FIELD OF APPLICATION

The present invention refers to a multiple-action solution for contact lenses, for industrial production, having as main element the l-methyl-4-isopropenilcilohex-l- ene, or D-Limonene, as cleaning and disinfecting agent, combined with other adjuvant products.

STATE OF THE ART

The increasing use of contact lenses, both rigid lenses as lenses called disposable requires growing care with these devices. It is well known that contact lenses require frequent cleaning, and, in special, that these cleaning procedures do not affect the healthiness of the optical devices, and do not provide a sharp increase in the retention of harmful microorganisms to the ocular body.

Hydrophilic contact lenses may exhibit contamination by various bacteria, especially Serratua marscences, Staphicoccus epidermidis, Pseudomonas aeruginosa, Candida albicans, as well as other fungi and bacteria. Several methods have been described for disinfection processes of contact lenses, such as U.S. patents US4,407,791, US4, 525, 346 that revealed the use of ammonium polyquaternary, the European patent EP89810455.3 that revealed the ammonium bromide, and the patent US4,029,817 that revealed the ammonium chloride triethanol.

The products available in the market do not add biocidal activity and degreasing. There is a need for broad- spectrum cleaning agents, effective against wide range of fungi and bacteria, which, at the same time, pursue degreaser function. Compositions performing multiple functions can be called multiple action cleaner solutions, together with other components. Ideally these agents should be biodegradable, non- irritating eye mucosa and facilitate the preservation of the physical integrity of the devices, in a known cleaning action without friction. DESCRIPTION OF THE INVENTION

The compositions disclosed in the present invention are multiple solutions based on D-Limonene, in conjunction with other products with the aim of promoting friction-free cleaning, preserving the integrity of the devices or lenses.

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

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

D-Limonene is especially useful due to its antibacterial, anti-fungal and anti-algae activity and it is obtained from citrus oils. Anke et al . , Planta 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, poligodial, methyl marasmato and bilobalida.

Similar products are described on Anke et al . , Fd.

Chem. Toxic. 27 (No. 6) : 393-397 (1989) ( lactaroviolina, deterrol) ; Anke et al., J. Antibiotics 42 (No.5): 738-744 (1989) (merulidial) ; Didry et al., Pharmazie, April 1993, 48(4): 301-304 (cinnamaldeido) ; Gundidza et al., Cent. Afr. J. Med., July 1992, 38(7): 290-293 (Zimbabwe) and Himejima et al., J. Nat. Prod. 55(5): 620-625 (May 1992) (Licaria puchuri extract) .

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

D-limonene can be used alone or in combination with other biocidal agents. Appropriate agents for ophthalmic applications are, but not limited to, quaternary ammonium salts such as polyquaternium.

The polyquaternary or poliquaternarium is a polycationic polymer together with the presence of quaternary ammonium in the center of the polymer. Comprises various polymers designated by a number following the name

"polyquaternium". The polyquaternary polymers from 1 to 47 can be used as a biocide in addition to other components of the compound .

Amidoamines or amidoamines alcohols may be used to potentiate the effect of the composition described herein. The preferred amidoamines are myristamidopropyl dimethylamine, and related compounds described in U.S. Patent No. 5,631,005 (Dassanayake, et al . ) .

Poloxamers are triblock copolymers composed of hydrophobic chain of polypropylene combined with hydrophilic chains of polyoxyethylene . The term poloxamer was coined by the inventor Irving Schmolka in 1973 and is also known by the trade name Pluronics. As the polymer blocks can be customized, there are many different poloxamers, designated with the letter P followed by three digits, on which the first two X 100 indicate the approximate molecular weight and the latter indicates percent polyoxypropylene . For the Pluronics designation the initial letter defines the physical state, the first digit X 300 the molecular weight of the hydrophobe and the last 10 X indicates the percentage of polyoxyethylene .

