RU2036846C1 - Method of obtaining nontoxic solution free of microorganisms - Google Patents

Abstract

FIELD: method of obtaining nontoxic solution of at least one water-soluble solid substance. SUBSTANCE: method involves introducing solid substance or concentrated solution of this substance into reservoir with selectively permeable membrane, whose one side is in contact with solid substance or its solution and opposite side is in contact with water; providing penetration of water free of microorganisms into reservoir under the action of osmosis, with at least one water-soluble substance having low molar weight. It allows this water-soluble substance to penetrate through membrane into water. At least one water-soluble substance with high molar weight may be further introduced into reservoir, with value of molar weight of this substance preventing it from penetrating into water through membrane. At least one of water-soluble substances is selected in the group consisting of sugar, polymeric glucoses, polysaccharides, rice flour, aminoacids, potassium chloride and sodium chloride. Method may be used for obtaining solution practiced in oral rehydration therapy, medicine preparations, blood substitutes, dehydrated food product, potable water etc. EFFECT: wider operational capabilities and increased efficiency. 13 cl, 4 dwg

Description

 The invention relates to methods for water treatment, in particular, to a method for producing water free of microorganisms and enterotoxins secreted by the species Vibrio cholerae and Shigella. It can be especially useful in emergency situations arising during natural disasters and in other situations when it is difficult to obtain microbiologically safe water.

 One of the leading causes of disease and mortality among young children in developing countries is diarrhea. This is mainly due to poor water quality in these countries. For example, in 1985, it was found that 59% of the rural population in these countries could not use safe water. In emergency situations caused by natural disasters, epidemics, war, etc. the possibility of obtaining safe water becomes even more limited, since conventional methods of water purification (filtration and chemical treatment), as well as boiling, are difficult to fulfill.

 The main water borne microbial pathogens are: Salmonella typhi, Salmonella paratyphi A, B and C, Entamoeba histolytica, Giardia lambbia, Vibrio cholerae shigella, Campylobacter jejuni, Escherichia coli, Vibrio parahaemolyticus, Ore virus and hepatitis A. In addition, contaminated water can be a source of other infectious diseases during a natural disaster. One of the main goals of water treatment is to remove such pests from it. In addition, some of these organisms can form enterotoxins, which are released from organisms and themselves can cause disease in the absence of a microbe. Such organisms include the two most important water borne pathogens, Vibrio cholerae and Shigella, causing cholera and bacterial dysentery. The molecular weights of these enterotoxins are 90 kD and 82 kD, respectively. Therefore, an ideal water treatment system should also ensure the removal of these enterotoxins, as well as the microbes themselves.

 Prevention of clean water is the best way to deal with these diseases. Persons infected with one of these infectious diseases suffer from gastroenteritis, which is often accompanied by diarrhea. In very young, very old and poorly fed people, diarrhea leads to death due to severe dehydration and the removal of electrolyte from the body. However, this condition can be treated with "oral rehydration" using an aqueous solution of a mixture of sugars and inorganic salts (Rehydration therapy in diarrhoea, D. Mohalanobis, "Acute enteric infections in ehifdreni new prospects for treatment and prevention", Eds. Holma. T. Holmgrem. I. Merso M. Molily R. Elsevier, 1981, pp. 303-318). A typical formulation includes (g) 23.28 sucrose, 16.36 glucose, 0.28 fructose, 1.76 citric acid, 1.76 sodium chloride, 1.52 potassium chloride, 1.68 sodium bicarbonate per liter of solution. However, much simpler formulations, which may include only glucose or sucrose, sodium chloride, potassium chloride and sodium bicarbonate, also have an effective effect. The simplest rehydration formulations may contain only glucose and sodium chloride, although it is preferred that they also include potassium chloride. This simple but effective treatment has led to a significant reduction in infant mortality due to gastrointestinal infections. It should be noted that, unlike typhoid, cholera and some forms of dysentery, antibiotics are not necessary to treat most gastrointestinal infections, which are also usually absent in developing countries.

The most important components of a mixture intended for oral rehydration are sugar, sodium ions and potassium ions. A contentious issue is the optimal concentration of these components, and currently available formulations have the following concentrations:
a) in the case of glucose-based mixtures (Bank S and Farthing MIG Advances in oral rehydration, Drugs Supplement, 36, 1988, pp 55, 83) mmol / L: glucose 67-200 sodium ions 35-90 potassium ions 10-25
b) in the case of sucrose-based mixtures (de Loysa I, Lindsay Smith E. Diarrhoea management and oral rehydration therapy in rural homes in Zimbabwe, save the Children Fund, 1983, p. 37) mmol / L: sucrose 50-149 sodium ions 30-100
In the published literature, it was noted that the causative agents of viral meningitis, rotaviruses and socites of the species Cryptosporidium are not destroyed by chlorination, which is a common method of purifying water from suspicious sources.

 The aim of the invention is to increase the efficiency of the process for producing a non-toxic solution.

