CN105669626A - Process for preparing nobiletin based on multiple solvents - Google Patents
Process for preparing nobiletin based on multiple solvents Download PDFInfo
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- CN105669626A CN105669626A CN201610148825.7A CN201610148825A CN105669626A CN 105669626 A CN105669626 A CN 105669626A CN 201610148825 A CN201610148825 A CN 201610148825A CN 105669626 A CN105669626 A CN 105669626A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/40—Separation, e.g. from natural material; Purification
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a process for preparing nobiletin based on multiple solvents. Any one or more of dried tangerine or orange peel (orange peel), fruits of immature citrons, fructus aurantii (bitter oranges) and shaddock peel are adopted as raw materials, the raw materials are smashed into coarse powder firstly, then methyl alcohol or ethyl alcohol with the volume concentration of 50%-95% is adopted as a solvent, and extraction is conducted through a percolation method or a reflux extraction method or an impregnation method; after an extracting solution is collected, vacuum concentration is conducted, and extract without the alcohol taste is obtained; the extract obtained after alcohol extraction is chloroformed with an organic solvent or extracted with ethyl acetate firstly, extractant is concentrated and then repeatedly extracted with a ternary two-phase solvent system formed by acetone, petroleum ether and water, the lower layer of the extractant which is repeatedly extracted is concentrated, coarsely crystallized and repeatedly recrystallized, and nobiletin crystals with the purity of 98% or above are obtained. The obtained nobiletin can be used for quality control over national standard substances/medicinal materials and decoction pieces or quality monitoring on Chinese patent medicine, and compared with the prior art, the process has the advantages of being simple in technological process, practical, low in cost, high in purity and yield and suitable for industrial production.
Description
Technical field
The present invention relates to the method for separating and preparing of monomer component in a kind of Chinese medicine, specifically a kind of technique preparing Nobiletin based on multi-solvent.
Background technology
Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Fructus Aurantii, Pericarpium Citri grandis are all the Chinese medicine that tcm clinical practice is conventional, its effect for regulating the flow of vital energy, circulation of qi promoting, dispelling the stagnated QI, reduce phlegm; And above-mentioned four kinds of materials all contain the compositions such as alkaloids, flavonoid, Coumarins. Nobiletin is a kind of clear crystal extracting from above-mentioned medical material and separating, fusing point 137-138 DEG C; It is slightly soluble in water and ether; Molecular formula is C21H22O8; Molecular weight 402.39. Structural formula is as follows:
。
Nobiletin (Naringenine-7-rhamnosidoglucoside) English name Nobiletin, has another name called Chuan Piting, nobiletin, is a kind of colourless crystallization, belongs to the one of polymethoxyflavone compounds.
Nobiletin has anti-hemagglutination, antithrombus formation, anticancer, antifungal, antiinflammatory, antiallergic, anticholinergic and antiepileptic action; Focal cerebral ischemia is had neuroprotective by Nobiletin, it is possible to improve neurologic impairment symptom, reduces cerebral infarction volume; Nobiletin can induce Non-small Cell Lung Cancer A 549 apoptosis; SGC-7901 cells is had stronger inhibited proliferation; Can promote that clinical chemotherapy medicine is to the inhibitory action of Cells Proliferation of Human Breast Cancer and apoptosis-induced effect; Nobiletin can suppress ira vitro tube albumen to be polymerized; Human liver cancer cells Hep G2 is had obvious In Vitro Anti proliferation function by Nobiletin, and mice transplanted tumor H22 is had certain inhibitory action; Also have and improve memory, antioxidation and affect the effects such as vascular smooth muscle. Modern pharmacological research show its promoting digestive tract power, eliminate the phlegm, relieving asthma, treat gastric and duodenal ulcers etc. in also have good curative effect.
Along with going deep into Nobiletin pharmacological research, it separates purification and also increasingly receives the concern of people, currently mainly has chemical synthesis, column chromatography, but there is the shortcomings such as complex operation, disengaging time length, separation purity difference.In view of on above-mentioned medical material, the processing of decoction pieces, Quality of Chinese Traditional Proprietary Medicine monitoring, the research and development of relevant new drug and market to Nobiletin reference substance in the urgent need to, it is thus desirable to grope complete set, simple and direct isolation and purification method from Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Fructus Aurantii, Pericarpium Citri grandis, extract the technique separating Nobiletin, its purity is made to be up to state standards the requirement of product, thus compensate for the deficiency of Nobiletin standard substance aspect, and offer help for the relevant various kinds of drug of exploitation further.
Summary of the invention
It is an object of the invention to provide a kind of technique preparing Nobiletin based on multi-solvent, to overcome the separation method complex steps of Nobiletin in prior art, disengaging time length, the defect such as separating power is poor, the Nobiletin purity that is separated to is low. The Nobiletin purity that the inventive method is simple, practical, disengaging time is short, separating power is strong, be separated to is high, has the good prospect of marketing.
