Immunomimetic peptide of chemical cancerogens with specific interaction effect on antibodies of benzo[α]pyrene and benzo[α]anthracene
SUBSTANCE: peptide is obtained from phage peptide library including set of static peptides with length of 12 aminoacid residues, by affine selection of phage clones containing peptide capable of specific linking to antibodies of benzo[α]pyrene and benzo[α]anthracene. Peptide displays specific interaction effect on antibodies of benzo[α]pyrene and benzo[α]anthracene and features molecular weight of 1.3 kDa and registered aminoacid sequence LHLPHHDGVGWG encoded by nucleotide sequence SEQ ID NO:1.
EFFECT: application in medicine as a base for peptide medicine development for immunologic prevention of malignant tumours of humans.
4 dwg, 3 ex
The invention relates to biotechnology, genetic and protein engineering, specifically to the peptide with the ability to interact specifically with antibodies against benzo[α]pyrene and Benz[α]anthracene.
Chemical carcinogens, being of low molecular weight substances, not able to induce an immune response. At the same time, immunization of animals with conjugates of the protein with the carcinogen as hapten leads to the appearance of specific antibodies and a significant inhibition of carcinogenesis [1, 2]. However, the presence of carcinogenic substances in the composition of such conjugates excludes their use as vaccines, as a carcinogen retains the ability to induce tumors.
The most closest to the claimed peptide-immunometric by function - prototype - is a monoclonal antiidiotypic antibody with internal immunological" benzo[α]pyrene, with the ability to interact specifically with antibodies against benzo[α]pyrene . Known antibody was prepared as follows. Conjugate benzo[α]pyrene were immunized rabbit and received 1 antibodies specific to benzo[α]pyrene. Antibodies 1 were immunized mice received hybridoma producing monoclonal antiidiotypic 2 antibodies, specific antibodies 1. Monoclonal antiadiotipiceskih 2 antibodies immunodeficiency who were seravalli rats then they were introduced benzo[α]pyrene. As a result, the rats were observed inhibition of tumors induced by benzo[α]pyrene, these tumors grew slower, and the life expectancy of rats was increased compared with control (without prior immunization with monoclonal antiadiotipiceskih antibodies 2). Thus was shown the principal possibility of inhibition of carcinogenesis by immunization of animal protein molecules that mimic the immunogenic properties of conjugates of carcinogen-protein and does not contain carcinogenic as hapten.
However antiidiotypic antibodies have drawbacks that prevent their use as anti-carcinogenic vaccines, and hybridoma technology has limitations for its use in order to receive any vaccines. When immunization alien immunoglobulins can be formed side individule and antihistimine antibodies that can lead to allergic and autoimmune complications, and hybridoma technology is characterized by high complexity and costs.
One way of overcoming these problems is to use peptides that mimic the immunogenic properties of conjugates of carcinogen-protein. A fundamentally new approach to the creation of anticarcinogenic vaccines is to use f the debt peptide libraries. It is possible to obtain peptides-immunogenetic chemical carcinogens that do not contain any carcinogen that can induce a tumor or related antigenic determinants that can cause adverse pathological complications.
An object of the invention is to obtain peptide-immunogenetic chemical carcinogens, specifically interacting with antibodies against benzo[α]pyrene and Benz[α]anthracene, and the determination of its amino acid sequence.
The inventive peptide derived from ragovoy peptide library containing a set of statistical peptides with a length of 12 amino acid residues (S.A.), by affinity selection of those phage clones that contain the peptide can specifically bind with antibodies against benzo[α]pyrene and Benz[α]anthracene. The peptide library displayed on the surface of phages in the composition of the minor envelope protein pIII .
Amino acid composition of the peptide-immunogenetic, located on the surface of phage particles was determined by sequencing of phage DNA using a modified method of Sanger  encodes a peptide region. The inventive peptide has a molecular mass of about 1.3 kDa and amino acid sequence LHLPHHDGVGWG encoded by the nucleotide sequence of SEQ ID NO: 1, are presented in figure 1.
With electrovanne of ragovoy peptide library peptide with the amino acid sequence LHLPHHDGVGWG has the ability to specifically interact with antibodies against benzo[α]pyrene and Benz[α]anthracene in vitro, and to induce the formation of antibodies against benzo[α]pyrene in vivo.
