TECHNICAL FIELD

The invention relates to medicine, namely to medical products for hemostasis with reparative properties, in particular to variants of a biodegradable hemostatic composition based on modified chitosan and xymedone.

PRIOR ART

A pharmaceutical composition for treating bums is known (Pharmaceutical composition for treating burns (versions) and a method for its production (versions): Patent No. 2317811, Russian Federation, application No. RU2006121794; appl. 19.06.2006; publ. 27.02.2008) containing active substance N- (b-oxyethyl) -4,6-dimethyldihydropyrimidone-2 (xymedone) and base-forming agents. As base-forming agents this composition contains a gelling agent representing sodium salts of biopolymers, glycerol as a water-retaining agent in an amount not less than 20 % by weight, a stabilizer, a preservative and distilled water. In addition to xymedone variants of the composition can contain such active substances as silver nitrate, or silver nitrate and sodium sulphacyl, or levomycetin and succinic acid. According to the patent, the tests showed a high efficiency of the created pharmaceutical composition that meets all biomedical requirements for modem treatment of burns and wounds. The pharmaceutical composition of the present invention can be used as a highly effective regenerating, wound healing, microcirculation improving agent for treating an infected bum wound. As a sodium salt of biopolymers sodium alginate providing hemostatic properties of the composition is used. The given composition is accepted as a prototype.

Drawbacks of the prototype are relatively weak hemostatic properties and possible allergenicity because of the use of silver. The relatively weak hemostatic properties are the result of the absence of strong hemostatics in the composition formulation. In addition, glycerol being in sufficiently high concentrations in the composition negatively affects the storage stability of the product. This is due to the purposeful creation of this composition for burn treating with strong regenerative properties that does not guarantee strong hemostatic ones. Another drawback of the prototype is the prolonged composition biodegradation due to the significant disadvantage of all currently industrially produced alginates, namely their low solubility in water. First of all, this is because of the to the tendency of the alginate particles to adhere intensively to each other in an aqueous medium to form hardly soluble agglomerates.

The technical problem lies in the need to develop a biodegradable and hypoallergenic hemostatic composition with reparative properties, free from the above drawbacks. SUMMARY OF THE INVENTION

The technical result consists in improving hemostatic properties and providing biodegradability and hypoallergenicity of the composition when maintaining high reparative properties.

The technical result is achieved due to the fact that the hemostatic composition with reparative properties in the form of a gel containing xymedone, biopolymer and water, according to the invention contains modified chitosan (MCh) as a biopolymer with the following ratio of components, % by weight: xymedone 2.00-5.00

MCh 2.25-5.00 water by 100 %by weight

When being in the preferred implementation version the composition additionally contains an antiseptic, in so doing its weight fraction can be from 0.05 to 0.15% by weight.

The technical result is also achieved due to the fact that the hemostatic composition with reparative properties in the form of a sponge containing xymedone, biopolymer, glycerin and water, according to the invention contains modified chitosan (MCh) as a biopolymer at the following ratio of components, % by weight: xymedone 42.80-45.00

MCh 40.10-48.20 glycerin 6.40-11.75 water by 100 %by weight

When being in the preferred implementation version the composition additionally contains an antiseptic, in so doing its weight fraction can be from 1.20 to 1.75% by weight. As an antiseptic some of the quaternary ammonium compounds such as Miramistin, octenidine, polyhexamethylene guanidine hydrochloride, benzalkonium chloride, dequalinium chloride can be used.

The combination of xymedone with MCh allows to obtain a synergistic effect in the composition, namely the presence of both strong hemostatic and reparative properties simultaneously. In so doing, glycerol acts as a plasticizer and allows the composition properties to be controlled to produce various finished products, in particular, sponges. The use of modified chitosan is due to its strong hemostatic properties compared to native chitosan.

The choice of the quantitative composition was carried out as follows. A set of samples with different concentrations of base components was prepared to investigate the effect of the quantitative composition on the therapeutic and consumer properties of the claimed composition. When developing the composition, it was taken into account in what form the claimed product will be used - gel or sponge.

