JP2015078235A - Eye drop for silicone hydrogel contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an eye drop for silicone hydrogel contact lenses (SHCL) which, when applied to the eyes wearing SHCL, exhibits an increased amount of vitamin B's reaching the cornea, because of the improved permeability of vitamin B's into SHCL.SOLUTION: The eye drop for SHCL is prepared by using (A) vitamin B's, in combination with (B) a surfactant.

Description

The present invention relates to an eye drop for a silicone hydrogel contact lens, which can improve the permeability of vitamin B ₁₂ to a silicone hydrogel contact lens.
The present invention also relates to a method of improving the permeability of vitamin B ₁₂ compound to silicone hydrogel contact lenses, as well as vitamin B to the silicone hydrogel contact lens
_The present invention relates to a method for imparting an action of improving the permeability of Class ₁₂ to eye drops. The invention also relates to agents for improving the permeability of vitamin B ₁₂ compound to silicone hydrogel contact lenses. Furthermore, the present invention relates to a method for screening a permeability enhancing substance to improve the permeability of vitamin B ₁₂ compounds to silicone hydrogel contact lenses.
Furthermore, the present invention relates to a method for suppressing the accumulation of pollen protein in an ionic silicone hydrogel contact lens.

In recent years, the number of wearers of contact lenses (CL) has increased, and in particular, the number of wearers of soft contact lenses (SCL) has increased. In general, it has been pointed out that when SCL is worn, the amount of oxygen supplied from the atmosphere decreases, which may result in suppression of corneal epithelial cell division and corneal thickening. Therefore, development of SCL having higher oxygen permeability has been advanced.

Under such circumstances, silicone hydrogel contact lenses have been developed in recent years as SCL having high oxygen permeability. Silicone hydrogel contact lenses achieve oxygen permeability several times that of conventional hydrogel contact lenses by blending silicone with hydrogel. Therefore, it is highly expected that the oxygen supply deficiency, which is a weak point of SCL, can be improved and the adverse effects on the cornea due to the oxygen deficiency can be greatly suppressed.

In addition, SCL is generally larger than a hard contact lens, and the cornea surface is almost entirely covered during wearing. And during SCL wearing, there is almost no inflow and outflow of tears between the SCL and the corneal surface (that is, tear exchange by pump action), and tear exchange under SCL is the tear fluid via SCL. It is known that it depends on transmission (see Non-Patent Document 1-2). In this way, most of the tear fluid exchange under SCL is performed by permeation of tear fluid through SCL,
Eye drops applied to the eyes of SCL wearers are required to sufficiently enhance the permeability of the pharmacological components to be blended into SCL.

Therefore, for eye drops applied to the eyes of SCL wearers, depending on the type of SCL,
It is indispensable to design in consideration of not only safety and other effects but also the permeability of pharmacologically active ingredients to SCL. In particular, SCL has different ionicity and moisture content depending on the material, so it is important to design the eye drops applied to the eyes of SCL wearers according to the nature of the SCL applied. It is.

By the way, hay fever is an allergic symptom caused by pollen protein contained in pollen becoming an antigen and contacting mucous membranes and the like. In recent years, the number of hay fever patients has increased,
It is becoming a big social problem. In the field of ophthalmology, there is a strong demand for the development of eye drops useful for the prevention of hay fever and suppression of deterioration.

On the other hand, vitamin B ₁₂ is used in eye drops for the purpose of imparting an effect of improving the focus adjustment function of the pupil (see Patent Document 1). And such vitamin B ₁₂
It is known that the action of vitamins ₁₂ is exerted when vitamin B ₁₂ class passes through the cornea and directly acts on the ciliary muscle existing in the back of the cornea. However, until now, it has not been clarified about the effects of applying vitamin B _{12 to} eyes wearing silicone hydrogel contact lenses. Moreover, the current situation is that even when vitamin B ₁₂ and a surfactant are used in combination and applied to a silicone hydrogel contact lens, it cannot be estimated.

JP 2003-128553 A

Journal of Japanese Contact Lens Society, Vol. 39, 111-115, 1997 Japanese Journal of Contact Lenses, Vol. 44, 34-37, 2002

The present inventors have, as a result of doing various studies about the effect of applying the vitamin B ₁₂ compounds for various SCL, that did not expect at all, silicone hydrogel contact lens (hereinafter, the SHCL in abbreviated sometimes to), the lens transmission amount of vitamin B ₁₂ compound compared to other SCL was obtained a finding entirely new that significantly less. Vitamin B ₁₂ include, but are due to their action exerted is essential outreach ciliary muscle in the back of the cornea, in this way the lens permeation amount is very small, the eye in SHCL wearing Even if an eye drop containing vitamin B ₁₂ is applied, a sufficient amount may not be supplied to the cornea and a satisfactory effect may not be obtained.

Therefore, when it is instilled in SHCL wearing, it has improved permeability of vitamin B ₁₂ compound to SHCL, developing SHCL ophthalmic agents which can increase the corneal arrival of vitamin B ₁₂ compounds are required .

The present inventors have made intensive studies in order to solve the above problems, when used in combination with surfactant in addition to vitamin B ₁₂ compounds were found to be significantly increased permeation amount for SHCL of vitamin B ₁₂ compound . Furthermore, the present inventors have further studied and found that the accumulation of pollen protein in ionic SHCL can be remarkably suppressed by using vitamin B ₁₂ and a surfactant in combination. Furthermore, the present inventors found that pollen protein accumulation inhibitory effect on the ionic SHCL is vitamin B ₁₂ compound and surfactant, was also found that it is possible to further improved by using further in combination terpenoids. The present invention has been completed by making further improvements based on such findings.

