Two crystal forms of ginsenoside C-K and method for preparing same

Abstract

Provided are ginsenoside C-K polymorphic forms and a method for preparing same. The ginsenoside C-K polymorphic forms are crystal form D and crystal form H.

Claims

1. A crystal form H of ginsenoside C-K, characterized in that there are diffraction peaks at 2 values () of 5.53, 6.71, 11.11, 13.36, 14.64, 15.59, 15.97, 17.25, 18.18, 19.67, 20.76, 22.40, 23.80, 24.69, 26.60, and 28.22 in the XRPD pattern, wherein the error range of 2 value is 0.2.

2. The crystal form H according to claim 1, wherein said crystal form also has diffraction peaks at 2 values () of 11.82, 12.77, 14.23, 19.12, 20.47, 32.29, and 42.29, wherein the error range of 2 value is 0.2.

3. The crystal form H according to claim 1, wherein said crystal form has diffraction peaks of the XRPD pattern substantially as shown in FIG. 3.

4. The crystal form H according to claim 1, wherein said crystal form has an endothermic peak at 1815 C. in the DSC pattern.

5. A method for preparing the crystal form H according to claim 1, comprising: (1) dissolving ginsenoside C-K in a mixed solvent of 1-methyl-2-pyrrolidone and butyl acetate; (2) removing a portion of the solvent slowly by evaporation at room temperature to obtain a suspension; (3) filtering, drying solid under vacuum to obtain the crystal form H of ginsenoside C-K.

6. A method for preparing the crystal form H according to claim 1, comprising: (1) placing ginsenoside C-K in acetone, heating and stirring the resultant suspension; (2) filtering, and drying under vacuum to obtain the crystal form H of ginsenoside C-K.

7. A method for preparing the crystal form H according to claim 1, comprising: (1) dissolving ginsenoside C-K in an organic solvent at above room temperature, wherein the organic solvent is selected from the group consisting of acetone, butanone, ethyl acetate, butyl acetate and a combination thereof; (2) cooling and standing to obtain a solid; (3) filtering, and drying the resultant solid to obtain the crystal form H of ginsenoside C-K.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is the X-ray powder diffraction pattern of the crystal form D of ginsenoside C-K obtained in Example 1;

(2) FIG. 2 is the DSC pattern of the crystal form D of ginsenoside C-K obtained in Example 1;

(3) FIG. 3 is the simulated X-ray powder diffraction pattern of the crystal form D of ginsenoside C-K monocrystalline obtained in Example 1;

(4) FIG. 4 is the X-ray powder diffraction pattern of the crystal form D product obtained in Example 2;

(5) FIG. 5 is the X-ray powder diffraction pattern of the crystal form H of ginsenoside C-K obtained in Example 4, and the X-ray powder diffraction pattern of the crystal form H obtained in Example 5 is consistent with FIG. 5;

(6) FIG. 6 is the DSC pattern of the crystal form H of ginsenoside C-K obtained in Example 4, and the DSC pattern of the crystal form H obtained in Example 5 is consistent with FIG. 6;

(7) FIG. 7 is the X-ray powder diffraction pattern of the crystal form H obtained in Example 6.

DETAILED DESCRIPTION OF THE INVENTION

(8) The crystal form of all of the materials used in the examples is crystal form G (obtained according to reference 1 mentioned above).

(9) 1. Preparation of the Crystal Form D of Ginsenoside C-K

Example 1

(10) 1 g ginsenoside C-K was added into 60 ml mixed solvent of acetonitrile and water (in a volume ratio of 3:1), and dissolved by stirring. After filtration, the filtrate was placed at room temperature for 2 days, from which rod-like crystals were taken out and analyzed by SXRD. The results suggested that the crystal belonged to monoclinic system, and had the following cell parameters: a=15.856(3) , b=7.582(2) , c=16.567(3) , ==90.00, =117.95 (3), cell volume V=1759.4(6) .sup.3, and the number of asymmetric unit in the cell Z=2. The simulated XRPD pattern was shown in FIG. 3.

Example 2

(11) 6 g ginsenoside C-K was placed in a container, into which 10 ml water and 30 ml n-propanol were added. After dissolution by stirring, 80 ml water was added dropwise. After filtration, the filter cake was washed twice using 40 ml water, dried at room temperature under vacuum to obtain the crystal form D of ginsenoside C-K. Its XRPD pattern was shown in FIG. 4.

Example 3

(12) 3 g ginsenoside C-K was placed in a container, into which 90 ml nitromethane and 10 ml dimethyl sulfoxide were added. After dissolution by stirring, a portion of the solvent was removed by evaporation slowly. After filtration, the filter cake was washed twice using 40 ml water, dried at room temperature under vacuum to obtain the crystal form D of ginsenoside C-K.

(13) 2. Preparation of the Crystal Form H of Ginsenoside C-K

Example 4

(14) 1 g ginsenoside C-K was placed in a container, into which 10 ml NMP was added followed by 60 ml butyl acetate. After dissolution, a portion of the solvent was removed by evaporation slowly to obtain the solid. After filtration, the solid was dried at room temperature under vacuum to obtain the crystal form H of ginsenoside C-K.

Example 5

(15) 2 g ginsenoside C-K was placed in a container, into which 20 ml acetone was added and warmed up to 50 C. to form a suspension. After stirring for 72 h, the suspension was filtered and the filter cake was dried under vacuum to obtain the crystal form H of ginsenoside C-K.

Example 6

(16) 2.3 g ginsenoside C-K was placed in a container, into which 100 ml acetone was added and warmed up to 55 C. After dissolution by stirring, the solution was cooled to room temperature and placed for 12 h to develop a solid. After filtration, the filter cake was dried under vacuum to obtain the crystal form H of ginsenoside C-K. Its XRPD pattern was shown in FIG. 7.

Example 7

(17) 0.7 g ginsenoside C-K was placed in a container, into which 15 ml ethyl acetate and 45 ml acetone were added and warmed up to 45 C. After dissolution by stirring, the solution was cooled to 4 C. to develop a solid. After filtration, the filter cake was dried under vacuum to obtain the crystal form H of ginsenoside C-K.

(18) 3. Thermostability Test

(19) The samples of crystal form D, crystal form H and crystal form G were each placed for 1 week at 80 C., and subsequently the changes of the crystal form were detected. The results showed that under such conditions, no change was observed for the crystal form D and crystal form H, whereas the crystal form G changed to crystal form D, which indicated that both crystal form H and crystal form D had better thermostability.

(20) TABLE-US-00003 TABLE 3 Results of the thermostability test The crystal Test Test The crystal form form before test temperature duration after test D 80 C. 1 week D H 80 C. 1 week H G 80 C. 1 week D