Additive cytoprotective effects of two bioactive regions of hormone pro-opiomelanocortine
FIELD: chemistry of peptides, medicine, pharmacology.
SUBSTANCE: invention relates to using the combination of bioactive regions SYSMEHFRWGKPV and YGGFM in pro-opiomelanocortine in manufacturing a medicine used in treatment of inflammatory, degenerative and autoimmune diseases, traumas, infections and burns. Also, invention relates to using polypeptide chosen from group: YGGFMSYSMEHFRWGKPVYGGEM, YGGFMSYSMEHFRWGKPV, SYSMEHFRWGKPVYGGFM and compositions eliciting cytoprotective properties. Invention provides enhancing in peptides effect.
EFFECT: valuable medicinal properties of peptides.
9 cl, 1 tbl, 1 dwg
1) the Technical scope of the invention.
This invention is a combination of two bioactive peptides isolated from hormone Pro-opiomelanocortin that contribute to the expression of cytoprotective effects and modulation of the inflammatory response and tone/wound healing. The combination of the two peptides of Pro-opiomelanocortin helps to bring out the best of the pharmacological effects and healing damaged tissue.
2) a Technical problem.
The bioactive part of the protein and gene sequences often contain from 5 to 15 amino acids and repetitive peptides, separated by large blocks of amino acids with uncertain function (1-5).
To select such areas and further manipulation of bioactive effects plots (1-5) can be used for computer analysis methods. This invention is a combination of two repetitive and bioactive sites of hormone Pro-opiomelanocortin, which manifests additive cytoprotective and pharmacological effects.
3) a Technical description.
Repeating peptide fragments within the same protein or family of proteins represent, together with appropriate complementary thereto sequences, sites that are associated with bioactivity larger molecular structures (1-5).
Modern methods the programme is financing, the development of applications and databases, protein and gene structures contribute to computer modeling repetitive, bioactive and complementary structures larger number of different proteins (1-5). Thus, the selection of short and repetitive fragments can be produced on a personal computer quickly and easily (1-5). The inventors have analyzed repetitive and bioactive peptides molecules Pro-opiomelanocortin using the SCAN (3-5) to obtain the possible combinations of elements with additive pharmacological and cytoprotective effects.
4) the Purpose of this invention.
The purpose of this invention to provide an additive cytoprotective pharmacological effects by combining two recurring and bioactive peptides molecules Pro-opiomelanocortin.
Innovation is the fact that instead of independent pharmacological screening of various fragments of Pro-opiomelanocortin used the SCAN to highlight two recurring and bioactive sequence SYSMEHFRWGKPV and YGGFM). Two selected sequences are present in the following molecules: the precursor Pro-opiomelanocortin; Pro-opiomelanocortin, corticotropin, melanotropin, beta-lipotropin, proenkephalin, preproenkephalin, beta-endorphin, adrenalin (table 1)./p>
Fragments of bioactive peptides and SYSMEHFRWGKPV YGGFM were tested separately and in combination, using the standard model of cell protection from the damage of the stomach of male Wistar rats induced by 96% ethanol (6, 7). In the control group of 8 animals that were injected with saline, the area of damage of the stomach was 255,5±78,1 mm2(average, standard deviation, see drawing) (7). In the group of 8 animals that were administered a combination of peptides SYSMEHFRWGKPV (1 mg/kg) and YGGFM (10 mg/kg) area of damage to the stomach was 0.3±07 mm2(p<0.05 compared with controls, see drawing) (7). In the group of 8 animals that were injected SYSMEHFRWGKPV (1 mg/kg) area of damage to the stomach amounted to 5.9±8 mm2(p<0.05 compared with controls, see drawing) (7). In the group of 8 animals that were injected YGGFM (10 mg/kg) area of damage to the stomach was 139,4±36,1 mm2(p<0.05 compared with controls, see drawing) (7). The combination of peptides and SYSMEHFRWGKPV YGGFM, which provided the best cytoprotective effect, patented under the name KOMET. The peptides or their combination did not show any irritants in normal gastric mucosa (7).
5) Drawing and tables.
Table 1 shows the combination of bioactive sequences Pro-opiomelanocortin called KOMET, and three combinations of chemical structural Faure the street KOMET-1, KOMET-2 and KOMET-3 (obtained by combining the individual structural formulas).
