Compound cis-diammineplatinum (ii) with a copolymer of na-salt of maleic acid and furan, with immunostimulatory and antitumor activity, with a wide interval of therapeutic doses of low nephrotoxicity
(57) Abstract:The invention relates to the field of high-molecular chemical compounds with antitumor and immunostimulating activity. Usage: in medicine in the treatment of cancer. Compound CIS-diammineplatinum (P) with a copolymer of Na-salt of maleic acid and furan has immunostimulating and antitumor activity at low nephrotoxicity. 5 table. The invention relates to the field of high-molecular chemical compounds with antitumor and immunostimulating activity.Known to be similar in structure connection: copolymer salt of maleic acid with furan (SFMC) of the following formula:
HH (I) where m 10-60, 2300-13600, but unlike the claimed compounds do not contain complex-bound platinum. There is information about weak antitumor activity of the compounds of formula (I)  However, the effectiveness of antitumor activity of tested compounds of formula (1) is low and is not of interest for practical chemotherapy of tumors (see table.1). The connection is also weak immunostimulirutuyu activity 
Nearest in formula
Cisplatin is widely used in clinical practice for the treatment of cancer. Mechanism of action refers to the drugs, the overwhelming DNA synthesis of tumor cells.However, during anticancer therapy cisplatin, as well as other drugs, in addition to the action on malignant neoplasms, have a significant toxic effect on the body. Cisplatin highly toxic substance (LD5012-14 mg/kg for mice and rats). The main factor which limits therapeutic course and forced to interrupt treatment the damage in varying degrees (depending on dose) the tortuous channel of the kidney 
One of the major drawbacks of applying currently anticancer drugs, including cisplatin, is their immunodepressant effect on the body (see tab.2).The aim of the invention is the creation of new polymeric platinum complex having immunostimulating and antitumor activity with a wide interval of therapeutic doses at low nephrotoxicity.The connection is an amorphous yellow powder, soluble in water and physiological CLASS="ptx2">When heated this complex decomposes without melting at a temperature of 190aboutC.Polymer complex obtained by interaction of the copolymer Na-salt of maleic acid and furan of formula II with Cys-his diaminedichloroplatinum (P) of the formula [Pt(NH3)2(OH)2] (NO3)2taken in a molar ratio of from 8:1 to 2:1 (excess polymer component) in aqueous solution.The composition of the reaction products (the parameter x in the formula (III) is adjusted by changing the molar ratio platypodinae and polymeric reagents of the reaction mixture (see examples).The structure of the obtained polymer complexes confirm methods of elemental analysis, atomic-absorption spectroscopy and IR spectroscopy.The inventive compound of formula (III) is characterized by the following vibrational frequencies in the IR spectra (obtained on a Specord M-80), cm-1:
1590-1600 stretching vibrations of C=0 connection ionized COOH groups;
1070-1110 stretching vibrations ties WITH-0;
517-490 stretching vibrations due PT nThe above spectral data and elemental analysis and atomic adsorption spectroscopy (see examples) indicates, analysis and atomic adsorption spectroscopy), n 20-25, =5000-12000 (determined by the molecular weight used for the synthesis of compounds of the copolymer Na-salt of maleic acid and furan) and the content of PT in the sample.For synthesis take as starting copolymer with =4500-5500 as at < 4500 biological activity of the compounds is markedly reduced, and when the > 5500 increases toxicity.Obtaining complex is illustrated by the following examples.P R I m e R 1. In distilled water (100 ml) dissolve 0.18 g (0,0006 mol) PT (NH3)2Cl2and add an aqueous solution 0,204 g (0,0012 mol AgNO3(reaction 1)
Pt(NH3)2Cl2+2AgNO3____ 2AgCl + (Pt(NH3)2(OH)(NO3)2(1)
Precipitated AgCl precipitate is filtered off and the filtrate is poured with stirring to a solution of the copolymer Na-salt of maleic acid and furan 0.28 to (0,0012 mol per comonomer link) dissolved in 100 ml of distilled water (reaction 2)
HH + Pt(NO3)2___
(2) ___ HH
To remove low molecular weight impurities (NaNO3, unreacted platinum complex) aqueous solution of complex compounds of platinum with a copolymer is subjected to ultrafiltration, are separated from the solution by lyophilic Duskwood molar ratio of 2:1 (excess polymer component). Output 0,230 g (73.5% of theory. ).The elemental composition of the obtained product:
Calculated, 30,04, N 2,82, N Of 4.38, Pt 30,5, PA 7,2.Found, C 31,02, H 2,95, N 4,87, Pt 26,07, Na 6,5.The obtained compound of the following formula:
