RU2755298C1 - Contact lens care solution - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to disinfection and sanitation, and is intended for the care of contact lenses. The solution for the care of contact lenses contains benzyldimethyl[3- (myristailomino)propyl] ammonium chloride monohydrate, dextran, sodium chloride, sodium phosphate disubstituted 12-water, potassium phosphate mono-substituted and purified water. The components are used in the stated quantities.

EFFECT: invention provides a highly effective universal solution for the care of contact lenses, combining both a moisturizing agent and an antimicrobial agent, and also has a prolonged effect of these agents when combined in the absence of preservatives. Prolongation allows reducing the frequency of contact lens treatment up to 1-2 times a day while maintaining both moisturizing and lubricating properties.

1 cl, 1 tbl, 1 ex

Description

The present invention relates to a solution for the care of contact lenses. Contact lenses are designed to correct visual acuity.

Contact lenses are in high demand in the market. Consumer preferences are influenced by the level of comfort while wearing contact lenses. Therefore, in the contact lens art, manufacturers are seeking to improve the wearer comfort of contact lenses. The level of comfort in wearing contact lenses depends on a number of factors. For example, an uncomfortable feeling while wearing contact lenses can be caused by excessive lens rigidity, poor wettability, as a result of which the lens surfaces become dry, rough.

The wettability and comfort level of lenses depends on their materials. They can also be affected by the lens storage solution and cleaning solution components. Therefore, to enhance the wettability of the lenses, hydrophilic substances are added to the solution, which prevent rapid drying of the lens surfaces.

In the treatment of patients with dry eye syndrome (DES), moisturizing drops of the "artificial tear" type are more often used, the action of which helps to restore the tear film. Moisturizing drops in the "artificial tear" format are aqueous solutions of hydrophilic polymers (hyaluronic acid, methylcellulose derivatives, dextran, etc.) with the addition of preservatives that have a lubricating and emollient effect. The choice by ophthalmologists of "artificial tear" preparations for a particular patient is carried out, focusing on the indicators of the stability of the tear film and his subjective sensations.

The frequency of instillation of the drug is determined by the time of the resumption of eye discomfort in each individual person.

The drug "artificial tear" in its composition contains dextran and hypromellose, as well as sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, water for injection, disodium edetate, sodium chloride, benzalkonium chloride, benzalkonium chloride preservative, which, as you know, with systematic frequent instillation affects the metabolism of the epithelium of the cornea and conjunctiva (Federal State Budgetary Institution "Helmholtz Moscow Research Institute of Eye Diseases" Ibragimova D.I., Candidate of Medical Sciences, "Choosing an algorithm for the treatment of various clinical forms of corneal lesions in dry eye syndrome (experimental clinical study)", https://helmholtzeyeinstitute.ru/diss/005/Dissertacija_Ibragimova.pdf) Experimental study the effect of benzalkonium chloride at the end concentrations of 0.01 and 0.2% with the same instillation regime demonstrates that 0.01% benzalkonium chloride causes epitheliopathy in 60% of cases, and 0.2% solution of this preservative leads to total superficial erosion and edema of the corneal stroma, which confirms toxic the effect of even low concentrations of this preservative. Known eye drops "Natural tear" (firm Alcon), which contain hydroxypropyl methylcellulose in a concentration of 3 g / l and dextran 70 - 1.0 g / l. The preparation additionally contains sodium chloride (7.7 g / l), potassium chloride (1.2 g / l), disodium edetate (0.5 g / l), benzalkonium chloride (0.1 g / l). The disadvantage of the drug is the presence of a preservative benzalkonium chloride at a concentration of 0.1 g / l, which, as you know, with systematic frequent instillation, adversely affects the metabolism of the epithelium of the cornea and conjunctiva (The description of the drug is based on the official instructions, prepared in 2008 for the 17th edition the reference book of drugs "Register of medicines of Russia radar drug encyclopedia", 2009).

Known keratoprotective agent, artificial tear "Slezin" (https://www.neboleem.net/slezin.php), containing as active substances: hypromellose - 3 mg; dextran-70 - 1 mg; auxiliary components: glycerol, boric acid, sodium tetraborate decahydrate, potassium chloride, sodium chloride, disodium edetate dihydrate, benzalkonium chloride, 1M hydrochloric acid solution or 1M sodium hydroxide solution (up to pH 7.4 ± 0.1), purified water. It contains a water-soluble polymer system, which, in cooperation with natural tear fluid, improves the hydration of the cornea and ensures the hydrophilicity of its surface by activating the usual adsorption processes at the interface between the tear film and the corneal surface. Slezin's action lasts for 1.5 hours after a single instillation. Slezin increases the stability of the tear film on the surface of the cornea due to physiological mixing with it. The drug helps to reduce the symptoms of irritation associated with keratoconjunctivitis dry and to protect the cornea from drying out. Clinical studies have shown that blurred vision was most often observed during the use of Slezin.

