JP5041660B2 - Eye drops for contact lenses containing a cooling agent - Google Patents

Description

  The present invention relates to eye drops for contact lenses containing a refreshing agent, and more particularly to eye drops that can be instilled when wearing contact lenses.

  Various artificial tear drops are commercially available to relieve discomfort when wearing contact lenses, but many of these contain inorganic salts and metal chelating agents, reducing tears. Even if it is useful for relieving the dryness of the eyes, there is no effect of relieving discomfort such as foreign body sensation and itchiness that are often appealed by contact lens wearers.

  Contact lenses are very easy to adsorb drugs, especially organic compounds, and easily accumulate in the lenses, and the physical parameters of the lens are significantly affected by the pH and osmotic pressure of the drug applied to the contact lenses. It is known to receive. Because of such special characteristics, the eye drops that can be applied when wearing contact lenses usually contain only inorganic salts. However, as described above, such eye drops do not eliminate any discomfort such as foreign body feeling or itchiness during wearing even if the dryness of the eyes due to supplementation of tears is eliminated or alleviated. Therefore, there has been a need for eye drops for contact lenses that are useful for comfortable wearing of contact lenses, eliminating the discomfort such as foreign body feeling and itchiness that are often appealed by contact lens wearers.

  Usually, it is known to add menthol or the like to eye drops as a cooling agent or a fragrance, and it is also disclosed in JP-A-7-118147 and JP-A-9-132526. However, since these eye drops are not premised on the use at the time of wearing a contact lens, the above problems cannot be solved. That is, since the refreshing agent is easily adsorbed on the contact lens and has a great influence such as changing the physicochemical parameters of the lens or lowering the wettability, the eye drop containing the refreshing agent is usually a contact lens. It is considered inappropriate for wearing. On the other hand, as a method for preventing the adsorption of components to the soft contact lens, Japanese Patent Publication No. 55-15008 discloses a bactericide composition capable of preventing the bactericide from adsorbing to the soft contact lens. The publication shows that nonionic surfactants prevent adsorption of chlorohexidine, paraoxybenzoates and quaternary ammonium salts to contact lenses. There is no suggestion of a method for preventing a change in the physicochemical parameters of the lens and / or a decrease in wettability.

  The contact lens wearer complains not only of dryness but also of foreign body sensation and itchiness at the time of wearing, but it has been difficult to eliminate the foreign body sensation and itchiness with conventional tear drops. As a means for resolving such discomfort, it is conceivable to develop eye drops containing a refreshing agent. Such a refreshing agent changes physical parameters of contact lenses or reduces wettability. Since it adversely affects the performance of contact lenses, it has been difficult to put eye drops for contact lenses containing a cooling agent into practical use.

  As a result of intensive studies to solve the above problems, the present inventors have mixed adverse effects such as changes in physicochemical parameters of contact lenses by adding a cooling agent to eye drops under certain conditions. However, the present inventors have succeeded in obtaining eye drops for contact lenses that have good lens wettability and have completed the present invention.

  That is, this invention provides the eye drop for contact lenses characterized by containing a refreshing agent.

  The eye drop of the present invention contains one or more surfactants, preferably contains a nonionic surfactant and / or an amphoteric surfactant, and particularly preferably contains them simultaneously. .

  In the present invention, when a specific surfactant is added to an eye drop containing a cooling agent such as menthol, the physicochemical parameters of the contact lens are not changed when the eye drop is used, and the wettability of the lens is reduced. It is based on the knowledge that it can prevent and rather improve the decline.

  As a refreshing agent contained in the eye drop of the present invention, 1-menthol, d-menthol, dl-menthol, d-camphor, dl-camphor, d-borneol, dl-borneol, geraniol, eucalyptus oil, bergamot oil, Examples include fennel oil, peppermint oil, rose oil, and cool mint, and the eye drop of the present invention may contain one or more of these.

