CN107739358B - Daidzein anhydrous crystal form II, preparation method and medical application thereof - Google Patents
Daidzein anhydrous crystal form II, preparation method and medical application thereof Download PDFInfo
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- 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
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- C07D311/36—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 3 only not hydrogenated in the hetero ring, e.g. isoflavones
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Abstract
The invention relates to a daidzein anhydrous crystal form II, a preparation method and medical application thereof. Dissolving appropriate amount of daidzein raw material in excess in single solvent or mixed solvent to make it in supersaturated state; suspending the obtained mixture at 20-60 deg.C for 12-24 hr; and (3) separating the solid and the liquid of the obtained product, and drying in a forced air drying oven to obtain the solid of the daidzein anhydrous crystal form II. The daidzein anhydrous crystal form II provided by the invention has the advantages of simple preparation method, easy control of crystallization process, high crystallinity, good reproducibility, good stability and dissolution rate. Mixing with excipient, and making into tablet, capsule, granule, etc. Can be used for preventing and treating cardiovascular diseases such as hypertension, coronary heart disease, angina pectoris, arrhythmia, osteoporosis and climacteric syndrome.
Description
Technical Field
The invention belongs to the field of pharmaceutical chemicals, and particularly relates to a daidzein anhydrous crystal form, a preparation method thereof, a pharmaceutical composition containing the daidzein anhydrous crystal form, and medical application.
Background
Polymorphism refers to the phenomenon of solid states with different physicochemical properties formed by solid substances in two or more different spatial arrangements. In the field of pharmaceutical research, polymorphs include multicomponent crystalline forms such as organic solvates, hydrates, and the like.
Drug polymorphism is a characteristic inherent in small organic molecule compounds and widely exists in the drug development process. In theory small molecule drugs can have an infinite number of crystal packing patterns-polymorphs, and studies have shown that the number of drug polymorphs found is directly proportional to the study time and resources they have been invested in. As far as the world has been the highest selling drug, Lipitor (Lipitor), there are as many as 35 crystal forms that are patented. Polymorphism is not only controlled by the intrinsic factors such as the spatial structure of the molecule itself, the properties of functional groups, intramolecular and intermolecular interactions, but is also influenced by various factors such as the design of pharmaceutical synthesis processes, crystallization and purification conditions, choice of formulation excipients, formulation process routes and granulation methods, storage conditions, and packaging materials. Different crystal forms have different colors, melting points, solubilities, dissolution properties, reactivities, chemical stabilities, mechanical stabilities and the like, and the physical and chemical properties or the processability sometimes directly influence the safety and the effective performance of the medicine. Therefore, research and control of crystal forms become important research content in the process of drug development.
The crystal form research comprises two stages of crystal discovery and crystal form optimization, in the crystal discovery stage, various crystallization means are mainly adopted, such as crystallization methods of melt crystallization, solution volatilization, rapid cooling, suspension method and the like, external factors influencing drug crystallization are changed through crystallization conditions, solvents, temperature, speed, suspension solvent proportion and the like, a high-throughput sample preparation platform is adopted, hundreds of crystallization tests are prepared simultaneously, and a trace sample preparation technology and an analysis test means are adopted to prepare and discover a new crystal form. In the crystal form optimization stage, new crystal form process amplification and preparation conditions are required to be searched, various solid characterization means such as x-ray diffraction, solid nuclear magnetic resonance, Raman spectroscopy, infrared spectroscopy and other means are adopted for crystal form crystal characterization, in addition, DSC, TG A, DVS, HPLC and the like are adopted for carrying out physical and chemical property research on the crystal form, and the hygroscopicity, the chemical stability, the physical state stability, the processability and the like of different crystal forms are compared for carrying out research. Finally, the most preferable solid form is selected for development.
Daidzein (D α idzein) having the following chemical formula:
daidzein is flavonoid, has various pharmacological actions, has estrogen-like action, and can be used for treating osteoporosis, resisting cancer and inducing differentiation of cancer cells. However, the clinical application of daidzein is limited due to the problems of poor water solubility and low dissolution rate of daidzein. So far, the research on daidzein polymorphic forms is less. Therefore, through crystal form research, new crystal forms can be searched for to improve the pharmaceutical properties of the crystal forms. Based on earlier stage research, we obtained anhydrous crystal form I, and further research finds that most of the daidzein raw materials sold in the market are crystal form I. However, the crystal form has crystal transformation phenomenon in various solvents, and in addition, the crystal transformation phenomenon also occurs under the heating condition. Therefore, for the problems of low dissolution rate and poor stability of the daidzein raw material, further research on the crystal form of the daidzein raw material is necessary, and a new crystal form which is suitable for industrial production and has excellent performance is found, so that the daidzein raw material is beneficial to later-stage drug development.