The drawing shows cytoprotective effects of bioactive fragments of peptides and SYSMEHFRWGKPV YGGFM molecule Pro-opiomelanocortin and combinations thereof KOMET model lesions of the stomach in rats induced by ethanol.
6) a Description of possible applications of the present invention.
Bioactive sequence KOMET and the combination of their structural formulas KOMET-1, KOMET-2, KOMET-3 defined in table 1, are used as bioactive peptides for the modulation of inflammation and wound healing. Determine structural formulas KOMET-1, KOMET-2 and KOMET-3 bioactive regions (oblasts) hormone Pro-opiomelanocortin (6-9) is to obtain the structural formula (sequences) of potential drugs fast and effective way.
The aim of the invention KOMET-1, KOMET-2 and KOMET-3 is receiving medication that prevents and stops the lesions as in inflammation and autoimmune diseases, and trauma, infections and injuries:
1. connective tissue, joints and bones,
2. Central and peripheral nervous system, optic nerve, eye and ear,
3. skin, hair and nails,
4. the digestive system, liver, pancreas, oral cavity, teeth and sinuses,
5. the immune system, bone marrow, lymphatics the x nodes and spleen,
6. cardiovascular system,
7. respiratory system
8. the reproductive system.
7) Industrial applications of the invention
Bioactive sequence Pro-opiomelanocortin COMETS, COMET-1 and COMET-2 and COMETS-3 injected subcutaneously, intramuscularly, intraperitoneally and intravenously. Dosage forms include ointments, creams, gels, suppositories, vaginal suppositories, eye drops and ear drops.
1. L.Baranyi, W.Campbell, K.Ohishima et al., Nature Medicine 1 (1995) 894-901.
2. J.E.Blalock, Nature Medicine, 1 (1995) 876-878.
3.On the Optimization of Complementary Protein Coding, in: S. Ohno, K. Aoki, M. Usui, E.Uchio (Eds.), Uveitis Today, Elsevier, Amsterdam, 1998, pp 315-318.
4.and P.Konjevoda, Period. Biol. 101 (1999) 363-368.
5.N.Gotovac, M.Martinis et al. Simple Three-step Method for the Analysis and Design of Repetitive and Bioactive protein Motifs, in:(Ed.), Advances in Systems, Signals, Control and Computers, vol. II, IAAMSAD, and ANS, Durban, 1998, pp 310-311.
6. P.Konjevoda,et al. Croat. Chem. Acta 73 (2000) 1111-1121.
7. P.Konjevoda,G.Aralica andJ.Physiol. Paris 95 (1-6) (2001) 277-281.
8. J.M.Lipton and A.Catania, Immunol. Today 18 (1997) 140-145.
9.N.Kopjar,et al. Croat. Chem. Acta 71 (1998) 591-605.
Tables and drawing
Table 1. The combination of two bioactive and repetitive frag the clients proteins (peptide YGGFM and peptide SYSMEHFRWGKPV) was calculated using the SCAN (3-5) of molecules of the precursor Pro-opiomelanocortin and Pro-opiomelanocortin.
Repeating peptide YGGFM also present in the molecules preproenkephalin, proenkephalin, lipotropina-beta endorphin, beta and adrenalinoman (a). Peptide SYSMEHFRWGKPV, also present in the molecules of melanotropin and corticotropin (b).
The combination of bioactive peptides YGGFM and SYSMEHFRWGKPV molecule Pro-opiomelanocortin patented under the name of COMETS.
Other combinations of two sequences of both peptides patented under the following names and structural formulas:
COMET-1 is characterized by the structural formula: YGGFMSYSMEHFRWGKPVYGGFM,
COMETS-2 is characterized by the structural formula YGGFMSYSMEHFRWGKPV and
COMETS-3 is characterized by the structural formula SYSMEHFRWGKPVYGGFM.
|No.||The sequence YGGFM||Balance|
|3||Preproenkephalin||54-58, 61-65, 90-94, 140-144, 164-168, 215-219|
|4||Proenkephalin||100-104, 107-111, 136-140, 186 to 190, 210-214, 261-265|
|6||The precursor Pro-opiomelanocortin||232-236|
|7||About-about eumelanosomes||3-7, 237-241|
|No.||The sequence SYSMEHFRWGKPV||Balance|
|3||The precursor Pro-opiomelanocortin||133-145|
A drawing. Cytoprotective effects of bioactive fragments of peptides and SYSMEHFRWGKPV YGGFM molecule Pro-opiomelanocortin in the model damage to the stomach in rats induced by ethanol. The combination of sequences of COMETS (SYSMEHFRWGKPV+YGGFM) demonstrates a strong cytoprotective effects than individual sequences of peptides.
