40 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 composite developing thermosensitive gel embolizing agent as well as a preparation method and application thereof. The preparation method comprises the following steps: firstly, preparing a mixed aqueous solution of an anticancer active substance, a thermosensitive material and a developing agent into composite developing thermosensitive gel; secondly, forming a composite developing thermosensitive gel embolizing agent by the composite developing thermosensitive gel and a coagulant on the scene, wherein the thermosensitive material is hydroxyl C1-4 alkyl cellulose, Pluronic, alginate or a mixture of the substances; the anticancer active substance is arsenic trioxide, docetaxel, cisplatin, carboplatin, nedaplatin, oxaliplatin, lobaplatin, miriplatin, siRNA or a mixture of the substances; the developing agent is a water-soluble developing agent of iodixanol, ioversol or iohexol and the like. The preparation method disclosed by the invention is simple and convenient, is suitable for industrial large-scale production, is particularly suitable for preparing an embolizing agent which is biodegradable and good in biocompatibility and is used for hemorrhagic diseases, and is especially suitable for preparing the composite developing thermosensitive gel embolizing agent for treating liver cancer, kidney cancer, lung cancer, prostate cancer, uterine myoma or splenic tumor and the like.

The invention provides a preparation method of lobaplatin and lobaplatin trihydrate. Trans-diamine methyl cyclobutane reacts and synthesizes with chloroplatinite in water at the atmosphere of inert gas to generate dichloride, wherein the trans-diamine methyl cyclobutane and the chloroplatinite are taken as raw materials, and the water serves as a solvent; replacement reaction is performed on the dichloride and silver nitrate, so that silver chloride sediments are generated after filtration; filter liquor reacts with L-lactic acid and/or L-lactate under a certain pH value condition so as to generate the lobaplatin; then water/acetone recrystallization is performed on the lobaplatin, so that high-purity lobaplatin trihydrate is obtained. The preparation method provided by the invention includes few reaction steps, and is short in reaction time, high in reaction efficiency, easy and convenient to operate and suitable for industrial production.

The invention belongs to the technical field of chemical pharmacy and in particular relates to a method for preparing an antitumor medical preparation. The method comprises the following steps of: (1) preparing solution by taking Lobaplatin as a raw material and adding a proper amount of cooled water for injection; (2) adding a proper amount of active carbon with needle uses and adding the water for injection until full content, stirring while preserving heat and then performing aseptic filtration; (3) bulking filtrate and half pressing the plug, collecting the filtrate to a free-drying plate; putting into a freeze fryer cooling chamber, prefreezing, vacuumizing and heating, performing sublimation drying and desorbtion drying and performing vacuum breaking and free-drying; (4) introducing dried and degermed high-purity nitrogen, taking the obtained product out of the freezer and rolling the cover to obtain Lobaplatin for injection.

The invention relates to a lobaplatin crystal, and a preparation method thereof and a pharmaceutical application thereof. The crystal has a crystal form of E, and has a melting point Tm.p.. of 214+/-5 DEG C. In an X-ray powder diffraction PXRD pattern of the crystal, diffraction peaks appear when 2theta angle values are 6.61, 8.09, 12.38, 13.03, 15.40, 16.66, 17.47 and 19.07, wherein an 2theta value error range is 0.2. The crystal form E is obtained through the following steps: glycol dimethyl ether is added into lobaplatin dihydrate; suspension stirring is carried out, and crystals are precipitated; the crystals are separated and dried, such that white powder is obtained. Therefore, the novel crystal form E of lobaplatin is obtained. Compared with existing lobaplatin trihydrate, the crystal form provided by the invention has better stability and solubility. The crystal form is suitable to be used for preparing various forms of pharmaceutical preparations, and is suitable for storage and application. The crystal can be better used for treating cancers such as breast cancer, small-cell lung cancer or chronic myelogenous leukemia.

The present invention relates to a lobaplatin crystal and a preparation method and drug application thereof, the lobaplatin crystal form is B, the melting point Tm. p. . is 230 +/-5 DEG C, diffraction peaks exist at the 2 theta angle values of 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 and 30.61 in an X-ray powder diffraction PXRD spectrum, wherein the 2 theta angle value error is in the range of 0.2. The crystal form B is obtained by solvent evaporation of lobaplatin trihydrate, or volatilization at room temperature after addition of a solvent in lobaplatin dihydrate or solvent-out crystallization, and drying. Compared with lobaplatin and the lobaplatin trihydrate in the prior art, the lobaplatin crystal in the crystal form B has better stability and solubility, is more suitable for the preparation of various forms of pharmaceutical preparations and storage and use, and can be better used to treat cancers such as breast cancer, small cell lung cancer or chronic granulocytic leukemia.