Thus, for the first time obtained a peptide specifically interacts with antibodies against benzo[α]pyrene and Benz[α]anthracene in vitro and is able to induce the formation of antibodies against benzo[α]pyrene in vivo.
The invention is illustrated by the following specific examples of its implementation.
Example 1. Way for affinity selection of peptides that specifically interact with antibodies against benzo[α]pyrene and Benz[α]anthracene.
The conjugates of benzo[α]pyrene and Benz[α]anthracene with BSA and the yeast gexokinaza synthesized by the method of covalent binding of the aldehyde group of the hapten with the amine groups of carrier protein .
To obtain monoclonal antibodies against benzo[α]pyrene mice of BALB/c mice subjected to immunization with a conjugate of benzo[α]pyrene-BSA. Hybridoma get through merge cells, mouse myeloma Sp2/0 and immune splenocytes of the mouse, according to the Protocol described by Kohler and Milstein . The obtained monoclonal antibodies cross-react with the conjugates of benzo[α]pyrene-BSA and Benz[α]anthracene-BSA.
To obtain polyclonal antibodies rabbits subjected to immunization with a conjugate of benzo[α]pyrene-BSA. From produce antisera monospecific antibodies against benzo[α]pyrene and Benz[α]anthracene using affinity chromatography on columns α]pyrene-glucokinase-Sepharose 4B and Benz[α]anthracene-glucokinase-Sepharose 4V.
The obtained monoclonal antibodies against benzo[α]pyrene and Benz[α]anthracene dissolved in phosphate-buffered saline, containing 137 mm NaCl; of 2.68 mm KCl; 8,1 mm Na2HPO4·12H2O; 1,47 mm KN2PO4to a final concentration of 10 μg/ml of the resulting solution of antibodies sensibiliser sterile polystyrene Petri dishes. The nonspecific binding sites blocked with 0.5%solution of BSA in phosphate-buffered saline. The original phage peptide library, diluted in phosphate-buffered saline to a final concentration of 2·1011CFU/ml (kolonialismus units/ml), incubated with the immobilized antibody for one hour at room temperature. Then Petri dishes washed with phosphate-saline buffer containing Tween 20. The elution of bound peroxidase antibody bacteriophages carried out with a solution of glycine buffer (0.2 M Glycine-HCl pH 2.2, 0.1% BSA) for 10 min with gentle rocking. Elyuirovaniya fraction is neutralized with 150 μl of 1 M Tris-HCl pH 9.1 and determine the titer of the phage. The resulting population of bacteriophages containing contacting a monoclonal antibody against benzo[α]pyrene and Benz[α]anthracene peptides, amplified by infection of cells of E. coli JM103 . Isolated phages and spend the second and third rounds of affinity selection as described above.
After the third round of selection receive individual phage to onii, which is used for producing single-stranded DNA and phage ELISA. Sequencing of the DNA insert carried out according to the modified method of Sanger .
Example 2. The study of peptide-immunogenetic-specific binding of antibodies against benzo[α]pyrene and Benz[α]anthracene in vitro.
To characterize the ability of peptide-immunogenetic specifically bind to a monoclonal antibody against benzo[α]pyrene and Benz[α]anthracene spend ELISA with serial dilution of phage exhibiting on its surface a peptide-immunogenetic from 1011up to 106CFU/well. In wells of polystyrene 96-well plates absorb monoclonal antibodies against benzo[α]pyrene and Benz[α]anthracene, diluted to a final concentration of 5 μg/ml in phosphate-buffered saline. The nonspecific binding sites blocked with 0.5%solution of BSA in phosphate-buffered saline. After that, the wells are incubated with the analyzed clones of phage diluted in phosphate-buffered saline containing 0.05% Tween 20, 0.5% BSA. Bound peroxidase bacteriophages, exhibiting on its surface a peptide-immunogenetic, reveal peroxidase-conjugated rabbit antibodies against total proteins M13mp8. The absorption solution in the wells was measured at a wavelength of 350 nm. To control for nonspecific binding of the use of amplified phage M13m8. The results of the specific binding of peptide-immunogenetic in the composition of the pIII protein of the phage with monoclonal antibodies against benzo[α]pyrene and Benz[α]anthracene presented in figure 2, where the abscissa axis indicate the dilution of the phage, and the ordinate axis is the optical density (OD 350); curve 1 - binding M13mp8 with monoclonal antibodies against benzo[α]pyrene and Benz[α]anthracene; curve 2 - binding peptide-immunogenetic in the composition of the pIII protein of the phage with monoclonal antibodies against benzo[α]pyrene and Benz[α]anthracene.