That is, the present invention provides the following eye drops for SHCL.
Item 1. An eye drop for a silicone hydrogel contact lens, comprising (A) vitamin B ₁₂ and (B) a surfactant.
Item 2. The eye drop for a silicone hydrogel contact lens according to Item 1, comprising as component (A) at least one selected from the group consisting of cyanocobalamin, mecobalamin, hydroxocobalamin, adenosylcobalamin, aquacobalamin, and salts thereof. .
Item 3. Item 3. The eye drop for a silicone hydrogel contact lens according to Item 1 or 2, comprising cyanocobalamin as a component.
Item 4. Item 4. The silicone hydrogel according to any one of Items 1 to 3, comprising as component (B) at least one selected from the group consisting of a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant. Eye drops for contact lenses.
Item 5. Item 5. The silicone hydrogel contact lens eye drop according to any one of Items 1 to 4, further comprising (C) a terpenoid.
Item 6. Item 6. The eye drop for a silicone hydrogel contact lens according to any one of Items 1 to 5, further comprising (D) a buffer.
Item 7. Item 7. The eye drop for a silicone hydrogel contact lens according to any one of Items 1 to 6, wherein the blending ratio of the component (A) is 0.0001 to 0.1 w / v%.
Item 8. Item 8. The eye drop for a silicone hydrogel contact lens according to any one of Items 1 to 7, wherein the blending ratio of the component (B) is 0.001 to 1.0 w / v%.
Item 9. Item 9. The eye drop for a silicone hydrogel contact lens according to any one of Items 1 to 8, wherein the silicone hydrogel contact lens is nonionic.
Item 10. Item 9. The eye drop for a silicone hydrogel contact lens according to any one of Items 1 to 8, wherein the silicone hydrogel contact lens is ionic.

In addition, the present invention provides a method for improving the permeability of vitamin B ₁₂ to SHCL as described below, and SH
Provided is a method for imparting an eye drop with an effect of improving the permeability of vitamin B ₁₂ to CL.
Item 11. (A), characterized in that the combined use of vitamin B ₁₂ compound and (B) a surfactant, a method of improving the permeability of the component (A) to a silicone hydrogel contact lens.
Item 12. (A) Permeability of the component (A) to a silicone hydrogel contact lens, characterized in that (B) a surfactant is added to an eye drop for a silicone hydrogel contact lens containing vitamin B ₁₂ A method of imparting an effect of improving eye drops to the eye drop.

Further, the present invention provides a permeation-enhancing agent of vitamin B ₁₂ compound to SHCL listed below.
Item 13. (B) (A) to a silicone hydrogel contact lens containing a surfactant
An agent for improving the permeability of vitamin B ₁₂ species.

Furthermore, this invention provides the screening method of the permeability | transmittance improvement substance hung up below.
Item 14. A screening method for a permeability-improving substance that improves the permeability of vitamin B ₁₂ to silicone hydrogel contact lenses,
(a) a control solution containing vitamin B ₁₂ compound, and a test solution containing vitamin B ₁₂ compound and a test substance, the step of each prepared as the test solution,
(b) the test solution respectively, measured only one side surface of the silicone hydrogel contact lens is contacted predetermined time, the amount of vitamin B ₁₂ such exuded from the other side surface not brought into contact with the test solution of the lens To determine the amount of permeation of vitamin B ₁₂ in each test solution, and
(c) a step of selecting a test solution having a permeation amount of vitamin B ₁₂ measured in the step (b) larger than that of a control solution, and selecting a test substance contained in the test solution as the permeability improving substance;
A screening method comprising:

In addition, the present invention provides a method for suppressing the accumulation of pollen protein in ionic SHCL and a method for imparting to the eye drops the action of suppressing the accumulation of pollen protein in ionic SHCL.
Item 15. An ionic silicone hydrogel contact characterized by bringing an eye drop for a silicone hydrogel contact lens containing (A) vitamin B ₁₂ and (B) a surfactant into contact with an ionic silicone hydrogel contact lens A method for suppressing the accumulation of pollen protein in a lens.
Item 16. To the eye drops for silicone hydrogel contact lenses, (A) Vitamin B ₁₂ and (
B) A method of imparting to the eye drop an action of suppressing the accumulation of pollen protein in an ionic silicone hydrogel contact lens, which comprises blending with a surfactant.

According to the eye drop for SHCL of the present invention, the permeability of vitamin B ₁₂ to SHCL can be remarkably improved, so that the amount of vitamin B ₁₂ reaching the cornea even when instilled during SHCL wearing. , And thus the eye focus adjustment function can be effectively improved.

Further, the screening methods of the present invention, since it enables the acquisition of permeability-enhancing substance capable of improving the permeability of vitamin B ₁₂ compound to SHCL, are enhanced permeability of vitamin B ₁₂ compound to SHCL It is useful for developing eye drops for SHCL that can effectively improve the focus adjustment function even when used while wearing SHCL.

In addition, studies by the present inventors have revealed that ionic SHCL has a unique problem that pollen proteins are remarkably easily adsorbed. In general, proteins are thought to be difficult to adsorb to SHCL, and this finding is completely unexpected. And in general,
When a contact lens is worn, the eyes are likely to dry out. As a result, the cleaning action by tears is reduced, and foreign substances such as pollen are likely to stay in the eyes, which is considered to increase the risk of developing hay fever. Moreover, if a large amount of pollen protein is adsorbed and accumulated on the contact lens, it will significantly increase the risk of developing hay fever and may contribute to allergic symptoms. Furthermore, if the pollen protein adsorbed on the contact lens is insufficiently removed, the wearing feeling of the contact lens is impaired, causing discomfort and shortening the use period. However, according to the ophthalmic solution for SHCL of the present invention, even when pollen protein and ionic SHCL come into contact with each other during wearing of ionic SHCL, it promotes removal of pollen protein from ionic SHCL and prevents reattachment. In this way, accumulation of pollen protein in ionic SHCL can be suppressed.
Therefore, according to the eye drop for SHCL of the present invention, the risk of developing allergic symptoms can be reduced for users of hay fever or the pollinosis reserve army, and ionic SHCL can be kept clean.

In the reference test example 1, it is a figure which shows the result of having evaluated the permeability | transmittance to the SCL of cyanocobalamin. In Experiment 1, it is a figure which shows the result of having evaluated the permeability | transmittance to SHCL of the cyanocobalamin of eyedrops (Example 1-3 and Comparative Example 1). In the reference test example 2, it is a figure which shows the result of having evaluated the permeability | transmittance to the SHCL of the pyridoxine hydrochloride of eyedrops (reference example 1-2). In the reference test example 3, it is a figure which shows the result of having evaluated the adsorptivity of the pollen protein to various soft contact lenses. In Test Example 2, it is a figure which shows the result of having evaluated the effect which the test liquid (Example 4 and Comparative Example 2-3) removes the pollen protein adsorbed to ionic SHCL.

