Polyactive terpenoid substance abisil-2, pharmaceutical composition on its basis and ways of its application |
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IPC classes for russian patent Polyactive terpenoid substance abisil-2, pharmaceutical composition on its basis and ways of its application (RU 2338547):
  
 Agent of immunomodulating activity / 2337700
Application of water-soluble polysaccharides made of coltsfoot leaves as agent of immunomodulating activity stimulating Th1-dependent immune response. Water-soluble polysaccharides made of coltsfoot leaves possess immunomodulating activity, effectively stimulate Th1-dependent immune response.
Method of obtaining shelf fungus ethanolic extract / 2336888
Invention concerns the pharmaceutical, food and cosmetic industry. Perform extraction of the raw material crushed with water with obtaining of a water extract and pulp. The pulp, obtained after extraction of raw materials by the water, is extracted in two steps with ethyl alcohol. At the first step of extraction the constrictor is extracted within 4-6 hours using the following proportion: ethyl alcohol 1:(5-7) with concentration of alcohol of 30% either 50%, or 70%, at temperature of 60-75°C, obtaining an ethanolic extract of the first step of extraction and pulp; then, this pulp is repeatedly extracted within 4-6 hours with ethyl alcohol using the following proportion: ethyl alcohol 1:(3-5) with concentration of alcohol of 30% either 50%, or 70%, at temperature of 60-75°C, obtaining an ethanolic extract of the second step of extraction and pulp. After that the ethanolic extract of the first step of extraction is aggregated with the ethanolic extract of the second step of extraction.
![Substituted 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoles, method of production and application thereof](http://img.russianpatents.com/img_data/159/1592084-s.gif) Substituted 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoles, method of production and application thereof / 2334747
Invention refers to of serotonin receptor 5-NT6 antagonists, simultaneously regulating calcium ions homeostasis in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of general formula I, its pharmaceutically acceptable salt and/or hydrate. In general formula I
 1,3-di(3-piperidine-2-hydroxypropyl)-6-methyluracil for increase of capacity for survival and yeild of poultry / 2334745
Invention refers to veterinary science, in particular to products intended to increase capacity for survival and yield of poultry. For this purpose common composition 1,3-di(3-piperidine-2-hydroxypropyl)-6-methyluracil of formula:
 Thienopyrimidindions and their application in autoimmune disease modulation / 2332420
(I)
 Thienopyrimidine diones and their use in modulation of autoimmune disease / 2331647
Invention pertains to thienopyrimidine diones with general formula (I),
 New compounds / 2331646
Invention pertains to thienopyridazinones with formula
Method for rehabilitation of infantile cerebral paralysis (icp) disabled children with infection background / 2331419
Invention relates to medicine and pediatrics. The method consists of clinical examination of a child and carrying out of therapeutic procedures. There are determined abnormalities in immunologic state of main cell markers: total leukocyte count, lymphocytes CD3, CD4, CD4/CD8, CD19, classes A, M, G of antibodies levels; antibodies to chlamydia, HSV (herpes simplex virus), CMV (cytomegalovirus), toxoplasma, toxocaria, lamblia, opisthorchis. Drug dosage regimen for children under four years is as follows: polyoxidonium intranasal by 5 drops 30 minutes before meal once a day for 2 days, then 2 days break, the course total duration is 20 days; administration of succinic acid by 25 mg after meal in the morning and at noon for 5 days, then 2 days break. Children four to seven years proposed to take bronchomunal P by 3.5 mg before meal every morning for 1 month; succinic acid by 50 mg twice a day as above; and ribomunil by 75 mg before meal in the morning, during first month on 4 first days of each week, and during 2nd to 6th months on 4 first days of each month. Regimen for children seven to eleven years is as follows: cyclopheron 12.5% by 2 ml once a day on 1st, 2nd, 3rd, 4th, 6th, 8th, 11th, 14th, 17th, 21st, and 25th day, then once a week for 2 months; methyluracil by 50 mg after meal three times a day for 1 month; cod-liver oil with garlic by 1 dragee after meal three times a day for 10 days; and succinic acid by 75 mg twice a day as above. Regimen for children eleven to sixteen years is as follows: timaline by 0.01 g intramuscularly by 2 ml for 20 days; cod-liver oil with garlic by 2 dragee after meal three times a day for 10 days; biologically active additive "Karvipar" by 1 dessert-spoon three times a day for 2 weeks; and succinic acid by 100 mg twice a day as above. Immune state correction course is carried out in late autumn and in early spring, in other time polyvitamins are administered every month.
 Agent of immunomodulating activity / 2329821
Invention refers to pharmaceutical industry, specifically to agent of immunomodulating activity. Application of water-soluble polysaccharides made of birch leaves, as an agent of immunomodulating activity, stimulating Th1-dependent type of immune response. Water-soluble polysaccharides described above produced of birch leaves are effective immunomodulators and activators of Th1-dependent immune response.
 New factors of fibroplast growth / 2329058
Invention concerns application of polypeptide FGF-9 or its biologically active fragment to produce medical product for multiple sclerosis treatment. Polypeptide can be 94-95% identical to sequence from amino acid 1 to amino acid 208 of human FGF-9, presented on fig. 3 (SEQ ID NO: 5).
Method of neoadjuvant chemotherapy of mammary gland cancer / 2338545
From the first day of treatment centrifugate the autoblood obtained by vascular access in volume of 2400-2600 ml, 1600 ml of supernatant plasmas select in sterile vials, expose to filtrational detoxicating with use of filter F60S with rate of perfusion of 250-300 ml/minute. Then the obtained albuminous concentrate of autoplasma in volume 700-800 ml place in sterile vials in the equal portions corresponding to number of planned introductions of cytostatics under the scheme. Vials contain in a refrigeration cabinet at t-20°C. At carrying out of polychemotherapy by cytostatics under the scheme, an albuminous concentrate defreeze at t +4°C, each antitumoral preparation plant in 10 ml of a normal saline solution, enter into a vial with an albuminous concentrate, incubate at t +37.0°C within not less than 30 minutes and reinfuse them intravenously driply, spend 1-2 courses of neoadjunt treatment.