 The present invention provides a simple method for producing pure water free of pathogenic microorganisms and enterotoxins of the species V. cholerae and Shigella without the need for chemical disinfection or boiling. This method may vary to produce drinking water or water for cooking, for medical purposes, such as the manufacture and administration of drugs by injection or intravenous infusion, for blood substitutes or plasma substitutes, as well as for the preparation of compositions intended for oral rehydration. This method can be applied in developing countries, in particular during natural disasters. It can also be used in other countries by travel lovers, tourists and climbers to receive microbial-free drinking water from streams and rivers, and medical care teams that do not have a constant supply of safe water. An important advantage of this method is the low weight of the equipment necessary to obtain clean water.

 The present invention provides a method for producing a non-toxic solution of at least one water-soluble solid that does not contain microorganisms, according to which a solid or its concentrated solution is placed in a tank equipped with a selectively permeable membrane, one side of which is in contact with the specified solid or its solution and the other side comes into contact with water for a predetermined minimum period of time, resulting in water entering into the tank under the influence of osmosis, but it is not permitted penetration of microorganisms from the reservoir water.

 A selectively permeable membrane allows water and low molecular weight solutes to pass into and out of the reservoir. Therefore, being in contact with water, the membrane allows water to penetrate into the reservoir and dissolve the solid therein. With an increase in contact time, more water enters the tank under the influence of osmotic pressure, resulting in a dilution of the solid solution. If the molecular weight of a solid is lower than the molecular cut-off of the membrane material, this solid will diffuse from the reservoir, with both processes leading to a gradual dilution of the solution. Depending on the choice of solid substance, contact time and contact conditions, this method allows to obtain solutions of a certain concentration or, continuing this process until infinite dilution is achieved, water can be obtained that is almost free of the initial water-soluble solid, which can be used, for example, as drinking water. At the same time, the membrane prevents the penetration of microorganisms and enterotoxins formed by species such as V. cholerae and Shigella, as a result of which the resulting water will not contain microorganisms and these enterotoxins, provided that the water-soluble solid and the inner surface of the tank are sterile and not contaminated by microorganisms during work. Of course, in the case of some applications, such as obtaining drinking water for healthy people, absolute sterility is not required; in such situations, the water-soluble solid and the inner surface of the tank should be clean and free of harmful amounts of pathogenic microorganisms. In other applications associated with the preparation of solutions for intravenous infusion, absolute sterility is mandatory; in these cases, the water-soluble solid and the inner surface of the tank must be sterilized or sterilized after manufacture and stored in a sterile condition until use.

 The term "free of microorganisms" means that this product contains less than 1 viable cell or spores in 1 ml.

 The method of the present invention can be carried out using commercially available or specially made material for a selectively permeable membrane and a water-soluble solid (which can be sterilized if necessary). Typical membrane materials are characterized by a molecular cut-off in the range of 12-14 kilodaltons (KD), which excludes the penetration of multicellular parasites, protozoa, bacteria, fungi and viruses that can be in water outside the tube, as well as enterotoxins formed by species such as V. cholerae Shigella. Some enterotoxins, such as the thermostable enterotoxin Escherichia coli, have a lower molecular weight, but can also be delayed when using a membrane with a molecular cutoff of approximately 4 kD. Such membranes also trap endotoxins, as they have a molecular weight in excess of 1000 kilodaltons. Endotoxins (pyrogens of bacterial origin) are part of the walls of gram-negative bacteria, it is necessary that all solutions intended for intravenous infusion do not contain endotoxins. Provided that the inner surface of the semipermeable membrane and its contents are sterile and do not contain endotoxins, the present invention can be used to obtain solutions intended for intravenous administration.

There are a number of semi-permeable materials with various molecular cutoffs, which creates a wide selection. These materials include:
cellulose widely used to demonstrate the phenomenon of osmosis and in the purification of substances through dialysis;
cellophane;
benzoylated cellulose;
viscose cellulose;
collagen.

 Cellulose is the preferred material since it can be obtained in a very pure form, it is non-toxic, it is difficult to tear or burst when wet and can remain in water for long periods of time without compromising on quality.

 The preferred molecular cut-off is 12-14 kD, since it eliminates all microbes and important enterotoxins (i.e., enterotoxins Vibrio cholerae, Shigella, Campylobacter jejuni and thermally unstable enrotrotoxin Escherichia coli). In addition, this material is most widely used for dialysis and therefore is cheap and readily available.

 In some applications of this method, a solid is present only to ensure water penetration and must be completely removed before using water. In such a situation, the nature of the solid does not matter, but it is preferable that it has a low molecular weight and is non-toxic, at least in the final (minimum) concentration. It is perfectly clear that if it is necessary to completely remove a solid through diffusion, its molecular weight should be lower than the molecular cutoff of the membrane.

 In other applications, it is necessary that the solid is present in the final solution obtained in accordance with this method. A solid can be completely retained in the tank if its molecular weight is higher than the molecular cutoff of the membrane, as is the case with dextrins, dextrans, or certain water-soluble glucose polymers. In the case of solids that must remain in the final solution but have a molecular weight below the cut-off value of the membrane, it is necessary to strike a balance between the losses resulting from the ingress of this substance into the water outside the tank and the time necessary to ensure that sufficient water the goal of obtaining the required final concentration.

 To obtain water with a minimum concentration of solids, it is preferable to contact the membrane with running water. If it is necessary to achieve a certain final concentration, this can be done using running water, but preferably using a predetermined initial volume of water: in the latter case, the water can be in a static state or mix.