HH where x 0,46; r 25; 12000.P R I m m e R 2. Conditions for obtaining complex compounds of platinum with a copolymer similar to that described in example 1. For the reaction to take 0,276 g (0,0012 mol) copolymer Na-salt of maleic acid and furan, and 0.09 g (0,0003 mol) PT (NH3)2CL2and 0,117 g (0,0006 mol AgNO3that corresponds to the ratio of SFMC:CPU=4:1 (excess of the copolymer). Output 0,233 g (71,2% of theoretical. ).The elemental composition of the obtained product:
Calculated, 35,1; N 2,7; N 2,6; Pt 17,8; Na 12,6.Found, C And 36.2; H 2,8; N 2,5; Pt 16,7; Na 11,5.Received the following connection:
HH where x 0,23; 8100; n 20.P R I m e R 3. Reaction conditions similar to those described in example 1. To obtain a polymer complex taking 0.28 g of copolymer Na-salt of maleic acid and furan, 0,045 (0,00015 mol) PT(NH3)2Cl2and 0,058 g (0,0003 mol AgNO3that corresponds to reagent ratio 8:1 (excess polymer component). Output 0,216 g (72.3% of theoretical.).The elemental composition polucen is Holocene connection formulas
_ __ where x 0,11; 5000; n20.Determination of acute toxicity of the compounds is carried out according to the method of C. B. Prozorovsky  found that LD50the tested substances ranged from 1500 to 1700 mg/kg depending on the percentage of platinum in the polymer complex. It should also be noted that even when using doses with a high content of platinum (in terms of metal) visible toxic effects not observed (example 13 of table.1).The study of antitumor activity of polymeric complexes of platinum carried out in experiments on outbred mice (females weighing 20-25 g) inoculated intraperitoneally with Ehrlich adenocarcinoma. Ascitic carcinoma, Ehrlich tumor, relatively resistant to widely used currently in the clinic cisplatin formula II recommended Farmkomiteta the USSR as one of the models for testing new drugs.Perepevku tumors carry intraperitoneally with the introduction of 0.5 ml of ascitic fluid. Drugs dissolved in saline and administered to the animals intraperitoneally once a day after tumor inoculation. The effectiveness of the treatment is evaluated on the basis of changes in the average long is presented in table.1.Studied the antitumor activity SFMC-P model lymphocytic leukemia P-388, also recommended by Farmkomiteta the USSR for testing new drugs. Testing of anti-tumor activity in this model showed that the complex is significantly more active compared to the CPU at a much lower toxicity of effective doses. So, when administered to mice with experimental lymphocytic leukemia P-388 SFMC-P at a dose of 600 mg/kg there was an increase ALE by 128% compared to control, while the introduction of the CPU at the maximum tolerated dose of 7 mg/kg leads to an increase in mean life span of only 30%
The influence of polymeric complexes of platinum on some parameters of the immune response. Studies conducted on mice-female line of the IAS. In the experiment using five groups of animals, each of which is injected, respectively, cisplatin (similar biological activity), a copolymer of furan and Na-salt of maleic acid (similar structure), their mechanical mixture or complex compound of platinum.The CPU is injected at the maximum tolerated dose of 7 mg/kg (containing 4.5 mg/kg of platinum). Mechanical mixture of the calculation 42 mg/kg SFMC and 7 mg/kg CPU (4.5 mg/kg of platinum). Drugs dissolved in physiological rocity sheep. In the course of the research study the following indicators: change in antibody productive activity of spleen cells (KLA) and the rosette activity of lymphoid cells of the spleen (AND ROCK). The results obtained are presented in table.2.Studied the effect of polymer complex of platinum on the kidneys. Experiments carried out on white rats-female line Wister weighing 180-200 g of tested compound dissolved in saline injected animals intraperitoneally. The effect of the claimed compounds on renal function compared with the effect on them of cisplatin. Through 5 days after the administration of cisplatin at a dose of 5 mg/kg (3.5 kg in terms of pure metal) in rats revealed a typical picture of acute renal failure: a marked violation of the excretory function of the kidney drops sharply diuresis, more than 20 times reduced glomerular filtration, which is determined by the clearance of endogenous creatinine concentration of urea in serum is increased 15 times, as well as the content of creatinine (table. 3,5). Significant changes are observed in kidney tissue and the body weight increased almost in 2 times, develops massive edema renal tissue, increased content of Na, K, CA and Mg (see table.4).From the data presented in table.3,4,5 shows that the proposed complex at a dose of 100 mg/kg for all indicators is considerably less toxic than cisplatin, despite the high (3 times higher than in the cisplatin) the content of platinum in terms of pure metal. Compound CIS-diammineplatinum (II) with a copolymer of Na-salt of maleic acid and furan General formula
< / BR>where X 0,11 0,46;
n 20 25,
with mol.m. 5000 12000,
possessing immunostimulatory and antitumor activity, with a wide interval of therapeutic doses at low nephrotoxicity.
