RU2794771C1 - METHOD FOR PRODUCING PHARMACEUTICAL SUBSTANCE XENON HYDRATE (Xe·6H2O) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to a method for obtaining a pharmaceutical substance xenon hydrate, obtained by holding distilled water for 15 days under xenon gas pressure from 0.4 to 10 MPa and at temperatures above 0°C to obtain a solid fraction, which is a clathrate compound consisting of water and xenon (Xe⋅6H₂O), which contains up to 200 volume units of xenon gas per 1 volume of water.

EFFECT: invention provides for the production of a xenon hydrate pharmaceutical substance for the production of a medicinal product.

1 cl, 1 ex, 1 tbl

Description

The invention relates to the field of pharmacy, medicine, veterinary science, physics, chemistry, specifically to a method for producing a pharmaceutical substance based on xenon hydrate.

Xenon is actively used in medicine, cosmetology and the food industry. There are a number of technical solutions that describe various ways of using xenon in the treatment and prevention of various diseases. Xenon is delivered to the human body both by inhalation and by ingestion using various substances containing xenon.

The method of xenon therapy is widely used, which is based on the inhalation of xenon, namely, the inhalation of a gas mixture of xenon and oxygen. But to carry out such therapy, trained specialists and special equipment are required, which makes it difficult to conduct xenon therapy at home and makes it impossible for the patient to treat xenon on his own.

Other methods of xenon therapy are known, based on the solubility of xenon in fats, and associated with the intake of pre-xenon-saturated carriers inside the body. The disadvantage of these methods is the low saturation of xenon carriers and the resulting need to consume an increased dose of fatty foods (butter, cream, etc.), which can negatively affect a person.

The above disadvantages are eliminated in patent No. RU 2706424 C1, which proposes a new method for introducing xenon into the human body during xenon therapy, in which xenon hydrate is used to introduce the amount of xenon necessary for the prevention and treatment of the disease into the body. However, it does not address the actual issue of obtaining a pharmaceutical substance.

The patent search does not provide information about the method of creating the pharmaceutical substance xenon hydrate. The literature describes several methods for obtaining xenon hydrate, but not as a pharmaceutical substance.

1. High-pressure boundary of hydrate formation in the tetrahydrofuran-water system / A. Yu. Manakov, Y. A. Dyadin, A. V. Kurnosov[et al.] // Mendeleev Communications. -2000. - Vol. 10. - No. 2. - P. 80-81

About 0.02 g of water and an inert filler (finely ground silicon carbide, quartz, glass) were placed in a working chamber with a volume of 0.05 ml. The chamber was connected by a capillary (internal diameter 0.8 mm) to a piston-cylinder vessel (maximum volume 6 ml), which was filled with gas at a pressure of up to 2 MPa, and then the cell was placed in a high-pressure chamber, where a pressure of 10 MPa or more was created using a mixture silicone oil with gasoline.

The disadvantage of this method is that in the finished product there will inevitably be a hit of the used fillers.

2. Calorimetric determinations of the compositions, enthalpies of dissociation, and heat capacities in the range 85 to 270 K for clathrate hydrates of xenon and krypton. Y.P. HANDA. J. Chem. Thermodyn 1986, 18. 891-902

To obtain the hydrate, xenon gas with a purity of 99.995% was used, approximately 30 g of powdered ice. The components were placed in a 500 cm ³ high pressure chamber connected to a manometer and containing six stainless steel bars (1.5 cm in diameter, 18 cm long). The required amount of hydrate-forming gas was pumped into the chamber, and the vessel was placed on a series of rollers to rotate along its longitudinal axis for 3 days at a temperature of (253.0 +/-0.5) K. Ice crystals were ground by falling bars, which accelerated the penetration of gas into the ice crystal structure . The reaction was usually complete within 24 hours as indicated by the pressure drop.

The disadvantage of this method is that in this production of xenon hydrate it will contain wear products of the rods and walls of the chamber.

3. Preparation of xenon clathrates in water and study of their properties by pulsed NMR / Rodin V.V., Arkhangelsky A.N., Isangalin F.Sh., Volkov V.Ya. // Problems of cryobiology and cryomedicine. - 1984. - No. 14. - P.8-11. – EDN SMQQAH.