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

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

EDTA (Ethylenediamine tetraacetic acid) is an organic compound which acts as a chelating agent to form very stable complexes with various metal ions, among them are magnesium and calcium, at pH values above 7 and manganese, iron (II), iron (III), zinc, cobalt, copper (II), lead and nickel at pH values below 7. EDTA is an acid that acts as a binder hexadentate, in other words, can complex the metal ion through six coordination positions that they are: through four anions carboxylate (-COO-), after the departure of 4H + of carboxylic groups, and also via the two N. EDTA is synthesized predominantly from 1, 2-diaminoethane (ethylenediamine) , formaldehyde (methanal) , water and sodium cyanide. The pioneering work on the development of EDTA was undertaken by Gerold Schwarzenbach in 1940.

Other compounds may be used in formulations of lens cleaning as polihidroxietil methacrylate, carboxymethylcellulose, non-ionic surfactants such as sorbitan, polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropylmethylcellulose and mixtures of the foregoing for the purpose of improvement of viscosity of the final product or adjustment pH.

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

The combined addition of biocidal agents, degreasing agents and chelants, as well as components for adjusting viscosity, density and pH as well as the addition of preservatives allow the final composition to be used as a cleaning agent for contact lenses without the need for prior friction, preserving the structure and integrity of the physical device.

Reducing agents are useful for stabilizing the final product, preferably being used thiols, acetylcysteine, organic carboxylic acids, amines, glutathione, homocysteine, cisteine, sodium bisulfate, sodium metabisulfite, sulfides and pirosulfetos .

The removal of proteinaceous deposits avoids affecting the clarity of the lenses, which substantially reduces its useful life.

D-limonene, employed according to the present invention, and yet in combination with other biocides, is employed in effective concentration. An effective disinfectant concentration is such that it reduces the total population of micro-organisms disinfection of the target obj ect .

Typically the concentration of D-limonene is 0.00001% (weight / volume) to 1.5% (weight / volume), preferably from 0.001% to 0.5%. Water-soluble compositions, incorporating D- limonene, can receive other agents, and their combination is highly effective. Thus, they can be incorporated as secondary biocide cationic polymers with quaternary ammonium known as polyquaternary comprising the polyquaternary from 1 to 47 at a concentration of 0.0001 to 1%. They may also be incorporated as additional biocidal agent and the anti- adherent agent dimethylamino myristamidopropyl at a concentration of 0.0001 to 1.0%.

May further contain a biocide concentration of polyhexamethylene biguanide at a concentration of 0.0001 to 1.0% and as surfactant agent polymer blend as polyoxypropylene and polyoxyethylene at a concentration of 0.0001 to 0.1%, and a chelating agent such as EDTA ( ethylenediaminetetraacetic acid acid) at a concentration of 0.0001 to 1.0%.

The liquid form, aqueous solution, is the preferred form of this composition, with or without preserving agents and agents for regulating 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 adjustment of viscosity, 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 Staphylococcus aureus 239, Pseudomonas aeruginosa 111 and Staphylococcus epidermidis 9142.

The test protocol followed the ISO 14729. Briefly,

30 contact lenses were inoculated with 100 microliters of inoculum on each side of the lens, yielding a concentration of bacteria of at least 5 X 105 CFUs for at least 10 minutes. Each lens was transferred to a culture plate with 24 wells, and applying the disinfectant, and this procedure after that was neutralized with 50 mL of DENB.

Each lens was centrifuged for 1 minute to remove the remaining bacteria adhering material and incubated for 48h at 35 ° C.

Results were expressed as log reduction unit (CFUs) .

The present invention should be used according to common procedures of this type of cleaning device. Thus, the lenses must be initially removed from the eye and immersed in aqueous solution containing biocides, surfactants, chelating agents, H, viscosity agents, preservatives, antioxidants and other components of the composition for sufficient time to disinfect the lenses.

Normally this time is from 6 to 8 hours, typically overnight used for greater user comfort.

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

The present invention is effective in cleaning contact lenses. Thus the compounds effectively remove deposits typically accumulated by human use.

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

Preferably an effective disinfectant concentration reduces the population of micro-organisms in the order of two logs at four hours. More preferably the reduction is approximately one log at one hour for all micro-organisms except A. fumigatus. More preferably this reduction occurs in contact lens.

An example of a composition of the present invention adopts the following formula:

D-Limonene - 0.1%

Poliquartenarium 1 to 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 the area of pharmaceutical production industry.

The aqueous solution should be mixed at room temperature for at least 30 minutes and bottled in sterile conditions, . according to current legislation.