FIELD: experimental medicine.
SUBSTANCE: on should introduce solution into fracture area at the following ratio of ingredients, g/l: 1-hydroxyethylidenediphosphonic acid 1.80 - 2.06, water-free calcium chloride 1.44 - 2.22, gadolinium (III) nitrate hexahydrate 0.30 - 0.40, dysprosium (III) chloride hexahydrate 0.038 - 0.076, moreover, solution's pH corresponds to 7.3 - 7.8. The present innovation enables to shorten the process of bony tissue regeneration in the site of its lesion or defect and, also, shorten the period for restoring normal physiological function of traumatized bone.
EFFECT: higher efficiency of regeneration.
22 ex, 1 tbl
FIELD: pharmaceutics, veterinary science.
SUBSTANCE: the present innovation deals with preventing and treating hypomicroelementosis in different farm and domestic animals, furred animals, and, also, for enhancing the growth in animals, and treating a number of specific diseases and, also, for maintaining microelemental composition of feedstuffs. The suggested preparation includes chelated complex of iron, manganese, zinc, copper, cobalt, selenium and iodine with organic ligand of complexone type and water. According to the innovation as a chelation ligand it contains trisodium salt of methionine succinic (α-amino-γ-methylthiobutyric-N-succinic) acid at a certain ratio of components. The innovation provides to obtain preparation in soluble form being capable to be well digested by the animal.
EFFECT: higher efficiency.
SUBSTANCE: after keeping during pharmaceutically acceptable period oxaliplatinum is placed in transparent, colorless and residue-free solution at concentration of, at least, 7 mg/ml, and a solvent contains sufficient quantity of, at least, one hydroxylated derivative chosen among of 1.2-propandiol, glycerol, maltite, saccharose and inositol. The innovation describes the way to obtain such a preparation. The preparation is stable during pharmaceutically acceptable period of time, that is it remains transparent, colorless and free of any residue within the range of 2-30 C that could be available during its transportation, storage and/or any handling.
EFFECT: higher efficiency of application.
14 cl, 6 ex, 4 tbl
FIELD: experimental medicine, oncology, biology.
SUBSTANCE: invention relates to a method for inhibition of tumor growth using radiation therapy as ionizing radiation with additional administration of mixture of octa-4,5-carboxyphthalocyanine sodium cobalt salt or oxocobalamine with sodium ascorbate in the ratio = (1:10)-(1:30). Method of combined using irradiation and indicated mixture of substances provides enhancing the effectiveness of anti-tumor treatment resulting to 70-100% recovery of experimental animals and reducing radiation loading and toxicity.
EFFECT: improved method for inhibition.
2 tbl, 3 dwg, 3 ex
FIELD: medicine, oncology.
SUBSTANCE: invention relates to a method for assay of efficacy on post-operative intrathecal chemotherapy of patients with intracerebral malignant tumors. Method involves determination of total protein level in cerebrospinal fluid before and after carrying out chemotherapy in autoliquor. Increase of the level of total protein by 5.6-6.3 times indicates on effectiveness of the post-operative chemotherapy. Method provides the objective evaluating dynamic of cytolysis of tumor cells that is the reliable method for estimation of efficacy of indicated treatment.
