80 results about "Irinotecan Hydrochloride" patented technology

The invention relates to a method for producing injection alcaine liposome, wherein it comprises that: dissolving liposome mixture into organic solvent; mixing liposome solution with buffer solution; compressing it via panlite film into uniform diameter, filtering out the organic solvent, to obtain blank liposome, adding alcaine solution, using pH adjuster to adjust pH value to alkali, to prepare the carrier liposome; or dissolving phosphatide, cholestrin and alcaine into organic solvent; atomizing and drying, vacuum drying or other method to remove organic solvent, to film the liposome; adding hydrating solution with drug to form carrier liposome. The inventive liposome has 50-200nm diameter and more than 95% package rate, with stable property.

The invention discloses an irinotecan or irinotecan hydrochloride lipidosome and a preparation method thereof. The lipidosome contains irinotecan or irinotecan hydrochloride, neutral phospholipid and cholesterol, wherein the weight ratio of the cholesterol to the neutral phospholipid is 1:(3-5), and the irinotecan or irinotecan hydrochloride lipidosome is prepared by an ion gradient method.

The present invention is to prepare efficiently 2'-amino-5'-hydroxypropiophenone corresponding to the AB-ring part of camptothecin (CPT) skeleton and a tricyclic ketone corresponding to the CDE-ring part in order to provide efficiently CPT by the total synthesis, which is a starting material for irinotecan hydrochloride and various kinds of camptothecin derivatives, and to provide stably CPT and its derivatives.

The invention relates to an irinotecan hydrochloride injection consisting of irinotecan hydrochloride (15-25g/L), sorbierite (17.5-22.5g/L), and the balance of phosphoric acid and injection water, wherein the phosphoric acid adjusts the pH of the injection to 3.0-3.8. The invention also relates to a preparation method of the irinotecan hydrochloride injection. Compared with the prior art, the irinotecan hydrochloride injection disclosed by the invention has the following beneficial effects: (1) the untoward effect is reduced; as shown in an animal test, the irinotecan hydrochloride injection disclosed by the invention can greatly reduce the untoward effect of delayed-onset diarrhea caused by irinotecan, which has an active promotion effect on the drug dependency and treatment effect of cancer patients; (2) the stability is high, as shown in an acceleration test, the character, acidity, solution clarity and color, insoluble particles, visible foreign matters, moisture, related substance and content of the irinotecan hydrochloride injection meet the regulations; and (3) the preparation method is simple and is favorable to the industrial mass production.

The invention provides an irinotecan hydrochloride liposome pharmaceutical composition and a preparation method thereof. The irinotecan hydrochloride liposome pharmaceutical composition comprises irinotecan hydrochloride, hydrogenated soy phosphatidylcholine (HSPC), distearoyl phosphatidylcholine (DSPC), cholesterol (CHol) and Phosphatidylethanolamine Pegol. The irinotecan hydrochloride liposome pharmaceutical composition obtained through the preparation method has a high encapsulation rate, a high drug loading amount and good stability.

The invention relates to an irinotecan hydrochloride composition, which comprises a blank lipid nano-preparation, an irinotecan hydrochloride solution and a pH adjustment solution. The blank lipid nano-preparation, the irinotecan hydrochloride solution and the pH adjustment solution have independent packaging respectively. Before clinical use, the three components are mixed and incubated, and are prepared into a clinical drug loaded nano-preparation through active drug loading. The composition provided by the invention adopts a three-bottle independent packaging design, and drugs are not loaded into the lipid nano-preparation in the storage process, so that the preparation is free of the easy drug leakage problem in existing preparations, and stability of the preparation is greatly improved. Before clinical use, the three components are mixed and incubated to be prepared into the drug loaded nano-preparation, which is simple and convenient for clinical use. The invention also relates to a preparation method for the irinotecan hydrochloride composition. The preparation process has the characteristics of simplicity and easy quality control, and is suitable for industrialized production.

The invention discloses a new crystal of irinotecan hydrochloride. The crystal has characteristic peaks under powder X-ray diffraction at the following angles (2 theta): 7.80 degrees, 9.96 degrees, 13.28 degrees, 15.62 degrees, 19.98 degrees, 20.36 degrees, 22.34 degrees, 22.66 degrees, 26.60 degrees and 30.18 degrees. In addition, the invention also discloses a method for preparing a new crystal form of the irinotecan hydrochloride. The irinotecan hydrochloride prepared by the method has good water-solubility, good storage stability, high content and purity and less impurity.

