Crystalline form A of rebaudioside D, and preparation method and application therefor

• US 10,611,789 B2
• Filed: 07/21/2016
• Issued: 04/07/2020
• Est. Priority Date: 07/23/2015
• Status: Active Grant

• Current Assignee: Zhucheng Haotian Pharm Co., Ltd.
• Original Assignee: Zhucheng Haotian Pharm Co., Ltd.
• Inventors: Zhu, Liping, Mei, Xuefeng, Huang, Ying, Wang, Jianrong, Zhang, Qi
• Primary Examiner(s): Lau, Jonathan S
• Application Number:
  US15/747,072
• Publication Number:
  US 20180371002A1
• Time in Patent Office: 1,356 Days
• CPC Class Codes: A23L 19/00 Products from fruits or vegetables; Preparation or treatment thereof marmalades, jams, jellies or the like A23L21/10; treating harvested fruit or vegetables in bulk A23N
• CPC Class Codes: A23L 2/02 containing fruit or vegetable juices
• CPC Class Codes: A23L 2/60 Sweeteners
• CPC Class Codes: A23L 27/30 Artificial sweetening agents
• CPC Class Codes: A23L 27/33 containing sugars or derivatives
• CPC Class Codes: A23L 33/00 Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07H 1/06 Separation; Purification
• CPC Class Codes: C07H 1/08 from natural products
• CPC Class Codes: C07H 15/24 Condensed ring systems having three or more rings
• CPC Class Codes: C07H 15/26 Acyclic or carbocyclic radicals, substituted by hetero rings

Abstract

Provided are crystalline form A of rebaudioside D, and a preparation method and application therefor. In X-ray powder diffraction analysis measured using Cu-Kα rays and with 2θ being expressed in degrees, crystalline form A of rebaudioside D has significant characteristic diffraction peaks at least at 4.53, 6.38, 12.76, 13.52, 17.48, 17.96, 20.07 and 22.63. The preparation method is a suspension method, a solvent evaporation method or a cooling method. The preparation method has a simple process, and is convenient to operate. A rebaudioside D crystalline form A product has a good degree of crystallinity, good water solubility, and high chemical stability.

Claims

1. A crystal form A of Rebaudioside D, wherein the crystal form A has characteristic diffraction peaks of X-ray powder diffraction analysis, which are measured by Cu-Kα

ray measurement and expressed as 2θ

value in degree with an error range of ±

1°

, and the characteristic diffraction peaks include 3 or more characteristic diffraction peaks selected from the group consisting of;

4.53, 6.38, 12.76, 13.52, 17.48, 17.96, 20.07 and 22.63.

2. The crystal form A of Rebaudioside D of claim 1, wherein the X-ray powder diffraction analysis of the crystal form A obtained using Cu-Kα

ray measurement has characteristic diffraction peaks expressed as 2θ

value in degree with an error range of ±

1°

, crystal plane spacings expressed as d in Å and

relative intensity of the diffraction peaks expressed as a percentage, which have the following characteristics;

3. The crystal form A of Rebaudioside D of claim 1, wherein the crystal form A has one or more characteristics selected from the group consisting of:

(1) the crystal form A has a differential scanning calorimetry analysis pattern substantially as shown in FIG. 2;

(2) the crystal form A has a thermogravimetric analysis pattern substantially as shown in FIG. 3;

(3) the crystal form A has a dynamic vapor sorption pattern substantially as shown in FIG. 4; and

/or

(4) the crystal form A has a infrared spectrogram substantially as shown in FIG. 5.

4. The crystal form A of Rebaudioside D of claim 1, wherein the crystal form A has characteristic diffraction peaks of X-ray powder diffraction analysis, which are measured by Cu-Kα

ray measurement and expressed as 2θ

value in degree with an error range of ±

0.1°

.

5. A food, beverage or pharmaceutical product, which contains a crystal form A of Rebaudioside D according to claim 1 as a sweetener.

6. A preparation method for the crystal form A of Rebaudioside D, wherein the preparation method is a suspension method, a solution volatilization method or a cooling method,

wherein the suspension method comprises the following steps:

(1) mixing Rebaudioside D with the solvent for 0.1-48 hat a temperature of 0°

C. to the boiling point of the solvent to obtain a suspension solution;

wherein the solvent is selected from the group consisting of water, methanol, ethanol, acetonitrile, tetrahydrofuran, acetone, methyl ethyl ketone, ethyl acetate, ethyl formate, 1-propanol, 2-propanol, and a combination thereof;

(2) filtering or centrifuging the suspension solution at a temperature of 0°

C. to the boiling point of the solvent to obtain a white solid; and

(3) drying the white solid at a temperature of 0°

C. to the boiling point of the solvent to obtain the crystal form A of Rebaudioside D,

wherein the solution volatilization method comprises the following steps;

(1) mixing Rebaudioside D with the solvent for 0.1-48 h at a temperature of 0°

C. to the boiling point of the solvent to obtain a suspension solution;

wherein the solvent is selected from the group consisting of water, methanol, ethanol, tetrahydrofuran, acetonitrile, and a combination thereof;

(2) filtering or centrifuging the suspension solution at a temperature of 0°

C. to the boiling point of the solvent to obtain a clear solution; and

(3) volatilizing the suspension solution of step (1) or the clear solution of step (2) at a temperature of 0°

C. to the boiling point of the solvent to obtain the crystal form A of Rebaudioside D, and

wherein the cooling method comprises the following steps;

(1) mixing Rebaudioside D with the solvent for 0.1-48 h at room temperature to the boiling point of the solvent to obtain a suspension solution;

wherein the solvent is selected from the group consisting of water, methanol, ethanol, 2-butanol, and a combination thereof;

(2) filtering or centrifuging the suspension solution at room temperature to the boiling point of the solvent to obtain a clear solution; and

(3) cooling the suspension solution of step (1) or the clear solution of step (2) to −

20-30°

C., precipitating a white solid, filtering and drying to obtain the crystal form A of Rebaudioside D.

7. The preparation method for the crystal form A of Rebaudioside D of claim 6, wherein the drying is one or two or more of drying modes of natural drying, air-blast drying, vacuum drying, freeze-drying, airflow drying, microwave drying, infrared drying or high frequency drying, wherein the natural drying means dried naturally at 50°

C.