(I) SHCL eye drops The SHCL eye drops of the present invention are vitamin B class ₁₂ (hereinafter, sometimes referred to as component (A)).
Containing. Vitamin B ₁₂ is a known compound having an effect of improving the focus control function of the eye, and may be synthesized by a known method or obtained as a commercial product.

Examples of the component (A) used in the present invention include cyanocobalamin, its analogs, and salts thereof.

The analog of cyanocobalamin is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, a ligand on cobalt in cyanocobalamin is substituted. And a compound obtained by substituting a functional group in cyanocobalamin. More specifically, analogs of cyanocobalamin include mecobalamin (methylcobalamin), hydroxocobalamin, adenosylcobalamin, aquacobalamin and the like. One of these analogs of cyanocobalamin may be selected and used alone, or two or more thereof may be used in any combination.

The salt of cyanocobalamin and its analogs is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Carboxylate (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylate (fumarate, maleate, succinate, malonate, etc.), oxy Carboxylate (lactate, tartrate, citrate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.)], inorganic acid salt (eg, hydrochloride, sulfate, Nitrates, hydrobromides, phosphates, etc.), salts with organic bases (eg methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine,
Salts with organic amines such as tripyridine and picoline), salts with inorganic bases [eg ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), metals such as aluminum, etc. Salt, etc.]. Among these salts,
Preferred are organic acid salts and inorganic acid salts, and more preferred are acetates and hydrochlorides. One of these salts may be selected and used alone, or two or more of these salts may be used in any combination.

In the eye drops for SHCL of the present invention, as the component (A), one kind may be selected from cyanocobalamin, its analogs, and salts thereof, and may be used alone. Any combination of these may be used. From the viewpoint of more effectively exhibiting the effect of improving the SHCL permeability by the surfactant, the component (A) used in the present invention is preferably cyanocobalamin, mecobalamin, hydroxocobalamin, and salts thereof; more preferably Cyanocobalamin, mecobalamin, hydroxocobalamin, and acetates and hydrochlorides thereof; more preferably, cyanocobalamin, mecobalamin, hydroxocobalamin, hydroxocobalamin acetate, and hydroxocobalamin hydrochloride; particularly preferably cyanocobalamin. The component (A) exemplified here is also suitable from the viewpoint of more effectively producing the pollen protein accumulation suppressing effect on ionic SHCL.

In the eye drop for SHCL of the present invention, the blending ratio of the component (A) is appropriately set according to the type of the component (A), the type of the other blended components, etc. (A
) Component in a total amount of 0.0001 to 0.1 w / v%, preferably 0.001 to 0.05 w / v%, more preferably 0.004 to 0.02 w / v%, still more preferably 0.01 to An example is 0.02 w / v%.

Furthermore, the eye drop for SHCL of the present invention contains a surfactant (hereinafter also referred to as component (B)) in addition to the component (A). By blending the surfactant in this way, SHCL
This makes it possible to improve the permeability of vitamin B ₁₂ to the water, and to remarkably suppress the accumulation of pollen proteins in ionic SHCL.

The surfactant used as the component (B) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and is a nonionic surfactant or amphoteric. Examples include surfactants, anionic surfactants, and cationic surfactants.

Specific examples of the nonionic surfactant that can be blended as the component (B) include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40), and monostearin. Acid POE (20) sorbitan (polysorbate 60),
POE sorbitan fatty acid esters such as tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80), poloxamer 407,
Poloxamer 235, Poloxamer 188, Poloxamer 403, Poloxamer 237, Poloxamer
POE / POP block copolymers such as 124; POE hydrogenated castor oil such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE alkyl ethers such as POE (9) lauryl ether; POE (20 ) POE-POP alkyl ethers such as POP (4) cetyl ether; POE alkyl phenyl ethers such as POE (10) nonyl phenyl ether. In the compounds exemplified above, POE is polyoxyethylene, POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added.

Further, as the amphoteric surfactant that can be blended as the component (B) (that is, a surfactant having both a cationic site and an anionic site in the molecule), specifically, an alkyldiamino Examples thereof include ethyl glycine and its salt (alkyldiaminoethyl glycine hydrochloride).

Specific examples of the cationic surfactant that can be blended as the component (B) include quaternary ammonium salt type cationic surfactants such as benzalkonium chloride and benzethonium chloride; chlorhexidine salts Examples include amine salt-type cationic surfactants such as chlorhexidine gluconate and chlorhexidine hydrochloride, and polyhexamethylene biguanide salts (such as polyhexamethylene biguanide hydrochloride).

Specific examples of the anionic surfactant that can be blended as the component (B) include alkylbenzene sulfonates, alkyl sulfates, polyoxyethylene alkyl sulfates, aliphatic α-sulfomethyl esters, α Examples include olefin sulfonic acid.

In the eye drop for SHCL of the present invention, the above surfactants may be used alone or in combination of two or more.

Among the component (B), from the viewpoint of effect of improving the permeability of vitamin B ₁₂ compound to SHCL is much increased, preferably nonionic surfactants, cationic surfactants, amphoteric surfactants More preferably nonionic surfactants; more preferably POE sorbitan fatty acid esters, POE hydrogenated castor oil, POE / POP block copolymers; more preferably POE sorbitan fatty acid esters, POE hydrogenated castor oil; Preferably polysorbate
80, polyoxyethylene hydrogenated castor oil 60 is exemplified. The component (B) exemplified here is also suitable from the viewpoint of significantly increasing the pollen protein accumulation suppressing effect on ionic SHCL.

In the eye drop for SHCL of the present invention, the blending ratio of the component (B) is appropriately set according to the type of the component (B), the type of other blending components, etc., as an example, (B
) Component is 0.001-1 w / v% in total, preferably 0.01-0.5 w / v%, more preferably 0.05-0.3 w / v%.

