US 12,390,503 B2
Ginkgo biloba leave extract capsule and preparation method therefor
Dandan Wang, Shanghai (CN); Qi Gao, Shanghai (CN); Jun Wang, Shanghai (CN); Baozhong Zhu, Shanghai (CN); Cunfa Li, Shanghai (CN); Xueyi Zhang, Shanghai (CN); and Yafang Wei, Shanghai (CN)
Assigned to SPH XING LING SCI. & TECH. PHARMACEUTICAL CO., LTD., Shanghai (CN)
Appl. No. 17/264,152
Filed by SPH XING LING SCI. & TECH. PHARMACEUTICAL CO., LTD., Shanghai (CN)
PCT Filed Sep. 12, 2018, PCT No. PCT/CN2018/105256
§ 371(c)(1), (2) Date Aug. 24, 2021,
PCT Pub. No. WO2020/037736, PCT Pub. Date Feb. 27, 2020.
Claims priority of application No. 201810945350.3 (CN), filed on Aug. 20, 2018.
Prior Publication US 2022/0080005 A1, Mar. 17, 2022
Int. Cl. A61K 36/16 (2006.01); A61K 9/48 (2006.01); A61K 31/365 (2006.01)
CPC A61K 36/16 (2013.01) [A61K 9/48 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61K 31/365 (2013.01)] 5 Claims
 
1. A method for preparing a ginkgo biloba ketone ester capsule, comprising:
mixing well a ginkgo biloba ketone ester raw material, dextrin, starch, low-substituted hydroxypropyl cellulose and carboxymethyl starch sodium according to a composition ratio, granulating, drying, adding magnesium stearate, mixing well, and filling into a capsule, to obtain the ginkgo biloba ketone ester capsule;
wherein the composition ratio of the ginkgo biloba ketone ester capsule, in parts by weight, includes the following:
35-45 parts of ginkgo biloba ketone ester raw materials;
35-45 parts of dextrin;
80-100 parts of starch;
15-25 parts of low-substituted hydroxypropyl cellulose;
6-10 parts of carboxymethyl starch sodium; and
1-3 parts of magnesium stearate;
wherein the preparation method of the ginkgo biloba ketone ester raw materials includes the following operations:
a) crushing ginkgo biloba leaves to obtain crushed ginkgo biloba leaves; adding 60% ethanol aqueous solution to the crushed ginkgo biloba leaves, extracting twice by heating at reflux and obtaining a first filtrate by filtration; adding water to the filtered residue left after the filtration, heating at reflux for extraction, and then obtaining a second filtrate by filtration; combining and concentrating the first filtrate and the second filtrate into a thick paste, dissolving in purified water, standing to cool, and filtering to obtain a filtrate;
b) concentrating the filtrate and performing water-sedimentation, centrifuging the supernatant to obtain a centrifugal liquid; wherein the filtrate is concentrated to have no alcohol smell;
c) loading the centrifugal liquid onto a macroporous resin column, then washing with water and eluting with solvent to obtain a first eluent; the first eluent includes a 50% ethanol eluent which is a high-concentration-solvent first eluent, and a combined solution of an 18% ethanol eluent and a 30% ethanol eluent which is a low-concentration-solvent first eluent;
wherein the washing with water is forward-washing with purified water for 1.5 hours first, and then backwashing for 1 hour; the eluting with solvent is eluting with 18% ethanol aqueous solution, 30% ethanol aqueous solution and 50% ethanol aqueous solution in sequence to obtain 18% ethanol eluent, 30% ethanol eluent and 50% ethanol eluent, respectively;
d) loading the low-concentration-solvent first eluent onto a polyamide column, then washing with water and eluting with ethanol to obtain a second eluent; wherein the low-concentration-solvent first eluent is concentrated to have no alcohol smell before being loaded onto the polyamide column, the washing with water is forward-washing by using purified water 0.5-2 times the volume of the polyamide column;
e) combining and concentrating the second eluent with the high-concentration-solvent first eluent, and then extracting, drying, crushing, sieving, and mixing to obtain the ginkgo biloba ketone ester raw materials;
wherein the ginkgo biloba ketone ester capsule, based on the loading weight of each capsule being 0.2 g, meets the following conditions:
1) the content of rutin is less than or equal to 1.60 mg/capsule;
2) the content of quercetin is less than or equal to 0.160 mg/capsule;
3) the content of bilobalide is 1.04-2.08 mg/capsule;
4) the content of ginkgolide J is 0.04-0.20 mg/capsule;
5) the residual content of ethanol is less than or equal to 0.2 mg/capsule;
6) the content of biflavonoids is less than or equal to 0.008 mg/capsule, the biflavonoids include amentoflavone, bilobetin, and ginkgetin; and
7) the content of genistin is 0, and the content of ginkgolide M is 0.