DK162140B - Solid disinfection preparation for adding to mains water for disinfecting hydrophilic, soft compact lenses, and a corresponding disinfection solution and its use - Google Patents

Description

in

DK 162140 B

The present invention relates to a solid disinfectant composition for the addition of tap water to produce a non-eye irritant aqueous disinfection solution for hydrophilic soft lenses and a non-eye irritating aqueous disinfection solution for hydrophilic soft contact lenses 5 and a method for disinfecting hydrophilic soft lenses.

Contact lenses are thin convex lenses that are placed directly on the surface of the eye to correct vision errors. There are two main categories of contact lenses, namely hard lenses and soft lenses. Hard lenses are made of glass or more commonly hard resins, especially cross-linked polymethyl methacrylate. Soft lenses can be made of hydrophobic resins, especially cross-linked dimethylpolysiloxane, but are generally made of hydrophilic resins, especially polyhydroxyethyl methacrylate cross-linked with hydroxyethyl dimethacrylate.

The disinfection of hydrophilic soft lenses using chemical agents presents a particular problem, as the lenses can absorb chemical agents from disinfectant solutions in which they are soaked. The most commonly used disinfectant solutions for soft contact lenses are aqueous solutions containing a chlorhexidine salt, and it is well known that a sufficiently high concentration of chlorhexidine can build up in the lens thus creating irritation and sometimes damage to the lens wearer's eye. Accordingly, the concentration of chlorhexidine salt in the disinfectant solution should be kept at a sufficiently low but effective level (below about 0.005% by weight calculated as chlorhexidine, digluconate) to reduce the risk of eye irritation. It has recently been proposed in GB Patent Application No. 2090013A that eye irritation as a result of chlorhexidine salt disinfection can be prevented by using a substantially isotonic aqueous solution containing 0.0012 to 0.003% of a chlorhexidine salt if the tonicity adjusting agent is ionic. particles provide a tonicity equivalent that is at most equivalent to a 0.3% solution of sodium chloride.

Aqueous disinfection solutions of the prior art for hydrophilic soft lenses are prepared with deionized or otherwise particularly purified water, avoiding the problems encountered with hard water and chlorination if tap water were to be used, the calcium and magnesium salts in hard water would cause opaque deposits to build up on the lenses. In addition, chlorine would be absorbed and concentrated in the lenses in the same way as chlorhexidine salt as mentioned above. Although there have been theoretical suggestions to provide

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2 chlorhexidine-containing tablets for solution to form aqueous disinfectant solutions, as far as we know, chlorhexidine-containing solutions have always been supplied to the user as ready-made solutions.

As used herein, the term "tap water" means water which has not been deionized or particularly purified, but is sufficiently free of contaminants to be of a potable standard. Such water is typically supplied as drinking water from treatment plants via wires to a tap.

However, the term is not limited to water supplied from a tap and includes water of similar quality from other sources.

DE Publication No. 30 07 397 discloses an aqueous in sotonic storage solution for contact lenses containing chlorhexidine (thiomersal) (i.e., sodium ethyl mercurithi osalicyl) and polyvinylpyrrolidone in a buffered saline solution having a pH of approx. 7.4. As an inventive feature, the addition of EDTA to the solution is stated as a chelating agent. There is no mention of the use of tap water to prepare the aqueous solution. In the only specific example, water is used for injection. There is also no mention of providing a solid composition for addition to tap water.

U.S. Patent No. 4,395,346 relates to the removal of inorganic deposits from contact lenses using an aqueous solution containing a sequestering agent. The sequestering agent is polymethaphosphate, gluconic acid or a salt thereof. It is stated that the composition may contain a sterilizing agent and / or a buffer. However, there is no mention of the use of chlorhexidine.

25 U.S. Patent No. 2,547,653 relates to fluids for use between contact lenses and the eye. The solutions are aqueous solutions containing all potassium metal phosphates. Among the listed phosphates are complex polyphosphates. Reference is made to the presence of other materials, including sodium chloride, in the solution. However, there is no mention of the use of chlorhexidine or the use of a dechlorinating agent.

GB-A-1,464,333 relates to a contact lens storage solution of a reducing agent and a bacteriostatic agent in a buffered saline solution. The reducing agents listed are sodium iodide, sodium sulfite and sodium thiosul fat. The bacteriostatic agent listed 35 is merthiolate (i.e., thiomersal). Chlorhexidine is mentioned only in connection with solutions of the prior art.

