CN108997293A - A kind of new crystal of Quercetin and preparation method thereof - Google Patents
A kind of new crystal of Quercetin and preparation method thereof Download PDFInfo
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- CN108997293A CN108997293A CN201810801509.4A CN201810801509A CN108997293A CN 108997293 A CN108997293 A CN 108997293A CN 201810801509 A CN201810801509 A CN 201810801509A CN 108997293 A CN108997293 A CN 108997293A
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- 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
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
- C07D311/62—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2 with oxygen atoms directly attached in position 3, e.g. anthocyanidins
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The invention discloses new crystal of a kind of Quercetin and preparation method thereof.Quercetin hydrate crystal of the invention is the new crystal of Quercetin, the X-ray powder diffraction collection that the hydrate crystal is indicated with the 2 θ ± 0.2 ° angles of diffraction is at 3.18 °, 8.71 °, 10.38 °, 11.60 °, 13.89 °, 14.98 °, 15.78 °, 16.65 °, 17.74 °, 20.01 °, 21.82 °, 23.56 °, 24.89 °, 25.21 °, 26.35 °, 26.56 °, 27.24 °, 27.98 °, 31.25 °, 32.21 °, 33.12 °, 35.02 °, 36.89 °, 37.65 °, 38.21 °, 39.65 °, 40 °, 41.21 °, 42.21 °, 43.86 °, Characteristic diffraction peak is shown at 45.21 °, the X-ray powder diffraction spectrogram obtained using Cu-Ka radionetric survey is as shown in Figure 1, entirely different with the prior art.The new crystal of Quercetin of the invention has preferable dissolubility and higher stability, is very suitable to clinical application.The invention also discloses the preparation methods of the new crystal, and the preparation method is simply mild, are suitble to industrialized production.
Description
Technical field
The present invention relates to pharmaceutical chemistry technical fields, and in particular to a kind of new crystal of Quercetin and preparation method thereof.
Background technique
Quercetin, chemical name: 3,5,7,3 ', 4 ' ,-pentahydroxyflavone;English name: Quercetin, the molecule knot of Quercetin
Structure is as follows:
Quercetin has preferable eliminating the phlegm, antitussive action, and has certain antiasthmatic effect.In addition there are reduce blood pressure, increase
The effects of strong capillary resistance, reduction capillary fragility, reducing blood lipid, coronary artery dilator, increase coronary blood flow.With
In treatment chronic bronchitis.Also there is auxiliary therapeutic action to coronary heart disease and hypertensive patient.Antitumor action and antiplatelet
Aggregation: Quercetin can significantly inhibit the effect of carcinogenic promoting agent, the growth for inhibiting in vitro malignant cell, inhibit ehrlich ascites cell
DNA, RNA and protein synthesis.
The Quercetin of institute of Materia Medica,Chinese Academy of Medical Sciences invention is described in Chinese patent CN200710177085
Two kinds of crystal-form substances, its preparation method and its pharmaceutical composition and purposes;Quercetin crystal-form substances are disclosed in CN201210519728
α, its preparation method and its pharmaceutical composition and purposes;Two kinds of Quercetin crystal form α and β prevent and treat the nervous system disease, heart and brain in preparation
It is had a good application prospect in vascular system disease, disease of immune system and anti-inflammatory drug.
As it is known by the man skilled in the art that the polymorph of drug has become drug research process and pharmaceutical production quality control
Essential important component in system and detection process.It is living that new drug compound biology is facilitated to the research of drug polymorph
Property selection, help to improve bioavilability, promote clinical efficacy, facilitate the selection and design of drug administration approach, with
And the determination of pharmaceutical preparation technology parameter, to improve pharmaceutical production quality.Same drug crystalline form is different, and bioavilability can
It can significant difference.Same drug, certain crystalline forms may have higher bioactivity than other crystalline forms.
We pass through continuous Improvement, after having carried out a large amount of test, provide it is a kind of new be different from it is existing
The quercitrin cellulose crystal of technology.
Summary of the invention
The object of the present invention is to provide a kind of new crystal of Quercetin, the new crystal stability, suitable range are extensively good, improve life
Object availability has widened range of choice of the Quercetin when preparing pharmaceutical composition.
In order to achieve the object of the present invention, the technical solution of use are as follows:
A kind of new crystal of Quercetin, which is characterized in that its X-ray powder diffraction indicated with the 2 θ ± 0.2 ° angles of diffraction
Map 3.18 °, 8.71 °, 10.38 °, 11.60 °, 13.89 °, 14.98 °, 15.78 °, 16.65 °, 17.74 °, 20.01 °,
21.82°、23.56°、24.89°、25.21°、26.35°、26.56°、27.24°、27.98°、31.25°、32.21°、33.12°、
Spy is shown at 35.02 °, 36.89 °, 37.65 °, 38.21 °, 39.65 °, 40 °, 41.21 °, 42.21 °, 43.86 °, 45.21 °
Levy diffraction maximum.
