Photosynthesised microorganisms rich in selenium from selenium-containing hydroxy acids, use thereof in food, cosmetics and pharmacy

FIELD: chemistry.

SUBSTANCE: invention relates to a method of enriching a photosynthesising microorganism, selected from green algae and blue-green algae with organic selenium. The photosynthesising microorganism is cultured in a medium containing a compound of the type of selenium-containing hydroxy acid of general formula , with a salt, ester or amide derivative of said acid. Content of organic selenium in the green algae or blue-green algae is higher than 1000 mcgSe/g of dry weight. Also disclosed is use of the enriched microorganisms as a cosmetic, pharmaceutical or food agent.

EFFECT: enriching photosynthesising microorganisms with non-toxic organic selenium with high output.

16 cl, 3 tbl, 4 ex

 

The invention relates to enrichment fotoindutsirovannykh microorganisms organic selenium, in particular, by using compounds of the type of selenium-containing hydroxyacids and more specifically by using 2-hydroxy-4-methylseleninic acid, in the form (D,L) or an enantiomer, salt, complex, ester or amide this compound, as well as the use of fotoindutsirovannykh microorganisms enriched thus, in the diet of the animal or human, cosmetics or pharmacy.

Selenium is micropatterned substance, essential for humans and mammals (Wendel, A.: Phosphorus, Sulfur Silicon Relat Elem., 1992, 67, 1-4, 405-415). More specifically, it participates in the form of L(+)-selenocysteine or L(+)-Selenomethionine (Muller, S. et al., Arch. Environ., 1997, 168, 421) in the biosynthesis of selenoproteins, such as glutathioneperoxidase, thioredoxins and selenoprotein R.

In humans, selenium deficiency has been identified, in particular, in the case of patients during long-time fed parenterally (Von Stockhausen, H.B., Biol. Trace Elem., Res., 1988, 15:147-155). A daily Supplement of 200 micrograms of selenium is considered to be reliable and adequate for an adult, with an average body weight (Schrauzer, G.N., J. Am. Col. Nutr., 2001, 20: 1-14).

In nature, selenium is found in two forms: organic and inorganic.

Inorganic compounds are often salts such as Selenite or sodium Selenite. This is compounds are very toxic to humans and most animals.

Organic compounds (organic selectabase connection) presents living organisms, in particular, the amino acid L(+)-Selenomethionine, L(+)-methylselenocysteine and L(+)-selenocysteine.

L(+)-Selenomethionine is the major source of organic selenium for humans and animals. However, people and animals are auxotrophic for this amino acid, which can only be obtained through food.

So ideally selenium should be included in the composition of food supplements for the treatment or prevention of selenium deficiency in this organic form.

Thus, it was shown that the introduction of the food of L(+)-Selenomethionine is significantly less toxic and more bioavailable than the introduction in the form of sodium Selenite (Mony, M.C. et al., J. of Trace Elem. Exp. Med., 2000, 13: 367-380).

At present unknown other metabolic pathways capture selenium living organisms, except those in which the substrates used inorganic selenium, mainly in the form of sodium Selenite and Selenomethionine.

Acceptable source of organic selenium can be found in higher plants (in particular, wheat, corn, soy), in which 80% of selenium is L(+)-Selenomethionine (Schrauzer, G.N., J. Am. Coll. Nutrit., 2001, 20(1):1-4). However, the selenium content in these plants is not sufficient to easily and with the least difficult the AMI to create nutritional supplements.

One of the tested ways to obtain compositions that are rich in Selenomethionine is to enrich some microorganisms organic selenium from inorganic selenium. These enriched microorganisms can serve as raw material for production of food or cosmetic products.

In numerous publications described, for example, yeast, selenium-enriched, and more specifically of the yeast Saccharomyces cerevisiae (Oh Tae-Kwang et al., patent KR950006950 from 26.06.1995) for use as such or for inclusion in food composition (Moesgaard S. et al., patent DK200200408 from 16.09.2003); or to obtain derivatives products enriched with selenium, such as bread (Wang Boaquan, patent CN 1817143 from 16.08.2006 some), milk (Jeng Chang-Yi, the patent TW565432 from 11.12.2003), egg (Cui Li et al., patent CN1302723C from 07.03.2007), chocolate (In Gyeong Suk et al., patent KR20040101145 from 08.11.2004) or beer (Jakovleva L.G. et al., patent RU2209237 from 27.07.2003), selenium-enriched. In the area of health food products containing yeast, selenium-enriched, it was also suggested for pregnant women (Wang Weiyi, patent CN1778199 from 31.05.2006) or to improve the intestinal microflora in patients with hypoglycemia (Li Tao Zhao, patent CN1810161 from 02.08.2006). In the field of dermocosmetics compositions containing yeast, selenium-enriched, were designed to reduce hair loss (Kazik Heinz, patent DE19858670 from 21.06.2000) or for preduprezhdeny the photoaging (Kawai Norihisa et al., patent JP07300409 from 14.11.1995). Pharmaceutical preparations containing yeast, selenium-enriched, used for the prevention and treatment of pathologies - inflammatory, such as retinopathy associated with diabetes (Crary J. Ely, patent US5639482 from 17.06.1997)or cardiovascular (Nagy P.L. et al., patent HUT060436 from 28.09.1992).

Bacteria and more specifically probiotic bacteria also have been used for enrichment of selenium (Calomme M. et al., Biol. Trace Elem. Res., 1995, 47, 379-383). Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus ferintoshensis, Lactobacillus buchnerilparabuchneri (Andreoni V. et al., patent US0258964) were described as food supplements enriched with selenium. Received probiotic mixture consisting of yeast and lactobacilli, to strengthen the immune system and resistance to diseases (Kehe Huang Qin, patent CN1283171C from 08.11.2006).

However, all these drugs microorganisms enriched with selenium, received only inorganic selenium. So, the most frequent source of selenium is Selenite or selenate sodium dissolved in the culture media of microorganisms. Enriched therefore microorganisms, although they synthesized a satisfactory amount of organic selenium absorbed by the human body, often have high residual content neprevyshenie inorganic selenium, which may be dangerous for the consumer who's actions.

In previous published application WO 2006/008190 new organic compounds of the type of selenium-containing hydroxyacids were described as likely to be the precursors for the synthesis of L(+)-Selenomethionine in humans and animals.

Unexpectedly, the applicant stated that the organic compounds of the type of selenium-containing hydroxyacids, such as described in the application WO 2006/008190, can be included in the culture medium for the enrichment of various fotoindutsirovannykh microorganisms organic selenium. The results showed that these compounds can be used to very effectively to enrich such microorganisms, in particular, L(+)-Selenomethionine with equal and even greater output than is obtained by using the commonly used inorganic compounds.