In summary, none of the listed publications specifically describe the preparation of contact lens disinfection solutions.

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3 containing chlorhexidine using tap water. Where chelating agents such as EDTA are required, the purpose of the chelating agent is to assist in the removal of deposits from the lenses. There is no suggestion to use the chelating agent for sequestering calcium and magnesium cations from tap water. The amounts of chelating agent used are well below the range that would be required for treating tap water. Where in the prior art reference is made to "dechlorination" agents such as sodium sulfite or sodium pyrosulfate, the intended use is not for dechlorination, but as a protease activator, antioxidant or reducing agent.

The present invention has for its object to provide an aqueous disinfectant solution for hydrophilic contact lenses produced with tap water which does not provide opaque deposits to the lenses and is not irritating to the wearer's eye, and to provide a tablet or other solid formulation of a composition which can be dissolved in tap water to form such a disinfection solution.

This object is achieved with the present composition and the corresponding solution.

The invention provides a non-irritating disinfectant solution for hydrophilic soft contact lenses, which solution is obtained by the addition to tap water (as defined above) of an ophthalmically acceptable chlorhexidine salt, sufficient amounts of a compatible sequestering agent to remove calcium or magnesium of a dechlorinating agent, and optionally a pH-regulating agent, a tonicity-adjusting agent and / or a solvent-enhancing agent, all of which are ophthalmically acceptable.

Similarly, a solid disinfectant composition is provided for addition to tap water (as defined above) to provide a non-eye irritant aqueous disinfection solution for hydrophilic soft lenses which contains an ophthalmically acceptable chlorhexidine salt, sufficient amounts of a compatible second-hand compatible for removing calcium or magnesium cations and a dechlorinating agent, and optionally a pH-regulating agent, a toxicity-adjusting agent and / or a solution-enhancing agent, all of which are ophthalmically acceptable.

The composition is in the form of a solid formulation, e.g. a capsule, granule, powder or especially a tablet. It is preferred that the composition be 4

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however, that a desired disinfection solution is provided when added to 10 ml of tap water.

The solution is used in a method for disinfecting hydrophilic soft lenses which comprises soaking the lens in a non-eye irritant aqueous disinfection solution obtained by adding to tap water (as defined above) an ophthalmically acceptable chlorhexidine salt, sufficient amounts of compatible sequestering agent for removing calcium or magnesium cations and a dechlorinating agent, and optionally a pH-regulating agent, a tonicity-adjusting agent and / or a solution-enhancing agent, all of which are ophthalmically acceptable.

The lens is soaked for sufficient time to provide the desired disinfection. It is usually soaked for several hours, more commonly overnight. However, the lens may also be soaked for a shorter period of time when it has been temporarily removed from the eye for a purpose other than routine disinfection, such as during a vision test or during swimming.

The disinfectant solution contains an antimicrobial concentration of an ophthalmically acceptable chlorhexidine salt, which concentration is insufficient to cause eye irritation. The concentration is appropriate (calculated as chlorhexidine, digluconate) in the range of 0.001 to 0.005 wt%, generally 0.003 to 0.005 wt% and preferably 0.004 wt%.

In the preferred composition for addition to 10 ml of tap water 25, the concentration corresponds to a chlorhexidine salt content (calculated as chlorhexidine, gluconate) of 0.0001 to 0.0005 g, 0.0003 to 0.0005 g and 0.0004 g, respectively.

The disinfectant is chlorhexidine (ie, 1,6-di- (4'-chlorophenyl di-guanido) hexane) in the form of an ophthalmically acceptable acid addition salt thereof, such as the dihydrochloride or preferably the diacetate or especially the dugluconate.

The sequestrant is used in an amount sufficient to remove calcium and magma ions from the tap water wrap of the disinfectant solution. While the minimum amount required varies depending on the hardness of the tap water, an amount of at least 0.1% by weight is generally used. Suitably, the amount may be in the range of 0.1 to 1% by weight, usually 0.2 to 0.8% by weight, and most preferably 0.3 to 0.6% by weight. In the preferred composition for addition to 10 ml of tap water,

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5 to 0.01 to 0.1 g, 0.02 to 0.08 g and 0.03 to 0.06 g, respectively.

