Agent possessing anti-inflammatory action
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely an agent possessing anti-inflammatory action. The agent possessing anti-inflammatory action contains as active ingredient in the form of a complex prepared of a coelomic fluid of sea urchins containing peptides and amino acids at a certain ratio of the ingredients.
EFFECT: agent possesses a manifested anti-inflammatory effect.
2 cl, 2 tbl, 10 ex
The invention relates to the field of medicine and veterinary medicine, namely to new medicines for the treatment of inflammatory diseases.
A new approach to the problem of correction of disorders of body functions is the creation of medicines on the basis of endogenous biologically active substances. The experimental results of clinical studies indicate that the peptide bioregulators have strong anti-inflammatory, immunomoduliruushimi, antimutagenic and anticarcinogenic properties, which allows their use for the prevention and treatment of systemic inflammatory and immunodeficieny diseases.
The problem of search of new high-performance anti-inflammatory drugs is still very relevant. Use for the treatment of diseases of the spine and joints (rheumatoid and psoriatic arthritis, osteoarthritis, deforming osteoarthritis, gout and other)due to the degeneration and destruction of connective tissue and cartilage, non-steroidal anti-inflammatory drugs (NSAIDs) (phenylbutazone, oxyphenylbutazone, indomethacin, voltaren, ortofen, brufen and others), drugs basic therapy (krizanol, cuprinol, delagil, resochin and others) and cytotoxic immunosuppressants (azathioprine, hlorbutin) leads to serious complications in 30-60% of cases is Yah. This suppressed the biosynthesis of prostaglandins, which negatively affects the functioning of the digestive, cardiovascular and Central nervous system, sensory organs and blood. NSAIDs can impair blood clotting, can cause depression of the stem cells of bone marrow, kidney damage and liver, can retain water and sodium can raise blood pressure, cause headaches, bronchospastic effects and allergic dermatitis [Mosquitoes FI, Kukes V., Setnew A.S. and other Internal diseases. - M.: Medicine, 1990. - 688 S.].
Thus, the creation of new funds with high pharmacological effect with minimal side effects, is an important task. The advantage of creating drugs from raw materials of natural origin is their high therapeutic activity and low toxicity that can be recommended for both treatment and prevention.
At the present stage of scientific and technological development, in conditions of rising raw material "hunger", is most acutely manifested in the field of biologically active substances as the basis of pharmacological preparations, promising research and development of new methods of extraction of biologically active compounds from marine organisms.
Representatives of the type echinoderms are attracted to with the boe sustained attention due to the high regenerative potential. It is known that a crucial role in regenerative processes in various echinoderms play free-living cells of the coelomic fluid - calamity. When the damage to the body echinoderms calamity perform at least a threefold function. First, they quickly aggregate into a damaged area of the wall of the body, thereby restoring the insulation of the internal environment. Secondly, during the regeneration function coelomocytes is the phagocytosis of cellular debris and microorganisms that penetrate into the internal environment of the body in the wound. Thirdly, calamity carry out the synthesis of many biologically active substances, which have protective and regulatory importance. Among the factors synthesized by coelomocyte echinoderms, applies heat shock protein HSP70, nitric oxide, components phenoloxidases protective system, reactive oxygen species, factors such as the homologs of the complement system, lectins, as well as proteins and peptides that regulate cell proliferation and migration. System coelomocytes echinoderms generally regarded as a primitive system of innate immunity, which probably has some degree of homology with the immune system of vertebrates, given the phylogenetic affinity of these groups of organisms.
It is known tool that has adaptogenic action of marine animal of the group, Lucaya sea urchin, crab, sea cucumbers, squid, Beluga whales (Pat. EN 2255747 C2, publ. 27.01.2005).
A method of obtaining biologically active substances from the coelomic cavity of the fish and the reptiles or the abdominal cavity of mammals, which can be used as an adaptogenic tools (Pat. EN 2222338 C2, publ. 27.01.2004).
Extract coelomocytes green sea urchins two antimicrobial peptide strongylocins 1 and 2 with molecular weight of 5.6 and 5.8 kDa (Li S, Haug T, Styrvold OB, J⌀rgensen T⌀, Stensvåg K. Strongylocins, novel antimicrobial peptides from the green sea urchin, Strongylocentrotus droebachiensis. Dev Comp Immunol. 2008: 32 (12): 1430-40).
