly, and manufacturing cycle is short; Technological process is simple, easy and simple to handle, low to the requirement of operating personnel's technical merit, is applicable to industrialization promotion.
Detailed description of the invention
The preparation method who the invention provides a kind of theophylline, comprises the following steps:
(1) extraction of theophylline
Get theophylline mother liquor 2kg, the KCl solution that the mass fraction of preparing its 8 times of volumes is 3.0%, and the pH value of chloride solution is adjusted to 2, while regulating KCl pH, the acid adopting is hydrochloric acid;
(2) enrichment of theophylline
To merge extract by the absorption of parahydroxyben-zaldehyde polymeric adsorbent column chromatography, this parahydroxyben-zaldehyde polymeric adsorbent is to be made up of following steps: styrene-divinylbenzene copolymer and chloromethylether are carried out to chloromethylation, introducing-CH2Cl active group, adds dichloroethanes, swelling 14h; Crosslinking agent P-hydroxybenzoic acid and ferric trichloride after adding under mechanical agitation, add hot reflux 3h under ultrasound condition, be cooled to room temperature and filter; With ethanol, hydrochloric acid, water, ethanol order washing resin, after Soxhlet is extracted and dried and get final product. Parahydroxyben-zaldehyde polymeric adsorbent volume is 1L:5L with (1) middle solution weight ratio, and adsorption rate is controlled at 2.0BV/h; After absorption, first use the water elution removal of impurities of 1.0BV; Use the hydrophilic solvent wash-out of 2.5BV, described hydrophilic solvent is the ethanol of mass concentration 30% again, collects eluent, obtains medicinal extract in 60 DEG C of reduced pressure concentrations;
(3) purifying
Medicinal extract is passed through to alumina column chromatography: the weight ratio of medicinal extract and filling alumina is 1:8, first adopt 4.0BV methylene chloride-methanol system wash-out, in methylene chloride-methanol system, the volume ratio of carrene and methyl alcohol is 9:1, then adopts 16.0BV methanol-eluted fractions, merges meoh eluate; The eluent of methanol-eluted fractions is carried out to reduced pressure concentration in 45 DEG C, and to make concentrate volume after concentrated be effluent volume 1/12, then concentrate is put under 4 DEG C of conditions of refrigerator and placed 48h, and crystallization, filtration drying, obtains theophylline monomer 5.1g.
Utilize reverse high performance liquid chromatography (RP-HPLC) to detect this routine theophylline purity, recording its purity is 85%.
Claims (1)
1. a method of extracting theophylline from theophylline mother liquor, is characterized in that comprising the following steps:
(1) extraction of theophylline: add chloride solution after theophylline mother liquor is filtered;
(2) enrichment of theophylline: by parahydroxyben-zaldehyde polymeric adsorbent column chromatography absorption for above-mentioned solution, wash-out after absorption, collect eluent, then reduced pressure concentration obtains medicinal extract;
(3) purifying: by alumina column chromatography, then wash-out, collects eluent, then reduced pressure concentration by medicinal extract, and concentrate, through refrigeration, crystallization, filtration drying, obtains theophylline compounds;
The making step of described parahydroxyben-zaldehyde polymeric adsorbent is as follows: styrene-divinylbenzene copolymer and chloromethylether are carried out to chloromethylation, and introducing-CH2Cl active group, adds dichloroethanes, swelling 12-15h; Crosslinking agent P-hydroxybenzoic acid and ferric trichloride after adding under mechanical agitation, add hot reflux 2-3h under ultrasound condition, be cooled to room temperature and filter; With ethanol, hydrochloric acid, water, ethanol order washing resin, after Soxhlet is extracted and dried and get final product;
In described (1) step, chloride solution mass fraction is the 3.0-5.0% aqueous solution, and pH value is adjusted to 2-4;
In described (2) step, para hydroxybenzene urea formaldehyde volume and dry tealeaves part by weight are 1L-1.5L:1Kg;
Wash-out in described (2) step is the water elution removal of impurities of first using 1.0BV, then uses the hydrophilic solvent wash-out of 2.5BV ~ 4.0BV, after wash-out at 60 DEG C of-75 DEG C of reduced pressure concentrations;
In described (3) step, the weight ratio of medicinal extract and aluminium oxide is 1:(8 ~ 12);
In described (3) step, wash-out is first to adopt 4.0BV ~ 6.0BV methylene chloride-methanol system wash-out, and in methylene chloride-methanol system, the volume ratio of carrene and methyl alcohol is 9-7:1-3, then adopts 16.0BV-20.0BV methanol-eluted fractions, merges meoh eluate; Eluent carries out reduced pressure concentration, the 1/12-1/8 that the concentrate volume after concentrating is effluent volume in 45 DEG C ~ 60 DEG C;
In described (3) step, concentrate is put under 4 DEG C of conditions of refrigerator and is placed 36h-48h, crystallization, and filtration drying, obtains purity and is greater than more than 80% theophylline compounds;
And: while regulating chloride solution pH value, the acid adopting is one or more the mixture in hydrochloric acid, sulfuric acid, nitric acid; Villaumite in described step (1) is NaCl, KCl or CaCl2One or more mixture.
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| CN201410610891.2A CN104341420B (en) | 2014-11-04 | 2014-11-04 | A kind of method of extracting theophylline from theophylline mother liquor |
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| CN201410610891.2A CN104341420B (en) | 2014-11-04 | 2014-11-04 | A kind of method of extracting theophylline from theophylline mother liquor |
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| CN104341420B true CN104341420B (en) | 2016-05-18 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102344450A (en) * | 2011-08-01 | 2012-02-08 | 西安蓝晓科技有限公司 | Method for extracting theophylline sodium salt or theophylline by styrene type macroporous resin |
| CN103992321A (en) * | 2014-06-09 | 2014-08-20 | 成都合瑞化工有限公司 | Preparation method of theophylline |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102344450A (en) * | 2011-08-01 | 2012-02-08 | 西安蓝晓科技有限公司 | Method for extracting theophylline sodium salt or theophylline by styrene type macroporous resin |
| CN103992321A (en) * | 2014-06-09 | 2014-08-20 | 成都合瑞化工有限公司 | Preparation method of theophylline |
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