Using Western blot analysis examined the binding of peptide-immunogenetic in the composition of the pIII protein onselectionchange clone with monoclonal and monospecific polyclonal antibodies against benzo[α]pyrene and Benz[α]anthracene and monospecific polyclonal antibodies against benzo[α]anthracene. After electrophoretic separation of recombinant and wild phage into its constituent proteins in 15%SDS page with sodium dodecyl sulfate spend their transfer to nitrocellulose membrane, which was then incubated with monoclonal antibodies and monospecific polyclonal antibodies against benzo[α]pyrene and Benz[α]anthracene (5 µg/ml). Contacting the target peptide antibodies is detected using peroxidase conjugates of antibodies against total IgG mouse or rabbit followed their krasivyi the m The Western blot turns specific binding of peptide-immunogenetic presented on figure 3, where I is the binding of monoclonal antibodies against benzo[α]pyrene and Benz[α]anthracene, II - the binding of monospecific polyclonal antibodies against benzo[α]pyrene, III - the binding of monospecific polyclonal antibodies against benzo[α]anthracene; 0 - linking pIII protein of native phage M13mp8 with antibodies against benzo[α]pyrene and Benz[α]anthracene; 1 - binding peptide-immunogenetic in the composition of the pIII protein with antibodies against benzo[α]pyrene and Benz[α]anthracene.
Example 3. The study of the obtained peptide-immunogenetic on the ability to induce the formation of antibodies against benzo[α]pyrene in vivo.
Three groups of ICR mice subjected to immunization intraperitoneally three different antigens (conjugate benzo[α]pyrene-BSA, native phage M13mp8 and peptide-immunogenetics in the composition of the pIII protein of the phage) three times every 2 weeks. The first immunization hold antigen in the mixture with complete adjuvant-blockers, subsequent antigen with incomplete adjuvant's adjuvant. The serum of the mice tested in ELISA for the presence of specific antibodies in 3 days after the final immunization. For this purpose, the wells of polystyrene tablets sensibiliser conjugate benzo[α]pyrene-BSA (5 μg/ml)diluted in podslashennoyi water. Block and incu is irout with samples of blood sera of immunized mice. Bound peroxidase antibodies reveal peroxidase-conjugated rabbit antibodies against total mouse Ig. The results of ELISA of serum antibodies to benzo[α]pyrene are presented in figure 4, where the abscissa axis is the serum dilution, and the ordinate axis is the optical density (OD 350); curve 1 - immunization native phage M13mp8 (negative control); curve 2 - immunization with peptide-immunogenetics in the composition of the pIII protein of the phage; curve 3 - immunization benzo[α]pyrene-BSA (positive control).
Thus, the specific peptide-immunogenetic chemical carcinogens, specifically interacting with antibodies against benzo[α]pyrene and Benz[α]anthracene and is able to induce the formation of antibodies against benzo[α]pyrene after immunization in vivo. Such peptide-immunogenetic can be successfully used as a hapten-specific component in the method of immunoassay of antibodies specific to chemical carcinogens. Replacement conjugate carcinogen-protein to the peptide-immunogenetic eliminates carcinogenic potential threat in the production and use of analytical test systems. On the basis of peptide immunogenetical you can also create complexes with known immunomodulatory agents (adjuvants)that have been approved for clinical use in order to enhance the immune response against chemical Kahn is erogeny (formation of antibodies against chemical carcinogens), i.e. for prophylaxis of malignant tumors in humans.
Sources of information
1. Curtis G.L., Ryan W.Z., Stenback F. Antibody stimulation of benzo[α]pyrene carcinogenesis. Cancer Lett. 1978, v.4: p.223-228.
2. Moolten F.L., Schreiber Century, Rizzone A. Protection of mice against 7.12-dimethylbenz(a)antracene-induced skin tumors by immunization with a fluorinated asnalog of carcinogen. Cancer Res. 1981, v.41: p.452-459.
3. Chagnaud J.L., Faiderbe S., Geffard M. Effects of a monoclonal anti-idiotypie antybody, internal image of benzo(α)pyrene, on rat sarcomas. Acad. Sci. Paris, Sciences de la vie. 1993, v.316: p.1266-1269.
