DEXTRAN — the representative of group of the polysaccharides of a bacterial origin consisting of the remains of D-glucose connected among themselves preferential alpha 1,6 - bonds. The drugs D. which are a part of blood substitutes are widely applied in medicine. Constitutional formula of the site of a molecule of a dextran:
Sewed by cross bonds epichlorohydrin — sephadex, and also the sefadeksa supporting ionogenic groups find broad application for cleaning and division of biologically active agents in biol, and medical researches (see. Gel filtering , Molecular sieves ).
Synthesized by various microorganisms differ on structure and physical. - to chemical properties. Final structure of D. and its pier. the weight (weight) are not established. D.'s most contain in branching points of a molecule also alfa-1,2-, alfa-1,3-, alpha 1,4 - bonds; alpha 1,3 - bonds sometimes meet also in a linear chain of a molecule.
The bacteria synthesizing D. most often concern to representatives of the Lactobacillaceae family, the sorts Lactobacillus, Leuconostoc and Streptococcus. Are synthesized from sucrose out of bacterial cells with the participation of the enzyme of dextraninvertase emitted by bacteria in culture medium (KF 22.214.171.124.), catalyzing splitting of sucrose and the subsequent synthesis of D. from the remains of glucose without formation of any intermediate products. Branching points in a molecule D. are defined, apparently, by the same enzyme.
The chemical way of synthesis of D. consists in polymerization of a levoglucosan in the presence of phosphorus pentafluoride at — 78 °. Synthesis is not of practical interest.
Native D. in water form opalescent colloid solutions with anomalous viscosity owing to formation of the associates of a helical structure stabilized as inside - and intermolecular hydrogen bindings. Drugs D. with the broken helical structure are dissolved in water better. Are optically active, their [a]D fluctuates from +199 ° to + 235 °. Solutions D. do not give coloring with iodine.
At presence to - the t at D.'s heating is hydrolyzed on glucosidic bonds. Its degradation happens also at heat treatment, heating in a dimethyl sulfoxide, at influence by ultrasound, gamma-rays.
For quantitative definition of D. in a blood plasma, urine and fabrics it is besieged in the form of a copper complex, and also use reactions with Anteronum, ortho-toluidine, rezor-tsinol-4,6-disulfonic to - that. and full acid hydrolysis with the subsequent quantitative definition of formed glucose (see).
In 1944 the Swede, scientists A. Gronwall and Ingelmann (V. of Ingelmann) for the first time received from partially hydrolyzed native D. about a pier. a blood substitute of antishock action weighing 80 Ltd companies, called «Macrodexum». Blood substitutes of this kind are made now commercially (the domestic drugs «Polyglucinum», «Reopoliglyukin», drug of the USA «A dextran the abbot», Swedish — «Macrodexum», «Reomakrodeks», etc.). For a wedge, uses the drugs D. having not less than 90% alpha 1,6 - glucosidic bonds are resolved. For their production various strains of Leuconostoc mesenteroides are used; abroad — L.m. NRRL V-512, etc., in the USSR — L.m. The Federation Council-4 forming the low-branched D. containing 93% alfa-1,6-and 7% of bonds of other types. Play an essential role in development of some types of caries of teeth (see Caries of tooth) at animals and the person. Food sucrose is substrate for D.'s synthesis by microbes of an oral cavity, generally streptococci. D.'s education promotes sticking of kariogenny bacteria to the surface of tooth and their colonization. Besides, for some of these bacteria of D. is reserve polysaccharide; products of utilization by its these bacteria are organic to - you, destroying an adamantine substance of tooth. Synthesized by kariogenny bacteria have strongly branched structure, badly rastvorima in water and form compact gels. Attempts of prevention of caries by addition to water or food of enzyme of the dextranase splitting D. Odnako these attempts were made were not successful. Experiments on vaccination enzyme dextraninvertase for prevention of synthesis of a dextran kariogenny bacteria were more perspective. This question is in a stage of development.
Use of a dextran in medicine
Process of receiving clinically used D. is based on partial acid hydrolysis of native D. with the subsequent fractionation on highly - and low-polymeric fractions and careful cleaning of the allocated middlemolecular fraction.
The most part of plasma substituting drugs D. is allocated with urine, their rest is postponed in fabrics and some bodies (e.g., in a liver) where it is split by enzyme acid alpha glucosidase to glucose.
Native D. cannot be entered intravenously since it causes heavy complications (fever, a leukopenia, etc.). The wedge, drugs D. have no negative effect on an organism and are completely deprived of toxic and pyrogenic properties.
In medicine along with plasma substituting solutions D. the complex D. with iron is successfully applied to treatment of iron deficiency anemias at animals and the person. In the USSR produce the drug «ferroglyukin» containing 50 — 75 mg of iron in 1 ml of solution.