In the eye drop for SHCL of the present invention, the ratio of the component (B) to the component (A),
Vitamin B ₁₂ to SHCL is not particularly limited as long as the above-mentioned blending ratio is satisfied.
From the viewpoint of more effectively improving the permeability of the component, the total amount of the component (B) is 5 to 10,000 parts by weight, preferably 20 to 5000 parts by weight per 100 parts by weight of the total amount of the component (A). It is desirable to satisfy the ratio of preferably 250 to 3000 parts by weight. Also,
By satisfying the above ratio, it becomes possible to more effectively suppress pollen protein accumulation in ionic SHCL.

The eye drop for SHCL of the present invention preferably contains a terpenoid (hereinafter also referred to as component (C)) in addition to the components (A) and (B). Thus, by further including the component (C), the action of suppressing the accumulation of pollen protein in ionic SHCL can be further enhanced.

The terpenoid used in the eye drop for SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. As such terpenoids,
Specific examples include menthol, menthone, camphor, borneol, geraniol, cineol, citronellol, carvone, anethole, eugenol, limonene, linalool, linalyl acetate, and derivatives thereof. These compounds may be d-form, l-form or dl-form. In the present invention, an essential oil containing the above compound may be used as a terpenoid. Examples of such essential oils include eucalyptus oil, bergamot oil,
Peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, rose oil, camphor oil and the like. These terpenoids may be used alone or in any combination of two or more.

Among these terpenoids, menthol, menthone, camphor, borneol and geraniol are preferred from the viewpoint of further enhancing the pollen protein accumulation inhibitory action on ionic SHCL, and the essential oils containing these include cool mint oil and peppermint oil. , Mint oil, camphor oil, rose oil and the like. More preferably, menthol and camphor, particularly preferably l-menthol, dl-menthol, d-camphor and dl-camphor are mentioned, and essential oils containing these include cool mint oil, peppermint oil, peppermint oil, camphor oil and the like. Illustrated.

When the above component (C) is added to the SHCL eye drop of the present invention, the mixing ratio of the component (C) is not particularly limited, but the effect of suppressing the accumulation of pollen protein in ionic SHCL is further enhanced. From this point of view, the total amount of terpenoids is 0.0001 with respect to the total amount of eye drops for SHCL.
-0.2 w / v%, preferably 0.0005-0.1 w / v%, more preferably 0.001-0
. 07 w / v%. In addition, when using the essential oil containing a terpenoid, the terpenoid content in the essential oil mix | blended is set so that the said mixing | blending ratio may be satisfy | filled.

Further, in the eye drop for SHCL of the present invention, the ratio of the component (C) to the component (A) is not particularly limited as long as the above-described blending ratio is satisfied, but pollen protein to ionic SHCL From the viewpoint of further improving the effect of suppressing the accumulation of the above, the total amount of the component (C) is 0.01 to 1000 parts by weight, preferably 0.08 to 400 parts per 100 parts by weight of the total amount of the component (A). It is desirable to satisfy the ratio of parts by weight, more preferably 0.1 to 280 parts by weight. In addition, when using the essential oil containing a terpenoid, it sets so that the terpenoid content in the essential oil mix | blended may satisfy | fill the said ratio.

The eye drop for SHCL of the present invention may further contain a buffering agent in addition to the components (A) and (B). The buffer that can be incorporated into the eye drops for SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. As an example of such a buffer,
Examples include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, Tris buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like.
These buffering agents may be used in combination. Preferred buffering agents are borate buffering agents, phosphate buffering agents, carbonate buffering agents, and citrate buffering agents, and more preferred buffering agents are boric acid buffering agents and phosphate buffering agents, and particularly preferred buffering agents. Is a borate buffer. Examples of the boric acid buffer include boric acid or boric acid salts such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphoric acid or phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the carbonate buffer include carbonates or carbonates such as alkali metal carbonates and alkaline earth metal carbonates. Examples of the citrate buffer include citric acid, alkali metal citrate, and alkaline earth metal citrate. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. As a more specific example, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.) as a boric acid buffer;
As phosphate buffer, phosphoric acid or its salt (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, dihydrogen phosphate Carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.); Citric acid or a salt thereof as a citrate buffer (Sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetic acid or a salt thereof (ammonium acetate,
Potassium acetate, calcium acetate, sodium acetate, etc.); Tris (hydroxymethyl) aminomethane or a salt thereof (hydrochloride, acetate, sulfonate, etc.); aspartic acid or a salt thereof (sodium aspartate, asparagine) Examples thereof include magnesium acid and potassium aspartate). These buffering agents may be used alone or in any combination of two or more.

When a buffering agent is blended in the SHCL eyedrops of the present invention, the blending ratio of the buffering agent varies depending on the type of buffering agent used, the type and amount of other blending components, the use of the eyedrops, etc. However, for example, the total amount of the eyedrops is 0.0% of the total amount of the buffer.
Examples are ratios of 1 to 10 w / v%, preferably 0.1 to 5 w / v%, more preferably 0.5 to 2 w / v%.

The pH of the eye drops for SHCL of the present invention is not particularly limited as long as it is within a range that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. PH of eye drops for SHCL of the present invention
As an example, 4.0 to 9.5, preferably 5.0 to 8.5, more preferably 5.5 to
The range which becomes 8.0, More preferably 6.0-8.0 is mentioned.