Known drug (eye drops (RU 2431470 C1, 20.10.2011) for moisturizing the surface of the eye, allowing you to reduce or remove the symptoms of irritation caused by dry eye syndrome, containing dextran in an amount of 0.5-1.5 g / l, and which can be used for local therapy for dry eye syndrome A well-known agent for moisturizing and lubricating (wetting) contact lenses has not been used and, at the same time, does not have an antiseptic effect, since it does not contain an antimicrobial substance).

Dry eye syndrome is often associated with inflammation. Dry eye syndrome or keratoconjunctivitis dry - a disease accompanied by discomfort, visual disturbances and damage to the surface structures of the eye due to a violation of the stability of the pre-corneal tear film. Disorders of tear production and formation of a tear film, an inflammatory process in the tissues of the anterior surface of the eye can lead to it. Known eye drops "Okomistin" (https://aptstore.ru/catalog/lekarstvennye-preparaty/organy-chuvstv-zrenie-slukh/okomistin-kapli-glazn-0-01-f1-kap-10ml-10013520/), in the composition of which per 100 milliliters contains an active drug compound benzyldimethyl [3- (myristoylamino) propyl] ammonium chloride monohydrate in an amount of 10 mg. Purified water and sodium chloride are included in eye drops as excipients. The drug Okomistin®, eye drops, is recommended for use in the complex treatment of infectious processes in the anterior part of the eye (acute and chronic conjunctivitis, blepharoconjunctivitis, keratitis, keratouveitis), eye injuries, eye burns (thermal and chemical); in the preoperative and postoperative periods for the treatment and prevention of purulent-inflammatory lesions of the eyes. It cannot be used as moisturizing drops, since it does not contain aqueous solutions of hydrophilic polymers for humidification (for example, hyaluronic acid, methylcellulose derivatives, dextran, etc.)

Known moisturizing drops Opti-Free containing dextran 70 1.0 mg, sodium chloride 6.0 mg, sodium borate (borax) 3.5 mg, potassium chloride 1.2 mg, polyquad solution (POLYQUAD ™, polyquaternium-1), equivalent to polyquad 0.01 mg, hydroxypropyl methylcellulose 4000 mPa.s (hypromellose) 3.0 mg, sodium hydroxide and / or concentrated hydrochloric acid to adjust the pH, purified water to 1.0 ml.

Polyquaternium-1 (PQ-1) is a polymeric preservative, developed and introduced into the ophthalmic pharmaceutical industry by Alcon in 1987. On the one hand, this is a quaternary ammonium compound, the classic representative of this group is benzalkonium chloride (BC) with a known cytotoxic effect. On the other hand, the hydrophobic macromolecule of the new preservative has a molecular weight of 5000 versus 340 for HD, which makes it possible to get rid of the cytotoxic properties. It is known that preservatives adversely affect the metabolism of the epithelium of the cornea and conjunctiva, and are also one of the external causes of impaired evaporation of lacrimal fluid. The tool also has a number of contraindications for use: hypersensitivity to any component of the drug.

(https://remedium-nn.ru/?id=9842;

https://clinopht.com/articles/oftalmologiya/konservanty-v-oftalmologicheskikh-preparatakh-ot-benzalkoniya-khlorida-k-polikvaterniyu/;

https://www.asna.ru/cards/opti-fri_kapli_glaznye_15ml_alkon.html).

Presently known compositions for treating contact lenses consist mainly of the following components: bactericidal active agent, surfactants, preservative and saline solution.

A known composition for the treatment of contact lenses (RU 2139094 C1, 10.10.1999). The composition contains, as a bactericidal active agent, antimicrobial substance Miramistin, taken in an amount of 0.001-0.05 wt. % in combination with sodium salt of carboxymethylcellulose, forming a complex, and disodium salt of ethylenediaminetetraacetic acid as a preservative and to remove calcium. The composition also contains surfactant cleaners - polysorbate-80 and polyethylene oxide and isotonic saline solution based on sodium chloride and phosphate buffer system. The composition does not cause sensitization of the body and does not have an immunotoxic effect, does not affect the mass and cellularity of the central and peripheral organs of the immune system. Miramistin is known as an antiseptic, its registration number is 91/146/2, and it is produced by domestic industry. However, the known composition is not intended to moisturize and lubricate contact lenses. The composition contains the disodium salt of ethylenediaminetetraacetic acid as a preservative. With prolonged use of compositions containing preservatives, many patients develop persistent intolerance to these components.

