A method of treating corneal injury in the experiment

 

(57) Abstract:

The invention relates to medicine, namely to ophthalmology, and can be used in the treatment of penetrating and non-penetrating injuries of the cornea. How is the instillation of eye drops containing glycosaminoglycan concentration from 0.35% to 1.0% with different ratio of their different classes (hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, heparan-sulfate, keratan-sulfate). The method allows to provide a corrective effect on all stages of reparative regeneration, to restore the optical properties of the cornea and improve the functional efficiency of the organ of vision. table 1.

The invention relates to medicine, namely to ophthalmology, and can be used to restore the integrity of the cornea and its optical properties.

There is a method of treatment of corneal injury drug polysaccharide nature - glucosamine obtained from biological tissues with reparative and ceratopetalum action, in the form of eye drops (Bezdetko P. A. et al. Histomorphological and histochemical studies of the mechanisms of reparative and karatopraklieva actions of glucose and origin (derived from shellfish), affects mostly only on one of the stages of regeneration, its use is not taken into account the stage of the reparative process that is not always possible to achieve full enlightenment of the cornea when it is epithelialization.

The prototype of the invention is a method of treatment of corneal injury, which used a solution of sodium hyaluronate with a concentration of 1 and 2% in the form of eye drops in alkaline burns of the cornea in rabbits (Jang-Hyun Chung et al. Hyaluronate in healing of corneal alkali wound in the rabbit // Exp. Eye Res. - 1989. - Vol. 48. - 4. - P. 569-576.). The duration of the healing process is 8 weeks. It is established that both 1% and 2% solution of sodium hyaluronate produced statistically significant positive impact on the process of reepithelization, especially during the late phase of healing. The effect of sodium hyaluronate on the healing process of stroma was also positive, with the cornea of the eye, treated with sodium hyaluronate, there was a higher content of dry stromal substance compared with the control. While sodium hyaluronate promoted cell immobilization, reduced inflammatory response, was inhibited invasion of polymorphonuclear leukocytes lacrimal moisture into the layers of the cornea.

The disadvantages of the prototype are carried out mainly on one of the stages of reparative regeneration, since there is only one of the classes of glycosaminoglycans (GAGS), there is no effective influence on the processes of differentiation and specialization of cells and tissues.

The technical result of the invention is to improve the functional efficiency of the organ of vision and the recovery of the optical properties of the cornea, reducing post-traumatic and postoperative complications.

The technical result is achieved through the use of glycosaminoglycans in the form of solutions with a concentration of from 0.35 to 1.0% (using different classes of GAGS, in different proportions and concentrations) for injuries and postoperative period.

The analysis of domestic and foreign literature has allowed to establish that GAG on the proposed scheme has never before been used. GAG available for use to restore the functional and optical properties of the cornea in trauma as a new destination for the first time. Previously they were used to treat wounds of the cornea, but without taking into account the stage of inflammation and characteristics of the course of reparative processes, and GAG content and ratios of different classes in the tissue at the injury site in the dynamics of the post-traumatic period (Jang-Hyun Chung et al. Hyaluronate in healing of corneal Cana humans and animals (the umbilical cord, placenta, cartilage and other tissue) of different age groups. This allows to obtain extracts GAG with different content and the ratio of their classes. Extracts GAG represent a clear solution odorless possible with a yellowish tinge.

A method of treatment of corneal injury (non-penetrating and penetrating) in the experiment is carried out as follows. In the eyes of 11 rabbits using round trephine drills are applied non-penetrating injury of the cornea to 1/2 of its thickness and a diameter of 3 mm, Then daily instilliruut glycosaminoglycans in the form of eye drops in the conjunctival cavity until complete epithelialization of the cornea according to the scheme below.

At 1 day after injury of the cornea using a solution of GAG concentration of 0.35% for instillation in the conjunctival cavity through every 1.5-2 hours. The ratio of different classes of GAGS in this solution was the following: hyaluronic acid is 68%, chondroitin-4-sulfate -19%, chondroitin-6-sulfate 9%, heparan-sulfate - 4%.