EFFECT: enhanced and improved method for treatment.
FIELD: veterinary science.
SUBSTANCE: the suggested preparation for treating diarrhea in farm animals youngsters contains bismuth salt in the form of bismuth-potassium ammonium citrate and, additionally, polyethylenoxide, moreover, preferably, it contains 1.5-2.5%-polyethylenoxide solution and 1.5-2.5%-bismuth-potassium ammonium citrate solution. The method for treating diarrhea deals with introducing the above-mentioned preparation once or twice daily for 1-2 d at the dosage of 1-75 ml/kg body weight. In young foxes it should be introduced at the dosage of 60-75 ml/kg body weight, in calves - at the dosage of 1-3 ml/kg body weight, in lambs - at the dosage of 2-3 ml/kg body weight. Application of the present complex preparation and therapeutic method enables to shorten terms of therapy by 1.5-2 times, decreases expenses for therapy by 3-5 times and provides decreased toxicological impact the preparation upon animal body.
EFFECT: higher efficiency of therapy.
6 cl, 3 ex, 2 tbl
FIELD: organic chemistry, medicine, oncology, pharmacology.
SUBSTANCE: invention relates to a composition used in treatment of proliferative diseases and comprising the platinum coordinating complex with an anti-tumor agent and derivative of pentafluorobenzene sulfonamide. Also, invention relates to a method for treatment by using the indicated composition. The composition possesses the synergetic effect.
EFFECT: improved and valuable method of therapy.
13 cl, 5 dwg, 1 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a medicinal preparation used in treatment of viral diseases and prophylaxis of infectious epizootic processes. The preparation comprises an active substance prepared on the base of antimony and represents a finely crystalline sorbent consisting of structural links of the formula:
and having particles size (1 x 10-5)-(9 x 10-5)μm and used in the dose 100-120 mg/kg. The preparation represents suspension for intramuscular or intravenous administration or it can be included into capsules for oral intake. The prepared preparation possesses higher antiviral activity and broader spectrum of antiviral effect.
EFFECT: improved and valuable medicinal properties of preparation.
3 cl, 8 tbl, 5 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical composition used for stabilization of homeostasis and arresting pathological processes in the body. Invention proposes a pharmaceutical composition as powder with particles size from 250 to 400 mcm comprising the following components by the first variant, wt.-%: carbon, 10.01-53.02; oxygen, 30.10-53.10; potassium, 0.26-1.99, and calcium, 0.20-31.37, and comprising the following components by the second variant, wt.-%: calcium, 0.35-31.20; carbon, 10.99-50.21; oxygen, 34.55-51.03; sulfur, 0.73-14.81, and phosphorus, 0.08-3.30. Invention provides compensation of trace elements unbalance that causes and accompanies many diseases, possibility for stabilization of trace element homeostasis and arresting pathological processes of different etiology.
EFFECT: improved and valuable medicinal properties of composition.
12 cl, 13 ex
SUBSTANCE: the present innovation deals with treating obesity of different genesis. One should regulate patient's appetite and body weight, and, also, lipid exchange with the help of chromium ions. For this purpose one should apply chromium oxide (VI) at the dosage of 0.35 mg/kg/d in drops in the form of solution. The suggested dosage corresponds to maximal curative action of this microelement. The innovation in question enables to adequately control chromium entrance into the body depending upon body weight, patient's sensitivity to therapy due to dosing by drops and has no side effects and contraindications.
EFFECT: higher efficiency of therapy.
SUBSTANCE: method is described for preparing aqueous solutions of copolymers, involving a fundamental step for copolymerisation of partially neutralised acrylic and maleic acid in the presence of hydrogen peroxide in amount of 2 to 4% of total mass of monomers at temperature ranging from 85 to 105°C in an aqueous medium, which is realised through gradual addition of an aqueous solution of hydrogen peroxide for 3 to 6 hours into an aqueous solution of partially neutralised maleic acid and simultaneous gradual addition of an aqueous solution of partially neutralised acrylic acid, or an aqueous solution of free acrylic acid, or aqueous solutions of free acrylic acid and a base, and subsequent addition of hydrogen peroxide for 30 to 60 minutes after completion of simultaneous addition of hydrogen peroxide and acrylic acid, and a step for pre-polymerisation by keeping the reaction mixture at polymerisation temperature, distinguished by that, the pre-polymerisation step is realised by keeping the reaction mixture at polymerisation temperature for 35 to 60 minutes, subsequent simultaneous addition of aluminium or potassium persulphate in amount ranging from 0.10 to 0.15% of total mass of monomers and subsequent keeping at polymerisation temperature for 45 to 90 minutes.