4. Scott J.K., Smith G.P. Searching for peptide ligands with an an epitope library. Science. 1990, v.249: p.386-390.
5. Kretz, K., W. Callen, V. Hedden Cycle sequencing. Methods of Enzimology. V.154: p.527-536.
6. RF patent 2141114 "a method of obtaining a conjugate of the hapten-protein", CL G01N 33/50, authors: Kostenko M.V., Glushkov A., publ. 10.11.1999.
7. Kohler g, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. Nature. 256: p.495-497.
8. Glushkov A.N., Kostyanko M.V., Anosova T.P., Polenok E.G., Mun S.A., Anosov M.P., Cherno S.V. Immunological images of polycyclic aromatic hydrocarbons. Experimental neology. 2006. V.28: p.93-176.
9. Brian K.Kay, Jeremy Kasanov, Montarop Yamabhai. Screening phage-displayed combinatorial peptide libraries. Methods. 2001. V.24: p.240-246.
Peptide-immunogenetic chemical carcinogens derived from ragovoy peptide library having a molecular weight of about 1.3 kDa, with the ability to interact specifically with antibodies against benzo[α]pyrene and Benz[α]anthracene having the amino acid sequence LHLPHHDGVGWG encoded by the nucleotide sequence of SEQ ID NO: 1.
SUBSTANCE: present invention relates to genetic engineering, more specifically to obtaining anticoagulative protein extracted from nematodes (NAP) and can be used in medicine. To obtain a medicinal preparation based on NAP, methanotrophic yeast host cells are cultured, encoding rNAPc2 or rNAPc2/praline, until attaining the desired cell density. NAP is then extracted from the said yeast host cells through cation-exchange chromatography on an expanding layer. To purify the NAP medicinal preparation, hydrophobic-interaction chromatography is used. NAP is extracted and purified at pH levels below 4.
EFFECT: simple and more efficient method of obtaining anticoagulation proteins from nematodes.
25 cl, 8 dwg, 7 tbl, 6 ex
SUBSTANCE: claimed are expression vectors for obtaining IL-21 in E.coli cells. IL-21 coding nucleotide sequence, included in composition of novel vectors, contains modifications aimed at optimisation of codons and secondary mRNA structure for translation in E.coli. As a result of transformation with claimed vector structures E.coli strains suitable for industrial scale application have been obtained. Methods of wide scale IL-21 production which use said strains have been elaborated, allowing to obtain more than 1g/l of recombinant cytokine.
EFFECT: novel compounds possess useful biological properties.
14 cl, 1 dwg, 12 tbl, 19 ex
SUBSTANCE: hybrid protein - human insulin precursor consists of N-end fragment of human gamma-interferon connected through peptide linker with amino acid sequence of human proinsulin. Recombinant human insulin is obtained by cultivation of Escherichia coli JM109/pHINS11 strain-producer, carrying plasmid pHINS11, isolation of inclusion bodies and their dissolving in buffer which contains urea and dithiotreitole. Then hybrid protein re-naturation, sedimentation of admixture compounds, purification of re-naturated hybrid protein by ion-exchanging chromatography, combined fermentative hydrolysis of hybrid protein with tripsin and carbopeptidase B are carried out. At the last stage insulin purification with cation-exchanging chromatography and method of highly efficient reverse phase liquid chromatography are carried out.
EFFECT: simplification of obtaining highly purified recombinant human insulin and increase of its output.
6 cl, 1 dwg, 4 tbl, 5 ex
FIELD: pharmacology; biotechnology.
SUBSTANCE: invention concerns biotechnology area, in particular to the gene-engineering way providing mass production multimeasured recombinant human Mannan-Binding Lectin (MBL), also can be used in the biomedical industry. The offered way includes a) a cultivation stage of cells-owners lines CHO, transfectant with a recombinant vector pMSG-MBL, containing sequence of human MBL coding area, and b) a clearing stage of the recombinant protein. Thus at the first stage preferably use new cellular line CHO MBL D1-3, deposited with the Korean collection of sample cultures at number KCTC 10472BP which is cultivated in a protein-free medium with bioreactor use, and on the second selective clearing of high-molecular form MBL of medium cultivation is spent, providing separation of samples with the help anion exchange chromatography, their drawing on a column with an immobilised MBL-binding protein on it , in particular with glycosilated protein of a cover of a virus pre-S, in the presence of ions of calcium and the subsequent elution using a buffered solution with EDTA or EGTA.
