JP2001122774A - Ophthalmic composition and method for suppressing adsorption on soft contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an ophthalmia composition formulated with a refreshing agent having an improving effect on ocular fatigue, etc., characteristic of a contact lens in use suppressing adsorption on a contact lens, applicable as a drop lotion in the eye while wearing a contact lens as it is. SOLUTION: This ophthalmic composition for a soft contact lens comprises 0.0001-0.1 g/100 mL of a refreshing agent and 0.01-10 g/100 mL of a polyhydric alcohol (a polymer compound is omitted).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an ophthalmic composition suitably applied to a soft contact lens wearer. Further, the present invention relates to a method for suppressing adsorption of a cooling agent to a soft contact lens in an ophthalmic composition for a soft contact lens containing the cooling agent.

[0002]

2. Description of the Related Art A contact lens user has a specific eye due to physical sensation of foreign matter due to wearing of the lens and drying of eyes due to evaporation of tears from the lens surface. Many patients complain of tiredness. Conventionally, eye drops containing a cooling agent have been marketed for the purpose of refreshing tired eyes, but soft contact lens users wear the lens because the cooling agent is easily adsorbed to soft contact lenses It was not possible to instill eye drops. In order to solve this problem, JP-A-11-130667 discloses a method containing a polyoxysorbitan ester and adjusting the pH to 5.5 or higher, and JP-A-11-180858 discloses a nonionic surfactant. An ophthalmic solution containing the compound is disclosed, but its effect is not always sufficient. In the case of repeated use, there is a concern that the nonionic surfactant may affect the soft contact lens and the cornea.

[0003] Accordingly, an object of the present invention is to mix a soft contact lens with a cooling agent having an effect of improving eye fatigue and the like, which is peculiar to the wearing of a soft contact lens, and to suppress adsorption to the soft contact lens. It is an object of the present invention to provide an ophthalmic composition that can be instilled as it is.

[0004]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that the ophthalmic composition for a soft contact lens containing a cooling agent is frequently used. By simultaneously admixing polyhydric alcohols, it was found that the adsorption of the cooling agent to the soft contact lens was suppressed, and at the same time, problems such as eye fatigue and dryness due to the soft contact lens could be alleviated.
The present invention has been completed. That is, the present invention provides an ophthalmic composition for a soft contact lens, comprising a cooling agent and a polyhydric alcohol. Further, the present invention provides a method for suppressing adsorption of a cooling agent to a soft contact lens, characterized by containing a polyhydric alcohol.

[0005] The first essential component of the present invention is a cooling agent such as fennel oil, d-camphor, dl-camphor and Coolmint No. 71212, geraniol, peppermint water, peppermint oil, bergamot oil, d-borneol, dl-borneol (ryuno), l-menthol, dl-menthol, eucalyptus oil, linalool, N-
Ethyl-p-menthan-3-carboxyamide (for example, WS-3, Takasago International Corporation) and the like,
It is not limited to these. These may be used alone or in combination of two or more, and it is more preferable to use them in combination of two or more. Of the above, menthol, camphor and borneol are particularly preferred from the viewpoint of effect and feeling of use. The amount of the cooling agent is 0.0
001-0.1 g / 100 mL is preferable, and 0.000
Particularly preferred is 5 to 0.08 g / 100 mL. Most preferably, it is in the range of 0.001 to 0.02 g / 100 mL. When the content is in the above range, a particularly good reduction in dry feeling and a cool feeling can be obtained.

The polyhydric alcohols as the second essential component of the present invention include, but are not limited to, ethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin and the like. In particular, propylene glycol and glycerin are preferable because of their high adsorption suppressing effect. The blending amount of polyhydric alcohol is 0.01
-10 g / 100 mL is preferred, and more preferably 0.1 g / 100 mL.
02 to 2 g / 100 mL. Moreover, it is preferable that it is 0.1-100,000 times amount (weight) with respect to a cooling agent, More preferably, it is 1-1000 time. In this range, the effect of suppressing the adsorption of the cooling agent to the soft contact lens is particularly good.