 The minimum time required to achieve the desired final concentration of dissolved substances can be determined using a simple trial and error method. This time is unlikely to be less than 1 minute, and convenience considerations indicate that periods exceeding 2 days are not likely to be of practical interest. The desired final concentration can usually be achieved over a period of time from 1 to 24 hours, preferably from 2 to 12 hours, for example, within 3, 4, 6, 8 or 10 hours

 If it is desirable to use several solids inside the tank, for example, for the manufacture of food products that are suspensions of solids, it is necessary that this mixture includes at least one soluble solid in order to create an osmotic pressure that will facilitate the flow of the desired amount of water.

 If there are two or more solids soluble in water in the tank, and it is desirable to obtain a solution with a certain concentration of each solid, then the initial amounts of all solids must be adjusted taking into account the osmotic effect and the rate of diffusion of each substance from the tank. A more detailed discussion of this process will be given in the examples below. In this case, it is preferable that the membrane is in contact with a predetermined initial volume of water, and the trial and error method can be used to determine the required minimum (and maximum) contact time.

 A simple way to achieve a final concentration of solute, the molecular weight of which is less than the molecular cutoff of the membrane, is to contact the membrane with a predetermined initial volume of water and continue contacting with or without stirring until a balance is reached between the concentrations inside and outside the tank. If there is a sufficient amount of solid in the tank to achieve the desired concentration in a predetermined initial volume of water, then a predetermined minimum contact time represents the time required to establish equilibrium. A similar method can be applied when the water-soluble solid is a mixture of dissolved substances, of which one or more substances have a molecular weight below the molecular cut-off of the membrane. In this case, contact with water continues until all dissolved substances reach equilibrium.

 When choosing a solid intended for use in the present invention, it is necessary to take into account the water-absorbing effect of various solutes. Since the osmotic pressure is partially determined by the number of particles in the solution, a low molecular weight dissolved substance will result in a higher osmotic pressure compared to a high molecular weight dissolved substance. However, water diffusion inward occurs over a limited period of time, so that the tendency of a low molecular weight substance to diffuse rapidly from the reservoir will reduce its water-absorbing effect. For example, sodium chloride ions quickly diffuse through cellulose membranes and have little effect on the volume of water absorbed by a mixture of sodium chloride and glucose, sucrose or fructose. Sugars are actually absorbed by much larger amounts of water, as can be seen from the examples below.

 Other water-soluble solids that can be placed in this reservoir are dry blood products, blood or plasma substitutes, components of more complex oral rehydration formulations, such as other electrolytes or amino acids, and nutrients such as dry nutrients, milk powder and partially dehydrated food containing water soluble solids. Such solids may be added to the nutrient component if they are not present in the component itself. Other preferred solids for absorbing water and food are soluble rice flour and rice flour. Nutrient suspensions prepared according to the method of the present invention can be heated during or after the absorption of water by a water-soluble solid.

 According to the method of the present invention, sugar-based oral rehydration formulations such as glucose, sucrose, or fructose and at least one electrolyte such as sodium chloride can be prepared. Preferably, they are obtained by contacting the membrane with a predetermined initial volume of water for a period of time sufficient to achieve equilibrium of the electrolyte (electrolytes) inside and outside the tank and diffuse the sugar outward, whereby the desired sugar and electrolyte concentrations are achieved inside the tank.

 Other dissolved substances, provided that their molecular weight is less than the molecular cut-off of the membrane material, can be introduced into the tank by diffusion from external (dirty) water or during the initial absorption of water by a water-soluble solid, or in a subsequent separation step.

 A certain aspect of the present invention provides a method that includes introducing a mixture of chemicals of known composition into a tube made of a semipermeable material (that is, a material that allows molecules to pass below a certain molecular weight "molecular cut-off"), sealing the tube at both ends (by tying knots or in another way) and the subsequent immersion of this tube in water. Water outside the tube passes through a semi-permeable membrane, forming a concentrated solution of the mixture inside the tube. Since this concentrated solution has a higher osmotic pressure compared to water outside the tube, an increasing amount of water diffuses into the tube, as a result of which the total volume of the solution inside the tube gradually increases. At the same time, a certain amount of the mixture gradually leaves the tube, since the membrane is permeable to the components of this mixture. If the molecular cut-off of a semipermeable material is 12-14 kD, then the simplest bacteria, fungi and viruses that can be in the water outside the tube cannot get into the solution contained in the tube. Moreover, most enterotoxins formed by water-borne pathogens are also too large to pass through the membrane into the solution. Therefore, a solution is formed inside the tube that does not contain microbes and the most important enterotoxins, provided that the inner surface of the tube and the water-soluble solid did not initially contain such microbes and enterotoxins.

 In addition to producing microbial-free water, the present invention also provides a solution suitable for oral rehydration if the duration of immersion of the tube in water is taken into account. The required immersion time depends on the material or design of the tube, as well as the quantity and composition of the feed mixture inside the tube (see the example below).