EFFECT: increased dispersion capacity of copolymers.
1 cl, 1 tbl, 8 ex
SUBSTANCE: flocculant has the following composition, wt %: partial magnesium salt of a copolymer of acrylic and methacrylic acid neutralised by 60% (with ratio of monomers: acrylic acid - 45%, and methacrylic acid - 55%) 2.4-3.5; sodium salt of a copolymer of acrylic and methacrylic acid (with ratio of monomers: acrylic acid - 35%, and methacrylic acid 65%) 3.8-5.8; polyacrylamide 1.1-1.5; water - the balance. The flocculant is used in form of process solutions with concentration 0.015-0.035 wt %. 0.035% aqueous flocculant solutions have the highest flocculating power.
EFFECT: flocculant has high solubility in water and ensures high efficiency when used to clarify waste water.
SUBSTANCE: invention relates to emulsifying polymers and use of these polymers for stable emulsification of hydrophobic additives in aqueous concrete plasticisers. Disclosed is a polymer P, obtained via copolymerisation (a) of at least one ethylenically unsaturated monomer A selected from a group consisting of unsaturated mono- and dicarboxylic acids, sulphonic acids, phosphonic acids in form of free acids or salts or partial salts or halide or anhydride, with (b) at least one ethylenically unsaturated monomer B of formula ,
where radicals and coefficients are as described in the claim and (c) with at least one ethylenically unsaturated monomer C of formula
where radicals and coefficients are as described in the claim and with (d) at least one ethylenically unsaturated monomer D of formula
where radicals and coefficients are as described in the claim and optionally (e) with at least one basic ethylenically unsaturated monomer E of formula ,
where radicals and coefficients are as described in the claim and optionally (f) with at least one other ethylenically unsaturated monomer W. Use of the polymer as a plasticiser for water-curable compositions and a water-curable composition are also disclosed.
EFFECT: polymer improves quality of mortar.
19 cl, 5 tbl
SUBSTANCE: group of inventions relates to curable water-based composition for obtaining coating on non-woven material, method of manufacturing treated non-woven material, treated with curable water-based composition, and non-woven material, treated with composition. Composition includes copolymer and cross-linking agent. As copolymerised units aid copolymer contains from 1 to 10 wt %, counted per dry weight, of itaconic acid copolymer and from 90 to 99 wt % of copolymerised ethylene-unsaturated monomer, selected from the group, including ethylacrylate, butylacrylate, styrene, methylmethacrylate, acrylic acid, methacrylic acid, acrylonitrile and their mixtures. Cross-linking agent has at least two hydrazine groups, with molar ratio of hydrazine group in cross-linking agent to carboxyl group in copolymer constituting from 0.05 to 2. Water-based composition is cured at temperature from 100°C to 250°C.
EFFECT: high tensile strength in dry, wet and submerged into isopropyl alcohol state.
6 cl, 13 tbl, 19 ex
SUBSTANCE: invention relates to methods of producing raw maleic anhydride. In particular, method includes steps where: reactor output stream, containing maleic anhydride, is fed into bottom part of absorption column, where it comes into contact with a non-cyclic solvent, that is fed close to its upper part and is a diester, having a boiling point under normal conditions between 250 °C and 350 °C, solubility of fumaric acid at least 0.06 wt% at temperature of 60 °C, solubility of maleic anhydride at least 10 wt% at temperature of 60 °C, water solubility not higher than 100 mg/l, density, different from water density at least to 0.020 g/ml, and a water-soluble hydrolysis product with molecular weight not higher than that of pentanol, with transfer of maleic anhydride of outlet stream of reactor into a solvent, wherein gas stream to be extracted is blown off from absorption column, and enriched solvent, containing maleic anhydride, is removed from absorption column near bottom of absorber and directed into flash tower near its middle part, untreated maleic anhydride is removed from stripping column near its middle or upper part.
EFFECT: methods make it possible to use cheaper solvent than phthalates.