Known combination of bioactive concentrate from the animal, or marine materials and chondroitin sulfate in combination with Energeticheskie substances (for example, heparin, vitamin E, herbal extracts and other)with antihyaluronidase and anti-inflammatory activity used in the form of injections, ointments, gels and suppositories (Pat. US 5965151, publ. 12.10.1999).
As a prototype of the selected remedy Alflutop produced in Romania. The drug is released in the form of a 1% solution for injection. The active ingredient is bioactive concentrate of small marine fish: sprat (Sprattus sprattus sprattus), the black sea whiting (Odontogadus merlangus euxinus), Pushka black sea (Alosa tanaica nordmanni) and black sea anchovy (Engraulis encrassicholus ponticus), obtained by extraction followed the deproteinization and delipidization. It consists of the glucosaminoglycans, including chondroitin, dermatan sulfate, amino acids, polypeptides and trace elements. The amino acid content is 3.7-12% (Rosoiu N. et al. Original bioactive complexes rich in glycosaminoglycans obtained from small fish // Roum. Biotechnol. Lett., 2008, 13 (5), 3944-3954). Indications for use of Alflutop adults are the primary and secondary osteoarthritis of different localization, osteochondrosis and spondylosis.
The problem solved by this invention is the extension of the range of agents that have anti-inflammatory activity.
The problem is solved by creating tools that have anti-inflammatory action, which contains as an active ingredient complex, derived from coelomic fluid of the sea urchin containing peptides and amino acids by following their quantitative ratio (1-2):(2-6), and does not contain high molecular weight protein contamination (negative reaction to the protein solution triperoxonane acid).
A significant feature of the new complex is the presence in it along with peptides and amino acids, which increases its effectiveness as a dietary means in comparison with other known similar systems. The composition of the obtained complex is directly dependent on the method of obtaining (Pat. RU # 2432956 (C1), publ. 10.11.011), according to which the coelomic fluid add 1.5-3 volume of ethyl alcohol (preferably 2-2 .5 volume), left overnight at a temperature of 3-15°C (preferably 8-12°C) and then filtered the precipitation (protein concentrate); the resulting extract was concentrated to 0.2-0.5 volumes, decanted lipid layer, frozen and freeze-dried, which in turn yields of peptide and amino acid complex.
In peptide and amino acid complex found 20-40% microelemental. Separated fraction of the trace elements did not show the claimed pharmacological properties.
The declared properties of the product shows only at the specified ratio of peptide and amino acid fractions. The selection of the product of individual peptide fractions or individual amino acids with subsequent determination of their pharmacological activity, evidenced a decrease in the severity of effects and not achieving its stated in the present invention, the total anti-inflammatory action.
The technical result provided by the present invention, is the use of peptide and amino acid complex derived from coelomic fluid of the sea urchin, as a means, which has anti-inflammatory effect by inhibiting the production of proinflammatory cytokines (TNF-α) and a decrease in the anti-shudder performance of neutrophils.
Given a set of distinctive features of the proposed complex is not described in literature, and their influence on the achievement of the technical result does not follow from the known level of knowledge in the field of production technology of medicinal drugs.
The technical result of the invention is to secure funds on the basis of peptide and amino acid complex in the form of finished dosage forms for parenteral application with a pronounced therapeutic effect. A new property of peptide and amino acid complex from the coelomic fluid of the sea urchin established by the authors for the first time experimentally.
Thus, the proposed solution meets the criteria of the invention, namely, a "novelty", "inventive step" and "industrial applicability".
The invention is illustrated by, but is not limited to the following examples of specific performance.
Example 1. The solution for parenteral use (in g per 100 g).
Peptide and amino acid complex is 0.001 to 1.0
The preservatives q.s
Water for injection to 100.
In a glass with a volume of 100 ml was placed 70-80 ml of water for injection and the calculated amount of auxiliary substances, stirred until complete dissolution of the components, then make peptide and amino acid complex, mixed and added on the remaining water to 100 g The resulting aqueous solution was filtered and subjected to sterilizing filtration in a stream of nitrogen and then poured into aseptic conditions into ampoules brown glass. The sealed ampoules and receive a stable injectable preparation containing peptide and amino acid complex from the coelomic fluid of the sea urchin.
Example 2. Gel for external use (in g per 100 g).
Peptide and amino acid complex - 0,05
Hydroxyethylcellulose - 1,15
Triethanolamine - 1,37
The glycol - 17,30
Preservatives - 0,13
Purified water is 80.
