JP5194218B2 - Preservation method of hydrous contact lens and hydrous contact lens preserved by the preservation method - Google Patents

Description

  The present invention relates to a method for preserving a hydrous contact lens and a hydrous contact lens preserved by the preserving method, and in particular, forming a pseudorotaxane structure composed of polyethylene glycol and cyclodextrin on the surface of the hydrous contact lens. Thus, the present invention relates to a storage method that improves the water retention of the lens, reduces the dryness and discomfort of the lens wearer, and maintains a good moist feeling.

  Contact lens material and surface structure have a special impact on contact lens wearers. Needless to say, the difference in wear feeling received by the patient is large due to the difference between soft and hard, and although there are individual differences, there are fewer patients who feel a foreign body feeling from the beginning of wearing the soft lens. This is because the hard lens is hard and easily recognized as an object, and also moves better than the soft lens after being placed on the corneal surface, so that it can be regarded as a foreign object sensation. Of course, hard lenses have superior characteristics compared to soft lenses in terms of vision correction and ease of detection of the onset of eye diseases. Which one to choose depends on the patient's eye condition, tear volume, tears It is determined based on various factors such as the quality and use of the liquid. In addition, the lens surface structure is important in relation to water wettability, friction with the cornea, adsorption of tear fluid components, etc., not only the material itself but also the contact area with the cornea or the three-layer structure of tear fluid. Consideration should be taken into account when considering the effects of

  By the way, as a trend in recent years, disposable type hydrous contact lenses have become mainstream in the field of soft lenses since the emergence of them, but the number of patients who complain of dryness and discomfort during wearing has increased among lens wearers. Seems to be. This is not only due to lens wear, but also due to the rapid development of the environment in which lenses are used, especially IT (information technology), VDT (Visual Display Terminals) work such as personal computers has been widely introduced in the workplace. Along with this, it is thought that there are also causes such as a decrease in the number of blinks due to gaze during work and a decrease in humidity in an air-conditioned room. As a means to eliminate the feeling of dryness while wearing the lens as a separate measure other than the effect of wearing the lens (for example, see “Guidelines for Occupational Health Management in VDT Work” published by the Ministry of Health, Labor and Welfare for VDT). In connection with the above-mentioned materials and surface structures, various improvement methods have been proposed.

  Specifically, the water retention of the lens is improved by introducing an ionic carboxyl group and a salt thereof into the copolymerized molecule of the polyvinyl alcohol lens (Japanese Patent Laid-Open No. 2004-70066), which can be polymerized. A method for modifying a surface by immersing a lens in an aqueous dispersion of a surfactant, a crosslinking agent and a radical polymerization initiator and irradiating with ultraviolet rays to form a durable surface coating (Japanese Patent Publication No. 6-503118) ), A polymerization initiator group is covalently bonded to the lens surface, a primary polymer coating is formed thereon by graft polymerization, and a hydrophilic telomer having a functional group that is co-reactive with the reactive group of the primary polymer coating. A method of modifying the surface by reacting (Japanese Patent Laid-Open No. 2001-163932), adsorbing polyvinylpyrrolidone on an ionic contact lens, A system for stabilizing the tear film existing around the lens (Japanese Patent Laid-Open No. 2001-247466), a contact lens mounting liquid containing a polymer compound and cyclodextrins (Japanese Patent Laid-Open No. 2001-125052) And a composition for preventing a decrease in the water content of a hydrous soft contact lens containing acidic mucopolysaccharide and glycerin (Japanese Patent Application Laid-Open No. 2004-77953).

  Even if an improvement effect is expected according to these proposals, each method also has its own problems. For example, can the method of introducing the ionic carboxyl group be universally applied to lenses other than polyvinyl alcohol lenses? For surface coating with a polymerizable surfactant and surface modification by reaction of the primary polymer coating with a hydrophilic telomer, these operations are required as post-treatment in addition to forming a lens, leading to increased costs. Isn't it? Also, the method for adsorbing polyvinylpyrrolidone is limited in the types of lenses as disclosed, what are the measures against other non-ionic contact lenses, and how is the effect sustained? In addition, contact lens mounting fluids that contain polymer compounds and cyclodextrins are less sticky than conventional viscous mounting fluids and have improved lens surface wettability. However, there are problems such as not considering the improvement of dryness. Furthermore, as a more essential problem, tear components and tear volume are all different for each patient, and it is difficult to seek an improvement method that can be applied to all patients. I must say it.

  Although the approach has been proposed, there is still a need for a safe, economical, and effective method that does not depend on existing methods.