In addition, for the osmotic pressure of the eye drops for SHCL of the present invention,
There is no particular limitation. As an example of the osmotic pressure ratio of the eye drop for SHCL of the present invention, preferably 0.7 to
The range which becomes 5.0, More preferably 0.9-3.0, Most preferably 1.0-2.0 is mentioned. The osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols, sugar alcohols, saccharides and the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to the osmotic pressure of 0.9w / v% sodium chloride aqueous solution based on the 15th revised Japanese Pharmacopoeia. The osmotic pressure is the osmotic pressure measurement method described in the Japanese Pharmacopoeia (freezing point depression method) Measure with reference to. The standard solution for measuring the osmotic pressure ratio was sodium chloride (Japanese Pharmacopoeia standard reagent) dried at 500-650 ° C for 40-50 minutes, and then allowed to cool in a desiccator (silica gel). Exactly 1 dissolved in water
Prepare as 00 mL or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

The eye drop for SHCL of the present invention may contain an appropriate amount of various pharmacologically active components and physiologically active components in addition to the above components as long as the effects of the present invention are not hindered. Such ingredients are not particularly limited. For example, over-the-counter drug manufacturing (import) approval standard 2000 version (supervised by the Pharmaceutical Affairs Research Committee)
The active ingredient in the ophthalmic drug described in 1 can be exemplified. Specifically, examples of the components used in the SHCL eyedrops of the present invention include the following components.
Antihistamines: for example, iproheptin, diphenhydramine, chlorpheniramine maleate and the like.
Decongestant: Tetrahydrozoline, naphazoline, epinephrine, ephedrine, methylephedrine, etc.
Bactericides: for example, acrinol, cetylpyridinium, etc.
Vitamins: sodium flavin adenine dinucleotide, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate, tocopherol acetate, etc.
Amino acids: potassium aspartate, magnesium aspartate, aminoethylsulfonic acid and the like.
Anti-inflammatory agents: for example, glycyrrhetinic acid, glycyrrhizic acid, pranoprofen, methyl salicylate, glycol salicylate, allantoin, azulene, azulenesulfonic acid, guaiazulene, tranexamic acid, ε-aminocaproic acid, berberine, lysozyme, licorice, etc.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Other: for example, neostigmine methyl sulfate, ketotifen fumarate, sodium cromoglycate, sodium chondroitin sulfate, sodium hyaluronate, sulfamethoxazole, indomethacin, ibuprofen, ibuprofen piconol, bufexamac, butyl flufenamic acid, bendazac, piroxicam, ketoprofen , Felbinac, purple root, horse chestnut, and salts thereof.

In addition, in the eye drops for SHCL of the present invention, various additives are appropriately selected according to conventional methods according to the use and form as long as they do not impair the effects of the invention, and one or more of them are selected. An appropriate amount may be contained in combination. Examples of such additives include various additives described in Pharmaceutical Additives Encyclopedia 2005 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous carrier such as water or hydrous ethanol.
Thickeners: for example, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, alginic acid, polyvinyl alcohol (completely or partially saponified), polyvinylpyrrolidone, macrogol, sodium chondroitin sulfate, sodium hyaluronate and the like.
Sugars: for example, glucose, cyclodextrin and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These are d
The body, l-form or dl-form may be used.
Preservatives, bactericides or antibacterials: for example, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate Oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds, glowkill (trade name, manufactured by Rhodia), etc.
pH adjuster: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, boro Sand, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, ammonium acetate etc.
Isotonizing agents: for example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, dihydrogen phosphate Sodium, sodium dihydrogen phosphate, potassium dihydrogen phosphate, glycerin, propylene glycol and the like.
Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, etc.
Perfume or refreshing agent: menthol, anethole, eugenol, camphor, geraniol,
Cineol, Borneol, Limonene, Ryuno etc. These may be either d-form, l-form or dl-form, and are formulated as essential oils (mint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil, etc.) May be.

The eye drop for SHCL of the present invention, for example, in the aqueous carrier such as purified water, physiological saline, etc., so that the above components (A) and (B), and other compounding components as required, at a desired concentration It is added and prepared according to a conventional method.

In the eye drop for SHCL of the present invention, the type of SHCL to be applied is not particularly limited, and all SHCL currently marketed or marketed in the future can be applied. Among these nonionic SHCL, compared to the ionic SHCL, permeability of vitamin B ₁₂ compounds tend to be less.
According to the eye drop for SHCL of the present invention, vitamin B ₁ can be used even for SHCL having such low permeability.
_{The two} types of permeability can be effectively improved. In view of the effects of the present invention, the present invention
Non-ionic SHCL is mentioned as an example of a suitable application target of the eye drops for SHCL. In addition, ionic SHCL has a unique problem that it is very easy to adsorb pollen protein,
According to the eye drop for SHCL of the present invention, it is possible to effectively suppress the accumulation of pollen protein in the ionic SHCL. In view of the effects of the present invention, ionic SHCL may be mentioned as an example of a suitable application target of the eye drop for SHCL of the present invention. Non-ionic here means that the content of ionic components in the contact lens material is less than 1 mol% in accordance with US FDA (US Food and Drug Administration) standards, as normally understood by those skilled in the art. The property means that the content of ionic components in the contact lens material is 1 mol% or more in accordance with US FDA standards.
Further, the moisture content of SHCL to be applied is not particularly limited, and examples thereof include 90% or less, preferably 60% or less, and more preferably 50% or less. Since SHCL contains a hydrogel material, it contains at least more than 0% moisture.

Also, the non-ionic SHCL, as the water content is low, the permeability of vitamin B ₁₂ compound tends to be low. According to the eye drop for SHCL of the present invention, the permeability of vitamin B ₁₂ can be effectively improved even for SHCL having such a low permeability. In view of the effect of improving the lens permeability of the present invention, an example of a suitable application target of the eye drop for SHCL of the present invention is nonionic SHCL having a low moisture content of 50% or less.

Here, the moisture content of SHCL indicates the ratio of water in SHCL, and is specifically determined by the following calculation formula.

Moisture content (%) = (weight of hydrated water / weight of hydrated SHCL) x 100
Such moisture content can be measured by a gravimetric method according to the description of ISO18369-4: 2006.

In addition, compared to non-silicone hydrogel contact lenses, which are generally soft, SHCL, which is a hard material, tends to cause deterioration of the feeling of use due to lens deformation and reduced wettability due to the adsorption of foreign substances, and tends to cause ocular mucosal damage. It is in. According to the eye drop for SHCL of the present invention, it is possible to effectively suppress the adsorption of pollen protein to the ionic SHCL, which is a hard material that easily causes deterioration in use feeling and eye mucous membrane damage, thereby deforming the lens. It is also possible to effectively prevent deterioration of the feeling of use and ocular mucosal damage by preventing or deterioration. In view of the pollen protein accumulation inhibitory effect of the present invention, ionic SHCL having a relatively high hardness can be mentioned as a suitable application target of the eye drop for SHCL of the present invention. Preferably, the hardness of the ionic SHCL to be applied is
The hardness when measured by the following measurement method using a texture analyzer is 3 g or more, preferably 4 g or more, more preferably 6 g or more, and still more preferably 8 g or more. Further, the upper limit of the hardness of the SHCL to be applied is not particularly limited, but preferably 15
g or less, more preferably 12 g or less.