  These compounds are preferably blended at concentrations that do not change the physicochemical parameters of the lens and do not cause eye irritation when instilled, and such concentrations vary depending on the material of the contact lens, Usually, it is used in the range of 0.0001 to 0.05%, and preferably in the range of 0.001 to 0.01%. If the concentration is less than 0.0001%, a refreshing effect cannot be expected, and discomfort when wearing contact lenses cannot be eliminated.

  Examples of the surfactant that can be used in the eye drop of the present invention include ophthalmically acceptable nonionic surfactants, amphoteric surfactants, anionic surfactants, and the like known in the art. It can be arbitrarily selected on the condition that the lens is not adversely affected.

  Nonionic surfactants include polyoxyethylene (POE) and polyoxypropylene (POP) block copolymers, POE sorbitan fatty acid esters such as monooleic acid POE (20) sorbitan, and POE curing such as POE (60) hydrogenated castor oil. Castor oil, POE alkyl ethers such as POE (9) lauryl ether, POE / POP alkyl ethers such as POE (20) POP (4) cetyl ether, POE alkyl phenyl ethers such as POE (10) nonylphenyl ether, etc. Is mentioned.

  Examples of the amphoteric surfactant include amphoteric surfactants such as a glycine type such as alkylpolyaminoethylglycine, a betaine acetate type such as lauryldimethylaminoacetic acid betaine, and an imidazoline type.

  Anionic surfactants include POE alkyl ether phosphates such as POE (10) sodium lauryl ether phosphate and salts thereof, N-acyl amino acid salts such as sodium lauroylmethylalanine, alkyl ether carboxylates, N-cocoyl. N-acyl taurine salts such as sodium methyltaurine, sulfonates such as sodium tetradecene sulfonate, alkyl sulfates such as sodium lauryl sulfate, POE alkyl ether sulfates such as POE (3) sodium lauryl ether sulfate, α-olefins Examples thereof include sulfonates.

  As the surfactant used in the present invention, a combination of a nonionic surfactant and an amphoteric surfactant is preferable. The amount to be blended is not particularly limited as long as it is an amount sufficient to prevent a change in physical parameters exerted by the cooling agent on the contact lens. Usually, it can mix | blend so that it may become 10 to 100 times with respect to a refreshing agent, It is preferable to mix | blend so that it may become 10 to 50 times. If the amount is less than 10 times, the physical parameters of the lens change, and if it exceeds 100 times, the surfactant itself may be adsorbed to the lens, which is not preferable.

  The eye drops of the present invention further include active ingredients such as inorganic salts, decongestants, anti-inflammatory agents, astringents, antihistamines, vitamins, amino acids, cell activators, antibacterial agents, buffers, isotonic agents, Add various additives such as thickeners, chelating agents, stabilizers, pH regulators, preservatives, etc., as long as they do not affect the physicochemical parameters of the contact lens and do not cause problems such as eye irritation. Can do.

  Buffers include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon aminocaproic acid, aspartate, and isotonic agents such as sodium chloride, potassium chloride, glycerin , Propylene glycol, glucose, mannitol, sorbitol and the like.

  Thickeners include gum arabic powder, sodium alginate, propylene glycol alginate, sodium chondroitin sulfate, sorbitol, dextran 70, tragacanth powder, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, polyvinyl alcohol, polyvinyl Examples include pyrrolidone and macrogol 4000. Among these, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, polyvinyl alcohol, and polyvinyl pyrrolidone are excellent in that a solution having an appropriate viscosity can be obtained even at a low concentration. Further, hydroxyethyl cellulose or polyvinyl pyrrolidone has an effect on contact lenses. There is no particular limitation, although it is preferable in terms of high safety. By blending these thickeners, the retention on the eye surface is increased, the moisturizing effect is enhanced, and the water wetting effect of the lens by the surfactant can be maintained.

