Method of intensifying antiaggregant activity
SUBSTANCE: method of intensifying antiaggregant activity in an experiment involves use of a chemical compound which is a conjugate of beta-cyclodextrin with acetylsalicylic acid.
EFFECT: wider range of agents for increasing antiaggregant activity.
The invention relates to medicine, namely to experimental pharmacology.
To date, the known method antiplatelet activation using acetylsalicylic acid (aspirin)with antiplatelet and anti-inflammatory properties , but at present this drug is outdated and has a number of side effects.
The purpose of the invention is the expansion of the means to increase antiplatelet activity.
This goal is achieved by the use of the new synthesized compound, which is the conjugate beta-cyclodextrin with acetylsalicylic acid.
Synthesis of applicable connection
Conjugate beta-cyclodextrin with acetylsalicylic acid synthesized in the research laboratory of organic chemistry Department of Moscow state pedagogical University.
To a solution of 0.50 g (0.441 mmol) of β-cyclodextrin in 8 ml of pyridine under stirring was bury 0.44 g (2.20 mmol) of the acid chloride acetilsalicilico acid in 2 ml of benzene was kept at 20°C 24 h of the pyridine Hydrochloride was filtered, the filtrate was evaporated, the residue was rubbed out in ethyl alcohol (10 ml), precipitated precipitate was filtered, washed with ethanol (2×5 ml) and dried in vacuum.
The yield of compound (I) 0.47 g (63%), TPL 203-205°C, Rf0.78 (n is the aluminum plates with a fixed layer of silica gel, in the system acetonitrile-water 5:2). An NMR spectrum1N (d6-DMSO), δ, M. D.: 2.05-2.35 m (10.5H, C(O)CH3), 3.13-4.08 m (42H; C2H-C5H, C6H2), 4.23-4.59 m (3.5H, C6OH), 4.81 ush. (7H, C1H), 5.60-6.04 m (14H; C2OH, C3OH), 7.05-8.11 m (14H, CHarene.). NMR13C (d6-DMSO), δ, M. D.: 20.8 (C(O)CH3), 59.4 (C6OH), 63.9 [C6OC(O)], 68.9 [C5C6OC(O)], 71.5-74.0 (C2C3C5), 80.1-83.0 (C4), 101.0-103.1 (C1), 122.1-135.0 (Carene.), 150.1 [COC(O)], 169.2 [C(O)]. Found, %: C, 51.11; H, 5.45. C73.5H91O45.5. Calculated, %: C, 51.85; H, 5.39.
The formula of the obtained compound
In the experiment in vitro was tested antiplatelet activity against platelet plasma rich. Drug comparison served as acetylsalicylic acid (aspirin).
To study the functional status of platelets by the photometric method used platelet-rich plasma (PRP) and a suspension of washed platelets. In the morning, before feeding laboratory animals (white outbred rats), took the blood from the jugular vein into a plastic syringe containing anticoagulant (3.8% (0.11 M) solution of sodium citrate in the ratio of 9:1. All manipulations with blood, plasma, platelet-rich, and a suspension of washed platelets was carried out in a plastic container. Received what I platelet-rich plasma, the blood was centrifuged in plastic tubes at room temperature for 10 minutes for sedimentation of erythrocytes and leukocytes. The platelet count of PRP was counted in the Goryayev camera on the microscope MBI-15 with a phase-contrast console and brought to 2×1011-2.5×1011platelets/l using plasma poor in platelets (PPP). PRP was obtained by repeated centrifugation of the blood within 10 minutes. PRP was stored at 4°C.
Assessment of platelet aggregation was performed on aggregometry PICA (model 330, USA), as well as dual aggregometry LaborAPACT (USA) with graphic recording and automatic calculation of the amplitude and maximum velocity of the aggregation. Agregatogramme analyzed the amplitude (maximum value drop optical density, expressed in %); the maximum rate of aggregation (expressed in %/min). All the experiments were carried out in six parallel test, where experimental sample was compared with a control sample. As inducers of platelet aggregation used thrombin at a final concentration of 0.5 units/ml of Blood were incubated 5 min with samples at 37°C.
As an example, in table 1 the data antiaggregatory activity of the conjugate beta-cyclodextrin with acetylsalicylic acid obtained in the experiment in vitro.
|Antiplatelet activity of the conjugate beta-tsiklodestrina with acetylsalicyl the howling acid|
|Sample||The concentration of anti-inflammatory drugs in the sample (mm)||Amplitude (%)||Speed (% / min)|
|Conjugate beta-cyclodextrin with acetylsalicylic acid||0,02||13.0±3.5*||13.0±6.1*|
|* p<0.05 compared with control|
Sources of information
1. Mashkovsky PPM Medicines. M.: Izd. "New wave", 2005, 1206 S.
2. Manual on experimental (preclinical) study of new pharmacological agents. Under the General editorship Rugarama. M.: 2005. 829 S.