Combined therapy for treatment of acute leukemia and myelodisplastic syndrome / 2338535
Invention can be used for treatment of an acute myelogenetic leukemia or myelodysplastic syndrome. For this purpose use a combination of preparations hemetuzumab ozohamicin, daunorubicin and cytarabinum in certain doses and regimens.
 Staufosporine derivatives as inhibitors of receptor tyrosine kinase flt3 activity / 2337692
Invention concerns application of N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9N-diindolo [1,2,3-gh:3', 2', 1'-lm] pyrrolo[3,4-j][1,7]benzodiasonine-11-yl]-N-methylbenzamide of formula
 Antitumoral agent on basis of immunopolisome biological structure, way of its obtaining and vectorial delivery in central nervous system at tumoral process / 2336901
Invention concerns biopharmacology and medicine area. The antitumor agent representing a immunoliposome biological structure, including a liposome containing the therapeutic agent, sewed with a vector of peptide nature, thus for treatment of CNS tumors is declared, the liposome contains the therapeutic agent in a water phase, as a vector contains monoclonal antibodies to CD34+, and a linking represents 2-iminotiolan (IT) in 0.1% concentration. As a therapeutic agent, immunoliposome contains the substance chosen from the group: Daunomycin, Carminomycinum, Melphtalan, Methotrexatum, Cytarabinum, Doxorubicinum, Ricine. The method of obtaining of an antitumoral agent and way of inhibition of a tumor of the brain, consisting in agent administering due to item 1 in a pharmaceutically suitable carrier in effective quantity is declared also. Thus preliminary administer parenterally a preparation of hematological stem cells CD34+.
Method of obtaining shelf fungus ethanolic extract / 2336888
Invention concerns the pharmaceutical, food and cosmetic industry. Perform extraction of the raw material crushed with water with obtaining of a water extract and pulp. The pulp, obtained after extraction of raw materials by the water, is extracted in two steps with ethyl alcohol. At the first step of extraction the constrictor is extracted within 4-6 hours using the following proportion: ethyl alcohol 1:(5-7) with concentration of alcohol of 30% either 50%, or 70%, at temperature of 60-75°C, obtaining an ethanolic extract of the first step of extraction and pulp; then, this pulp is repeatedly extracted within 4-6 hours with ethyl alcohol using the following proportion: ethyl alcohol 1:(3-5) with concentration of alcohol of 30% either 50%, or 70%, at temperature of 60-75°C, obtaining an ethanolic extract of the second step of extraction and pulp. After that the ethanolic extract of the first step of extraction is aggregated with the ethanolic extract of the second step of extraction.
 Pyrimidine derivatives, characterised by antiproliferative activity, and pharmaceutical composition / 2336275
Invention relates to new pyrimidine derivatives of formula I and their pharmaceutically acceptable salts, which are selective inhibitors of kinases KDR, FGFR and PDGFR and can be used for treatment of oncological diseases. Compound of formula I corresponds to structural formula
Method of rectal cancer treatment / 2336038
Within preoperative period patients are drew with blood sample in amount 200 ml. Using centrifugation process plasma is separated from blood. Autoplasma in amount 40 ml is placed to the first bottle added with 5-fluorouracil 500 mg. The second bottle contains remained blood corpuscles, plasma and 5-fluorouracil 1000 mg. Bottles are incubated separately within 40 minutes at 37°C. Then rectum is excised. During operation incubated blood of the second bottle with chemical added is introduced intravenously drop-by-drop. After tumour rectum is extracted, haemostatic sponge impregnated with incubated autoplasma of the first bottle with chemical added is placed in tumour box (on sacral bone). Then perineal wound is tampon or cut down.
 Coordination complex of platinum (ii) diaminocyclohexane with block copolymer containing polycarboxylic acid segment and including anticancer agent / 2335512
Invention concerns coordination complex of platinum (II) diaminocyclohexane with block copolymer containing structure of the general formula PEG-block-poly(carbo), where PEG is a poly(ethyleneglycol) segment, and carbo is a repeating chain containing carboxylic group in the side chain, and platinum (II) diaminocyclohexane is immobilised by block copolymer due to linkage between carboxylic carbo residue anion and platinum; as well as method of obtaining the complex and anticancer composition including effective anticancer quantity of coordination complex and pharmaceutically acceptable carrier. In addition, invention concerns coordination complex of platinum (II) diaminocyclohexane and block copolymer with structure of the general formula (1-a)
Peptide analogues gh-rh with opposing action, way of depression of gh level, way of depression of igf-inigf-ii level, application for inhibition of growth of cancer cells, pharmacologically acceptable composition (variants) / 2335506
New types of synthetic opposing analogues hGH-RH(1-29)NH2 are offered. The given analogues inhibit interaction of endogenous hGH-RH with hypophyseal GH-RH receptors and thus interfere with release of a growth hormone. The analogues also suppress a proliferation in cancer tissues of the person by immediate influence on cancer cells. Increased inhibitory efficiency of the new analogues, in comparison with earlier described, is a consequence of replacement of different amino acids.