LIST of AMINO acid SEQUENCES
<110> Ademovic, Zlatko and other
<120> Additive cytoprotective effects of two bioactive areas hormone Pro-opiomelanocortin.
<140> PCT/VA 01/00005
<170> Version 3.1 patent
<213> Artificial sequence
<223> Artificial amino acid sequence with a gap, numbered as a set (combination) of two separate sequence is, have a separate identifiers of sequences 1 and 2 (or Vice versa). Combination (set) of sequence identifiers 1 and 2, called COMETS, contributes to the development of better and more strong cytoprotective and pharmacological effects than those obtained using the individual identity of amino acid sequence.
<213> Artificial sequence
<223> Artificial amino acid sequence with a gap, numbered as a set (combination) of two separate sequences, determined by the individual identifiers of sequences 1 and 2 (or Vice versa). Combination (set) of sequence identifiers 1 and 2, called COMETS, contributes to the development of better and more strong cytoprotective and pharmacological effects than those obtained using the individual identity of amino acid sequence.
<213> Artificial sequence
<223> Constructed amino acid sequence, which consists of two non-contiguous segments of a larger sequence or of segments of different sequences, numbered as a separate sequence, with the identifier in a sequence (SEQ ID NO: 3). This artificial sequence named COMET-1.
<213> Artificial sequence
<223> Constructed amino acid sequence, which consists of two non-contiguous segments of greater posledovatelnostei of segments of different sequences, numbered as a separate sequence, with the identifier in a sequence (SEQ ID NO: 4). This artificial sequence named COMET-2.
<213> Artificial sequence
<223> Constructed amino acid sequence, which consists of two non-contiguous segments from different sequences are numbered as a separate sequence, with the identifier in a sequence (SEQ ID NO: 5). This artificial sequence named COMETS-3.
1. Applying a combination of two bioactive peptides derived from Pro-opiomelanocortin, SEQ ID No.1: SYSMEHFRWGKPV and SEQ ID No.2: YGGFM, in the manufacture of medicaments for the treatment of inflammatory, degenerative and autoimmune diseases as well as injuries, infections and burns.
2. The use according to claim 1, characterized in that the content of the peptide SYSMEHFRWGKPV in medicine is from 9.1 to 16.7 wt.%.
3. The use according to claim 1, characterized in that the content of the peptide YGGFM in medicine is 83,3 to 90.9 wt.%.
4. The use according to claims 1 to 3, characterized in that the peptides used in the manufacture of medicaments for the treatment of inflammatory bowel disease.
5. The use according to claims 1 to 3, characterized in that the peptides used in the manufacture of medicaments for the treatment of syndrome of inflamed bowel (IBD).
6. A polypeptide containing an amino acid sequence selected from the group including
SEQ ID No.3.: YGGFMSYSMEHFRWGKPVYGGFM,
SEQ ID No.4.: YGGFMSYSMEHFRWGKPV and
SEQ ID No.5.: SYSMEHFRWGKPVYGGFM.
7. Composition, characterized in that it exhibits cytoprotective properties and contains the polypeptide of claim 6.
8. Composition, characterized in that it exhibits cytoprotective properties and contains a polypeptide that includes the amino acid sequence of SEQ ID No. 1: SYSMEHFRWGKPV, and a polypeptide that includes the amino acid sequence of SEQ ID No.3.: YGGFMSYSMEHFRWGKPVYGGF.
9. The composition according to claim 7 or 8, characterized in that it is a pharmaceutical composition for the treatment or prevention of injury, infection, burns, inflammatory diseases or autoimmune diseases.
FIELD: medicine, pharmacy.
