Adsorbent for peroral administration

FIELD: medicine.

SUBSTANCE: claimed adsorbent contains spherical activated carbon having size diameter of 0.01-1 mm, specific surface determined in accordance to Langmuir equation of 1000 m2/g or more, ratio of diffraction intensities R of 1.4 or more (R is determined as R = (I15-I35)/(I24-I35) (1), wherein I15 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 15°C; I35 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 35°C; I24 is diffraction intensity at diffraction angle (2θ) of X-ray diffraction is 24°C), and pore volume having diameter of 7.5-15000 nm is less than 0.25 mg/ml. In another embodiment claimed adsorbent contains abovementioned spherical activated carbon with modified surface. Also disclosed are pharmaceutical composition and method for prevention or treatment of kidney or liver diseases containing said adsorbent.

EFFECT: new adsorbent for peroral administration.

20 cl, 5 ex, 2 tbl, 12 dwg

 

The technical field to which the invention relates.

The present invention relates to an adsorbent, intended for oral administration and containing spherical activated carbon, which has a specific porous structure, and the adsorbent, intended for oral administration and containing spherical activated carbon with a modified surface, obtained by oxidation and restoration of the spherical activated carbon, which has a similar specific porous structure.

The adsorbent intended for oral administration, the present invention has a selective adsorption capacity, i.e. has a high adsorption capacity in relation to harmful toxins and at the same time low adsorption ability with respect to useful components in the body, such as digestive enzymes. In addition, the adsorbent has a specific porous structure and thus has a much better selective adsorption capacity in comparison with a conventional adsorbent for oral administration. Thus, the adsorbent is intended for oral administration, the present invention is effective for the treatment of patients suffering from liver disease or kidney disease.

The level of technology

In the body is the ZMA, for example, in the blood of patients suffering from renal failure or insufficiency of the liver, accumulate or are harmful toxic substances, which leads to the development of impaired organ function, and, thus, there encephalopathy, in particular impairment of consciousness or uremia. Every year the number of such patients increases, and therefore, a serious problem is the development of a replacement body device and medicines, is able to delete, instead of these damaged organs, toxic substances from the body. Predominant is a method of removing toxic substances hemodialysis in the form of an artificial kidney. However, artificial kidney, which use the method of hemodialysis requires the use of a special device and, thus, from the point of view of security, for its operation requires experienced specialist. In addition, the patient must take the blood, which is a disadvantage, because patients have to endure the physical and mental hardships and to bear the financial costs. Thus, hemodialysis is not satisfactory.

Recently, as a means to overcome the above drawbacks of considerable interest acquired oral adsorbent, which can be administered orally and may treat the breach is of the kidneys and the liver. In particular, the adsorbent disclosed in the examined patent application of Japan (Kokoku) No. 62-11611 includes spherical particles of carbonaceous matter, containing the specific functional group (hereinafter it is called a spherical activated carbon surface modified); enjoys high levels of security and sustainable in the body; has a useful selective adsorption ability, i.e. excellent adsorption ability with respect to harmful substances in the intestine in the presence of bile acids and low adsorption ability with respect to useful substances in the intestine, such as digestive enzymes. For these reasons, oral adsorbent is widely used in clinical practice for the treatment of patients suffering from disorders of the liver and kidneys, as adsorbent, with minor side effects such as constipation. The above-mentioned adsorbent disclosed in the examined patent application of Japan (Kokoku) No. 62-11611, obtained by molding a spherical activated carbon of the resin, such as petroleum pitch as a carbon source, and then spend processing oxidant and processing of a reducing agent.

Description of the invention

The authors of the present invention conducted intensive studies in order to develop an adsorbent, p is rednaznachenie for oral administration, which possesses greater selective adsorption ability than selective adsorption capacity of the above oral adsorbent containing conventional porous spherical carbonaceous substance obtained by molding of resin spherical activated carbon and processing of activated carbon oxidant and reductant, and suddenly discovered that the spherical activated carbon obtained from a thermosetting resin as a carbon source, even without treatment with the oxidizing agent and reducing agent exhibits an excellent selective adsorption capacity, i.e. on the one hand, has excellent adsorption ability with respect to β-aminoadamantane acid, which is one of the substances in the body caused by uremia, on the other hand, has a low adsorption capacity compared to useful substances such as digestive enzymes, such as α-amylase, and the level of its selective adsorption abilities superior to those of the selective adsorption ability of the adsorbent disclosed in the examined patent application of Japan (Kokoku) No. 62-11611. Since the above-mentioned spherical activated carbon obtained from a thermosetting resin as a carbon source, has excellent hell is orcinol ability to β -aminoadamantane acid, it is believed that the above spherical activated carbon has excellent adsorption ability with respect to other toxic substances, molecular weight which is close to the molecular weight β-aminoadamantane acid, such as octopamine or α-aminobutyric acid, or dimethylamine, aspartic acid, or arginine, which is a toxic substance or its predecessor in renal disease, or other water-soluble substances with basic or amphoteric properties.

Believed that the usual spherical particles of carbonaceous matter, i.e. the spherical activated carbon with a modified surface, which are used in the adsorbent described in the previous examination of the patent application of Japan (Kokoku) No. 62-11611, begin to show their selective adsorption capacity, as described above, after they injected a functional group processing of the spherical activated carbon obtained from the resin oxidizing agent, and treatment with reducing agent. So very suddenly spherical activated carbon exhibits selective adsorption capacity prior to treatment with an oxidising agent and treatment with reducing agent, its adsorption capacity is itself superior to adsorpti is nnow the ability of a conventional adsorbent, intended for oral administration.

In addition, the authors of the present invention have found that a useful selective adsorption capacity, i.e. on the one hand, excellent adsorption ability with respect to β-aminoadamantane acid, which is one of the substances in the body caused by uremia, and on the other hand, the low adsorption capacity in relation to the useful substances such as digestive enzymes, such as α-amylase that improves in the spherical activated carbon with a modified surface obtained by the oxidation and recovery of the above spherical activated carbon, as compared with the adsorbent disclosed in the examined the patent application of Japan (Kokoku) No. 62-11611. Therefore, assume that the spherical activated carbon with a modified surface has a greater adsorption capacity also in relation to other toxic substances, molecular weight which is close to the molecular weight β-aminoadamantane acid, such as octopamine or α-aminobutyric acid, or dimethylamine, aspartic acid, or arginine, which is a toxic substance or its predecessor in renal disease, or other water-soluble substances with basic or amphoteric the properties.

The present invention is based on the above first established facts.

Thus, the present invention relates to an adsorbent for oral administration, characterized in that it contains a spherical activated carbon, while the diameter of its particles is from 0.01 to 1 mm, specific surface area, determined by the equation of the Langmuir adsorption, is 1000 m2/g or more, and the ratio of intensity of diffraction, the value of R, defined by equation (1):

R = (I15-I35)/(I24-I35)(1)

where I15indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 15°I35indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 35°and I24indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 24°is 1.4 or more.

The present invention relates also to the adsorbent for oral administration, characterized in that it contains a spherical activated carbon with a modified surface, the diameter of its particles is from 0.01 to 1 mm, specific surface area, determined by the equation of adsorption of L is gmur, is 1000 m2/g or more, the total number of acid groups is from 0.40 to 1.00 mEq/g, the total amount of basic groups is 0.40 to 1.10 mEq/g, and the ratio of intensity of diffraction, the value of R, defined by equation (1):

R = (I15-I35)/(I24-I35)(1)

where I15indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 15°I35indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 35°and I24indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 24°is 1.4 or more.

Figure 1 shows the x-ray spherical activated carbon with a modified surface, known from the prior art (curve A), the x-ray pasty substances based spherical activated carbon with a modified surface, known from the prior art (curve B), and x-ray spherical activated carbon with a modified surface that is used as the adsorbent for oral administration according to the present invention (curve C).

Figure 2 p is redstavlena micrograph, obtained using scanning electron microscope (magnification: X50)showing the surface structure of the spherical activated carbon surface modified according to the present invention.

Figure 3 presents a micrograph obtained by scanning electron microscope (magnification: h)showing the cross section of a cut structure of the spherical activated carbon surface modified according to the present invention.

4 shows a micrograph obtained by scanning electron microscope (magnification: X50)showing the surface structure of the spherical activated carbon with a modified surface, known from the prior art.

Figure 5 presents a micrograph obtained by scanning electron microscope (magnification: h)showing the cross section of a cut structure of the spherical activated carbon with a modified surface, known from the prior art.

Figure 6 shows a histogram showing the results of a study of the action of the adsorbent, intended for oral administration, according to the present invention for creatinine in serum.

Figure 7 shows the histogram showing the results of the research action is desorbent, intended for oral administration, according to the present invention in urea nitrogen in the blood.

On Fig shows a histogram showing the results of a study of the action of the adsorbent, intended for oral administration, according to the present invention on creatinine clearance.

Figure 9 shows a histogram showing the results of a study of the action of the adsorbent, intended for oral administration, according to the present invention on the number of extracted urine protein.

Figure 10 shows a histogram showing the results of a study of the action of the adsorbent, intended for oral administration according to the present invention, ICG (indocyanine green).

Figure 11 shows a histogram showing the results of a study of the action of the adsorbent, intended for oral administration according to the present invention, on the GOT (glutamic-oxaloacetic the transaminase).

On Fig shows a histogram showing the results of a study of the action of the adsorbent, intended for oral administration according to the present invention, GPT (glutamic-pyruvic the transaminase).