Domestic drug D. Polyglucinum consists preferential of middlemolecular fractions of partially hydrolyzed D. in isotonic solution of sodium chloride. Polyglucinum represents colourless (slightly yellowish) liquid. Average pier. weight 60 000 ± 10 000, relative viscosity 2,8 — 4,0, pH 4,5 — 6,5. Abroad analogs of Polyglucinum — Dextraven, Expandex, Macrodex, etc. are issued. Polyglucinum is plasma substituting antishock drug. Existence in it of low-polymeric fractions which form harmless conjugates with various toxics in an organism, explains disintoxication effect of drug.
Transfusion of Polyglucinum increases the volume of the circulating blood (VCB) due to increase in volume of plasma by the size equal or even big, than the volume of the entered solution that is explained by the high osmotic pressure of drug by 2,5 times exceeding the osmotic pressure of proteins of a blood plasma; raises a circulation time of blood and minute volume of heart; improves a coronary blood stream, exerts the normalizing impact on hemodynamic indicators. Rather big pier. the weight close to a pier. to weight albumine (see), does not allow Polyglucinum to get through vascular membranes therefore at introduction to a blood channel Polyglucinum long in it circulates. To 50% of the entered Polyglucinum remains in a circulatory bed during 12 — 24 hours, supporting the reached OTsK and ABP level during this time. Polyglucinum is non-toxical. It is allocated partially with kidneys.
Use of Polyglucinum is shown at the acute circulator disorders developing at traumatic, hemorrhagic, thermal, operational, toxic and septic shock. Use of Polyglucinum at shock in many respects facilitates a problem of rendering emergency antishock treatment at a pre-hospital stage — on site incidents or during the transportation of the victim.
At the expressed phenomena of a hypovolemia (see. Oligemiya ) the drug needs to be administered struyno and only after raising of the ABP above a critical level it is admissible to pass to a drop method. At critical conditions (shock of the IV degree, a preagonal state) Intra arterial injection of Polyglucinum is shown.
The optimum dosage of Polyglucinum in each case is various, but on average at shock of the I degree 250 — 500 ml, at shock of the II degree — 500 — 750 ml, shock of the III degree — 1000 — 1500 ml are required, to the IV degree — to 2000 ml.
As traumatic shock often is followed by massive blood loss, pertinently to combine use of Polyglucinum with hemotransfusion or a packed red cells.
With success Polyglucinum is used at acute blood loss when the threat for life of the patient consists not so much in considerable loss of erythrocytes, how many in falloff of OTsK. Therefore the main objective of the doctor in these cases consists, first of all, in holding the actions providing bystry recovery of OTsK that can effectively be reached infusion of Polyglucinum. Transfusion of 1 — 2 l of this drug allows to bring quickly the patient out of a condition of an adynamia, to normalize hemodynamic disturbances, to stimulate oxidizing processes in an organism and to liquidate heavy displays of a hypoxia.
At the proceeding bleeding (went. - kish., pulmonary, wound etc.) infusions of Polyglucinum (especially jet) can quickly raise the ABP and strengthen bleeding. Therefore use of Polyglucinum is admissible only at critical condition of the patient, at decrease in the ABP is lower than a critical level and furthermore with not determined pressure. Transfusion of Polyglucinum in such cases not only is justified, but also is vital. After removal of the victim from a critical state transition to hemotransfusion or a packed red cells and other haemo static drugs is shown.
With success Polyglucinum at exchange hemotransfusions is used, at a hemodialysis, especially when the expressed hemodynamic disturbances take place.
Patients usually transfer transfusions of Polyglucinum well. Seldom or never intravenous administrations of the first several milliliters of drug led to emergence of feeling of constraint in a breast, to difficulty of breath, a hyperemia of the person with the subsequent cyanosis, tachycardias, to decrease in the ABP, the back pain, a fever appeared. Development of such complication is caused by an idiosyncrasy of the patient to. For the prevention of these complications during the use of Polyglucinum it is necessary to carry out biol, test: after intravenous administration of the first 5 and subsequent 10 — 15 drops of drug to take a break for 2 — 3 min. In the absence of reactions the transfusion of Polyglucinum can be continued. When unpleasant feelings as a result of a transfusion of Polyglucinum already appeared, it is necessary to stop transfusion of drug and to enter intravenously 10 ml of 10% of solution of calcium chloride, 20 ml of 40% of solution of glucose, to use cardiacs, antihistaminic drugs.
As Polyglucinum containing sodium chloride in the structure can be contraindicated at a row patol, states, in particular at pathology of kidneys, in these cases it is necessary to use Polyglucinum prepared on solution of glucose.
Transfusion of Polyglucinum considerably increases OTsK and raises the ABP, therefore, it it is necessary to refrain from infusions in all cases when sharp increase in the ABP is undesirable: at the expressed cerebral hypertensia (at injuries of a skull, hematencephalons and so forth), an idiopathic hypertensia, the proceeding bleeding (at the ABP good level), at diseases of kidneys (with an anury), heart failure.
The possibility of long-term storage of Polyglucinum (more than 5 years), simplicity of transportation and use considerably increase the value of this most effective antishock drug in a wedge, practice, especially in an urgent surgery.