Thus, it was found that the enrichment fotoindutsirovannykh microorganisms organic selenium from organic compounds of the type of selenium-containing hydroxyacids allows you to get organic selenium containing no inorganic selenium, and solve, thus, problems of toxicity associated with the methods of the prior art.

Fotoindutsirovannyi microorganisms enriched in this manner can be used directly in food through prevention or treatment of selenium deficiency, in particular, for pharmaceutical, food is whether cosmetic products and compositions.

Detailed description of the invention

The purpose of the present invention is to obtain fotoindutsirovannykh microorganisms, i.e. microorganisms, the growth of which depends on the source of light energy.

Under microorganism understand any living single-celled organism belonging to one of the following kingdoms: Monera, protists, nicety or protoshare with eukaryotic or prokaryotic structure, microscopic or ultramicroscopic size, with metabolic and reproductive potential. These unicellular organisms can participate in the formation of filaments or biofilms.

Preferably fotoindutsirovannyi microorganisms according to the invention are eukaryotic microalgae, preferably green algae of the genus Chlorella or prokaryotic microalgae, such as cyanobacteria, preferably of the genus Spirulina or Arthrospira (spirulina). These latter are well known to the expert for use as food additives, in particular in developing countries.

Under organic selenium understand the totality of molecules containing at least one compound with at least one selenium atom in its chemical structure, which can be produced from a living organism, such as amino acids village is metionin, methylselenocysteine and selenocysteine, peptides or proteins containing them.

Fotoindutsirovannyi microorganisms enriched so selenium can be used as such or as a food additive. For example, they may be subjected to dehydrogenation to obtain a stable powder that can be included in the composition, which is the basis for the transformed products, and you can use them live as probiotics in the process of transformation of food in order to obtain, for example, fermented milk or drinks.

Thus, an object of the present invention is a new way of enriching fotoindutsirovannykh microorganisms Selenomethionine and/or selenocysteine, characterized in that the said photosynthetic microorganism is cultivated in a culture medium containing the connection type selectarray hydroxy acids.

Preferably the connection type selectarray hydroxy acid is a compound of General formula (I), precursor, salt or complex ether or Amida, a derivative of this acid:

formula where:

n is 0, 1 or 2;

R1denotes OH, OCOR3, ORO3H2, OPO3R4R5or or6;

R2represents OH, R3, Other72represents OH, R1cannot designate OH;

R3denotes alkoxy, ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6A and 6b, S-cysteinyl, S-glutathionyl or a group selected from the following groups:

or

Preferably R3denotes alkoxy, S-cysteinyl, S-glutathionyl;

OR4means (C1-C26)alkoxyl, ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6A and 6b, or a group selected from the following groups:

or

Preferably OR4means (C1-C26)alkoxyl;

OR5means (C1-C26)alkoxyl, ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6A and 6b, or a group selected from the following groups:

or

Preferably OR5means (C1-C26)alkoxyl;

OR6means pyruvate, lactate, citrate, fumarate, maleate, myristate, palmitate, stearate, palmitoleate, oleate, linoleate, natural fatty acid or 13-CIS-retinoate;

R7denotes H, (C1-C )alkyl or a natural amino acid or natural Amin.

In the above formula (I)

under the alkyl understand group containing from 1 to 26 carbon atoms, linear or cyclic, possibly branched, may fluorinated or polyfluorinated, and may contain one or more double carbon-carbon bonds, such as, for example, methyl, ethyl, isopropyl, trifluoromethyl, linoleyl, linoleyl, Palmitoyl;

under alkoxyl understand group derived from a primary, secondary or tertiary alcohol containing from 1 to 26 carbon atoms, linear or cyclic, possibly branched, may fluorinated or polyfluorinated, and may contain one or more double carbon-carbon bonds, such as, for example, methoxyl, ethoxyl, isopropoxy, trifloromethyl, linoleoyl, linolenate, Palmitoyl;

structure of radicals of the type ceramides are described, in particular, in Cosmetic Lipids and the Skin Barier”, Thomas Forster Ed. 2002, Marcel Dekker, Inc., p.2, fig.2;

under natural understand any appropriate connection, discovered in metabolism in organisms from plant, animal world and in the human body (Steglich W., Rompp Encyclopedia Natural Products, G. Thieme ed.);

- floor oligomer understand any compound consisting of a sequence of 2-15 monomers linked pore the STW communications type of ester;

under polymer understand any compound consisting of a sequence of more than 15 monomers, connected by communication type of ester.

According to the invention, these compounds of formula (I) preferably used in the form of salts of calcium, zinc or magnesium, which mainly provides the best solubility in culture medium, as well as better digestion fotoindutsirovannyi microorganisms.

In a preferred variant of the invention, the photosynthetic microorganism is chosen from the group formed by blue-green and green algae. Thus, the photosynthetic microorganism mainly choose from blue-green or green algae, preferably chosen from the group formed by green algae of the genus Chlorella and blue-green algae of the genus Spirulina or Arthrospira.

More specifically the invention relates to the use of compounds of formula (I)are selected (or taken) from:

- L-2-hydroxy-4-methylseleninic acid,

- D-2-hydroxy-4-methylseleninic acid,

- DL-2-hydroxy-4-methylseleninic acid,

or salts of these compounds.

These compounds are described in the application WO 2006/008190.

The object of the invention is also photosynthetic microorganism enriched with organic selenium, which may be the floor of the EN method according to the invention. This microorganism contains mainly organic selenium in the amount of more than 500 ppm, preferably more than 1000 ppm, more preferably more than 2000 ppm in selenium equivalent, and inorganic selenium in the amount of less than 0.5%, preferably less than 0.2% and more preferably less than 0.1% of the dry weight of the specified microorganism. Preferably the invention relates to cases, when photosynthetic microorganism contains less than 1.5%, preferably less than 0.5%, more preferably less than 0.1% of the mass. inorganic selenium in relation to the total amount of selenium.

In other words, the remains of selenium in inorganic form, present in fotoindutsirovannykh microorganisms enriched by the method according to the invention, comprise mostly less than 1.5% of the total selenium present in the microorganisms, which mainly represents less than 0.5% of the total dry biomass (dry weight) of the specified microorganism.

More specifically the invention relates to fotoindutsirovannogo the microorganism enriched with organic selenium, characterized in that the content of selenium in the form of Selenomethionine in the specified microorganism is more than 50%, preferably more than 70%, more preferably more than 80% and more preferably more than 90% of the mass. in relation to the total number of selenium, soteriades is in the specified fotoindutsirovannogo the microorganism. Such content Selenomethionine is an improvement in the quantity and quality of organic selenium that is present in the microorganism, the essential and predominant in comparison with what has been achieved in the prior art.