There is no contact lens care solution on the market that contains both hydrophilic and antimicrobial agents. Accordingly, there is a need for a contact lens care solution containing both hydrophilic and antimicrobial agents. It should have properties that enhance the wettability of contact lenses, prevent rapid drying of their surfaces, improve eye health to reduce fatigue caused by prolonged wear of contact lenses, and increase the comfort level of contact lenses, as well as provide an antiseptic (antimicrobial, disinfectant) effect in the absence of preservatives ... The presence of preservatives in lens treatment compositions is disadvantageous for contact lens wearers with dry eye syndrome, as it manifests itself in a worsening of the clinical course of dry eye syndrome. The technical objective of the present invention is to expand the range of solutions for the care of contact lenses that simultaneously moisturize and lubricate, as well as antimicrobial properties with prolonged action, without preservatives.

The task is achieved by the proposed solution for the care of contact lenses containing benzyldimethyl [3- (myristaylomine) propyl] ammonium chloride monohydrate, dextran, sodium chloride, sodium phosphate disubstituted 12-water, potassium phosphate monosubstituted and purified water at the following ratio of components, g / l:

benzyldimethyl [3- (myristailomine) propyl] ammonium chloride monohydrate - 0.05-0.1 dextran 40,000 - 70,000 - 40.00- 60.00 sodium chloride - 5.0-5.5 sodium phosphate disubstituted 12-water - 11.5-11.96 potassium phosphate monobasic - 1.35 - 1.37 purified water - rest

The proposed solution ("LK-Tear") is suitable for the care of soft and hard contact lenses. It contains phosphate buffer, sodium chloride, benzyldimethyl [3- (myristailomine) propyl] ammonium chloride monohydrate as an antimicrobial agent and dextran as a moisturizer and lubricant.

In the proposed solution, the auxiliary substances are disubstituted sodium phosphate 12-aqueous and monosubstituted potassium phosphate, maintaining the buffer properties of the solution and sodium chloride, which allows you to adjust the isotonicity of the solution

The solution for the care of contact lenses in terms of toxicological and sanitary-chemical indicators meets the requirements for medical devices.

To increase the comfort when wearing contact lenses, instill (1-2 drops) of the LK-tear solution on the surface of the contact lens. This eliminates the feeling of dryness by moisturizing and lubricating the contact lens.

In a subacute toxicological experiment on rabbits with repeated instillation of a composition for treating lenses and extracts from samples, no irritating effect on the mucous membrane was detected. There were no clinical symptoms of intoxication in animals.

Dextran in combination with an antimicrobial agent - benzyldimethyl [3- (myristaylomine) propyl] ammonium chloride monohydrate gives an additional effect - the rejection of preservatives and prolongation of two main components, which individually do not have such an effect. Dextran increases the viscosity of the solution and promotes longer contact of the drug with the surface of the eye, which contributes to a long-term moisturizing effect in contact lens wearers. Prolongation involves the gradual release of the antimicrobial agent benzyldimethyl [3- (myristailomine) propyl] ammonium chloride, which is a significant positive addition, since contact lens wearers suffer not only from insufficient moisture, but also from inflammatory processes when wearing any contact lenses. These all contribute to the reduction of symptoms such as stinging, irritation, and burning associated with dry eye syndrome in carriers. The solution does not cause sensitization of the contact lens organism.

A big advantage is the absence of a preservative in the proposed solution for the care of contact lenses, since, recently, everyone is trying to find a way to introduce a less toxic preservative into the composition for treating lenses. Specifically, the presence of preservatives in lens treatment compositions is disadvantageous for dry eye contact lens wearers, as this results in a worsening of the clinical course of dry eye syndrome. with the eye. It is enough to apply a few drops of the product to the inner surface of the lens, after which it can be put on. The solution can also be used without removing contact lenses during the day if dryness or discomfort occurs. The proposed solution contains a derivative of myristic acid, which is allowed in ophthalmology and relieves the inflammatory process in dry eye syndrome in relation to 4 groups of pathogens - bacteria, fungi, viruses and protozoa, unlike other drops that contain dextran, but with preservatives that have an adverse effect on the metabolism of the epithelium of the cornea and conjunctiva.

Example 1.

Active ingredients, g / l: benzyldimethyl [3- (myristailomine) propyl] ammonium chloride monohydrate - 0.05, dextran 40,000 - 70,000 - 60.00, sodium chloride - 5.0, sodium phosphate disubstituted 12-water - 11.96 , monobasic potassium phosphate - 1.37, purified water - up to 1 liter. The solution is a clear, colorless, colorless and odorless liquid designed to moisturize and lubricate soft and hard contact lenses, pH 7.4. The premises in which the production of the LK-Sleza solution was carried out is equipped with general exchange supply and exhaust ventilation in accordance with GOST 12.4.021.

Transparency check.