 The reservoir and membrane used in the present invention may be of any convenient shape. To produce large amounts of drinking water, the reservoir may be provided with a membrane with a large surface area, the shape of which allows contact with running or standing water, such as a river or reservoir, while the reservoir may provide a device for adding water-soluble solids and / or removing purified water. To obtain less pure water, for example, in the manufacture of individual doses of an oral hydration composition, the reservoir may be a tube-shaped membrane having at least one closed end. Such a reservoir (or at least its closed end) is immersed in a bucket or jug of water in order to obtain a composition in an amount of from several milliliters to 1 liter, for example, from 50 ml to 500 ml, preferably from 100 ml to 200 ml of an oral composition rehydration after a predetermined minimum diving period. In accordance with other variants of implementation of the present invention, this tank can be enclosed in an external tank, integral with it and designed for dirty water to be cleaned, and / or equipped with a device for removing purified water, such as a drain hole, a drinking pipe, a partition , an injection needle with a syringe or an intravenous infusion device connected to it.

 In accordance with other embodiments of the invention, the reservoir may be a reusable device and include several waterproof sealed compartments containing specific amounts of a water-soluble solid. Each time you reuse this tank, one such compartment opens to remove the solids in it. These compartments may have a conventional opening device, such as screw or snap-on covers, tear strips or other weak areas, or they may be opened by cutting or tearing depending on the material, manufacturing method and intended use. Compartments containing certain amounts of drugs, additional soluble substances, insoluble materials or liquids may be provided in the reservoir, while the contents of these compartments may enter the purified water immediately after separation of the membrane from the dirty source water. With this, accurate dosing can be achieved and expensive or rare materials cannot penetrate as a result of diffusion into the source water. For some applications, reservoirs containing a membrane and at least one water-soluble solid can be made in the form of a continuous roll with ruptureable perforations or other means for separating individual reservoirs from a roll with multiple reservoirs. The tanks can also be equipped with a device that protects the membrane and / or other fragile, thin or sterile components during transportation and storage. The tank may also be equipped with a suspending device. A device may also be provided to prevent access to a clean solution until dirty water is removed.

 When designing reservoirs equipped with a membrane (or consisting of a membrane) and intended for use in the present invention, it is necessary to provide a sufficient internal volume to ensure that the desired final volume of purified water is maintained, and this is preferably achieved without any back pressure. Such back pressure will distract from the osmotic pressure created by solutes, and in the most serious cases it can cause membrane destruction, which will lead to loss or contamination of purified water. A device for removing purified water from the tank should be designed to prevent pollution from the external environment, and in particular, dirty water that came into contact with the membrane (and the tank).

 The tank may also be equipped with a device indicating that a predetermined minimum contact time has elapsed, and / or a device showing that the inner surface of the tank is no longer sterile. This can be achieved, for example, by indicating contamination with a high molecular weight blue dextrate placed on the outside of the membrane, as a result of which the contaminated water is colored. Thus, any contamination of the "sterile" solute (for example, if the membrane was broken) will be shown in blue color of the solution. To indicate the concentration of salt and sugar, you can use indicator paper, similar to that used in the analysis of urine. Such paper strips may have several sections with different indicators intended for color indication (for example, pH, glucose, sodium chloride and potassium chloride. This type of paper strip is manufactured by BDH Limited (Poole, United Kingdom).

 In accordance with one aspect of the present invention, the preferred shape of the material is a long narrow tube, as this allows an increase in the ratio of surface area to volume, providing faster absorption of water. A number of oral rehydration formulations are proposed, the simplest of which is a glucose electrolyte solution recommended by the World Health Organization. This composition includes (mmol / L) sodium 90, potassium 20, chloride 80, bicarbonate 30 and glucose 11. A more complex composition contains (mmol / l) sodium 50, potassium 20, chloride 50, bicarbonate 20, glucose 91, fructose 2, sucrose 94, citrate 9.

 Flavoring agents as well as high molecular weight soluble proteins and / or polysaccharides and any other components necessary in the final solution can be added to these formulations.

 The water treatment system is preferably a long semipermeable tube containing a mixture for oral rehydration or another mixture of chemical compounds. This tube is sealed at one end with a clamp or assembly, or by welding or gluing. The other end is preferably sealed with a clamp so that after the tube is immersed in water overnight (or for another period of time) it can be opened and access to the clean water inside. After immersing the tube in water overnight (or for another necessary period of time), the user removes the tube from the water, draws water from the outer surface of the tube, removes the clip, and either pours the contents of the tube into a drinking container or drinks directly from the tube using the open end of the tube as an outlet. The tube is then preferably thrown away, and since it is biodegradable, it can be used to make compost and improve soil structure. Alternatively, the water treatment system may be supplied as a kit, including: 1) a long, semi-permeable tube, sealed at one end and equipped with a funnel at the other end; 2) a clamp for temporary sealing of the open end when the tube is immersed in water; 3) a mixture for oral rehydration or another mixture of chemical compounds. The user pours the mixture into the tube through the funnel-shaped end, seals the funnel-shaped end with a clamp, and immerses the tube in water. After the appropriate immersion period, the user removes the tube from the water, wipes the water from the outside of the tube, removes the clamp and pours the solution into the drinking tank or drinks the solution directly from the tube, using the funnel-shaped end as an outlet. After this, the tube is preferably thrown away, since re-filling with a fresh mixture is technically difficult when the tube is wet, and with insufficient care, contamination of the inner surface of the tube may occur.