Best mode for carrying out the present invention

The spherical activated carbon or spherical activated carbon surface modified, CA is used as the adsorbent, intended for oral administration according to the present invention, as described above, has a ratio of intensity of diffraction (the value of R calculated according to equation (1), the value of which is equal to or greater than 1.4.

First will be explained the setting of the ratio of intensity of diffraction (the value of R).

When the spherical activated carbon surface modified, derived in the usual way, which is described in examples 1-3 of the previous examination of the patent application of Japan (Kokoku) No. 62-11611, examined by powder x-ray diffractometry, you get a chest x-ray showing the same trend as the curve As shown in figure 1. Curve And represents the x-ray spherical activated carbon surface modified, received, as listed below, in accordance with comparative example 1. As can be seen from curve a, when the angle of diffraction (2θ), is approximately equal to 20 to 30°, there is a diffraction peak corresponding to the 002 plane. The intensity decreases with decreasing x-ray diffraction in the range where the diffraction angle (2θ) exceeds 30°. On the other hand, in the range where the diffraction angle (2θ) less than 20°strong x-ray diffraction is observed even in the range where the diffraction angle (2θ) is less than 15°i.e. the range is not, where x-ray diffraction from the plane 002 is rarely observed. Further, when the spherical activated carbon surface modified, derived in the usual way, which is described in examples 1-3 of the previous examination of the patent application of Japan (Kokoku) No. 62-11611, examined by powder x-ray diffractometry after absorbing water, you get a chest x-ray showing the same trend as the curve is shown in figure 1. Curve represents the x-ray spherical activated carbon surface modified, received, as described below in example 1, after absorbing water. As can be seen from the curve, the x-ray intensity curve In significantly reduced in the range of small angles, compared with the curve A. This phenomenon can be interpreted in such a way that the x-ray intensity in the range of small angles is influenced by fine pores, and the absorption of water by then, the intensity of x-ray scattering is reduced.

On the other hand, as shown in the examples below, in the case of a spherical activated carbon or spherical activated carbon with a modified surface obtained by the method developed by the authors of the present invention, generally receive x-rays, which in the case when water is not absorbed, is it shows the same trend, that and a curve C shown in figure 1. Curve C represents the x-ray spherical activated carbon surface modified, received, as described below in example 1. Thus, the intensity of the scattering curve in the range of small angles, where the diffraction angle (2θ15° or less is obviously more powerful compared to the intensity of the scattering curve A. Each of curves a, b and C in figure 1 are normalized so that the intensity of diffraction at an angle of diffraction (2θ)of 24°was equal to 100.

Obviously, a porous substance, x-ray which shows the same trend as the curve As shown in figure 1, has a pore structure that is different from the structure of the pores of the porous substance, the x-ray which shows the same trend as the curve C, shown in figure 1. In addition, from a comparison of curve a and curve b it is obvious that the intensity of scattering observed in the range of small angles x-ray diffraction of a spherical activated carbon with a modified surface, is reflected from the porous structure, and a substance showing bóthe greater the intensity of the scattering, contains more then. When establishing the relationship between the scattering angle and the diameter of pores, the assumption is that the larger the scattering angle, the smaller the e, the diameter of pores. For analysis of the structure of then well-known is the method of determining the distribution of pore through adsorption. However, in many cases it is difficult to conduct a precise analysis of the structure of the pores due to differences in the size or shape of the pores, the amount of adsorbed compounds, the conditions of adsorption, etc. the Authors of the present invention accept that the intensity of scattering at approximately 15° has only a minor influence on the x-ray diffraction from the plane 002 affected by scattering from small pores that she is an index, indicating the presence of the ultrafine pores that are difficult to detect by the methods of adsorption, and that the presence of such pores is useful for adsorption of harmful substances - β-aminoadamantane acid. Thus, the authors of the present invention accept that the greater the intensity of the scattering at the angle of diffraction (2θ), is approximately equal to 15°, the more effective adsorption of harmful substances - β-aminoadamantane acid, for spherical activated carbon or spherical activated carbon surface modified.

In addition, as shown in the following examples, the authors present invention experimentally confirmed that the spherical activated carbon or spherical activated carbon with modifier the bath surface, chest x-ray which shows the same trend as the curve C, shown in figure 1, possesses greater selective adsorption capacity compared with conventional spherical activated carbon or the usual spherical activated carbon with a modified surface, the x-ray which shows the same trend as the curve As shown in figure 1.

Therefore, in the present description in order to identify the above relation, the spherical activated carbon or spherical activated carbon surface modified characterized by the ratio of intensity of diffraction, the values of R calculated by equation (1). In the above equation (1) I15indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 15°i.e. in the range where the difference between the intensity of the diffraction curve and the diffraction intensity curve increases With; I24indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 24°i.e. in the range where the difference between the intensity of the diffraction curve and the diffraction intensity curve decreases; and I35indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 35°and uses the I for the correction of measurement errors between the tested samples, caused by the background disturbance.

Thus, the ratio of intensity of diffraction, the value of R, which is calculated from equation (1)is

R = t/u

for curve a and

R = s/v

for curve C.

The authors of the present invention confirmed that the ratio of intensity of diffraction, the value of R, any of the known spherical activated carbons with surface modified intended for oral administration, is less than 1.4 and not found, as far as is known to the authors of the present invention, no known oral appointed by the well-known spherical activated carbon with a modified surface, the ratio of intensity of diffraction, the value of R, which is 1.4 or more. In addition, as shown in the examples below, the spherical activated carbon with a modified surface, the ratio of intensity of diffraction, the value of R, which is 1.4 or more, has better adsorption ability with respect to β-aminoadamantane acid compared with the spherical activated carbon with a modified surface, the ratio of intensity of diffraction, the value of R, which is less than 1.4, and thus, it is obvious that the spherical activated carbon surface modified, intense is vnesti diffraction, the value of R, which is 1.4 or more, useful as an adsorbent, intended for oral administration and has a better adsorption ability with respect to toxic substances.

The ratio of intensity of diffraction, the value of R, defined by equation (1) for the spherical activated carbon or spherical activated carbon with a modified surface that is used as the adsorbent for oral administration according to the present invention, is preferably 1.4 or more, more preferably 1.5 or more, or still more preferably 1.6 or more.

The authors of the present invention found that the spherical activated carbon or spherical activated carbon with a modified surface, the ratio of intensity of diffraction, the value of R, which is 1.4 or more, can be obtained by using a thermosetting resin as a carbon source, instead of the pitch used as a carbon source for conventional adsorbents intended for oral administration. Otherwise it can be obtained from the pitch as a carbon source, as for conventional adsorbents intended for oral administration, by creating a cross-linked structure during processing, which makes the infusible substance, and R is zrusenie network structure of hexagonal planes of carbon.

First of all, you will learn how to obtain using a thermosetting resin as a carbon source.

Substance with spherical particles based on thermosetting resins initially activated at a temperature in the range from 700 to 1000°With the current capable of interacting with carbon gas (such as steam or gaseous carbon dioxide), to obtain a spherical activated carbon used as the adsorbent, intended for oral administration according to the present invention. The term "spherical activated carbon used in the text of this description to denote a porous product obtained by thermal treatment of carbon-containing precursor, such as a thermosetting resin spherical particles, with subsequent activation of the particles of which, in accordance with the present invention have a spherical shape, and the specific surface area is 100 m2/g or more, preferably 1000 m2/g or more.

If the substance with spherical particles based on thermosetting resin is softened by heat treatment, and its particles lose their spherical shape or fused with each other in the process of heat treatment, before carrying out the above-mentioned activation softening can be prevented by the oxidation of p and a temperature in the range from 150 to 400° C in an atmosphere containing oxygen, which makes the infusible substance.

In addition, if in the process of pyrolysis or thermal processing of thermosetting resin, a large amount of gases, before treatment, which makes the infusible substance, the products of pyrolysis can be removed in advance by conducting appropriate pre-firing.

To further improve the selective adsorption ability of the spherical activated carbon according to the present invention, the obtained spherical activated carbon is then oxidized at a temperature in the range from 300 to 800°With, mainly at a temperature in the range from 320 to 600°C, in an atmosphere containing from 0.1 to 50% vol., preferably from 1 to 30% vol. most preferably from 3 to 20% vol. oxygen and then restore heat treatment at a temperature in the range from 800 to 1200°With, mainly at a temperature in the range from 800 to 1000°C, in an atmosphere of non-oxidizing gas and thereby obtain a spherical activated carbon surface modified, used as adsorbent, intended for oral administration according to the present invention. The term "spherical activated carbon surface modified" in the text of the present description means a porous product, polucen the th by oxidative and reductive treatment of the spherical activated carbon, as indicated above, while on the surface of the spherical activated carbon balanced form of acid and basic sites and thereby improve the adsorption capacity in relation to harmful substances in the intestine.

The diameter of the spherical particles of the product on the basis of thermosetting resin used as starting material, is preferably from about 0.02 to 1.5 mm

For thermosetting resin used as starting material, it is important that it could be formed product with spherical particles, which would not softened and not melted, or the form of particles which were not changed by heat treatment at a temperature of 500°or less. Can be used a thermosetting resin, which may be oxidizing melting, turning it into the infusible substance.

As source material, it is preferable thermosetting resin, which can give a high yield of carbonization. If the output of carbonation is low, the strength of the spherical activated carbon becomes low. In addition, the formation of undesirable pores and decreases the volume density of the spherical activated carbon and thereby reduces the specific surface area per unit volume. For this reason, increases the amount of compound that n is to be administered orally and, thus, there is a problem with the fact that oral administration is difficult. Therefore, it is preferable thermosetting resin, which gives a higher yield of carbonization. Output by heat treatment at a temperature of 800°C in an atmosphere of non-oxidizing gas is preferably 40% by weight. or more, more preferably 45 wt.%. or more.