In a glass with a volume of 100 ml was placed 80 ml of purified water, heated to 70-75°C. add 0,13 g preservatives and stirred until complete dissolution of the components. Then a solution of preservatives cooled to a temperature of 35-40°C. contribute 0.05 g of peptide and amino acid complex, mixed. At the same temperature under stirring in small portions make hydroxyethyl cellulose and continue to mix until a homogeneous composition. After swelling of the polymer contribute triethanolamine is added and stirred for a sufficient time to obtain a homogeneous transparent or slightly opalescense gel. The obtained gel with peptide and amino acid complex Packed in vials with cap and spout.
Example 3. Cream for external use (in g per 100 g).
Peptide and amino acid is fair complex 1,0
Cetylstearyl alcohol - 10,87
Ceteareth-25 - 3,25
Ceteareth-6 - 3,25
Mineral oil - 12,00
Propylene glycol - 7,30
Preservatives - 0,13
Purified water up to 100
In a glass with a volume of 100 ml was placed purified water, heated to 70-75°C. add 0,13 g preservatives and stirred until complete dissolution of the components. At the same time preparing the melt cetylstearyl alcohol. Ceteareth-25, ceteareth-6 and mineral oil at a temperature of 75-80°C. Then to the melt with stirring a solution of preservatives (solution I). Stirring is continued until a homogeneous mass. Peptide and amino acid complex is dissolved in propylene glycol (solution II). Connect the solutions I and II with stirring, cooled to room temperature and stand until thick mass. The finished cream is Packed in aluminium tubes.
Example 4. To 3.4 l coelomic fluid was added to 8 l of ethyl alcohol, left overnight at 10°C and then precipitated is filtered off the precipitate. The obtained extract was concentrated to 1 l, decanted lipid layer containing phospholipids, frozen and freeze-dried. The resulting complex contains 16% of the peptides (method Christian-Warburg), 47% of the amino acids by the reaction with o-phthaldialdehyde), response to protein solution triperoxonane acid negative.
Example 5. To 2.0 liters a whole is practical fluid was added 3 l of ethyl alcohol, left overnight at 10°C and then precipitated is filtered off the precipitate. The obtained extract was concentrated to 0.5 l, decanted lipid layer containing phospholipids, frozen and freeze-dried. The resulting complex contains 12% of the peptides (method Christian-Warburg), 25% of the amino acids by the reaction with o-phthaldialdehyde), response to protein solution triperoxonane acid negative.
Example 6. To 2.5 l coelomic fluid was added 7.5 l of ethyl alcohol, left overnight at 10°C and then precipitated is filtered off the precipitate. The obtained extract was concentrated to 0.5 l, decanted lipid layer containing phospholipids, frozen and freeze-dried. The resulting complex contains 20% of the peptides (method Christian-Warburg) and 60% of the amino acids by the reaction with o-phthaldialdehyde), response to protein solution triperoxonane acid negative.
Example 7. Study of anti-inflammatory activity in models of inflammation "carrageenophyte pouch in rats.
The study design was performed in accordance with Current Protocols in Pharmacology, Models of inflammation: Carrageenan Air Pouch in the rat (UNIT 5.6.2): six days before the start of treatment, rats were placed in CO2the camera to achieve anesthesia for 30 seconds. Sterile syringe with a volume of 20 ml filled with air to create an air bag was introduced 15 m the air subcutaneously into the intracapsular region of the back of the rat. After 3 days to maintain the integrity of the air bag without increasing the wounds were injected with 7.5 ml of air in the same place.
6 days under short-term CO2anesthesia caused inflammation, injecting 3 ml of 0.5% solution carragenine directly into the bag.
The tool of example 1 was administered for preventive scheme, within 6 days, once a day, intramuscularly in a dose of 1.2 mg/kg rats. The first injection is performed immediately after the formation of the air bag, the latter directly for one hour prior to the introduction of carragenine.
Later, 6 hours after injection carragenine animals were subjected to euthanasia in CO2the camera, after which the interior of the bag has introduced 10 ml of physiological saline at room temperature. After a light massage air bag he opened the sagittal section, the exudate is collected in sterile tubes with a volume of 15 ml and centrifuged for 10 minutes at 1860 g and a temperature of +4°C.
For determination of TNFα supernatant was stored at -20°C.
The results of the study are presented in table 1.
It was found that the product prepared according to example 1, causes a decrease to the level of intact animals, the levels of cytokines TNFα, triggering a cascade of inflammatory reactions, and neutrophil - main cells involved in acute inflammation that is vidualistic about reducing the inflammatory process.