 If this invention is supposed to be used in developing countries only as a source of clean water that does not contain microbes, and not to obtain a composition for rehydration therapy, the range of compositions of the mixtures enclosed in the tube is significantly expanded. For this purpose, for example, it is possible to significantly increase the total sugar content (since the final concentration is not as critical as in the case of the composition for oral rehydration), resulting in a correspondingly increased diffusion rate, and the duration of the tube immersion is reduced. In addition, high molecular weight water-soluble proteins and / or polysaccharides may be included in this mixture, since they also increase the rate of water absorption. In addition, flavors are of great importance, allowing to improve the taste of drinking water.

 The present invention further provides reservoirs for the implementation of the above method, as well as their use for the production of purified water and medicines, and methods for treating a person or animal using solutions obtained in accordance with the method of this invention. Such solutions, reservoirs and methods form another aspect of the present invention.

Certain areas in which the present invention may be applied include:
A method of obtaining a solution of non-toxic water-soluble solids, which serve to create an osmotic pressure that does not contain microorganisms and enterotoxins formed by Vibrio cholerae species, characterized in that it involves immersing a mixture of these compounds in water in a sealed drinking tank equipped with a membrane, which is selectively permeable, allowing water to enter the reservoir under the influence of osmosis, but retaining microorganisms and molecules whose molecular weight exceeds 70 k D, until a sufficient amount of water enters the tank to dissolve the salts and dilute them to a concentration that makes the resulting solution suitable for drinking;
a similar method, characterized in that the tank is a tube sealed at both ends, and one end of this tube can be opened for use as a drain or for drinking;
a similar method, characterized in that the membrane prevents the passage of molecules with a molecular mass above 12 kD;
a similar method, characterized in that the membrane is made from cellulose or from its derivative or regenerated form;
a similar method, characterized in that the non-toxic water-soluble salts form a mixture, the composition of which allows you to get a solution suitable for oral rehydration therapy;
a kit intended for use in the implementation of the method described here, which includes: 1) a mixture of solid chemical compounds for rehydration therapy; 2) a drinking container equipped with a membrane described herein; 3) a device for temporary sealing of the specified capacity when immersed in water;
a similar set, characterized in that the drinking container comprises a tube tightly closed at one end and provided with a clip at the other end for temporary sealing;
a similar kit, characterized in that a mixture of chemical compounds is placed in a drinking container;
a similar kit, characterized in that it further includes a funnel connected to the specified capacity, which forms a drain hole for safe drinking from the tank and a device for filling this tank with salts;
a similar kit, characterized in that the membrane prevents the penetration of molecules with a molecular mass exceeding 12 kD;
a similar kit, characterized in that the membrane is made of cellulose or its derivative or regenerated form;
the use of osmosis to produce water in order to dissolve a mixture of water-soluble chemical compounds, resulting in a solution for drinking or for rehydration therapy, in combination with simultaneous dialysis to remove microorganisms or harmful macromolecular substances from the solution, and the same is used for osmosis and dialysis membrane.

 In FIG. 1 is a front view of a partial cut-out tank for use in accordance with the present invention; in FIG. 2 is a side view of the device of FIG. 1; in FIG. 3 is a front view of an alternative reservoir for use in accordance with the present invention; in FIG. 4 is a graph showing the results shown in example 2.

 In FIG. 1 shows a tank 1, including a suspension device 2, a filling hole 3 with a stopper, and a blocked protrusion 4, which serves to remove purified water. Inside the tank there are two compartments, respectively, for dirty water 5 and for purified water 6, which are separated from each other by a separator 7, which is a selectively permeable membrane forming a waterproof seal with the walls of the tank. In the compartment 6 is introduced a certain amount of water-soluble solid substance 8, which is in contact with the separator 7.

 In the process of use, dirty water is poured into the compartment 5 through the filling hole to a predetermined level, and the tank is suspended on an appropriate hook for a period of time during which the compartment 6 is filled with clean water. The remaining dirty water can be drained through the filling hole 3 until the purified water is removed through the blocked protrusion 4.

 Alternative filling devices and devices for removing purified water, such as taps or nozzles, may be provided. It is not necessary that the separator between the two compartments is completely made of partially permeable membrane material, it is sufficient if the part of the separator 7 in contact with the solid material 8 is made of such material. The location of the separator 7 inside the tank does not matter, while alternatives such as horizontal or diagonal separator.

 An alternative reservoir for use in accordance with the present invention is the reservoir of FIG. 3, but instead of a single amount of solid 8, as shown in FIG. 1, 2, it contains several sachets 10 consisting of a solid or a concentrated solution of a solid.

 The tank depicted in FIG. 3, is used as follows. One of the sachets 10 is torn and the solid is brought into contact with the membrane in the separator 7, after which the compartment 6 is filled with dirty water, and the purified water is removed as described above. After draining the remaining dirty water and removing purified water, this tank can be reused by tearing the second sachet 10 and pouring a new volume of dirty water into the tank. Additional sachets containing solid or liquid components, such as drugs that break, may be provided, and their contents, in the form of solid or liquid components, are released into purified water. The purified water compartment can be divided into several sealed compartments, each of which contains a portion or several portions of a water-soluble solid and each of which has a semi-permeable membrane and a device for removing water.

 Different sachets can be encoded with their own code, for example, they can be painted in different colors and contain certain substances that are intended to be added to the solution.