Contact lens hardness is measured with a texture analyzer (Product name: TA.XT.plus TEXTURE
Using ANALYSER (manufactured by Stable Micro Systems Limited)), it can be measured specifically as follows.

First, remove the contact lens to be measured from the package, wipe off excess water, rinse with physiological saline (0.9% sodium chloride solution), and then raise the convex surface on the bottom of the plastic petri dish filled with physiological saline. Arrange so that Next, the contact lens is adjusted to be directly below the probe of the measuring instrument, and measurement is performed under the following measurement conditions.

[Measurement condition]
Instrument settings:
Test mode Compression measurement Probe type φ10mm cylinder probe
Target Mode Distance
Distance 2.5mm
Triger Type Auto
Triger Force 0.1g
Test Speed 1.0mm / sec
Measure the stress when crushing the lens 2.5mm (2.5 seconds) after the probe starts to push down the lens apex, and record the maximum value as hardness.

  The eye drop for SHCL of the present invention can be applied directly to the eye wearing the SHCL.

The eye drops for SHCL of the present invention can increase the amount of vitamin B ₁₂ that reaches the cornea, which is effective in improving the focus adjustment function of the eye. Reducing agent for eye fatigue induced by wearing contact lenses (for example, eyes generated when using contact lenses with overcorrected power, or when performing near vision work on a PC for a long time while wearing contact lenses) It is useful as a remedy for fatigue, etc.). In addition, since the eye drop for SHCL of the present invention can be easily used during ionic SHCL wearing, it can effectively suppress the adsorption and accumulation of pollen protein during ionic SHCL wearing. It is possible to comfortably wear ionic SHCL by preventing discomfort during wearing. Therefore, the pollen protein adsorbed on the contact lens is prevented from being kept in contact with the eye for a long time, and it is also effective in preventing allergy and preventing deterioration due to pollen. Therefore, it is suitable for application to ionic SHCL users of hay fever or hay fever reserve.

(II) a method improving the permeability of vitamin B ₁₂ compound to SHCL, and vitamin B ₁₂ compound to SHCL
Method for imparting an eye drop with an effect of improving permeability As described above, the permeability of the component (A) to SHCL can be improved by the component (B).

Accordingly, the present invention may be further improved from another perspective, the characterized in that the combined use of (A) vitamin B ₁₂ compound and (B) a surfactant, the permeability of the component (A) to SHCL Provide a method. In addition, the present invention improves the permeability of the component (A) to SHCL, characterized in that (B) a surfactant is added to (A) SHCL eye drops containing vitamin B ₁₂ types. There is also provided a method of imparting the effect of the ophthalmic solution.

In the method, the types and blending ratios of the components (A) and (B) to be used, the types and blending ratios of other components, the types of SHCL to be applied to the eye drops for SHCL, etc. (I
) SHCL ophthalmic solution ".

(III) Agent for improving the permeability of vitamin B ₁₂ to SHCL As described above, the permeability of the component (A) to SHCL can be improved by the component (B).

Accordingly, the present invention, from yet another point of view, comprises (B) a surfactant as an active ingredient, SHC.
An agent for improving the permeability of (A) vitamin B ₁₂ to L is provided.

In the agent, the type of component (B) that is an active ingredient, the target SHCL, the type of component (A) that is subject to permeability to SHCL, etc., the above ((I) SHCL eye drops) It is the same.

(IV) A screening method for substances that improve the permeability of vitamin B _{12 to} SHCL Further , as described above, the present inventor has a new finding that the component (A) has extremely low permeability to SHCL. Has been obtained. Therefore, further, the present invention is, for SHCL, also provides a method of screening a permeability enhancing substance to improve the permeability of vitamin B ₁₂ compound.
Specifically, this screening method is a method including the following steps (a) to (c).
(a) a control solution containing vitamin B ₁₂ compound, and a test solution containing vitamin B ₁₂ compound and a test substance, the step of each prepared as the test solution,
(b) the test solution respectively, measured only one side surface of the silicone hydrogel contact lens is contacted predetermined time, the amount of vitamin B ₁₂ such exuded from the other side surface not brought into contact with the test solution of the lens To determine the amount of permeation of vitamin B ₁₂ in each test solution, and
(c) transmission of the measured vitamin B ₁₂ compounds in the above step (b), select the larger test solution than the control solution, the step of selecting the test substance contained in said test solution as the permeation enhancing substance.

In the present screening method, the test substance is a candidate substance for the permeability improving substance to be used for screening. Moreover, it is desirable that the candidate substance is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable so that the candidate substance can be incorporated into the eye drops for SHCL.

In step (a), the test solution was added such that the vitamin B ₁₂ such as, for example 0.01~0.03w / v% in water or an aqueous carrier such as a buffer solution, further adding an appropriate amount of the test substance To be prepared. Here, it is desirable to dilute the test substance in stages and prepare a test solution containing a plurality of concentrations of the test substance. Moreover, it is desirable that the control solution containing vitamin B ₁₂ has the same composition as the test solution except that the test substance is not added. Using the test solution and the control solution thus prepared as test solutions, the following (b)
Provide to process.

The step (b) can be performed using an apparatus or the like that has two compartments (cells) capable of containing a solution and these two compartments are separated via SHCL. As such an apparatus, for example, a membrane permeation experiment apparatus manufactured by Beadrex can be used. Specifically, one compartment of the device is filled with the test solution (control solution or test solution), and the other compartment is not filled with anything, or preferably a solution containing no vitamin B ₁₂ ( Less than,
The other compartment (when the blank solution is filled, the blank solution) after a predetermined time (for example, about 4 to 24 hours) has passed and the other compartment is filled.
The amount of vitamin B ₁₂ transferred to the side is quantified. The amount of vitamin B ₁₂ thus determined is the permeation amount of vitamin B ₁₂ determined in the step (b). In addition, as for the said blank solution, it is desirable that the osmotic pressure is equivalent to the test solution (control solution or test solution) with which it is filled.