Disclosure of Invention
One of the objects of the present invention is: provides a pure daidzein anhydrous crystal form II with high crystallinity, good stability and fast dissolution rate.
The second purpose of the invention is: provides a preparation method of the daidzein anhydrous crystal form II, which has simple preparation and good reproducibility and is suitable for industrial production.
In order to solve the technical problems, the invention is realized by the following technical scheme:
an anhydrous daidzein crystal form II, which is characterized in that the diffraction angle of the X-ray powder diffraction measured by Cu-Kalpha ray and expressed by 2 theta has characteristic peaks at 10.26 +/-0.20 degrees, 15.81 +/-0.20 degrees, 16.92 +/-0.20 degrees and 24.54 +/-0.20 degrees, wherein the relative intensity of the characteristic peak at 24.54 +/-0.20 degrees is 100%. Further, the crystal form has characteristic peaks at 6.78 +/-0.20 °, 8.36 +/-0.20 °, 12.90 +/-0.20 °, 13.72 +/-0.20 °, 18.92 +/-0.20 °, 22.22 +/-0.20 °, 24.54 +/-0.20 °, 25.26 +/-0.20 °, 26.46 +/-0.20 °, 28.06 +/-0.20 °, 28.68 +/-0.20 ° and 29.78 +/-0.20 °.
According to a more preferred technical scheme of the invention, the diffraction angle of the anhydrous crystal form II expressed by 2 theta of X-ray powder diffraction measured by using Cu-Kalpha rays has characteristic peaks shown in the following table 1.
TABLE 1X-ray powder diffraction List of Anhydrous crystalline form II
| Peak numbering | 2-Thetα | d-value (A) | Strength of | L/L0 |
| 1 | 6.78 | 13.02 | 85 | 8.3 |
| 2 | 8.36 | 10.57 | 147 | 14.3 |
| 3 | 10.26 | 8.61 | 743 | 72.3 |
| 4 | 12.90 | 6.86 | 60 | 5.8 |
| 5 | 13.72 | 6.45 | 30 | 2.9 |
| 7 | 15.81 | 5.60 | 927 | 90.2 |
| 8 | 16.92 | 5.24 | 754 | 73.3 |
| 9 | 18.92 | 4.69 | 34 | 3.3 |
| 10 | 22.22 | 3.40 | 44 | 4.3 |
| 11 | 24.54 | 3.62 | 1028 | 100.0 |
| 12 | 25.26 | 3.52 | 360 | 35.0 |
| 13 | 26.46 | 3.37 | 323 | 31.4 |
| 14 | 28.06 | 3.18 | 291 | 28.3 |
| 15 | 28.68 | 3.11 | 271 | 26.4 |
| 16 | 29.78 | 2.30 | 152 | 14.8 |
An anhydrous crystalline form II according to the present invention having a d-value (Α) as shown in the above table. Preferably, the anhydrous crystalline form has characteristic peak intensities as shown in the above table.
Anhydrous crystalline form II according to the present invention, characterized in that said crystalline form has an X-ray powder diffraction pattern as shown in figure 1.
According to a preferred embodiment of the present invention, the crystal form is an orthorhombic system, and the space group is P2 12121Cell parameter of
α ═ β ═ γ ═ 90 °, unit cell volume is
According to a preferred embodiment of the present invention, the water content of the anhydrous crystalline form II is less changed with the change of the relative humidity. For example, at a relative humidity of from 30% to 95%, there is no significant increase in the mass percentage of the water content (less than 0.5%), and under such conditions there is little hygroscopicity.
According to the invention, the change in the moisture content with relative humidity is shown in fig. 2.
According to the preferred technical scheme of the invention, the anhydrous crystal form II is stable within the relative humidity range of 30-95%, and the crystal form can be kept unchanged. The specific X-ray powder diffraction is shown in FIG. 3.