For achieving the above object, the present invention provides following technical scheme:
A kind of technique preparing Nobiletin based on multi-solvent, concretely comprises the following steps:
(1) raw material: with any one or a few in Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Fructus Aurantii, Pericarpium Citri grandis for raw material;
(2) alcohol extraction: first raw material powder is broken into coarse powder, then extracts for solvent percolation or reflux extraction or infusion process with methanol or volumetric concentration for 50-95% ethanol, and after collecting extracting solution, concentrating under reduced pressure obtains the extractum without alcohol taste;
(3) extracting: first by the extractum organic solvents, chloroform after alcohol extraction or extraction into ethyl acetate, the ternary two phase solvent system formed with acetone, petroleum ether and water again after then being concentrated by extract extracts repeatedly;
(4) recrystallization: by the extract lower floor after repeatedly extracting then through concentration, coarse crystallization, to be recrystallizing repeatedly so as to obtain purity be more than 98% Nobiletin crystalline solid.
As the further scheme of the present invention: the organic solvent in step (3) adopts chloroform or ethyl acetate, repeatedly extract 2-5 time.
As the further scheme of the present invention: the ternary two-phase solvent body that the organic solvent in step (3) adopts volume ratio to be the acetone of 1.2-2:1:1, petroleum ether and water composition, repeatedly extract 5-10 time.
As the further scheme of the present invention: in step (4), recrystallization is using methanol and/or ethyl acetate as recrystallization reagent.
Compared with prior art, the invention has the beneficial effects as follows:
The Nobiletin that the present invention obtains can as the quality control/Quality of Chinese Traditional Proprietary Medicine monitoring of national standard/medical material, decoction pieces. Good element task is provided for developing single structure product further; Compared with prior art, it has technological process simple, and practical, cost is low, and purity is high, and yield is high, it is adaptable to industrialized production in this invention, it is possible to provide a kind of quality testing means and detection sample (standard substance) reliably for plantation, manufacturing enterprise.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the technical scheme of this patent is described in more detail.
Embodiment 1
A kind of technique preparing Nobiletin based on multi-solvent, concretely comprises the following steps:
(1) raw material: with Pericarpium Citri Reticulatae for raw material;
(2) alcohol extraction: first raw material powder is broken into coarse powder, then extracts with methanol for solvent percolation, and after collecting extracting solution, concentrating under reduced pressure obtains the extractum without alcohol taste;
(3) extracting: first extracted 3 times by the organic solvents, chloroform of the extractum after alcohol extraction, the ternary two phase solvent system of the acetone, petroleum ether and the water composition that are 1.4:1:1 with volume ratio again after then being concentrated by extract extracts 6 times;
(4) recrystallization: by the extract lower floor after repeatedly extracting then through concentration, coarse crystallization, to be recrystallizing repeatedly so as to obtain purity be 98.2% Nobiletin crystalline solid, described recrystallization is using methanol and ethyl acetate as recrystallization reagent.
Embodiment 2
A kind of technique preparing Nobiletin based on multi-solvent, concretely comprises the following steps:
(1) raw material: with Pericarpium Citri Reticulatae and Fructus Aurantii Immaturus for raw material;
(2) alcohol extraction: first raw material powder is broken into coarse powder, then extracts for solvent reflux extraction with volumetric concentration for 70% ethanol, and after collecting extracting solution, concentrating under reduced pressure obtains the extractum without alcohol taste;
(3) extracting: first by the organic solvent extraction into ethyl acetate 4 times of the extractum after alcohol extraction, the ternary two phase solvent system of the acetone, petroleum ether and the water composition that are 1.6:1:1 with volume ratio again after then being concentrated by extract extracts 7 times
(4) recrystallization: by the extract lower floor after repeatedly extracting then through concentration, coarse crystallization, to be recrystallizing repeatedly so as to obtain purity be 98.8% Nobiletin crystalline solid, described recrystallization is using ethyl acetate as recrystallization reagent.
Embodiment 3
A kind of technique preparing Nobiletin based on multi-solvent, concretely comprises the following steps:
(1) raw material: with Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Fructus Aurantii and Pericarpium Citri grandis for raw material;
(2) alcohol extraction: first raw material powder is broken into coarse powder, then extracts for solvent infusion process with volumetric concentration for 90% ethanol, and after collecting extracting solution, concentrating under reduced pressure obtains the extractum without alcohol taste;
(3) extracting: first extracted 5 times by the organic solvents, chloroform of the extractum after alcohol extraction, the ternary two phase solvent system of the acetone, petroleum ether and the water composition that are 2:1:1 with volume ratio again after then being concentrated by extract extracts 10 times;
(4) recrystallization: by the extract lower floor after repeatedly extracting then through concentration, coarse crystallization, to be recrystallizing repeatedly so as to obtain purity be 98.9% Nobiletin crystalline solid, described recrystallization is using methanol as recrystallization reagent.