SUBSTANCE: invention describes hydrophilic and hydrophobic compositions used in treatment of infectious or viral diseases and a method for treatment. Hydrophilic composition comprises polynitro-compound of the formula: R-(NO2)n wherein n ≥ 2, dimethylsulfoxide and ethyl alcohol wherein the composition comprises dinitrotoluene and/or tetranitrotoluene, and pentanitrotoluene or mixture of at least one of them with trinitrotoluene as polynitro-compound of the formula R-(NO2)n. Hydrophobic composition comprises polynitro-compound of the formula: R-(NO2)n wherein n ≥ 2 and vegetable and/or animal fat wherein dinitrotoluene and/or tetranitrotoluene, and/or pentanitrotoluene or mixture of at least one of them with trinitrotoluene is used as polynitro-compound of the formula R-(NO2)n. Proposed compositions relate to lipotropic substances that are able to penetrate into tissues rapidly and blood and contact with pathogenic microflora actively.
EFFECT: valuable medicinal properties of compositions.
4 cl, 2 tbl, 10 ex
FIELD: medicine, angiology.
SUBSTANCE: one should apply total siliceous baths at 100-150 mg/l concentration followed by applying a "Branolind N" ointment bandage after each bath onto the region of trophic ulcer for 24 h. The present innovation accelerates the process of purifying and healing the ulcerous defect, shortens terms of therapy, prolongs the period of remission, in patients with accompanying pathology, as well.
EFFECT: higher efficiency of therapy.
1 cl, 2 ex
FIELD: medicine, dermatology, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to a medicament as an ointment formulation used in treatment of hyperkeratosis, ingrown nail and in hygienic treatment of nails deformed as result of trauma and/or aging changes. Proposed agent contains urea, its stabilizing agents, namely a mixture of glycine and aliphatic (C1-C3)-alcohol, and vaseline oil and glycerol as a lipid base and emulsion wax as an emulsifying agent.
EFFECT: valuable medicinal properties of agent.
7 tbl, 1 dwg, 18 ex
FIELD: medicine industry, bioactive substances.
SUBSTANCE: claimed medium is designed for treatment of burn-associated damaged skin and mucous tissues. Medium contains mineral salts, antibiotics and nutrients sufficient to maintain vitality and growth of human marrow mesenchymal stem cells, including metabolism products thereof. Conditioning medium is produced in static growth step of cultural stable cell line of mesenchymal stem cells in Go-period of cell cycle followed by medium collection.
EFFECT: medium of improved therapeutic effect.
FIELD: medicine, microbiology.
SUBSTANCE: invention proposes a pharmaceutical composition that comprises active slightly water-soluble components as a single unique composition against microorganisms showing pathogenic properties for humans and animals, at least one active component showing effectiveness against some opportunistic strains from the group consisting of fungi Candida, Aspergillus and/or Fusarium, aerobic microorganisms: gram-negative bacilli, such as Proteus, Pseudomonas, enterobacteria, such as Escherichia coli, Klebsiella, Serratia marcenscens, Citrobacter, Aeromonas, gram-negative cocci, such as Neisseria, Acinetobacter spp., gram-positive bacilli, such as Corynebacterium spp., Bacillus sphaericus, gram-positive cocci, such as Streptococcus spp., anaerobic bacteria: gram-negative cocci, such as Bacteroides, Fusobacteria, gram-positive cocci, such as Peptococcus, Peptostreptococcus spp., gram-positive bacilli, such as Clostridium, Propionibacterium, Eubacterium spp., and mycobacteria, such as Mycobacterium ulcerans, bacterium-like microorganisms of Chlamydium type, such as Chlamydia trachomatis. The composition comprises at least one fungicide of azole or polyene type, antibacterial substance of erythromycin, azalide, lincosamide, polypeptide or a bacteriostatic sulfonamide dispersed in a pharmaceutically acceptable by locus using carrier. Additional components comprise zinc oxide and azulene. The composition is used as ointment, tablets, carbonated tablets, suppositories and foam. Invention provides a wide spectrum of antibacterial effect in treatment of injured skin surface or body cavity and long-termed protection against fungi and microorganisms.
EFFECT: valuable medicinal properties of composition.
21 cl, 28 tbl, 4 dwg, 28 ex
FIELD: pharmacological industry, in particular pharmaceuticals for physiotherapy using sonic phoresis with medicaments.
SUBSTANCE: claimed cream comprising lanoline and petrolate addinionally contains dimexide and 0.25 % verapamile solution in specific component ratio. Cream of present invention makes it possible to prevent necessity of surgical correction, to reduce pathological semiology and to prevent formation of keloid and hypertrophy cicatrix.
