UA58983U - Method for manufacturing composition for treating tuberculosis - Google Patents

Abstract

A method for manufacturing the composition for treating tuberculosis comprises mixing sodium para-aminosalicylate, sodium sulfite anhydrous and water for injections. In 800 mL of the water for injections cooled to the temperature of 15-25 °C, disodium salt of ethylene diaminotetraacetate (0.2-) and sodium sulfite anhydrous (4.75-) are dissolved for 5-10 minutes. Upon the complete dissolution, 27.0- of sodium para-aminosalicylate is added for dissolution within further 10-15 minutes. The solution is completed to volume of 1000 mL with the water for injections. Then the samples of the solution are analyzed. When the composition corresponds to the specified parameters, the solution is filtered through FTV prefilter with retaining threshold of 1 µm followed by the final filtration through Pall filter with retaining threshold of 0.2 µm.

Description

with a bacteriostatic property relative to mycobacteria, its pharmacological property is bacteriostat- bacterium tuberculosis, the use of which has a sputum effect relative to mycobacteria tuberculosis. This pharmacological property, which is similar to more active anti-tuberculosis drugs, must be preserved by drugs, helps to slow down the development of the drug when receiving the infusion dosage form of this resistance and to enhance the action of the corresponding drug. At the same time, it is necessary to provide stabilizers. no properties and the required level of quality during

There is a known method of making 5, 10 and 20 95 solutions for long-term preservation. In the process of research, PASK-sodium in ampoules of 5 ml was used, for which it was established that it was the additional introduction of water saturated with carbon dioxide that added 1.5 g to the composition of the product as a disodium salt stabilizer (for 5 and 10 95) and 3 g (for 20 95 solution) crystalline ethylenediaminetetraacetic acid (or Trilon B) sodium sulfite (sodium sulfuric acid significantly increases the stability of the solution and increases the anhydrous). The solution is sterilized with flowing steam, its purity due to binding to this surface at 100 "C for 30 minutes (where sodium para- active substance of residual amounts of aminosalicylate is PASK) (IA Muravyov. Ucheb- of metal ions that are catalysts for the decomposition of active substances in the technology of drugs and galenic preparations, which makes it possible to store the solution

M.: Medgiz, 1961. - p. 718-719). The shelf life of this product at the temperatures used for the preservation of pharmaceutical preparations is one month. ratov, for two years.

The specified method does not allow to obtain the Disodium salt of ethylenediaminetetraacetic acid with stability and a high level of quality of the infusion slot (or Trilon B) is an organic substance that dissolves during long-term storage, as it forms strong compounds with the cations of many metals when it is stored for more than one month watch- plexes. It is used in medicine as an antidote - clouding or discoloration of the solution, it is a means of removing metals from the body. It is known that it becomes unstable, that is, it loses its therapeutic use of Trilon B intravenously at 2-4 g of properties, such a solution is not suitable for use in 500 ml of 5 95 glucose solution for 3-4 hours. or small every 6 hours with ectopic ari-

The basis of a useful model is the problem of tmia, pathological ossification of the skeleton, sclero- creation of a method of manufacturing a remedy for leukodermia, deposition of calcium salts in muscles, kidneys, and tuberculosis, which would provide stable joints |BMUZ. Complex - M.: Moscow. Productivity of properties and the required level of quality Sov. Encyclopedia. - 1979. - p. 2781|. of the infusion dosage form of this agent in relation to its preservation for two years. tives used in the manufacture of the product,