 Polymorphs of pyrrol-substituted 2-indolinone proteinkinase inhibitors / 2335502
Invention concerns polymorphs of 1-pyrrol-substituted 2-indolinone compound (2-pyrrolidine-1-ylethyl)amide 5-(5-fluor-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrol-3-carboxylic acid, namely polymorphic form of the formula I:
 Agent for bacterial infections treatment / 2337711
Agent contains Rifabutin sorbated in polymeric nanoparticles matrix, potassium cholesterylphosphate, or sodium glycocholate, or hexadecyl dihydrogen phosphate, or a-tocopheryl succinate, water-soluble polymeric stabiliser and bulking agents. Polymeric nanoparticles sized 100-800 nm include lactic acid polymer/polymers and/or lactic and glycolic acid copolymer/copolymers at glycolic acid content in specified copolymers up to 50 mole %. Molecular weight of specified polymers and copolymers is 5 to 300 kDa. Molecular weight of water-soluble polymeric stabiliser is no more than 70 kDa and is selected from the group including polyvinyl alcohol, polyvinylpyrrolidone, polysorbate and seralbumin.
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FIELD: medicine; pharmacology. SUBSTANCE: agent possessing wound-healthing, antiinflammatory, antibacterial, immunomodulating, anaesthetising and antitumoral activity on a basis of terpenoids, contains a capsule extract of plants of Pinaceae bloodline exposed to short-term stressful influence, enriched with monoterpenes, obtained from a capsule extract. The pharmaceutical composition possessing wound-healthing, antiinflammatory, antibacterial, immunomodulating, anaesthetising and antitumoral activity, contains the above described agent in effective quantity and the target additive. Application of the above described agent for preparation of a medicinal preparation for treatment of pyoinflammatory diseases. EFFECT: increased wound-healthing; antiinflammatory; antibacterial; immunomodulating; anaesthetising and antitumoral activities. 8 cl, 1 dwg, 6 tbl, 8 ex
The invention relates to the field of medicine and pharmaceutical industry. Specifically to methods of obtaining and identifying possible spectrum of pharmacological activity and the development of appropriate pharmaceutical compositions, cosmetic and hygiene products containing new polyactivity set terpenoids. Identification and development of methods of preparation, as well as possible ways to use the new polyactive pharmaceutical substances, able to show not just the biological activity of a particular property, and to provide a high therapeutic effect, is the purpose and priority in the development of new drugs, medical cosmetics and hygiene products. One of the fundamental conditions for this is the presence of polyactive the active ingredients substances, more effective than the well-known counterparts. It seems reasonable to focus the field of search of promising substances among natural plant terpenoid compositions. This is facilitated by several factors: 1. To terpenoids include compounds with different numbers of carbon atoms, which occurred from isoprene units (C5H8). Their numerous oxygen derivatives represented by alcohols, aldehydes, to the tones, acids, etc. Despite the fact that the difficult task is the identification of new terpenes is not finished yet, of these compounds, there are already tens of thousands and they are already fixed most of the known types of biological activity. 2. These natural compounds - monoterpene (C10H16), sesquiterpenes (C15H24), diterpenes (C20H32), triterpenes (C30H48), tetraterpene (C40H64and polyterpenes, in primary forms found in almost all tissues of medicinal plants. 3. Functions of plant terpenoids, many of which are formed in the mass in the final stages of a specialized (secondary) metabolism is not fully understood, but is currently fundamental to the role attributed their environmental component. It is believed that terpenoids ensure the survival of plants under adverse environmental influences (temperature, exposure to pathogenic microbes, fungi, insects, presence of toxic substances in air masses, the imbalance of nutrients and so on). 4. Terpenoids are active participants in metabolic processes, while the hydrocarbon chains of many of their representatives are key intermediates in the biosynthesis pathway of such biologically active substances such as steroid hormones, enzymes, ant the oxidants, vitamins D, E, K, bile acids, etc. However, there is a huge gap between the number of known terpene compounds, the amount of information about their biological activity, but limited, though long, their use in medical practice (camphor, tincture of Valerian, Zelenin drops, Corvalol, valocordin, etc.). The explanation for this may lie in the fact that research are, as a rule, individual members of this large class, isolated in pure form. This approach leads to toxicity and lack of polyactive that deprives such compounds necessary benefits. So the work of several scholars (Inoule etal, 1986; Doll et al, 1962) have shown that tridecemlineatus acid is able to inhibit the enzymes involved in the biosynthesis of leukotrienes, including 5-lipoxygenase activity, which makes it responsible for anti-inflammatory activity. Therefore in the study were taken as a separate derivative of glycyrrhetic acid, which has anti-inflammatory, antiulcer, antiallergic, protivogerpetical and antiviral activities. Was asked a series of such compounds for use as a means of prevention and treatment of gastric ulcer: carbromal (U.S. patent No. 3070623), amino acid salts glycerrhetinic acid (paten the Japan-44-32798), amide derivatives of 11-desoxycortisol acid (patent of great Britain No. 1346871), amide derivatives of glycyrrhetinic acid (Belgium patent No. 753773) etc. As you know, these connections did not solve the problem of the treatment and prevention of stomach ulcers, but simply outlined a possible way to fix it. Also known triterpene compositions and methods for their preparation and use for the inhibition of the epithelial cells of a mammal in pre-malignant or malignant condition on the background of the regulation of angiogenesis. Such triterpene composition selected from the species Acacia victorial. They are acacia or Cleanaway acid, to cotrim attached oligosaccharides and monoterpenoid components. Received triterpene compositions are characterized by limited or varying degrees of effectiveness in the treatment of pathological States in mammals or humans (U.S. patent US 99/11041, WO 99/59578). Also known pharmaceutical composition R-tetrol based on faction ladyoysterrolex acids from zivic softwood species Pinus sibirica, and/or Pinus cembra, and/or genus Abies, and/or genus Larix (patent RU 2196581 C2 on CL AC 31/337, 41/00, 35/78, C07D 305/14, OR 