JP 2004-70066 A JP-T 6-503118 JP 2001-163932 A JP 2001-247466 A JP 2001-125052 JP 2004-77953 A

  An object of the present invention is to provide a preservation method that gives water retention to a water-containing contact lens so as to give a moist feeling when worn, and the method has a simple process, excellent water retention effect and its sustainability, and is safe. Another object of the present invention is to provide a method for storing a highly water-containing contact lens and a water-containing contact lens using the method.

The results In the present invention was investigated in order to solve the above problems, a water-absorptive contact lenses containing Po triethylene glycol, by immersing stored in liquid containing cyclodextrin, moisture from the lens It has been found that evaporation is suppressed. As is well known, polyethylene glycol and cyclodextrin form a pseudorotaxane structure penetrating a cyclic molecule of cyclodextrin with a polyethylene glycol chain as an axis. It is considered that the effect of the present invention is that the cyclodextrin coats the lens surface by the structure, so that water evaporation from the lens is suppressed.

Polyethylene glycol is macrogol 4
It is listed in the Japanese Pharmacopoeia with names such as 0 0, macro goal 1 5 0 0, macro goal 4 0 0 0, etc. It is a highly safe polymer that is frequently used as a base for pharmaceuticals and cosmetics, and is used as an isotonic agent, a solubilizing agent and the like for eye drops. To affix the structure of interpenetrating intact Filling the lens the polymeric object.

  On the other hand, cyclodextrin is a compound in which D-glucose is linked cyclically with α-1,4 bonds, and those composed of 6, 7, and 8 are respectively α-cyclodextrin, β-cyclodextrin, γ- It is called cyclodextrin. Cyclodextrins are listed in the Pharmaceutical Additives Standard, and pharmaceutical application research has been used in various attempts including the use of the so-called host-guest relationship between cyclodextrins and drugs. This is also a highly safe compound like the polyethylene glycol.

  The pseudorotaxane structure formed by polyethylene glycol and cyclodextrin does not require any special operation or chemical reaction, and is produced by simple mixing. Therefore, it is not necessary to introduce new equipment when manufacturing the contact lens, and a new water retention effect can be imparted while maintaining the manufacturing cost as in the conventional case.

  The method for preserving a water-containing contact lens according to the present invention is such that by introducing a polyethylene glycol chain into a lens material, the lens surface is covered with a pseudorotaxane structure simply by immersing in a preservative solution containing cyclodextrin. It is possible to suppress moisture evaporation from the water. In addition, since both polyethylene glycol and cyclodextrin are highly safe compounds, there is no concern that the resulting lens may have a problem with safety. Furthermore, since the operation is simple, it is possible to maintain the same manufacturing cost as the conventional method, which is an economical method.

Hereinafter, the present invention will be described in more detail.
Polymer chain of polyethylene glycol (hereinafter referred to as P E G) is not good by fixing in the lens material by polymer blends in a single. P like this
Examples of E G include macro goal series such as Macro Goal 1 0 0 0, Macro Goal 4 0 0 0, Macro Goal 6 0 0 0, etc. of Sanyo Chemical Industries, Ltd. These preferable addition amounts are the above-mentioned P.
It is the same as E G monomer, but P E G with a low molecular weight is difficult to form an interpenetrating structure of molecular chains, and it is eluted in the preservation solution without remaining in the lens material. It cannot be maintained. Accordingly, those having a high molecular weight that can be fixed in the lens material by entanglement of molecular chains are preferable. Specifically, the molecular weight is 1.
Although it is 0 0 0 or more, preferably 4 0 0 0 or more, the upper limit of the molecular weight is determined from the problem of compatibility with the lens-forming monomer. N commonly used for hydrous contact lenses
-Hydrophilic monomers such as vinylpyrrolidone and N, N-dimethylacrylamide are compatible with PEG, but are not compatible with hydrophobic monomers such as methylmethacrylate to give the lens strength. . Therefore, depending on the existing lens-forming monomer to be combined, 2
In some cases, a polymer P E G of 0 0 0 0 or more cannot be used. However, if a block copolymer with polyoxypropylene or the like is used instead of a homopolymer of P E G, compatibility with the hydrophobic monomer is also improved.
It is also possible to use a polymer having 0 00 0 or more. In short, the molecular weight although larger is easily fixed into the lens material, Ru Nodea that need to be adjusted to the extent that compatibility with the lens-forming monomer solution is not impaired.

On the other hand, in addition to the above methods for introducing Ri P E G I lens polymerization step, after the lens forming, it is also possible to employ a method of securing a P E G lens material surface. And an example, surfactants having a polyoxyethylene chain (
For example, a method of adsorbing polyoxyethylene nonylphenyl ether or the like on the lens surface is also conceivable. According to these methods, the P E G chain is fixed only to the lens surface portion.
The E G content is set lower than the above range. This method tends to increase the manufacturing cost because a post-processing step is provided, but since there is no change in the material of the existing lens, a lens having the same physical properties can be obtained, and the added value of improving the water retention is provided. be able to.