Example 8. The antioxidant activity against the DPPH radical.
Not so long ago managed to establish the role of toxic derivatives of oxygen (superoxide anion to oxygen and hydroxyl radical) in the development of inflammatory changes in the joint.
Natural objects often contain complex compounds that have different and multilateral action on the human body. Antioxidants are a class of biologically active substances that bind excessive free radicals, prevent rapid oxidation of lipids and the formation of undesirable oxidation products.
In vitro found that the IC50for funds in example 1 is about 5.9 mg/ml, which is comparable with IC50for drug Alflutop (4,6 mg/ml).
Example 9. Determination of analgesic and anti - (anti-inflammatory) activity on the model of formalin-induced edema in hind paw of the rat.
The circulation and the formation of edema are the main signs of inflammation as emerged during the evolution of the reaction of living tissue to local inflammation. In the formation of acute inflammatory reactions involved numerous mediators and modulators of inflammation, education, and stage-to-stage allocation which reflects not only the nature and intensity of harmful factors is about and duration of its impact. The change in the ratio of nutrients promotes the transition of acute inflammation in chronic phase with a predominance of proliferative component of tissue reaction. In this regard, the evaluation of anti-inflammatory action, it is appropriate to study the action of the product on the basis of peptide and amino acid complex from the coelomic fluid of the sea urchin as in models of acute exudative and chronic proliferative inflammation.
The study design is made in accordance with the guidelines for experimental and clinical study of new drugs (1980, pagination 126-133): in the right hind paw of the rat was injected with 50 μl of water of 2.5%formalin solution in subplantar space. The left rear paw, which was not injected with formalin, served as a control.
The drugs were injected intramuscularly daily for 7 days. The first injection of drugs studies were conducted for one hour before induction of inflammation (formalin test), intramuscularly in the hind left leg. The product of example 1 was injected in a volume of 0.5 ml per animal. The control group was injected intramuscularly with saline in a volume of 0.5 ml.
On the eighth day after the induction of pathology animals were subjected to euthanasia by inhalation of CO2. Immediately after manasarovara was conducted exarticulation in galanopoulos is the first joint and weighing both severed limbs.
Primary data was recorded in the form of quantitative measurements per unit time (minute) two types of response to pain reactions, so-called pattern - bending + shaking and active licking the affected limb in two phases: 0-10 min acute (neurogenic phase) is characterized by a centrally mediated pain with the release of substance P; 11-60 min tonic (inflammatory phase) is characterized by peripheral inflammatory way pain could result in the release of inflammatory mediators. Anti-inflammatory activity was evaluated by the degree of influence on the white blood cell count and erythrocyte sedimentation rate, and swelling of the tissues by measuring the lifetime of the thickness and volume of the paws and posthumous weighing clipped paws.
Experimental data showed that the proposed means of example 1 containing peptide and amino acid complex from the coelomic fluid of the sea urchin, has a pronounced analgesic effect in chronic phase, which is manifested in significantly reducing the number of patterns "bending + shake" by 47% and the decrease in the number of patterns "licking" 65% compared with the control group.
Evaluation of anti-inflammatory effect was conducted on a model of acute inflammation in the paws of rats 3 hours after induction of inflammation formalin. Criterion e is the efficiency (for alternative assessment of the reaction) on the test was considered significant decrease swelling of the legs not less than 30% compared to control.
Studies have shown (table 2)that the tool has quite a pronounced anti-inflammatory effect (a significant decrease in edema of the legs, more than 30% compared with control).
Example 10. Antihyaluronidase activity
Antihyaluronidase activity and the synthesis of hyaluronic acid explain a wide range of pharmacological actions: anti-inflammatory, trophic, and regenerative bio-stimulating activity. Alflutop®injection Antirheumatic drug with pronounced antihyaluronidase activity belongs to the group of chondroprotective ensuring the stability of the cartilage by improving the metabolism of chondrocytes. The mechanism of action of Alflutop caused by blockade of the activity of hyaluronidase during stimulation of hyaluronic acid synthesis, amplification of reparative processes in the cartilage tissue.
