3, 4'-O-dimethyl ellagic acid, derivative and pharmaceutical application thereof

Abstract

The invention relates to 3, 4'-O-dimethyl ellagic acid, a derivative and pharmaceutical application thereof. The invention relates to 3, 4'-O-dimethyl ellagic acid and a derivative thereof. The derivative is 3, 4'-O-dimethyl ellagic acid-4-O-alpha-D-glucoside. The invention further relates to drugs prepared from the 3, 4'-O-dimethyl ellagic acid and / or the 3, 4'-O-dimethyl ellagic acid-4-O-alpha-D-glucoside or application thereof. The invention finds that the above-mentioned two sanguisorba officinalis active ingredients can be related to a plurality of genes and signal paths by regulating thedifferentiation effect of megakaryocytes, and are closest to NF-E2 promoter demethylation.

Description

technical field

[0001] The present invention relates to natural active ingredients, especially active ingredients extracted from Burnet eucalyptus. The use of the active ingredient in pharmacy, especially the use of the active ingredient in the medicine for treating thrombocytopenia. Background technique

[0002] Thrombocytopenia is closely related to some diseases, including infections, malignant tumors, autoimmune diseases, liver diseases, disseminated intravascular coagulation, drugs, pregnancy and coagulation disorders, and is a common clinical hematological disease. Insufficient production of platelets, retention of platelets by the spleen, increased platelet destruction or utilization, and other factors can cause thrombocytopenia. Patients with thrombocytopenia are more prone to spontaneous bleeding, that is, mucosal, intracranial, gastrointestinal and genitourinary bleeding, which can even be life-threatening in severe cases.

[0003] Most of the traditional treatme...

Examples

Embodiment 1

[0055] Example 1 Extraction and separation of 3,4'-O-dimethyl retro-gallic acid and 3,4'-O-dimethyl retro-gallic acid-4-O-α-D-glucoside

[0056] According to the article "Two Ellagic Acids Isolated from Roots of Sanguisorba officinalis L.Promote Hematopoietic Progenitor Cell Proliferation and Megakaryocyte Differentiation" published by the inventor or the method for extracting the active ingredients of Burnet elata disclosed in CN 108714149 A, the active ingredient of Sanguisorba was isolated and purified to obtain Sanguisorba officinalis Burnet species natural active ingredients.

[0057] Or use the following methods to separate:

[0058] Grind 500 g of dried Burnet root, reflux extract with 10 times the weight of 75v% ethanol for 3 times (3×5 L, 1 h each time), combine the extracts, evaporate and concentrate to obtain the ethanol extract. Add water to resuspend and incubate at 60°C for 30 minutes. Then, it was extracted three times with ethyl acetate (500 mL). Evaporate t...

Embodiment 2

[0069] Example 2 Screening of Burnet eucalyptus components for promoting megakaryocyte differentiation in vitro

[0070] Take the Burnet component stock solution (10 mg / mL) prepared in Example 1 and dilute it to 400 μg / mL with RPMI 1640 medium for use. A 6-well plate was taken, and 200 μL of drug was added to each well, with 3 replicate holes for each drug group, and an equal volume of DMSO was added to the solvent control group. Select the HEL cells in the logarithmic growth phase and mix well, and count the cells for later use. Then take the counted cell suspension and adjust the cell density to 2×10 4 Cells / well were inoculated in a 6-well plate, with 1.8 mL of cell suspension per well, so that the final concentration of the drug was 40 μg / mL. at 5% CO 2 , with a relative saturated humidity of 95%, and cultured in a 37°C incubator for 6 days.

[0071] Detection: Observe the morphological changes of cell differentiation in the well plate (megakaryocyte differentiation, t...

Embodiment 3

[0073] Example 3 Study on Time and Concentration Changes of DMAG in Promoting Megakaryocyte Differentiation in Vitro

[0074] Take the prepared DMAG stock solution (10 mg / mL) and dilute it with RPMI 1640 medium to 400, 200, 100, 50 μg / mL for later use. A 6-well plate was taken, and 200 μL of drug was added to each well, with 3 replicate holes for each drug group, and an equal volume of DMSO was added to the solvent control group. Select the HEL cells in the logarithmic growth phase and mix well, and count the cells for later use. Then take the counted cell suspension and adjust the cell density to 2×10 4 Cells / well were inoculated in 6-well plate, 1.8mL cell suspension per well, so that the final drug concentration was 40, 20, 10, 5 μg / mL. at 5% CO 2 , with a relative saturated humidity of 95%, and cultured in a 37°C incubator for 6 days.

