RU2171107C1 - Ophthalmic drops - Google Patents

Abstract

FIELD: medicine, ophthalmology. SUBSTANCE: invention proposes ophthalmic drops containing sulfated glycoseaminoglycans and sodium salt physiological solution. Drops have tobramycin additionally. EFFECT: decreased treatment period. 6 cl, 5 ex

Description

 The invention relates to medicine, namely to ophthalmology, and can be used to treat diseases and injuries of the cornea.

 Known eye drops "Balarpan" containing sulfated glycosaminoglycans, sodium chloride, mono- and disubstituted sodium salts and water (US Pat. RF N 2128975), which have a specific effect on reparative processes in the cornea.

 The disadvantage of such eye drops is a mild anti-inflammatory effect.

 The objective of the invention is the creation of eye drops that stimulate the restoration of a transparent stroma of the cornea in case of damage and have a pronounced antibacterial effect.

 The technical result is a significant reduction in treatment time for inflammatory eye diseases due to the antimicrobial action and stimulation of reparative and metabolic processes, as well as a reduction in the number of complications associated with corneal opacity.

The technical result is achieved in that the eye drops, including sulfated glycosaminoglycans and a physiological solution of sodium salts, according to the invention, additionally contain tobramycin in the following ratio, wt.%:
Sulfated glycosaminoglycans - 0.005-0.1
Tobramycin - 0.1-1.0
Saline solution of sodium salts - Else
One embodiment of the invention is one in which the eye drops according to the invention further comprise carnosine in an amount of 0.05-2.0%, and / or nipagin in a concentration of 0.005-0.03%, and / or water-soluble cellulose derivatives in an amount of 0 , 05-1.0%, and as a physiological solution of sodium salts use an aqueous solution of 0.85-0.92% sodium chloride or phosphate buffer with a pH of 6.8-7.6, including sodium chloride, mono- and disubstituted phosphates sodium and water in the following ratio, wt.%:
Sodium Chloride - 0.85-0.92
Monosubstituted sodium phosphate - 0.018-0.072
Disubstituted sodium phosphate - 0.079-0.141
Purified Water - Else
Sulfated glycosaminoglycans are integral components of connective tissue. The sulfated glycosaminoglycans (sGAG) of the corneal stroma include keratan sulfate, chondroitin sulfate, heparan sulfate, heparin. They stimulate keratocytes of the corneal stroma in case of damage, normalize the water-salt balance and contribute to the restoration of the transparent corneal stroma.

 Tobramycin is an antibiotic from the aminoglycoside class, has a wide spectrum of antibacterial action against gram-positive bacteria (Staphylococcus aureus and epidermal, pneumococcus, some types of streptococci, etc.) and gram-negative bacteria (Escherichia coli, Enterobacter, Haemophilus influenzae, Pseudomonas aeruginosa, and others. including resistant to gentamicin). Tobramycin is better tolerated and less cytotoxic compared with gentamicin, which is widely used in ophthalmic practice.

 Carnosine - a histidine-containing dipeptide, is found in many human tissues, including the ocular. It is an active antioxidant, it stabilizes cell membranes, helps restore them in case of damage, and normalizes metabolic processes in damaged tissues.

 Nipagin is a preservative. It must be introduced into the composition of the eye drops with volumes of packaging exceeding the daily requirement to prevent the propagation of extraneous microflora in the open package.

 Water soluble cellulose derivatives are used as prolongators. They are hydrophilic polymers that bind aqueous solutions well and have an enveloping effect. Water-soluble cellulose derivatives include alkyl derivatives, carboxyalkyl derivatives, hydroxyalkyl derivatives.

 Physiological saline solutions are isotonic solutions, the osmotic pressure of which is close to the physiological fluids of mammals. The main osmotic component of physiological fluids is sodium chloride. It is generally accepted that the amount of sodium chloride 0.9 ± 0.05% ensures the isotonicity of the solution. To obtain a physiological saline solution with a certain pH value, sodium phosphates are added to it.

 Eye drops are prepared as follows. A physiological solution of sodium salts is prepared. Then a portion of sGAG in an amount of 0.005-0.1 g is dissolved in 50 ml of physiological saline until completely dissolved. Tobramycin in an amount of 0.1-1.0 g is added to the obtained sGAG solution and the volume of the resulting mixture is adjusted with physiological saline to 100 ml. After complete dissolution of all ingredients, the solution is filtered, poured into vials and sterilized. Eye drops may additionally contain carnosine and / or nipagin. In this case, carnosine in an amount of 0.05-2.0 g and / or nipagin in an amount of 0.005-0.03 g is added to 50 ml of a solution of sGAG and tobramycin and the volume of the resulting mixture is adjusted to 100 ml with physiological saline. After mixing and complete dissolution of the components, the solution is filtered, poured into vials and sterilized.

One of the options for eye drops is one that additionally contains a water-soluble cellulose derivative. In this case, a weighed portion of a water-soluble cellulose derivative in an amount of 0.05-1.0 g is poured into 40 ml of physiological saline and allowed to swell overnight at 4-8 ^° C. The next day, the solution is thoroughly mixed, filtered and 50 ml of the mixture in which sGAG, tobramycin and other components are dissolved in accordance with the claims are added. Again, thoroughly mix and bring the volume of the resulting solution to 100 ml with physiological saline. After stirring, the solution is filtered, packaged and sterilized.

 Examples.

