JP3247831B2 - Composition for disinfecting, neutralizing and cleaning contact lenses and method of using the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

FIELD OF THE INVENTION The present invention relates to a one -part combination preparation for disinfecting, neutralizing and cleaning contact lenses and a method for using the same. More specifically, the present invention relates to a one -part combination preparation suitable for quickly and easily disinfecting, neutralizing and cleaning a soiled contact lens, and a method for using the same.

[0002]

2. Description of the Related Art Methods for disinfecting soft contact lenses are roughly classified into a boiling disinfection method and a chemical disinfection method and are currently used. Boiling disinfection is practically effective for killing all microorganisms such as bacteria, viruses, and molds, but the protein and other adsorbed substances adhering to the soft contact lens are denatured by heat and coagulated, and the lens becomes cloudy. And heating for a long time may cause deformation and discoloration of the lens. In addition, there is an inconvenience that cannot be used without a power supply.

[0003] A number of chemical disinfection methods are also known, and 3% hydrogen peroxide and biguanide-based disinfectants have a low bactericidal effect depending on the type of microorganism. In addition, when misused, the corneal epithelium and conjunctiva are stimulated too strongly and may cause corneal damage.

[0004] Among various halogen-based disinfectants, an iodine-based disinfectant is a chemical disinfectant excellent in both its bactericidal activity and eye safety. Examples of using an iodine-based disinfectant include British Patent No. 1,604,020, US Patent No. 4,312,833, Contacto, 33-37.
Page (1975), Nichi-Ko Magazine 23, pp. 150-154 (1981), Nichi-Ko Magazine 20, 196-101 (1
978). However, in these methods, after disinfection with an iodine-based disinfectant, removal and neutralization of the used residual disinfectant is performed by natural sublimation peculiar to iodine or by using a weak reducing agent. It takes time and the neutralization may be insufficient. As a result, the iodine agent is adsorbed in the matrix of the soft contact lens, which may cause discoloration of the lens or deformation and deterioration of the lens due to the reaction between iodine and the lens material.

Further, although the iodine preparation is relatively safe for the eyes, if it is adsorbed and accumulated in the lens due to insufficient neutralization, the iodine-based drug is gradually released during wearing, and
As described in alsOphthalmology, pp. 361 to 364 (1981), there is a possibility of causing inflammation and corneal disorder of eyes such as allergic persons. It is also important in the care of soft contact lenses to remove proteins and lipids attached to the lens,
A cleaning agent for this is needed. However, a one-part combination preparation of an iodine disinfectant, a neutralizing agent, a protease, and a surfactant has not yet been known.

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a one-part combination preparation for disinfection, neutralization and washing together in one part. It is another object of the present invention to provide a one-part combination preparation suitable for quickly and simply disinfecting, neutralizing and cleaning a soiled contact lens. Still another object of the present invention is to improve the drawbacks of a preparation containing a conventional neutralization method using an iodine disinfectant that shows a strong bactericidal effect and is relatively safe.
Another object of the present invention is to provide a one-pack type combination preparation for easily disinfecting, neutralizing and washing soft contact lenses by combining two kinds of preparations. Still another object of the present invention is to provide a method for quickly and easily cleaning a soiled contact lens using the one-component combination preparation of the present invention. Still other objects and advantages of the present invention will become apparent from the following description.

[0007]

According to the present invention, the above objects and advantages of the present invention are as follows: first, (A) a first preparation containing an iodine fungicide and a protease; and (B) A combination of a second formulation comprising a sulfur-containing reducing agent and a foaming agent and having a delayed release coating, and wherein at least one of the first formulation and the second formulation comprises a non-ionic surfactant. This is achieved by a one-part combination preparation for disinfecting, neutralizing and cleaning contact lenses, characterized in that it comprises:

The one-part combination preparation of the present invention comprises a first preparation (A) and a second preparation (B), and at least one of them contains a nonionic surfactant. The first formulation contains an iodine-based fungicide, a proteolytic enzyme and optionally a non-ionic surfactant. The iodine-based fungicide preferably used in the present invention is a polyvinylpyrrolidone (P) in which the iodine molecule (I ₂ ) is a macromolecule.
VP) or povidone-iodine or PVA known from ancient times to be included in polyvinyl alcohol (PVA)
Iodine. Compared to free iodine agents, these polymer-bound iodine agents are more water-soluble, stabilize sublimable and unstable iodine molecules in the solid state, and further reduce the toxicity. It is an extremely excellent disinfectant having a strong bactericidal action equivalent to the disinfectant. That is, the disinfectant has a broad antibacterial spectrum against bacteria, antibiotic-resistant bacteria, molds, viruses, and the like.

[0009] The proteolytic enzyme suitably used in the present invention must sufficiently maintain the detergency of the lens protein stain in the presence of the iodine disinfectant which is a strong oxidizing agent. In particular, sulfur groups, i.e., sulfur atoms such as thiol groups and dithio groups, are susceptible to oxidation by iodine compounds. Therefore, enzymes having a large number of these sulfur groups, such as papain, bromelain, ficin, pancreatin and cathepsin, are used as the iodine disinfectants. Under the coexistence, the enzyme titer is greatly reduced and is unsuitable as the enzyme detergent of the present invention. Therefore, these are not used in the present invention.
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As a result of carrying out stability experiments using various enzymes in the presence of the iodine preparation, it was revealed that proteolytic enzymes produced by microorganisms belonging to the genus Bacillus and enzymes derived from animal pancreas are relatively stable. Was. Used in the present invention
Proteolytic enzymes include the iodine preparations described above.
On the other hand, it is relatively stable. Commercially available proteolytic enzymes include, for example, bioprase, biotamylase (Nagase Seikagaku Corporation), protease N "Amano" (Amano Pharmaceutical Co., Ltd.), subtilisin A, alcalase, esperase, trypsin, chymotrypsin (Novo Norr). Disc Bioindustry Japan). They are conveniently selected from them.

In the first preparation, the iodine-based fungicide is preferably contained at a concentration of effective iodine of 1 to 500 ppm, more preferably 10 to 150 ppm. If the concentration is less than 1 ppm, the bactericidal activity is reduced. If the concentration is more than 500 ppm, the neutralization time is delayed and the lens is affected, so that handling becomes difficult.
The concentration of the proteolytic enzyme is appropriately determined depending on the washing effect and the enzyme titer, but is preferably 0.005 to 0.005.
Used to give a concentration of 2% by weight.

The non-ionic surfactant which may be contained in the first preparation includes, for example, poloxamer (or
Loxamer), poloxamine (or poloxamer)
) , Polysorbate 80, polyoxyl stearate 40 and polyoxyethylene hydrogenated castor oil 60 are preferably used. The nonionic surfactant is preferably 0.001-1% by weight, more preferably 0.01% by weight.
Used at 1-0.5% by weight.

On the other hand, the second formulation contains a sulfur-containing reducing agent, a foaming agent and optionally further non-ionic surfactants and has a delayed release coating. As the sulfur-containing reducing agent,
What are known as strong reducing agents for iodine and halogenating agents can be used. Especially sodium sulfite,
Sodium bisulfite and sodium thiosulfate are particularly preferred because they effectively reduce iodine molecules remaining on the soft contact lens after disinfection. In addition, as a foaming agent,
For example, sodium hydrogen carbonate and sodium carbonate are preferably used. Further, examples of the nonionic surfactant that may be contained in the second preparation include the same nonionic surfactants as those exemplified for the first preparation.

The second formulation has a delayed release coating.
The reason is as follows. The aqueous solution of iodine molecules
Depending on its concentration, the color changes from black-brown to yellow, and iodine also easily adheres to organic compounds as used as a color former in thin-layer chromatography on silica gel or alumina. The material of the soft contact lens to be disinfected is composed of a polymer of an organic compound such as a methacrylic acid derivative, an acrylamide derivative and N-vinylpyrrolidone, so that iodine molecules easily adhere to the lens matrix at the time of disinfection. The lens is colored brown. If this state continues for a long time, there is a possibility that effects such as denaturation and deterioration of the lens material may be exerted. After sterilization, the molecular iodine by the reducing agent are subjected to reduction, little iodine anion adsorption ability of the colorless safe and lens matrix ^- changes a is for example, sodium iodide (I).