3. K.Uekama, F.Hirayama, T.Irie, Chem. Rev, 98(5), 2045-2076 (1998).
4. M.E.Davis, M.E.Brewster, Nature Rev. Drug Discovery, 3, 1023-1035 (2004).
5. Cyclodextrins and their complexes. Chemistry, analytical methods, applications. // Ed. H. Dodziuk, Wiley-VCH, Weinheim. 2006. 489 p.
6. K.Uekama, Campam, F.Hirayama, J. Med. Chem, 40 (17), 2755-2761 (1997).
A way to enhance the antiplatelet activity in the experiment, characterized by the fact that h is about as antiplatelet tools used chemical compound, representing conjugate beta-cyclodextrin with acetylsalicylic acid when the degree of substitution of 3.5.
SUBSTANCE: method of obtaining complex with inclusion of cyclodextrin can include dry mixing of cyclodextrin and hydrocolloid for formation of dry mixture and mixing solvent and guest with dry mixture for formation of complex with inclusion of cyclodextrin. In some versions of realisation method of obtaining complex with inclusion of cyclodextrin can include mixing of cyclodextrin and hydrocolloid for formation of first mixture, mixing of first mixture with solvent for formation of second mixture and mixing of quest with second mixture for formation of third mixture.
EFFECT: elaboration of efficient method of obtaining complex with inclusion of cyclodextrin.
41 cl, 17 ex
SUBSTANCE: molar ratio of cyclodextrin to the acid in the complex comprises 1:1. The complex is obtained by introduction of concentrated water cyclodextrin solution heated to boiling point to glacial acetic acid of room temperature, with further separation and drying of crystalline sediment. Complex of α- or β-cyclodextrin with acetic acid is stable in dry state, but in water solution it is decomposed into components. Obtained solution gains properties of dilated acetic acid, and therefore can be used as flavouring in food concentrates, as preservation agent, solution acidity regulator, and as buffer component in biochemistry and analytical chemistry.
EFFECT: enhanced efficiency of composition.
3 cl, 4 ex, 1 tbl
SUBSTANCE: invention relates to cyclodextrin-containing polymeric compounds, which are carriers for delivery of therapeutics, and pharmaceutical preparations based on them. Invention also relates to method of treating subjects with therapeutically effective quantity of said cyclodextrin-containing polymeric compound. Claimed cyclodextrin-containing polymers improve medication stability, increase its solubility and reduce toxicity of therapeutics when used in vivo. Furthermore, by selecting from a variety of linker groups and targeting ligands of said polymers it is possible to realise controlled delivery of therapeutic agents.
EFFECT: obtaining cyclodextrin-containing polymer compounds, improving medication stability, increasing its solubility and reducing toxicity of therapeutics when used in vivo.
56 cl, 13 dwg, 7 tbl, 46 ex
FIELD: chemical technology.
SUBSTANCE: invention relates to the inclusion complex of cyclodextrins with elemental sulfur. Complex can be prepared using different homologues of cyclodextrins, for example, beta- and gamma-cyclodextrins and hydroxypropylated forms of gamma- and beta-cyclodextrins. Proposed complex can be used as a biologically active compound for medicinal, veterinary and agricultural designation. Invention provides the possibility for further preparing true solutions of elemental sulfur in water in the concentration up to 250-300 mg/l.
EFFECT: improved preparing method, valuable properties of complex.
7 cl, 7 ex
FIELD: chemical technology.
SUBSTANCE: invention describes a method for preparing immobilized β-cyclodextrin. Method involves pretreatment of organic and inorganic sorbents - polyvinyl alcohol and sorbitol based on silica with glutaraldehyde for incorporation of aldehyde group molecules into sorbents, washing out with water and dimethylsulfoxide on glass porous filter, drying on glass porous filter followed by addition of prepared sorbents to dimethylsulfoxide solution containing dissolved β-cyclodextrin in the ratio sorbent : β-cyclodextrin : dimethylsulfoxide = 1.0:(0.4- 2.0);10, respectively, stirring the prepared suspension at temperature 25-70°C for 30-180 min, washing out and drying. Method provides preparing an insoluble sorbent with immobilized β-cyclodextrin used for removing cholesterol or its derivatives.