It is preferable that the ophthalmic composition of the present invention further contains an amino acid. Examples of the amino acids include potassium L-aspartate, magnesium L-aspartate, potassium magnesium L-aspartate (a mixture of equal amounts), aminoethylsulfonic acid (taurine), sodium chondroitin sulfate, epsilon aminocaproic acid, L-glutamic acid, and L-glutamic acid. -Sodium glutamate and the like. Amino acid amount is 0.01 ~
It is preferably 10 g / 100 mL, particularly preferably 0.1 g / 100 mL.
It is 1-5 g / 100 mL. By adding an amino acid, the feeling of dryness can be reduced, and the discomfort and foreign body sensation when wearing a soft contact lens can be more effectively eliminated.

[0008] The ophthalmic composition according to the present invention has a pH of 5.0.
By adjusting to 8.0, the effect of suppressing adsorption of the cooling agent to the soft contact lens is particularly good. p
H is an alkali agent such as sodium hydroxide, potassium hydroxide, sodium carbonate, hydrochloric acid, citric acid, phosphoric acid, acetic acid,
It can be adjusted using an acid such as boric acid. Further, the composition preferably contains a buffer such as boric acid-borax.

The osmotic pressure of the ophthalmic composition according to the present invention is preferably adjusted to an osmotic pressure ratio of 0.1 to 5,
0.5 to 2.5 is more preferred. Outside this range, eye irritation and physical properties of the soft contact lens may be adversely affected. .

The ophthalmic composition of the present invention may contain, in addition to the above-mentioned components, if necessary, various components usually used for preparing ophthalmic compositions such as eye drops in the usual amounts. Can be.

For example, anti-inflammatory agents such as dipotassium glycyrrhizinate, allantoin, berberine chloride, berberine sulfate, sodium azulene sulfonate, zinc sulfate, zinc lactate, lysozyme chloride, flavin adenine dinucleotide sodium (active vitamin B2), hydrochloric acid Pyridoxine (vitamin B6), cyanocobalamin (vitamin B
12), vitamins such as vitamin E acetate, panthenol, calcium pantothenate, sodium pantothenate, retinol acetate, retinol palmitate (vitamin A palmitate), epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride , Decongestant components such as tetrahydrozoline hydrochloride, antihistamines such as diphenhydramine hydrochloride, chlorpheniramine maleate, sulfa drugs such as sulfamethoxazole, sodium sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium, cromoglyc Acid, anti-allergic agents such as sodium cromoglycate, tranilast, pemirolast potassium, active ingredient such as neostigmine methyl sulfate, and boric acid PH adjusters and buffers such as borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, crystalline sodium phosphate, potassium dihydrogen phosphate, citric acid, sodium citrate, hydrochloric acid, sodium hydroxide, chloride Sodium, potassium chloride, calcium chloride,
Inorganic salts such as sodium bicarbonate, sodium carbonate, dried sodium carbonate and magnesium sulfate; tonicity agents such as glycerin; ethylenediaminetetraacetic acid; disodium ethylenediaminetetraacetate (sodium edetate);
Stabilizers such as cyclodextrin, β-cyclodextrin, γ-cyclodextrin, polyoxyethylene hydrogenated castor oil 60 (eg, HCO-60, Nikko Chemicals Co., Ltd.), polyoxyethylene sorbitan monooleate (eg, TO-10) Nonionic surfactants such as Nikko Chemicals Co., Ltd. (the amount is 0.5 g / 100 mL considering the effect on soft contact lenses and cornea)
It is preferable that the content be 0.2 g / g or less.
100 mL or less, most preferably 0.05 g / 100 m
L. A) a polymer solubilizing agent such as polyoxyethylene polyoxypropylene block copolymer (eg, Poloxamer 407, NOF Corporation), an antioxidant such as dibutylhydroxytoluene (BHT), ascorbic acid, sorbic acid, potassium sorbate; Preservatives such as chlorhexidine gluconate, benzalkonium chloride, benzethonium chloride, alkylpolyaminoethylglycine (for example, TEGO-51, KOTOBUKI CO. LTD.), Methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,
Additives such as hydroxypropylmethylcellulose, hydroxypropylethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, thickeners such as hyaluronic acid, sodium hyaluronate, and glucose, and local anesthetics such as chlorobutanol are blended within the range that does not impair the effects of the present invention. can do. The ophthalmic composition such as the eye drops and the eye wash of the present invention can be prepared by a conventional method.

The use of the ophthalmic composition of the present invention is not particularly limited, and it can be used as an eye drop or an eye wash regardless of whether it is for medical use or for general use. Especially for soft contacts that can be instilled with soft contact lenses, because it reduces eye fatigue and discomfort when wearing soft contact lenses, frequently exchangeable soft contact lenses, daily exchangeable soft contact lenses Useful as eye drops.

