Lact-pyrondridin and its pharmaceutical composition

Abstract

The invention provides lact-pyrondridin and its pharmaceutical composition, more specificly, the invention provides compound of formula I, wherein n is 1 to 4, or its solvate, crystal type, amorphous material. The invention also provides a pharmaceutical composition comprising compound of formula I, compound pharmaceutical combination comprising compound of formula I and arteannuin analog, medicine kit product comprising compound of formula I and arteannuin analog, and uses of the compound of formula I, pharmaceutical composition or compound pharmaceutical combination in preparing medicine for prevention and / or cure for the malaria. The compound of formula I possesses higher bioavailability and synergistic effect with arteannuin analog.

Description

technical field

[0001] The invention belongs to the technical field of medicine and relates to a new pyronaridine salt. Specifically, the present invention relates to the lactate of pyronaridine, and the present invention also relates to a pharmaceutical composition comprising the lactate, a compound drug combination comprising the lactate and an artemisinin analog, including the lactate A medicine box product with artemisinin analogues, and the use of the lactate salt, pharmaceutical composition or compound drug combination in the preparation of medicines for preventing and / or treating malaria. Background technique

[0002] Malaria is the most widespread tropical parasitic infectious disease with the highest morbidity and mortality in the world. According to the statistics of the World Health Organization (WHO), malaria is prevalent in more than 90 countries and regions, and the number of clinical cases reaches 300-500 million Person-time / year, 1.5 to 2.7 million people di...

Examples

preparation example 1

[0078] Compound Preparation Example 1: Preparation of Pyrenaridine Lactate

[0079] Precisely take 0.1 mol of pyronaridine, 1 liter of 95% ethanol, heat to dissolve, add 0.13 mol of lactic acid, reflux for 1.5 hours, concentrate in vacuo, stand for 12-24 hours, collect the precipitate, dry to obtain pyronaridine lactic acid.

[0080] Test results: pyronaridine lactate, amorphous powder, n=1, molecular weight 608, melting point 113°C, cm -1 : 3500 (NH), 3334 (OH), 1740 (C=O); mass spectrum m / z: 518.

preparation example 2

[0081] Compound Preparation Example 2: Preparation of Pyrenaridine Lactate

[0082] Precisely take 0.1 mol of pyronaridine and 1 liter of ethyl acetate, put them in a container, heat to dissolve, add 0.13 mol of lactic acid, and reflux for 1.5 hours; concentrate in vacuo, let stand for 12-24 hours, collect crystals, dry to obtain pyronaridine lactic acid Pyridine.

[0083] Test result: pyronaridine lactate, amorphous powder, n=1, molecular weight 608, cm -1 : 3500 (NH), 3334 (OH), 1740 (C=O); mass spectrum m / z: 518.

preparation example 3

[0084] Compound Preparation Example 3: Preparation of Pyrenaridine Lactate

[0085] Precisely take 0.1 mol of pyronaridine and 1 liter of ethyl acetate, put them in a container, heat to dissolve, add 0.26 mol of lactic acid; reflux for 2 hours; concentrate in vacuo, let stand for 12-24 hours, collect the precipitate, and dry to obtain pyronaridine lactate Pyridine.

[0086] Test result: pyronaridine lactate, viscous, n=2, molecular weight 698, cm -1 : 3500 (NH), 3334 (OH), 1740 (C=O); mass spectrum m / z: 518.

technical field

[0001] The invention belongs to the technical field of medicine and relates to a new pyronaridine salt. Specifically, the present invention relates to the lactate of pyronaridine, and the present invention also relates to a pharmaceutical composition comprising the lactate, a compound drug combination comprising the lactate and an artemisinin analog, including the lactate A medicine box product with artemisinin analogues, and the use of the lactate salt, pharmaceutical composition or compound drug combination in the preparation of medicines for preventing and / or treating malaria. Background technique

[0002] Malaria is the most widespread tropical parasitic infectious disease with the highest morbidity and mortality in the world. According to the statistics of the World Health Organization (WHO), malaria is prevalent in more than 90 countries and regions, and the number of clinical cases reaches 300-500 million Person-time / year, 1.5 to 2.7 million people di...

Examples

preparation example 1

[0078] Compound Preparation Example 1: Preparation of Pyrenaridine Lactate

[0079] Precisely take 0.1 mol of pyronaridine, 1 liter of 95% ethanol, heat to dissolve, add 0.13 mol of lactic acid, reflux for 1.5 hours, concentrate in vacuo, stand for 12-24 hours, collect the precipitate, dry to obtain pyronaridine lactic acid.

[0080] Test results: pyronaridine lactate, amorphous powder, n=1, molecular weight 608, melting point 113°C, cm -1 : 3500 (NH), 3334 (OH), 1740 (C=O); mass spectrum m / z: 518.

preparation example 2

[0081] Compound Preparation Example 2: Preparation of Pyrenaridine Lactate

[0082] Precisely take 0.1 mol of pyronaridine and 1 liter of ethyl acetate, put them in a container, heat to dissolve, add 0.13 mol of lactic acid, and reflux for 1.5 hours; concentrate in vacuo, let stand for 12-24 hours, collect crystals, dry to obtain pyronaridine lactic acid Pyridine.

[0083] Test result: pyronaridine lactate, amorphous powder, n=1, molecular weight 608, cm -1 : 3500 (NH), 3334 (OH), 1740 (C=O); mass spectrum m / z: 518.

preparation example 3

[0084] Compound Preparation Example 3: Preparation of Pyrenaridine Lactate

[0085] Precisely take 0.1 mol of pyronaridine and 1 liter of ethyl acetate, put them in a container, heat to dissolve, add 0.26 mol of lactic acid; reflux for 2 hours; concentrate in vacuo, let stand for 12-24 hours, collect the precipitate, and dry to obtain pyronaridine lactate Pyridine.

[0086] Test result: pyronaridine lactate, viscous, n=2, molecular weight 698, cm -1 : 3500 (NH), 3334 (OH), 1740 (C=O); mass spectrum m / z: 518.

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