35/00). The obtained pharmaceutical composition is similar to the anticancer drug Taxol. It can be used for production is as anticancer drug with less cost. However, both of these pharmaceutical compositions have a limited spectrum of biological activity and a wide range of spam related impacts. Renowned pharmaceutical composition comprising the terpenoid derivatives (euglobulin), formula23H30About5or28H38O5have antibacterial, antiviral and anti-inflammatory activity with a range of applications in gynecology and proctology (patent RU 2102977, CL. AC 9/02, 61J 3/08). For reasons that impede the achievement described below therapeutic effect, this is a known pharmaceutical composition includes low biological activity taken active substances, and the limitation on the range of dosage forms and routes of administration of the drug in the body. Nevertheless, attempts were carried out to create and use complex pharmaceutical compositions on the basis of terpenoids, which could satisfy the criterion of "activity". This is a series of known drugs, as active substances which are terpenes contained in the fir oil (patent RU 2074730, CL AC 35/78; patent RU 2127584, CL AC 9/06, 35/64, 35/78; RU patent No. 2127884 C1, AC 9/06; SU, patent 178047, CL AC 9/06). In this case, the method of obtaining is based on the selection is not the individual patient, the s, but the whole group, namely monoterpenoids, which is characterized by the same restrictions. For reasons that impede the achievement described below therapeutic effect, is their high toxicity, inherent in all turpentines (including cedar and pine), as well as restrictions on the applied dosage forms, routes of their application and spectrum of biological activity. More intimate complex terpenoid compositions in the methods of production and levels of biological activity are antimicrobial (SU 1767737 A1 from 14.06.90.) and antitumor (SU 1663819 A1 from 14.06.89). But these terpenoid compositions have a high, but limited field of biological activity, in addition, they are not pharmacologically significant. The closest source, which can be specified as a prototype, is a "Tool "Abisil-1", which has anti-inflammatory, antibacterial and wound healing activity" (RU Patent No. 2054945 from 28.06.1995). As you know, of the described method of obtaining terpenoid composition Abisil-1, it consists of natural capsular extract of Siberian fir (Abies sibiricus Led.), enriched monoterpenoid compounds, taken in a certain ratio. However, there are a number of limitations and obstacles to achieve high shortly after the wow effect. These reasons include: - lack of standardization-known terpenoid composition; - restriction on the use of primary sources, as well as the possible applications for terpenoid pharmaceutical compositions. A disadvantage of the known solution is, first, that the lack of standardization does not allow terpenoid composition with the maximum possible for her biological activity, which consequently hinders the effective funds, created on its basis. The aim of the present invention is: - increase the biological activity of terpenoid composition by means of identified and developed ways to activate incoming ingredients; - development of a new method of obtaining terpenoid composition on the basis of which it will be possible exercise is absolutely necessary standardization of new drugs, cosmetics or hygiene products; - getting a new standardized dosage forms other than Abisil-1", with increased biological activity, on the basis of the activated and standardized ingredients terpenoid substance; - identify the diversity of the spectrum of clinical features and uses of a new dosage form; - removing the ogran the values in respect of the application is a set of biologically active substances; - expansion of raw material sources. This goal is achieved by the proposed composition that provides a standardized terpenoid substance Abisil-2, obtained on the basis of capsular extract of the few Pinaceae plant family that includes the following components in mass fraction %, namely: - sesquiterpenoid (3-6%) neutral diterpenoids (11-15%) - diterpene acids (23-24%) triterpene acids (8-16%) unsaturated and saturated fatty acids (0.1 to 0.3%) - phenolic compounds (0,1-0,2%) monoterpenoid else, moreover, the contents monoterpenoid of barcelonetta should be not less than 10.0% of the total composition of terpenoids. Terpenoid composition is a thick liquid from transparent yellow to milky white color with a specific smell and has certain physical constants, namely: acid number (70-90 mg) the saponification number (100-130 mg) - ester value (10-60 mg) the refractive index (1,500 to 1,520) The new substance polyactive, therapeutically highly effective; non-toxic and has a long shelf life. Monoterpenoid are a mixture of natural compounds specified family and can include the following in table 1 of monoterpenoid. The composition includes sesquiterpenoid, such as LON is iphlen, caryophyllene, α-Humulin, α and j-marulan, bisabolene, γ-cadinen, chamazulene and other In the composition of neutral diterpenes include hydrocarbons (Tinbergen, pemartin), oxide (maniaxe), alcohols (abitol, pomarina, lyrical) and aldehydes (levopimaric). Diterpene or resin acids include compounds such as levopimaric, pimaric, palustria, abietic, dehydroabietic and other The composition includes a natural triterpene acids such as Abasova, abesolutely, Paramonova, α-allgreave preferable. Unsaturated and saturated fatty acids selected from natural acids as malic, citric, tartaric, salewoman, Gallic, and other acids, fatty acids, like oleic, linoleic, linolenic and other The composition comprises a phenolic compound specified family of plants, including simple phenols (family, phenol, phenolic acids, coumarins and other), phenols with two aromatic rings (flavonoids, flavones, isoflavones, and other), polymeric phenols (polyphenols) - tannins or tannins, cachectins etc. In studies of the biological activity of terpenoid substances depending on the source capsule content of terpenes and received monoterpenoids showed a large variability of activity. In about the response to the impact of various stress factors, for example, fungal or viral infections of the trunk, crown or root systems in the vegetation communities of the few Pinaceae family, belonging to 4 genera: Pinus (pine), Picea (spruce), Abies (fir), Larix (larch) there is a shift in the synthesis of secondary metabolites, namely increasing the degree of unsaturation of fatty acids of lipids, increased synthesis of monoterpenoids and low molecular weight fatty acids. These processes are protective aimed at stopping the development of pathological changes in plant cells. Search similar ways among