According to a preferred embodiment of the present invention, the thermogravimetric analysis (TG Α) of the anhydrous crystalline form II is free from weight loss phenomenon before heating to decomposition. As shown in particular in fig. 4.
According to a preferred technical scheme, the Differential Scanning Calorimetry (DSC) pattern of the anhydrous crystal form II has a characteristic melting peak at 331.1 +/-2 ℃. As shown in particular in fig. 5.
According to the invention, the infrared spectrum of the anhydrous crystal form II is 3202, 1632, 1596, 1519, 1387, 1280, 1239, 1097, 899, 888 and 844cm-1Has characteristic peaks. As shown in particular in fig. 6.
According to the invention, the Raman spectrum of the anhydrous crystal form II is 3085, 1620, 1309, 1220, 1195, 1046, 957, 891, 791 and 783cm-1Has characteristic peaks. As shown in particular in fig. 7.
According to the invention, the anhydrous crystal form II can be kept unchanged in common solvent systems, such as water, methanol, ethanol, acetonitrile and ethyl acetate, as shown in figure 8.
The invention also provides a preparation method of the daidzein anhydrous crystal form II, which is characterized by comprising the following steps:
(1) dissolving appropriate amount of daidzein raw material in excess in single solvent or mixed solvent to make it in supersaturated state;
(2) suspending the mixture obtained in the step (1) at the temperature of 20-60 ℃ for 12-24 hours;
(3) and (3) carrying out solid-liquid phase separation on the product obtained in the step (2), and drying in a forced air drying oven to obtain the solid of the daidzein anhydrous crystal form II.
The daidzein raw material is of crystal form I, and its X-ray powder diffraction pattern is shown in figure 10.
The single solvent is methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, nitromethane, ethyl acetate, methyl tert-butyl ether, methyl isobutyl ketone, toluene, dichloromethane or water; the mixed solvent is prepared by mixing two or more than two of the solvents according to any proportion.
The suspension temperature of 20-60 ℃ varies depending on the solvent chosen, i.e. it cannot exceed the boiling point of the solvent.
The invention also provides a pharmaceutical composition, which is characterized by comprising the daidzein anhydrous crystal form II and pharmaceutically acceptable excipient.
According to the invention, the excipients in the pharmaceutical composition comprise diluents, binders, wetting agents, disintegrants, lubricants.
The diluent can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, and calcium carbonate.
The wetting agent can be water, ethanol, isopropanol.
The binder can be starch slurry, dextrin, syrup, Mel, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, carboxymethylcellulose sodium, methylcellulose, hydroxypropyl methylcellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, and polyethylene glycol.
The disintegrant may be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, crosslinked sodium carboxymethylcellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitol fatty acid ester, and sodium dodecyl sulfate.
The lubricant can be pulvis Talci, silicon dioxide, stearate, tartaric acid, liquid paraffin, and polyethylene glycol.
The invention also provides a pharmaceutical preparation, which is characterized by comprising the pharmaceutical composition.
The pharmaceutical preparation according to the present invention is characterized in that the preparation comprises dosage forms such as tablets, capsules, granules and the like. More preferably capsules.
The invention also provides a preparation method of the pharmaceutical preparation, which is characterized in that the pharmaceutical composition is mixed with excipient and then prepared into different dosage forms such as tablets, capsules, granules and the like. The preparation method of the dosage forms of the pharmaceutical composition, such as tablets, capsules, granules, and the like, is the same as the preparation method of the dosage forms of the tablets, capsules, granules, and the like which are conventional in the field.
The invention also provides the application of the daidzein anhydrous crystal form II in preparing a raw material of a medicament for preventing and treating cardiovascular diseases such as hypertension, coronary heart disease, angina, arrhythmia, osteoporosis and climacteric syndrome of women.
The invention has the beneficial effects that:
the daidzein anhydrous crystal form II provided by the invention has the advantages of simple preparation method, easy control of crystallization process, high crystallinity, good reproducibility, good stability and dissolution rate.