The invention provides a method for preparing irinotecan hydrochloride. The method reacts the intermediate 7-ethyl-10-hydroxycamptothecin with 4-piperidinylpiperidine carboxylic acid chloride or its salt in the presence of 4-dimethylaminopyridine or its salt, or its analogue, The final product is obtained through steps such as concentration, washing, and salt formation. The method of the invention avoids the use of malodorous and easily discolored pyridine to participate in the reaction, reduces side reactions, improves the purity and yield of the product, improves the color of the product at the same time, and is easy for large-scale production.

The invention relates to an irinotecan hydrochloride composition, which is a composition by using irinotecan hydrochloride as a main drug and an auxiliary solution consisting of sorbic alcohol, lactic acid, alkaline regulation solution and injection water as dissolving solution. The preparation method comprises the following steps: weighing sorbic alcohol and lactic acid in a container according to the prescription, adding the injection water, stirring to dissolve, and regulating the pH to be between 3.0 and 4.0 with the alkaline regulation solution; adding the irinotecan hydrochloride with the amount of the prescription, dissolving, adding 0.1 percent activated carbon, stirring for 20 minutes, and decarburizing; filtering with a 0.22mu m microporous filter membrane until the mixture is clear; detecting the intermediate substance; filling in a penicillin bottle, plugging a butyl rubber plug, and rolling a cap; and performing leakage inspection and light inspection to the sample after high-pressure sterilization, and packaging after the sample is qualified in quality inspection.

The invention discloses a method for encapsulating a hydrophobic antitumor drug by an amphiphilic medicament, comprising: (1) adding the amphiphilic medicament and the hydrophobic antitumor drug into an organic solvent, and uniformly mixing; (2) adding distilled water into an obtained mixture, and uniformly mixing to obtain a preparation solution; and (3) removing the organic solvent in the preparation solution, adding a freeze-drying protective agent, and carrying out freezing and drying treatment, to obtain an antitumor drug pulvis encapsulated with the hydrophobic antitumor drug. The invention further discloses a medicinal preparation prepared by the method. The amphiphilic medicament irinotecan hydrochloride or topotecan hydrochloride is used as an emulsifier to encapsulate a water insoluble anticancer medicament, which greatly increases solubility of the hydrophobic medicament in water and reserves high antineoplastic activity characteristics of the medicament itself, has advantages of simple preparation technology, strong applicability and convenience for large scale production, and develops a new approach for in vivo conveying of the hydrophobic medicament.

The invention provides a prescription and a preparation process for an irinotecan hydrochloride injection. The preparation process comprises the following steps: weighing and re-checking; preparation of a soup; removal of bacteria through filtration; sterile filling; and terminal sterilization. The invention is characterized in that since the process employs rotating water-bath for terminal sterilization, fast production is realized, the amount of related substances can be effectively controlled, the period of validity is prolonged and irinotecan hydrochloride in the injection is allowed to be more stable.

The invention provides a preparation method of an irinotecan hydrochloride injection. Each ml of the injection contains 20mg of irinotecan hydrochloride, 45mg of sorbitol, 0.9mg of lactic acid and thebalance of pH regulator and injection water. The preparation method includes: a), taking 50-70% of total volume of the injection water at room temperature, sequentially adding lactic acid, sorbitol and irinotecan hydrochloride of prescription volume sequentially, stirring, heating to 70-80 DEG C, and cooling to the room temperature after irinotecan hydrochloride is fully stirred and dissolved; b), using the pH regulator to adjust pH of medicine liquid to 3.0-4.0 (3.5 preferably), supplementing the injection water, and fixing volume to the total volume; c), filtering, filling, plugging and capping, sterilizing, and packaging to obtain the injection. Compared with the prior art, the preparation method has the advantages that the problem of separation-out of irinotecan hydrochloride in a solution is solved effectively, the injection is reliable in quality, and the preparation method is simple, convenient and suitable for industrial mass production.

The invention provides an irinotecan hydrochloride lipidosome composition, which consists of the following ingredients in parts by weight: 1 part of irinotecan hydrochloride, 2-6 parts of hydrogenated soybean phosphatide, 1.0-2.25 -parts of cholesterol and 0.04-0.20 parts of distearoyl phosphoethanolamine-polyethylene glycol 2000. The invention also provides a preparation method of the lipidosome composition. The lipidosome disclosed by the invention significantly reduces cost, and the lipidosome is good in stability,low in content of impurities, high in safety and easy for industrial mass production.