A thermosetting resin used as starting material, may represent, for example, phenolic resin, such as phenolic Novolac resin, rezol phenol resin, Novolac alkylphenol resin or rezol alkylphenol resin or furan resin, urea resin, melamine resin, epoxy resin. As thermosetting resin may be used a copolymer of divinylbenzene and styrene, Acrylonitrile, acrylic acid or methacrylic acid.

In addition, as a thermosetting resin can be used ion-exchange resin. In the General case, the ion-exchange resin is a copolymer of divinylbenzene and styrene, Acrylonitrile, acrylic acid or methacrylic acid, that is a thermosetting resin, and basically has a structure in which the ion exchange groups are associated with the matrix copolymer, forming a three-dimensional frame. Ion exchange saloobin classify, in accordance with the types contained in the ion-exchange groups on a strongly acidic ion-exchange resin having sulfonic acid groups, weak acid ion exchange resin having carboxyl and sulfonic acid groups, on strong-base ion-exchange resin containing Quaternary ammonium salt, and weakly basic ion-exchange resin containing primary and tertiary amines. In addition, the present invention as a special ion-exchange resin includes a so-called hybrid ion-exchange resin containing both acidic and basic ion-exchange group. In the present invention as a starting material can be used all of the above ion-exchange resin, however, the phenolic resin is preferred.

The following describes the method of obtaining spherical activated carbon or spherical activated carbon with a modified surface that is used as the adsorbent for oral administration, of the pitch as a carbon source by creating a cross-linked structure during processing, which makes the infusible substance, and the destruction of the network structure of hexagonal planes of carbon.

First, as an additive to bake, such as petroleum pitch or wood peck, enter bicyclic or tricyclic aromatic with the unity or their mixture, having a boiling point of 200°s or greater. The resulting mass is heated and mixed, and then give it form in order to obtain molded peck. The spherical activated carbon or spherical activated carbon surface modified intended for oral administration and source material, from the viewpoint of security, must have sufficient purity and stable properties.

Then moulded peck is dispersed and granularit with stirring in hot water in order to obtain peck with particles microspheric forms. After this Supplement is extracted and removed from the molded pitch with a solvent which has a low solubility in relation to bake, but high dissolving power with respect to the additive. The obtained porous Paek oxidized by the action of the oxidizing agent in order to obtain porous pitch which does not melt under the action of heat. Obtained infusible porous pitch is subjected to processing in a stream of gas, such as steam or gaseous carbon dioxide that can interact with carbon to obtain a spherical activated carbon.

Next, the resulting spherical activated carbon are oxidized by heating in an atmosphere containing oxygen and then restore in the atmosphere of non-oxidizing gas, to receive the spherical activated carbon or spherical activated carbon with a modified surface, used as adsorbent, intended for oral administration according to the present invention.

In the above method of obtaining atmosphere containing oxygen in a given volume can be pure oxygen, oxides of nitrogen or air as the oxygen source. As an atmosphere inert to carbon, can be used, for example, nitrogen, argon or helium, both individually and as mixtures thereof.

The purpose of the addition of aromatic compounds to the original bake is that the fluidity of the source electrode is improved, and the production of granules from it becomes easier and porous pitch obtained by extraction and removal of the additive from the shaped pitch, while at later stages easier control over the structure and the burning of carbonaceous matter in the oxidation process. As an additive can be used, for example, naphthalene, methylnaphthalene, phenylnaphthalene, benzoylnaphthalene, methylanthracene, phenanthrene or biphenyl, both individually and in mixtures with each other. The amount of additive introduced into peck, is preferably from 10 to 50 mass parts of aromatic compound per 100 mass parts of the pitch.

Peck and additive preferably mixed with each other in terms of melting when heated in order to achieve a homogeneous mixing of the mixture of pitch and additives are preferably molded with the to give them the form of particles with a size of from about 0.01 to 1 mm and to control the particle size (diameter) of the obtained spherical activated carbon or spherical activated carbon surface modified. Molding can be performed under conditions of melting or by grinding the mixture after cooling.

The preferred solvent used for extraction and removal of the additive from a mixture of pitch and additives can be, for example, aliphatic hydrocarbons such as butane, pentane, hexane or heptane, a mixture containing an aliphatic hydrocarbon as a main component, such as naphtha or kerosene, or an aliphatic alcohol, such as methanol, ethanol, propanol or butanol.

The additive can be removed from the molded mixture by extraction of the additive solvent formed from a mixture of pitch and additives, and the form is saved. It is assumed that the extraction process in the molded product in place of the additive are formed through the pores and can be obtained molded peck, containing uniform pores.

Next, a molded porous Paek processed, which makes it infusible, namely, the obtained porous molded peck oxidized using an oxidizing agent, preferably in the range from room temperature to 300°in order to obtain porous infusible fourmeau the p peck, which does not melt under the action of heat. As the oxidizing agent can be used, for example, gaseous oxygen (O2) or a mixture gas obtained by diluting gaseous oxygen (O2) air or nitrogen.

The spherical activated carbon or spherical activated carbon with a modified surface that is used as the adsorbent for oral administration according to the present invention, receive, for example, using the methods above, using as source material thermosetting resin or pitch and he has a particle diameter of from 0.01 to 1 mm, If the diameter of the spherical particles of activated carbon or spherical activated carbon with a modified surface is less than 0.01 mm, the area of the external surface of the spherical activated carbon or spherical activated carbon with a modified surface increases, and easily adsorbed useful substances such as digestive enzymes. This is undesirable. When the particle diameter exceeds 1 mm, the distance of diffusion of toxic substances inside the spherical activated carbon or spherical activated carbon with a modified surface increases, and the rate of absorption is reduced. This is also undesirable. The diameter is preferably from 0.02 to 0.8 mm, the Expression "diameter ranges from Dl to Du" the text of this description means, the last sorting percentage (%) in the range of hole sizes of sieves from Dl to Du is 90% or more for the standard curve of accumulation of particle size obtained in accordance with JIS K 1474, as described below, in connection with the method of determining the average diameter of the particles.

In the spherical activated carbon or spherical activated carbon surface modified, used as adsorbent, intended for oral administration according to the present invention, the specific surface area (hereinafter the present description it is denoted as "SSA"), which is determined by the equation of the Langmuir adsorption, is 1000 m2/g or more. In the case when the spherical activated carbon or spherical activated carbon surface modified SSA has a value smaller than 1000 m2/g, the adsorption capacity in relation to toxic substances is reduced. The value of SSA is preferably 1000 m2/g or more. The upper limit value of SSA is not specifically limited, however, SSA is preferably 3000 m2/g or less from the point of view of bulk density and strength.

In the spherical activated carbon or spherical activated carbon surface modified, used as adsorbent used for peror the form of further introduction of the present invention, pore volume in the range of specific pore diameter is not specifically limited. For example, in the above last examination of a patent application in Japan (Kokoku) No. 62-11611 disclosed adsorbent containing spherical activated carbon with a modified surface, in which the volume of voids having the pore radius of 100 to 75,000 angstroms, i.e. the volume of pores with a diameter of 20 to 15000 nm is from 0.1 to 1 ml/G. However, in the spherical activated carbon or spherical activated carbon surface modified, used as adsorbent, intended for oral administration according to the present invention, the volume of pores having a diameter of 20 to 15000 nm, may be from 0.1 to 1 ml/g or 0.1 ml/g or less. In the case when the volume of pores having a diameter of from 20 to 1000 nm, is more than 1 ml/g, the adsorbed quantity of useful substances such as digestive enzymes, can increase. Therefore, the volume of pores having a diameter of from 20 to 1000 nm, is preferably 1 ml/g or less.

In the spherical activated carbon or spherical activated carbon surface modified, used as adsorbent, intended for oral administration according to the present invention, the volume of pores having a diameter of 7.5 to 15000 nm, preferably less than 0.25 ml/g, more PR is doctitle 0.2 ml/g or less, since in this case can be achieved significantly better selectivity of adsorption capacity.

In the composition of functional groups of the spherical activated carbon surface modified, i.e. the product obtained by the oxidation and restore the spherical activated carbon used as the adsorbent, intended for oral administration according to the present invention, the total amount of acid groups is from 0.40 to 1.00 mEq/g, and the total amount of basic groups is 0.40 to 1.10 mEq/g In the case when the composition of the functional groups satisfies the requirement that the total number of acid groups ranged from 0.40 to 1.00 mEq/g, and the total number of basic groups ranged from 0.40 to 1.00 mEq/g the selectivity of adsorption capacity is improved, in particular significantly increases the adsorption capacity in relation to hazardous substances. In the composition of functional groups, the total number of acid groups is preferably from 0.40 to 0.90 mEq/g, and the total amount of basic groups is preferably from 0.40 to 1.00 mEq/g

In that case, when the adsorbent of the present invention is used as a means for treating or preventing liver disease or kidney disease, a preferred composition of functional groups such that the amount of acid groups is from 0.40 to 1.00 mEq/g, the total number of basic groups is 0.40 to 1.10 mEq/g, the number of phenolic hydroxyl groups is from 0.20 to 0.70 mEq/g, the amount of carboxyl groups is 0.15 mEq/g or less, the ratio (a/b) total amount of acidic groups (a) to the total number of basic groups (b) is in the range from 0.40 to 2.5, and the ratio [(b+c)-d] between the total number of basic groups (b), a phenolic hydroxyl groups (C) and carboxyl groups (d) is 0.60 or more.