The transparency was determined by comparing the LK-TEZA solution with water for injection. The test was carried out under illumination with a 40 W frosted glass electric lamp against a black background with glass bottles with a solution placed vertically. When testing the "LK-TLEZA" solution, packaged in bottles made of polymer material, we proceeded as follows:

- glass cylinders were selected with a capacity corresponding to the amount of LK-Sleza solution in a packaging unit (10 ml)

- the dishes were thoroughly washed, rinsed with water for injection, dried;

- the solution "LK-TLEZA" was poured from polymer vials - 10 ml into the prepared vessel and examined as indicated above.

The solution "LK-TEARS" is transparent, since when examined by comparison with water for injection with the naked eye, no insoluble particles were observed.

Determination of chromaticity.

The color of the LK-TEZA solution was determined by comparison with water. The comparison was made in test tubes of the same glass and diameter under daylight reflected light on a matte white background, viewing from top to bottom through the entire liquid layer. Under these conditions, the color of the solution and the water standard was indistinguishable.

Determination of pH.

The determination was carried out by a potentiometric method using a universal type ionomer EV-74 in accordance with GOST 22261. The LK-TLEZA solution was placed in a beaker so that the ionomer electrodes were completely immersed in the solution. The pH was determined at (25 + 2) ° C. The time for establishing the readings did not exceed 5 minutes. pH 7.4, which corresponds to the norm (the permissible norm of pH is from 6.0 to 7.6.)

Determination of sterility.

Conducted by the method of direct inoculation or membrane filtration according to the State Fund of the Russian Federation Edition XIV, Volume 1 (OFS.1.2.4.0003.15).

Result - the solution is sterile

Toxicological tests.

According to the results of an experiment on laboratory animals using preliminary intradermal sensitization, multiple epicutant applications and a provocative intradermal test, the sensitizing effect of the LK-Tear solution and extracts from samples of the dispenser nozzle and cap, the presence of which was also judged by the reaction of specific lysis of blood leukocytes ( RSLL), no irritating effect on the skin was found. Autopsy of the animals did not reveal macroscopically pathological changes in the internal organs and tissues of the experimental animals. The mass coefficients of the internal organs of the experimental animals do not have statistically significant differences from those of the control animals.

In a subacute toxicological experiment on rabbits with repeated installations of the LK-Tear solution and extracts from the samples of the dispensing nozzle and the lid into the conjunctival sac, no irritating effect on the mucous membrane was detected. There were no clinical symptoms of intoxication in animals.

A study of cytotoxicity was carried out on a suspension culture of motile cells with the determination of the toxicity index. The toxicity index ranged from 72% to 84% with the standard value from 70% to 120%.

Conclusions based on the test results: The solution for moisturizing and lubricating soft and hard contact lenses "LK-Sleza" meets the requirements for medical devices in terms of toxicological and sanitary-chemical indicators.

Example 2.

Differs from example 1 in that the initial components are taken in the following ratio: active ingredients, g / l: benzyldimethyl [3- (myristaylomine) propyl] ammonium chloride monohydrate - 0.1, dextran 40,000 - 70,000 - 40.00, sodium chloride - 5.5, sodium phosphate disubstituted 12-water - 11.5, potassium phosphate monosubstituted - 1.35, purified water - up to 1 liter. The solution is a clear, colorless, colorless and odorless liquid designed to moisturize and lubricate soft and hard contact lenses, pH 7.1.

Below is a table comparing the proposed solution with known agents used in DES syndrome.

As can be seen from the data in the Table, the proposed solution for contact lens care can be used to combat DES. The use of the proposed tool allows to reduce the frequency of instillation in patients with DES in comparison with known agents up to 2 times a day

The technical result of the present invention is the creation of a highly effective universal solution for the care of contact (soft and hard) lenses, combining both a moisturizing agent (dextran) and an antimicrobial (benzyldimethyl [3- (myristailomine) propyl] ammonium chloride monohydrate), and possessing with an additional significant positive effect of prolonging the action of these 2 components when combined in the absence of preservatives. Prolongation allows you to reduce the frequency of contact lenses to 1-2 times a day. The technical result obtained was unexpected and did not follow from the prior art.

Claims (2)

A solution for the care of contact lenses containing benzyldimethyl [3- (myristailomine) propyl] ammonium chloride monohydrate, dextran, sodium chloride, sodium phosphate disubstituted 12-aqueous, potassium phosphate mono-substituted and purified water at the following ratio of components, g / l: benzyldimethyl [3- (myristailomine) propyl] ammonium chloride monohydrate 0.05-0.1 dextran 40,000 - 70,000 40.00- 60.00 sodium chloride 5.0-5.5 sodium phosphate disubstituted 12-aqueous 11.5-11.96 potassium phosphate monobasic 1.35 - 1.37 purified water rest