The invention discloses an irinotecan hydrochloride lipid nanoparticles injection and a preparation method thereof. Mixed phase is formed by dissolving irinotecan hydrochloride and stearic acid in organic solvent and dissolving lecithin in buffer salt solution; aqueous solution of PEG (polyethylene glycol) 400, glycerol and trehalose is adopted as aqueous phase; and then irinotecan hydrochloride is loaded in lipid nanoparticles by combining stirring emulsification and high-pressure emulsion homogenizing to obtain the irinotecan hydrochloride lipid nanoparticles injection. The inventive lipid nanoparticles preparation has the advantages of high drug loading rate, uniform particle size, long drug retention time in blood circulation, better sustained-release and controlled-release effect, simple preparation method and device, easy operation, improved product quality, reduced toxic and side effects, and suitability for industrialized production.

The invention discloses a preparation method of irinotecan hydrochloride. The preparation method comprises following steps: 1, chemical raw materials of racemic indolizine derivatives are taken as initial raw materials, ring closing reaction and alkali ring-opening reaction are carried out so as to obtain an organic acid intermediate; 2, a chiral amine and the organic acid intermediate are subjected to salt forming resolution so as to obtain a chiral intermediate; 3, the chiral intermediate is subjected to acid ring-opening reaction so as to remove the chiral amine; 4, esterification with a piperidine derivative, and salt forming are carried out so as to obtain the target product irinotecan hydrochloride. The preparation method is used for total synthesis of irinotecan hydrochloride, large scale production is realized, reaction conditions are mild, the preparation method is easy to control, product purity is 98% or higher, and the largest individual impurity content is lower than 0.1%.

The invention relates to a preparation method of irinotecan hydrochloride. The method comprises the steps that a mother ring reacts with propionaldehyde by taking camptothecin as a raw material to generate 7-ethylcamptothecin, and then hydrogen peroxide is used for oxidization to generate N-oxide-7-ethylcamptothecin; illumination rearrangement is carried out to generate 7-ethyl-10-hydroxycamptothecine; 4-piperidinopiperidine reacts with dimethyl carbonate to generate 4-piperidinopiperidine methyl carbonate; 7-ethyl-10-hydroxycamptothecine reacts with 4-piperidinopiperidine methyl carbonate togenerate irinotecan monomer; the irinotecan monomer and hydrochloric acid are salified to obtain an irinotecan hydrochloride finished product. Compared with the prior art, in the reaction process, phosgene, chloroform and other toxic substances are prevented from being used, and the irinotecan hydrochloride has the advantages of being safe, convenient to use, little in pollution and the like during production. Besides, the synthesis method avoids the defect that a chromatographic column is needed for separation and purification in the prior art, the production cost of irinotecan is reduced, and huge economic benefits are achieved.

The invention relates to a method for preparing an irinotecan hydrochloride trihydrate pure product, which belongs to the field of medicinal chemistry. The method comprises the steps of first preparing dissociative 4-piperidyl piperidine formyl chloride, performing condensation reaction of the 4-piperidyl piperidine formyl chloride and 7-ethyl-10-hydroxycamptothecine with the presence of 4-dimethylamino piperidine or 4-dimethylamino pyridinium or analogues, and finally performing salifying to obtain an end-product. By means of the method, fetid and easily-discoloring piperidine participated condensation reaction is avoided, side reaction is decreased, the defects including increased period, large solvent dosage and the like caused by the fact that the product is purified through column chromatography are overcome, the purity and the yield of the product are improved, simultaneously color and luster of the product are improved, and the scale production is easy to achieve.

The invention discloses a making method of alcaine yilitikang drug, which comprises the following steps: 1) ethylizing camptothecine to produce 7-ethyl camptothecine; 2) hydrogenating the 7-ethyl camptothecine; obtaining hydrogenated-7-ethyl camptothecine; 3) oxidizing the hydrogenated-7-ethyl camptothecine to produce 7-ethyl-10-hydroxy camptothecine; 4) coupling the 7-ethyl-10-hydroxy camptothecine and 4-piperidine radical piperidine formyl chloride to obtain the product with simple operation, high efficiency, high receiving rate, lost and high quality.