  Chelating agents include edetic acid, edetate (disodium edetate, disodium calcium edetate, trisodium edetate, tetrasodium edetate), nitrilotriacetic acid and its salts, trihydroxymethylaminomethane, sodium hexametaphosphate Examples of stabilizers such as citric acid include edetates and sodium bisulfite.

  Examples of the pH adjuster include sodium hydroxide, potassium hydroxide, sodium carbonate, hydrochloric acid, citric acid, phosphoric acid, acetic acid and the like.

  Examples of preservatives or preservatives include sorbic acid, potassium sorbate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, chlorohexidine gluconate, benzalkonium chloride, benzethonium chloride, alkylpolyaminoethylglycine, chloro Examples include butanol.

  The eye drop for contact lenses of the present invention is adjusted to a pH of about 5.0 to 9.0, preferably 6.5 to 8.5, using the above pH adjuster or the like. When applied to soft contact lenses, it is adjusted in the range of 5.5 to 8.0. Further, the osmotic pressure ratio is adjusted to 0.5 to 2.0, more preferably around 1.0 using the above-mentioned tonicity agent and the like.

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

比較例１
１００ｍｌ中
塩化ナトリウム ０.４４ｇ
塩化カリウム ０.０８ｇ
ホウ酸 ０.３０ｇ
ホウ砂 ０.０３５ｇ
滅菌精製水 適量
全量 １００ｍｌ
以上を無菌的に調合充填し、人工涙液型点眼剤とする。 Examples 1-6
The eye drop for contact lenses of the present invention is prepared according to the formulation described in Table 1 below.

Comparative Example 1
In 100 ml
Sodium chloride 0.44g
Potassium chloride 0.08g
Boric acid 0.30g
0.035 g of borax
Sterilized purified water
100ml total volume
The above is prepared and filled aseptically to obtain an artificial tear solution type eye drop.

Test Example 1 Wetting effect (Measuring method of contact angle)
The water wetting effect on the contact lens surface of the eye drop of the present invention was evaluated using the following experimental system. That is, when a single droplet is placed on the solid plane, the droplet becomes hemispherical on the solid plane due to the combination of the solid material, the droplet, and the air layer. At that time, at the point where the surface of the liquid droplet intersects the solid surface, the angle (angle including the liquid droplet) formed by the cut line drawn on the water surface and the plane is measured. When the angle is expressed by theta (abbreviated as θ), the smaller θ is, the greater the affinity of the droplet to the solid surface, and the liquid (eg, eye drops) constituting the droplet is a so-called solid. It means that the solution is easily wetted, or the contact lens surface is easily wetted. In the following experimental examples, an experimental system in which this evaluation method is further developed in accordance with the object of the present invention is used. Specifically, the contact lens is placed horizontally and a drop of eye drop is placed on the front curve (the side not in contact with the cornea), and the water wetting effect is evaluated by measuring the θ. Since the contact lens itself is a part of a sphere having a certain curvature, the angle derived from the contact lens is measured in advance (referred to as θa), and the droplet angle (θb) measured later on the contact lens is measured. It is necessary to correct by subtracting. (Θ = θb−θa)

  The measurement of θ can be easily performed by a method of taking a photograph of a droplet placed on a contact lens from the side or a method using an image processing apparatus using a video camera.

(Test method)
The eye drops of Examples 7 to 9 and Comparative Example 2 were prepared according to the formulation described in Table 2, and used as test solutions. Moreover, seed A-1 (The seed company make, oxygen-permeable hard contact lens) was used for the test.

  Before starting the test, distilled water was placed on a one-drop lens, and θ was measured according to the above evaluation method. Thereafter, 5 ml of the test solution was placed in a glass bottle with a 15 ml stopper, the lens was immersed, and immersed in a water bath at 34 ° C. for 70 times / minute for 24 hours. After immersion, the lens was taken out, and distilled water was placed on the one-drop lens, and θ was measured again according to the above evaluation method. The measurement of θ was performed using an image processing apparatus, and the water wetting effect was evaluated by comparing θ before the start of the test (before immersion) and after the immersion.