the known solutions have shown that this distinctive feature has not been used previously in the development of various methods of obtaining plant extracts, including missing his description and upon receipt of terpenoid composition Abisil-1 (RU, patent No. 2054945). Classic installation, as it is known (Pharmacognosy, Moscow: Medicine, 1991) is an indication that the collection of various plant materials should be implemented in the period most favorable for plant communities, because during this period they have all the necessary range of biologically active substances. Variations in the collection of various plant materials are marked only on the indication of the period of flowering, blooming or fading. We have found that when using the AI of raw materials, collected in the period of maximum plant growth (July), celebrated the maximum output monoterpenoids and it allows you to save raw materials. In addition, the collection of raw materials to receipt of monoterpenic compounds which are components of terpenoid substance Abisil-2, it is preferable to carry out during the period of higher daytime temperatures, because at this time is the increased content of essential oils. However, as established by us, you can get significant advantages in activity, if you collect raw materials in times of stress plants (trees along trails, sharp fluctuations in day and night temperatures, the defeat of the trunks and crowns of the trees, fungi, parasitic lichens etc). For example, low temperature or the tapping of tree trunk provoke the synthesis of lipids liquid consistency, to prevent the formation in living cells of ice or the occurrence of anatomical destruction. Enriched by these compounds raw materials allows to obtain the substance Abisil-2 with higher biological activity (table 2, example 1). Thus, upon receipt of terpenoid composition Abisil-2 is proposed to use a new, more radical way than just the selection of one or another specific agent from a natural set of terpene is, prisoners in fir capsule. He is creating short-term stress for the trees by mechanical tapping the trunks or the emergence of independent stress in plant life (sharp fluctuations in day and night temperatures during the growing season, smoke, the development of various diseases and so on). Substance Abisil-2 during its receipt of the capsular extract enriched monoterpenoid compounds, which are produced from original raw material collected in example 1 (Example 2). Thus, an important aspect of the present invention is to develop the most effective composition of terpenoid composition Abisil-2, one of which is the use of raw materials with provoked by the release of a certain set of terpenes, and to obtain monoterpenoids, along with this, it is preferable to certain atmospheric temperature. Another important aspect of the present invention is the expansion of the raw materials sources to obtain a terpenoid substance. Currently in the genus Abies allocated 56 Botanical species, 6 of which are natural habitats on the territory of the Russian Federation is the Siberian fir (Abies sibiricus Led.), fir belkora (Abies nephrolepis Maxim}, Sakhalin fir (Abies sachalinensis), fir the Kamchatka (Abies gracilis), Manchurian fir (Abies holophylla Maxim) and fir Myra (Abies mayriana Miyabe et Kudo). We have found that group chemical composition of natural substances Abisil-2 (table 3, example 2) are almost identical, while obtaining 6 different species of fir. Changes in the quantitative composition also vary in identical intervals for all 6 species of fir, but they are characteristic of intraspecific communities. Thus, a raw material for obtaining polyactive terpenoid composition Abisil-2, acting as the substance for medicinal, cosmetic and hygiene products, can serve as components of capsules of different types of fir. The study of anti-inflammatory activity of a medicinal product derived from substance Abisil-2" from 6 different species of fir (example 4, table 3) on the model of infected wounds (Staphylococcus+Klebsiella) in rabbits, showed his identity, as expected, on the basis of their identity group chemical composition. In addition, it is known that terpenoids other members of the family few Pinaceae belonging to 3 genera: Pinus (pine), Picea (spruce), Larix (larch), do not differ by group chemical composition from each other. Terpenoids their Ivic synthesized in the epithelial cells, presents a mixture of monoterpenic hydrocarbons (C10H16), a mixture of the diterpene acids (C 19H29COOH), neutral Sesqui-and diterpenoids. Chemical composition of volatile components derived from zivic various coniferous trees, is almost constant. It includes: tricycle, lemon, α-pinene, β-pinene, MIRCEN, Δ3-Karen, camphene, β-MIRCEN, α-terpinen, terpinolene, α-phellandrene, β-phellandrene, 1,8-cineole, γ-terpinen, n-cimal, citral, camphor, barcelonetta, caryophyllene, longifolene, α-Humulin, terpineol, α-cadinen, β-cadinen, bisabolol, chamazulene and other As you know, capsular extract of fir differs from other terpenoids coniferous trees by the presence of structurally-modified lanostanoid carbon skeleton of the three-terpene acids. All other components are identical to the members of the family few Pinaceae. However, all terpenoids coniferous trees differ in the quantitative content of individual compounds, and hence the physico-chemical properties. However, given the presence of the developed methods of separation of terpenoids on a separate group of fractions and their rearrangement, there is a real possibility of obtaining raw materials for the production of substances Abisil-2 on the basis of terpenes derived from the genera: spruce, pine and larch, provided their enrichment missing triterpene acids and assests is of the required quantitative combinations. The use of this approach will be used as raw materials not only capsular extract of various species of fir in examples 1-3, but the resin of various species of trees of the few Pinaceae family. In favor of this approach is evidenced by the fact that at the present time is set common to all terpenoids antimicrobial and antiviral activity. Terpenoids stimulate various physiological processes in wood, including can carry signaling information, providing stability during times of stress or the development of plant diseases. This common biological functions common to all terpenoids, natural, as it is caused by the presence of the same compounds. Thus, the stated goal is the expansion of the raw materials sources to obtain polyactive terpenoid composition. According to this invention terpenoid composition Abisil-2 can be used as active substances for the manufacture of medicines, cosmetic or hygiene products. As already noted, it is known