RU2114587C1 - Solution "visiton-1" for protection of cornea from damage - Google Patents

Abstract

FIELD: medicine, ophthalmology. SUBSTANCE: solution containing cellulose derivative, buffer salts and water, pH = 7.2-7.4, has additionally glycoseaminoglycanes. Alkyl-derivative, or carboxyalkyl-derivative, or hydroxyalkyl-derivative are used as cellulose derivative at the following ratio of components, g/l: alkyl-derivative, or carboxyalkyl-derivative, or hydroxyalkyl-derivative of cellulose 2.1-60.0; sodium chloride 8.5-9.5; sodium dihydrogen phosphate 0.025-0.040; sodium hydrogen phosphate 0.115-0.135; glycoseaminoglycanes 0.051-0.80, and purified water - the rest. Alternative variant: solution has additionally carnosine at amount 0.5-20.0 g/l. EFFECT: enhanced effectiveness of solution as compared with the known ones. 2 cl, 3 ex

Description

 The invention relates to medicine, namely to ophthalmology, and can be used both in refractive and abdominal ophthalmic surgery.

 Known for a viscous solution containing tylose with a globule size of less than 0.4 μm in a 0.85% solution of sodium chloride with a buffer solution of pH 7.2 - 7.4, used to protect the cornea (FR patent 2663850, A 61 K 31 / 715, 1992).

 The disadvantage of this solution is the lack of protective effect when performing phacoemulsification, as well as the absence of anti-esudative effects on the damaged cornea during surgery.

 The objective of the invention is to obtain a viscous solution with protective and antiexudative properties in various surgical interventions.

The technical result is achieved by the fact that a solution comprising cellulose derivatives, buffer salts and water and having a pH of 7.2 - 7.4, according to the invention additionally contains glycosaminoglycans, and an alkyl derivative, or a carboxyalkyl derivative, or a hydroxyalkyl derivative is used as the cellulose derivative in the following ratio of components, g / l:
Alkyl derivative, or carboxy-alkyl derivative, or hydroxy-alkyl derivative of cellulose - 2.1 - 60.0
Sodium chloride - 8.5 - 9.5
Monosubstituted sodium phosphate - 0.025 - 0.040
Disubstituted sodium phosphate - 0.115 - 0.135
Glycosaminoglycans - 0.051 - 0.80
Purified Water - Else
One embodiment of the invention is one in which the solution for protecting the cornea from damage further comprises L-carnosine in an amount of 0.5 to 20.0 g / L.

 The concentration of the cellulose derivative is given over a wide range, which is explained by the need to use solutions of different viscosities. So, for example, with phacoemulsification of the lens, it is preferable to use a more concentrated solution to maintain the volume of the anterior chamber for a sufficiently long time. Whereas during refractive operations on the cornea, it is preferable to use a solution with a low concentration to prevent drying of the epithelium. Solutions with an average concentration of cellulose derivative are successfully used for cataract extraction and IOL implantation according to a standard technique. The boundary concentration values of the cellulose derivative were determined experimentally. To determine the lower value, the freshly cut rabbit cornea was placed in a test solution or in a 0.9% sodium chloride solution (the latter served as a control) for 2 hours and the corneal thickness was measured. At a concentration above 2.1 g / l, an increase in the thickness of the cornea was 2–5 times less than in the control. This suggests that the proposed solution has a protective effect. At a concentration above 60 g / l, a very thick solution forms, which makes it impossible to aspirate through the cannula.

 The concentration of sodium chloride 8.5 - 9.5 g / l is physiological for human cells and tissues. At concentrations less than 8.5 g / l and more than 9.5 g / l, the solution is not isotonic with respect to human tissues.

 Mono- and disubstituted phosphates are the natural ingredients of a buffering mechanism that maintains a constant pH in tissue fluids. The specified amount of phosphate provides a pH value of the solution in the range 7.2 - 7.4.

 Glycosaminoglycans (GAGs) are components of the connective tissue, they include chondroitin sulfate, keratan sulfate, heparan sulfate, heparin, hyaluronic acid. They have the ability to reduce the inflammatory and exudative reaction, contribute to lower intraocular pressure, normalize the corneal metabolism, and stimulate corneal repair. The GAG molecule consists of repeating disaccharide components that contain amino sugar and uronic acid. GAG can be identified by staining with Schiff's reagent with iodic acid, which reveals aldehyde sugar groups formed by the action of iodic acid.