Therefore, after the sterilization is effectively performed with iodine, it is necessary to immediately reduce the remaining excess iodine molecules with a sulfur-containing reducing agent. Therefore, the second formulation is the first
After the sterilization of the contact lens is completed with the above formulation, a delayed release coating is provided so as to release the sulfur-containing reducing agent and the like. That is, only by holding the soiled lens in an aqueous solution containing both the first and second preparations, first, the first preparation sterilizes and cleans the contact lens, and when the sterilization is almost completed, If the delayed release coating of the second preparation is dissolved and destroyed, the extra iodine molecules remaining are reduced (neutralized) by the sulfur-containing reducing agent contained in the second preparation. Will be. The foaming agent contained in the second preparation assists the reduction reaction to proceed advantageously and smoothly.

The delayed release coating preferably used in the present invention is a chemically modified cellulose or gelatin. Among them, hydroxypropyl cellulose (HP
C), hydroxypropyl methylcellulose (HPM
C) and hydroxyethyl cellulose (HEC) are more preferred. The delayed release coating is preferably designed so that foaming starts in 1 to 10 minutes. That is, contact lens disinfection and cleaning with the first preparation, i.e., with respect to disinfection with an iodine-based bactericide and cleaning with a protease, since sufficient sterilization and sufficient washing are performed while suppressing the deactivation of the protease, Since the disinfection time is appropriately about 1 to 10 minutes, it is desirable that the active ingredient of the second preparation is allowed to act thereafter. To that end , the first formulation is preferably a powder or granules, and the second formulation is preferably a tablet or capsule.

According to the present invention, therefore, secondly, the soiled contact lens containing the one-part combination preparation of the present invention and containing the first preparation in a dissolved yellow-brown solution is retained. Also provided is a method for disinfecting, neutralizing and cleaning contact lenses, comprising separating the contact lens from the aqueous solution after the second formulation has dissolved and the aqueous solution has become substantially colorless. The aqueous solution containing the one-part combination preparation is at least one tonicity agent selected from the group consisting of sodium chloride and potassium chloride, and at least one tonicity agent selected from the group consisting of phosphate , boric acid and borate. buffering agents and is desirable that the aqueous solution obtained by dissolving a chelating agent to purified water selected from disodium ethylenediaminetetraacetate and disodium ethylenediaminetetraacetate group consisting of potassium. Since this aqueous solution can also be used as a lens rinsing liquid after disinfecting and cleaning the soft contact lens, it is desirable that the aqueous solution is isotonic with human tears and has the same pH.

The disinfecting, neutralizing and cleaning methods of the present invention can be applied to all known hydrous soft contact lenses. Specifically, the lens is fixed in a vial with a cap, and after filling the aqueous solution into the vial, the granule or powder disinfecting / cleaning agent and the neutralizing / cleaning agent, which is a tablet or capsule, are prepared.
Add the detergent at the same time, close the cap and shake it several times. First, the first disinfecting / cleaning agent is dissolved, and sterilization of microorganisms adhering to the lens and cleaning of proteins are started. Next, after 1 to 10 minutes, the foaming of the second neutralizing agent starts, and the solution and the soft contact lens colored yellow or tan gradually fade and can be visually observed. During that time, the cleaning is continued, and the cleaning time is completed in 10 to 240 minutes from the start of the cleaning. The lens which has been disinfected, neutralized and washed is rinsed with the above-mentioned rinsing solution, and then worn on the eye.