the use of terpenoids as active substances in obtaining drugs "Abisil-1". The composition has anti-inflammatory, antibacterial and wound healing activity. Also known medicinal the form terpenoids, representing polyactive rectal or vaginal suppositories for the treatment and/or prevention of urology, proctology or gynecological diseases (EN, No. 2198653). New song shows Polichinelle, namely for her committed multiple types of biological activity, wound healing, anti-inflammatory, antibacterial, immunomodulatory, obezbolivaushee and antitumor. In addition, medicines, created on the basis of the substance Abisil-2, suitable for local use, and effects on the body as a whole, as in various pathological conditions associated with impaired synthesis of neurotransmitters, triggers the synthesis of humoral mediators of nerve endings in the brain. In the prototype the same way clinical use has never been developed. Declare us paliativa terpenoid composition Abisil-2 gave substance to obtain pharmacopoeial substance Abisil and for the manufacture of dosage forms: "Abisil - a solution for local and external use oil 20%". For its preparation it is preferable to use olive oil, sunflower oil or soybean oil. Clinical trials of a new drug conducted in the Institute of surgery. Avissawella FRAMES is, in the Central research Institute of dentistry, Regional clinical hospital, Irkutsk, Morozov children's city clinical hospital in Moscow, the Inter-regional burn center of Irkutsk and other centers recommended by the Pharmacological Committee of the Russian Federation confirmed its high efficiency for treatment: 1. In General surgical practice: purulent-inflammatory diseases of the skin and soft tissues (trophic ulcers and nonhealing purulent post-operative and post-traumatic wounds, fistulas, pressure sores, burns and frostbite, abscesses, cellulitis, including the maxillofacial region). 2. In dentistry: stomatitis, periodontal disease, gingivitis, alveolitis, complications of dental prosthetics. 3. In otorhinolaryngology: otitis, evstaheit, sinusitis, rhinitis, rhinopharyngitis, pharyngitis, tonsillitis, post-tonsillectomy, laryngitis. 4. In dermatology: erysipelas, pyoderma. Methods have been developed for local or topical application, namely: 5. When purulent-inflammatory diseases of the skin and soft tissues previously conducted surgical treatment of the wound and then applied the product 1-2 times a day even, thin layer. The duration of treatment depends on the form and severity of the disease (usually 5-10 days) and ends when wiih granulation, Islands of epithelium or complete epithelialization. 6. In inflammatory processes of maxillofacial area after autopsy and surgical treatment of abscesses and phlegmon in his pockets and postoperative wounds injected tampons soaked in a 20%solution of Abisola-2. The procedure is repeated every 5-7 days. 7. Diseases of the oral cavity to treat the affected mucosal surface 2-3 times a day or apply pads soaked in the solution preparation. 8. When otitis - enter the ear canal swab drug. 9. In the treatment of rhinitis, sinusitis instilled in each nostril 1-2 drops 3-4 times a day. When sinusitis drug is injected into the maxillary sinus after its preliminary reorganization. 10. In the treatment of psoriasis and other inflammatory diseases of the pharynx and larynx - process drug mucous membranes 2-3 times per day. 11. Skin diseases - drug applied 1-3 times daily in a thin layer on the affected areas. The course duration is individual and depends on the severity of the disease. Paliativa terpenoid composition Abisil-2 may constitute the main active ingredient and is intended for the manufacture of various drugs. Depending on ways of introduction for preparation of compositions are required pharmacist who Cesky acceptable excipients and carriers. The average effective dose of the composition is preferably from 50 to 200 mg/kg The claimed composition is compatible with any pharmaceutical carriers having a lipophilic base: solvents, ointments, geleobrazuyuschie substances, fillers. It is possible to use solutions, ointments, emulsions, capsules. The possibility of carrying out the invention shown in the examples below. Example 1. Capsular extract, serving as raw material for obtaining polyactive terpenoid composition Abisil-2, obtained from various species of fir (Abies) by direct puncture and collected in a light-proof bottles. Moreover, the natural composition of terpenes should contain provoked (on yield and synthesis) composition for biosecurity from stress factors, enriched identical monoterpenoid compounds. As stress factors can be natural is sharp fluctuations between day and night temperatures, smoke, destruction of trees of various diseases or parasitic mosses, lichens, etc., or deliberately induced (intermittent tapping the trunks of trees - mechanical effect on the crust pressure arbitrary value). Chemical and quantitative composition thus obtained capsule extract op is delali by GLC (gas liquid chromatography) Chromatograph conditions were as follows: - gas chromatograph with a plasma-ionization detector type "Crystal 2000"; - capillary column Zebron ZB-1 (length 30 m, diameter 0.53 mm) or similar, which provides the required separation; - temperature thermostat columns programmable: initial temperature of 135°C for 6 min, followed by heating up to 210°With a speed of 4 deg/min and maintaining this temperature for 5 min; the detector temperature 250°C; - the temperature of the evaporator 250°C; - rate of carrier gas (nitrogen OFS) - 4 ml/min; - the division of the flow 1:7; the analysis time is 30 minutes Check chromatograms performed using the computer program "chromatic Analyst". The content of barcelonetta in percent (x) calculated by the formula:
where a is the sample of the RIS barcelonetta in grams; m - suspension of the drug in grams; S, Sathe peak area of Barceloneta on the chromatogram of the test solution and solution SBM, respectively; Prepare separately a solution of the RIS barcelonetta. About 0.08 g (accurately weighed) of barcelonetta (firm "Fluka") is placed in a volumetric flask with a capacity of 200 ml, dissolved in 40 ml of ether, bring the volume of the solution up to the mark with chloroform, and mix. The shelf life of a solution of 1 day. 2. To test the suitability of chromatog epicheskoi system. Chromatographic system is considered suitable if the following conditions are true: - register at least three reproducible chromatograms of a solution of the RIS barcelonetta; - efficiency speakers designed for peak barcelonetta must be not less than 80,000 theoretical plates; the asymmetry factor of the peak of barcelonetta should be not more than 1.2; the relative standard deviation of the peak area of barcelonetta should be no more than 4%. On the chromatograms of the drug and the solution of the RIS barcelonetta the retention times of the peaks of barcelonetta should not differ by more than 2%. The content of barcelonetta must be at least 10.0 percent. Therefore, if the content is less, to the extract add the required quantity of chemically pure barcelonetta. The relative retention times of components of essential oil were:
Collected raw materials should be stored in light-proof bottles with glass stopper, preventing p is skogo temperature fluctuations and the ingress of condensate or moisture into vials because violation of these terms will exclude the possibility of standardization of tools, made on the basis of this raw material, such as an external criterion. Example 2. Upon receipt of monoterpenic compounds that serve to enrich the feedstock, it is necessary to take into account the fact that their content in the capsules of different types of fir kind of fir varies during the year. Maximum contents observed in July-August and minimum in cold growing season. For example, in may of raw materials, their level does not exceed 20-25%, and in July 30-40%. Because the allocation of monoterpenic compounds is an intermediate process in the manufacture of substance Abisil-2 and requires identical raw materials to obtain preferable to use the July extract in order to save raw materials. Collected raw material is a translucent liquid amber-yellow color with a specific smell. Indicators data analysis from raw materials: 1. PD 20=1.5170, 2. dn20=1.0358 g/ml 3.LD=-12° 4. The data of elementary analysis: With-77,82; N-10,19; S-no, N-no. The allocation fraction monoterpenoids carried out according to the scheme shown in the drawing. Take 250 g of raw materials (capsular extract of example 1) and placed in a three-necked flask with thermometer and barbaroi tube. Water Bastile nozzle for filling and intermediate rings. Copper steam wand has a water gauge glass, safety tube and tee for collecting condensate. The Clevenger apparatus, connected to a three-neck flask, equipped with a heat-insulated section of drop pipe, finger fridge and graduated pipette with a drain tap. Raw materials are heated to stop shedding vapors that condense and dry. Collected under this scheme the equipment already in 7-10 hours allows you to get the necessary monoterpenoid. The number of received monoterpenoids is 33% by weight of mixture taken and corresponds to literature data (from 30 to 40%). Monoterpenoid dried over svezheproseyannym magnesium sulfate. Their physico-chemical properties: dn20=0.884, PD 20=1.4753, LD=-30.2°. The composition of monoterpenoids determined by means of gas-liquid chromatography (GLC) on the chromatograph LHM-7A with a heat conductivity detector (katharometer) and Packed column length 3.0 m, diameter 5 mm, stationary phase "Apiezon-L" on the polychrome, the flow of carrier gas (helium) 30 ml/min, column temperature 125°C, the temperature of the evaporator 180°C. identification of the major components of monoterpenoids conducted on the relative retention time (ECA) and by means of grafting compounds witnesses. Quantitative chemical composition of monoterpenoid composition
Example 3. Polyactive terpenoid composition Abisil-2, which provides the substance for the manufacture of medicinal, cosmetic and hygiene products, prepared on the basis of capsule terpenes various representatives of the genus fir (Abies), obtained in example 1, and monoterpenoids allocated according to example 2. The enrichment monoterpenoids is carried out at room temperature, bringing the contents of barcelonetta in the mixture to the level of not less than 10,0% Based on terpenoid composition Abisil-2 complying with the standardized parameters specified above, will receive a standardized drug "Abisil - a solution for local and external use oil 20%", by dissolving this substance in oil - olive, sunflower or soy. A comparative study of anti-inflammatory and wound healing activity identity of medicines obtained on the basis of various substances of Abisola-2, was carried out on the model of infected wounds (Staphylococcus+Klebsiella) in rabbits (table 2). Experimental data show a significant difference in terms of wound healing in animals. The drug, derived from the materials collected on the background stress the new changes, has higher anti-inflammatory - wound healing on 12-13 day, against 17-19 days for raw materials collected from resting capsules and 28 days in the control. Example 4. Capsular extract, serving as raw material for obtaining polyactive terpenoid composition Abisil-2, prepared as in Example 1, with the only difference that it is carried out by using not only the Siberian fir (Abies sibiricus Led.), but other species of fir (Abies), growing on the territory of the Russian Federation, namely: - fir belkora (Abies nephrolepis Maxim) - Sakhalin fir (Abies sachalinesis) - fir Kamchatka (Abies gracilis) - Manchurian fir (Abies holophilla Maxim) - fir Myra (Abies mayriana Miyabe et Kudo) In the experiment studied the biological activity of all 6 samples, which were obtained in examples 1-3, 6 samples of the drug Abisil - a solution for local and external use oil 20%". The experiments were conducted on models of infected wounds (Staphylococcus+Klebsiella) in rabbits. The results of the study on this model, anti-inflammatory activity (table 4) 6 series drug "Abisil - a solution for local and external use oil 20%", obtained on the basis of the substance Abisil-2, manufactured from raw materials of the 6 species of fir (Abies) indicate identical biologist is political activity. So, for 17 days of the experiment, the percentage healing of surface wounds in rabbits varies in the intervals of 89.9 99.3 percent, and 18 days was 100% in all 6 series of the drug, against 29 days in the control. Example 5 Trials of immunomodulating actions Experiments to study the effects of the claimed terpenoid compositions were performed on mice of BALB/C (males weighing 18-25 g). In each experimental group included 10 animals. As a T-dependent antigen used sheep erythrocytes in the form of a 5%suspension in 0.5 ml. Simultaneously with intraperitoneal immunization with antigen control group of animals is carried out by the injection of olive oil, which is used as a solvent for the studied substance. In the experimental groups of animals simultaneously immunization with T-dependent antigen was injected claimed composition, dissolved in olive oil in a volume of 0.2 ml dose 200,100, 10,1, and 0.1 mg/kg from the weight of the animals. Effectiveness evaluation was carried out based on the analysis of the ability to influence the final level of immunogenesis. These data were obtained 