The sequestering agent can be any compound which at least sequesteres calcium and magnesium ions from tap water and is compatible with the other ingredients and with ophthalmic application of the disinfectant solution. In particular, the sequestrant should be non-irritating to the eye at the concentrations used in the solution. The sequestering agent is preferably a complex polyphosphate, e.g. sodium hexametaphosphate, sodium pyrophosphate or especially sodium tripolyphosphate.

The de-chlorinating agent is used in an amount that prevents chlorine transfer from chlorinated water through the lens to the eye. The minimum amount needed will vary depending on the degree of chlorination of the tap water, but generally 0.001% by weight will suffice. Suitably, the amount 15 may be in the range of 0.001 to 1% by weight, generally 0.005 to 0.1% by weight, in particular about. 0.01% by weight. These concentrations correspond to 0.0001 to 0.1 g, 0.0005 to 0.01 g, and 0.0001 g, respectively, in the preferred composition for addition to 10 ml tap water.

The deburring agent can be any compound that removes chlorine 20 from tap water and is compatible with the other ingredients and the ophthalmic application of the disinfectant solution. In particular, the detergent should be non-irritating to the eye at the concentrations used in the solution. The dichlorinating agent is preferably sodium metabisulite, sodium sulphite or especially sodium thiosulphate. The sodium thiosulfate may be added in the form of the pentahydrate thereof, but preferably in the anhydrous form.

The solution may contain other ingredients commonly present in disinfectant solutions for hydrophilic soft contact lenses.

In particular, it may contain an acid (to adjust the pH) and / or a tonic adjusting agent.

The acid will generally be present in an amount sufficient to give the solution a pH in the range of 4.0 to 8.0, preferably 5.5 to 8.0, and most preferably 6.0 to 7.5. With respect to the composition aspect of the invention, it is preferred that the acid be in solid form.

Suitable acids include fumaric acid, citric acid, maleic acid, adipic acid and preferably malic acid. If necessary, the solution can be pre-buffered to the desired pH.

The composition for the disinfectant solution will generally be formulated.

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6 is selected to be substantially isotonic, but the isotonicity may be provided by constituents present in the solution for other purposes. If a tonicity adjusting agent is needed, sodium chloride can be used.

It is particularly preferred that the disinfectant solution of the invention contains a solution enhancing system comprising urea and a nonionic surfactant.

Chlorhexidine is incompatible with certain sequestrants, including the preferred complex polyphosphates, in that no clear solution is obtained when both are dissolved in tap water at the same time. It has been found that this problem can be overcome by adding chlorhexidine (or a salt thereof) in solution in urea together with a nonionic surfactant. Generally, chlorhexidine is dissolved in molten urea, after which the resulting solution is cooled and granulated.

Suitably, urea is used in an amount of 0.5 to 2% by weight, preferably 1 to 1.6% by weight. In the preferred composition to be added to 10 ml of tap water, the concentrations correspond to 0.05 to 0.2 g and 0.1 to 0.16 g respectively. Urea affects the tonicity of the solution, so the amount of urea used will usually be limited to the 20 amount which results in tonicity.

Suitable nonionic surfactants for use with urea in the solution-enhancing system include polyoxyethylene alkyl ethers, polyoxyethylene alkyl phenyl ethers and polyoxyethylene sorbitan and other sugar based alkyl esters. Currently preferred surfactants are polyethylene glycol monocetyl ethers (e.g., Cetomacrogols), polyoxyethylene (20) sorbitan monooleate (e.g., polysorbate 80), sucrose monostearate, nonylphenol ethoxy (e.g. available under the trademarks of Antarox CO- 630 "and" EMPILAN N 92 "), and in particular polyoxyethylene (20) stearyl ether (eg available under the trademark" Brij 78 ").

As previously stated, the compositions of the invention are preferably in the form of tablets. Such tablets are prepared using conventional techniques, optionally by the addition of conventional tableting additives such as lubricants in such amounts as are necessary to provide tablets of the desired strength and solution profile. Suitable additives include polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG).

The invention is further illustrated in the following examples.

