RU2073523C1 - Preparation for treatment of burn disease of eye of i-iv degree - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: proposed preparation contains (weight %): base inhibitor of protein 0.196-0.66, nipagin 0.08-0.12, sodium chloride 0.68-0.73, nicotinic acid 0.45-0.50, sodium oxide 0.14-0.16, polyvinyl alcohol 1.35-1.40 and apyretic water. Proposed preparation with prolonged action is non-toxic and is stable within 1.5 years. EFFECT: improved quality of desired product.

Description

 The invention relates to medicine, specifically to drugs used in ophthalmology in the treatment of burn eye disease.

 The basis of this drug is the main inhibitor of proteinases (IPRs) of the salivary glands, lungs, and pancreas of cattle (c.p.s.).

 Gordox (Hungary), Kontrikal, Zimofren (France), Aprotinin (England) and others, known abroad as proteinase inhibitors, are available in 3 and 5 ml bottles.

 The use of IPRs in ophthalmology was begun with experimental studies in animals.

 We studied the effects of trasilol, conrical, gordoks and ingitril in experiments on thermal burns of the cornea. At the same time, corneal epithelization occurred on the 7-8th day, and an increase in the scarring process was noted. We studied the effect of instillation of contracal on the course of ophthalmic herpes. The anti-inflammatory effect of the inhibitor was noted.

 The Gordoksa solution was successfully used in the complex in the form of subconjunctival or intravenous injections, or in combination in the treatment of patients with severe uveitis.

 In the treatment with proteolase inhibitors, the working solutions of Contrikal and Gordox were diluted physiologically with a solution to an activity of 1000 and 3000 KIU / ml; in the case of electrophoretic and phonophoresis treatment, the working concentration of the inhibitor was 200 KIU / ml. The lack of a finished dosage form of a proteinase inhibitor in the practice of ophthalmology, both domestic and foreign, allowed the applicants to conduct directed research work to create a stable prolonged dosage form of a basic proteinase inhibitor.

The Gordoks preparation (Hungary) was taken as a prototype when creating the dosage form for the IPR, which, when diluted with physiological saline to an activity of 1000-2000 KIE / ml, was used to treat eyes with the following composition:
IPR 100000 KIE
Sodium Chloride 85 mg
Thiomersal (ethyl mercury thiosalicylate) 0.1 mg
Water Up to 10 ml in each ampoule
Gordox solution pH 5.0 7.0
However, the disadvantage of this drug is the toxicity of the preservative ethylmercury thiosalicylate. In addition, one of the disadvantages of proteinase inhibitors is that they are rapidly excreted from the body (from 10 to 60 minutes).

 The active principle of eye drops in our development is the main proteinase inhibitor (IPR) of molecular weight 6513, consisting of 58 amino acids, with an isoelectric point pJ of 10.5.

 Studies have shown that the most effective doses for treating burns are 10,000 and 30,000 KIU / ml. Therefore, in the development of the dosage form of IPRs, available and low-toxic preservatives were used: benzyl alcohol, nipagin.

According to the antimicrobial and stabilizing effect of preservatives in a dosage form in the neutral pH region, nipagin was chosen as a preservative (LD ₅₀ -1300-3000 mg / kg, concentration 0.1 0.2% pH 5.0 8.0). Sodium chloride was taken as isotonic. A necessary component involved in the redox processes of the body in the studied dosage form is nicotinic acid.

 Polyglucin (m. 35000 Daltons), methyl cellulose, polyvinyl alcohol (m. M. 1000-2000), proxanol (m. M. 700), hydrolyzed ethoxylated starch “Volekam” (m. m. 200000).

 Based on experimental data, a medical polyvinyl alcohol corresponding to the requirements of FS 2299-85 was chosen as a prolongator.

 In our research, polyvinyl alcohol with a molecular weight of 10,000 to 2000 Daltons was used.

 The proposed qualitative composition of the components and their quantitative ratio allowed us to create an effective drug for the treatment of burns of I-IV degrees in ophthalmology. The drug is non-toxic, with a prolonging effect, does not cause irritation, pathological changes, allergic deviations, has good tolerance, the drug is stable in time (1.5 years).

 The drug was tested on rabbits.

This drug has the following composition (weight.):
Basic Proteinase Inhibitor (IPR) (4500-5100 KIE / mg substance activity) 0.196 0.66
Nipagin 0.8 1.2
Sodium chloride 0.68 0.73
Niacin 0.45 0.50
Sodium hydroxide 0.14 0.16
Polyvinyl alcohol (medical) 1.36 1.40
Pyrogen-free water Else
pH 6.5 6.5
If necessary, add the calculated amount of 1 N. NaOH to bring to the desired pH value.

 The solution is sterile filtered, poured into vials of 3 and 5 ml and sealed with sterile plugs and aluminum caps.

 The method of applying eye drops to experimental rabbits by instillation of two drops in both eyes for a month.

 Animal experiments have shown that in the treatment of light burns of the cornea of the eye of I-II degrees, it is recommended to use a drug with an activity of 10,000 KIU / ml to accelerate epithelization, and for severe burns of the III-IV degree - 30,000 KIU / ml.

Claims (1)

 A preparation for the treatment of burn disease of the eyes of I-IV degrees, including a basic proteinase inhibitor, preservative, isotonic, water, characterized in that the preparation additionally contains polyvinyl alcohol, nicotinic acid and sodium oxide, nipagin and isotonic sodium chloride as a preservative in the ratio of components, wt. The main inhibitor of proteinases 10,000 30,000 KIE / ml (activity of the substance 4,500 5,100 KIE / mg) 0.196 0.660
Nipagin 0.08 0.12
Sodium chloride 0.68 0.73
Niacin 0.45 0.50
Sodium oxide 0.14 0.16
Polyvinyl alcohol 1.35 1.40
Pyrogen-free water