Drawings
FIG. 1 is an X-ray powder diffraction (XRPD) pattern of daidzein anhydrous crystalline form II provided by the present invention;
FIG. 2 is a dynamic moisture sorption (DVS) diagram of the daidzein anhydrate form II provided by the present invention;
FIG. 3 is an XRPD pattern of the daidzein anhydrous crystal form II provided by the invention after dynamic moisture adsorption;
FIG. 4 is a thermogravimetric analysis (TG) diagram of daidzein anhydrous crystal form II provided by the present invention;
FIG. 5 is a Differential Scanning Calorimetry (DSC) chart of the daidzein anhydrous crystal form II provided by the present invention
FIG. 6 is an Infrared (IR) spectrum of daidzein anhydrous form II provided by the present invention;
FIG. 7 is a Raman spectrum (R α m α n) of daidzein anhydrous crystal form II provided by the present invention;
FIG. 8 is an XRPD pattern of the stability of daidzein anhydrate form II provided by the present invention in various solvent systems;
FIG. 9 is an XRPD pattern for the anhydrous crystalline form II obtained in example 1 of the present invention;
FIG. 10 is an XRPD pattern for daidzein starting material form I as used in example 1 of the present invention;
FIG. 11 is an XRPD pattern for crystalline anhydrate form II obtained by example 2 of the present invention;
FIG. 12 is an XRPD pattern for crystalline anhydrate form II obtained by example 3 of the present invention;
FIG. 13 is an XRPD pattern for crystalline anhydrate form II obtained by example 4 of the present invention;
FIG. 14 shows the percentage of dissolution of powder of daidzein starting material form I and form II in pure water within 20 minutes;
FIG. 15 is a UV calibration curve of daidzein according to the present invention.
Detailed Description
The present invention will be described in further detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. Any modifications and variations made on the basis of the present invention are still within the scope of the present invention.
Example 1
Placing 30mg of daidzein raw material in a 4mL sample bottle, adding 2mL of water, performing ultrasonic treatment to dissolve the daidzein raw material and make the daidzein raw material in a supersaturated state, suspending the daidzein raw material at room temperature for 24 hours, centrifuging the suspension, removing supernatant, and drying the centrifuged solid to obtain the daidzein anhydrous crystal form II, wherein XRPD results of the daidzein anhydrous crystal form II are shown in figure 9. The daidzein raw material crystal form XRPD is shown in figure 10.
Example 2
Placing 30mg of daidzein raw material into a 4mL sample bottle, adding 2mL of ethyl acetate, performing ultrasonic treatment to dissolve the daidzein raw material and make the daidzein raw material in a supersaturated state, suspending the daidzein raw material at room temperature for 24 hours, centrifuging the suspension, removing supernatant, and drying the centrifuged solid to obtain the daidzein anhydrous crystal form II. The XRPD pattern is as shown in figure 11. The daidzein raw material crystal form XRPD is shown in figure 10.
Example 3
Placing 30mg of daidzein raw material into a 4mL sample bottle, adding 2mL of methanol, performing ultrasonic treatment to dissolve the daidzein raw material and make the daidzein raw material in a supersaturated state, suspending the daidzein raw material at room temperature for 24 hours, centrifuging the suspension, removing supernatant, and drying the centrifuged solid to obtain the daidzein anhydrous crystal form II. The XRPD pattern is as shown in figure 12. The daidzein raw material crystal form XRPD is shown in figure 10.
Example 4
And (4) amplifying the experiment. Weighing 600mg of daidzein raw material into a 100mL crystallizer, adding 40mL of methanol, controlling the stirring speed to be 300rpm by using mechanical stirring, sampling and testing XRPD after 24 hours at room temperature, thus obtaining the daidzein anhydrous crystal form II, wherein the XRPD result is shown in figure 13.
Example 5
About 3mg of the solid daidzein anhydrous crystal form II sample prepared in example 3 was subjected to dynamic water adsorption analysis using VTI-AsA instrument company of America+And (5) measuring by using a dynamic moisture adsorption instrument. The temperature is 25 ℃ and the relative humidity is in the range of 30-95%. The results show that this anhydrous form II had little hygroscopic weight gain under this condition, as shown in figure 2. And the crystal form is kept unchanged, and an XRPD pattern is shown as figure 3.
The daidzein anhydrous crystal form II provided by the invention is prepared by X-ray powder diffraction (XRPD), thermogravimetric analysis (TG), Differential Scanning Calorimetry (DSC), dynamic moisture adsorption (DVS) and liquid nuclear magnetism (H)1-NMR), Infrared (IR) and raman (R α m α n).