[0019]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 First formulation (powder) component mg / formulation Povidone-iodine (iodine fungicide) 3 Subtilisin A (protease) 6 Lactose (excipient) 91 Second formulation (tablet) Component mg / formulations sodium bisulfite (reducing agent) 3 poloxamer (nonionic surfactant) 5 sodium carbonate (foaming agent, pH adjusting agents) 30 citric acid (pH adjusting agent) 10 lactose (excipient) 12 HEC (coating 5) After tablet molding, it was coated with HEC. Dissolved aqueous solution (liquid) Ingredient mg / ml Sodium chloride (isotonizing agent) 8 EDTA · 2Na (chelating agent) 1 Boric acid (buffering agent) 5 Borax (buffering agent) 1 Purified water (dissolving agent) Appropriate amount 1st above (Powder) and the second preparation (tablet) were packaged in an aluminum three-side sealed package to obtain a one-pack combination preparation. The aqueous solution (liquid) is dissolved in polyethylene (P
E) Filled bottles.

Example 2 First preparation (granule) Ingredient mg / preparation povidone-iodine (iodine fungicide) 3 trypsin (protease) 3 polyoxyl stearate 40 (nonionic surfactant) 5 lactose (excipient) ) 87 Second formulation (tablet) Ingredient mg / formulation Sodium sulfite (reducing agent) 3 Sodium carbonate (foaming agent, pH adjuster) 30 Citric acid (pH adjuster) 10 Lactose (excipient) 12 HPMC (coating agent) 5) After tablet molding, it was coated with HPMC. Dissolved aqueous solution (liquid) Ingredient mg / ml Sodium chloride (isotonizing agent) 7 EDTA · 2Na (chelating agent) 1 Potassium phosphate (buffer) 1 Disodium phosphate (buffer) 1.5 Purified water (dissolved ) Agent) Appropriate amount The first preparation (granules) and the second preparation (tablets) were packaged in an aluminum three-side sealed package to obtain a one-pack combination preparation. In addition, the dissolved aqueous solution (liquid) was filled in a PE bottle.

[0022] Example 3 the first formulation (powder) Component mg / formulation Povidone iodine (iodine-based disinfectant) 3 Trypsin (proteolytic enzyme) 1 chymotrypsin (protease) 1 poloxamer (nonionic surfactant) 5 Lactose (excipient) 90 Second formulation (capsule) Ingredient mg / formulation Sodium thiosulfate (reducing agent) 2 Sodium bicarbonate (foaming agent, pH adjuster) 30 Citric acid (pH adjuster) 5 Lactose (additive) Excipient) 13 Gelatin (encapsulating agent) 5 After granulation, it was filled in a gelatin capsule. Dissolution aqueous solution (liquid) Ingredient mg / ml Sodium chloride (isotonizing agent) 6 EDTA · 2Na (chelating agent) 1 Boric acid (buffering agent) 6 Borax (buffering agent) 1.5 Purified water (dissolving agent) The first preparation (powder) and the second preparation (capsule) were packaged in an aluminum three-side sealed package to obtain a one-pack combination preparation. In addition, the dissolved aqueous solution (liquid) was filled in a PE bottle.

Comparative Example 1 First Preparation (Powder) Component mg / Formulation Povidone Iodine (Iodine Fungicide) 3 Papain (Proteolytic Enzyme) 7 Lactose (Excipient) 90 Second Preparation (Tablet) Component mg / Formulation sodium sulfite (reducing agent) 3 poloxamer (nonionic surfactant) 5 sodium carbonate (foaming agent, pH adjusting agents) 30 citric acid (pH adjusting agent) 10 lactose (excipient) 12 dissolved solution (liquid) Ingredient mg / ml Sodium chloride (isotonizing agent) 8 EDTA · 2Na (chelating agent) 1 Boric acid (buffering agent) 5 Borax (buffering agent) 1 Purified water (dissolving agent) Appropriate amount First formulation (powder) And the second preparation (tablet) were packaged in an aluminum three-side sealed package to obtain a one-pack combination preparation. In addition, the dissolved aqueous solution (liquid) was filled in a PE bottle.