Antihyaluronidase activity was measured by the method of Morgan-Elson in our modification. It was found that the product of example 1 containing peptide and amino acid complex from the coelomic fluid of the sea urchin, has antihyaluronidase activity already at a concentration of 0.05%by inhibiting the activity of the enzyme hyaluronidase to 35%. This Alflutop in the same concentration showed almost no antihyaluronidase act shall want to make - inhibition of hyaluronidase was 10%. Its maximum antihyaluronidase activity Alflutop expressed only at a concentration of 1% (inhibition of hyaluronidase was 83%).
Thus, it is found that the proposed remedy containing peptide and amino acid complex from the coelomic fluid of the sea urchin is an anti-inflammatory agent that possesses anti-inflammatory, analgesic, antioxidant and antihyaluronidase activity.
|Anti-inflammatory activity on the model of "carrageenophyte bag"|
|Group||The leukocyte count, ×109CL/l||Lymphocytes, ×109CL/l||Macrophages, ×109CL/l||Neutrophils, ×109CL/l||TNFα, PG/ml|
|Means for app.1||5,6±0,4***||1,1±0,1||0,94±0,21*||3,6±0,4***||78,0±30,5**|
* - statistically significant difference compared with the intact group criterion Student, at p<0,05
** - statistically significant difference compared with the control group by criterion Student, at p<0,05
|Action products containing peptide and amino acid complex from the coelomic fluid of the sea urchin, the severity of paw edema in rats during the development of acute exudative inflammation (M±m)|
|Group||Observation period, days.||The severity of edema||The criterion for the effectiveness of anti-inflammatory activity (%)|
|Control (volume paws, ml)||0||0,0±0,0||100|
|Means for app.1 (volume paws, ml)||0||0,0±0,0||-||-|
|Note: * - significance of differences from control, p<0,05|
1. The agent with anti-inflammatory action, which contains as an active ingredient complex, derived from coelomic fluid of the sea urchin containing peptides and amino acids by following their quantitative ratio (1-2):(2-6), and does not contain high molecular weight protein contamination (negative re the Ktsia protein solution triperoxonane acid).
2. The tool according to claim 1, characterized in that it can be made in the form of solution for injection, gel or cream.
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is the use of L-carnosine for making a nanopreparation having antihypoxic and antioxidant activity combined with a combination of substances selected from the group of phospholipids, non-polar lipids in the following ratio, wt %: L-carnosine - 1.1-1.2, non-polar lipids such as triglycerides, cholesterol, free fatty acids, DL-α-Tocopherol - 1.2-2.5, phospholipids such as phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin - 95.3-96.3 for preparing a drug having antihypoxic and antioxidant activity. The drug can be presented in the form of liposomes containing L-carnosine.
EFFECT: invention provides higher stability of L-carnosine and its lifetime up to three days with underlying higher effectiveness in small doses, as well as to improve the cerebral ischemia tolerance, the recovery after acute hypoxia and to increase the antioxidant status of the brain tissue.
3 cl, 4 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to a method for preparing a carbon sorbent with the antibacterial properties, and to the carbon sorbent with the antibacterial properties prepared by this method. The declared method involves impregnation of the carbon hemosorbent granules in an initiator solution in N-vinylpyrrolidone at pH 7.0-7.5 and a residual pressure of 15-20 mm Hg. The hemosorbent : initiator solution in N-vinylpyrrolidone ratio is 1:1.4-2.0. Then the temperature is raised to 65-75°C, kept at that temperature for 0.5-8 hours in an inert medium and washed in water from the residual monomer at room temperature.
EFFECT: carbon sorbent with the antibacterial properties prepared by the specified method represents the round granules, contains polyvinylpyrrolidone in an amount of 4,5-5,5% and is characterised by a specific surface adsorption of less than 50 m2/g and total pore volume of less than 0,30 cm3/g.
2 cl, 2 tbl, 1 dwg, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to an antioxidant containing a cyclolanostan derivative selected from 9,19-cyclolanostan-3-ol and 24-methylene-9,19-cyclolanostan-3-ol, and a lophenol derivative selected from 4-methylcholest-7-en-3-ol, 4-methylergost-7-en-3-ol and 4-methylstigmast-7-en-3-ol, in the concentration of min. 0.0001 wt %, as an active ingredient. The invention also concerns a method for preparing the specified antioxidant. The antioxidant may be used as a drug preparation, a food or a beverage, a food additive, a drug preparation for topical skin application.
EFFECT: mentioned antioxidant provides the inhibition of lipid peroxide formation.