In particular, the purpose of the invention is that the microorganism differs in that it is a green and cuts, preferably of the genus Chlorella, selenium-enriched, and the fact that the microorganism contains Selenomethionine in number mainly more than 50 micrograms in selenium equivalent per gram (Se/g), preferably more than 70 Se/g and more preferably more than 100 Se/g dry weight of the specified microorganism.

The amount of selenium contained in the microorganisms, expressed as organic (Selenomethionine, selenocysteine or otherwise) or inorganic molecules (salts of selenium) by weight of selenium per gram (Se/g) dry weight of the microorganism. In other words, the content of selenium in fotoindutsirovannykh microorganisms set by calculating the mass of selenium present in these molecules, organic or inorganic, referred to the total dry biomass of the microorganism. Additionally, the massive amount of selenium present in organic and inorganic form, set and expressed in percentage in respect to the tion to the weight of selenium in whole.

The total selenium content and content in the form of Selenomethionine in fotoindutsirovannykh the microorganisms according to the invention can be defined respectively mineralization and enzymatic digestion after centrifugation and freeze-drying of microorganisms, for example, by the method Lobinsky et al., described in Mester, Z. et al., (2006) Annal. Bioanal. Chem. 385: 168-180.

Obtained according to the present invention results, which illustrate examples of the present invention, show that fotoindutsirovannyi microorganisms, more specifically, green and blue-green microalgae accumulate selenium in the form of Selenomethionine in number, mainly in excess of 100 micrograms in selenium equivalent per gram (Se/g), preferably more than 200 Se/g, more preferably more than 1000 Se/g dry weight, and even more than 1400 Se/g dry weight of these microalgae.

More specifically the aim of the invention are green or blue-green algae, enriched with organic selenium, characterized in that contain organic selenium in the form of Selenomethionine, mainly in the more than 100 Se/g, preferably more than 200 Se/g, more preferably more than 500 Se/g and even more preferably more than 1000 Se/g dry weight.

Such green or blue-green algae, enriched with organic selenium, mainly distinguished by the, the content of organic selenium in the form of Selenomethionine is more than 50%, preferably more than 70%, more preferably more than 80%, even more preferably more than 90%, even more than 95% of the total amount of selenium, which they contain, as well as the fact that the residual content of inorganic selenium in them, mostly consisting of less than 1.5%, preferably is less than 0.5%, more preferably less than 0.1% of the total selenium, which it contains. Mainly residual content of inorganic selenium is less than 1%, preferably less than 0.5%, more preferably less than 0.2% and more preferably less than 0.1% of the total biomass of these green algae dry weight.

In addition, the invention relates to the production of food, cosmetics or pharmaceutical products of these fotoindutsirovannykh microorganisms, selenium-enriched by the method according to the present invention. For this get using technology known to the expert.

Fotoindutsirovannyi microorganisms according to the invention can also be suitable for animal food, in particular, to obtain second derivatives enriched with selenium, in particular, fish, milk or eggs.

Derivative molecules and the products thus obtained can have various applications, including chiclete, as mentioned in the introductory part, in particular, as a cosmetic, pharmaceutical or nutritional agent.

The object of the invention is also the use of fotoindutsirovannykh microorganisms enriched with selenium, according to the present invention, as a cosmetic, pharmaceutical (or therapeutic) or nutritional product (or agent).

The invention also relates to compositions, mainly cosmetic, pharmaceutical or nutritional containing the specified fotoindutsirovannyi microorganisms.

The invention relates also to the culture medium for fotoindutsirovannykh microorganisms, characterized in that it contains one or more of the compounds of formula (I), defined above. This cultural environment suitable for implementing the method of enrichment fotoindutsirovannykh microorganisms selenium according to the invention.

In particular, the invention relates to solid or liquid culture medium containing at least one compound of formula (I), preferably 2-hydroxy-4-methylseleninic acid or one of its salts at a concentration of from 0.5 to 2000 mg/l, preferably from 1 to 1000 mg/l, more preferably from 2 to 500 mg/l, i.e. respectively from about 0.2 to 800 mg/l of the compounds in selenium equivalent, predpochtite the flax from 0.4 to 400 mg/l of the compounds in selenium equivalent, more preferably from 0.8 to 200 mg/l of the compounds in selenium equivalent.

When using microalgae marine origin of the compounds of formula (I) can be diluted in sterile filtered seawater or in synthetic sea water, for example, obtained from environment “Crystal Reef” by Aquarium Systems Inc., to get a minimal culture medium.

The method of obtaining microalgae according to the invention can, in particular, to include one or more of the following stages:

- getting culture medium, preferably, a minimal medium containing the chemical elements necessary for the growth of microalgae;

- introduction to the culture medium of the compounds of formula (I), preferably 2-hydroxy-4-methylseleninic acid as an organic source of selenium;

- regulation of the pH of the mixture to a value from 6 to 10;

- cultivation of inoculum preculture specified microalgae in the thus obtained mixture at a temperature of from 12 to 45°C, in conditions of orbital mixing speeds ranging from 100 to 500 rpm, and in the atmosphere, which may contain from 0 to 20% oxygen and from 0.3 to 20% carbon dioxide, preferably within 24-120 hours;

- centrifugation of the mixture at a speed ranging from 400 to 10,000 rpm for several minutes or filtration through a filter with holes of 0.2 mi is romera and rinse saline solution on the filter;

- removing cellular sludge from saline;

repeat the centrifugation speed from 4,000 to 10,000 rpm for several minutes.

- removing wet cell sludge which contains microalgae enriched with selenium.

Wet cell precipitate can be liofilizirovanny or to dry in the air.

Other characteristics and advantages of the invention are shown in the following examples. The following examples are given solely as an illustration and in no way limit the scope of the invention.

EXAMPLES

Example 1

Getting Autotravel microalgae Chlorella vulgaris, selenium-enriched, in a medium containing 2-hydroxy-4-methylseleninic acid (THD-177)

Experimental conditions

As photoautotrophic strain used Chlorella vulgaris SAG211-11B: original axenically strain from the collection of SAG at the University of göttingen (SAG: Sammlung von Algenkulturen der Universitat Gottingen).