The properties of the spherical activated carbon or spherical activated carbon with a modified surface that is used as the adsorbent for oral administration according to the present invention, namely, the average particle size, specific surface area, pore volume, the total number of acid groups and the total number of basic groups, define the following methods.

(1) Average particle diameter

A standard curve of accumulation of particle sizes to get the spherical activated carbon or spherical activated carbon surface modified in accordance with JIS K 1474. The average particle diameter determined by the size of the sieve mesh (in mm) at the point of intersection with a line which is horizontal with respect to the x-axis starts from the intersection point standard curve of accumulation of particles p is pendicular line, restored from a point 50% on the x-axis.

(2) Specific surface area

The amount of adsorbed gas is measured using a device for determining the specific surface area (for example, ASAP2010, manufactured by MICROMERITICS) in accordance with the method of adsorption for sample spherical activated carbon or spherical activated carbon surface modified, and the value of the specific surface area can be calculated by the equation of the Langmuir adsorption. In particular, the spherical activated carbon or spherical activated carbon with a modified surface is placed as a sample in a test tube and dried under reduced pressure at a temperature of 300°C. then measure the mass of the dried sample. Then the tube is cooled down to minus 196°and filled with nitrogen, and the nitrogen adsorbed by the sample spherical activated carbon or the sample spherical activated carbon surface modified. Determine the ratio of the partial pressure of nitrogen adsorbed amount (line adsorption isotherms).

Build a graph on the Langmuir equation, taking the relative pressure of nitrogen for p, and the adsorbed amount at this time for v (cm3/g under standard conditions). Thus, build the graph in the range in which the value is s p ranges from 0.05 to 0.3, in the region where the longitudinal axis is p/v and the abscissa is equal to p. Assuming that the gradient at this time is equal to b (g/cm3), the specific surface area S (unit = m2/g) can be calculated from the equation:

where MA denotes the cross-sectional area of the nitrogen molecule and is rate £ 0.162 nm2.

(3) pore Volume, determined by the method of injection of mercury under pressure

Pore volume can be measured using mercury porosimetry (for example, AUTOPORE 9200, manufactured by MICROMERITICS). The spherical activated carbon or spherical activated carbon with a modified surface is placed as a sample in a test tube and Tegaserod under pressure to 2.67 PA or less within 30 minutes Then the test tube is placed mercury, the applied pressure is gradually increased (maximum pressure = 414 MPa) in order to cause the mercury to penetrate into the sample spherical activated carbon or spherical activated carbon surface modified. The pore size distribution of a sample of the spherical activated carbon or spherical activated carbon with a modified surface is determined from the relationship between pressure and amount of mercury, which is forced to penetrate, on the following equation.

In particular, measure the amount of mercury introduced into the sample areas the economic activated charcoal or spherical activated carbon surface modified as as the applied pressure increases the pressure (0.06 MPa), corresponding to a pore diameter of 22 μm, up to the maximum pressure (414 MPa), corresponding to a pore diameter of 3 nm. The diameter of the pore can be calculated as follows. When the mercury due to the applied pressure (P) is forced to penetrate into the cylindrical micropores having a diameter (D), surface tension (γ) mercury is balanced by the pressure acting on the cross section of the micropores, and thus get the following equation:

-πDγcosθ = π(D/2)2·P

where θ denotes the contact angle of mercury and the walls of the micropores.

Thus have the following equation:

D = (-4γcosθ)/P.

In the present description, the relationship between pressure (P) and pore size (D) is calculated by the equation:

D = 1,27/P,

assuming that the surface tension of mercury is 484 Dyne/cm, the contact angle of mercury and carbon is 130°the unit pressure P is in MPa, and the unit of measurement of diameter D is in microns. The volume of pores having a diameter of from 20 to 1000 nm, in accordance with the present invention corresponds to the volume of mercury introduced by increasing the applied pressure from 1.27 MPa to 63.5 MPa.

(4) the Ratio of intensity of diffraction, the value of R

A sample of the spherical activated carbon or the sample spherical activerow the frame of coal with a modified surface is dried at a temperature of 120° C for 3 h under reduced pressure and placed on a test plate made of aluminum, namely on the plate (35×50 mm2; t=1.5 mm)having a hole 20×18 mm2. Then by x-ray diffraction reflective type is used as the radiation source line CuKα (wavelength λ=0,15418), monochromatizing using a graphite monochromator, determine the magnitude of the intensity of diffraction of I15, I24and I35at angles of diffraction (2θ), equal to 15°, 24° 35°. The device parameters that generate x-rays and cracks, the following: applied voltage = 40 kV, current = 100 mA, divergence slit = 1/2°a gap sensor = 0.15 mm, the slit scattering = 1/2°. X-rays are not adjusted relative to the polarization factor of LJ, absorption factor, atomic scattering factor, etc., however, the diffraction angle adjust using the diffraction line (111) of powder of high purity silicon as a standard substance.

(5) the Total number of acid groups

The total number of acid groups represents the total amount of NaOH, which can be determined by adding 1 g of the sample spherical activated carbon or the sample spherical activated carbon surface modified after it is crushed with education is the use of particles with a size of 200 mesh or less, to 50 ml of 0.05 n NaOH solution; shake the mixture for 48 h, then filtered sample of the spherical activated carbon or the sample spherical activated carbon surface modified and titrated to neutralize.

(6) the Total number of basic groups

The total number of basic groups represents the total amount of HCl, which can be determined by adding 1 g of the sample spherical activated carbon or the sample spherical activated carbon surface modified after it is crushed to form particles with a size of 200 mesh or less, to 50 ml of 0.05 n HCl solution; shaking the mixture for 24 h, then filtered sample of the spherical activated carbon or the sample spherical activated carbon surface modified and titrated to neutralize.

As shown in the examples below, the spherical activated carbon or spherical activated carbon surface modified, used as adsorbent, intended for oral administration according to the present invention, has excellent adsorption ability, i.e. excellent adsorption ability with respect to the factors aggravating liver disease, or harmful substances in the kidney, however, the smaller the hell is orcinol ability to useful substances, such as digestive enzymes, and therefore can be used as adsorbent, intended for oral administration in the treatment or prevention of kidney disease or liver disease.

As kidney disease can be mentioned, for example, chronic renal failure, acute renal failure, chronic pyelonephritis, acute pyelonephritis, chronic nephritis, acute nephritic syndrome, acute progressive nephritic syndrome chronic nephritic syndrome, nephrotic syndrome, nephrosclerosis, interstitial nephritis, tubulopathy, lipoid nephrosis, diabetic nephropathy, renovascular hypertension or hypertensive syndrome, or secondary renal diseases caused by these primary disease, or mild renal failure before dialysis therapy and the adsorbent can be used to improve mild renal failure before dialysis therapy or painful for the patient state during dialysis therapy (see "Clinical Nephrology", Asakura-shoten, Nishio Honda, Kenkichi Koiso, and Kiyoshi Kurokawa, 1990; and "Nephrology" Igaku-shoin, Teruo Omae and Sei Fujimi, ed., 1981).

As liver disease can be mentioned, for example, fulminant hepatitis, chronic hepatitis, viral hepatitis, alcoholic hepatitis, liver fibrosis, liver cirrhosis, RA the liver, autoimmune hepatitis, drug allergic hepatopathy, primary biliary cirrhosis, tremor, encephalopathy, a disorder of metabolism or impaired liver function. In addition, the porous spherical carbonaceous substance may be used in the treatment of diseases caused by toxic substances in the body, such as psychosis.

Therefore, in the case where the adsorbent is intended for oral administration, is used as a means for treating or preventing renal disease, as an effective component, it contains a spherical activated carbon or spherical activated carbon surface modified. When the adsorbent is intended for oral administration, is used as a means for treating or preventing liver disease or kidney disease, its dosage depends on the subject (human or other animal), age, individual characteristics, status, etc. So in some cases it may be appropriate using the dosage, which is outside the following ranges of dosages, however, in the General case of oral dosing in the case of a person usually from 1 to 20 g of adsorbent per day, while the daily dosage may be divided into three or four portions. Dose the dose may accordingly, vary depending on the state of the disease. The composition may be in any form such as powders, granules, tablets, coated sugar tablets, capsules, suspensions, sticks, separate packaging or emulsion. In the case of capsules, usually can be used gelatin capsule, or, if necessary, capsules with intersolubility shell. In the case of tablets structures inside the body must be split up into the original tiny particles. The adsorbent can be used in the form of a mixture with an agent, controlling the content of electrolytes, such as gel, aluminum oxide or kayexalate.

EXAMPLES

The present invention is further illustrated, but in no case is not limited to, the following examples.

The following examples test is done on the adsorption α-amylase and on the adsorption of DL-β-aminoadamantane acid in accordance with the following methods, and the speed of selective adsorption calculated in the following way.

(1) Test on the adsorption α-amylase

A sample of the spherical activated carbon or the sample spherical activated carbon surface modified dried and 0.125 g of the dried sample is accurately weighed and placed in a conical flask fitted with a glass stopper. On the other hand, accurately weighed 0,100 g α-amylase (liquid form) and RAS is varaut, adding phosphate buffer (pH 7.4)to prepare the initial solution with the exact volume of 1000 ml. Exact amount of the original solution volume of 50 ml is placed in a specified conical flask, equipped with a glass stopper. The flask is shaken at a temperature of 37±1°C for 3 hours the Product in the flask is filtered through the vacuum membrane filter with a pore size of 0.65 μm. The first portion of the filtrate (approximately 20 ml) is poured, and the next portion of the filtrate (approximately 10 ml) is used as the test solution.