The daidzein anhydrous crystal form II samples obtained in examples 1-4 were subjected to X-ray powder diffraction analysis using a D/McAX 2500 type diffractometer from Japan, using Cu-Ka rays
The voltage is 40 kilovolts, the current is 200 milliamps, the scanning speed is 8 degrees/minute, and the scanning range is 2-40 degrees.
The solid daidzein anhydrous crystal form II samples obtained in examples 1 to 4 were subjected to thermogravimetric analysis using a type thermogravimetric analyzer of Mettlerlatidol TG A/DSC 1, Switzerland, under nitrogen, at a temperature increase rate of 10 ℃/min.
Differential scanning calorimetry was performed on the daidzein anhydrous crystalline form II solid samples obtained in examples 1-4, and the results were examined by DSC1 type differential scanning calorimeter of Mettlerlatido Switzerland under nitrogen at a heating rate of 10 ℃/min.
Infrared spectroscopic analysis of the daidzein anhydrous crystalline form II solid samples obtained in examples 1-4 was performed using a Nicolet-Magna FT-IR 750 Infrared Spectroscopy from Nicol, Nykul, USARoom temperature detection, the detection range is 4000-400cm-1Wave number. The analysis results are shown in FIG. 6.
The daidzein anhydrous crystal form II solid samples prepared in examples 1-4 were subjected to Raman spectroscopy, which was performed at room temperature using DXR micro-Raman spectrometer from pyroelectric corporation, and the detection range was 3450-50cm-1And (4) Raman shift. The analysis results are shown in FIG. 7.
Example 6
Stability test of daidzein anhydrous crystal form II in solution
The experimental conditions are as follows: weighing about 15mg of the daidzein anhydride II prepared in example 1, dissolving the daidzein anhydride in a 2mL sample bottle, adding 1mL of methanol, ethanol, acetonitrile, ethyl acetate and water respectively, dissolving the daidzein anhydride in a supersaturated state by ultrasonic treatment, suspending the daidzein anhydride at room temperature for 24 hours, centrifuging the suspension, discarding the supernatant, drying the centrifuged solid, and testing the obtained product for XRPD.
In the invention, the anhydrous crystal form II can be kept unchanged in methanol, ethanol, acetonitrile, ethyl acetate and water. The specific results are shown in FIG. 8.
Example 7
Dissolution test of daidzein crystal form II powder
The experimental conditions are as follows: dissolution experiments were performed using a dissolution tester model RC-6. The dissolution media were 500mL of pure water. The rotation speed was controlled at 100rpm, the temperature was controlled at 37 ℃ and 50mg of each of the test samples were added. The sample used in the method is the anhydrous crystal form II in the invention, and the anhydrous crystal form II is sieved by a 100-mesh sieve, so that the particle size is prevented from influencing the dissolution result. Sampling 4ml after 5min,10min,15min,20min and 24h, supplementing 4ml of dissolution medium with 37 ℃ for each sampling, filtering the sampled product by a 0.45 mu m microporous membrane, and quantifying by an ultraviolet spectrum standard curve after proper dilution. The results are shown in fig. 14, wherein the dissolution rate of form II is approximately 2 times that of form I. After the completion, an undissolved solid sample was recovered and subjected to test analysis by X-ray powder diffraction, and the result showed that the form II in the present invention could be kept unchanged.
Ultraviolet standard curve: using a U-3010 type UV spectrophotometer, a 1.000cm quartz cuvette and an analytical wavelength of 248nmA blank was run on a quartz cuvette with dissolution media. A standard curve was prepared using concentration standards of 0.52,1.04,2.08,3.12,4.16,5.2,6.24, 7.28. mu.g/mL as shown in FIG. 15 to obtain R2Linear coefficient of 0.9998.
Example 8
The formulation of the pharmaceutical composition is shown in the following table:
firstly, uniformly mixing daidzein (anhydrous crystal form II) and starch, adding 2g of microcrystalline cellulose sodium and a proper amount of water to prepare a soft material, sieving with a 20-mesh sieve for granulation, drying, sieving with a 18-mesh sieve for granulation, adding crosslinked polyvinylpyrrolidone and magnesium stearate, uniformly mixing, and preparing 100 capsules.