This strain was cultured in medium BG-11 (Blue-green medium), as described [Stanier RY et al. 1971 Bacteriol. Rev. 35:171-205], having the following composition (per 1 liter):

(1) NaNO3: 1.5 g

(2) K2HPO4: 0.04 g

(3) MgSO4.7H2O: 0.075 g

(4) CaCl2.2H2O: 0,0036 g

(5) citric acid: 0,006 g

(6) iron ammonium citrate: 0,006 g

(7) EDTA-Na2: 0.001 g

(8) Na2CO3: 0.02 g

(9) Distillers the fair water 1.0 l

(10) the Solution of trace elements 1 ml/l

H3BO3: 2.86 g

MnCl2.4H2O: 1,81 g

ZnSO4.7H2O: 0,222 g

Na2MoO4.2H2: 0.39 g

CuSO4.5H2O: 0.08 g

Co(NO3)2.6H2O: 0.05 g

The pH value was set to 7.1 and the medium was sterilized in autoclave at 121°C for 15 minutes.

This photoautotrophy strain was cultured at 25°C, 2400 +/-200 Suite within 2-7 days with orbital stirring (80 rpm), DOinitit660nm=0,05. DO660nmstrain of 0.5 within 48 hours.

The cultivation conditions

Organic source of selenium, namely 2-hydroxy-4-methylseleninic acid (THD-177, Tetrahedron SAS, France, CAS: 873660-49-2), was injected at a concentration of 0.5 mg/l to 100 mg/l in selenium equivalent, i.e. respectively 1.25 mg/l and 250 mg/l of 2-hydroxy-4-methylseleninic acid. Introduction selectabase compounds were carried out in one step (i.e. the amount of from 0.125 mg to 25 mg per 100 ml of culture) at the beginning of the cultivation or in several stages at regular intervals, the duration of which ranged from 6 to 24 hours, and the cultivation was continued for 2-7 days.

Example 2

Getting the microalgae Chlorella vulgaris, selenium-enriched, in a medium containing 2-hydroxy-4-methylseleninic acid (THD-177) (example of invention), or in an environment that contains Asa sodium Selenite (comparative example) in mixotrophic conditions of supply (the presence of light and carbohydrate - glucose - environment):

In these experiments used a strain of Chlorella vulgaris SAG211-11B: original axenically strain from the collection of SAG at the University of göttingen (SAG: Sammlung von Algenkulturen der Universitat Gottingen), which were cultured in mixotrophic nutrition in the following environment:

Yeast extract0.33 g
Meat extract0.33 g
Tryptose0.66 g
FeSO40.66 g
Glucose3.3 grams
Distilled waterthe number to 1.0 l

The pH value was set to 7.1 and the medium was sterilized in autoclave at 121°C for 15 minutes.

Organic source of selenium, namely 2-hydroxy-4-methylseleninic acid (THD-177, Tetrahedron SAS, France, CAS: 873660-49-2), was injected at a concentration of 20 mg/l in selenium equivalent, ie 50 mg/l of 2-hydroxy-4-methylseleninic acid.

Inorganic selenium source (SeNa, sodium Selenite) was injected at a concentration of 20 mg/l in selenium equivalent,i.e. the 43,9 mg/l of sodium Selenite.

Introduction selectabase compounds were carried out in one step in the exponential growth phase of the strain of Chlorella vulgaris, (i.e. 3 days after inoculation).

Obtaining samples for analysis

7 days after the start of the incubation medium was filtered through a membrane Nalgène 0.2 micron (Ref a-Pes, diameter 90 mm) and cell retentate was washed with a physiological solution. Wet cell mass was subjected to lyophilization for analysis of selenium-containing components (the total amount of selenium, Selenomethionine and sodium Selenite).

Analysis of selenium-containing components in Chlorella vulgaris

The total number of selenium were dosed out using ICP combined with detection by mass after mineralization of the sample. Analysis of selenium was carried out by high performance liquid chromatography in combination with detection weight-weight after enzymatic digestion according to the method described Lobinsky et al. in Mester, Z. et al. (2006) Annal. Bioanal. Chem. 385: 168-180.

Results

In the following table 1 shows the average value in selenium equivalents received three times during the incubation period is 7 days.

Table 1
Analysis of selenium-containing components of the microalgae Chlorella vulgaris
Total number Se Se/kg biomassSe-methionine
Se/kg biomass
Se(IV)
Se/kg biomass
Introduction THD177 20 Se/l1293±231274±109
(98,5% of total Se)
6±1
(0,4% of total Se)
Introduction SeNa 20 Se/l144±529±2
(20% of total Se)
4,1±0,4
(2,7% of total Se)

The results obtained with the same dose of selenium entered as THD177 or SeNa, in this case 20 Se/l, showed that:

it was found nine times more the total number of Se obtained by injection in the form THD177 than those obtained with the introduction in the form of SeNa;

the amount of selenium accumulated intracellularly in the form of Selenomethionine, obtained by the introduction THD177, 44 times the amount of selenium obtained with the introduction of SeNa;

the amount of selenium accumulated intracellularly in the form of Selenomethionine, reaches almost 100% (98.5 per cent) in intracellular selenium forms when introduced in the form of THD177 compared with 20% with the introduction in the form of SeNa; and that

only 0.4% of Se(IV) in the total amount of selenium was detected in the introduction as TH177, whereas 2.7% of Se(IV) was detected in the total amount of selenium in the introduction of SeNa.

Example 3

Getting Autotravel Arthrospira platensis microalgae enriched selenium in the medium containing 2-hydroxy-4-methylseleninic acid (THD-177) (example according to the invention) or in medium containing sodium Selenite (comparative example)

In these experiments used a strain of Arthrospira platensis 3054-E.

Strain 3054-E cultivated as autotrophy in the following environment:

Yeast extract0.33 g
Meat extract0.33 g
Tryptose0.66 g
FeSO40.66 g
Distilled waterthe number to 1.0 l

The pH was set to 7.2 and the medium was sterilized in autoclave at 121°C for 15 minutes.

Organic source of selenium, namely 2-hydroxy-4-medicalinsurance acid (THD-177, Tetrahedron SAS, France, CAS: 873660-49-2) was injected at a concentration of 25 mg/l in selenium equivalent, i.e. at 62.5 mg/l of 2-hydroxy-4-methylseleninic acid.

Inorganic selenium source (SeNa, sodium Selenite) was administered at the end of the ation of 25 mg/l in selenium equivalent, i.e. of 54.4 mg/l of sodium Selenite.

Introduction selectabase compounds were carried out in one step immediately after inoculation of the strain of Arthrospira platensis (i.e. T=0).

Obtaining samples for analysis:

10 days after the beginning of incubation the cell residue was filtered through a membrane Nalgène 0.2 micron and cellular retentate was washed with a physiological solution. Wet cell mass was subjected to lyophilization for analysis of selenium-containing components (the total amount of selenium, Selenomethionine and sodium Selenite).