Select or any one of the above means, or is a P E G that is used in the present invention can be prepared lenses "fixed", selects the Izure of each unit is obtained lens material It is appropriately selected on the basis of having no adverse effects such as white turbidity and deformation, and suppressing the manufacturing cost. In the present invention, P
The "fixed" in E G, as is clear from the foregoing description refers to a state of being held by the lens by entanglement and the lenses constituting molecule and P E G molecules.

  In the storage method according to the present invention, the lens storage solution contains CD. As described above, CD is a compound in which glucose is linked in a cyclic manner with α-1,4 bonds, and a compound in which five or more glucoses are bonded is known. The general ones are α, β, and γ shown above, and the solubility in water is 14.5 g / 100 mL for α form, 1.8 g / mL for β form, and 23.2 g for γ form at 25 ° C. / 100 mL, β-form is the lowest. The inside of the cyclic structure of CD is a pore that is large enough to include other relatively small molecules, and a pseudorotaxane structure is formed by PEG penetrating through this pore. In the present invention, PEG is fixed to the lens, but since at least one end is in a free state, the CD is covered on the lens through this free end. CD and PEG form a supramolecular structure by weak intermolecular interaction and cannot be easily removed, but it is also possible to provide a rotaxane structure by providing a stopper at the PEG end. However, further processing steps are required for this purpose, and the manufacturing cost is increased accordingly. Therefore, it can be performed as required, and is not necessarily required in the present invention.

  For the CD of the present invention, a CD derivative having a saccharide cyclic structure of CD can be used in addition to the general α-form. Examples of such CD derivatives include alkyl CD, hydroxyalkyl CD, sulfoalkyl CD, sulfobutyl CD, and sulfated CD. One or more of these can be used in appropriate combination, and the concentration thereof is 0.05 to 5%, more preferably 0.5 to 2%. When β-CD is used, it is basically difficult to achieve a concentration of 1.8% or more in relation to solubility, but by using α-CD or γ-CD, a storage solution having the above concentration range is used. Can be prepared. When the CD concentration is lower than 0.05%, it becomes difficult to form PEG and pseudorotaxane on the lens surface, and the surface covering effect by PEG, that is, the moisture evaporation suppressing effect cannot be expected. On the other hand, even if a larger amount of CD is contained than 5%, the CD that does not contribute to the formation of pseudorotaxane is only dissolved in the solution and contains unnecessary CD. May lead to

  Various additive components commonly used in lens solutions can be added to the CD-containing preservation solution of the present invention as necessary. These components include isotonic agents, buffering agents, chelating agents, preservatives, thickeners, surfactants, and the like, and these can be used in appropriate combination of one or more.

  More specifically, examples of the isotonic agent include sodium chloride, potassium chloride, propylene glycol, and glycerin. Examples of the buffer include citrate buffer, borate buffer, and phosphate buffer. Succinate buffer, oxalate buffer, tris-citrate buffer, tris-glycine buffer, tris-EDTA buffer, tris-hydrochloric acid buffer and the like. Further, EDTA and salts thereof, citric acid, polyphosphoric acid and the like as chelating agents, chlorohexidine, benzalkonium chloride, polyhexamethylene biguanide, polyquaterium-1 and the like as preservatives, polyvinylpyrrolidone, polyvinyl alcohol, Examples thereof include hydroxymethylcellulose, hydroxypropylmethylcellulose, sodium chondroitin sulfate, and hyaluronate. Furthermore, examples of the surfactant include polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene sorbitan alkyl ester and the like.

  In addition, as other additive ingredients, various medicinal ingredients such as chlorpheniramine maleate, aminoethylsulfonic acid, neostigmine methylsulfate, refreshing agents such as menthol, camphor and borneol, vitamins such as vitamin A and vitamin B, etc. As long as they are safe for the living body and do not adversely affect the material of the lens to be handled, any conventionally known materials can be used, and they can be used as necessary. , And can be used in combination within a quantitative range that does not inhibit the action and effect of the present invention.

  According to the method of the present invention, by immersing the lens with PEG immobilized in the CD-containing storage solution, a CD coating based on the pseudorotaxane structure is formed on the lens surface. For example, it may be stored overnight at room temperature. The CD coating formed by the storage has an effect of suppressing moisture evaporation from the lens surface, softens the feeling of dryness and foreign matter caused by wearing the lens, and gives a moist feeling to the patient's eyes, and the effect continues.

  In order to clarify the present invention more specifically, several examples of the lens storage method according to the present invention are illustrated below.