The set task is solved by what has been established experimentally. manufacture of a means for the treatment of tuberculosis, experimentally also established, which includes mixing sodium paraleno, that with a decrease in the quantitative content of compo-aminosalicylate, sodium sulfuric acid anhydrous, the stability of the means is not ensured and water for injections, according to with useful mo- and the required level of quality, namely, the agent loses its therapeutic properties in a tank with 800 ml of water for injections, while it is observed cooled to a temperature of (2055) "С, at first cloudiness of the solution or a change in color, and when 0.2-0.8 g of disodium salt is dissolved in ethylenediamine - the agent exhibits a toxic effect. of tetraacetic acid and 4.75-5.25 g of sodium sulfur - the method of manufacturing the agent for the treatment of anhydrous acidosis within 5-10 minutes, post-tuberculosis is carried out as follows. For complete dissolution of the components, load To obtain the remedy, namely, from 95 g of a solution of 27.0-33.0 g of sodium para-aminosalicylate powder and for infusions, which intended for the treatment of tuberculosis - dissolve it for 10-15 minutes, dissolve it in culosis, in a tank with 800 ml of water for injections, bring the tank up to 1000 with water for injections cooled to a temperature of 1-25 "С, dissolve ml, then a sample is taken for analysis and with 0.2-0.8 g of disodium salt of ethylenediaminetetraacetate - compliance of the solution with the determined indicators of its acid (Trilon B) and 4.75-5.25 g of sodium sulfur - filtered through a pre-filter of acid anhydrous during 5-10 minutes. After the type of FTV with a delay threshold of 1 μm and a filter of the type of complete dissolution of the components, download "Rai!" with a delay threshold of 0.2 μm. 27.0-33.0 g of sodium para-aminosalicylate powder and

After filtering the solution in the absence of mecha- dissolve it for 10-15 minutes. The solution in night inclusions is poured into bottles with a tank capacity of 1000, 100, 200 or 400 ml with water for injections, closed with rubber stoppers. and sealed with aluminum caps, a sample is taken for analysis: the pH of the solution, then the bottles with the Z 95 solution of the agent are sterilized in from 6.8 to 8.8, the quantitative content of sodium in a steam sterilizer at a temperature of 105 "C, aminosalicylate (C/NbMMaoz ) in 1 ml of the prepared pressure of 0.025-0.035 MPa for 20 minutes, the sterile solution should be 0.03g, disodium linen bottle with the agent after viewing on mechanical salts of ethylenediaminetetraacetic acid (Trilon B) the inclusions are labeled and packed in packs. С1ТонНИТ4М2Ма20872Н209 ) in 1 ml of solution - 0.0005 g;

Sodium para-aminosalicylate (4-Amino-2-oxy- content of sodium sulfuric acid anhydrous (Ma2503) sodium benzoate) is the active substance of the product, added to 1 ml of solution - 0.005 g. When the solution is suitable, it is soluble in water and practically insoluble in spir- to the above indicators, it is filtered through those, white or white with a slightly yellowish or light- pre-filtration filter of the FTV type with a threshold ka pink tint powder. Its main delay is 1 μm and a filter of the "Raya" type with a delay threshold of 0.2 μm. specified intervals, in g/l:

The solution in the absence of mechanical inclusions of sodium para-aminosalicylate 30.0 is poured into bottles with a capacity of 100, 200 or disodium salt of ethylenediamine - 400 ml, closed with rubber stoppers and sealed with aluminum caps. Bottles made of disodium sulfuric acid anhydrous 5.0 of C 95 are sterilized in steam steroid-water for injections up to 1000 ml. lyzer at a temperature of 105 "C, a pressure of 0.025-0.035 The obtained solution was a colorless

MPa for 20 minutes. Sterile bottles with transparent liquid. The stability of the solution is checked by itself, after checking for mechanical inclusions under sterilization conditions, as well as during long-term storage, it is labeled and packed in packs. To obtain ganna and by the method of accelerated aging. Before and after the quality certificate, control of this sterilization is carried out, as well as in the process of accelerated sterilization in accordance with the AND on all indicators. After that, the color of the solution was controlled in order to obtain a quality certificate for the finished product and the quantitative content of the active substance of the product - it is transferred to the warehouse, after which it is filled with sodium para-aminosalicylate. It was also established by the consumer. it was found that the medicinal properties of the remedy remain

A useful model is explained by examples. remained stable after and during sterilization

Example 1 storage for two years.

