41 results about "Lobaplatin" patented technology

The invention relates to a method for preparing a lobaplatin trihydrate by using oxalate, diaminomethyl cyclobutane oxalate, potassium chloroplatinite and potassium iodide are taken as raw materials, and the method comprises the following steps: firstly replacing the potassium chloroplatinite to potassium iodoplatinite, neutralizing the oxalic acid in diaminomethyl cyclobutane under alkaline condition, enabling the diaminomethyl cyclobutane to be freed, and then reacting the diaminomethyl cyclobutane with K2PtI4 (potassium iodoplatinate) for synthesizing a diiodide; enabling the diiodide to carry out replacement reaction with silver nitrate to generate silver iodide precipitate, enabling reactants after filtering out the precipitate to carry out ion exchange with anion exchange resin, then synthesizing a lobaplatin anhydride with lactic acid, re-crystallizing the anhydride in water / acetone mixed solution, and finally obtaining a lobaplatin trihydrate product. The raw materials used in the method have stable performances, the reaction is fuller and more complete, and the yield of the lobaplatin trihydrate is high.

The invention relates to a preparation method of diaminomethyl cyclobutane oxalate, which comprises the following steps: carrying out dimerization on acrylonitrile used as a raw material to generate a cis-dinitrile cyclobutane / trans-dinitrile cyclobutane mixture, carrying out distillation separation on the generated cis-dinitrile cyclobutane / trans-dinitrile cyclobutane mixture, and converting into trans-dinitrile cyclobutane by reduction; by using active nickel as a catalyst, introducing ammonia, and pressurizing with hydrogen to react, thereby obtaining trans-diaminomethyl cyclobutane; adding oxalic acid to obtain a crude diaminomethyl cyclobutane oxalate product; and finally, purifying with alcohol to obtain the finished diaminomethyl cyclobutane oxalate product. By using the method provided by the invention, the raw material is accessible, the operation is easy to control, the obtained product can be used as an intermediate to participate in the synthesis of Lobaplatin, and the obtained Lobaplatin has more stable properties and is more suitable for industrial production.

The present invention relates to the application of lobaplatin in the preparation of drugs for treating prostate cancer, especially the application in the preparation of drugs for treating non-hormone-dependent prostate cancer. The effective therapeutic dose of lobaplatin is 20-50 mg / m2 body surface area. The present invention It provides new therapeutic drugs for prostate cancer and expands the clinical application of lobaplatin and its preparations.

The invention relates to a lobaplatin crystal, a preparation method and a drug application. The lobaplatin crystal form is B, its melting point Tm.p..=230±5°C, and its X-ray powder diffraction PXRD pattern has a 2θ angle value of There are diffraction peaks at 8.25, 9.77, 11.70, 13.13, 15.28, 16.48, 17.22, 17.74, 19.01, 19.56, 22.28, 23.72, 24.04, 24.30, 25.62, 26.20, 28.57, 30.22, 30.61, and the error range of 2θ is 0. The crystal form is obtained by solvent volatilization of lobaplatin trihydrate, or adding a solvent to lobaplatin dihydrate and volatilizing at room temperature or drying after elution and crystallization. Compared with the existing lobaplatin and lobaplatin trihydrate, the lobaplatin compound with crystal form B has better stability and solubility, is more suitable for the preparation of various forms of pharmaceutical preparations, storage and use, and can be more It is preferably used in the treatment of cancer such as the treatment of breast cancer, small cell lung cancer or chronic myelogenous leukemia.

The invention relates to the technical field of drug synthesis, in particular to a method for synthesizing a lobaplatin intermediate. The method uses low-toxicity dimethyl malonate as a starting material, and undergoes coupling, bromination, cyclization, hydrolysis, Synthesis of high-purity trans-1,2-dicyanocyclobutane after amidation and dehydration reactions. In the synthesis of the whole route, all the raw and auxiliary materials used are easy to purchase, cheap and low in toxicity. The reaction conditions are not harsh and uncontrollable. The reaction conditions of each step can be applied to scale-up production. Although the reaction steps are increased, the yield of the product However, the yield has been greatly improved, thereby greatly reducing the cost, and the obtained trans-1,2-dicyanocyclobutane has improved purity, fully meets the subsequent use requirements, and greatly improves market competitiveness.

The invention relates to a lobaplatin crystal, a preparation method and a pharmaceutical application. The lobaplatin crystal form is F, the melting point Tm.p..=229±5°C, and the 2θ angle value in the X-ray powder diffraction PXRD spectrum is 8.21 、11.60、12.99、15.24、16.44、17.11、17.55、18.42、19.01、19.20、19.42、21.81、22.17、22.42、23.33、23.85、24.18、24.40、24.77、25.46、25.98、26.13、27.89、28.42、29.03、30.32 There are diffraction peaks at , 31.17, 31.94, 33.30, 36.20, 37.62, and 39.66, and the error range of the 2θ value is 0.2. The crystal form F is obtained by adding methanol or ethanol to lobaplatin dihydrate, stirring at room temperature until the solid is dissolved, filtering off the insoluble matter, and then slowly adding an organic solvent. After the crystal is separated, the crystal is separated and dried. get. Compared with the existing lobaplatin and lobaplatin trihydrate, the lobaplatin crystal of crystal form F has better stability and solubility, and is more suitable for the preparation, storage and use of various forms of pharmaceutical preparations, and can better For the treatment of cancer such as the treatment of breast cancer, small cell lung cancer or chronic myelogenous leukemia.

The invention provides a preparation method of lobaplatin and its trihydrate, using trans-diaminomethylcyclobutane and chloroplatinite as raw materials, using water as a solvent, and reacting to synthesize dibasic acid under an inert gas atmosphere. Chloride; dichloride and silver nitrate replacement reaction, filter the resulting silver chloride precipitate, react the filtrate with L-lactic acid and / or its salt at a certain pH value to synthesize lobaplatin, and then regenerate it with water / acetone Crystallization to obtain high-purity lobaplatin trihydrate. The preparation method of the invention has few reaction steps, short reaction time, high reaction efficiency, simple and convenient operation, and is suitable for industrialized production.

The invention relates to a lobaplatin crystal, a preparing method and a medicine application. The crystal form of the lobaplatin crystal is C, and the melting point Tm.p.. is 228+ / -5 DEG C; in a PXRD pattern of the lobaplatin crystal, diffraction peaks exist when the 2theta value is 6.79, 8.07, 12.24, 12.61, 13.50, 16.50, 17.83, 18.32, 18.79, 20.09, 21.64, 22.27, 23.19, 24.73, 27.34, 28.35, 29.12 and 31.92, and the error range of the 2theta value is 0.2. The preparing method for the crystal form C includes the steps that isobutanol or normal propyl alcohol is added into lobaplatin dihydrate, the mixture is stirred in a suspension mode, and the crystal is dissolved out, separated out, dried and then obtained. Compared with existing lobaplatin and lobaplatin trihydrate, better stability and better solubility are achieved, and the lobaplatin crystal can be better suitable for preparing medicine preparations in various forms, can be better stored and used and can be better used for treating cancers such as the breast cancer, the small cell lung cancer and the chronic granulocytic leukemia.