Next, repeat the same operations, except that they use only phosphate buffer (pH 7.4), in order to obtain a filtrate, which is used as a corrective solution. The analyzed solution and corrective solution analyzed by the method of photometric absorption using phosphate buffer (pH 7.4) as a control. Measure the absorbance at a wavelength of 282 nm. The difference between the absorption of the test solution and the absorption correction solution is taken as the study of absorption.

A standard curve is obtained by adding the exact amount of the original solution α-amylase average of 0 ml, 25 ml, 50 ml, 75 ml or 100 ml in a volumetric flask by adding phosphate buffer (pH 7.4), 100 ml and measuring absorption at a wavelength of 282 nm. From the value of the research the constituent absorption and the standard curve, calculate the quantity (in mg/DL) remaining in solution α -amylase.

To obtain depending on the number of sample spherical activated carbon or the sample spherical activated carbon surface modified repeat the same operations except that the used amount of the sample spherical activated carbon or the sample spherical activated carbon surface modified is 0,500 g, and the dimension of the studied acquisitions and the calculation of the amount remaining in solution α-amylase is carried out, as described above.

(2) Test on the adsorption of DL-β-aminoadamantane acid

A sample of the spherical activated carbon or the sample spherical activated carbon surface modified dried and 2,500 g of dried sample is accurately weighed and placed in a conical flask fitted with a glass stopper. On the other hand, accurately weighed 0,100 g DL-β-aminoadamantane acid and dissolved by adding phosphate buffer (pH 7.4)to prepare the initial solution with the exact volume of 1000 ml. Exact amount of the original solution volume of 50 ml is placed in a specified conical flask, equipped with a glass stopper. The flask is shaken at a temperature of 37±1°C for 3 hours the Product in the flask is filtered through the vacuum membrane filter with a pore size of 0.65 μm. The first portion of the filtrate (approx is Ino 20 ml) drained, and the next portion of the filtrate (approximately 10 ml) is used as the test solution.

Then 0.1 ml of the test solution accurately weighed and placed in a test tube. There also put the exact amount of phosphate buffer (pH 8.0), equal to 5 ml, and mix. Then add the exact amount, amounting to 1 ml of a solution obtained by dissolving 0,100 g fluorescamine in 100 ml of acetone (for non-aqueous titration), the resulting mixture is stirred and left for 15 minutes the resulting solution was analyzed by the method of fluorometry, and the wavelength of the fluorescence excitation is 390 nm, and the wavelength of fluorescence is 475 nm.

A standard curve was prepared as follows: to prepare 100 ml of a mixture of 0 ml, 15 ml, 50 ml, 75 ml and 100 ml stock solution of DL-β-aminoadamantane acid using for the balance of phosphate buffer (pH 7.4), stirred and filtered the mixture, then in the test tube is placed the exact amount of the obtained filtrate is equal to 0.1 ml add the exact amount of phosphate buffer (pH 8.0), equal to 5 ml, mix the mixture, add a solution of (exact number: 1 ml)obtained by dissolving 0,100 g fluorescamine 100 ml acetone (for non-aqueous titration), mix, leave for 15 minutes, analyze the resulting solution method fluorometry, and the wavelength of fluorescence excitation with the hat 390 nm, and the wavelength of fluorescence is 475 nm. Finally, using the standard curve, calculate the quantity (in mg/DL) DL-β-aminoadamantane acid remaining in solution.

To obtain depending on the number of sample spherical activated carbon or the sample spherical activated carbon surface modified repeat the same operations except that the used amount of the sample spherical activated carbon or the sample spherical activated carbon surface modified is 0,500 g, and the dimension of the studied acquisitions and the calculation of the amount of remaining in a solution of DL-β-aminoadamantane acid were carried out as described above.

(3) selective adsorption

Speed selective adsorption calculated from the amount remaining in solution α-amylase in a test on the adsorption α-amylase, where the number of used sample of the spherical activated carbon or the sample spherical activated carbon surface modified is 0,500 g, and the number remaining in a solution of DL-β-aminoadamantane acid in the test on the adsorption of DL-β-aminoadamantane acid, where the number of used sample of the spherical activated carbon or the sample spherical activated carbon with modifica vannoy surface is 0,500 g, using the following equation:

A = (10-Tr)/(10-Ur),

where And denotes the index of selective adsorption, Tr denotes the number of remaining in a solution of DL-β-aminoadamantane acid, and Ur denotes the number remaining in the solution α-amylase.

Example 1

Spherical phenolic resin (particle diameter from 10 to 700 μm, trade name Vysokotsentralizovannym resin spherical shape type "Maririn" HF500; Gun Ei Chemical Industry Co., Ltd.) sift through a sieve with a pore size of 250 microns to remove fine powders. Then 150 g of the obtained spherical phenolic resin is placed in a vertical tubular quartz reactor with a grid, heated to 350°C for 1.5 h in a stream of nitrogen, then heated to 900°C for 6 h and maintained at 900°within hours, getting to 68.1 g of spherical carbonaceous substance. After that activate the product at a temperature of 900°C in an atmosphere of a gas mixture consisting of nitrogen gas (3 l/min) and steam (2.5 l/min). When the bulk density of the spherical activated carbon is reduced to 0.5 ml/g, the activation of stop and get a 29.9 g of the spherical activated carbon (output 19,9% wt.).

The intensity of diffraction of the obtained spherical activated carbon be 743 count per second at an angle of diffraction (2θ), equal to 15°, 90 samples per second at an angle to dip the functions (2θ )equal to 35°and 473 sample per second at an angle of diffraction (2θ), equal to 24°. Thus, the ratio of intensity of diffraction, the value of R, is 1,71.

Properties of the resulting spherical activated carbon are shown in Tables 1 and 2.

Curve in figure 1 represents a diffraction curve obtained by measurement of the intensity of the product prepared by vacuum drying the spherical activated carbon obtained in example 1, at a temperature of 120°C for 2 h, according to the same methodology that the above method of measuring the ratio of intensity of diffraction, the magnitude of R.

Example 2

Repeat the same procedure as example 1, except that to obtain a spherical activated carbon instead of spherical phenol resin used in example 1, i.e. the spherical phenol resin, manufactured by Gunei Depending K.K., use spherical phenolic resin (particle diameter of 700 μm; trade name of a Spherical cured phenolic resin ACS series PR-ACS-2-50C; Sumitomo Bakelite Co., Ltd.) (output = 26,5%).

The intensity of diffraction of the obtained spherical activated carbon are 788 samples per second at an angle of diffraction (2θ), equal to 15°, 72 count per second at an angle of diffraction (2θ)equal to 35°and 492 sample per second at an angle of diffraction (2θ), equal to 24 . Thus, the ratio of intensity of diffraction, the value of R, is 1,71.

Properties of the resulting spherical activated carbon are shown in Tables 1 and 2.

Example 3

The spherical activated carbon obtained in example 1 was oxidized at a temperature of 470°C for 3 h, and then for 15 min in the fluidized bed in the atmosphere of a gas mixture of gaseous nitrogen and gaseous oxygen (oxygen concentration of 18.5% vol.), and then restore at 900°C for 17 min in the fluidized bed in the atmosphere of nitrogen gas and obtain a spherical activated carbon surface modified.

The intensity of diffraction of the obtained spherical activated carbon surface modified form 627 samples per second at an angle of diffraction (2θ), equal to 15°, 66 samples per second at an angle of diffraction (2θ)equal to 35°and 400 samples per second at an angle of diffraction (2θ), equal to 24°. Thus, the ratio of intensity of diffraction, the value of R is 1,68.

Properties of the resulting spherical activated carbon surface modified are shown in Tables 1 and 2.

Example 4

Repeat the same procedure as example 3, except that to obtain a spherical activated carbon surface modified as the e source material take spherical activated carbon used in example 2.

The intensity of diffraction of the obtained spherical activated carbon surface modified 702 is count per second at an angle of diffraction (2θ), equal to 15°, 74 sample per second at an angle of diffraction (2θ)equal to 35°and 428 samples per second at an angle of diffraction (2θ), equal to 24°. Thus, the ratio of intensity of diffraction, the value of R is 1,77.

Properties of the resulting spherical activated carbon surface modified are shown in Tables 1 and 2.

Example 5

Repeat the same procedure as example 3, except that to obtain a spherical activated carbon surface modified in the source material, take ion-exchange resin (styrene resin; the effective diameter of from 0.50 to 0.65 mm; trade name Amberlite 15WET; Organo Corporation).

The intensity of diffraction of the obtained spherical activated carbon surface modified form 765 samples per second at an angle of diffraction (2θ), equal to 15°, 82 count per second at an angle of diffraction (2θ)equal to 35°and 485 samples per second at an angle of diffraction (2θ), equal to 24°. Thus, the ratio of intensity of diffraction, the value of R is 1,69.

Properties of the resulting spherical activated carbon with modi is tirovannoj surface are shown in Tables 1 and 2.

Further, the micrograph (magnification X50), which shows the structure of the surface of the spherical activated carbon with a modified surface obtained with a scanning electron microscope, is shown in figure 2, a micrograph (magnification h), which shows the structure of a cross-section of the finished spherical activated carbon with a modified surface obtained with a scanning electron microscope, is shown in figure 3.