A means for the treatment of tuberculosis is obtained Example C with a minimum content of all its components in the Means was obtained according to the scheme, as in example 1, within the limits of the indicated intervals, in g/l: but the quantitative content of the components was maximal - sodium para-aminosalicylate 27.0 them within of the specified intervals, in g/l: disodium salt of ethylenediamine sodium para-aminosalicylate 33.0 tetraacetic acid 02 disodium salt ethylenediamine sodium sulfuric acid anhydrous 4.75 tetraacetic acid 0.8 water for injections up to 1000 ml. sodium sulfuric acid anhydrous 5.25

In a tank with 800 ml of water for injections, water for injections up to 1000 ml. cooled to a temperature of (205) "С, dissolved 0.2 The resulting solution was also a colorless, acidic transparent liquid of the disodium salt of ethylenediaminetetraacetic acid. The stability of the solution of perevolate (Trylon B) and 4.75 g of rhenium sodium sulphite under sterilization conditions , as well as with long-term anhydrous for 5-10 minutes. After complete storage and the method of accelerated aging. Before and dissolving the components, 27.0 g of sodium para-aminosalicylate powder was loaded after sterilization, as well as in the process of accelerated aging of sodium para-aminosalicylate and its aging was controlled coloration within 10-15 minutes. The solution in the tank was filled with water for injections up to 1000 ml, after which sodium para-aminosalicylate was added to the tank. the medicinal properties of the remedy also left

FTV with a delay threshold of 1 μm and a "Rai!" type filter. are stable after sterilization and during sterilization with a delay threshold of 0.2 μm. cut within two years, i.e. the selection of compo-

The solution, in the absence of mechanical inclusions and their quantitative content, is poured into bottles with a capacity of 100, 200 or 400 ml and fully fulfills the task set in the invention. corked with rubber stoppers and sealed with aluminum caps. Bottles with a solution of this agent were used in a complex drug. The agent was sterilized in a steam sterilizer bath in 30 patients with destructive tuberculosis at a temperature of 105 "C, a lung pressure of 0.025-0.035 MPa, which was diagnosed for the first time, and in 20 patients with within 20 minutes. Sterile bottles with the drug, relapse and exacerbation of the process with poly- and multi- after reviewing the mechanical inclusions of the label- resistance to rifampicin and isoniazid. were rolled and packed in bundles. To obtain a certificate, at the first intravenous administration of Z 95, quality control was carried out in accordance with the solution of the drug no more than 250 were administered drop by drop

AND on all indicators. After receiving the certificate In the future, in the absence of adverse effects of the quality of the finished products, the product was transferred to the volume of the product, brought up to 500 ml per day, 5-6 ingredients, after which it was delivered to the consumer. fusions per week for 1-2 months. It was proved

The solution of the obtained agent is an abyss, that the agent has antimycobacterial properties - a colored transparent liquid. At the same time, it was possible to obtain high reverine stability of the solution in sterilization conditions, as well as with its long-term concentration in the blood, in connection with which the chemotherapeutic preservation and the accelerated therapeutic effect increased. In addition, aging. Before and after sterilization, as well as during the administration of the agent in combination with more active anti-tuberculosis drugs, control was carried out with anti-tuberculosis drugs, such as the concentration of the solution and the quantitative content of the active repyrazinamide, ethambutol, ethionamide and others, up to the iron of the drug - sodium para- aminosalicylate. in which the sensitivity of mycobacterium tuberculosis is preserved

It was found that the medicinal properties of iron, enhances the effect of the corresponding drugs and the treatment, made by the claimed method, prevents the development of drug resistance. Conducted remained stable after sterilization, and when testing this product, no allergic reactions were found - its preservation for two years. noy or toxic action.

Example 2 Thus, the conducted studies show

The remedy was obtained according to the scheme, as in example 1, but whether the received means for the treatment of tuberculosis - the quantitative content of the components was average within the limits of the full extent of its therapeutic properties -

exactly within the limits of the selected components and their quantity and the required level of quality, i.e. leaving the specified ratio; infusion is transparent after sterilization and when stored in the medicinal form of this agent, it remains stable in the form of a solution for a long time (for two years).

Computer layout A. Krulevskyi Signature Circulation 23 approx.

Ministry of Education and Science of Ukraine

State Department of Intellectual Property, str. Urytskogo, 45, Kyiv, MSP, 03680, Ukraine

SE "Ukrainian Institute of Industrial Property", str. Glazunova, 1, Kyiv - 42, 01601