Ligustrazine phosphate compound and drug composition containing ligustrazine phosphate compound and ginkgo leaf effective ingredients

Abstract

The invention belongs to the technical field of medicines and in particular relates to a ligustrazine phosphate compound and a drug composition containing a ligustrazine phosphate compound and ginkgo leaf effective ingredients. The ligustrazine phosphate compound has a chemical structure formula as shown in a formula (I) and an X-ray powder diffraction pattern which is obtained by measuring Cu-K alpha rays and is as shown in a figure 1. The drug composition contains the ligustrazine phosphate compound and the ginkgo leaf effective ingredients, wherein the ginkgo leaf effective ingredients are ginkgo leaf extracts extracted from ginkgo leaves, the weight of the ligustrazine phosphate compound is 1-100 times, preferably 5-50 times, more preferably 5-20 times, best preferably 10 times that of the ginkgo leaf extracts, and the weight of the ginkgo leaf extracts is calculated by total ginkgo flavones. The ligustrazine phosphate compound provided by the invention is a novel crystal form compound different from that in the prior art, and the novel crystal form compound is remarkably improved in stability.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a ligustrazine phosphate compound and a pharmaceutical composition containing the ligustrazine compound and ginkgo biloba active ingredients. Background technique

[0002] Ginkgo biloba extract contains active ingredients such as total flavonoids and total lactones, and total flavonoids are the main active ingredients of Ginkgo biloba extract. The content of total flavonoids in Ginkgo biloba leaves is 0.5% to 1% (W / W), mainly in the form of glycosides, and the main aglycones are quercetin, kaempferol and isorhamnetin. Ginkgo biloba total flavonoids contained in Ginkgo biloba extract can expand coronary vessels, cerebral blood vessels, promote blood circulation and remove blood stasis, and improve symptoms and memory functions caused by cerebral ischemia. Ginkgo biloba extract can improve cerebral circulation, glucose metabolism and respiration in patients with cereb...

Examples

Embodiment 1

[0037] Embodiment 1, the preparation of ligustrazine phosphate compound

[0038] 1) Take 100g of ligustrazine phosphate monohydrate raw material at room temperature, add 300ml of a mixed solvent of ethanol and tetrahydrofuran (the volume ratio of ethanol to tetrahydrofuran is 3:1), stir and dissolve, and obtain the ethanol / tetrahydrofuran solution of ligustrazine phosphate;

[0039]2) Add 0.01% w / v activated carbon to the ethanol / tetrahydrofuran solution of ligustrazine phosphate obtained in step 1), stir and adsorb for 15 minutes, filter, collect the filtrate, and set aside;

[0040] 3) Add chloroform to the filtrate dropwise under an ultrasonic field with a frequency of 18KHz until crystallization occurs;

[0041] 4) Turn off the ultrasonic field, lower the temperature to 0° C., and stand at this temperature for 6 hours; filter, wash the filter cake with chloroform, and dry it in vacuum for 2 hours to obtain the ligustrazine phosphate compound.

[0042] The X-ray powder dif...

Embodiment 2

[0043] Embodiment 2, the preparation of ligustrazine phosphate compound

[0044] 1) Take 100g of ligustrazine phosphate monohydrate raw material at room temperature, add 1000ml of a mixed solvent of ethanol and tetrahydrofuran (the volume ratio of ethanol to tetrahydrofuran is 8:1), stir and dissolve, and obtain the ethanol / tetrahydrofuran solution of ligustrazine phosphate;

[0045] 2) Add 0.01% w / v activated carbon to the ethanol / tetrahydrofuran solution of ligustrazine phosphate obtained in step 1), stir and adsorb for 15 minutes, filter, collect the filtrate, and set aside;

[0046] 3) Add chloroform to the filtrate dropwise under an ultrasonic field with a frequency of 20KHz until crystallization occurs;

[0047] 4) Turn off the ultrasonic field, lower the temperature to 5° C., and stand at this temperature for 2 hours; filter, wash the filter cake with chloroform, and dry it in vacuum for 2 hours to obtain the ligustrazine phosphate compound.

[0048] The X-ray powder d...

Embodiment 3

[0049] Embodiment 3, the preparation of ligustrazine phosphate compound

[0050] 1) Take 100g of ligustrazine phosphate monohydrate raw material at room temperature, add 700ml of a mixed solvent of ethanol and tetrahydrofuran (the volume ratio of ethanol to tetrahydrofuran is 5:1), stir and dissolve, and obtain an ethanol / tetrahydrofuran solution of ligustrazine phosphate;

[0051] 2) Add 0.01% w / v activated carbon to the ethanol / tetrahydrofuran solution of ligustrazine phosphate obtained in step 1), stir and adsorb for 15 minutes, filter, collect the filtrate, and set aside;

[0052] 3) Add chloroform to the filtrate dropwise under an ultrasonic field with a frequency of 23KHz until crystallization occurs;

[0053] 4) Turn off the ultrasonic field, lower the temperature to 3° C., and stand at this temperature for 4 hours; filter, wash the filter cake with chloroform, and dry it in vacuum for 4 hours to obtain the ligustrazine phosphate compound.