EFFECT: anti-cicatrix cream of increased effectiveness.
1 ex, 1 tbl
FIELD: medicine, endocrinology, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical composition comprising epidermal growth factor (EGF) used in treatment of wounds on skin and soft tissues of lower limb in diabetic patient. Method of treatment involves topical infiltration of EGF-containing solution into different points and by contours of tissue damaged zone to provide administration of the solution into wound in the total volume 4-20 ml and irrigation of all deep surface of wound base and edges with the indicated composition. Invention provides prevention of diabetic limb amputation, stimulation of cellular proliferation in patients with foot ulcer being especially in geriatrics.
EFFECT: valuable medicinal properties of pharmaceutical composition.
19 cl, 1 tbl, 9 ex
SUBSTANCE: method involves first introducing chemical compound of local anesthetic activity into paraneural space of sympathetic trunk and retroperitoneal space under ultrasonic control. Next, chemical compound causing superficial injury of sympathetic nerve is introduced.
EFFECT: avoided negative consequences of total sympathectomy and radiation loading.
SUBSTANCE: the present innovation deals with obtaining compositions being of bactericidal, antiphlogistic, regenerating, antioxidant and antimicrobial properties at no allergic action. Wound-healing preparation (variant 1) contains: stearic acid 4.5-6.0; purified lanolin and its derivatives 3.0-6.0; vegetable oil 3.0-5.0; Vaseline 1.5-2.5; glycerol 4.0-8.0; castor oil 8.0-12.0; zinc stearate 1.0-2.5; 70%- alcoholic extract of phytospecies 2.5-3.5; extract of common John's wort grass 3.5-8.5; dog rose oil or sea buckthorn oil 2.6-6.0; Na-salts of fatty acids of wool fat 0.3-0.6; triethanolamine 0.7-1.1; anesthesin 2.0-3.0; 10%-butyric solution of propolis 0.3-1.0; boric acid 0.4-0.6; purified water - the rest. Wound-healing preparation (variant 2) contains: stearic acid 4.5-6.0; purified lanolin and its derivatives 3.0-6.0; vegetable oil 3.0-5.0; Vaseline 1.5-2.5; glycerol 4.0-8.0; castor oil 8.0-12.0; zinc stearate 1.0-2.5; 70%-alcoholic extract of phytospecies 2.5-3.5; extract of common John's wort 3.5-8.5; dog rose oil or sea buckthorn oil 2.6-6.0; Na-salts of fatty acids of wool fat 0.3-0.6; triethanolamine 0.7-1.1; anesthesin 2.0-3.0; levomycetin or gentamycine 2.0-3.0; 10%-butyric solution of propolis 0.3-1.0; boric acid 0.4-0.6; purified water - the rest. Additional introduction of the extract of common John's wort has increased antioxidant properties; 10%-butyric propolis - antioxidant and bactericidal properties, and levomycetin and gentamycine - has widened the range of antimicrobial action. Application of the preparation suggested in patients with burns and wounds revealed positive therapeutic effect without any cicatricial neoplasms and allergic action. No contraindications had been established.
EFFECT: higher efficiency of application.
4 cl, 8 ex
SUBSTANCE: the present innovation deals with compositions of ingredients that have curative indication due to external application at patient's body. The suggested ointment contains vegetable oil, wax as fatty product, rivanol, tannin, glycerol as antiseptic at the following ratio of components, weight%: wax 13-15; rivanol solution 1.2-1.3; tannin 3-5; glycerol 15-20; vegetable oil - the rest. The innovation provides increased efficiency of healing action at no side complications.
EFFECT: higher efficiency of therapy.
4 ex, 1 tbl
FIELD: biotechnology, medicine, pharmacy.
SUBSTANCE: invention proposes peptides as agonists of corticotropin-releasing factor CRF2R prepared by solid-phase synthesis. Synthesized agonists of CRF2R are used as components of pharmaceutical composition used in prophylaxis or treatment of diseases modulated by CRF2R. Proposed invention provides enhancing effectiveness of therapeutic effect and avoiding by-side responses in treatment of disorders modulated by CRF2R. Invention can be used in synthesis of novel peptides possessing activity of agonists of corticotropin-releasing factor-2 (CRF2R).
