CN102093383A - Potassium cantharidate and preparation method thereof - Google Patents

Abstract

The invention discloses potassium cantharidate of a structural formula below. The preparation method comprises: adding trichloromethane or isopropanol into pure cantharidin according to a weight ratio of (30-50):1, heating to dissolve the trichloromethane or isopropanol, and adding distilled water into potassium hydroxide according to a molar ratio of the potassium hydroxide to the cantharidin of 3:(2-3) to prepare solution at a weight concentration of 10 percent; adding the solution of potassium hydroxide into the trichloromethane or isopropanol solution containing cantharidin, heating the mixed solution to 60 to 75 DEG C, volatilizing trichloromethane or isopropanol till dryness, and filtering to obtain colorless transparent solution; and adding trichloromethane or isopropanol in a volume which is 2 to 5 times that the filtrate into filtrate, separating to obtain upper colorless transparent aqueous solution, placing the colorless transparent aqueous solution in an oven for concentration and drying to obtain white crystalline powder. The potassium cantharidate has high anticancer activity, the process is simple, easy to operate and very safe, and the finished product is stable in properties and high in purity.

Description

Cantharidin acid potassium and preparation method thereof

Technical field

The invention belongs to technical field of chemistry, particularly a kind of Cantharidin acid potassium also relates to the preparation method of this Cantharidin acid potassium simultaneously.

Background technology

China just brings into use Chinese blister beetle to treat tumour in oneth, two century of Christian era.After be proved Chinese blister beetle excretory Cantharidin and cantharidin derivative for mainly containing effective substance.Be often used as oral pharmaceutical uses because of Cantharidin is water insoluble, limited the range of application of Cantharidin like this, back people have developed Cantharidin acid sodium increases the water-soluble toxicity that reduced simultaneously, utilize this excellent properties, developed Cantharidin acid sodium injection, can use by direct injection, the sodium injection of Cantharidin acid at present has been successfully applied to clinical, and has obtained significant effect.But Cantharidin acid sodium is reducing the toxic while, and antitumour activity is along with great reduction, and this presses for exploitation, and other new have more that the cantharidin derivative of high anti-cancer activity solves this problem.

Summary of the invention

The objective of the invention is to overcome above-mentioned shortcoming and a kind ofly having than high anti-cancer activity of providing, technology is simple, easy handling, and security is good, and end properties is stable, the Cantharidin acid potassium that purity is high.

Another object of the present invention is to provide the preparation method of this Cantharidin acid potassium.

Cantharidin acid potassium of the present invention, its structural formula is:

The preparation method of Cantharidin acid potassium of the present invention comprises the steps:

(1) get the pure product of Cantharidin and add trichloromethane or Virahol by the weight ratio of 1:30-50, heating makes its dissolving, and getting simultaneously and making weight concentration with the potassium hydroxide adding distil water of Cantharidin mol ratio 3:2-3 is 10% solution;

(2) potassium hydroxide solution is joined in the chloroform soln or aqueous isopropanol of dissolving Cantharidin, be heated to 60-75 ℃ after, trichloromethane or Virahol are volatilized, filter, colourless transparent solution;

(3) trichloromethane of 2-5 times of volume of adding or Virahol extraction in filtrate, separatory obtains the upper strata water white transparency aqueous solution, puts in the baking oven to concentrate, and drying gets white crystalline powder promptly.

Beneficial effect of the present invention, by above technical scheme as can be known, it is simple that the present invention has technology, easy handling, the Cantharidin acid potassium that obtains is an analog derivative of Cantharidin, has the antitumor mechanism similar to Cantharidin, experimental results show that it has higher anti-cancer activity.And molecular weight is little, easily goes in the cancer cells, produce cytotoxicity, thereby have stronger antitumor action, and be a kind of comparatively ideal cancer therapy drug.Can be mainly used in the treatment of late primary liver cancer and advanced lung cancer clinically.Its security is good.The finished product stable in properties that present method makes, the purity height.Because it has better water solubility, can be applicable to the antitumor drug production of multiple formulations such as injection, solution, ointment.

 

Embodiment

The below routine by experiment beneficial effect that further specifies the inventive method.