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Example 1

A tablet was prepared by conventional tableting technique from the following:

Sodium pyrophosphate 0.04 g 5 * Chlorhexidine, digluconate (20% aqueous solution) 0.002 ml

Sodium thiosul fat 0.001 g

Sodium chloride 0.09 g

Polysorbate 80 0.001 g 10 ("Tween 80") Malic acid 0.005 g ♦ Equivalent to 0.0004 g chlorhexidine, digluconate.

When the tablet was dissolved in 10 ml tap water, a solution was formed which was effective for disinfecting hydrophilic soft contact lenses by soaking overnight.

Example 2 A tablet was prepared by conventional tabletting technique from the following:

Sodium hexametaphosphate 0.04 g ♦ Chlorhexidine, diacetate 0.0003 g

Sodium Metabisulfite 0.005 g Urea 0.15 g

Cetomacragol 0.0025 g Malic Acid 0.005 g ♦ Equivalent to 0.0004 g chlorhexidine, digluconate.

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Chlorhexidine, di acetate was dissolved in the urea (melted) and the resulting solution was cooled and granulated prior to addition to the other tablet ingredients.

When the tablet was dissolved in 10 ml tap water, a solution was formed which was effective in disinfecting hydrophilic soft contact lenses by soaking overnight.

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Example 3

A tablet was prepared by conventional tableting technique from the following:

Sodium tripolyphosphate 0.04 g 5 * Chlorhexidine, digluconate 0.002 ml (20% aqueous solution)

Sodium thiosul fat 0.001 g

Urea 0.15 g "Brij 78" 0.001 g 10 Malic acid 0.005 g * Equivalent to 0.0004 g chlorhexidine, digluconate.

Chlorhexidine, the digluconate was dissolved in the urea (melted) and the resulting solution was cooled and granulated prior to addition to the other tablet ingredients.

Claims (13)

1. Solid disinfectant composition for addition to tap water to produce a non-eye irritant aqueous disinfection solution 5 for hydrophilic soft lenses, characterized in that it contains an ophthalmically acceptable chlorhexidine salt, sufficient amounts of a compatible sequestrant and calcium removal agent, and of a dechlorinating agent, and optionally a pH regulating agent, a tonicity adjusting agent and / or a solvent enhancing agent, all of which are ophthalmically acceptable. 2. A composition according to claim 1, characterized in that it is in the form of a tablet. A composition according to claim 1, characterized in that it contains 0.0003 to 0.0005 g of chlorhexidine salt (calculated as chlorhexidine, digluconate), 0.02 to 0.08 g of sequestering agent and 0.0005 g to 0.01 g of detergent. 4. A composition according to claim 1, characterized in that the chlorhexidine salt is selected from chlorhexidine, diacetate and chlorhexidine, digluconate, the sequestering agent is selected from sodium hexametaphosphate, sodium pyrophosphate and sodium tripolyphosphate, 25 5. A composition according to claim 1, characterized in that it contains as an pH regulating agent an acid selected from fumaric, citric, maleic, adipic and malic acids. 6. A composition according to claim 1, characterized in that it contains sodium chloride as a tonic adjusting agent. 7. A composition according to claim 1, characterized in that it contains as a solvent-enhancing agent urea and a non-ionic surfactant. 8. A composition according to claim 7, characterized in that it contains 0.1 to 0.16 g of urea. DK 162140 B 9. A composition according to claim 7, characterized in that the nonionic surfactant is selected from polyoxyethylene alkyl ethers, polyoxyethylene alkyl phenyl ethers, polyoxyethylene sorbitan and other sugar based alkyl esters. 10. Non-eye irritant aqueous disinfection solution for hydrophilic soft contact lenses, characterized in that the solution is obtained by the addition to tap water (as defined above) of an ophthalmic 10 acceptable chlorhexidine salt, sufficient amounts of a compatible sequestrant to remove calcium or magnesium cations and of a dechlorinating agent, and optionally a pH regulating agent, a tonicity adjusting agent and / or a solution enhancing agent, all of which are ophthalmically acceptable. 15 A solution according to claim 10, characterized in that it is obtained by dissolving a composition according to claim 1 in tap water. A solution according to claim 11, characterized in that the composition is a tablet according to claim 2 and that it is dissolved in 10 ml tap water. A method of disinfecting hydrophilic soft lenses, characterized in that the lenses are soaked in a non-eye irritant solution according to claim 10.