 In accordance with the present invention, many other tank options are provided.

 This invention is further illustrated by the following examples, which in no way limit the scope of the claims.

 PRI me R 1. The following experiments were performed to determine the conditions for obtaining the composition for oral rehydration in accordance with the method of the present invention. Unless specifically indicated, it is assumed that glucose determinations were performed using Technicom (trademark / RA1000 / Technicon, Basingstoke, United Kingdom), and the concentration of sodium and potassium ions was determined using an IL 343 flame photometer (Instrumentation Laboratory LMT ", Vorington, United Kingdom). In many cases, the solutions intended for analysis were initially diluted to the required degree.

EXPERIMENT 1. 40 gram portions of the following composition: 20 parts glucose, 5.25 parts sodium chloride, 1.5 parts potassium chloride (all parts by weight) were placed in sections of a cellulose dialysis tube with a diameter of 38 mm or 29 mm, which was then sealed at both ends. Tube section with a diameter of 29 mm was immersed in 1 liter of still water at a temperature of 17 or 30 ^C. The results are shown in Table. 1-6.

 The use of this composition in running water does not provide the necessary balance of glucose (sodium ions) of potassium ions for oral rehydration therapy. As a result of immersion for 8 hours or more, this composition allows you to get a sterile glucose solution intended for drinking (table. 1-4).

 Using this composition in a constant external volume of water makes it possible to obtain a solution with the correct balance of glucose and salts for oral rehydration (Tables 5 and 6).

Increasing the temperature from 17 to 30 ° ^C leads to increased water absorption speed and the rate of attaining equilibrium between glucose and salts (Table. 5 and 6).

 The diameter of the tube apparently affects the rate of water absorption and the composition of the resulting solution. A tube with a smaller diameter is characterized by a higher rate of water absorption and loss of glucose and salts compared to a tube with a larger diameter (Tables 1 and 2). This is probably due to the large ratio of surface area to volume.

 EXPERIMENT 2. The purpose of this experiment is to study the effect of changes in the external volume of water on the absorption of water and the composition of the resulting solution.

10-gram portion of the mixture of glucose, sodium chloride and potassium chloride, similar to that used in Experiment 1 was placed in a tube length of 22 cm and a diameter of 29 mm, which was then immersed in 50-600 ml of water at a temperature of 30 ^C. The internal volume and concentrations were measured after 24 hours. The results are shown in table. 7.

 A change in the volume of water into which this composition is immersed affects the total volume of absorbed water and the composition of the resulting solution. From the obtained results it is seen that it is possible to obtain a solution for oral rehydration having the appropriate composition by immersing 100 g of the above composition in 400-500 ml of water.

 EXPERIMENT 3. The following experiment was carried out to study the effect of changes in the composition of the mixture on the composition of the resulting solution.

Used a new composition containing 5.22 parts of sodium chloride, 1.125 parts of potassium chloride and various amounts of glucose, comprising from 16 to 32 parts by weight. Portions of this mixture were placed in a tube with a diameter of 29 mm and incubated in 1 liter of water at 30 ^C. The internal volume and concentrations were measured after 24 hours, the results are shown in Table. 8.

This experiment was repeated using a mixture consisting of 36 g glucose, 10.44 g sodium chloride and 2.25 g of potassium chloride, which was placed in a tube with a diameter of 29 mm and immersed in 2 liters water at ³⁰ ° C for 18 and 24 hours The results are shown in table. nine.

 If a mixture containing from 16 g to 20 g of glucose, 5.22 g of sodium chloride and 1.125 g of potassium chloride is immersed in 1 l of water; solutions suitable for oral rehydration therapy are formed (Table 8).

 Large volumes of solutions suitable for oral rehydration therapy can be obtained by using large amounts of the mixture provided that the volume of water in which it is immersed increases (Table 9).

EXPERIMENT 4. Repeat experiment 3 using a mixture containing 18 g of glucose, 5.22 g of sodium chloride and 1.125 g of potassium chloride, which was placed in a tube with a diameter of 29 mm and kept in 1 l of water at 4 ° ^C. The glucose concentration was determined using a diagnostic kit, manufactured by "Sigma lmt", (Poole, United Kingdom). Sodium ion concentrations were determined using a sodium sensitive electrode (Fatman International lmt, Madestone, United Kingdom). The results are shown in table. 10.

The results show that solutions suitable for oral rehydration therapy can be obtained within 24 h even when the water temperature of 4 ° ^C.

 EXPERIMENT 5. Although solutions containing glucose, sodium chloride and potassium chloride are recommended for use in oral rehydration therapy, it has been shown that simpler formulations containing only sucrose and sodium chloride can have an effective effect. .

 Portions containing 50 g of sucrose and 120 g of sodium chloride were placed in a 38 mm tube section and immersed in running water at room temperature for various periods of time, while the internal volume and concentration were measured. Sucrose concentrations were determined using the phenol and sulfuric acid method proposed by Lubois et al. (Analytical Chemistry, 1966, 39, p. 350-356). Concentrations of sodium ions were determined using a sodium sensitive electrode (Fatman International LMT). The results are shown in table. eleven.