The daidzein anhydrous crystal form II provided by the invention is also daidzein, and the daidzein has certain application in the medicines for preventing and treating cardiovascular diseases such as hypertension, coronary heart disease, angina pectoris, arrhythmia, osteoporosis and female climacteric syndrome.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (10)
1. An anhydrous daidzein crystal form II, which is characterized in that the anhydrous daidzein crystal form II has characteristic X-ray diffraction peaks at diffraction angles of 10.26 +/-0.20 degrees, 15.81 +/-0.20 degrees, 16.92 +/-0.20 degrees and 24.54 +/-0.20 degrees, wherein the relative intensity of the characteristic peak at 24.54 +/-0.20 degrees is 100 percent, which are expressed by an X-ray powder diffraction pattern measured by Cu-Kalpha rays; and the crystal form is an orthorhombic system, and the space group is P212121Cell parameter of
α ═ β ═ γ ═ 90 °, unit cell volume is
2. The daidzein anhydrous crystalline form II according to claim 1, characterized in that said daidzein anhydrous crystalline form has characteristic peaks at 6.78 ± 0.20 °, 8.36 ± 0.20 °, 12.90 ± 0.20 °, 13.72 ± 0.20 °, 18.92 ± 0.20 °, 22.22 ± 0.20 °, 24.54 ± 0.20 °, 25.26 ± 0.20 °, 26.46 ± 0.20 °, 28.06 ± 0.20 °, 28.68 ± 0.20 °, 29.78 ± 0.20 ° in its X-ray powder diffraction pattern.
3. The daidzein anhydrate form II as claimed in claim 1, characterized by an increase in water content of less than 0.5% by mass over a range from 30% relative humidity to 95% relative humidity.
4. The daidzein anhydrous crystalline form II according to claim 1, wherein the thermal weight loss analysis (TG Α) of daidzein anhydrous crystalline form II is free of weight loss prior to heating to decomposition;
a Differential Scanning Calorimetry (DSC) spectrum of the daidzein anhydrous crystal form II has a characteristic melting peak at 331.1 +/-2.0 ℃, and is unchanged before.
5. The daidzein anhydrate form II of claim 1 having an IR spectrum of 3202, 1632, 1596, 1519, 1387, 1280, 1239, 1097, 899, 888, 844cm-1Has a characteristic peak;
the daidzein anhydrous crystal form II has Raman spectra of 3085, 1620, 1309, 1220, 1195, 1046, 957, 891, 791 and 783cm-1Has characteristic peaks.
6. The method for preparing daidzein anhydrous crystal form II according to claim 1, wherein said method comprises the steps of:
(1) dissolving excessive daidzein raw material in single solvent to make it in supersaturated state;
(2) suspending the mixture obtained in the step (1) at the temperature of 20-60 ℃ for 12-24 hours;
(3) separating the solid-liquid phase of the product obtained in the step (2), and drying in a forced air drying oven to obtain a solid of the daidzein anhydrous crystal form II;
the single solvent is methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, nitromethane, ethyl acetate, methyl tert-butyl ether, methyl isobutyl ketone, toluene, dichloromethane or water.
7. A pharmaceutical composition prepared using the daidzein anhydrate form II of claim 1, wherein said pharmaceutical composition comprises the daidzein anhydrate form II of claim 1, and a pharmaceutically acceptable excipient;
the excipient in the pharmaceutical composition is selected from diluent, adhesive, wetting agent, disintegrating agent and lubricant;
the diluent is starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate or calcium carbonate;
the wetting agent is water, ethanol or isopropanol;
the binder is starch slurry, dextrin, syrup, Mel, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, carboxymethylcellulose sodium, methylcellulose, hydroxypropyl methylcellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone or polyethylene glycol;
the disintegrant is dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone, crosslinked sodium carboxymethylcellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitol fatty acid ester or sodium dodecyl sulfate;
the lubricant is pulvis Talci, silicon dioxide, stearate, tartaric acid, liquid paraffin, and polyethylene glycol.
8. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition is in the form of a tablet, capsule or granule.
9. Use of the daidzein anhydrate form II of claim 1 in the manufacture of a medicament for the prevention or treatment of cardiovascular disease, osteoporosis and female climacteric syndrome.
10. The use according to claim 9, characterized in that the cardiovascular disease is hypertension, coronary heart disease, angina pectoris or arrhythmia.
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