EFFECT: improved preparing method.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention describes a derivative of 6-mercaptocyclodextrin of the general formula (I):
wherein n = 0-7; n = 1-8 and m + n = 7 or 8; R represents (C1-C6)-alkylene substituted optionally with 1-3 OH-groups, or (CH2)o-phenylene-(CH2)p wherein o and p = 0-4 independently; X represents COOH, CONHR1, NHCOR2, SO2OH, PO(OH)2, O(CH2-CH2-O)q-H, OH or tetrazole-5-yl; R1 represents hydrogen atom (H) or (C1-C3)-alkyl; R2 represents carboxyphenyl; q = 1-3; or its pharmaceutically acceptable salt in mixture with pharmaceutically acceptable accessory substances. Also, invention describes a set and pharmaceutical composition for reversing drug-induced neuromuscular blocking comprising derivative of 6-mercaptocyclodextrin of the general formula (I), and a method for reversing drug-induced neuromuscular blockade in patient that involves parenteral administration to indicated patient the effective dose of 6-mercaptocyclodextrine derivative of the general formula (I) by cl. 1.
EFFECT: valuable medicinal properties of agents.
11 cl, 1 tbl, 20 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to medical pharmacology. Pharmaceutical composition with antibacterial activity includes fluoroquinolone, cyclodextrin and hydrochloric acid, and molar ratio of fluoroquinolone to cyclodextrin consists 1:0.5-2.0, composition additionally contains buffer component with the following component ratio, wt %: fluoroquinolone 0.5-10.0; cyclodextrin 3.0-45.0; hydrochloric acid 0.0005-1.0; buffer component 0.1-2.0; water to 100.0.
EFFECT: invention insures high composition stability.
6 cl, 4 dwg, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, particularly, to a preparation for treating heartburn and/or gastroesophageal reflux disease. A pharmaceutical preparation for treating heartburn and/or gastroesophageal reflux disease containing an effective amount of water-soluble branched or linear polysaccharide which represents galactomannan made of fenugreek seeds. A method of treating heartburn and/or gastroesophageal reflux disease in a human. Application of fenugreek seed galactomannan for producing the drug for treating heartburn and/or gastroesophageal reflux disease. Application of fenugreek seed galactomannan for producing the drug for delay or prevention of onset and development of acid-peptic disorders or the diseases caused by the other injures of gastric mucosa and epithelium. Application of fenugreek seed galactomannan for producing the drug for abatement of pregnancy-related temporary acid reflux.
EFFECT: preparation is effective for abatement of heartburn and/or gastroesophageal reflux disease.
12 cl, 1 dwg, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, more specifically concerns a method for making an aqueous solution containing beta-cyclodextrin in the concentration more than 0.5 wt/wt %, involving combining in an aqueous liquid beta- cyclodextrin and niacin amide or niacin wherein an amount of niacin amide or niacin combined in the aqueous liquid is enough to provide the concentration of dissolved beta- cyclodextrin more than 0.5 wt/wt % at temperature 5°C. The prepared solution is used for preparing a pharmaceutical drug containing an amphiphilic or lipophilic drug.
EFFECT: invention provides better solubility of beta-cyclodextrin in the aqueous liquid.
10 cl, 5 ex, 6 tbl, 1 dwg
SUBSTANCE: invention concerns microbiology and biotechnology. There is offered a method for prepared activated mononuclear leukocytes involving the use of interleukin-2 in combination with cyclodextrin for mononuclear cell activation, a lymphocyte and macrophage concentrate recovered from donor or patient blood is activated in vitro with a complex containing a pharmacopeia preparation of recombinant interleukin-2 within the range of suboptimal doses 50-100 MU in 1 ml of the culture medium and β-cyclodextrin in concentration 1×10-5-1×10-3 M in the culture medium at the molar ratio of components either 1:1, or 1:3, or 1:10, the lymphocyte and macrophage concentrate of donor or patient blood is processed in vitro with a complex containing a pharmacopeia preparation of recombinant interleukin-2 within the range of suboptimal doses 50-100 MU in 1 ml of the culture medium and β-cyclodextrin in concentration 1×10-5-1×10-3 M in the culture medium the molar ratio of components either 1:1, or 1:3, or 1:10.
EFFECT: invention provides the preparation of IL-2/CD-MNL with high cytotoxic activity to tumour cell lines; 10-fold reduction of IL-2 doses with preserved clinical effectiveness of the activated cells allows reducing the intensity of systemic by-effects of the preparation, and also the use of immunotherapy in debilitated oncological patients, including in the patients with a hyperreactive response to the IL-2 introduction.