試験例２ 官能試験
（試験方法）
実施例１のコンタクトレンズ用点眼剤及び比較例１の人工涙液型点眼剤を調製し、酸素透過性ハードコンタクトレンズ装用者２１名に対して、コンタクトレンズ装用時の乾燥感、痒み、異物感、疲れ目改善効果に関する官能試験を実施した。試験期間中に症状が現れた回答者数に対し、何らかの改善効果があったと評価した回答者数の割合で評価した。
（結果）
結果を表３に示す。その結果、実施例１の点眼剤が眼乾燥感以外の全ての項目において比較例１の点眼剤よりも高い改善率を示し、本発明の点眼剤はコンタクトレンズ装用中の痒み、異物感、疲れ目などに対して優れた改善効果を有することが明らかとなった。

試験例３
コンタクトレンズのサイズに及ぼす影響
（試験方法）
表４に記載の処方で、実施例１０、１１及び比較例３の１-メントールと界面活性剤とを含有する点眼剤を調製して試験液とした。 (result)
The results are shown in Table 2. In the eye drop of Example 7, it can be seen that θ after immersion is lower than that before immersion, and wettability is considerably improved. Moreover, there was almost no change in the eye drops of Examples 8 and 9. On the other hand, in the eye drop of Comparative Example 2, θ is considerably increased and the wettability is deteriorated.

Test example 2 sensory test
(Test method)
The eye drop for contact lens of Example 1 and the artificial tear liquid type eye drop of Comparative Example 1 were prepared, and the dry feeling, itchiness, and foreign body sensation at the time of wearing the contact lens were given to 21 oxygen permeable hard contact lens wearers. Then, a sensory test on the effect of improving fatigue eyes was performed. The number of respondents who evaluated that there was some improvement effect was evaluated against the number of respondents who developed symptoms during the study period.
(result)
The results are shown in Table 3. As a result, the eye drop of Example 1 showed a higher improvement rate than the eye drop of Comparative Example 1 in all items other than dry eye feeling, and the eye drop of the present invention was itchy while wearing contact lenses, feeling of foreign matter, and fatigue. It has been clarified that it has an excellent improvement effect on eyes and the like.

Test example 3
Influence on contact lens size
(Test method)
Eye drops containing 1-menthol and surfactants of Examples 10 and 11 and Comparative Example 3 according to the formulations shown in Table 4 were prepared as test solutions.

  For the test, Menicon EX (manufactured by Menicon Corporation), O2 Fresh (manufactured by Nichicon Corporation), Bossrom EX-02 (manufactured by Bossrom Corporation), Hoya Hard / 58 (manufactured by HOYA Corporation), and seed A1 (manufactured by Seed Corporation) were used.

  One lens was immersed in each eye drop and shaken at 34 ° C. for 1 month. The test solution was changed every week. After immersion, the lens was taken out, the lens size was measured with a universal projector (V-12A (manufactured by NIKON)), and the presence or absence of change was observed by comparing with the size at the start of the test. According to the vision correction contact lens standard, it was determined that there was a change when the change in the lens size at the start and end of the test was ± 0.05 mm or more.

(result)
The results are shown in Table 4. A change in size was observed in the eye drop of Comparative Example 3, but not in the eye drops of Examples 10 and 11.

Claims (4)

  A method for preventing menthol in an eye drop for wearing a soft contact lens from adsorbing to the soft contact lens, comprising blending polyoxyethylene (20) sorbitan monooleate with the eye drop.   The method according to claim 1, wherein polyoxyethylene (20) sorbitan monooleate is blended 10 to 50 times as much as menthol.   The method according to claim 1 or 2, further comprising a thickener.   The method according to any one of claims 1 to 3, wherein the pH is adjusted to 5.5 to 8.0.