BRPI1107166A2 - LENS CLEANING SOLUTION CONTACT - Google Patents

Abstract

LENS CLEANING SOLUTION CONTACT. The invention provides contact lens cleaning compounds containing D-limonene as a biocidal and degreasing agent, further containing other biocidal agents and auxiliary surfactants as well as pH, viscosity control agents and preservatives. The present invention promotes reduction of total bacterial amount of one log in one hour.

Description

LENS CLEANING SOLUTION CONTACT APPLICATION FIELD

The present invention relates to a multi-action contact lens solution for industrial production having as its main element l-methyl-4

isopropenylcylhex-1-ene, or D-limonene, as a cleaning and disinfecting agent, combined with other adjuvant products.

STATE OF ART

The increasing use of contact lenses, both lenses

Rigid as so-called disposable lenses requires increasing care with these devices. Contact lenses are commonly required to require frequent cleaning, and in particular these cleaning procedures do not affect the optical health of the devices, as well as provide for markedly increased retention of microorganisms.

harmful to the eye organ.

Hydrophilic contact lenses can be contaminated with various bacterial types, especially Serratua marscences, Staphicoccus epidermidis, Pseudomonas aeruginosa, Candida albicans, as well as other bacteria and fungi. Several methods have been described for contact lens disinfection processes, such as US patents US4,407,791 and US4,525,346 which disclose the use of polyquaternary ammonium, European patent EP 89810455.3 which disclosed ammonium bromide, and US4 patent , 029,817 which revealed triethanol ammonium chloride.

Commercially available products do not add to the biocidal activities and degreasing properties. There is a need for broad spectrum cleaning agents, effective against a wide variety of fungi and bacteria, which at the same time play a degreasing role. Compositions that perform multiple functions may be termed multi-action cleaning solutions in conjunction with other components.

Ideally these agents should be biodegradable, non-irritating to the eye mucosa and facilitate the preservation of the physical integrity of the devices in known cleansing action without friction.

DESCRIPTION OF THE INVENTION

The compositions disclosed in the present invention are multiple D-limonene-based solutions, in conjunction with other products for the purpose of cleaning without prior friction while preserving the integrity of the devices or lenses.

D-limonene is used in effective concentration 15 for disinfection and equally effective as a degreasing agent. D-limonene may be used in conjunction with other disinfection systems such as oxidative and non-oxidative disinfection systems, with surfactants and other products useful for conservation and industrial production.

The solution object of the present invention can be used with all contact lenses such as conventional rigid lenses, flexible lenses, silicone lenses, gas permeable and especially for soft lenses prepared as hydroxylethyl methacrylate hydrogel, hydroxymethyl methacrylate, vinylpyrrolidone, glycerol methacrylate, methacrylic acid, or all lenses that absorb water between 20 and 80% by weight.

D-Limonene is especially useful for its antibacterial, anti-fungal and anti-algal activities and is obtained from citrus fruit oils. Anke et al. , Plant Med. 57: 344-345 (1991), and Atzori et al., Antimicrobial Agents and Chemotherapy 37 (No. 7): 1492-1496 (1993) describe several similar products, such as isoveleral, polygodial, methyl marasmate and bilobalide. .

Similar products are further described by Anke et al., Fd. Chem. Toxic 27 (No. 6): 393-397 (1989) 5 (lactaroviolin, deterrol); Anke et al. , J. Antibiotics 42 (No.5): 738-744 (1989) (merulidial); Didry et al. Pharmazie, April 1993, 48 (4): 301-304 (cinnamaldehyde); Gundidza et al., Cent. Afr. J. Med., July 1992, 38 (7): 290-293 (Zimbabwe) and Himejima et al., J. Nat. Prod. 55 (5): 620-10625 (May 1992) (Licaria puchuri extract).

D-limonene derivatives as acetylated or methylated compounds are also useful according to the present invention. A derivative has one or more substituents such as alkyl groups, carboxyl groups, hydroxyl groups. Preferably these clusters do not diminish the effectiveness of D-limonene as a disinfectant and or a disinfectant as described by Meshnick et al. , Antimicrobial Agents and Chemotherapy, May 1993, p. 1108-1114, the contents of which are incorporated herein by reference.

D-limonene may be used alone or in combination with

combination with other biocidal agents. Suitable agents for ophthalmic applications are, but not limited to, quaternary ammonium salts such as polyquaternium.