6 days after a single immunization. Quantification was determined by the nature of the formation of antibody productive cells (AFC) in the system in vivo. The level of stimulation of antibody productions was determined by the method of local hemolysis reaction EPHE in the Gard on the 6th day after the immunization of animals. Determined the amount of AFC on the whole spleen and calculated the coefficient of stimulation relative to control. In the reaction of haemagglutination (DSA) with sheep erythrocytes was determined by antibody titer. Received by experience data was compared with a control and was treated by the method of mathematical statistics using student's criterion. The results are presented in table 5. Example 6 The study of antitumor action In experiments were used mouse BALB/c mice. As models of transplantable tumors in mice were used strains - carcinosarcoma Walker 256, melanoma b-16. In each experimental group included 10 animals. Injection was carried out per rectum. As a T-dependent antigen used sheep erythrocytes in the form of a 50% suspension in 0.5 ml. Simultaneously with intraperitoneal immunization with antigen control animal groups carry out the injection of olive oil. Inoculation of tumor strains were intraperitoneally. In the experimental groups of animals simultaneously immunization with T-dependent antigen was carried out per rectum injection of the claimed composition in a volume of 0.2 ml at a dose of 100 mg/kg animal mass. Over the next 6 days experienced animal 2 times a day (every 12 h) was administered per rectum medicinal substance. The evaluation was carried out by able is t to induce transformation of lymphocytes in antibody productive cells of the spleen in animals carriers of tumour and the level of life expectancy. The results are shown in table 6. There is a remission of the tumor using strain carcinosarcoma Walker and a significant percentage of the increase in life expectancy relative to the control - 75%, in the case of tumor strain of melanoma b-16. Example 7 Study of analgesic action. The study was conducted on a group of 30 people (20 men and 10 women) aged 20 to 75 years. Inclusion criteria in the study were: the presence of pain in the lumbar-sacral area, caused by osteochondrosis and spondylarthrosis of the spine. Assessment of intensity of pain patients was carried out in the course of everyday activities on a ten-point visual analogue scale and the characteristic of the effectiveness of treatment on subjective report sick. Applied topically to the affected area a 20% solution of the substance of terpenoids in olive oil. After 1 hour, a significant decrease in pain was observed in approximately 12% of patients. When applied twice a day over two days - at least half of the patients. Pain when moving significantly decreased in 56% of patients, 12% of patients the effect was questionable. However, two weeks to 89% noted the lack of pain during movement. Example 8 The study of the acute toxicity of samples used substance Abisil-2" in Lakers the governmental form 20% oil solution, carried out on outbred white mice, showed that LD508.5 and 9.3 ml/kg and the LD100- 15 ml/kg Thus the composition according to the invention has the following advantages: on the basis of the substance Abisil-2 designed according to the proposed methods of preparation, can be manufactured drugs of any desired concentration; - drug Abisil-2 is suitable for the manufacture of medicinal products intended for the treatment of diseases of different localization; - drug Abisil-2 convenient storage and transport; - clinical applications of drugs manufactured on the basis of polyactive terpenoid composition Abisil-2, allows us to provide a local therapeutic effect, but also the body as a whole. - use of drugs, based on the drug Abisil-2, is economically advantageous, because, given its Polichinelle, eliminates the use of various integrated tools.
Group chemical composition of natural terpenoid composition Abisil-2, obtained from 6 different species of fir (Abies)
Trials of immunomodulating actions
Studies of antitumor action tr>
The drawing shows the apparatus used to highlight monoterpenoids from the feedstock (capsular extract of example 1). The necessary equipment presents two electric adjustable heated copper engine, equipped with a water gauge glass, safety tube and tee for collecting condensate and water bath, three-neck flask (which is placed in the capsular extract), Clevenger apparatus with a heat-insulated section outlet pipe, a finger fridge and graduated separating the pipette with a drain tap. Monoterpenoid arrive at the receiver. 1. The tool that has wound-healing, anti-inflammatory, antibacterial, immunomodulatory, analgesic and antitumor activity on the basis of terpenoids, characterized in that the capsule contains extract of plants of the family few Pinaceae subject to short-term stress effects, enriched in monoterpenoids separated from the capsular extract, if e is ω it contains the following components, wt.%:
and has the following physical constants: acid number of 70 to 90, the number of saponification 100-130, ester value 10-60, the refractive index of 1,500 to 1,520, and the content of monoterpenoid of barcelonetta is not less than 10.0% of the total composition of terpenoids. 2. The tool according to claim 1, characterized in that the few Pinaceae plant family selected from the group: Siberian fir (Abies sibiricus Led.), fir belkora (Abies nephrolepis Maxim), Sakhalin fir (Abies sachalinensis), fir Kamchatka (Abies gracilis), Manchurian fir (Abies holophylla Maxim) and fir Myra (Abies mayriana Miyabe et Kudo). 3. Pharmaceutical composition with wound healing, anti-inflammatory, antibacterial, immunomodulatory, analgesic and antitumor activity, characterized in that it includes a tool according to claim 1 in an effective amount and the target for seconds. 4. Farmatsevticeski the composition according to claim 3, characterized in that as the target additives it contains oil selected from sunflower, olive and soybean oil. 5. The use according to claim 1 for the preparation of a medicinal product for the treatment of inflammatory diseases. 6. The use according to claim 5, where these inflammatory diseases are diseases of the skin, mucous membranes or soft tissue. 7. The use according to claim 5 or 6, where these purulent-inflammatory diseases selected from otitis, evstaheit, sinusitis, rhinitis, rhinopharyngitis, pharyngitis, tonsillitis, post-tonsillectomy, laryngitis. 8. The use according to claim 5 or 6, where these purulent-inflammatory diseases selected from stomatitis, periodontal disease, gingivitis, alveolitis, complications of prosthesis.
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