The invention relates to lobaplatin dihydrate, a preparation method and drug application. The melting point Tm.p.. of the lobaplatin dihydrate is 220+/-5 DEG C, and the crystal form of the lobaplatin dihydrate is A. An X-ray powder diffraction PXRD pattern has diffraction peaks when the 2theta value is 11.04, 12.32, 12.61, 13.85, 15.14, 15.55, 16.68, 17.67, 17.86, 19.03, 20.06, 21.00, 22.68, 22.92, 23.76, 25.39, 25.58, 26.37, 26.77, 27.00, 27.71, 28.13, 29.71, 31.42, 31.94, 32.89, 34.29, 34.60, 36.10, 36.93, 37.66, 40.78 and 43.41, wherein the error range of the 2theta value is 0.2. The lobaplatin dihydrate is obtained by adding lobaplatin trihydrate into suspension crystallization solvent and performing suspension crystallization. Compared with the prior art lobaplatin and lobaplatin trihydrate, the lobaplatin dihydrate has better stability and solubility, is more suitable for preparation of drug preparations of different forms, storage and usage and can be better used for treating breast cancer or small cell lung cancer or chronic myeloid leukemia or the like.

The invention relates to a method for preparing hydroxy carboxylic acid platinum complexes, in particular to a method for preparing platinum anticancer drugs of nedaplatin and lobaplatin. The preparation method includes that: compounds (I) and (II) and silver oxide in molar ratio of 1:1: 1, and certain quantity of water are added to a reactor and stirred to conduct light-shielding reaction for 1-20 hours at the temperature of 0-80 DEG C. The filtrate after filtration is concentrated to be dry, is cooled and rinsed by water, filtrated and rinsed by ethanol and is finally pumped out to obtain the product (III) after vacuum drying for 2-3 hours at the temperature of 40-45 DEG C. The invention obtains the product water solution through one-step reaction, concentrates the water solution to obtain the final product, has no need to adjust the pH value in the synthesis process, avoids the Na<+>, NO<3->, SO4<2->, Ba<2+> interference reaction, and accordingly realizes high productivity and good purity.

The invention discloses a preparation method of lobaplatin trihydrate, which comprises the following steps: by using potassium chloroplatinite, potassium iodide and trans-1,2-diaminomethylcyclobutanehydrochloride as raw materials and water as a solvent, replacing potassium chloroplatinite with potassium iodo-platinite, and reacting potassium iodo-platinite with trans-1,2-diaminomethylcyclobutanewhich is dissociated from the 1,2-diaminomethylcyclobutane hydrochloride under an alkaline condition through neutralization to generate a diiodide; and refining the diiodide, carrying out hydrolysis reaction on the refined diiodide and silver nitrate, filtering out generated silver iodide precipitate, reacting filtrate with sodium lactate to generate a lobaplatin anhydrous substance, and recrystallizing the lobaplatin anhydrous substance in an acetone-water mixed solvent to obtain the lobaplatin trihydrate. The method has the advantages of short synthesis time and simple operation, the precursor chemical acetone involved in the reaction process can be recycled, and the obtained lobaplatin trihydrate has the advantages of high purity, high yield and good stability, and is suitable for industrial production.

The invention relates to the technical field of medicine synthesis, in particular to a novel synthesis method of a lobaplatin intermediate, the method comprises the following steps: taking low-toxicity dimethyl malonate as an initial raw material, carrying out coupling, bromination, cyclization, hydrolysis, amidation and dehydration reaction to synthesize high-purity trans-1, 2-dicyanocyclobutane. In the whole route synthesis, all adopted raw and auxiliary materials are easy to purchase, low in price and low in toxicity, the reaction conditions are not harsh and uncontrollable, the reaction conditions of each step can be suitable for amplified production, although the reaction steps are increased, the yield of the product is greatly improved, so that the cost is greatly reduced, and the purity of the obtained trans-1,2-dicyanocyclobutane is improved and completely meets the subsequent use requirements, and the market competitiveness is greatly improved.