Embodiment 1:

A kind of preparation method of Cantharidin acid potassium comprises the steps:

(1) add pure product 1 g of Cantharidin in the Erlenmeyer flask of 50ml, add the 30ml chloroform soln, heating makes its dissolving, gets potassium hydroxide 0.5g simultaneously and adds 5ml distilled water to make weight concentration be 10% solution;

(2) potassium hydroxide solution is joined in the chloroform soln of dissolving Cantharidin, be heated to 60 ℃, trichloromethane is volatilized, filter, get colourless transparent solution, the chloroform extraction of 10ml will be added in the filtrate, separatory obtains the upper strata water white transparency aqueous solution, puts in the baking oven to concentrate, drying gets white crystalline powder and is the pure product of Cantharidin acid potassium.

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Embodiment 2:

A kind of preparation method of Cantharidin acid potassium comprises the steps:

(1) add the pure product 1g of Cantharidin in the Erlenmeyer flask of 100ml, add 50 ml aqueous isopropanols, heating is dissolved it, gets potassium hydroxide 0.4 g simultaneously and adds 4 ml distilled water to make weight concentration be 10% solution;

(2) potassium hydroxide solution is joined in the aqueous isopropanol of dissolving Cantharidin, be heated to 75 ℃, Virahol is volatilized, filter, get colourless transparent solution, the Virahol extraction of 40 ml will be added in the filtrate, separatory obtains the upper strata water white transparency aqueous solution, puts in the baking oven to concentrate, drying gets white crystalline powder and is the pure product of Cantharidin acid potassium.

 

Product purity is checked

Cantharidin acid potassium does not have the quality determination standard of national regulation, so measure at this measuring method with reference to the Cantharidin acid sodium national drug standards [standard No.: WS-10001-(HD-0044)-2002].

Assay

Chromatographic condition and system suitability test are weighting agent with the octadecylsilane chemically bonded silica; Methyl alcohol-water (51:49) is moving phase; Flow velocity is 1.0ml/min; The detection wavelength is 227nm; Sensitivity is 0.005AUFS.Number of theoretical plate is pressed the Cantharidin peak and is calculated, and should be not less than 2000.

The preparation of reference substance solution: it is an amount of to get the Cantharidin reference substance, and accurate the title decides, and adds methyl alcohol and makes the solution that per 1 ml contains Cantharidin 0.15mg, product solution in contrast.

The preparation of need testing solution: precision takes by weighing this product 10mg, to the 100ml flask, adds the 50ml water dissolution, add 1mol/L H2SO4 solution 10ml again, shake up, put in 65 ℃ of water-baths and refluxed 30 minutes, move in separating funnel after cold slightly, with trichloromethane 25 ml, 15 ml, 10 ml extraction three times, each 10 minutes, combining extraction liquid, put in 70 ℃ of water-baths and volatilize solvent, residue changes appearance to 50 ml measuring bottles with methyl alcohol, constant volume, shake up, be need testing solution.

Assay method: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject liquid chromatograph, the record color atlas calculates Cantharidin content with external standard method, multiply by the molecular weight of the molecular weight/Cantharidin of 1.48(Cantharidin acid potassium again), promptly get Cantharidin acid potassium content.

The Cantharidin acid potassium purity that detected result embodiment 1,2 obtains is more than 95%.

 

After testing, Cantharidin acid potassium is to concentration (IC in the inhibition of liver cancer QGY-7703 ₅₀ ) be17.53 μ mol/L is higher than the activity of Cantharidin acid sodium sodium, active close with Cantharidin. Cantharidin acid potassium is rightCancer of the stomach SGC7901 cell Inhibition in concentration (IC ₅₀ ) be20.41 μ mol/L is higher than the activity of Cantharidin acid sodium, a little less than the activity of Cantharidin.

Claims (2)

1. Cantharidin acid potassium, its structural formula is:

。

2. the preparation method of Cantharidin acid potassium as claimed in claim 1 comprises the steps:

(1) get the pure product of Cantharidin and add trichloromethane or Virahol by the weight ratio of 1:30-50, heating makes its dissolving, and getting simultaneously and making weight concentration with the potassium hydroxide adding distil water of Cantharidin mol ratio 3:2-3 is 10% solution;

(2) potassium hydroxide solution is joined in the chloroform soln or aqueous isopropanol of dissolving Cantharidin, be heated to 60-75 ℃ after, trichloromethane or Virahol are volatilized, filter, colourless transparent solution;

(3) trichloromethane of 2-5 times of volume of adding or Virahol extraction in filtrate, separatory obtains the upper strata water white transparency aqueous solution, puts in the baking oven to concentrate, and drying gets white crystalline powder promptly.