11 cl, 1 dwg, 1 tbl
SUBSTANCE: polyvinyl alcohol and magnesium or calcium chlorides polyhydrated complexes are obtained by dissolution of polyvinyl alcohol and magnesium or calcium chlorides in water on boiling water bath. Said components are taken in the next ratio (mass%): polyvinyl alcohol 11.5-11.6; magnesium or calcium chloride 23.2-24.0; and balance: distilled water.
EFFECT: new complex compounds having antiinflammation, resolution and analgesic action.
SUBSTANCE: invention relates to a multifunctional polymer which contains a graft polymer formed from: a) polyolefin, b) nitrogen-containing ethylene-unsaturated aromatic or aliphatic monomer which contains from 2 to approximately 50 carbon atoms; and c) an organometallic compound capable of reacting with the said polyolefin. The invention also discloses multifunctional polymers (versions), a synthesis method thereof, and lubricating oil (versions).
EFFECT: invention enables to obtain a multifunctional polymer which acts as a dispersing agent, viscosity index improver and an antiwear additive.
62 cl, 7 ex, 3 tbl
SUBSTANCE: polymer, whose chain ends are modified, contains a product of reacting a living anionic elastomeric polymer and a silane sulphide modifier of formula: (RO)x(R)ySi-R'-S-SiR3. The invention also relates to a vulcanised composition based on the elastomeric polymer and a method of preparing said composition. The method involves combining filler, vulcanising agent, elastomeric polymer modified on chain ends and vulcanisation of the elastomeric polymer composition. The composition is used to make articles such as pneumatic tyres, tyre protectors, belts and suchlike.
EFFECT: preserving good technological properties and good balance of physical and mechanical properties, including wear resistance, breaking strength, apparent tensile stress and breaking elongation.
23 cl, 9 tbl, 19 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to creation of novel chemical compounds, which can be used in medicine as hemostatic medications of local action. Described in incomplete lithium salt of polyacrylic acid (liacryl), which is characterised by correespondance to formula: (-CH2-CHCOOH-)n(-CH2CHCOOLi-)m, where n=13496-28570; m=1672-4499, content of lithium constituting 6-8 wt % (0.0011-0.0012 g-at), and content of carboxyl groups constitutes 0.0118-0.0121 g-equiv per 1 g of polymer, molecular weight is 1000000-3000000. Also described is incomplete double lithium-zinc salt of polyacrylic acid (licicryl), corresponding to general formula: (-CH2CHCOOH-)n(-CH2CHCOOLi-)m(-CH2CHCOOZn-)k, where n=13777-18255; m=4227-4679, k=1666-2180, total content of metals constitutes 6-8 wt % (0.0010-0.0011 g-at), content of carboxyl groups constitutes 0.0117-0.0120 g-equiv, molecular weight is 1000000-3000000. Described are methods of obtaining said above incomplete salts of polyacrylic acid. Also described is medication, possessing efficient hemostatic action in external application, which contains said above incomplete lithium salt of polyacrylic acid, characterised by the fact that it is made in form of solutions with ratio 1-10 g of principal substance per 100 ml of water (1-10%). Described is medication, which possesses efficient hemostatic and expressed antiseptic action in external application, which contain said above incomplete lithium-zinc salt, characterised by the fact that it is made in form of solution with ratio 2-5 g of principal substance per 100 ml of water (2-5%).
EFFECT: obtaining novel chemical compounds, which can be used in medicine as hemostatic medication of local action, possessing high hemostatic effect.
6 cl, 1 tbl, 7 ex
SUBSTANCE: described is incomplete cesium salt polyacrylic acid characterised by the fact that it corresponds to formula
Also described is method of obtaining said incomplete cesium salt of polyacrylic acid, characterised by the fact that to water solution of polyacrylic acid added is water solution of cesium chloride, reaction mixture is mixed for 30-40 minutes, obtained water solution is passed through cationite and dried in vacuum at temperature not higher than 50 degrees. Described is medication, possessing hemostatic action if applied externally, containing i.1 substance, characterised by the fact that it made in form of solution with ratio from 1- 10 g of basic substance per 100 ml of water.
EFFECT: obtaining novel chemical compound, which can be applied in medicinal practice as hemostatic medication of local action.
3 cl, 5 ex