28 cl, 2 tbl, 2 ex
SUBSTANCE: invention refers to a formulation of (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide possessing modulatory activity with an adequate effect, to a pharmaceutical substance of (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide containing: 2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide - min. 99.0% and max. 100.5% at a dry substance; individual accompanying impurities, either single or total - max. 0.2%; the residual quantities of organic solvents, either single or total - max. 3000 ppm. The invention also refers to a method for preparing a pharmaceutical substance differing by the fact that the raw material is purified, crystallised, stabilised by treating the formulation in demineralised water that is followed by isothermal crystallisation from propanol, and drying. The invention also refers to compositions for internal and external application.
EFFECT: invention provides higher efficacy, safety, stability and width of therapeutic application.
55 cl, 3 dwg, 80 tbl, 27 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is the use of 3,5-seco-4-norcholestan-5-one oxim-3-ole, or one of its acceptable acid addition salts, or one of its esters, or one of its acceptable acid ester addition salts as an antioxidant. What is shown is that the compound possesses systemic activity per os; it does not absorb visible UV-lights and interact with common sun protection products; it is presented in the form of a crystalline powder and keeps well at room temperature for at least 12 months; it is colourless, tasteless and odour-free.
EFFECT: properties make the compound to be preferred in cosmetic and food fields, and as antioxidant preserving agent used in particular in cosmetic, food and pharmaceutical products.
9 cl, 1 dwg
SUBSTANCE: invention relates to amides of 2-(2-hydroxyphenylthio)acetic acid, having antioxidant activity, which are phenol derivatives having in the ortho-position a thioacetamide fragment of general formula: , where R1=H, Me; R2=H, CH2COOMe, CH(Me)COOMe, CH(Et)COOMe, CH(i- Pr)COOMe, CH(i-Bu)COOMe, CH(Bn)COOMe, CH(4-HOBn)COOMe, CH(CH2CH2SMe)COOMe, CH2COOH, CH(Me)COOH, CH(Et)COOH, CH(i- Pr)COOH, CH(i-Bu)COOH, CH(Bn)COOH, CH(4-HOBn)COOH, CH(CH2CH2SMe)COOH, CH2CH2CH2CH2CH(MH2)COOH, CH2CH2CH2CH(NH2)COOH; R3=H; R2R3=CH2CH2N(C(O)CH2S(2-OHPh))CH2CH2; R2,R3=CH2CH2CH2CH(COOMe); R2,R3=CH2CH2CH2CH(COOH). The invention also relates to a method of producing the said compounds.
EFFECT: compounds have antioxidant activity, which enables use thereof to reduce the rate of peroxide oxidation of lipids.
2 cl, 3 tbl, 8 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely a therapeutic preparation of male larval bees having immunomodulatory action. The therapeutic preparation of male larval bees having immunomodulatory action possessing a yellow powder prepared by grinding male larval bees to a homogenous biomass added with an aqueous-alcohol propolis extract and fine pollen; it is followed by freezing the paste and sublimation drying in a vacuum chamber in the certain environment.
EFFECT: preparation described above shows evident immunomodulatory action.
SUBSTANCE: compound is a pyrrolidine derivative having a fragment of a sterically hindered phenol, having general formula: where R1 denotes H, Me, Et; R2 denotes Me, Et, i-Pr, i-Bu; Ar denotes Ph, 2-HalPh, 3-HalPh, 4-HalPh, (where Hal denotes F, Cl, Br, I), 2,6-diMePh, 2,3,5,6-tetraFPh, 2-MeOPh, 3-MeOPh, 4-MeOPh, (naphthalen-1-yl), (naphthalen-2-yl), 2-NO2PH, 3-NO2Ph, 4-NO2Ph. The compounds are obtained by mixing a solution of azomethine of formula: where values of R1, R2 are given above, with N-substituted malemide in air and reaction thereof is induced by catalytic amounts of N-tert-butoxycarbonyl derivatives of alpha-amino acids (glycine, alanine, phenylalanine), followed by concentration of the organic phase at low pressure, and cleaning the residue by chromatography on silica gel using CHCl3/MeOH as the eluent.
EFFECT: prolonged antioxidant activity.