 The rate of absorption of water and the composition of the solution depend on the diameter of the tube used. Using an 83 mm tube, large quantities (650 ml) of a solution suitable for oral rehydration were obtained after 16 hours (Table 11). If the immersion period is longer than 16 hours, this method is also useful for obtaining large quantities of sterile solutions containing sucrose, for drinking, and other purposes. The absorption of water by sucrose is significantly more effective than with glucose.

EXPERIMENT 6. The purpose of this experiment was to study the process of immersion of mixtures containing sucrose in constant volumes of water. Portions of the following mixtures were placed inside sections of 32mm tubing and immersed in water at ³⁰ ° C for various periods of time, the measured internal volume and concentration. The results are shown in table. 12.

 A. 20 g sugar, 5.22 g NaCl, 1.13 g KCl.

 B. 20 g sucrose, 7.83 g NaCl, 1.69 g KCl.

 C. 20 g of sucrose, 10.44 g of NaCl, 2.25 g of KCl.

 D. 30 g of sucrose, 5.22 g of NaCl, 1.13 g of KCl.

 Solutions having a composition suitable for oral rehydration can only be obtained after 8 hours immersion in 1, 1.5 L or 2 L of water (Table 12). The absorption of water by sucrose is much more effective than the absorption provided by glucose.

 EXPERIMENT 7. The purpose of the experiments described below was to study the ability of a membrane to exclude the penetration of particles present in an external solution.

A 38 mm tube containing 40 g of a mixture of glucose, sodium chloride and potassium chloride was immersed in still water containing Pseudomonas aeruginosa and blue dextran (0.2 g / l, molecular weight 2 x 10 ⁶ D).

The final optical density of the liquid outside the tube: A ₆₂₀ = 0.241.

The final optical density of the liquid inside the tube: A ₆₂₀ = 0.

The content of pseudomonads in the liquid outside the tube is 45 x 10 ⁶ organisms in ml.

 After immersion for 8 1/4 h, no pseudomonads were found inside the tube. The analysis method used allowed us to detect bacteria in an amount of 1 organism per ml.

The membrane successfully excluded the penetration of blue dextran (molecular weight 2 x 10 ⁶ ) and Pseudomonas aeruginosa. Since pathogens are larger than blue dextran molecules, these results suggest that this membrane will not miss harmful bacteria and viruses.

 EXPERIMENT 8. The purpose of this experiment was to study the behavior of the individual components of mixtures intended for oral rehydration when they are in a semipermeable membrane.

100 millimolar portions containing glucose (18 g), sodium chloride (5.8 g) or calcium chloride (7.4 g) were placed in sections of 29mm tubing and each section of tubing was immersed in 1 liter of water at ³⁰ ° C In this case, the internal volume was measured, as well as the internal and external concentrations of glucose, sodium chloride and potassium chloride. The results are shown in table. thirteen.

 These results show that the greatest absorption of water occurs during the first 8 hours of immersion and that glucose has the largest water absorption potential per mole of test compounds.

 Sodium chloride and potassium chloride quickly balance (within 8 hours) with a solution located outside the membrane, while glucose requires much more time to reach equilibrium.

 By varying the volume of the external solution and the amount of substance initially present inside the membrane, this system can be used to produce sterile glucose solutions and saline solutions having almost any desired composition. Due to the fact that most of the water is absorbed by sugar and a quick equilibrium of salts is achieved, this system has two very important practical applications. Firstly, this means that there is little chance (when potassium salts are used in the oral or injection therapy of this invention) that the salt remains in a dangerous concentration until at least half of the required water has penetrated the container. Secondly, this means that sugar, dextran and even “pure” water can be immersed in the appropriate saline solution, and these salts will penetrate into the container under the influence of diffusion. This allows you to easily enter the components if you want to obtain a simple composition.

 EXPERIMENT 9. The ability of other water-soluble compounds to absorb water was investigated as follows.

Servings Containing
(a) 1 g of dextran (clinical grade, molecular weight 60-90000),
(b) 10 g of dextrin (type 3),
(c) 10 g of dextrin and 5 g of sucrose,
(d) 5 g of sucrose,
placed in sections of a 29 mm tube and this tube was immersed in running water (room temperature). The internal volume was measured. The results are shown in table. fourteen.

 Based on the mass of dextran, it is most effective in absorbing water.

 EXPERIMENT 10. Dextran solutions containing saline are commonly used as plasma substitutes administered by intravenous infusion. The purpose of this experiment was to determine the possibility of using dextran to absorb water through a semipermeable membrane and thus obtain solutions that do not contain microbes.

Portions containing (a) 2 g of dextran (clinical grade, molecular weight is approximately 70,000) or (b) 2 g of dextran and 9 g of sodium chloride were placed inside sections of a 29 mm tube, and sections of this tube were immersed in 1 L of water at a temperature 20 ^° C. Another portion containing 2 g of dextran was placed in a 29 mm tube and immersed in 1 L of saline (9 g per liter): 40 ml aliquot of a 5% dextran solution (prepared as described in experiment 9 above) placed in a 29 mm tube, which was then immersed in saline (9 g per liter).

The volume of the obtained solutions and the content of sodium ions in them were determined (using an electrode sensitive to Na ⁺ ions) through various periods of immersion. The results are shown in table. fifteen.