The new crystal of the Quercetin, which is characterized in that the X-ray powder diffraction figure obtained using Cu-K alpha ray measurement
As shown in Figure 1.
The present invention also provides the methods for preparing the new crystal of Quercetin:
(1) by the aqueous sulfuric acid of 1% percent by volume, rutin is added after being heated to boiling, reacts filtering, water after 1.5h
It washes, dry, obtain Quercetin crude product;
(2) above-mentioned Quercetin crude product is added in refining solvent and is washed, filters pressing, separation, drying obtain high-purity quercetin
New crystal.
Preferred a kind of preparation method of the new crystal of Quercetin, which is characterized in that the rutin and the sour water mixture
Solid-liquid ratio is 1kg:20~45L.
Preferred a kind of preparation method of the new crystal of Quercetin, which is characterized in that the solvent is selected from ethyl acetate, first
One kind of alcohol, ethyl alcohol, methanol solution or ethanol solution.
A kind of preferred preparation method of the new crystal of Quercetin, which is characterized in that the solid-liquid ratio of Quercetin crude product and solvent
For 1kg:15L.
Preferred a kind of preparation method of the new crystal of Quercetin, which is characterized in that in the filters pressing step, pressurized conditions are
0.4MPa reacts 2h.
The present invention has an advantage that preparation process of the present invention is simple in the art, obtains with good stability
The new crystal of Quercetin, high income, it is at low cost, be suitable for industrialized production, the purity of products obtained therefrom widens 99.5% or more
The range of choice of Quercetin substrate in preparation pharmaceutical composition.
Detailed description of the invention:
Fig. 1 is the X-ray powder diffraction figure of the new crystal of Quercetin of the present invention;
Fig. 2 is the heat differential scanning calorimetry figure of the new crystal of Quercetin of the present invention;
Following embodiment is only that the present invention will be described in detail, is not intended to limit the present invention.
Specific embodiment:
Embodiment 1: the preparation of the new crystal of Quercetin
By the aqueous sulfuric acid of 1% percent by volume, it is heated to that refined rutin is added after boiling, solid-liquid ratio 1kg:45L,
Filtering, washing, drying, obtain Quercetin crude product after reaction 1.5h;
Above-mentioned Quercetin crude product is added in ethanol solution with the ratio of 1kg:15L and is washed, 0.4MPa is pressurized to, reacts 2h
Filters pressing is carried out, rear separation, drying obtain the new crystal of high-purity quercetin.
Embodiment 2: the preparation of the new crystal of Quercetin
By the aqueous sulfuric acid of 1% percent by volume, it is heated to that refined rutin is added after boiling, solid-liquid ratio 1kg:30L,
Filtering, washing, drying, obtain Quercetin crude product after reaction 2h;
Above-mentioned Quercetin crude product is added in methanol solution with the ratio of 1kg:15L and is washed, 0.4MPa is pressurized to, reacts 2h
Filters pressing is carried out, rear separation, drying obtain the new crystal of high-purity quercetin.
Embodiment 3: the preparation of the new crystal of Quercetin
By the aqueous sulfuric acid of 1% percent by volume, it is heated to that refined rutin is added after boiling, solid-liquid ratio 1kg:20L,
Filtering, washing, drying, obtain Quercetin crude product after reaction 3h;
Above-mentioned Quercetin crude product is added in ethyl alcohol with the ratio of 1kg:15L and is washed, 0.4MPa is pressurized to, reaction 2h is carried out
Filters pressing, rear separation, drying, obtains the new crystal of high-purity quercetin.
Embodiment 4: the preparation of the new crystal of Quercetin
By the aqueous sulfuric acid of 1% percent by volume, it is heated to that refined rutin is added after boiling, solid-liquid ratio 1kg:20L,
Filtering, washing, drying, obtain Quercetin crude product after reaction 3h;
Above-mentioned Quercetin crude product is added in methanol with the ratio of 1kg:15L and is washed, 0.4MPa is pressurized to, reaction 2h is carried out
Filters pressing, rear separation, drying, obtains the new crystal of high-purity quercetin.
Embodiment 5: the preparation of the new crystal of Quercetin
By the aqueous sulfuric acid of 1% percent by volume, it is heated to that refined rutin is added after boiling, solid-liquid ratio 1kg:20L,
Filtering, washing, drying, obtain Quercetin crude product after reaction 3h;
Above-mentioned Quercetin crude product is added in ethyl acetate with the ratio of 1kg:15L and is washed, 0.4MPa is pressurized to, reacts 2h
Filters pressing is carried out, rear separation, drying obtain the new crystal of high-purity quercetin.
