Oxaliplatin medicament composition, preparation method thereof and method for synthesizing oxaliplatin as raw medicinal material

Abstract

The invention relates to an oxaliplatin medicament composition as an anticancer medicament, a preparation method thereof and a method for synthesizing oxaliplatin as raw medicinal material. The composition comprises oxaliplatin and lactose, wherein the mass ratio of the oxaliplatin to the lactose is 1:12-1:20. The composition can be added with injection water and pH regulator and made into freeze-dried powder injection through freeze drying. The freeze-dried powder injection not only has the advantages of good formability, plump shape and the like, but also overcomes the prejudice that oxaliplatin freeze-dried powder injection taking the lactose as a freeze-drying carrier is not good in formability and the like. The synthesis method comprises: 1) taking K2PtCl4 and trans-diaminocyclohexane as raw materials to prepare an intermediate (I); 2) forming an intermediate (II) through intermediate reaction; and 3) forming the oxaliplatin through the reaction of the intermediate (II) and potassium oxalate solution, wherein the step 2) also comprises a process of adding KI for reaction. The method has the advantages of simple reaction, mild conditions, short time and no silver ions in products.

Description

technical field [0001] The invention relates to an anticancer drug oxaliplatin pharmaceutical composition, a preparation method thereof, and a synthesis method of a crude drug oxaliplatin. Background technique [0002] Oxaliplatin (Oxaliplatin) was first disclosed in 1978, and the compound was claimed in US Patent No. 4,169,846A, and the preparation method of the compound was given. The basic steps of the method are: (1) reacting dichlorocyclohexane diammine platinum with silver nitrate solution; (2) removing silver chloride precipitate; (3) adding dibasic acid such as oxalic acid to react. [0003] [0004] Although the above-mentioned synthetic route is relatively simple, the requirements are harsh, and each step needs to be stored away from light, which undoubtedly increases equipment, and the reaction yield of the last step is very low, and the ratio of raw materials required is also relatively high, thus increasing the production cost. Conducive to industrialized pr...

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Problems solved by technology

But, the problem that this method exists is: silver ion exists in the product

[0011] U.S. Patent US5290961A discusses in the background technology that the synthetic technique that contains silver nitrate, oxalic acid in the prior art exists problem is: silver ion exists in the product

[0018] However, mannitol as a carrier also has some disadvantages: mannitol for injection is expensive as a lyophilized carrier, and oxaliplatin has a large filling volume and is easy to separate out due to its poor solubility. To a certain extent, it has a stabilizing effect on the solution, but it also brings problems. Due to the high solid content and large filling volume, there is a high risk of frying bottles in the production process of oxaliplatin freeze-dried powder injection. Ratio, greatly reducing the product yield, causing a lot of waste of production capacity, raw and auxiliary materials and inner packaging materials, due to the high toxicity of oxaliplatin, the drug leaked with the bomb bottle is likely to cause injury to the operator, and also to the Production clearance creates difficulties and increases risk of cross-contamination

[0020] It can be seen that in the prior art, it is generally believed that the oxaliplatin freeze-dried powder injection with lactose as the freeze-drying carrier has defects such as poor molding, fragility and inconvenient storage and transportation, and easy moisture absorption after shrinking, resulting in a decrease in content.

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