Thus, for the gel form the viscosity of the composition must be taken into account. For hemostatic properties it is important that the gel applied to the wound is not flushed with the exudate or blood current and can be held by surface tension to provide a hemostatic effect. For this purpose, different amounts of MCh having both hemostatic and gelling properties were added to the composition. Acceptable range of dynamic viscosity was accepted to be the value falling inside the limits of 45-65 Pa-s which corresponds to the content of MCh from 2.5 to 5.0 % by weight. Below this value, the consistency of the gel was sufficiently liquid, which can result in removing the gel off the wound. Production of gels with a concentration more than 5.0 % by weight is related to great technological difficulties such as long dissolution time, use of high temperatures, high energy costs.

For sponge products, the major criterion was the absorbing power of sponges, which was measured relative to physiological salt solution - 0.9% water sodium chloride solution. In the MCh concentration range of 40.10-48.20 % by weight, the maximum absorbing power of 50 g of physiological salt solution per 1 g of sponge (with minor deviations that can be neutralized by varying the content of other components) was achieved. An increase in the MCh content more than 48.2% by weight results in a slight decrease in the absorbing power.

The content of xymedone in the composition affects both the reparative activity and consumer properties of the finished product. An increase in the xymedone content more than 45.00 % by weight results in a decrease in the sponge elasticity, an increase in the sponge stiffness, can cause its cracking and tearing and also discomfort at the first moment of its contact with the wound surface. Thus, the optimal content of xymedone should be considered within a range of 42.80 to 45.00 % by weight, in which case the wound healing period is reduced while retaining good elasticity and sponge strength. A decrease in the lower limit results to an increase in both the wound healing period and in the periods of replacement of wound coverings on affected areas of living tissue.

The action of glycerol is opposite to that of xymedone. It is possible to use the gel form without glycerin. For a sponge form glycerin acts as a plasticizer and increases the product elasticity to defined limits. The glycerin content less than 6.40 % by weight in the sponge results in the increased fragility of the product when bending. When increasing the glycerin content more than 11.75 % by weight the sponges become sticky and viscous.

The claimed invention is explained by examples below

Example 1.

Production of gel.

95.6 g of water purified was placed in a thermostatically-controlled reactor, 2 g of crystalline xymedone was added thereto at room temperature and when stirring to obtain visually dissoluted xymedone. To the resulting solution 0.15 g of antiseptic substance Miramistin was added when stirring. After completed dissolving, the temperature was raised to 35 degrees Celsius by supplying warm water to the reactor jacket. At this temperature 2.25 g of modified chitosan was added into the solution and the resulting gel was stirred to its total homogeneity. The resulting viscous mass was placed to the 150 ml syringe without cooling and sealed into polyethylene bag under vacuum.

Example 2.

Application of gel.

The gel produced as described in the Example 1 was used to stop bleeding in an animal. The effectiveness of the gel for controlling bleeding from parenchymal organs was experimentally evaluated when modeling the massive bleeding from a grade I liver wound (according to the classification of the American Association for Surgery of Trauma) in large laboratory animals (pigs). To do this, a 5x5 cm capsule was cut off on the liver, the resulting bleeding was not been stopped for 1 minutes. The effused blood was collected with napkins, which were then weighed.

Bleeding from the liver wound was stopped by applying a hemostatic gel to the wound. The gel was pressed to the liver wound with a napkin for 3 minutes, the napkin was then removed. During this time a complete hemostasis occurred, which was assessed by the absence of blood leaking from the wound.

Example 3.

Production of sponge from gel.

The gel produced as described in the Example 1 was used to produce a hemostatic sponge with the only difference that after obtaining a homogeneous gel, 1.0 g of glycerol was added to it and again stirred to its total homogeneity. The resulting mass was poured in a thin layer into the prepared molds and subjected to low-temperature sublimation drying for 24 hours slowly raising the temperature from -40°C to +26°C. The resulting sponge was sealed into paper-foil-polyethylene bags under vacuum.

Example 4.

Application of sponge.

The sponge obtained as described in Example 3 was used for the treatment of grey rabbits. The effectiveness of this sponge for the treatment of abraded skin areas and wounds, partial-thickness and full-thickness skin bums (Ilia) at its external skin application in the burn wound area was assessed by the relative reduction of the bum wound area.

The intensity of the stimulating effect on wound healing was maximally exerted in the first 5-7 days after the damage. The wound area decreased 4-5 times for this period. Sloughing and tissue regenerating were observed. All other things being equal, the use of the sponge 1.3 -1.5 times surpasses the traditional healing methods, for example with using napkins medicated with 10% methyluracil ointment.