Comparative example 1

Petroleum pitch (68 kg) (softening temperature 210°s; content of substances insoluble in quinoline no more than 1% wt.; the ratio of hydrogen atoms/carbon atoms 0.63) and naphthalene (32 kg) was placed in an autoclave (internal volume of 300 l), equipped with paddles for mixing, melt at a temperature of 180°and mix. The mixture is extruded at a temperature in the range from 80 to 90°with the formation of filamentary products. Then filamentary products crushed, so get the ratio of the diameter to the length equal to from 1 to 2.

The obtained crushed products are added to an aqueous solution obtained by dissolving 0,23% wt. polyvinyl alcohol (saponification 88%) when heated to 93°and dispersed with stirring to implement the spheroidizing. Next, the mixture is cooled, replacing the aqueous solution of watering delovogo alcohol with water at 20° C for 3 h, while peck hardens, are naphthalene and formed suspension obtained from coal tar products of the spherical shape.

After most of the water is separated by filtration, naphthalene from coal tar is extracted and removed using n-hexane, the amount of which is approximately 6 times higher than the number obtained from coal tar products of the spherical shape. The resulting porous spherical pitch was heated to 235°passing hot air through the fluidized bed, and maintained at a temperature of 235°C for 1 h, while undergoing oxidation, so get oxidized porous spherical pitch which does not melt when heated. The oxygen content of the oxidized porous spherical pitch is 14% wt.

Then received oxidized porous spherical pitch activate within 170 minutes in the fluidized bed at a temperature of 900°C in an atmosphere of nitrogen gas containing 50% vol. pair, and get a spherical activated carbon. Next, the resulting spherical activated carbon oxidized for 195 minutes in the fluidized bed at a temperature of 470°C in an atmosphere of nitrogen - oxygen containing 18.5% to about. oxygen, and restore in the fluidized bed for 17 min at a temperature of 900°C in an atmosphere of gaseous nitrogen and receive the spherical and teverovsky coal surface modified.

The intensity of diffraction of the obtained spherical activated carbon surface modified form 647 samples per second at an angle of diffraction (2θ), equal to 15°, 84 count per second at an angle of diffraction (2θ)equal to 35°and 546 samples per second at an angle of diffraction (2θ), equal to 24°. Thus, the ratio of intensity of diffraction, the value of R is 1,22.

Properties of the resulting spherical activated carbon surface modified are shown in Tables 1 and 2.

Curve a in figure 1 represents a diffraction curve obtained by measurement of the intensity of the product obtained by vacuum drying the spherical activated carbon with a modified surface prepared in comparative example 1, at a temperature of 120°C for 2 h, according to the same methods as above for measuring the ratio of intensity of diffraction, the values of R; and the curve In figure 1 represents a diffraction curve obtained by the measurement by the above methods, the intensity of the paste-like product prepared by adding 2-3 drops of deionized with ion exchange water to 200 mg of the spherical activated carbon surface modified obtained in comparative example 1.

Further, the micrograph (magnification X50), on which the show is on the structure of the surface of the spherical activated carbon with a modified surface, obtained with a scanning electron microscope, is shown in figure 4, and micrograph (magnification h), which shows the structure of a cross-section of the finished spherical activated carbon with a modified surface obtained with a scanning electron microscope, is shown in figure 5.

Comparative example 2

Repeat the same procedure as comparative example 1, except that to obtain a spherical activated carbon oxidative and reductive treatment of the spherical activated carbon is omitted.

The intensity of diffraction of the obtained spherical activated carbon surface modified form 651 sample per second at an angle of diffraction (2θ), equal to 15°, 81 sample per second at an angle of diffraction (2θ)equal to 35°and 548 samples per second at an angle of diffraction (2θ), equal to 24°. Thus, the ratio of intensity of diffraction, the value of R is 1,22.

Properties of the resulting spherical activated carbon are shown in Tables 1 and 2.

Table 1
The original substanceSSAHg pore volumeAverage particle diameter, microns
Langmuir, m2/gBET m2/g20˜1000 nm7.5 to 15000 nm
Example 1Phenolic resin239018600,01850,04300
Example 2Phenolic resin210017200,02720,06430
Example 3Phenolic resin210016700,01420,04280
Example 4Phenolic resin193015600,01850,06410
Example 5The ion-exchange resin163012500,24370,42350
Comparative example 1Peck205015400,07500,11350
Comparative example 2Peck210016500,08500,15350

Pore volume, Hg in Table 1 is determined according to the method of injection of mercury under pressure, and it corresponds to the volume of pores having a diameter of from 20 to 1000 nm.

The value of SSA (BET) in Table 1 is found the value of specific surface area, which are for reference only, and it is determined in the following way.

In accordance with the method of determining the specific surface area according to the equation of the Langmuir adsorption, nitrogen is absorbed by the sample spherical activated carbon or the sample spherical activated carbon surface modified with a temperature of minus 196°and then measure the ratio of the partial pressure of nitrogen and ingested amount (build adsorption isotherm).

Build a graph by BET method, taking account of the relative pressure of nitrogen for p, and the adsorbed amount at this time for v (cm3/g under standard conditions). Thus, build the graph in the range in which the value of p ranges from 0.05 to 0.3, in the region where the longitudinal axis is p/(v(1-R)), and the abscissa is equal to p. Assuming that the gradient at this time is equal to b (g/cm3), and cut, cut on the coordinate axis is equal to (g/cm3), the specific surface area S (m2/g) can be calculated from the equation:

where MA denotes the cross-sectional area of the nitrogen molecule and is rate £ 0.162 nm2.

Table 2
The total number of acid groups, mEq/gThe total number VI the x groups, mEq/gThe amount remaining in solution α-amylase (mg/DL)The amount remaining in solution of DL-β-aminoadamantane acid (mg/DL)Selective adsorption capacityThe value of R
0.125 g0.50 g0.50 g2.50 g
Example 10,270,829,19,15,90,14,61,71
Example 20,210,659,09,07,41,32,61,71
Example 30,670,729,18,94,80,2the 4.71,68
Example 40,720,579,08,95,60,44,01,77
Example 50,650,598,97,24,10,12,11,69
Comparative example 10,670,548,57,25,240,141,71,2
Comparative example 20,180,588,67,78,464,30,71,22

Test 1 for confirmation of pharmacological action: function improvement in renal disease

For the test, confirming the pharmacological effect of renal failure by assigning the adsorbent for oral administration according to the present invention, using a rat model of renal failure, which induce incomplete removal 3/4 kidneys. As the samples used adsorbents prepared in examples 1 and 3 of the present invention. Six weeks after the establishment of rat model of rats divided into control group (6 rats; hereinafter referred to as group C1), the group which introduced the adsorbent prepared in example 1 (6 rats; hereinafter referred to as group P1), and the group which introduced the adsorbent prepared in example 3 (6 rats; hereinafter referred to as group P2), so that between the groups was not achieved.

Rats of these groups give powdered food. The amount of food the rats of different groups is determined on the basis of the average amount of food that you consume rats group C1 for 2 or 3 days. Rats groups P1 and P2 give a mixed food containing 5 wt. the adsorbent for oral administration in the same powdered food, and food that give the rats of group C1. 8 weeks after the start of the introduction of adsorbents for oral administration to measure the content of creatinine in serum, the content of urea nitrogen, creatinine in urine, creatinine clearance and the number of the extracted protein. Further, the same test is administered to six normal rats were incomplete removal of the kidney is not carried out (normal group).

The results are shown in Fig.6-9. 8 weeks after the start of introduction of the groups P1 and P2 the quantity of creatinine in serum (6) and urea nitrogen (Fig.7) is significantly reduced, respectively, in comparison with a group C1. As for creatinine clearance (Fig), which is an indicator of kidney function, decrease the set C1, while for groups P1 and P2 showed a significant suppression of reduction in relation to the group C1. Further, as the number of extracted protein (Fig.9), which is the indicator function of the renal tubules, the increase is set for a group C1, while for groups P1 and P2 showed a significant suppression of increase in relation to the group C1. In addition, similar results were obtained for the content of creatinine in the urine.

From the above results it is seen that as the adsorbent for oral administration according to the present invention are able to suppress the progression of chronic renal failure, to improve the condition of chronic renal failure, and to prevent kidney hypofunction or maintain kidney function.

Test 2 for confirmation of pharmacological action: function improvement in liver disease

For the test, confirming pharmacological action functional liver failure by assigning the adsorbent for oral administration according to the present invention, using a rat model of hepatitis, which induce the introduction of carbon tetrachloride. As the samples used adsorbents prepared in examples 1 and 3 of the present invention.

Namely continuously for about 4 months, until the end of the test to confirm the pharmacological actions, rats Sprague-Dauley (provider: company Clea Japan, Inc.; males; age 7 weeks) twice a week injected subcutaneously carbon tetrachloride in the amount of 12 mg/kg in two months after the start of injection of carbon tetrachloride confirm the reduction of liver function and, thus, rats divided into control group (6 rats; hereinafter referred to as group C2), the group which introduced the adsorbent prepared in example 1 (6 rats; hereinafter referred to as group Q1), and the group which introduced the adsorbent prepared in example 3 (6 rats; hereinafter referred to as the group Q2), so that between the group and no imbalance in relation to the pathological condition.

Rats of these groups give powdered food. The amount of food the rats of different groups is determined on the basis of the average amount of food that you consume rats group C2 for 2 or 3 days. Within two months after splitting into groups of rats groups Q1 and Q2 give mixed food containing 5% wt. the adsorbent for oral administration in the same powdered food, and food that give groups C2. Further, the same test is administered to six normal rats that were not injected carbon tetrachloride (normal group).