Form of release: hermetically the corked glass bottles on 400 ml. Storage at a temperature from — 10 ° to +20 °. Freezing of Polyglucinum does not serve as an obstacle to its use.
Domestic drug Rheopolyglucinum colloid solution of partially hydrolyzed D. about a pier represents 10%. weighing 35 000 ± 5000 in isotonic solution of sodium chloride. On the structure and to lay down. it is similar to action the Swede, to the drug Rheomacrodex. Solution of a reopoliglyukin — transparent colourless (or weak-yellow) liquid with relative viscosity 4,0 — 5,5 and pH 4,0 — 6,5. Reopoliglyukin reduces aggregation of uniform elements of blood (see. Aggregation of erythrocytes ), promotes transition of liquid from fabrics in a blood channel in this connection it raises OTsK (due to increase in volume of the circulating plasma and volume of the circulating erythrocytes) and suspension stability of blood, reduces its viscosity, accelerates a blood stream, promotes a redeponirovaniye of blood and normalization of microcirculation, has disintoxication effect. Reopoliglyukin possesses expressed, but less resistant, than Polyglucinum, antishock action. The positive impact of a reopoliglyukin on a hemodynamics and microcirculation) provides its antishock and diuretic action.
As the drug possessing high colloid and osmotic, rheological, anti-aggregation and antitrombotichesky action reopoliglyukin in a dose of 400 — 1500 ml is applied at the acute circulator disorders which are followed by the expressed hypoxia and a hypovolemia (extensive injuries, heavy burns, massive blood loss, it is purulent - septic processes, intoxications). At heavy intoxications of infusion of a reopoliglyukin it is reasonable to produce in the first 1 — 2 bucketed day at 6 — 8 o'clock, 3 — 4 times a day 400 ml, and in the next days on 400 ml daily (kapelno). Transfusions of a reopoliglyukin are especially valuable in the hard cases of shock complicated by disturbances of the microcirculation expressed by a hypoxia and acidosis. Efficiency of rheological action of a reopoliglyukin is in certain dependence on a dose of drug: the dosage of 10 — 15 ml on 1 kg of weight of the patient is most justified. At surgeries with artificial circulation add to the transfused blood reopoliglyukin at the rate of 10 — 20 ml on 1 kg of weight of the patient. Infusions of a reopoliglyukin positively influence haemo renal indicators that provides increase in a diuresis. Use of a reopoliglyukin on purpose hemodilutions (see) at the open heart operations performed with extracorporal blood circulation allows to lower number of the complications connected with massive transfusions of donor blood, to improve biorheological properties of blood, to reduce hemolysis, to raise a diuresis. Use of a reopoliglyukin after the termination of artificial circulation promotes removal of excess liquid from an organism, normalization of composition of blood. Positively proved reopoliglyukin and at the heart operations performed under a hypothermia.
Transfusions of a reopoliglyukin are shown for the purpose of prevention of a thrombogenesis in the early postoperative period after reconstructive operations on vessels, at an angioaortografiya, and also at acute and hron, okklyuziruyushchy defeats of vessels, at acute fibrinferments of arteries and veins, an endarteritis, a postflebitichesky syndrome. The earlier use of a reopoliglyukin at acute tromboflebitichesky defeat of vessels is begun, the result is better. At hron, okklyuziruyushchy processes of vessels repeated injections of drug (8 — 10 infusions) in a dose of 10 ml on 1 kg of weight of the patient are required.
Contraindications to transfusion of a reopoliglyukin: heavy cardiopulmonary insufficiency, the organic pathology of kidneys proceeding with an oliguria and furthermore with an anury; thrombocytopenia. It is necessary to avoid massive and bystry transfusions of a reopoliglyukin at dehydration of an organism.
Form of release: hermetically the corked bottles on 400 ml. Store at a temperature of 10 — 40 °.
Polyglucinum and reopoliglyukin are steady and maintain sterilization at 120 ° within 30 min.
See also Plasma substituting solutions .
Bibliography: Koziner V. B. and Fedorov N. A. Mekhanizm of action of Polyglucinum, M., 1974, bibliogr.; Blood substitutes, under the editorship of A. N. Filatov, page 56, L., 1975; Pokrovsk G. A. Transfusion therapy of traumatic shock, M., 1973; Preobrazhenskiy M. E. Dextrans and dextranases, in book: Progress biol, chemical, under the editorship of B. N. Stepanenko, t. 16, page 214, M., 1975, bibliogr.; A t i k M. Dextran 40 and dextran 70, Arch. Surg., v. 94, p. 664, 1967; Dextrans, ed. by J. R. Derrick a. M. Mason Guest, Springfield, 1971; Sidebotham R. L. Dextrans, Advanc. Carbohyd. Chem., v. 30, p. 371, 1974, bibliogr.; T h o m a s J. M. a. Silva J. R. Dextran 40 in the treatment of peripherial vascular diseases, Arch. Surg., v. 106, p. 138, 1973.
G. Ya. Rosenberg, A. A. Hachaturyan, A. B. Livshits; D. M. Grozdov (pharm.).