EFFECT: high output of functionally active product opens possibilities of its application by working out of therapeutic agents for treatment of virus, bacteriemic or fungoid infections.
6 cl, 11 dwg, 9 ex
SUBSTANCE: invention relates to biotechnology, in particular to production of hormones and can be used for culturing invertebrates. Gonadotrophin, selected from the invertebrate Asterina pectinifera is a peptide with molecular weight 4500-4900, it has two subunits, the protein structure of which is combined with SS-bridges, formed between residues of SH cysteine contained in the subunits.
EFFECT: interfusion and oxidation of these two subunits after synthesis allow producing gonadotrophin having gonadal promoting activity.
4 cl, 8 dwg, 1 tbl, 2 ex
FIELD: chemistry; biochemistry.
SUBSTANCE: invention relates to biotechnology, in particular to hepatic cells production, and may be used in medical science. From the whole liver or resected part thereof, a cell population enriched with living cells of human liver, including hepatic stem cells/precursor cells, is obtained. Cell population contains functional hepatocytes and biliary cells expressing cytokeratin 19 (CK19), but not expressing albumin, as well as hepatic stem cells/precursor cells 9 to 13 mcm in diameter and expressing EP-CAM, CD 133 markers. Resulting cell population is used for hepatotherapy.
EFFECT: production of living population of hepatic cells sufficiently efficient for regeneration.
60 cl, 16 dwg
FIELD: medicine; biotechnologies.
SUBSTANCE: adenoviral vector carrying in the genome structure a human lactoferrin gene, administer into an allantois of the 9-10 day chicken embryoses. The subsequent planting is performed by egg incubation at temperature of 37°C within 70-75 hours. Then allocate the recombinant protein from the allantoic liquid of a chicken embryos.
EFFECT: depression of expenses and obtaining simplification of the recombinant human lactoferrin.
FIELD: medicine, biotechnologies.
SUBSTANCE: invention can be used for obtaining of the factor VII of blood coagulation. Derivatives of a polypeptide of the factor VII with amino-acid replacements Q250C, R396C and P406C are obtained or with Cysteinum attached to the S-end of native sequence of the factor VII. Obtain derivatives with use of transgene technologies in eucariotic cells-owners of mammals.
EFFECT: invention allows obtaining derivatives of the factor VII with the kept activity of the coagulative factor VII and with increased ability conjugate with PEG, in comparison with the natural form of a polypeptide.
20 cl, 2 dwg, 8 ex
FIELD: chemistry, biotechnology.
SUBSTANCE: invention relates to biotechnology. Method includes addition to fermentation broth or homogenate from E. coli of efficient quantity of ethacridinlactate solution for sedimentation of contamination from host-cells in conditions, when greater part of polypeptide remains dissolved, and isolation of heterological polypeptide from broth or homogenate.
EFFECT: simplification of target polypeptide purification and obtaining it with high degree purity.
23 cl, 15 dwg, 3 tbl
FIELD: chemistry, biotechnology.
SUBSTANCE: invention relates to field of biotechnology and preparation chemistry and can be used in biopharmacology and medicine. Cells of yeast P.pastoris are successively transformed by two different genetic structures, containing gene of human serum albumin (HAS) precursor. Obtained strain-producent is cultivated in nutrient medium. Recombinant HAS is isolated from cultural medium by clarification of said medium, as well as carrying out stages of successive centrifuging at 2000 and 10000 g, ultrafiltration, dialysis and cation-exchanging chromatography on column Source S. Target product represents eluate, including recombinant human serum albumin, 50 mM phosphate buffer, containing 400 mM of sodium chloride, with pH 9. Application of said iclaimed invention allows to extend arsenal of means, directed at production of recombinant HAS, and to obtain recombinant HAS in form of product, which in addition to recombinant HAS contains 50 mM phosphate buffer, containing 400 mM of sodium chloride and has pH 9.
EFFECT: extension of arsenal of means directed at obtaining recombinant HAS.
2 cl, 7 dwg
FIELD: immunology, biotechnology, medicine.
SUBSTANCE: invention relates to antiidiotypical monoclonal antibody or fragment thereof for BSW17 antibody effecting on LgE Cε3-region bonding to high affinity LgE receptor. Amino acid sequence is as described in specification. antiidiotypical antibody is useful as pharmaceutical composition ingredient for LgE-mediated disease treatment. Invention make in possible to prevent allergic disorders and inflammations due to inhibiting interaction between LgE Cε3-region with high affinity receptor by claimed antibody.