Analysis of selenium-containing components in Arthrospira platensis

The total amount of selenium was determined using ICP combined with detection by mass after mineralization of the sample. Analysis of selenium was carried out by high performance liquid chromatography in combination with detection weight-weight after enzymatic digestion according to the method described Lobinsky et al. in Mester, Z. et al. (2006) Annal. Bioanal. Chem. 385: 168-180.

Results

In the following table 2 shows the average value in selenium equivalents received three times during the incubation period is 10 days.

Table 2
Analysis of selenium-containing components of the algae Arthrospira platensis
Total number Se Se/kg biomassSe-methionine
Se/kg biomass
Se(IV)
Se/kg biomass
Introduction THD177 25 Se/l1431±681402±47
(98% of total Se)
17,2±0,7
(1,2% of total Se)
Introduction SeNa 25 Se/l177±213±3
(7% of total Se)
5,1±0,3
(2,9% of total Se)

The results obtained with the same dose of selenium entered as THD177 or SeNa, in this case 25 Se/l, showed that:

it was found eight times greater total number of Se obtained by injection in the form THD177 than those obtained with the introduction in the form of SeNa;

the amount of selenium accumulated intracellularly in the form of Selenomethionine, obtained by the introduction THD177, 108 times the amount of selenium obtained by injection in the form SeNa;

the amount of selenium accumulated intracellularly in the form of Selenomethionine, reaches 98% in the intracellular selenium forms when introduced in the form of THD177 compared to 7% with the introduction in the form of SeNa; and that

only 1.2% of Se(IV) in the total amount of selenium was detected in the introduction as THD177, whereas 2.9% of Se(IV) was detected is in the total amount of selenium in the introduction as SeNa.

Example 4

Getting the algae Arthrospira platensis, selenium-enriched, in a medium containing 2-hydroxy-4-methylseleninic acid (THD-177) (example of invention)

In these experiments used a strain of Arthrospira platensis 3054-E. Compare the results:

- the previous example 3, in which the introduction of the invention selectabase connection THD-177 carried out in one step immediately after inoculation of the strain of Arthrospira plantensis

the results of a new experiment in which the introduction of the invention selectabase connection THD-177 was performed in the exponential phase of the cultivation of the specified strain of Arthrospira platensis, as in example 2.

Results

In the following table 3 shows average values in selenium equivalents received three times during the incubation period is 10 days.

Table 3
Analysis of selenium-containing components of the algae Arthrospira platensis
Analysis of selenium-containing components in the algae Arthrospira platensisTotal number Se Se/kg biomassSe-methionine
Se/kg biomass
THD177 Se/kg biomassSe(IV)
Se/kg biomass
1431±681402±47
(98% of total Se)
5±1
(0,35% of total Se)
17,2±0,7 (1,2% of total Se)
Introduction THD177 25 Se/l in the exponential phase1274±161078±89 (85% of total Se)11±2 (0,86% of total Se)14±2
(1,1% of total Se)

The results showed that 12% more than the total selenium, and 30% more selenium as Selenomethionine was obtained in the test of "introduction to t0 compared to the test "introduction to exponential phase". This difference may be due to longer duration of contact of the biomass with THD177 test "introduction to t0 compared with another test of the "introduction to exponential phase".

In both these cases, the intracellular content of Se(IV) remains insignificant and amounts to 1% of the total selenium.

1. A method of enrichment of organic selenium photosynthetic microorganism selected from green algae and blue-green algae, characterized in that the said photosynthetic microorganism is cultivated in a medium containing the compound t is PA selectarray hydroxy acids of General formula (I), such as defined below, salt, ester or amide derivative of this acid:

2. The method according to claim 1, wherein said microorganism is enriched with Selenomethionine.

3. The method according to claim 1 or 2, characterized in that the compound of General formula (I) chosen from:
- L-2-hydroxy-4-methylseleninic acid,
- D-2-hydroxy-4-methylseleninic acid,
- DL-2-hydroxy-4-methylseleninic acid,
or salts of these compounds.

4. The method according to any one of claims 1 to 3, characterized in that the compounds of formula (I) are in the form of salts of calcium, zinc or magnesium.

5. The method according to any one of claims 1 to 4, wherein the photosynthetic microorganism is chosen from the group formed by green algae of the genus Chlorella and blue-green algae of the genus Spirulina or Arthrospira.

6. Photosynthetic microorganism selected from green algae and blue-green algae, enriched with organic selenium, which can be obtained by the method according to any one of claims 1 to 5, with specified photosynthetic microorganism characterized in that the content of the specified microorganism of selenium in the form of Selenomethionine is more than 50%, preferably more than 70%, more preferably more than 80% and even more preferably more than 90 wt.% selenium in relation to the total amount of selenium available is properly specified in photosynthetic microorganism.

7. Photosynthetic microorganism enriched with organic selenium, according to claim 6, wherein the photosynthetic microorganism contains less than 1.5%, preferably less than 0.5%, more preferably less than 0.1 wt.% inorganic selenium in relation to the total amount of selenium.

8. Green algae, enriched with organic selenium, which can be obtained by the method according to any one of claims 1 to 5, characterized in that the content of organic selenium in the form of Selenomethionine is more than 1000 Se/g dry weight.

9. Green algae, enriched with organic selenium, according to claim 8, characterized in that the residual content of inorganic selenium is less than 2%, preferably less than 1.5%, more preferably less than 1 wt.% inorganic selenium in relation to the total weight of selenium, which they contain.

10. Blue-green algae, enriched with organic selenium, which can be obtained by the method according to any one of claims 1 to 5, characterized in that the content of organic selenium in the form of Selenomethionine is more than 1000 Se/g dry weight.

11. Blue-green algae, enriched with organic selenium, according to claim 10, characterized in that the residual content of inorganic selenium is less than 2%, preferably less than 1.5%, more preferably less than 1 wt.% reorgani the definition of selenium in relation to the total weight of selenium, they contain.

12. Blue-green algae according to any one of p-11, characterized in that they belong to the genus Spirulina or Arthrospira.

13. The use of photosynthetic microorganism enriched with organic selenium on any of PP-12, as a cosmetic, pharmaceutical or nutritional agent.

14. Composition for the treatment or prevention of selenium deficiency, containing at least one photosynthetic microorganism enriched with organic selenium on any of PP-9.

15. The composition according to 14, characterized in that the said composition is a cosmetic, pharmaceutical or food.

16. Culture medium for photosynthetic microorganism, characterized in that it contains one or more compounds of the type selectarray hydroxyacids of formula (I)such as defined in claim 1.



 

Same patents:

FIELD: biotechnology.