 Example 1

Patient G. A photorefractive keratectomy operation was performed for myopia-5D using a Nidek laser. In order to prevent infectious complications in the postoperative period, an instillation of eye drops of the following composition was prescribed, wt.%:
sGAG - 0.005
Tobramycin - 0.1
An aqueous solution of 0.92% sodium chloride - The rest
Instillation was carried out in the first three days after surgery 4-5 times a day, 2 drops. The course of the postoperative period without complications. Toxic-allergic reaction was absent. Corneal syndrome on the 1st day after surgery of a weak degree. After complete epithelization, on the 3rd day, the instillation of eye drops was stopped.

 Example 2

 Patient T., the diagnosis is a corneal ulcer of the right eye. Before hospitalization, the patient received outpatient and inpatient treatment at the place of residence for 6 weeks, where topical zovirax ointment, chloramphenicol drops, gentamicin drops, dexamethasone drops, riboflavin subconjunctival were used. Against the background of treatment, positive dynamics were not observed.

When hospitalizing from the first day of treatment, eye drops of the following composition were used, wt.%:
sGAG - 0.1
Tobramycin - 1.0
Carnosine - 2.0
Sodium Chloride - 0.85
Monosubstituted Sodium Phosphate - 0.072
Disubstituted Sodium Phosphate - 0.079
Purified Water - Else
The pH of the eye drops is 6.8.

 During microbiological research, epidermal staphylococcus was determined in the culture. From the 2nd day of treatment, positive dynamics were noted: ulcer resorption began and during microbiological studies staphylococcus was not sown, on the 3rd day of treatment there were foci of ulceration epithelization. There was no allergic reaction. Complete epithelialization occurred on the 8th day, the ulcer was resorbed on the 16th day of treatment.

 Example 3

Patient G., the diagnosis of stromal keratitis with ulceration of the left eye. I did not receive treatment before hospitalization. When hospitalized in smears and cultures from the conjunctiva, pneumococcus was determined. From the first day of treatment, eye drops of the following composition were used, wt.%:
sGAG - 0.01
Tobramycin - 0.3
Nipagin - 0.03
Sodium Chloride - 0.85
Monosubstituted Sodium Phosphate - 0.018
Disubstituted Sodium Phosphate - 0.141
Purified Water - Else
The pH of the eye drops is 7.6.

 Positive dynamics was noted from the 2nd day of treatment: pneumococcus was not detected in smears and cultures, resorption of the infiltrate began. On the 4th day of treatment, corneal epithelization began. Toxic-allergic reaction was absent. Complete epithelization occurred on the 6th day, the infiltrate was resorbed on the 14th day of treatment.

 Example 4

Patient F., the diagnosis of stromal keratitis with ulceration of the left eye. I did not receive treatment before hospitalization. When hospitalized in smears and cultures from the conjunctiva, staphylococcus epidermal and pneumococcus were determined. From the first day of treatment, the installation of eye drops of the following composition was prescribed, wt.%:
sGAG 0.01 - 0.01
Tobramycin - 0.3
Cellulose - 0.05
An aqueous solution of 0.9% sodium chloride - The rest
Positive dynamics was noted from the 2nd day of treatment: pathological flora in the crop was not detected. On the 4th day of treatment, corneal epithelization and resorption of the infiltrate began. Complete epithelization occurred on the 9th day of treatment, the infiltrate resorbed on the 18th day. No toxico-allergic reaction was observed.

 Example 5

Patient P., the diagnosis of purulent corneal infiltration of the right eye. Prior to hospitalization, gentamicin was treated - eye drops. After hospitalization, an instillation of eye drops of a follow-up composition, wt. %:
sGAG - 0.01
Tobramycin - 0.3
Carnosine - 0.1
Nipaginum - 0,005
Methyl hydroxyethyl cellulose - 1.0
An aqueous solution of 0.85% sodium chloride - The rest
The instillation was carried out every hour, 2 drops in the daytime and every 4 hours at night. Positive dynamics were noted from the 2nd day of treatment. On the 3rd day, the frequency of instillation was reduced to 4-5 times a day. On the 5th day, resorption of the infiltrate was noted. Complete epithelization occurred on the 8th day of treatment, the infiltrate resorbed by the 19th day. An allergic reaction was not observed.

Claims (5)

1. Eye drops, including sulfated glycosaminoglycans and physiological saline solution of sodium salts, characterized in that they additionally contain tobramycin in the following ratio of components in wt.%:
Sulfated glycosaminoglycans - 0.005 - 0.1
Tobramycin - 0.1 - 1.0
Saline solution of sodium salt - The rest
2. Eye drops according to claim 1, characterized in that they additionally contain carnosine in an amount of 0.05 - 2.0%.  3. Eye drops according to claim 1 or 2, characterized in that they additionally contain nipagin in an amount of 0.005 to 0.03%.  4. Eye drops according to claim 1, or 2, or 3, characterized in that they additionally contain water-soluble cellulose derivatives in an amount of 0.05 - 1%.  5. Eye drops according to claims 1 to 4, characterized in that an aqueous solution of 0.85-0.92% sodium chloride is used as a physiological solution of sodium salts. 6. Eye drops according to claims 1 to 4, characterized in that a phosphate buffer with a pH of 6.8-7.6 is used as a physiological solution of sodium salts, including sodium chloride, mono- and disubstituted sodium phosphates and water in the following ratio of components in wt.%:
Sodium Chloride - 0.85 - 0.92
Monosubstituted sodium phosphate - 0.018 - 0.072
Disubstituted sodium phosphate - 0.079 - 0.141
Purified Water - Rest