The present invention relates to a lobaplatin crystal and a preparation method and drug application thereof, the lobaplatin crystal form is F, the melting point Tm. p. . is 229 +/-5 DEG C, diffraction peaks exist at the 2 theta angle values of 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, 31.17, 31.94, 33.30, 36.20, 37.62 and 39.66 in an X-ray powder diffraction PXRD spectrum, wherein the 2 theta angle value error is in the range of 0.2. The crystal form F is obtained by adding methanol or ethanol into lobaplatin dihydrate, stirring at room temperature until the solid is dissolved, filtering insoluble matters out, adding dropwise slowly an organic solvent, after precipitation of a crystal, separating the crystal, and drying. Compared with lobaplatin and lobaplatin trihydrate in the prior art, the lobaplatin crystal in the crystal form F has better stability and solubility, is more suitable for the preparation of various forms of pharmaceutical preparations and storage and use, and can be better used to treat cancers such as breast cancer, small cell lung cancer or chronic granulocytic leukemia.

The invention relates to a pharmaceutical composition for treating small cell lung cancer and application, a kit and package thereof. The pharmaceutical composition, kit and package contain a treatment effective dose of lobaplatin and a treatment effective dose of etoposide as a combination for simultaneous, separated or sequential use. When used for treating the small cell lung cancer, the pharmaceutical composition, kit and package provided by the invention can obtain excellent treatment effect and have small toxic side effect.

The anticancer composition containing both platinum compound and sirolimus is one kind of slow releasing injection or slow releasing implant. The slow releasing injection consists of slow released microsphere and special solvent containing suspending agent. The platinum compound is selected from cisplatin, carboplatin, lobaplatin, etc; the slow releasing supplementary material is selected from polylactic acid, lactic acid copolymer, polifeprosan, etc; and the suspending agent is selected from sodium carboxymethyl cellulose, iodine glycerin, etc. The slow releasing injection and the slow releasing implant are injected or set into solid tumor to diffuse and produce synergistic curative effect.

The invention discloses an application of lobaplatin in preparing medicines for treating malignant trophoblastic tumor. The lobaplatin is represented in dosage forms of lyophilized powder for injection, a small -volume injection or a large-volume injection, with an effective therapeutic dose of 30-60mg/m<2> body surface area. The lobaplatin and a preparation thereof are relatively strong in action of resisting the malignant trophoblastic tumor; and the lobaplatin and the preparation thereof are significant in therapeutic effect, low in toxicity and safe; therefore, a novel effective means is provided for the treatment of the malignant trophoblastic tumor and clinical application of the lobaplatin and the preparation thereof is widened.

The invention discloses an application of lobaplatin in preparing medicines for treating malignant pleural mesothelioma. The lobaplatin is represented in dosage forms of lyophilized powder for injection, a small -volume injection or a large-volume injection, with an effective therapeutic dose of 30-60mg/m<2> body surface area. The lobaplatin and a preparation thereof are relatively strong in action of resisting the malignant pleural mesothelioma; and the lobaplatin and the preparation thereof are significant in therapeutic effect, low in toxicity and safe; therefore, a novel effective means is provided for the treatment of the malignant pleural mesothelioma and clinical application of the lobaplatin and the preparation thereof is widened.

The invention relates to a purification method of a high-purity lobaplatin trihydrate for preparing an antitumor drug. The method comprises the following steps: 1, dissolving a lobaplatin crude product in a high-temperature aqueous solution, filtering, crystallizing at low temperature, re-filtering, and drying to obtain the lobaplatin trihydrate; and 2, dissolving the lobaplatin crude product in a high-temperature aqueous solution, filtering, adding diethyl ether into the filtrate, crystallizing at low temperature, filtering, and drying to obtain the lobaplatin trihydrate. According to the invention, the purification can be repeated multiple times until the high-purity lobaplatin trihydrate is obtained; according to the purification method, the lobaplatin crude product with the content of 55-95% is purified, the purity of the lobaplatin crude product can be improved to 98% or above, the used purification solvent is water or diethyl ether, and after the sample is fully washed with water, the obtained product is high in safety; purification belongs to conventional operation, and preparation is easy; the prepared high-purity lobaplatin trihydrate can be applied to antitumor drugs; and the preparation method is short in preparation time, simple to operate, low in production cost and suitable for industrial production.

The invention discloses application of lobaplatin in preparation of a medicine for treating bladder cancer, belongs to the technical field of new applications of chemical medicines, and particularly relates to application of a platinum medicine in bladder cancer. The lobaplatin dosage form is a freeze-dried powder injection, a small-volume injection or a large-volume injection, and the effective treatment amount is 45-55 mg/m<2> body surface area. The lobaplatin and the lobaplatin preparation have the advantages of strong bladder cell tumor resistance, substantial treatment effect, low toxicity, safety, provision of a new treatment medicine for bladder cancer, and expansion of the clinical application of lobaplatin and the lobaplatin preparation.