SUBSTANCE: method of cultivation of microalgae for biofuel purpose comprises two stages of algolisation. At the first stage the algolisation is carried out by primary inoculum of the culture, preferably Chlorella vulgaris BIN, obtained in the photobioreactor synchronously or time-shifted, of multifunctional indoor pools with translucent railing. The total volume of the said pools is from 1/30 to 1/15 of the total amount of open water reservoirs. The secondary inoculum is grown with a bulk density of 109-1011 cells/l, at that the cultivation is started in spring with an average daily temperature of water in the pools in the range of 12-18°C. The second stage of cultivation the microalgae is started by selection from the pools of secondary inoculum at a temperature of water in the open water reservoirs of 12-18°C, and continue its supply to the open water reservoirs to reach in them of the bulk density of microalgae 2·108-109. The secondary inoculum is partially taken from the pool as a finished product in spring and autumn with the water temperature in them is in the range of 8-12°C, at that in multifunctional pools the equal amount of water with dissolved biogens is added. The resulting microalgae contain 33.9 % cellulose, 51.0 % proteins, 7.3% fats.

EFFECT: increased productivity of microalgae cultivation method.

3 cl, 1 dwg, 4 ex

FIELD: biotechnology.

SUBSTANCE: plant comprises a frame with a container for suspension of microalgae mounted on it, light fittings each of which is designed in the form of a glass pipe with lamps placed in it and has a ventilator installed under the glass pipe, pipelines for supplying nutrient medium, solution of carbon dioxide, discharge of the finished suspension, temperature and pH sensors, the service system of the plant. The additional containers for the suspension are mounted on the frame. Each of the containers is formed with an aquarium having a vortex turbine and made in the form of a rectangular parallelepiped of translucent glass with one opening on the lower plane for drainage of the finished suspension and its discharge through the pipeline to the container for storage of suspension, and with at least three openings in the upper plane for location of the sensors inside the aquarium, installation of pipelines to supply nutrient medium, discharge of oxygen and sanitation. The light fittings are mounted vertically between the aquariums equidistant from each other with the ability of their free displacement or removal when transition to solar illumination and have reinforced in the upper part of each light fitting plates with protruding ends to be placed between the aquariums and with the ability to rest on them. The service system is made with the ability to operate in an automatic mode and comprises pumps-dispensers, automatic system of dosing, a hot-water boiler with a predetermined temperature, temperature and pH sensors, chlorella. The PH sensor is mounted in each aquarium lower than the level of suspension, the timer relay for switching on and off the lamps.

EFFECT: increased productivity of growth, ease of use and safety in operation.

4 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to cultivating blue-green microalgae of the genus Spirulina to obtain golden yellow algae with high content of carotenoids. The method involves cultivating algae of the genus Spirulina in a culture medium containing 0.1-0.15 g/l of a compound which contains carbon as a carbon source and 0.06-0.35 g/l of a compound which contains nitrogen as a nitrogen source, for 5-7 days. Further, concentration of the carbon source is increased from 0.2 g/l to 1.5 g/l and concentration of the nitrogen source is reduced from 0.005 g/l to 0.03 g/l and cultivation continues for the next 5-7 days. A citrate compound is then periodically added to the culture medium in amount of 0.5-10 mg/l or an acetate compound is periodically added in amount of 75-250 mg/l or combinations thereof are added. The obtained golden yellow microalgae of the genus Spirulina, having high content of carotenoids, are collected.

EFFECT: obtained algae contain at least 600 mg/g of dry cell mass of mixed carotenoids.

19 cl, 6 tbl, 1 ex

FIELD: process engineering.

SUBSTANCE: biomass of Chlorella species unicellular algae dried to 10%-humidity is activated by activator of planetary, vibratory or vibratory-rotary types that allows acceleration of grinding bodies of 60-400 m/s2, time of stay in activation zone making 0.5-10 minutes. Ground biomass is suspended in organic solvent, i.e. gasoline or ethyl alcohol, added in extraction in amount of 5-7 litres per 1 kg of dry biomass, and extracted at room temperature for 3-5 hours. Produced extract is filtered to produce soluble and insoluble portions to be dried to produce dry lipid-pigment complex. Extract dried insoluble fraction is mixed with enzymatic agents ''Cellulox-A'' and '' Protocubtillin r3x'' or mixes thereof, and subjected to hydrolysis for 4-8 hours at pH 4-6, and 50-65°C. Note here that enzymic preparations are added to extract insoluble fraction in amount of 0.5-10 wt %.

EFFECT: enzymic hydrolysate separated by centrifugation into soluble and insoluble fractions, and dried to yield dry products.

3 cl, 4 ex

FIELD: process engineering.

SUBSTANCE: proposed method comprises remote determination of concentrations of total suspensions and chlorophyll in analysed region while chlorophyll index (Ichl), equal to Ichl=chl oc 3/(tsm clark-0.25), where chl oc 3 is concentration of chlorophyll while tsm dark is concentration of total suspension (tsm clark - 0.25) is concentration of total micro diatoms biomass in Japanese Sea, is calculated by magnitude of chlorophyl index. The larger chlorophyll index, the smaller fraction of diatoms relative to total biomass of diatoms.

EFFECT: higher efficiency of monitoring. 4 dwg

FIELD: medicine.

SUBSTANCE: initial nutrient medium together with an inoculated autotrophic microorganism is supplied from a technological container into an input section of a photobioreactor with forming a suspension film of a photoautotrophic microorganism flowing down by gravity on an internal surface of transparent cylindrical tubes. Simultaneously, mixed air and carbon dioxide are reverse-flow supplied inside the tubes with using sleeves with suspension film outflow. The photoautotrophic microorganism suspension flowing in the internal surface of the transparent cylindrical tubes gets into a light section wherein it is continuously illuminated with a fluorescent tube. From the transparent cylindrical tubes, the photoautotrophic microorganism suspension flows down in an output section of the photobioreactor wherein it is bubbled to saturate the cells with carbon dioxide additionally and illuminated with a horizontal toroidal lamp. An external surface of the transparent cylindrical tubes is sequentially cooled in cooling air in the light section and in cooling water in the cooling section with cooling air and cooling water flowing in the respective recirculation loops. The photoautotrophic microorganism suspension is added with a nutrient medium of main and correction flows supplied into a technological container at first and then into the suspension recirculation loop at the input of the input section of the photobioreactor. Waste mixed air and carbon dioxide are supplied from the photobioreactor into the mixer by means of a compressor through the mixed air and carbon dioxide recirculation loop and temporarily collected in a gas tank. Post-bubble foam is continuously discharged from a lower section of the photobioreactor into an anti-foaming separator and separated into a suspension supplied into the input section of the photobioreactor and mixed air and carbon dioxide combined with waste mixed air and carbon dioxide in a regulation loop, while being temporarily collected in the gas tank and supplied into the mixer with extra saturation of waste mixed air and carbon dioxide with a required amount of carbon dioxide. Carbon dioxide saturated mixed air and carbon dioxide are discharged from the mixed by two ducts one of which being a main flow is reverse-flow directed inside the transparent cylindrical tubes; the other one is supplied into the output portion of the photobioreactor when bubbling the suspension. From the output portion of the photobioreactor, the microorganism suspension is discharged from the suspension recirculation loop with intermediate vented out oxygen release accompanying a cultivation process with using a desorber; another portion of the photoautotrophic microorganism suspension is discharged in a finished biomass collector to be measured for the required values for the purpose of creating optimal conditions for photoautotrophic microorganism cultivation.

