Ginsenoside C-K polymorphic compounds and method for preparing same
09670245 ยท 2017-06-06
Assignee
Inventors
- Guobin Ren (Shanghai, CN)
- Changliang Dai (Zhejiang, CN)
- Jinyao Chen (Shanghai, CN)
- Feng Chen (Zhejiang, CN)
- Minghui Qi (Shanghai, CN)
- Wenming Zhu (Zhejiang, CN)
- Minghuang Hong (Shanghai, CN)
- Hua Bai (Zhejiang, CN)
Cpc classification
International classification
Abstract
Provided are several types of ginsenoside polymorphic substances and a method for preparing same. In particular, new crystal form A, crystal form B, crystal form C, crystal form E, crystal form F, crystal form I, crystal form K, crystal form L, crystal form M, crystal form N, and crystal form O are involved.
Claims
1. A crystal form A of ginsenoside C-K, characterized by an XRPD pattern comprising peaks at 2 values of 5.44, 7.06, 8.94, 11.61, 13.70, 14.43, 15.81, 17.22, 17.84, 18.71, and 19.01 degrees, wherein the error range of the 2 values is 0.2 degrees.
2. The crystal form A according to claim 1, wherein the XRPD pattern further comprises peaks at 2 values of 9.51, 12.28, 16.14, 20.90, 21.90, 25.68, and 27.71 degrees, wherein the error range of the 2 values is 0.2 degrees.
3. A method for preparing the crystal form A of ginsenoside C-K according to claim 1, comprising: (1) dissolving ginsenoside C-K in 1-methyl-2-pyrrolidone or a mixed solvent consisting of 1-methyl-2-pyrrolidone and acetone; (2) removing the solvent slowly by evaporation; and (3) drying the resultant solid under vacuum to obtain the crystal form A of ginsenoside C-K.
4. The crystal form A according to claim 1, wherein the XRPD pattern is substantially the same as
5. The crystal form A according to claim 1, further characterized by a DSC pattern comprising an endothermic peak at 1175 C.
6. The crystal form A according to claim 2, further characterized by a DSC pattern comprising an endothermic peak at 1175 C.
7. The crystal form A according to claim 4, further characterized by a DSC pattern comprising an endothermic peak at 1175 C.
8. A method for preparing the crystal form A of ginsenoside C-K according to claim 1, comprising: (1) dissolving ginsenoside C-K in 1-methyl-2-pyrrolidone; (2) adding an anti-solvent dropwise, wherein the anti-solvent is selected from the group consisting of isopropyl ether, water, and nitromethane; and (3) after stirring for a while, filtering the resultant suspension, and drying the filter cake under vacuum to obtain the crystal form A of ginsenoside C-K.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE INVENTION
(19) The crystal form O of ginsenoside C-K is prepared using the crystal form G of ginsenoside C-K as raw material, whereas the rest crystal forms of ginsenoside C-K are prepared using the crystal form O of ginsenoside C-K as raw material.
(20) All reagents used in the examples are of analytical grade.
1. Preparation of the Crystal Form a of Ginsenoside C-K
Example 1
(21) 10 g ginsenoside C-K was placed in a container, into which 100 ml 1-methyl-2-pyrrolidone was added and evaporated slowly until solid occurred. Subsequently, it was filtered, washed twice using 60 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form A of ginsenoside C-K.
Example 2
(22) 1 g ginsenoside C-K was placed in a container, into which 10 ml 1-methyl-2-pyrrolidone and 80 ml acetone were added. After dissolution by stirring, it was evaporated slowly until solid occurred. Subsequently, it was filtered, washed twice using 20 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form A of ginsenoside C-K.
Example 3
(23) 4 g ginsenoside C-K was placed in a container, into which 40 ml 1-methyl-2-pyrrolidone was added. After dissolution, 60 ml water was slowly added dropwise, and stirred for 1 h. Subsequently, it was filtered, washed twice using 40 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form A of ginsenoside C-K.
Example 4
(24) 4 g ginsenoside C-K was placed in a container, into which 40 ml 1-methyl-2-pyrrolidone was added. After dissolution, 100 ml isopropyl ether was slowly added dropwise, and stirred for 1 h. Subsequently, it was filtered, washed twice using 40 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form A of ginsenoside C-K.