Embodiment 6: the physical property characteristic of the new crystal of Quercetin
The new crystal of Quercetin according to the preparation of 1 method of embodiment after dry, grinding are taken, sampling carries out X-ray powder and spreads out
It penetrates, radiation source Cu-Ka, map is shown in Fig. 1, the rear new crystal of Quercetin prepared again according to embodiment 2-5 the method, diffraction pattern
It composes identical as Fig. 1.
1 X-ray powder diffraction collection of table
Embodiment 7: being detected with the new crystal of Quercetin of the heat differential scanning calorimetry to embodiment 1, as shown in Figure 2 its
There is absorption heat at 158.5 DEG C and 330 DEG C.
Embodiment 8: it is straight that crystal α and β known to the new crystal of Quercetin prepared by the present invention and two kinds are dissolved in deionized water
To saturation, the water solubility of saturated solution is analyzed by HPLC, the solubility for measuring it at 25 DEG C is as shown in table 2.Wherein quercitrin
Cellulose crystal α is prepared according to preparation method described in the embodiment 1 recorded in Chinese patent CN200710177085, quercitrin cellulose crystal β
It is prepared according to preparation method described in the embodiment 3 recorded in Chinese patent CN200710177085.
2 three kinds of Quercetin Crystal solubility comparisons of table
The new crystal of Quercetin | Alpha-crystal | Β crystal | |
Solubility mg/mL | 186.5 | 89.5 | 131.4 |
Embodiment 9: heat stabilization test
Under the stress conditions of 40 ± 2 DEG C and 75% relative humidity, by the new crystal of Quercetin prepared in accordance with the present invention and
Crystal α and β are stored known to two kinds with sealing state, and pass through the new crystal of active Quercetin after HPLC measurement 15,30,60,90 days
Surplus, as a result such as table 3.Wherein quercitrin cellulose crystal α is according to 1 institute of embodiment recorded in Chinese patent CN200710177085
Preparation method preparation is stated, quercitrin cellulose crystal β is according to preparation side described in the embodiment 3 recorded in Chinese patent CN200710177085
Method preparation.
3 three kinds of quercitrin cellulose crystal surpluses of table
The amount (ug/mg) of the new crystal of Quercetin | The amount of alpha-crystal | The amount of Β crystal | |
Initial value | 998 | 998 | 998 |
15 days | 997 | 997 | 997 |
30 days | 998 | 985 | 993 |
60 days | 997 | 960 | 976 |
90 days | 997 | 932 | 943 |
As shown in table 3, it can prove that the new crystal of Quercetin of the invention has by the result obtained under accelerated ageing conditions
There is high stability.
Claims (7)
1. a kind of new crystal of Quercetin, which is characterized in that its X-ray powder diffraction figure indicated with the 2 θ ± 0.2 ° angles of diffraction
Spectrum 3.18 °, 8.71 °, 10.38 °, 11.60 °, 13.89 °, 14.98 °, 15.78 °, 16.65 °, 17.74 °, 20.01 °,
21.82°、23.56°、24.89°、25.21°、26.35°、26.56°、27.24°、27.98°、31.25°、32.21°、33.12°、
Spy is shown at 35.02 °, 36.89 °, 37.65 °, 38.21 °, 39.65 °, 40 °, 41.21 °, 42.21 °, 43.86 °, 45.21 °
Levy diffraction maximum.
2. the new crystal of Quercetin as described in claim 1, which is characterized in that the X-ray obtained using Cu-K alpha ray measurement
Powder diagram is as shown in Figure 1.
3. a kind of preparation method of any new crystal of Quercetin of claim 1-2, which is characterized in that the preparation method
Specific steps are as follows:
(1) by the aqueous sulfuric acid of 1% percent by volume, rutin is added after being heated to boiling, reacts filtering, water after 1.5-3h
It washes, dry, obtain Quercetin crude product;
(2) above-mentioned Quercetin crude product is added in refining solvent and is washed, it is newly brilliant to obtain high-purity quercetin for filters pressing, separation, drying
Body.
4. the preparation method of the new crystal of Quercetin as claimed in claim 3, which is characterized in that the rutin and the sour water are mixed
Conjunction material liquid ratio is 1kg:20~45L.
5. the preparation method of the new crystal of Quercetin as claimed in claim 3, which is characterized in that the solvent is selected from acetic acid second
One kind of ester, methanol, ethyl alcohol, methanol solution or ethanol solution.
6. the preparation method of the new crystal of Quercetin as claimed in claim 3, which is characterized in that the material of Quercetin crude product and solvent
Liquor ratio is 1kg:15L.
7. the preparation method of the new crystal of Quercetin as claimed in claim 3, which is characterized in that in the filters pressing step, pressurization
Condition is 0.4MPa, reacts 2h.
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CN110452207A (en) * | 2019-09-12 | 2019-11-15 | 河北医科大学 | A kind of Quercetin novel crystal forms and preparation method thereof |
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