EFFECT: invention provides higher effectiveness of photoautotrophic microorganism cultivation, enabled integration of the presented method into the current production lines, improved energy efficiency and performance of photoautotrophic microorganism cultivation.

2 ex, 1 dwg

FIELD: agriculture.

SUBSTANCE: water is taken, which contains algae. The algae mass 8 is centrifuged together with water at the speed of not more than 1000 rpm. Afterwards the algae weight 8 is exposed to a light diode device 5 including radiators of blue, green and red colours. Light radiators 5 are installed at the distance of not more than 50 cm from the surface of the centrifuged algae mass 8. The algae mass 8 is dried with dry warm air without access of direct sunlight. The system to produce the mass of blue-green algae from water reservoirs comprises a water-intake device, a centrifuge 1, light radiators 5, a heat gun or a heat fan 4. The water-intake device sends the algae mass 8 into the centrifuge 1. The centrifuge 1 is made as capable of centrifuging the mixture at the speeds of up to 1000 rpm. Inside or near the centrifuge 1 there are radiators 5 of blue, green and red colours. Light radiators 5 are installed at the distance of not more than 50 cm from the surface of the centrifuged algae mass 8. The heat gun or the heat fan 4 are installed as capable of blowing through the algae mass 8. The system comprises a cover 6 or is made in the form of a box restricting access of direct sunlight to the algae mass 8.

EFFECT: higher efficiency in production of dry blue-green algae mass from a water reservoir.

2 cl, 15 dwg, 4 tbl

FIELD: chemistry.

SUBSTANCE: when culturing phototrophs, the culture fluid is stirred and aerated through agitation by moving cultivators back and forth in the horizontal plane at given temperature and pH values. The cultivators are illuminated with a pulsed light source with pulse duration of 0.00001-0.001 s and pulse spacing of 0.01-0.1 s. In the apparatus used, the culture fluid is illuminated with diodes located under transparent bottoms of vessels of the same geometric shape and powered by a pulse generator with controlled frequency and light pulse duration.

EFFECT: group of inventions enables to reduce power consumption when culturing phototroph biomass.

2 cl, 2 dwg, 2 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a Saccharomyces cerevisiae VKPM Y-3415 yeas strain which produces ethyl alcohol. The strain is adapted to culturing on dairy cheese whey.

EFFECT: strain is capable of producing ethyl alcohol with high output and is antagonistic to accompanying microflora.

1 ex

FIELD: chemistry.

SUBSTANCE: biosensor contains photo-autotrophic microalgae cells, the fluorescent characteristics of the photosynthesis system of which vary in the presence of cytotoxic chemical compounds in their surroundings: heavy metal ions and herbicides. Cells of green and diatomic microalgae are immobilised in cryogenic gel of polyvinyl alcohol: a cell suspension is deposited on a surface and the cells enter macropores of the polymer carrier under the effect of centrifugal force (5000-14000 g) for 1-10 minutes. A highly sensitive and stable biosensor is obtained based on components taken in the following ratio in wt %: microalgae cells 0.015-1.1; polyvinyl alcohol 7-15; aqueous phase - up to 100. Low concentrations of heavy metals and herbicides in aqueous systems are determined at flow rate of up to 360 ml/h based on the change in the value of relative variable fluorescence chlorophyll cells in the biosensor. The biosensor can be used for a maximum of 60 days.

EFFECT: high sensitivity of the biosensor.

2 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: claimed invention relates to application of effective quantity of selenate or its pharmaceutically acceptable salt in methods and compositions for treatment or prevention of neurological disorders, which are are not related to tauopathy. Neurological disorder, which is not related to tauopathy, is not a-synucleinopathy. Effective quantity of selenate or its pharmaceutically acceptable salt delivers over-dietary quantity of selenium. In some implementations invention relates to application of selenate or its pharmaceutically acceptable salt in combination with other means of therapy for application in methods of treatment or prevention of neurological disorders, which are not related to tauopathy.

EFFECT: treatment or prevention of neurological disorders, which are not related to tauopathy.

2 ex, 9 dwg

FIELD: chemistry.

SUBSTANCE: method comprises the following steps: reaction of 3-methylselenopropion aldehyde of formula (I): with an alkali metal cyanide of formula M+CN-, preferably in the presence of an alkali metal bisulphite salt of formula M+HSO3-, where M denotes an alkali metal atom, in a polar protic solvent, to obtain 2-hydroxy-4-methylselenobutyronitrile of formula (II): , hydrolysis of the compound of formula (II) in the medium of hot concentrated sulphuric acid, in a polar protic solvent, to obtain the desirable compound of formula (IV): , or hydrolysis of the compound of formula (II) in the medium of hot concentrated sulphuric acid, in a polar protic solvent, to obtain a compound of formula (III): , which can be hydrolysed in the medium of hot concentrated strong acid to obtain a compound of formula (IV). The compound of formula (IV) can be converted to one of its salts after adding a physiologically acceptable base. The invention also discloses a method of preparing a mixture of 2-hydroxy-4-methylselenobutyric acid and 2-hydroxy-4-methylthiobutyric acid and use thereof, 2-hydroxy-4-methylselenobutyronitrile and use thereof, and a dietary composition.

EFFECT: invention simplifies production of 2-hydroxy-4-methylselenobutyric acid.

17 cl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to N,Se-substotuted of N'-1-(alkyl(hetero)aryl)-N'-1-(alkyl(hetero)aryl)isoselenourea: , where R1 represents alkyl, cycloalkyl, alkenyl, aryl; R2 - hydrogen or lower alkyl; R3, R4 can be similar or different and independently represent aryl, heteroaryl; R5 represents hydrogen or lower alkyl; m=0-2, n=1-3; X represents anion residue of inorganic or organic acid, symbol "*" means possibility of presence of chiral carbon atom.