This paper describes the closest analogue of the prior art, a method for obtaining xenon hydrate similar to that proposed in this application. But there are also significant differences. 0.1-0.2 ml of water was taken in a Pyrex ampoule and placed in a thermostat at a temperature of 274-278°K under a xenon gas pressure of 0.2-1.2 MPa until a homogeneous snow-like mass was formed. However, as the authors themselves point out, the obtained "samples were a mixture of clathrate ice and a significant amount of liquid water (70-80% of the molecules in the sample)". With this result, the saturation of the obtained samples cannot exceed 40 volume units of xenon gas per unit volume of water. The authors did not make direct measurements of saturation. Obviously, with such saturation, xenon hydrate cannot be used as a pharmaceutical substance.

The technical result achieved by using the proposed invention is the production of a pharmaceutical substance xenon hydrate for the production of a medicinal product.

The technical result is achieved by the fact that the pharmaceutical substance xenon hydrate is obtained by keeping distilled water under xenon gas pressure from 0.4 to 10 MPa and temperatures above 0 ° C for 15 days, until a solid fraction is obtained, which is a clathrate compound consisting of water and xenon (Xe⋅6H ₂ O), which contains up to 200 volume units of xenon gas per 1 volume of water.

The choice of such conditions is due to the following. In the work of Istomin, V.A. Gas hydrates in natural conditions / V.A. Istomin, V.S. Yakushev. - Moscow: Nedra Publishing House, 1992. - 235 p. - ISBN 5-247-02442-7, data on the stability limit of xenon hydrate on the P-T diagram are given. They can be presented in the form of Table 1

At a temperature above 0°C and a gas pressure above the values indicated in Table 1, the local formation of ice microcrystals, in the cavities of the crystal lattice of which xenon gas atoms are located - a clathrate compound, is energetically favorable, and the formed microcrystals will be stable. After a time of two or three days, the entire interface between water and xenon gas will be converted into a clathrate compound. Holding for 15 days under pressure allows xenon gas to penetrate into deeper layers and continue the growth of the clathrate compound.

The essence of the method is as follows:

The working chamber for the formation of the pharmaceutical substance xenon hydrate is made of materials acceptable for use in the food and medical industry, for example, stainless steel AISI 304 (grade 08X18H10). There are no moving parts in the working chamber to prevent the formation of wear products. The use of any catalysts to speed up the process is also excluded.

The process of formation of the pharmaceutical substance xenon hydrate proceeds even at room temperature under the conditions of using xenon gas pressure of 6-10 MPa. However, at such pressures, additional requirements arise for the strength and reliability of the working chamber, which requires special conditions when working with high pressures and makes it difficult to visually control the formation of a pharmaceutical substance.

When developing the technology for the production of a pharmaceutical substance - xenon hydrate, it was found that the most optimal were the temperature parameters of 3-5 ° C and pressure of 0.4-0.8 MPa or 6-10 ° C and pressure of 0.8-1.2 MPa . For these parameters, both viewing windows and a completely transparent working chamber can be used.

The proposed method is illustrated by an example implementation.

Example.

20 ml of distilled water is added to the working chamber with a volume of 500 ml. The cylinder with medical gas xenon of special purity is connected. The gas pressure in the chamber is set by a balloon reducer of 1.2 MPa. The equipped chamber is placed in a thermostat at a temperature of 6°C. Xenon with water begins to form a clathrate compound. The amount of xenon gas in the working chamber will decrease, which will be noticeable by a decrease in pressure. The choice of these volume parameters is due to the fact that the finished xenon hydrate will contain 20 ml of water and up to 4 liters of xenon gas. A decrease in pressure from 1.2 to 0.4 MPa in a volume of 500 ml exactly corresponds to a decrease in gaseous xenon by 4 liters. If the initial pressure in the working chamber was less, then when the pressure drops to 0.4 MPa, it must be raised again to the original level. The procedure stops after the complete disappearance of the liquid fraction of water and obtaining a solid fraction. Exposure up to 15 days allows you to get xenon hydrate with high saturation. Completion of the process of formation of the pharmaceutical substance is confirmed by a constant level of xenon gas pressure in the working chamber.

After completion of the process of formation of the pharmaceutical substance, the equipped chamber must be cooled to temperatures of -5-10°C. After releasing the pressure and opening the chamber, we extract the pharmaceutical substance, ready for use.

Claims (1)

A method for obtaining a pharmaceutical substance xenon hydrate obtained by keeping distilled water under xenon gas pressure from 0.4 to 10 MPa and at temperatures above 0 ° C for 15 days until a solid fraction is obtained, which is a clathrate compound consisting of water and xenon ( Xe⋅6H ₂ O), which contains up to 200 volume units of xenon gas per 1 volume of water.