[0075] Detection: Observe the morphological changes of cell differentiation in the well plate (megakaryocyte differentiation, the cell...

technical field

[0001] The present invention relates to natural active ingredients, especially active ingredients extracted from Burnet eucalyptus. The use of the active ingredient in pharmacy, especially the use of the active ingredient in the medicine for treating thrombocytopenia. Background technique

[0002] Thrombocytopenia is closely related to some diseases, including infections, malignant tumors, autoimmune diseases, liver diseases, disseminated intravascular coagulation, drugs, pregnancy and coagulation disorders, and is a common clinical hematological disease. Insufficient production of platelets, retention of platelets by the spleen, increased platelet destruction or utilization, and other factors can cause thrombocytopenia. Patients with thrombocytopenia are more prone to spontaneous bleeding, that is, mucosal, intracranial, gastrointestinal and genitourinary bleeding, which can even be life-threatening in severe cases.

[0003] Most of the traditional treatme...

Examples

Embodiment 1

[0055] Example 1 Extraction and separation of 3,4'-O-dimethyl retro-gallic acid and 3,4'-O-dimethyl retro-gallic acid-4-O-α-D-glucoside

[0056] According to the article "Two Ellagic Acids Isolated from Roots of Sanguisorba officinalis L.Promote Hematopoietic Progenitor Cell Proliferation and Megakaryocyte Differentiation" published by the inventor or the method for extracting the active ingredients of Burnet elata disclosed in CN 108714149 A, the active ingredient of Sanguisorba was isolated and purified to obtain Sanguisorba officinalis Burnet species natural active ingredients.

[0057] Or use the following methods to separate:

[0058] Grind 500 g of dried Burnet root, reflux extract with 10 times the weight of 75v% ethanol for 3 times (3×5 L, 1 h each time), combine the extracts, evaporate and concentrate to obtain the ethanol extract. Add water to resuspend and incubate at 60°C for 30 minutes. Then, it was extracted three times with ethyl acetate (500 mL). Evaporate t...

Embodiment 2

[0069] Example 2 Screening of Burnet eucalyptus components for promoting megakaryocyte differentiation in vitro

[0070] Take the Burnet component stock solution (10 mg / mL) prepared in Example 1 and dilute it to 400 μg / mL with RPMI 1640 medium for use. A 6-well plate was taken, and 200 μL of drug was added to each well, with 3 replicate holes for each drug group, and an equal volume of DMSO was added to the solvent control group. Select the HEL cells in the logarithmic growth phase and mix well, and count the cells for later use. Then take the counted cell suspension and adjust the cell density to 2×10 4 Cells / well were inoculated in a 6-well plate, with 1.8 mL of cell suspension per well, so that the final concentration of the drug was 40 μg / mL. at 5% CO 2 , with a relative saturated humidity of 95%, and cultured in a 37°C incubator for 6 days.

[0071] Detection: Observe the morphological changes of cell differentiation in the well plate (megakaryocyte differentiation, t...

Embodiment 3

[0073] Example 3 Study on Time and Concentration Changes of DMAG in Promoting Megakaryocyte Differentiation in Vitro

[0074] Take the prepared DMAG stock solution (10 mg / mL) and dilute it with RPMI 1640 medium to 400, 200, 100, 50 μg / mL for later use. A 6-well plate was taken, and 200 μL of drug was added to each well, with 3 replicate holes for each drug group, and an equal volume of DMSO was added to the solvent control group. Select the HEL cells in the logarithmic growth phase and mix well, and count the cells for later use. Then take the counted cell suspension and adjust the cell density to 2×10 4 Cells / well were inoculated in 6-well plate, 1.8mL cell suspension per well, so that the final drug concentration was 40, 20, 10, 5 μg / mL. at 5% CO 2 , with a relative saturated humidity of 95%, and cultured in a 37°C incubator for 6 days.

[0075] Detection: Observe the morphological changes of cell differentiation in the well plate (megakaryocyte differentiation, the cell...

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