RU2191581C1 - Method of fluorouracil solution preparing - Google Patents

Abstract

FIELD: medicine, pharmacy. SUBSTANCE: invention relates to methods of preparing fluorouracil-base antitumor composition designated for injections. Method of preparing involves preparing fluorouracil solution by dissolving sodium hydroxide taken in the amount 13-17 g/l in water for injection followed by addition of fluorouracil taken in the amount 45-55 g/l. Before addition of sodium hydroxide water is subjected for treatment by ultrasonic oscillation in frequency 1.0-1.5 MHz for 10-15 min. Invention provides development of simple and available form of medicinal agent as injections. EFFECT: improved method of preparing, enhanced solubility of fluorouracil in water. 1 tbl

Description

 The invention relates to medicine, in particular to preparations based on fluorouracil in the form of injections. Fluorouracil is used for inoperable and recurrent cancer of the stomach, colon and rectum, cancer of the breast, ovaries, as well as cancer of the pancreas.

 Fluorouracil - 2,4-dioxo-6-fluoropyrimidine, or 5-fluorouracil is slightly soluble in water, very little in alcohol / Mashkovsky M.D. Medicines, t.1, M., 2000, p. 425 /.

 Various forms of a medicinal product based on fluorouracil are known, for example, in the form of a gel, solid forms, aerosols, etc.

 A known method of producing a gel base of an aerosol, in which fluorouracil, previously dissolved in a diluent, is used as the main substance. As a gel, a carboxyvinyl polymer with a certain viscosity is used (RF Patent 2028146 dated 04/05/1989). The method for producing the gel consists in introducing fluorouracil into the gel base, followed by adjusting the viscosity of the mixture by introducing sodium chloride or potassium chloride or calcium chloride. The disadvantage of this form is the low absorption capacity of fluorouracil when applied to a living organism.

 A known method of obtaining a pharmaceutical composition for oral administration, which consists in obtaining a clathrate complex of cyclodextrin derivatives with a medicinal substance - fluorouracil (Patent 2113442 from 07.26.1993).

 A known method of producing a hydrogel preparation with a prolonged release of fluorouracil by introducing into the form an additive that allows water to penetrate into the core of the preparation and a hydrogel-forming polymer comprising at least one polyethylene oxide (Patent 2121830 from 09/10/1998).

 A known method of obtaining a solid pharmaceutical preparation containing a physical mixture of sulfoalkyl ether cyclodextrin and fluorouracil (Patent 2173172 from 04/20/1998).

 A known method of obtaining an aqueous medicinal composition, which consists in mixing a pharmaceutically effective amount of a medicinal product fluorouracil, methyl cellulose, citric acid, polyethylene glycol (Patent 2108112 from 10.11.1993).

 The main disadvantages of the known methods for producing forms are: the inability to obtain a dosage form with prolonged release of the active substance since fluorouracil has a short half-life of the drug, a multi-stage method for producing the dosage form.

 The closest technical solution to the claimed object relates to a known method for producing an antitumor composition comprising fluorouracil intended for injection. The method consists in obtaining particles consisting of a surface modifier on which fluorouracil is adsorbed. The surface modifier is selected from the group consisting of polyvinyl alcohol, tetrafunctional block copolymer obtained by sequential addition of ethylene oxide and propylene oxide to ethylene diamide, gum arabic, block copolymer of ethylene oxide and propylene oxide, polyoxyethylene sorbitan fatty acid ester and fatty acid ester. The antitumor composition, in addition to particles, contains a pharmaceutically acceptable carrier. (RF patent 2130781 from 06.30.1993).

 The known method for producing a dosage form in the form of injections according to the prototype has several disadvantages: the complexity of the composition and technology for its preparation.

 The purpose of this invention is the creation of a simple and affordable form of the drug in the form of an injection containing fluorouracil as an active ingredient, increasing the solubility of fluorouracil in water.

 This goal is achieved through the use of a method for producing an antitumor composition based on fluorouracil intended for injection, which consists in preparing a solution of fluorouracil by dissolving sodium hydroxide in water for injection, taken in an amount of 13-17 g / l, followed by the addition of fluorouracil in an amount of 45-55 g / l At the same time, water for injection before exposure to sodium hydroxide is subjected to ultrasound for 10-15 minutes with a frequency of 1.0-1.5 MHz.

An example implementation of method 1
Water for injection is subjected to ultrasound for 10-15 minutes with a frequency of 1-1.5 MHz, then at a temperature of 25-35 ^o With load the calculated amount of sodium hydroxide. The estimated amount of fluorouracil powder is fed into the solution. The solution is bubbled with an inert gas (nitrogen) and filtered with a dilution of 0.4 ati.

 Ultrasonic treatment of the solution allows to increase the solubility of fluorouracil in water, which in turn leads to an increase in the activity of the dosage form.

 The experimental results are summarized in the table.

Claims (1)

 A method of obtaining an antitumor composition intended for injection and comprising fluorouracil, which consists in preparing an aqueous solution of fluorouracil, characterized in that the water for injection is first subjected to ultrasound for 10-15 minutes with a frequency of 1-1.5 MHz, then sodium hydroxide is added to the amount of 13-17 g / l, after which fluorouracil in the amount of 45-55 g / l is added to the solution.

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