 Experimental studies in rabbits showed that with a GAG concentration of less than 0.051 g / l, a slight exudative reaction is observed a day after the test solution was introduced into the anterior chamber. At a concentration of more than 0.8 g / l, mild bleeding was observed.

 L-Carnosine is an antioxidant and protector of the water membrane and lipid phase of biological membranes. The amount of L-carnosine was determined experimentally. To this end, chinchilla rabbits were replaced with moisture in the anterior chamber by a solution of carnosine or a 0.9% sodium chloride solution (as a control). At a carnosine concentration of 0.5 g / L to 20 g / L, a decrease in the corneal stack was observed biomicroscopically as compared to the control. When the concentration of carnosine is less than 0.5 g / l, the effect was not achieved. At a concentration of more than 20.0 g / l, narrowing of the pupil was observed, i.e. unwanted adverse reaction.

 Thus, the proposed solution is a balanced composition and can be used both for insertion into the cavity of the eye, and in the form of instillations during refractive surgery on the cornea.

 The solution "Visiton I" is obtained as follows. The cellulose derivative is dissolved in saline, centrifuged, decanted. The solution is filtered on a membrane filter. Further, according to the invention, glycosaminoglycans and, if necessary, L-carnosine are added. The solution is stirred, filtered again, poured into vials and sterilized by autoclaving.

 Experimental and clinical trials of the solution "Visiton I" confirmed the positive effect when it is used both in refractive and abdominal operations. So, when using the solution as a protector of the corneal endothelium with standard extracapsular cataract extraction with IOL implantation in a group of 200 patients, there was no exudative reaction and corneal edema the next day after surgery. Endothelial loss was 4–7%.

 Example 1

Patient S. underwent extracapsular cataract extraction with IOL implantation. As a protector, "Visiton I" of the following composition was used:
Hydroxyethyl methyl cellulose - 20.0 g / l
Sodium chloride - 8.5 g / l
Monosubstituted sodium phosphate - 0.025 g / l
Disubstituted sodium phosphate - 0.135 g / l
Glycosaminoglycans - 0.80 g / l
Purified Water - Else
A day after the operation, the eye is calm, the cornea is transparent, there is no exudative reaction. Intraocular pressure is normal.

 Example 2

Patient G. underwent surgery for the correction of myopia by keratotomy. During the operation, repeated instillation of the proposed solution was carried out with the following ratio of components in g / l:
Carboxymethyl cellulose - 2.1
Sodium Chloride - 9.2
Monosubstituted sodium phosphate - 0.040
Disubstituted Sodium Phosphate - 0.115
Glycosaminoglycans - 0.051
L-carnosine - 20.0
Purified Water - Else
Biomicroscopically, a day after surgery, the cornea is transparent, there is no clouding, hyperemia is weak. After 7 days there is no conjunctival hyperemia. Tearing and photophobia are absent.

 Example 3

Patient K. underwent phacoemulsification of cataract with IOL implantation. As a protector and to maintain the volume of the anterior chamber, “Visiton I” of the following composition was used in g / l:
Cellulose - 60.0
Sodium Chloride - 9.5
Monosubstituted sodium phosphate - 0.040
Disubstituted Sodium Phosphate - 0.115
Glycosaminoglycans - 0.1
L-carnosine - 0.051
Purified Water - Else
During the operation, 0.2 ml of the solution was introduced into the anterior chamber. The thick solution retained well the volume of the anterior chamber. After the operation, "Visiton I" was washed out of the anterior chamber by irrigation solution. After a day, the eye is calm, there is no exudate in the anterior chamber. Intraocular pressure is normal. Endothelial cell loss was 4%.

 Thus, the use of the proposed solution allows you to save the cells of the corneal endothelium during surgery, as well as accelerate the epithelialization process in refractive surgery of the cornea.

Claims (1)

1. A solution to protect the cornea from damage, including a cellulose derivative, buffer salts and water and having a pH of 7.2 - 7.4, characterized in that it further comprises glycosaminoglycans, and an alkyl or carboxyalkyl or hydroxyalkyl derivative is used as the cellulose derivative in the following ratio of components g / l:
Alkyl or carboxyalkyl or hydroxyalkyl-derived cellulose - 2.1 - 60.0
Sodium Chloride - 8.5 - 9.5
Monosubstituted sodium phosphate - 0.025 - 0.040
Disubstituted sodium phosphate - 0.115 - 0.135
Glycosaminoglycans - 0.051 - 0.80
Purified Water - Else
2. The solution according to claim 1, characterized in that it additionally contains L-carnosine in an amount of 0.5 to 20.0 g / L.