2 cl, 2 tbl, 9 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is an antihypoxic agent differing by the fact that it represents a complex compound of divalent zinc substituted by 3-hydroxypyridine and diorganodichalcogenide - hexakis(3-hydroxy-2-ethyl-6-methylpyridinato)[tris(dibenzylselenido)dizinc(P)pentadeca-semihydrate of formula [Zn(II)]2A6B3·15.5H2O (the same πQ1983). [Zn(II)]2A6B3·15.5H2O wherein A: B:
EFFECT: efficacy of the reference antihypoxants (antisol, bemityl) is significatly second to πQ1983 by all resistance criteria to acutely developing hypoxia; unlike the reference antihypoxants, πQ1983 is still effective after the intake; reduces rectal temperature, slows down heart rate, reduces respiratory rate and depth, as well as body oxygen consumption; prolongs a period of cortex activity in acutely developing hypoxic condition.
4 dwg, 3 tbl
SUBSTANCE: invention refers to medicine and aims at treating necrotic ulcers of oral mucosa in patients with multiple myeloma. Luminal-dependent chemiluminescence of oral fluid is conducted to determine fluorescence light sum and maximum flash. If the light sum value is within the range of 1.02 to 6.6 standard units, and the maximum flash value is 0.7 to 2.5 standard units, the toothpaste Lacalut fluor is used 2 times a day and solcoseryl dental adhesive paste 4 times a day after meals and before bedtime to relieve symptoms completely. The light sum value 8.3 to 13.5 standard units and the maximum flash value 3.4 to 4.2 standard units, the toothpaste Colgate total propolis is used 2 times a day and the film preparation Oblecol three times a day to relieve symptoms completely.
EFFECT: use of the invention reduces a length of epithelisation of necrotic ulcers of oral mucosa.
SUBSTANCE: invention relates to medicine, particularly to paediatrics, X-ray surgery, paediatric surgery, and concerns the hemostatic disorder correction in the children with hepatic hemangiomas. For this purpose, three days before the endovascular embolisation of the hepatic hemangioma, Protromplex 600 - a preparation of plasma factors II, VII, IX, X is administered intravenously in a dose of 20 IU/kg at max. 2 ml/min; on the first postoperative day, Protromplex is administered in the same dose, and further Fraxiparine is administered subcutaneously in a dose of 158 IU/kg of body weight for 3 days.
EFFECT: presented dose schedule of the preparations provides the effective and safe correction of hemostatic disorders in the children with hepatic hemangiomas due to normalising the internal and external mechanisms of blood coagulation and fibrinolysis.
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to introducing dairy fat or an analogue thereof, optionally with at least one additional therapeutic factor, preferentially with lactoferrin or lactoferrin containing a metal ion, preferentially lactoferrin containing iron, preferentially bovine lactoferrin containing iron or a functional version thereof containing metal ions or a functional fragment to inhibit the tumour formation or growth, to maintain or improve one or more parameters, such as leukocyte count, erythrocyte count, or myelocyte count, to reduce the manifestations of cachexia, mucositis and anemia, to stimulate the immune system and to treat or prevent a malignancy and malignant symptoms, and side effects of treating the malignant tumour. Methods and therapeutic use according to the invention may be implemented by the use of a diet (in the form of food products or food additives), nutrient or pharmaceutical composition. There are also presented compositions applicable in the methods according to the invention.
EFFECT: group of inventions provides the higher clinical effectiveness or prevention of the malignant tumour or its symptoms.
39 cl, 7 tbl, 21 ex
SUBSTANCE: invention relates to medicine, namely to gynecology, and can be used for treatment of benign diseases of cervix. For this purpose rectal viferon suppositories are preliminarily introduced for ten days in dose 1000000 IU. After that, cervix is treated with solcovagin solution with 30-60 sec exposure 1-2 times during the day on the 5-7 day of the following menstrual cycle. After 4-5 days medication viferon is applied in form of gel on cervix in dose 1-2 applications per day, course length being 7-8 days.
EFFECT: method makes it possible to increase treatment efficiency due to certain successive combined application of mutually complementing each other as to mechanism of action medications, which leads to acceleration of healing process and provides etiopathogenic mechanism of treating benign diseases of cervix.
SUBSTANCE: there are presented versions of the peptide (A) or (B) with the amino acid sequence of SEQ ID NO: 1 or 2 respectively presented in this description. The peptide has activity to induce a cytotoxic T-cell when an antigen-presenting cell carrying HLA-A2 (A*0201) presents it. There are described the versions of the peptide antibodies prepared by immunisation by the proper peptide. There are presented: an agent, methods for inducing: a cytotoxic (killer) T-cell, an antigen-presenting cell, CDH3 expressing cancer immunity; as well as a method of treating CDH3 expressing cancer on the basis of the peptide. What is presented is an isolated cytotoxic T-cell induced by said method on the basis of the peptide. There are described: the antigen-presenting cell and exosome presenting the complex containing the peptide and HLA-A2 (A*0201).