-Creation of PEG fixed lens material-
For each composition shown in Table 1, a rod of a lens material on which PEG was fixed was polymerized under the following conditions. As the polymerization conditions, the temperature was gradually increased from 30 ° C. for 16 hours, 40 ° C., 50 ° C., 60 ° C. for 3 hours, and 70 to 120 ° C. over 18 hours. Each of the rods obtained in this manner was cut to prepare 10 disc-shaped plates each having a thickness of 1 mm and a diameter of 11 mm when dried. By boiling this plate in physiological saline, unreacted monomers in the material were eluted and used for the following tests. All of these plates were sufficiently transparent as lenses in a water-containing state. In addition, test example No. of Table 1 is shown. No. 5 was not a PEG chain fixed to the lens material, but was used as a comparative example in this example.

-Moisture evaporation suppression effect test-
Using the water-containing plate prepared as described above, it is immersed and stored overnight in various storage solutions shown in Table 2 (5 plates / 50 ml). Remove the plate after storage, wipe the surface moisture with a Kimwipe, place it gently on a precision balance with the side of the plate facing down, and gradually evaporate the moisture from the plate one by one (every minute). Measured and compared the rate of weight loss. Preservative solution No. in Table 2 No. 5 is a preservation solution containing no cyclodextrin, and was used as a control when showing the effect of the present invention. And control was always measured as a comparison when examining the effect of each preservation solution. This is because the moisture evaporation rate is naturally greatly influenced by the surrounding environment, so that even the same sample has a large difference in evaporation amount depending on the temperature, humidity, etc. on the measurement day. If the environment around the balance can be maintained at a constant temperature and humidity, there will be little difference in the test date, that is, the measurement environment will be a problem, but even if the test cannot be performed in such an environment, always keep control. This makes it possible to make a relative evaluation under the same environment in comparison with it. In this test example, control and sample measurement (measurement of aging for 10 minutes per minute per plate) were performed alternately for 5 cycles (measurement for 5 plates per cycle per plate). The change in water evaporation (mg) was shown as an average value at the time of measurement for 5 cycles, compared with that of the control.

  Originally, it is desirable to measure the water evaporation rate in the shape of a lens. However, since the weight per lens is extremely light (about 30 mg), the amount of water evaporated from the lens is reduced, resulting in a measured value. Error is likely to occur. Therefore, in this example, the change in water evaporation was measured by increasing the overall weight (around 330 mg per wet plate) and increasing the scale. From each figure, according to the storage method of the present invention, an effective water evaporation suppression effect is recognized. For example, Fig. 1 shows the case where PEG is fixed to the lens by mutual intrusion and the case where it is stored in a liquid containing CD, but the water evaporation is more effectively suppressed than when the storage liquid does not contain CD (control). Is recognized. For example, FIG. 4 shows that when a PEG side chain is used as a lens constituent molecule and the preservation solution contains CD, an effect of suppressing moisture evaporation is recognized.

  Next, as Comparative Example 1, when a lens material not fixed with PEG (the plate of Test Example No. 5) was immersed in a storage solution (No. 6) containing CD and PEG, it was compared with the control. Changes in water evaporation were measured and the results are shown in FIG. In this test, when PEG is not fixed to the lens, it is shown that the effect of suppressing the evaporation of moisture is not observed only when CD and PEG are present in the storage solution.

FIG. 1 is a diagram showing water evaporation of the plate taken out after the plate of Test Example No. 2 was stored in the storage solution No. 1 (Example 1) and the storage solution No. 5 (control). FIG. 2 is a diagram showing moisture evaporation of the plate taken out after the plate of Test Example No. 1 was stored in the storage solution No. 2 (Example 2) and the storage solution No. 5 (control). FIG. 3 is a view showing water evaporation of the plate taken out after the plate of Test Example No. 3 was stored in the preservation solution No. 1 (Example 3) and the preservation solution No. 5 (control). FIG. 4 is a diagram showing water evaporation of the plate taken out after storing the plate of Test Example No. 4 in the preservation solution No. 3 (Example 4) and the preservation solution No. 5 (control). FIG. 5 is a diagram showing water evaporation of the plate taken out after the plate of Test Example No. 4 was stored in the preservation solution No. 4 (Example 5) and the preservation solution No. 5 (control). FIG. 6 is a diagram showing moisture evaporation of the plate taken out after the plate of Test Example No. 5 was stored in the preservation solution No. 6 (Comparative Example 1) and the preservation solution No. 5 (control).

Claims (2)

Polyethylene glycol with a molecular weight of 4000 or more in hydrous contact lens material 0
. The water-containing contact lens containing 0.5% to 10% is treated with cyclodextrin 0. A method for preserving a hydrous contact lens, wherein the preservative is preserved in a liquid containing 5 to 5% . The water evaporation amount is suppressed as compared with the water-containing contact lens when the water evaporation amount of the water-containing contact lens stored by the method is stored in physiological saline. the method of.

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