In the 2nd day of use 0,55% solution GAG every 1.5-2 hours. The ratio of different classes of GAGS in this solution was the following: hyaluronic acid - 61,5%, chondroitin-4-sulfate - 21,5%, chondroitin-6-sulfate -13%, heparan-sulfate - 4%.

On day 4 after injury of the cornea was instillirovti 0.7% solution GAG every 1.5-2 hours. The ratio of different classes of GAGS of this solution was as follows: hyaluronic acid of 40.8%, chondroitin-4-sulfate - 23,2%, chondroitin-6-sulfate, and 25.8%, heparan-sulfate - 6%, keratan-sulfate - 4,2%.

On day 5-7 of the cornea was instillirovti of 0.75% solution GAG every 1.5-2 hours. The ratio of classes GAG of this solution was as follows: hyaluronic acid - 36.5%), and chondroitin-4-sulfate - 23,5%, chondroitin-6-sulfate - 29,2%, heparan-sulfate-6%, keratan-sulfate-4,8%.

8-10 days after trauma to the corneal surface was instillirovti 0,85% solution GAG every 1.5-2 hours. The ratio of classes GAG of this solution was as follows: hyaluronic acid - 32,9%, chondroitin-4-sulfate - 25%, chondroitin-6-sulfate 31%, heparan-sulfate - 6%, keratan-sulfate - 5,1%.

On the 11th day after the injury until complete epithelialization of the cornea on its surface was instillirovti 1,0% solution GAG every 1.5-2 hours. The ratio of classes GAG of this solution was as follows: hyaluronic acid is 28.5%, chondroitin-4-sulfate - 27,5%, chondroitin-6-sulfate in penetrating and non-penetrating injuries of the cornea developed on the basis of experimental data. We have traced the stages of the process of reparative regeneration of damaged cornea using morphological methods (histological, histochemical, electron microscopic, electron histochemical). In the damage zone of the cornea observed changes in cellular composition, but also of the intercellular matrix. Marked changes were observed by us and in the structure of the GAG and the ratio of different classes. Such changes in the tissues when the damage observed in the works of both domestic and foreign authors (Serov centuries, Schechter A. B., 1981; Yurina N. A., Radostina A. I., 1990; Hughes, R., 1985; J. Marsh, 1985; M. Biffoni et al., 1991 and others).

In the experiment on animals in the injury of the cornea were used GAGS extracted from human tissues, different ages, which was used in the form of eye drops. When applied after injury of cornea inflammation and allergic reactions were absent. Comprehensive morphological studies have shown that correction of reparative processes of the cornea in the damage zone solutions GAG on the above scheme is monitored at all stages of regeneration with the formation of this differentiated and spetsializirovany negative influence on the optical properties of the cornea. These drugs, used in the above scheme, have a pronounced reparative effect with the formation of differentiated and specialized transparent structure as that of the normal cornea.

The proposed method of application GAG when injury of the cornea can be used both in an inpatient and outpatient basis.

The proposed method of application of glycosaminoglycans in corneal injury compared with the prototype has the following advantages: allows you to restore the normal structure of the cornea, to restore its optical properties, reduce inflammation, reduce the percentage of post-traumatic and postoperative complications.

A method of treating corneal injury in the experiment by instillation of eye drops, characterized in that the buried solutions glycosaminoglycans with increasing concentrations of from 0.35 to 1.0% daily every 1.5-2 hours to complete epithelialization of the wound, and in 1 and 2 day treatment use solutions glycosaminoglycans consisting of hyaluronic acid with a concentration of 68 and 61.5%, respectively, chondroitin-4-sulfate 19 and 21.5%, chondroitin-6-sulfate 9% and 13% and heparan-sulfate 4%, and other days ispot from 23 to 27.5%, chondroitin-6-sulfate from 21 to 33.5%, heparan-sulfate from 5 to 6%, keratan-sulfate from 3.5 to 5.5% until complete epithelialization of the cornea.

 

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