Further, in the step (c) relating to the selection of the permeability enhancing substance, vitamin B ₁₂ to SHCL
The effect of improving the permeability of the class to select a strong permeability enhancing substance may be selected more test solution than the amount of transmitted control solution of vitamin B ₁₂ compound obtained in step (b).

Permeability enhancing substance obtained by the present screening method, for the purpose of improving the permeability of vitamin B ₁₂ compound to SHCL, may be formulated SHCL for eye drops containing vitamin B ₁₂ compound.

(V) Method for suppressing the accumulation of pollen protein in ionic SHCL, and flower in ionic SHCL
Method for imparting an eye drop with an action to suppress accumulation of powdered protein As described above, by using the above components (A) and (B) in combination, even if the ionic SHCL wearing eye is exposed to pollen, it is ionic. Since removal of pollen protein from SHCL can be promoted to prevent reattachment, accumulation of pollen protein in ionic SHCL can be suppressed.

Accordingly, the present invention, from yet another point of view, is characterized in that an ophthalmic solution for SHCL containing (A) vitamin B ₁₂ and (B) a surfactant is brought into contact with ionic SHCL. A method for suppressing the accumulation of pollen protein in a potato is provided. Further, the ophthalmic solution has an action of suppressing the accumulation of pollen protein in ionic SHCL, characterized in that (A) vitamin B ₁₂ and (B) a surfactant are blended in the ophthalmic solution for SHCL. Provide a way to grant.

In the method, the types and blending ratios of the components (A) and (B) to be used, the types and blending ratios of other components, the types of ionic SHCL to be applied, etc. SHCL
It is the same as “eye drops for use”.

EXAMPLES The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

Reference Test Example 1: Comparative evaluation of SCL permeability of cyanocobalamin Using SCL shown in Table 1, the lens permeability of cyanocobalamin was evaluated.

Measurement of SCL permeability evaluation of cyanocobalamin is performed by a membrane permeation experiment device (made by Beadrex)
Was carried out according to the following method. Each soft contact lens shown in Table 1 was set in a membrane permeation experiment apparatus, and one cell I had 5 ml of physiological saline (0.9 w / v% sodium chloride),
The other cell II was filled with 5 ml of a 0.02 w / v% cyanocobalamin-containing solution (boric acid 0.5 w / v%, appropriate amount of borax, sodium chloride 0.7 w / v%; pH 7.5). Subsequently, 1 ml of the physiological saline solution was collected after 24 hours, and the concentration of cyanocobalamin was measured by HPLC according to a conventional method, and the amount of cyanocobalamin transferred to cell I was calculated. From the amount of cyanocobalamin transferred to cell I thus calculated, the lens transmittance of cyanocobalamin was calculated according to the following equation.

The results are shown in FIG. As is apparent from FIG. 1, the lenses A and B, which are silicone hydrogel contact lenses, were found to have significantly poorer cyanocobalamin lens permeability than the lens C, which is a hydrogel contact lens.

Test Example 1: Cyanocobalamin lens transmission test 1:
Using eye drops shown in Table 2 (Examples 1-3 and Comparative Example 1), SHCL of cyanocobalamin
The permeability was evaluated.

Measurement of SHCL permeability evaluation of cyanocobalamin was performed using a membrane permeation experiment device (by Beadrex).
Was carried out according to the following method. The lens B (SHCL) shown in Table 1 is set in a membrane permeation experiment apparatus. One cell I has 5 mL of physiological saline (0.9 w / v% sodium chloride), and the other cell II has Table 2 Each eye drop was accurately filled with 5 mL. Incidentally, the osmotic pressures of the respective eye drops were arranged to be substantially the same. Next, 1 mL of the physiological saline solution was collected after 24 hours, and the concentration of cyanocobalamin was measured by HPLC according to a conventional method, and the amount of cyanocobalamin transferred to Cell I was calculated. From the amount of cyanocobalamin transferred to cell I thus calculated, the lens transmittance (%) of cyanocobalamin was calculated in the same manner as in Reference Test Example 1. Based on the lens transmittance calculated in each of the examples and the comparative examples, the relative ratio of the lens transmittances when the lens transmittance of the comparative example 1 was set to 100 was obtained.

The results are shown in FIG. As apparent from FIG. 2, it was found that the ophthalmic preparation of Example 1-3 had a marked increase in the lens transmittance of cyanocobalamin compared to the ophthalmic preparation of Comparative Example 1.
That is, it has been clarified that the use of cyanocobalamin and a surfactant (polysorbate 80 or polyoxyethylene hydrogenated castor oil 60) improves the permeability of cyanocobalamin to SHCL. In particular, when polysorbate 80 was used as the surfactant, extremely high SHCL permeability was observed. From this result, it was also confirmed that when polysorbate 80 was used, the lens transmittance of cyanocobalamin was significantly increased if the concentration was 0.1 w / v% or more.

Reference Test Example 2: Lens Permeability Test of Pyridoxine Hydrochloride Pyridoxine hydrochloride is known to exhibit the action of promoting metabolism of corneal cells and relieving eye fatigue. Therefore, to mix pyridoxine hydrochloride with SHCL eye drops,
As with the case of blending the vitamin B ₁₂ compound, it is required that pyridoxine hydrochloride is formulated designed to reach the cornea through the SHCL. Therefore, the following tests were conducted to evaluate the permeability of pyridoxine hydrochloride to SHCL.

Specifically, using the eye drops shown in Table 3 (Reference Example 1-2), a test was conducted in the same manner as in Test Example 1 above, and the SHCL permeability of pyridoxine hydrochloride was evaluated.

The results are shown in FIG. From this result, it was confirmed that, although pyridoxine hydrochloride also has low SHCL permeability, it does not improve SHCL permeability even when a surfactant (polysorbate 80) is used in combination.