2. Preparation of the Crystal Form B of Ginsenoside C-K
Example 5
(25) 3 g ginsenoside C-K was placed in a container, into which 10 ml DMF was added followed by the addition of 90 ml butyl acetate. Subsequently, it was stirred and evaporated slowly until solid occurred. It was then filtered, washed twice using 60 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form B of ginsenoside C-K.
Example 6
(26) 3 g ginsenoside C-K was placed in a container, into which 10 ml DMF was added followed by the addition of 90 ml butanone. Subsequently, it was stirred and evaporated slowly until solid developed. It was then filtered, washed twice using 60 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form B of ginsenoside C-K.
Example 7
(27) 3 g ginsenoside C-K was placed in a container, into which 10 ml DMF was added followed by the addition of 90 ml methyl tert-butyl ether. Subsequently, it was stirred and evaporated slowly until solid developed. It was then filtered, washed twice using 60 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form B of ginsenoside C-K.
Example 8
(28) 4 g ginsenoside C-K was placed in a container, into which 50 ml dimethyl sulfoxide and 10 ml water were added. After dissolution by stirring, 90 ml water was slowly added dropwise, and solid developed. After stirring for 2 h, it was filtered, washed twice using 60 ml distilled water, and dried under vacuum to obtain the crystal form B of ginsenoside C-K.
3. Preparation of the Crystal Form C of Ginsenoside C-K
Example 9
(29) 9 g ginsenoside C-K was placed in a container, into which 30 ml ethanol was added. After dissolution by stirring, it was evaporated slowly until solid occurred. It was then filtered, washed twice using 60 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form C of ginsenoside C-K.
Example 10
(30) 3 g ginsenoside C-K was placed in a container, into which 10 ml ethanol was added followed by the addition of 90 ml isopropyl acetate. After dissolution by stirring, it was evaporated slowly until solid occurred. It was then filtered, washed twice using 60 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form C of ginsenoside C-K.
4. Preparation of the Crystal Form E of Ginsenoside C-K
Example 11
(31) 10 g ginsenoside C-K was placed in a container, into which 150 ml methanol was added and the temperature was increased to 40 C. After dissolution by stirring, the solution was cooled down to 25 C., and it was still clear. Subsequently, 95 ml water was added dropwise at a rate of 15 ml/min. It was then filter by suction to obtain crystal, which was dried at 50 C. for 24 h in an oven to obtain the crystal form E of ginsenoside C-K.
5. Preparation of the Crystal Form F of Ginsenoside C-K
Example 12
(32) 1 g ginsenoside C-K was placed in a container, into which 10 ml NMP and 80 ml 1,2-dichloroethane were added. After dissolution by stirring, it was evaporated slowly until solid occurred. It was then filtered, washed twice using 20 ml distilled water, and dried at room temperature under vacuum to obtain the crystal form F of ginsenoside C-K.
6. Preparation of the Crystal Form I of Ginsenoside C-K
Example 13
(33) 500 mg ginsenoside C-K was dissolved in 50 ml ethanol at room temperature. Subsequently, the solution was evaporated slowly at room temperature for 1 day to obtain the crystal form I of the monocrystal.
7. Preparation of the Crystal Form K of Ginsenoside C-K
Example 14
(34) 2 g ginsenoside C-K was placed in a container, into which 20 ml isopropanol (analytical grade) was added. After dissolution by stirring, a portion of the solvent was removed by evaporation slowly and the solution was filtered to obtain the solid. Subsequently, the resultant solid was dried at room temperature under vacuum to obtain the crystal form K of ginsenoside C-K.