[0054] The X-ray powder dif...

technical field

[0001] The invention belongs to the technical field of medicine, and in particular relates to a ligustrazine phosphate compound and a pharmaceutical composition containing the ligustrazine compound and ginkgo biloba active ingredients. Background technique

[0002] Ginkgo biloba extract contains active ingredients such as total flavonoids and total lactones, and total flavonoids are the main active ingredients of Ginkgo biloba extract. The content of total flavonoids in Ginkgo biloba leaves is 0.5% to 1% (W / W), mainly in the form of glycosides, and the main aglycones are quercetin, kaempferol and isorhamnetin. Ginkgo biloba total flavonoids contained in Ginkgo biloba extract can expand coronary vessels, cerebral blood vessels, promote blood circulation and remove blood stasis, and improve symptoms and memory functions caused by cerebral ischemia. Ginkgo biloba extract can improve cerebral circulation, glucose metabolism and respiration in patients with cereb...

Examples

Embodiment 1

[0037] Embodiment 1, the preparation of ligustrazine phosphate compound

[0038] 1) Take 100g of ligustrazine phosphate monohydrate raw material at room temperature, add 300ml of a mixed solvent of ethanol and tetrahydrofuran (the volume ratio of ethanol to tetrahydrofuran is 3:1), stir and dissolve, and obtain the ethanol / tetrahydrofuran solution of ligustrazine phosphate;

[0039]2) Add 0.01% w / v activated carbon to the ethanol / tetrahydrofuran solution of ligustrazine phosphate obtained in step 1), stir and adsorb for 15 minutes, filter, collect the filtrate, and set aside;

[0040] 3) Add chloroform to the filtrate dropwise under an ultrasonic field with a frequency of 18KHz until crystallization occurs;

[0041] 4) Turn off the ultrasonic field, lower the temperature to 0° C., and stand at this temperature for 6 hours; filter, wash the filter cake with chloroform, and dry it in vacuum for 2 hours to obtain the ligustrazine phosphate compound.

[0042] The X-ray powder dif...

Embodiment 2

[0043] Embodiment 2, the preparation of ligustrazine phosphate compound

[0044] 1) Take 100g of ligustrazine phosphate monohydrate raw material at room temperature, add 1000ml of a mixed solvent of ethanol and tetrahydrofuran (the volume ratio of ethanol to tetrahydrofuran is 8:1), stir and dissolve, and obtain the ethanol / tetrahydrofuran solution of ligustrazine phosphate;

[0045] 2) Add 0.01% w / v activated carbon to the ethanol / tetrahydrofuran solution of ligustrazine phosphate obtained in step 1), stir and adsorb for 15 minutes, filter, collect the filtrate, and set aside;

[0046] 3) Add chloroform to the filtrate dropwise under an ultrasonic field with a frequency of 20KHz until crystallization occurs;

[0047] 4) Turn off the ultrasonic field, lower the temperature to 5° C., and stand at this temperature for 2 hours; filter, wash the filter cake with chloroform, and dry it in vacuum for 2 hours to obtain the ligustrazine phosphate compound.

[0048] The X-ray powder d...

Embodiment 3

[0049] Embodiment 3, the preparation of ligustrazine phosphate compound

[0050] 1) Take 100g of ligustrazine phosphate monohydrate raw material at room temperature, add 700ml of a mixed solvent of ethanol and tetrahydrofuran (the volume ratio of ethanol to tetrahydrofuran is 5:1), stir and dissolve, and obtain an ethanol / tetrahydrofuran solution of ligustrazine phosphate;

[0051] 2) Add 0.01% w / v activated carbon to the ethanol / tetrahydrofuran solution of ligustrazine phosphate obtained in step 1), stir and adsorb for 15 minutes, filter, collect the filtrate, and set aside;

[0052] 3) Add chloroform to the filtrate dropwise under an ultrasonic field with a frequency of 23KHz until crystallization occurs;

[0053] 4) Turn off the ultrasonic field, lower the temperature to 3° C., and stand at this temperature for 4 hours; filter, wash the filter cake with chloroform, and dry it in vacuum for 4 hours to obtain the ligustrazine phosphate compound.

[0054] The X-ray powder dif...

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