Within about two months from the start of the assignment of the adsorbent for oral administration until the end of the test measure the content of ICG (indocyanine green), GOT (glutamic-oxaloacetic transaminase levels) and GPT (glutamic-pyruvic transaminase levels). The results obtained through the two months since the introduction of the adsorbent for oral administration, is shown in figure 10 (ICG), 11 (GOT) and Fig (GPT). Comparing ICG test, which reflects the function of the liver mesenchyme, we can conclude that the groups Q1 and Q2 show significantly lower values than the values of the group C2. Next, the groups Q1 and Q2 show significantly lower values than group C2, for values of GOT and GPT, which determine the expiration of cellular enzymes.

From the results given above, Thu the adsorbent, intended for oral administration according to the present invention may slow down the degradation of the liver.

Industrial applicability

The adsorbent intended for oral administration according to the present invention, has a specific porous structure and, thus, when administered orally has excellent selective adsorption ability, i.e. excellent adsorption ability with respect to the harmful toxins in the gut with a low adsorption capacity compared to the useful substances in the body, such as digestive enzymes and the like, and selective adsorption capacity is significantly improved compared to the selective adsorption ability of the conventional adsorbent, intended for oral administration.

The adsorbent intended for oral administration according to the present invention, can be used as the adsorbent for oral administration, intended for the treatment or prevention of kidney diseases, or as an adsorbent, intended for the treatment or prevention of liver diseases.

As kidney disease can be mentioned, for example, chronic renal failure, acute renal failure, chronic pyelonephritis, acute pyelonephritis, chronic nephritis, the stry nephritic syndrome, acute progressive nephritic syndrome chronic nephritic syndrome, nephrotic syndrome, nephrosclerosis, interstitial nephritis, tubulopathy, lipoid nephrosis, diabetic nephropathy, renovascular hypertension or hypertensive syndrome, or secondary renal diseases caused by these primary disease, or mild renal failure before dialysis therapy and the adsorbent can be used to improve mild renal failure before dialysis therapy or pathological States for the patient during dialysis therapy (see "Clinical Nephrology", Asakura-shoten, Nishio Honda, Kenkichi Koiso, and Kiyoshi Kurokawa, 1990; and "Nephrology" Igaku-shoin, Teruo Omae and Sei Fujimi, ed., 1981).

As liver disease can be mentioned, for example, fulminant hepatitis, chronic hepatitis, viral hepatitis, alcoholic hepatitis, liver fibrosis, cirrhosis, liver cancer, autoimmune hepatitis, drug allergic hepatopathy, primary biliary cirrhosis, tremor, encephalopathy, a disorder of metabolism or impaired liver function. In addition, the porous spherical carbonaceous substance may be used in the treatment of diseases caused by toxic substances in the body, such as psychosis.

Although the present invention is described with reference to con the specific methods of its implementation, there are various changes and modifications obvious to a person skilled in the art that fall within scope of the following claims.

1. The adsorbent for oral administration, containing spherical activated carbon particle diameter is from 0.01 to 1 mm, specific surface area, determined by the equation of the Langmuir adsorption, is 1000 m2/g or more, and the ratio of intensity of diffraction, the value of R, defined by equation (1)

where I15indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 15°I35indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 35°and I24indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 24°is 1.4 or more and the volume of pores having a diameter of 7.5 to 15000 nm is less than 0.25 ml/year

2. The adsorbent for oral administration according to claim 1, in which the volume of pores having a diameter of from 20 to 1000 nm is 0.1 ml/g or less.

3. The adsorbent for oral administration according to claim 1, in which the spherical activated carbon obtained from thermosetting resin as a carbon source.

4. The adsorbent for the PE the oral administration according to claim 1, in which the spherical activated carbon obtained from thermosetting resin as a carbon source, which gives the yield of carbonization of 40 wt.% or more by heat treatment at a temperature of 800°C in an atmosphere of non-oxidizing gas.

5. The adsorbent for oral administration, containing spherical activated carbon with a modified surface, the diameter of the particles is from 0.01 to 1 mm, specific surface area, determined by the equation of the Langmuir adsorption, is 1000 m2/g or more, the total number of acid groups is from 0.40 to 1.00 mEq/g, the total amount of basic groups is 0.40 to 1.10 mEq/g, and the ratio of intensity of diffraction, the value of R, defined by equation (1)

,

where I15indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 15°I35indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 35°and I24indicates a diffraction intensity when a diffraction angle (2θ) x-ray diffractometry is 24°is 1.4 or more and the volume of pores having a diameter of 7.5 to 15000 nm is less than 0.25 ml/year

6. The adsorbent for oral administration according to claim 5, in which the volume of pores having the x diameter from 20 to 1000 nm, is 0.1 ml/g or less.

7. The adsorbent for oral administration according to claim 5, in which the spherical activated carbon obtained from thermosetting resin as a carbon source.

8. The adsorbent for oral administration according to claim 5, in which the spherical activated carbon obtained from thermosetting resin as a carbon source, which gives the yield of carbonization of 40 wt.% or more by heat treatment at a temperature of 800°C in an atmosphere of non-oxidizing gas.

9. Pharmaceutical composition for treating or preventing diseases of the kidney containing the adsorbent for oral administration according to claim 1 and a pharmaceutically acceptable carrier or diluent.

10. Pharmaceutical composition for treating or preventing diseases of the kidney containing the adsorbent for oral administration according to claim 5 and a pharmaceutically acceptable carrier or diluent.

11. Pharmaceutical composition for treating or preventing the disease, dependent uremic substances or exacerbated uraemic substance containing the adsorbent for oral administration according to claim 1 and a pharmaceutically acceptable carrier or diluent.

12. Pharmaceutical composition for treating or preventing the disease, dependent uremic substances or exacerbated uraemic substance containing adsorbent for oral administration according to claim 5 and a pharmaceutically acceptable carrier or diluent.

13. Pharmaceutical composition for treating or preventing diseases of the liver containing the adsorbent for oral administration according to claim 1 and a pharmaceutically acceptable carrier or diluent.

14. Pharmaceutical composition for treating or preventing diseases of the liver containing the adsorbent for oral administration according to claim 5 and a pharmaceutically acceptable carrier or diluent.

15. A method of treating or preventing renal diseases, including the appointment of the needy in this subject an effective amount of the adsorbent for oral administration according to claim 1.

16. A method of treating or preventing renal diseases, including the appointment of the needy in this subject an effective amount of the adsorbent for oral administration according to claim 5.

17. A method of treating or preventing the disease, dependent uremic substances or exacerbated uraemic substance, including the appointment of the needy in this subject an effective amount of the adsorbent for oral administration according to claim 1.

18. A method of treating or preventing the disease, dependent uremic substances or exacerbated uraemic substance, including the appointment of the needy in this subject an effective amount of the adsorbent for oral administration according to claim 5.

19. A method of treating or preduprezhdeny the liver disease, including the appointment of the needy in this subject an effective amount of the adsorbent for oral administration according to claim 1.

20. A method of treating or preventing liver disease, including the appointment of the needy in this subject an effective amount of the adsorbent for oral administration according to claim 5.



 

Same patents:

FIELD: organic chemistry, medicine, hepatology.

SUBSTANCE: invention relates to using 2-methylthiopyrimido[4,5-b]indole of the formula (1): showing melting point at 243°C (with decomposition) and value LD50 > 1000 mg/kg used in liver protection from poisoning with carbon tetrachloride. Proposed compound exceeds activity of the "Essentiale" as a comparison preparation.

EFFECT: valuable medicinal property of compound, enhanced effectiveness.

1 tbl

FIELD: pharmaceutical industry.

SUBSTANCE: claimed adsorbent contains spherical active carbon, obtained from thermosetting resin as carbon source, having particle size of 0.001-1 mm, specific surface determined by Langmuir adsorption equation of 1000 m2/g or more and pore volume of 7.5-15000 nm in diameter less than 0.25 ml/g. Also disclosed is adsorbent being similar to abovementioned one, wherein total content of acidic groups is 0.40-1.00 meq/g; total content of basic groups is 0.4-1.1 meq/g. Pharmaceutical compositions contain said adsorbents and pharmaceutically acceptable carriers and recipients. Agents of present invention are useful in treatment of kidney or liver diseases or disorders associated with uremic substance by administration of said adsorbents.

EFFECT: products of increased selectivity.

21 cl, 5 ex, 2 tbl, 11 dwg

FIELD: chemical and pharmacological industry.

SUBSTANCE: invention relates to encapsulated form of Acyzol containing Acyzol and pharmaceutically acceptable fillers in specific component ratio.

EFFECT: encapsulated mass with high technological characteristics, high biological availability and effectiveness of Acyzol component.

5 tbl, 3 dwg

FIELD: veterinary science.

SUBSTANCE: in case of dioxine intoxication animals should be prescribed with dimephosphon at the dosage of about 50-150 mg/kg body weight daily for 10-30 d. The innovation provides decreased embryonic lethality in animals.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

FIELD: medicine, toxicology.

SUBSTANCE: invention proposes applying 15% aqueous solution of 1-methyl-5-[2'-(benzyldimethylammonio)ethyl]carbamoyl pyridinium-2-aldoxime dichloride that exceeds the 15% solution of dipiroxime (TMB-4, trimedoxime bromide) used in native medicinal practice by the curative effectiveness. Invention can be used in urgent treatment of acute poisoning with organophosphorus poisonous substances eliciting neuroparalytic effect.

EFFECT: enhanced effectiveness, valuable medicinal properties of agent.