Poliquaternarium is a set of polycationic polymers, with the presence of quaternary ammonium in the center of the polymer. It comprises several polymers, designated by a number after the name "polyquaternary". Polyquaternary polymers from 1 to 47 may be used as biocides, in addition to another 30 components of the compound.

Amidoamines or amidoamine alcohols may be used to enhance the effects of the composition described herein. Preferred amidoamines are myristamidopropyl dimethylamine, and related compounds, described in U.S. Pat. No. 5,631,005 (Dassanayake, et al.).

Poloxamers are triblock copolymers composed of polypropylene hydrophobic chain conjugated with polyoxyethylene hydrophilic chains. The term poloxamer was coined by the inventor Irving Schmolka in 1973 and is also known by the trade name Pluronics.

As polymer blocks can be customized, there are many different poloxamers, named 10 P followed by three digits, the first two X 100 indicating approximate molecular weight and the last one indicating polyoxypropylene percent. For the Pluronics denomination the initial letter defines the physical state, the first digit X 300 the molecular weight of the hydrophobe and the last X 10 15 indicates the percentage of polyoxyethylene.

As they are amphiphilic poloxamers have surfactant properties, increasing the aqueous solubility of oily substances.

Polyhexamethylene biguanide (PHMB) is an effective biocide at low concentrations against Gram + and Gram - bacteria and is also a broad spectrum virucide. It interacts with the surface of bacteria, transferring to the cytoplasm and causing cell death.

EDTA (Ethylenediamine tetraacetic acid) 25 Ethylenediamine tetraacetic acid is an organic compound that acts as a chelating agent, forming very stable complexes with various metal ions, including magnesium and calcium, at pH values above 7 and manganese, iron (II), iron (III), zinc, cobalt, copper (II), lead and 30 nickel at pH values below 7. EDTA is an acid that acts as a hexadent binder, ie it can complex the metal ion through six coordinating positions, namely: through four carboxylate anions (-C00-), after the 4H + leaving of the carboxylic groups, and also through the two N. EDTA is predominantly synthesized from 1,2-diaminoethane. (ethylenediamine), formaldehyde (metanal), water and sodium cyanide. The pioneering work on the development of EDTA was done by Gerold Schwarzenbach in the 1940s.

Other compounds may be used in lens cleaning formulations such as polyhydroxyethyl methacrylate, carboxymethyl cellulose, nonionic surfactants such as sorbitan, polyvinylpyrrolidone, polyvinyl alcohol,

hydroxypropyl methylcellulose and mixtures of the foregoing for the purpose of final product viscosity improvements or pH adjustment.

Preferred compounds are those water soluble as sodium carboxymethylcellulose, nonionic surfactants such as polyoxyethylene sorbitan monooleate, known as Tween 80. Carboxymethyl cellulose is a synthetic cellulose containing 0.4 to 1.5 carboxymethyl groups per glucose unit in cellulose.

The combined addition of biocidal agents, degreasing and chelating agents as well as viscosity, density and pH regulation components as well as the preservative addition allows the final composition to be used as a contact lens cleaning agent without the need for friction. preserving the physical structure and integrity of the device.

Reducing agents are useful for stabilizing the end product, preferably thiols, acetylcysteine, organic carboxylic acids, amines, glutathione, homocysteine, cysteine, sodium bisulfate, sodium metabisulfite, sulfides and pyrosulfides are used.

Removing proteinaceous deposits avoids affecting lens clarity, which substantially shortens lens life. D-limonene employed in accordance with the present invention and in combination with other biocidal agents is employed in effective concentration. An effective disinfectant concentration is such that it reduces the total microorganism population of the disinfected object.

Typically the concentration of D-limonene is from 0.00001% (weight / volume) to 1.5% (weight / volume),

preferably from 0.001% to 0.5%.

Water-soluble compositions incorporating D-limonene may receive other agents, and their

combination is highly effective. Thus, ammonium quaternary cationic polymers known as polyquaternaries can be incorporated as a secondary biocidal agent, comprising polyquaternaries from 1 to 15 at a concentration of 0.0001 to 1%. They may further incorporate as a supplemental biocidal agent and anti-adherent agent dimethylamino myristamidopropyl in a concentration of from 0.0001 to 1.0%.

In addition they may contain the polyhexamethylene biguanide biocidal agent at a concentration of 0.0001 to 1.0% and as a surfactant polymeric blend of polyoxypropylene and polyoxyethylene at a concentration of 0.0001 to 0.1%, and also as a chelating agent EDTA (ethylenediamine acid). tetraacetic acid) at a concentration from 0.0001 to 25 1.0%.