 Dextran has an effective effect on the absorption of water through the membrane, although unlike other solutes tested, the absorption of water by dextran takes a long time until it reaches saturation. Another difference from sucrose, glucose and sodium chloride is that dextrin itself cannot penetrate the semipermeable membrane (its molecular weight is 70,000), and therefore it is completely stored inside the tube. This was confirmed by taking 10 ml of the sample from the tube and evaporating it to dryness. The mass of the obtained dextran in a dry state showed that all of its amount was stored in the tank. Immersion of a mixture of 2 g of dextran and 9 g of sodium chloride in 1 l of water for 24 hours led to the formation of a solution with an ideal composition for intravenous infusion, in particular, it contained 5% dextran and 0.9% sodium chloride. Such a solution could also be obtained by immersing a 5% dextran solution (prepared as described above) in a 0.9% sodium chloride solution for 4 hours. This approach can also be used to obtain dextran-based solutions supplemented with other dissolved substances, including various medicines.

PRI me R 2. A mixture suitable for oral rehydration, was obtained using the following chemicals (per 100 g of mixture):
3.18 g of sodium chloride,
2.75 g of potassium chloride,
3.04 g sodium bicarbonate,
3.18 g of citric acid,
29.55 g glucose
58.31 g of sucrose.

 11 g of this mixture was poured into a dialysis cellulose tube 30 cm long and 4.2 cm in diameter, the molecular cut-off of which was 12-14 kDa (Medisel LMT, Aislington, London). Then the tube was sealed by tying a knot at each end (after thoroughly moistening both ends) and immersed in a large tank through which a constant stream of tap water flowed. After various periods of time, this tube was removed from the water and the volume of solution inside the tube was measured. This solution was then again poured into a tube, which was again sealed and immersed in running water.

 After 8 hours of immersion in running water, the solution in the tube was analyzed using a pocket refractometer to determine its total sugar content (Bellingham and Stanley Lmt. Tunbridge, United Kingdom). Then, we plotted the dependence of the volume of water in the tube on time (Fig. 4, curve "a").

 Then this experiment was repeated, increasing the amount of the mixture and, if necessary, extending the dialysis tube of the same type. Curve b shown in FIG. 4 shows the absorption of water when the initial amount of the mixture was 22 g, curve "c" was obtained when the initial amount of the mixture was 33 g, and curve "d" was obtained when the initial amount of the mixture was 55 g.

 In the table. 16 shows data on the effect of the amount of the mixture used on the final volume of the resulting solution and the final sugar concentration. From FIG. Figure 4 shows that for each quantity of the mixture used, the volume of water diffused into the tube first increases, and then equalizes, aiming at the maximum level.

 The dipping period was chosen to be 8 hours, as this is the average duration of sleep of an adult. Therefore, the tube can be immersed in water before bedtime, and after waking up, the solution inside the tube will have a concentration suitable for oral rehydration therapy.

 From the table below 16 shows that the volume of "purified" water (that is, seeped into the dialysis tube) increases with an increase in the initial amount of the mixture used. The final sugar concentration in each case ranged from 3 to 4.75% after an 8-hour immersion.

Claims (13)

 1. A METHOD FOR PRODUCING A NON-TOXIC SOLUTION FREE OF MICRO-ORGANISMS of at least one water-soluble solid, including introducing a solid or its concentrated solution into a reservoir equipped with a selectively permeable membrane, one side of which is in contact with the solid or its solution, and the opposite side is in contact with water and the penetration of water free of microorganisms into the tank under the action of osmosis, characterized in that, in order to increase the efficiency of the process, of at least one water soluble solid has a low molecular weight, allowing it to penetrate through the membrane into the water.  2. The method according to claim 1, characterized in that they use a membrane whose pore sizes exclude the entry of microorganisms and enterotoxins of the species V. cholerae and Shigella into the reservoir.  3. The method according to claims 1 and 2, characterized in that at least one water-soluble solid substance, which has a high molecular weight, preventing its penetration through the membrane into the water, is additionally placed in the tank.  4. The method according to PP.1 to 3, characterized in that at least one of the water-soluble solids selected from the group of sugar, water-soluble glucose polymers, water-soluble polysaccharides, rice flour, amino acids, potassium chloride and sodium.  5. The method according to claim 4, characterized in that the water-soluble solid substance of the sugar class is selected from the group of glucose, dextrose, fructose and sucrose.  6. The method according to PP.1 to 5, characterized in that the membrane is brought into contact with running water.  7. The method according to claim 6, characterized in that the contacting is carried out for a time sufficient to diffuse from the reservoir almost all low molecular weight substances that the membrane passes.  8. The method according to PP.1 to 5, characterized in that the membrane is brought into contact with a given amount of still or stirred water.  9. The method according to claim 8, characterized in that the contacting is carried out for a time sufficient to achieve on both sides of the membrane an equilibrium concentration of at least one low molecular weight substance.  10. The method according to PP.1 to 9, characterized in that the water-soluble solids are the starting mixture to obtain a solution for oral rehydration therapy.  11. The method according to PP.1 to 9, characterized in that the water-soluble solids are drugs.  12. The method according to PP.1 to 9, characterized in that the water-soluble solids are blood products, blood or plasma substitutes.  13. The method according to PP.1 to 9, characterized in that the water-soluble solids are a dry or partially dehydrated food substance.

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