Above the better embodiment of this patent is explained in detail, but this patent is not limited to above-mentioned embodiment, in the ken that one skilled in the relevant art possesses, it is also possible to make a variety of changes under the premise without departing from this patent objective.
Claims (4)
1. the technique preparing Nobiletin based on multi-solvent, it is characterised in that concretely comprise the following steps:
(1) raw material: with any one or a few in Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Fructus Aurantii, Pericarpium Citri grandis for raw material;
(2) alcohol extraction: first raw material powder is broken into coarse powder, then extracts for solvent percolation or reflux extraction or infusion process with methanol or volumetric concentration for 50-95% ethanol, and after collecting extracting solution, concentrating under reduced pressure obtains the extractum without alcohol taste;
(3) extracting: first by the extractum organic solvents, chloroform after alcohol extraction or extraction into ethyl acetate, the ternary two phase solvent system formed with acetone, petroleum ether and water again after then being concentrated by extract extracts repeatedly;
(4) recrystallization: by the extract lower floor after repeatedly extracting then through concentration, coarse crystallization, to be recrystallizing repeatedly so as to obtain purity be more than 98% Nobiletin crystalline solid.
2. the technique preparing Nobiletin based on multi-solvent according to claim 1 and 2, it is characterised in that the organic solvent in step (3) adopts chloroform or ethyl acetate, extracts 2-5 time repeatedly.
3. the technique preparing Nobiletin based on multi-solvent according to claim 1 and 2, it is characterized in that, the ternary two-phase solvent body that organic solvent in step (3) adopts volume ratio to be the acetone of 1.2-2:1:1, petroleum ether and water composition, extracts 5-10 time repeatedly.
4. the technique preparing Nobiletin based on multi-solvent according to claim 1 and 2, it is characterised in that in step (4), recrystallization is using methanol and/or ethyl acetate as recrystallization reagent.
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| CN201610148825.7A CN105669626B (en) | 2016-03-16 | 2016-03-16 | A kind of technique that Nobiletin is prepared based on multi-solvent |
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| CN201610148825.7A CN105669626B (en) | 2016-03-16 | 2016-03-16 | A kind of technique that Nobiletin is prepared based on multi-solvent |
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| CN105669626A true CN105669626A (en) | 2016-06-15 |
| CN105669626B CN105669626B (en) | 2018-04-13 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111763188A (en) * | 2020-07-10 | 2020-10-13 | 陕西慧科植物开发有限公司 | Refining method of nobiletin in immature bitter orange flavone |
| CN116003366A (en) * | 2022-12-30 | 2023-04-25 | 陕西嘉禾药业有限公司 | Method for preparing nobiletin from immature bitter orange |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102875509A (en) * | 2012-11-02 | 2013-01-16 | 陕西慧科植物开发有限公司 | Method for extracting high-purity nobiletin from citrus peels |
-
2016
- 2016-03-16 CN CN201610148825.7A patent/CN105669626B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102875509A (en) * | 2012-11-02 | 2013-01-16 | 陕西慧科植物开发有限公司 | Method for extracting high-purity nobiletin from citrus peels |
Non-Patent Citations (3)
| Title |
|---|
| 张艳艳 等: "陈皮黄酮川陈皮素的分离纯化及抗炎止血作用研究", 《辽宁中医杂志》 * |
| 罗世坤 等: "陈皮中川陈皮素的提取分离及改性", 《食品科学》 * |
| 韦正 等: "Box-Behnken 效应面法优化陈皮中橙皮苷及川陈皮素提取工艺", 《中国实验方剂学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111763188A (en) * | 2020-07-10 | 2020-10-13 | 陕西慧科植物开发有限公司 | Refining method of nobiletin in immature bitter orange flavone |
| CN116003366A (en) * | 2022-12-30 | 2023-04-25 | 陕西嘉禾药业有限公司 | Method for preparing nobiletin from immature bitter orange |
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| CN105669626B (en) | 2018-04-13 |
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Effective date of registration: 20201110 Address after: Room 101, building 9, No. 96, Kechuang Road, Nancheng street, Dongguan City, Guangdong Province Patentee after: Dongguan Zhijun Pharmaceutical Technology Co., Ltd Address before: 330000 Jiangxi city of Nanchang province Wanli District cloud Bay Avenue Patentee before: JIANGXI University OF TRADITIONAL CHINESE MEDICINE |