The liquid form, aqueous solution, is the preferred form of this composition, including or not preserving agents and agents for adjusting the pH and viscosity of the final composition. Preservatives are used in the range from 0.0001 to 0.05% by weight.

The compositions are in aqueous form requiring viscosity adjustments such as hydroxypropyl methyl cellulose and other cellulose derivatives, tonicity agents such as sodium chloride and mannitol, pH adjusting agents such as borates, citrates, phosphates and carbonates.

The solution thus prepared is effective against adherence of bacteria Staphylococcus aureus 23 9, Pseudomonas aeruginosa 111 and Staphylococcus epidermidis 9142.

The test protocol followed ISO 14729. Briefly, contact lenses 30 were inoculated with 100 microliters of inoculum on each side of the lens, obtaining a bacterial concentration of at least 5 X 105 CFUs for at least 10 minutes. Each lens was transferred to a 24-well culture plate and disinfectant was applied and neutralized after this procedure with 50 mL DENB.

Each lens was centrifuged for 1 minute to

removal of remaining adherent bacteria and material incubated for 48h at 35 ° C.

The results were thus obtained expressed in unit reduction Iog (CFUs).

Lens Contents S aureus Water P. epidermidis aeruginosa Purevision 36% 2.45 3 .38 4 .55 Focus 24% 2 .38 4. 15 5.13 Night and Acuvue 2 Day Acuvue 2 58% 3 .15 2. 4. The present invention should be used in accordance with

common cleaning procedures for this type of device. Thus, the lens should initially be removed from the eyes and immersed in the aqueous solution containing biocides, surfactants, chelators, pH agents, viscosity agents, preservatives, oxidizers and other components of the composition long enough to disinfect the lens. Usually this period is 6 to 8 hours, usually worn at night for the user's comfort.

The lenses are then rinsed in running water or sterile wash solution before use.

The present invention has an effect on cleaning contact lenses. Thus the compounds effectively remove deposits typically accumulated by human use.

Debris deposits vary from individual to individual, but typically include proteins, lipids, polysaccharides, and mixtures of these products. The compounds exhibit a cleaning effect when typical concentrations of these products are removed.

Preferably an effective disinfectant concentration reduces the microorganism population by two Yogs in four hours. Most preferably the reduction is on the order of one Iog in one hour for all microorganisms except A. fumigatus. More preferably, this reduction occurs in contact lenses.

An example composition of the present invention follows

the following formula:

D-Limonene - 0.1%

Poliquartenarium 1 - 0.001%

Myristamidopropyl dimethylamine - 0.0005%

Polyhexamethylene biguanide - 0.001%

Poloxamer - 0.001%

Preservative - 0.1%

Sterile water - q.s.p

This mixture should be made in appropriate reactors, in a sterile environment, in an industrial pharmaceutical production area.

The aqueous solution should be mixed at room temperature for at least 30 minutes and bottled under sterile conditions in accordance with current legislation.

Claims (7)

1. Multiple contact lens cleaning solution characterized in that it contains as its main agent 1-methyl-4-isopropenylcylhex-1-ene in a concentration of 0.00001% (w / v) to 1.5% (w / v), preferably from 0.001% to 0.5%. Multiple contact lens cleaning solution according to Claim 1, characterized in that it contains as an antibacterial secondary agent cationic ammonium quaternary polymers comprising polyquaternaries from 1 to 47 in a concentration of 0.0001 to 1%. Multiple contact lens cleaning solution according to Claim 1, characterized in that it contains as a antibacterial secondary agent and an anti-adherent agent the dimethylamino myristamidopropyl in a concentration of 0.0001 to 1.0%. Multiple contact lens cleaning solution according to Claim 1, characterized in that it contains as a antibacterial secondary agent polyhexamethylene biguanide in a concentration of 0.0001 to 1.0%. Multiple contact lens cleaning solution according to claim 1, characterized in that it contains as a surfactant a polyoxypropylene and polyoxyethylene polymer blend at a concentration of 0.0001 to 0.1%. Multiple contact lens cleaning solution according to claim 1, characterized in that it contains as its chelating agent EDTA (ethylenediamine tetraacetic acid) in a concentration of 0.0001 to 1.0%. Multiple contact lens cleaning solution according to Claim 1, characterized in that it is in the form of an aqueous solution.