EFFECT: improved method of synthesis, valuable medicinal properties of agonists.
3 tbl, 3 ex
SUBSTANCE: invention relates to method for decreasing of nutrient availability, method for appetite suppression or reducing of food consumption. Claimed method includes application of PYY substance (YY peptide) or PYY agonist in peripheral administration. Method provides decreasing of nutrient availability in mouse females hungered for one night, reducing stomach ejection, inhibition of acid secretion in stomach, preventing cholecyst ejection, and inhibition of amylase secretion in pancreas.
EFFECT: preparation for decreasing of nutrient availability of improved effect.
35 cl, 10 ex, 8 dwg, 1 tbl
FIELD: medicine, oncology.
SUBSTANCE: invention relates to a method for treatment of malignant tumors. Method involves administration in a patient the chemotherapeutically active dose of antitumor platinum compound, foe example, cisplatin or carboplatin and erythropoietin or erythropoietin-like substance wherein the latter is administrated before administration of platinum compound or simultaneously with its. This method provides attaining the synergistic antitumor effect.
EFFECT: improved and valuable medicinal effect.
8 cl, 2 tbl, 2 dwg, 2 ex
FIELD: medicine, endocrinology, biochemistry, peptides.
SUBSTANCE: invention represents new peptides that act in vivo as stimulators of insulin secretion by pancreas beta-cells in glucose-dependent regimen. Such peptides as enhancers of insulin secretion stimulate insulin secretion by insula cells in rats in vitro and in vivo. Proposed peptides represent a new way for treatment of patients with reduced secretion of endogenous insulin, in particular, for treatment of diabetes mellitus type 2. In particular, invention represents polypeptide taken among the specific group VIP/PACAP-related polypeptides or their functional equivalents. Also, invention claims method for preparing both recombinant and synthetic peptides. The advantage of invention involves new peptides that can be used as stimulators of insulin secretion.
EFFECT: improved and valuable medicinal properties of peptides.
47 cl, 4 tbl, 10 dwg, 18 ex
FIELD: medicine, therapy, gastroenterology, pharmacy.
SUBSTANCE: method involves oral intake of solid medicinal formulation at vertical position of patient and change of medicinal formulation position into stomach is carried out in each 5 min, not rare. Change of medicinal formulation position is carried out by pressing on epigastrium region by hand or by cyclic change of position of patient body from its vertical position to horizontal position and back. Method provides enhancing safety in enteral using a solid medicinal formulation due to diminishing its ulcerogenic effect. Invention can be used in enteral using solid medicinal formulations.
EFFECT: improved method for diminishing ulcerogenic effect.
FIELD: medicine, endocrinology, pharmacy.
SUBSTANCE: invention relates to medicinal agents, in particular, to the hormonal pharmaceutical composition. Invention proposes new pharmaceutical compositions and a method for preparing such compositions formed by the estrogen-gestagen combination with a single gestagen compound in mixture with one or some nontoxic, inert pharmaceutically acceptable carriers designated for oral administration. Also, invention relates to the estrogen-gestagen mixture wherein estrogenic component and gestagenic component are used by the combined method. Proposed composition is designated for treatment of estrogenic insufficiency, prophylaxis of osteoporosis and cardiovascular diseases in women in the menopause period. Invention provides the development of the new estrogen-gestagen combination showing activity in the oral route of applying and administrated by the combined method.
EFFECT: improved and valuable medicinal properties of composition.
12 cl, 8 tbl, 3 ex
FIELD: medicine, otorhinolaryngology.
SUBSTANCE: one should treat deformation in laryngeal and tracheal lumen due to excessive growth of granulation tissue in the sites of their lesions. One should introduce hormonal preparations, moreover, one should apply Diprosan as a hormonal preparation injected once intramucosally at 0.1 ml/sq. cm of granulation tissue, but not more than 0.3 ml.
EFFECT: higher efficiency of therapy.
3 ex, 1 tbl
FIELD: medicine, immunotherapy based on peptides.
SUBSTANCE: invention relates to peptide B fragments, in particular specific fragments thereof for immunization or therapy of mammalian, including human, suffering from ischemic cardiovascular diseases.
EFFECT: new antigen alipoprotein B-100 peptides for arteriosclerosis therapy.
21 cl, 1 tbl