2 ex, 1 tbl, 10 dwg
SUBSTANCE: formulation is adapted for introduction to a subject by dispersing with any known spray; said formulation can be included in a kit. The formulation is introduced in the form of an aqueous solution; however it can be stored as a dry powder, a prepared solution or a concentrated composition. The formulation is used in advanced spray system for corticosteroid inhalation. SAE-γCD found in the formulation considerably improves chemical stability of budesonide. There is described a method for inhalation of the formulation. The formulation can be also administered by a common intranasal apparatus. The formulation can contain one or more additional therapeutic agents to be used in combinations with said corticosteroid. SAE-γCD is especially effective for solubilisation of etherified corticosteroids.
EFFECT: development of the inhalation formulation containing SAE-γCD and said corticosteroid.
27 cl, 2 tbl, 5 dwg, 20 ex
SUBSTANCE: invention relates to chemical-pharmaceutical industry and concerns an inhalation composition containing SAE-β-CD and a corticosteroid. The composition is adapted to sprayed administration with the help of a dispenser. The composition can be provided in a set. The composition is administered in the form of water solution, however, it can be stored as dry power, ready-to-use solution or concentrated composition. The composition is applied with the help of an advanced spray system for corticosteroid inhaled administration. SAE-β-CD contrained in the composition significantly enhances budesonide chemical stability. Invention also concerns method for inhaled administration of the composition. The composition can also be administered nasally with the help of an ordinary device for preparation nasal administration.
EFFECT: composition is characterised with high stability and bioavailability.
37 cl, 20 ex, 18 dwg
SUBSTANCE: invention concerns to medicine, namely experimental pharmacology. The invention purpose is examination of antiphlogistic (antiinflammatory) activity of a synthetic agent for creation of a new antiinflammatory medicinal substance. For this purpose a model of acute inflammatory edema is created experimentally. Then the agent received by covalent imposing of the rests of acetylsalicylic acid to betacyclodextrins is administered to a laboratory animal. Introduction of the given agent provides reliably significant inflammation reduction.
EFFECT: provision of reliably significant reduction of inflammation.
1 ex, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention concerns medical products and concerns capsules for delivery of biologically active agent, containing: a water-soluble, washed away, blasted and-or bulking up cover; and b) the water filling composition including one or more active agents, the water which is in quantity from at least approximately 10% of masses/masses, to less than approximately 70% of masses/weights; and water-soluble derivative cyclodextrin, present at quantity of at least 30% of mass/mass, in recalculation on a total weight of water and derivative cyclodextrin in a filling composition where the quantity derivative cyclodextrin is enough for suppression of dissolution, washing out, destruction and-or a swelling of the cover, caused by water in a filling composition and where the capsule has a period of storage at least one week. Also the way of stabilisation of a capsule is opened.
EFFECT: creation of capsules with steady against dissolution, washing out, destruction and swelling covers.
51 cl, 11 dwg, 11 tbl, 10 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention concerns area of medical products, in particular to application of complex bonds of iron (III) with carbohydrates or their derivatives for reception of a medical product for improvement of immune protection and-or activity of a brain at patients without an anaemia caused by deficiency of iron or deficiency of iron in which complex bond of iron (III) is iron (III)-polymaltose complex bond or complex bond of iron (III) with a product of oxidation one or several maltodextrins.
EFFECT: development of preparations for improvement of immune protection and-or activity of a brain at patients without an anaemia caused by deficiency of iron or deficiency of iron.
7 cl, 1 tbl, 1 ex
FIELD: medicine, polymeric materials, pharmacy.
SUBSTANCE: invention describes biomaterial as a deposit comprising at least one suitable anion-active polymeric water-soluble component and amphiphilic component of ammonium type comprising a cationic surfactant. Deposit is prepared in the following steps: (1) contacting anion-active polymeric component and cyclodextrin component in aqueous medium, and (2) addition of the above said amphiphilic component of ammonium type to mixture prepared in the step (1) wherein components are taken in amounts providing formation of above said deposit. Biomaterial is used for preparing a depot-composition with regulated release and acceptable for prolonged feeding pharmaceutical substances. Also, invention describes a medicinal agent comprising biomaterial and representing a sheet material or film for closing and healing wounds, or surgery thread, and medicinal implant, or insert comprising the preliminary molded biomaterial.
EFFECT: improved preparing method, valuable properties of material.
27 cl, 34 ex
SUBSTANCE: invention relates to medicine, namely to endocrinology and can be used for reduction of hypoglycemia acute exacerbation or severe hypoglycemia exacerbation in patients with type II diabetes after treatment with insulin. For this purpose vildagliptin or its salt is introduces to patient in combination with insulin.
EFFECT: invention ensures reduction of risk of hypoglycemia development, as well as necessity to apply several antihyperglycemic medications.
12 cl, 1 tbl, 1 ex