EFFECT: higher effectiveness of the use of the invention in treating CDH3 expressing cancer.
15 cl, 5 dwg, 2 tbl, 5 ex
SUBSTANCE: disclosed is a method of producing pure crystalline D-isoglutamyl-D-trytophan which involves a step of removing protection from essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan or diester thereof to yield essentially pure D-isoglutamyl-D- tryptophan. An amorphous ammonium alt of D-isoglutamyl-D- tryptophan (1:1) is also disclosed. Also disclosed is a method of producing a pure monoammonium salt of D-isoglutamyl-D-tryptophan from essentially pure N-tert-butoxycarbonyl-D- isoglutamyl-D-tryptophan. Disclosed is a compound H-D-Glu-(γ-D-Trp-OR2)-α-OR1 and pharmaceutically acceptable acid addition salts thereof. Disclosed is a solid pharmaceutical composition and use thereof as an immunodepressant or anti-psoriasis agent.
EFFECT: improved method.
51 cl, 14 ex, 8 dwg, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry and represents a thermoreversible, thermoplastic pharmaceutical composition comprising: (a) a biologically active botulinum toxin and (b) a thermoplastic poloxamer wherein poloxamer stabilises botulinum toxin so that botulinum toxin keeps biological activity with botulinum toxin release from the pharmaceutical compositions in vivo, wherein the pharmaceutical composition can be prepared with no substances contained in blood, such as albumin and therefore without any infectious substances of blood components, such as prion.
EFFECT: invention provides high stability and high percentage of the toxin activity recovery.
18 cl, 6 ex
SUBSTANCE: invention refers to medicine and is intended to prevent the age-related changes of hepatic tissue in rats experimentally. What is used is the biologically active additive "Rekicen RD" added to the diet of inbred laboratory rats at the age of two years old. A dose is 2 grams a day for 14 days.
EFFECT: method enables improving the hepatic tissue state ensured by increasing the regeneration activity of hepatocytes.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine and concerns a pharmaceutical composition in the form of a capsule either acid-resistant, or with an acid-resistant coating containing recombinant interferon specified from alpha, beta, gamma recombinant interferon; a stabiliser of the biological, physical and chemical properties specified in low-molecular polyvinylpyrrolidone, macrogol 400-12000, propylene glycol, hydroxypropyl methylcellulose; a stabiliser of microbial contamination resistance specified in dexamethasone, diflorazone, boric acid, phospholipids, cyclodextrins, calcium stearate, and/or magnesium stearate, a thickly-forming base specified in hydrophilic, lipophilic, hydrophilic-lipophilic bases.
EFFECT: invention provides a higher therapeutic effect and prolonged shelf life.
3 cl, 4 ex
SUBSTANCE: invention refers to veterinary science, and aims at treating viral diseases in animals. What is declared is a composition for treating viral diseases in animals, containing two subtypes of vertebrate recombinant interferon mixed in equal molar proportions.
EFFECT: use of the declared composition enables ensuring the substantial increase of the therapeutic effect of recombinant interferons and minimising the potential adverse effects associated with their use.
SUBSTANCE: invention refers to medicine. What is declared is an agent inducing the hematopoietic stem cell differentiation into thrombocytes, representing a recombinant human cyclophilin A (rhCfA).
EFFECT: invention provides the extended range of products for specified application.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely to a method for preparing a pharmaceutical preparation for treating inflammatory intestinal diseases. The method for preparing a pharmaceutical preparation for oral administration for inflammatory intestinal diseases, particularly chronic inflammatory gastrointestinal diseases containing a storage-stable suspension of vital eggs of the parasitic, non-pathogenic to humans helminthes Trichuris suis, which involves preparing the suspension of helminth eggs in an acid at pH max. 2 at the first stage; at the following stage, the pH value is increased to min. 4, and a pharmacologically acceptable preserving agent is added. A pharmaceutical preparation for oral administration for inflammatory intestinal diseases, particularly chronic inflammatory intestinal diseases. The use of the pharmaceutical preparation for oral administration for inflammatory alimentary diseases, particularly chronic inflammatory alimentary diseases.
EFFECT: method enables more effective storage of the produced preparation of vital helminth eggs not accompanied by dangerous intergrowths of fungal spores and yeast propagation.
11 cl, 3 tbl, 5 ex