EFFECT: new agent for allergic and inflammation disorder treatment.
7 cl, 32 dwg, 5 tbl, 10 ex
SUBSTANCE: invention concerns pharmaceutical compositions for preventive maintenance of development and treatment of an initial stage of an age cataract. The pharmaceutical composition (versions) contains the active beginning an admixture of two short-chain peptides and the suitable pharmaceutical carrier. In the first version - admixture of D-pantethine and N-acetylcarnosin at the following concentration of components: D-pantethine-not less than 0.001%, N-acetylcarnosin - not less than 0.001%, a normal saline solution - to 100%. In the second version - admixture D-pantethine and L-carnosin at the following concentration of components: D-pantethine - not less than 0.001%, L-carnosin - not less than 0.001%, a normal saline solution - to 100%.
EFFECT: high efficiency of the offered pharmaceutical composition is caused by that the components entering into composition; selectively protect different fibers of the lens of an eye.
2 cl, 7 dwg
SUBSTANCE: invention concerns ophthalmology and can be used for improvement of visual functions at primary open angle glaucoma with the normalised intraocular tension. Parabulbar introduction of the 5% Mexidol solution is performed within 10-12 days. In addition nimodipine is administered intravenously in a dose of 10 mg once a day within 10-12 days. Noopept is administered perorally in a dose of 10 mg 2 times a day within 1 month.
EFFECT: method allows strengthening antioxidising activity and circulation in eye tissues, increasing regenerating effect of nervous fibers.
8 tbl, 4 ex
SUBSTANCE: invention refers to application of peptides of antagonistic action in the relation bradykinin, suitable for medical products for prevention and treatment of diseases influenced by increased activity of matrix metalloproteinase. They are degenerative arthropathies, e.g., osteoarthrosis, spondylosis, as well as cartilage atrophy caused by joit injury or prolonged joint immovability following meniscus or patella damage or ligamentous rupture.
EFFECT: invention provides more effective brake of matrix splitting in comparison with only MMP inhibition of already released or formed tissues.
3 cl, 1 tbl
SUBSTANCE: 2 blood samples are taken with interval 3 days against complex medicinal supplement under the following scheme. Therapy of the first exfusion day is characterized with single introduction of phetabolyl 0.4 mg/kg intramuscularly, 5% vitamin B1 - 50 mg intravenously, vitamin B12 - 500γ st. units intramuscularly, 5%vitamin C - 150 mg intravenously and 10 % aminoplasmal E - 250 ml intravenously drop-by-drop. The same day and the next two days imply intramuscular injection of ferrum lek 100 mg once, sorbypher 325 mg twice a day, folic acid - 5 mg 3 times a day. For the second day exfusion is accompanying with single subcutaneous introduction of epocryne in dosage 4 thausand UNITS. Then for the third day control inspection is carried out. The second day of exfusion implies single introduction of 5% vitamin B6 - 50 mg intravenously, 5% vitamin C - 150 mg intravenously, vitamin B12 - 500γ st.units intramuscularly and 10% aminoplasmal E - 250 ml intravenously drop-by-drop. This day and in the subsequent two - three days imply intramuscular introduction of ferrum lek 100 mg once, sorbypher 325 mg twice a day, folic acid - 5 mg 3 times a day. For the second day exfusion is accompanying with single subcutaneous introduction of epocryne in dosage 4 thausand UNITS. Then for the third day control inspection is carried out again. Since the first exfusion and before autoblood preparation nutritive supplement is carried out using module protein added to mix "Berlamine Modular" 50 g twice a day daily. After exfusion autoblood is divided on erythrocyte mass and fresh frozen plasma.
EFFECT: prevention of dangerous erythropoiesis and metabolic disorders.
1 ex, 3 cl
SUBSTANCE: disclosed are peptides derived from proenzyme forms of matrix proteinases which represent inhibitors of matrix proteinases. Amino acid sequence is disclosed in description. Described are composition for stimulation of healthy skin formation, containing therapeutically effective amount of peptides. Also disclosed are dressing for wounds, method for stimulation of healthy skin formation and wound healing. Disclosed is using of composition in production of drug for wound healing.
EFFECT: new anti-aging and wound-healing agents.
15 cl, 28 dwg, 6 tbl, 7 ex