Example 4 The disinfecting effects of the preparations described in Examples 1 to 3 and Comparative Example 1 were examined. Number of bacteria 10 ⁶ cfu / ml in aqueous solution
The first preparation and the second preparation of Examples 1 to 3 and Comparative Example 1 were individually added simultaneously to each 10 ml of the prepared solution, and these solutions were added after the dissolution of the second preparation was completed. Each 1 ml was collected in a petri dish and the viable cell count was confirmed. Table 1 shows the results.

[0025]

[Table 1]

As is apparent from Table 1, the disinfecting effects of the preparations of Examples 1 to 3 were completely recognized. In Comparative Example 1, since the second preparation did not have the delayed release coating, the disinfectant was neutralized immediately, and no disinfecting effect was obtained.

Example 5 The cleaning effects of the preparations described in Examples 1 to 3 were examined. Put the HEMA lens in a 0.1% lysozyme solution,
Heating to 80 ° C. for 30 minutes allowed heat-denatured lysozyme to adhere to the lens. This lens was rubbed and washed with a physiological saline solution to obtain an artificially soiled lens. Put artificial dirt lens into individual vials, in the 500nm exemplary formulations described in Examples 1-3 were placed in individual vials, the lens is removed after 4 hours, fouling after your <br/> preliminary treatment after the lens The transmittance was measured, and the lysozyme removal rate was calculated by the following equation to confirm the cleaning effect.

[0028] Lysozyme removal ratio _{(%) = (T 2 -T} 1 / T 0 -T 1) × 100 T 0: stain was with wearing the lenses before the transmittance T _1: lens transmittance after with dirty wearing T ₂ : Lens transmittance after treatment The results are shown in Table 2.

[0029]

[Table 2]

As is apparent from Table 2, the cleaning effects of the preparations of Examples 1 to 3 were recognized. In Comparative Example 1, the protease was inactivated, and the cleaning effect was hardly observed.

The preferred embodiments of the present invention are described as follows. 1. a combination of (A) a first formulation containing an iodine fungicide and a proteolytic enzyme and (B) a second formulation containing a sulfur-containing reducing agent and a blowing agent and having a delayed release coating, and A one-part combination preparation for disinfecting, neutralizing and cleaning contact lenses, wherein at least one of the first preparation and the second preparation contains a nonionic surfactant. 2. The one-part combination preparation according to the above item 1, wherein the iodine-based fungicide of the first preparation is povidone iodine or polyvinyl alcohol iodine. 3. The one-pack combination preparation according to the above item 1, wherein the protease of the first preparation comprises an enzyme derived from a Bacillus microorganism or an enzyme derived from an animal pancreas. 4. The one-component combination preparation according to the above item 1, wherein the nonionic surfactant of the second preparation is selected from poloxamer, poloxamine, polysorbate 80, polyoxyl stearate 40 and polyoxyethylene hydrogenated castor oil 60. 5. The iodine-based fungicide of the first preparation is povidone iodine or polyvinyl alcohol iodine, and the protease is an enzyme derived from a microorganism of the genus Bacillus or an enzyme derived from animal pancreas. 2. The one-component combination preparation according to the above item 1, wherein the nonionic surfactant is selected from poloxamer, poloxamine, polysorbate 80, polyoxyl stearate 40 and polyoxyethylene hydrogenated castor oil 60. 6. The one-component combination preparation according to the above item 1, wherein the sulfur-containing reducing agent of the second preparation is selected from sodium bisulfite, sodium sulfite and sodium thiosulfate. 7. The one-component combination preparation according to the above item 1, wherein the foaming agent of the second preparation is selected from the group consisting of sodium bicarbonate and sodium carbonate. 8. The one-part combination preparation according to the above item 1, wherein the delayed-release coating of the second preparation is selected from hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and gelatin. 9. The sulfur-containing reducing agent of the second formulation is sodium bisulfite, sodium sulfite or sodium thiosulfate, and the blowing agent is sodium hydrogen carbonate or sodium carbonate, and the delayed release coating is hydroxyethyl cellulose, hydroxy Propylcellulose,
2. The one-component combination preparation according to the above item 1, which is selected from hydroxypropylmethylcellulose and gelatin. 10. The one-pack combination formulation according to claim 1, wherein the first formulation is a powder or granules and the second formulation is a capsule. 11. Keeping the soiled contact lens in a yellow or brown aqueous solution containing the one-part combination preparation described above and in which the first preparation is dissolved, and contacting the aqueous solution after the aqueous solution becomes almost colorless. A method for disinfecting, neutralizing and cleaning a contact lens, comprising separating the lens. 12. The above one-part combination preparation contains the first preparation, and the first preparation contains at least one tonicity agent, phosphate and borate selected from the group consisting of sodium chloride and potassium chloride. A yellow or brown aqueous solution obtained by dissolving at least one buffer selected from the group and a chelating agent selected from the group consisting of disodium ethylenediaminetetraacetic acid and dipotassium ethylenediaminetetraacetic acid in an aqueous solution in purified water. 12. The washing method according to the above item 11, wherein 13. The second formulation, which contains the one-part combination formulation as described above, and holds the soiled contact lens in a yellow or brown aqueous solution in which the first formulation, which is a powder or granules, is dissolved, is a capsule. 12. The method according to the above item 11, wherein the contact lens is separated from the aqueous solution after the solution becomes almost colorless by dissolution and neutralization.