Comprehensive Consideration Regarding Lens Permeability Test From the above results, the eye drops combined with Vitamin B ₁₂ and surfactants can reach the cornea with an effective amount of Vitamin B ₁₂ even when applied to the eye wearing SHCL. It was confirmed that the pharmacological effect based on vitamin B ₁₂ can be effectively exhibited. Moreover, it was also confirmed that the improvement of SHCL permeability of the active ingredient by the combined use with such a surfactant is a unique effect recognized by selecting vitamin B ₁₂ as an active ingredient.

Reference Test Example 3: Evaluation of Pollen Protein Adsorption Characteristics to SCL Four kinds of soft contact lenses shown in Table 4 were used in the test to evaluate the pollen protein adsorption characteristics to the soft contact lenses.

First, the lenses used for the test were immersed one by one in 4 mL of physiological saline and stored overnight at room temperature (lens pretreatment).

Pollen protein antigen (CEL Pollen Extract-Ja, manufactured by LSL Co., Ltd.) Properties: Lyophilized powder (Cedar Pollen crude extract Mountain ceder, extracted from pollen of Juniperus Asheii)
) Was dissolved in physiological saline to prepare a 5 mg / 30 mL pollen protein solution. In each hole of the 24-well plate, 1.0 mL of pollen protein solution was put, and after wiping off excess moisture from the pretreated lens, it was immersed and shaken at 34 ° C. and 120 rpm for 18 hours. Next, take out the lens, quickly soak (about 1 second) in 100 mL of physiological saline, rinse the excess liquid, and then lightly drain the water using the edge of a beaker, then put the pollen protein into each hole of the 24-well plate. It was immersed in 1 mL of separation liquid (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34 ° C. and 120 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein in the pollen protein separation solution was quantified as an albumin equivalent value to determine the amount of pollen protein adsorbed to the lens.

Note that the hardness of each soft contact lens is determined by the texture analyzer (
Product name: TA.XT.plus TEXTURE ANALYSER (manufactured by Stable Micro Systems Limited)).

The results are shown in FIG. As shown in FIG. 4, when the lens 1 that is ionic SHCL is used, the lens 3 and the lens 4 that are non-silicon soft contact lenses, and the non-ionic SH
As compared with the lens 2 which is CL, a significantly higher pollen protein adsorption was observed. From this result, pollen protein tends to adsorb very large amount to ionic SHCL among soft contact lenses, and ionic SHCL has a unique problem that it is very easy to adsorb pollen protein. Was confirmed.

Test Example 2: Evaluation of suppression of pollen protein accumulation against ionic SHCL (1)
Lens 1 (ionic SH) in which significant adsorption of pollen protein was confirmed in Reference Test Example 3 above
The following test was conducted using CL).

First, the lenses 1 were immersed one by one in 5 mL of physiological saline and stored at room temperature for 5 hours (
Lens pretreatment). Pollen protein antigen (CEL Pollen Extr, manufactured by LSL)
act-Ja, Properties: Lyophilized powder (Cedar Pollen crude extract Mountain ceder, Juniperus Asheii
Extracted from pollen)) was dissolved in physiological saline to prepare a 5 mg / 50 mL pollen protein solution. 1.0 mL of the pollen protein solution was put into each hole of the 24-well plate, the excess moisture of the pretreated lens was wiped off and immersed, and shaken at 34 ° C. and 400 rpm for 24 hours.

The lens 1 immersed in the pollen protein solution was taken out, quickly immersed in 100 mL of physiological saline (about 1 second), rinsed with excess solution, wiped off moisture, and placed in a 24-well plate. Immerse in 1.0 mL of the test solution (Example 4, Comparative Example 2-3, and control) at 34 ° C., 400 rp
Shake for 18 hours at m. Then remove the lens 1 and quickly (approx.
1 second) After immersing and rinsing excess liquid, use a beaker to lightly drain the water,
It was immersed in 0.5 mL of pollen protein separation liquid (aqueous solution containing 1% sodium carbonate and 1% SDS) placed in a hole plate. The mixture was shaken at 34 ° C. and 400 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

Moreover, in order to calculate the amount of pollen protein adsorption more accurately by subtracting the influence of each test solution, as a blank group, except that the step of treating with the pollen protein solution was changed to treatment with physiological saline, In the same manner as described above, a sample treated with each test solution and treated with a pollen protein separating solution was prepared.

Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein present in the pollen protein separation solution was quantified as an albumin equivalent value,
The amount of pollen protein detached from the lens 1 (pollen protein adsorption amount) was determined. In calculating the amount of pollen protein adsorbed, the amount of pollen protein adsorbed was determined by subtracting the absorbance of the blank group from the absorbance of each sample and calculating it as an albumin equivalent value. Then, according to the following formula, the pollen protein adsorption improvement rate (%) is calculated from the ratio of the amount of pollen protein adsorbed when the test solution of the comparative example and the example is used to the amount of pollen protein adsorbed when the control test solution is used. Calculated.

The results are shown in FIG. As a result, when combined with cyanocobalamin and a surfactant, the improvement rate of pollen protein adsorption is synergistically increased compared to the case of using them alone, and the pollen protein of ionic SHCL It was revealed that the amount of adsorption can be effectively reduced and accumulation can be suppressed (Example 4).

Test Example 3: Evaluation of suppression of pollen protein adsorption to ionic SHCL (2)
Pollen protein for ionic SHCL when each test solution shown in Table 6 (Examples 5 and 6) is applied using lens 1 (ionic SHCL) in Table 4 by the same method as in Test Example 2 above. The amount of adsorption was determined. Then, according to the following formula, the pollen protein adsorption improvement rate (%) from the ratio of the pollen protein adsorption amount when the test solution of Example 6 is used to the pollen protein adsorption amount when the test solution of Example 5 is used. ) Was calculated.

The results are also shown in Table 6. As shown in Table 6, when terpenoids (1-menthol, d-camphor) were used in combination with cyanocobalamin and surfactant (Example 6), when cyanocobalamin and surfactant were used It was revealed that the pollen protein adsorption improving action was further enhanced as compared with (Example 5).

Formulation Examples With the formulation described in Table 7, eye drops for SHCL (Examples 7-25) are prepared.

Claims (1)

An eye drop for a silicone hydrogel contact lens, comprising (A) vitamin B ₁₂ and (B) a surfactant.

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