EFFECT: obtaining N,Se-substotuted of N'-1-(alkyl(hetero)aryl)-N'-1-(alkyl(hetero)aryl)isoselenourea, possessing neuroprotective action.

8 ex

FIELD: medicine.

SUBSTANCE: invention refers to a new product in the form of solution for treatment of benign, virus, premalignant and malignant nonmetastasing skin affections, dysontogenetic lesions of visible mucous membranes, skin mycoses, wrinkle correction and senile pigment spots. The product represents a compound of general formula H2SeO3·x·[R-CXY-(CH2)m-COOH], where x=2-6 prepared from reaction of selenium dioxide and haloid carboxylic acids of general formula R-CXY-(CH2)m-COOH, where R = phenyl, alkyl of general formula CnH2n+1; n=1-5, X=H or Y, Y=F, CI, Br or J, m = 0-10. Besides, the invention concerns a product in the form of solution for treatment benign, virus, premalignant and malignant nonmetastasing skin affections, dysontogenetic lesions of visible mucous membranes, skin mycoses, wrinkle correction and senile pigment spots, containing 0.1-50 wt % of said product, 1-99 wt % of haloid carboxylic acids and the rest - water. Also the invention concerns method of treatment of various skin diseases, including topic applications of the product.

EFFECT: improved clinical effectiveness of the product and method of treatment.

6 cl, 3 dwg, 1 tbl, 68 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of butyric acid of the formula (I): wherein A means carboxyl or (C6-C18)-alkoxycarbonyl; B means ethylene group -CH2-CH2-; R1 means benzyl optionally substituted in phenyl ring, optionally substituted phenyl or optionally substituted pyridyl; Z represents sulfur (S) or selenium (Se) atom; n means a whole number = 0, 1 or 2; R2 represents radical chosen from optionally substituted phenyl, optionally substituted benzopyridine, optionally substituted benzothiazole, optionally substituted quinolyl, optionally substituted naphthyl, optionally substituted triazole and radical of the formula: Also, invention describes methods for synthesis of compounds of the formula (I) and pharmaceutical composition based on thereof. Compound can be used in preparing a medicine designated for treatment or prophylaxis of dyslipidemia and diabetes mellitus.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

9 cl, 1 tbl, 81 ex

The invention relates to medicine and applies to new analogues of fatty acids of General formula (1), pharmaceutical compositions for and methods of treating or preventing obesity, hypertension, fatty infiltration of the liver, multiple metabolic syndrome nutritional compositions and method of improving the quality of such products as meat, milk and eggs

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of butyric acid of the formula (I): wherein A means carboxyl or (C6-C18)-alkoxycarbonyl; B means ethylene group -CH2-CH2-; R1 means benzyl optionally substituted in phenyl ring, optionally substituted phenyl or optionally substituted pyridyl; Z represents sulfur (S) or selenium (Se) atom; n means a whole number = 0, 1 or 2; R2 represents radical chosen from optionally substituted phenyl, optionally substituted benzopyridine, optionally substituted benzothiazole, optionally substituted quinolyl, optionally substituted naphthyl, optionally substituted triazole and radical of the formula: Also, invention describes methods for synthesis of compounds of the formula (I) and pharmaceutical composition based on thereof. Compound can be used in preparing a medicine designated for treatment or prophylaxis of dyslipidemia and diabetes mellitus.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

9 cl, 1 tbl, 81 ex

FIELD: medicine.

SUBSTANCE: invention refers to a new product in the form of solution for treatment of benign, virus, premalignant and malignant nonmetastasing skin affections, dysontogenetic lesions of visible mucous membranes, skin mycoses, wrinkle correction and senile pigment spots. The product represents a compound of general formula H2SeO3·x·[R-CXY-(CH2)m-COOH], where x=2-6 prepared from reaction of selenium dioxide and haloid carboxylic acids of general formula R-CXY-(CH2)m-COOH, where R = phenyl, alkyl of general formula CnH2n+1; n=1-5, X=H or Y, Y=F, CI, Br or J, m = 0-10. Besides, the invention concerns a product in the form of solution for treatment benign, virus, premalignant and malignant nonmetastasing skin affections, dysontogenetic lesions of visible mucous membranes, skin mycoses, wrinkle correction and senile pigment spots, containing 0.1-50 wt % of said product, 1-99 wt % of haloid carboxylic acids and the rest - water. Also the invention concerns method of treatment of various skin diseases, including topic applications of the product.

EFFECT: improved clinical effectiveness of the product and method of treatment.

6 cl, 3 dwg, 1 tbl, 68 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to N,Se-substotuted of N'-1-(alkyl(hetero)aryl)-N'-1-(alkyl(hetero)aryl)isoselenourea: , where R1 represents alkyl, cycloalkyl, alkenyl, aryl; R2 - hydrogen or lower alkyl; R3, R4 can be similar or different and independently represent aryl, heteroaryl; R5 represents hydrogen or lower alkyl; m=0-2, n=1-3; X represents anion residue of inorganic or organic acid, symbol "*" means possibility of presence of chiral carbon atom.

EFFECT: obtaining N,Se-substotuted of N'-1-(alkyl(hetero)aryl)-N'-1-(alkyl(hetero)aryl)isoselenourea, possessing neuroprotective action.

8 ex

FIELD: chemistry.

SUBSTANCE: method comprises the following steps: reaction of 3-methylselenopropion aldehyde of formula (I): with an alkali metal cyanide of formula M+CN-, preferably in the presence of an alkali metal bisulphite salt of formula M+HSO3-, where M denotes an alkali metal atom, in a polar protic solvent, to obtain 2-hydroxy-4-methylselenobutyronitrile of formula (II): , hydrolysis of the compound of formula (II) in the medium of hot concentrated sulphuric acid, in a polar protic solvent, to obtain the desirable compound of formula (IV): , or hydrolysis of the compound of formula (II) in the medium of hot concentrated sulphuric acid, in a polar protic solvent, to obtain a compound of formula (III): , which can be hydrolysed in the medium of hot concentrated strong acid to obtain a compound of formula (IV). The compound of formula (IV) can be converted to one of its salts after adding a physiologically acceptable base. The invention also discloses a method of preparing a mixture of 2-hydroxy-4-methylselenobutyric acid and 2-hydroxy-4-methylthiobutyric acid and use thereof, 2-hydroxy-4-methylselenobutyronitrile and use thereof, and a dietary composition.

EFFECT: invention simplifies production of 2-hydroxy-4-methylselenobutyric acid.

17 cl, 7 ex

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