[0032]

According to the present invention, a preparation containing an iodine-based bactericide and a protease is combined with a preparation containing a neutralizing agent and a surfactant provided with a delayed-release coating. by simultaneously charged into a vial, after can be reliably performed in a short time sterilization of attached bacteria to the lens, iodine coloration of the aqueous solution and the lens is neutralized completed by a colorless with a neutralizing agent to the naked eye Since the confirmation can be performed and the cleaning of the protein and lipid stains on the lens can be automatically performed, a series of lens cares of disinfection, neutralization and cleaning can be performed easily, efficiently and safely.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI C11D 3:48) C11D 3:48) (72) Inventor Hiroshi Tauchi 3-219-16 Nishi, Suwanomorimachi, Hamadera, Sakai-shi, Osaka ( 56) References JP-A-4-229822 (JP, A) JP-A-3-284604 (JP, A) JP-A-2-289255 (JP, A) JP-A-59-206816 (JP, A) (58) ) Surveyed field (Int.Cl. ⁷ , DB name) C11D 10/02 C11D 3/34 C11D 3/386 C11D 3/48 G02C 13/00

Claims (6)

(57) [Claims] 1. A combination of (A) a first formulation containing an iodine fungicide and a protease, and (B) a second formulation containing a sulfur-containing reducing agent and a foaming agent and having a delayed release coating. One-part combination for disinfecting, neutralizing and cleaning contact lenses, characterized in that at least one of the first preparation and the second preparation contains a nonionic surfactant. Formulation. 2. The method according to claim 1, wherein the first preparation is a powder or granules.
And wherein the second formulation is a tablet or a capsule.
The one-part combination preparation according to the above. (3) These are added to the first preparation and the second preparation.
3. The method according to claim 1, further comprising an aqueous solution for dissolution.
One-pack type combination preparation described above. 4. The method of claim 1, wherein the aqueous solution comprises a tonicity agent, a buffer,
4. The one-part combination according to claim 3, comprising a chelating agent.
Formulation. 5. The one-pack type according to claim 1,
Using the combination preparation, the first preparation is dissolved yellow or
Keep dirty contact lenses in a brown aqueous solution
After the second formulation is dissolved and the aqueous solution becomes almost colorless
In particular, the method includes separating a contact lens from the aqueous solution.
How to disinfect, neutralize and clean contact lenses
Law. 6. The first preparation and the second preparation are dissolved and dissolved in water.
When they are added at the same time as dissolving in the liquid,
The first formulation dissolves, thereby causing contact lens
After washing and disinfection, the reducing agent and the second formulation
And the dissolution of the blowing agent substantially begins, thereby causing iodine
The method according to claim 5, wherein neutralization of the system bactericide is performed.