3 tbl

The invention relates to the field of organic chemistry and medicine and relates to a derivative of imidazo-[1,2-a]-benzimidazole, specifically: 9-diethylaminoethyl-2-(3,4-dioksifenil)-imidazo-[1,2-a]-benzimidazole of dihydrobromide formula (I) providing cerebroprotective effect in radiation damage

The invention relates to organic chemistry, in particular to derive SIM-triazine-2-ethylamino-4-piperidyl-6-[(4’-methylcarbamyl-5’-methyl-1’,2’,3’,-triazole)-1-yl]-1,3,5-triazine structure:

as an antidote from fetotoksicheskoe action of the herbicide 2,4 - dichlorophenoxyacetic acid on the sunflower sprouts
Drug // 2229882
The invention relates to a new combination drug, which can be used as a means of protecting the person from the early transient incapacitation and edema of the primary reaction to radiation

The invention relates to new stable crystalline calcium or magnesium salts of (6R,S),(6S) - or (6R)-tetrahydrofolate acid, method for their production and pharmaceutical compositions based on them

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: Described are derivatives of general formula I (all symbols are as described in specification), pharmaceutically acceptable salts thereof or cyclodextrin clathrates. Such compounds hardly bind of EP2 subtype of PGE receptor and are useful in prophylaxis of immune diseases, allergy, death of neuronal cells, liver or kidney insufficiency, etc.

EFFECT: new agent for prophylaxis of various diseases.

18 cl, 388 ex, 68 tbl, 3 dwg

FIELD: medicinal industry.

SUBSTANCE: invention relates to a method for isolating biologically active substance from mammalian kidney and preparing a medicinal formulation for parenteral administration that can be used in medicine as agent normalizing kidney functions. Agent is made as a medicinal formulation for parenteral administration and represents peptide complex with the content of low-molecular fraction from 70% to 90%, molecular mass of its peptide components in the range from 70 to 456 Da and concentration of polypeptides 2.5-2.9 mg/ml. Agent if prepared from calf kidneys (age is 12 months, not above) or pigs by extraction of tissue with acetic acid in the presence of zinc chloride. Method for preparing the agent involves freezing calf kidneys (age is 12 months, not above) or pigs at temperature -40°C (not less), keeping at temperature -20-22°C for 2 months (not less), milling adding 3% acetic acid solution in the volume ratio = 1:5 at temperature 20 ± 5°C. Extraction is carried out at constant stirring and 1% zinc chloride solution is added to the prepared homogenous suspension in the volume ratio = 50:1. Then suspension is cooled at constant stirring up to temperature 7-16°C followed by stirring for 1 h each 4 h in settling for 48 h. Extract is separated from inert substances by separating and acetone is added to extract in the volume ratio = 1:5 and kept at temperature 3-5°C for 4 h. Formed homogenized deposit is precipitated repeatedly with acetone twice (not less) and deposit containing active substance is washed out on Nutch filter with two-fold volumes of acetone cooled to temperature 7-16°C up to preparing light-gray deposit. Deposit is rubbed through metallic sieve, dried and dissolved in distilled water at room temperature and constant stirring up to the concentration of polypeptides 2.5-2.9 mg/ml. Solution is centrifuged, filtered and subjected for ultrafiltration treatment in device at anti-pressure 1.0 kgf/cm2 (not above) through materials with retaining capacity 15000 Da. Glycocol is added to filtrate up to its final concentration 10-20 mg/ml at pH = 5.6-6.6 and solution is subjected for sterilizing filtration under pressure 2.0 kgf/cm2 (not above), poured into ampoules by volume 2 ml and subjected for autoclaving at temperature 120°C for 8 min and under atmosphere pressure 1.1 kgf/cm2. Invention provides optimal technology in isolating peptide complex from calf kidneys (age is 12 months, not above) or pigs with the content of low-molecular fraction from 70% to 90%, molecular mass of its peptide components from 70 to 456 Da and preparing aqueous solution of extract with the concentration of polypeptides 2.5-2.9 mg/ml. Invention provides both purification of the end product from impurities and enhancing its yield. Also, the isolated substance differs from the known substances early prepared from mammalian raw by molecular mass of its peptide components, absence of toxicity and apyretic properties based on the complete removing impurities.

EFFECT: improved preparing method, valuable medicinal properties of agent.

3 cl, 2 tbl, 1 dwg, 4 ex

FIELD: medicine, obstetrics, nephrology.

SUBSTANCE: invention relates to a method for prophylaxis of chronic pyelonephritis exacerbation in pregnant women. Method involves carrying out pharmacotherapy in combination using position therapy and physiotreatment beginning from the second half of pregnancy. The preparation "Yantar'-antitoks" is prescribed additionally in the dose 0.5 g, 3 times per a day after eating for 2 weeks. Then the schedule of treatment is 0.5 g per a day for 3 weeks. Then courses in dosing the preparation are alternated up to fetus delivery. Method provides reducing toxic effect of bacterial flora, shows the cytoprotective effect, eliminates energetic misbalance in kidney tissue, effects on inflammation process and improves secretory and disintoxication function of kidneys.

EFFECT: improved method of prophylaxis.

2 ex

FIELD: medicine, in particular nephrology.

SUBSTANCE: claimed method includes diet therapy in combination with antioxidant preparation triovit administrated in dose of 1 capsule 2 times per day for 1 month.

EFFECT: inflammation process arresting; improvement of filtration processes in kidney.

FIELD: pharmaceutical industry.

SUBSTANCE: claimed adsorbent contains spherical active carbon, obtained from thermosetting resin as carbon source, having particle size of 0.001-1 mm, specific surface determined by Langmuir adsorption equation of 1000 m2/g or more and pore volume of 7.5-15000 nm in diameter less than 0.25 ml/g. Also disclosed is adsorbent being similar to abovementioned one, wherein total content of acidic groups is 0.40-1.00 meq/g; total content of basic groups is 0.4-1.1 meq/g. Pharmaceutical compositions contain said adsorbents and pharmaceutically acceptable carriers and recipients. Agents of present invention are useful in treatment of kidney or liver diseases or disorders associated with uremic substance by administration of said adsorbents.

EFFECT: products of increased selectivity.

21 cl, 5 ex, 2 tbl, 11 dwg

FIELD: experimental biology and medicine, hepatology, nephrology.

SUBSTANCE: invention proposes using extracts of porcine or human fetal adrenal gland cortex for correction of acute renal insufficiency in toxic hepatorenal syndrome caused by carbon tetrachloride (CCl4). For realization for correction method involves carrying out course of subcutaneous injections of extract of porcine or human fetal adrenal gland cortex by 1 injection per 24 h in the dose 2.0-2.5 ml/kg of body mass by total course 10 every day injections. Using the proposed method provides enhancing effectiveness of regenerative processes in kidneys and reducing symptoms of adverse effects.

EFFECT: valuable medicinal properties of agent.

2 cl, 2 tbl

FIELD: medicine.

SUBSTANCE: invention relates to application of 2-ethyl-6-methyl-3-oxypyridine succinate for treatment of nephritis and nephropathy of various ethiology in combination with conventional therapy including rheolytic, anticoagulant and antiaggregant agents, APP inhibitors and anti-inflammatory agents.

EFFECT: effective preparation for treatment of nephritis and nephropathy.

2 tbl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a combined medicinal preparation used in treatment of disturbance of thiol-disulfide status in kidney transplantation that comprises ambroxol as an effector of glutathione metabolism, α-lipoic acid and additives. Also, invention relates to using inhibitors of activity of angiotensin-converting enzyme - kaptopril, enalapril and ramipril or ambroxol along with α-lipoic acid for preparing a medicinal agent used in treatment of disturbance of thiol-disulfide status in kidney transplantation. Invention provides enhancing effectiveness of treatment.

EFFECT: valuable medicinal property of agent and its enhanced effectiveness.

14 cl, 7 dwg, 7 tbl, 6 ex

FIELD: medicine, nephrology.

SUBSTANCE: invention proposes a method for treatment of patients with chronic renal insufficiency and receiving treatment by renal dialysis or hemodiafiltration. Increase concentration of blood homocysteine in such patients causes the severe disturbances in vessels function and represents risk factor for vascular diseases. Method involves prescription of dithiothreitol or 2,3-dimercaptopropane sodium sulfonate (unithiol) before or during hemodialysis or hemofiltration. Method provides reducing blood level of homocysteine in patients in case of its increased content (in these patients the concentration of low- and mean-molecular metabolic products is increased sharply due to damage or complete ceasing formation of urine) to practically normal values that is based on release of homocysteine from its bound form with proteins.

EFFECT: improved treatment method of patients.

1 tbl, 5 ex

FIELD: veterinary science.

SUBSTANCE: the suggested aqueous gel for preventing and treating diseases of inferior urinary tract in cats and dogs includes: (a) efficient quantity of gel-forming agent being kappa-carragheenan, (b) efficient quantity of a substance that increases appetite in cats or dogs, and (c) at least, 85 weight% water. The innovation provides decreased concentration of mineral components in urine as a result of its increased production.

EFFECT: higher efficiency.

18 cl, 1 ex, 1 tbl

FIELD: gastroenterology.

SUBSTANCE: method involves simultaneously introducing Panavir and Ganavir. Panavir is introduced intravenously in daily dose 5 ml of 0.004% solution, course: 3 injections with interval 48 h and then, 3 days latter, 2 injections with interval 48 h. Galavin is introduced intramuscularly in daily dose 100 mg, course: 5 injections with interval 24 h and then 10 injections with interval 48 h.

EFFECT: achieved elimination of virus, normalization of clinical and biochemical characteristics in absence of side effects.

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