Example 15
(35) 2 g ginsenoside C-K was placed in a container, into which 10 isopropanol (analytical grade) was added followed by the addition of 30 ml cyclohexane. After dissolution by stirring, the solution was filtered, and the filtrate stood for a while until bulk crystal developed. The resultant crystal was detected by single-crystal X-ray diffraction, and the following results were obtained: the crystal belongs to monoclinic system with the space group of P2.sub.1, and has the cell parameters: a=11.643(2) , b=12.385(3) , c=14.365(3) , ==90.00, =96.06(3), cell volume V=2059.8(7) .sup.3, and the number of asymmetric unit in the cell Z=2. Its simulated XRPD pattern was shown in
Example 16
(36) 2 g ginsenoside C-K was placed in a container, into which 10 ml isopropanol (analytical grade) was added followed by the addition of 30 ml n-pentane. After dissolution by stirring, a portion of the solvent was removed by evaporation slowly and the solution was filtered to obtain a solid. Subsequently, the resultant solid was dried at room temperature under vacuum to obtain the crystal form K of ginsenoside C-K.
Example 17
(37) 4 g ginsenoside C-K was placed in a container, into which 20 ml isopropanol (analytical grade) and 20 ml water were added, and the temperature was increased to 70 C. After dissolution by stirring, another 40 ml water was added slowly, and it was filtered to obtain a solid. Subsequently, the resultant solid was dried at room temperature under vacuum to obtain the crystal form K of ginsenoside C-K. Its XRPD pattern was shown in
8. Preparation of the Crystal Form L of Ginsenoside C-K
Example 18
(38) 8 g ginsenoside C-K was placed in a container, into which 120 ml methanol was added and the temperature was increased to 40 C. After dissolution by stirring, the solution was cooled down to 25 C., and it was still clear. Subsequently, 80 ml water was added dropwise at a rate of 1 ml/min. It was then filtered, and the filter cake was dried at 40 C. in a vacuum drying oven to obtain the crystal form L of ginsenoside C-K.
9. Preparation of the Crystal Form N of Ginsenoside C-K
Example 19
(39) 2 g ginsenoside C-K was placed in a container, into which 20 ml water and 100 ml acetonitrile were added, and the temperature was increased to 45 C. After dissolution by stirring, it was cooled down to 4 C., and the solution was still clear. 120 ml water was slowly added dropwise, and it was filtered to obtain the solid. Subsequently, the resultant solid was dried under vacuum to obtain the crystal form N of ginsenoside C-K.
Example 20
(40) 3 g ginsenoside C-K was placed in a container, into which 20 ml water and 100 ml acetonitrile were added, and the temperature was increased to 50 C. After dissolution by stirring, it was cooled down to 20 C., and the solution was still clear. 200 ml water was slowly added dropwise, and it was filtered to obtain the solid. Subsequently, the resultant solid was dried under vacuum to obtain the crystal form N of ginsenoside C-K.
Example 21
(41) 2.5 g ginsenoside C-K was placed in a container, into which 20 ml water and 100 ml acetonitrile were added, and the temperature was increased to 50 C. After dissolution by stirring, it was cooled down to 12 C., and the solution was still clear. 150 ml water was slowly added dropwise, and it was filtered to obtain a solid. Subsequently, the resultant solid was dried under vacuum to obtain the crystal form N of ginsenoside C-K.
10. Preparation of the Crystal Form O of Ginsenoside C-K
Example 22
(42) 6 g ginsenoside C-K was added to 50 ml ethanol, and the temperature was increased to 50 C. After dissolution, the solvent was removed by rotary evaporation at 50 C. to obtain the solid, which was then dried under vacuum to obtain the crystal form O of ginsenoside C-K.
Example 23
(43) 0.7 g ginsenoside C-K was added to 15 ml ethyl acetate and 45 ml acetone, and the temperature was increased to 50 C. After dissolution, the solvent was removed by rotary evaporation at 50 C. to obtain the solid, which was then dried under vacuum to obtain the crystal form O of ginsenoside C-K.
Example 24
(44) 6 g ginsenoside C-K was added to 20 ml DMF. After dissolution by stirring, 40 ml water was added. It was then stirred for 10 min and filtered. The resultant solid was dried under vacuum to obtain the crystal form O of ginsenoside C-K.
11. Preparation of the Crystal Form M of Ginsenoside C-K
Example 25
(45) 1 g the crystal form O of ginsenoside C-K was added to 20 ml ethanol and 80 ml benzene. After dissolution by stirring, the solvent was removed by evaporation slowly. It was then filtered, and the resultant solid was dried under vacuum to obtain the crystal form M of ginsenoside C-K.