[0013]

According to the present invention, the simultaneous addition of a cooling agent and a polyhydric alcohol is effective in suppressing adsorption of the cooling agent to a soft contact lens,
Further, an ophthalmic composition capable of reducing a dry feeling when a soft contact lens is attached can be obtained. Further, the composition of the present invention does not adversely affect the physical properties of the cornea and the soft contact lens, and thus is useful as an ophthalmic solution for soft contact.

[0014]

The present invention will be described below in more detail with reference to Examples, but the present invention is not limited to the following Examples.

(Preparation of the ophthalmic composition of Example 1) 0.5 g of boric acid, 0.05 g of borax, 0.3 g of sodium chloride
g, potassium sorbate 0.1 g and sodium edetate 0.1 g were dissolved in sterilized purified water 90 g. Separately, a solution prepared by dissolving l-menthol 0.005 g in propylene glycol 0.5 g was added, and sodium hydroxide solution was used. PH
Was adjusted to 7.0 and sterilized purified water was added to bring the total amount to 10
It was 0 mL. After filtration, the mixture was filled in a container to prepare an eye drop. Other compositions were prepared according to Example 1.

<Eye irritation test by Draize method> The eye irritation preservative in the Ministry of Health and Welfare Scientific Research Report (1970) was performed according to the short-term test method for ocular mucosal irritation. ：: Average score of 0 or more and less than 2 points △: 2 or more and less than 5 points ×: 5 or more points

<Adsorption Test of Softener on Soft Contact Lenses> From four classifications of soft contact lenses by the FDA (Food and Drug Administration), representative lenses such as Sequence (Bausch & Lomb Japan), Softmu (( Nippon Contact Lens Co., Ltd.), High Flow Ace (HOYA Corp.), Accuview (Johnson & Johnson Medical Co., Ltd.)
After immersing one lens in mL at 37 ° C. for 7 days, a cooling agent was extracted from the remaining liquid and quantified by gas chromatography. In addition, an ophthalmic solution in which a lens was not immersed was treated in the same manner, and the adsorption rate for each lens was calculated from the ratio to the control. A: The average adsorption rate of the cooling agent to the four lenses is 1%
If less than. B: The average adsorption rate of the cooling agent to the four lenses is 1%
More than 5%. C: The average adsorption rate of the cooling agent to the four lenses is 5%
More than that.

<Test of Improvement Effect on Dry Feeling> Evaluation was made by 10 volunteers who used soft contact lenses. Legends in the table are as follows. ：: When the proportion of persons who answered that the dry feeling when the soft contact lens was attached was remarkably reduced was 70% or more. ：: When the proportion of persons who answered that the dry feeling when the soft contact lens was attached was reduced was 50% or more and less than 70%. Δ: When the proportion of the persons who answered that the dry feeling when wearing the soft contact lens was reduced was less than 50% (when there was no particular problem in using the contact lens).

With respect to Examples 1 to 76 and Comparative Example 1, ophthalmic solutions having the formulations shown in Tables 1 to 12 were prepared in the same manner as in Example 1; The effect of improving the feeling of dryness by the user was evaluated, and the results are shown in the table.

[0020]

[Table 1]

[0021]

[Table 2]

[0022]

[Table 3]

[0023]

[Table 4]

[0024]

[Table 5]

[0025]

[Table 6]

[0026]

[Table 7]

[0027]

[Table 8]

[0028]

[Table 9]

[0029]

[Table 10]

[0030]

[Table 11]

[0031]

[Table 12]

────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] October 23, 2000 (2000.10.
23)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Name of invention

[Correction method] Change

[Correction contents]

Patent application title: Ophthalmic composition and method for suppressing adsorption to soft contact lens

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] Claims

[Correction method] Change

[Correction contents]

[Claims]

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0002

[Correction method] Change

[Correction contents]

[0002]

2. Description of the Related Art A contact lens user has a specific eye due to physical sensation of foreign matter due to wearing of the lens and drying of eyes due to evaporation of tears from the lens surface. Many patients complain of tiredness. Conventionally, eye drops containing a cooling agent have been marketed for the purpose of refreshing tired eyes, but soft contact lens users wear the lens because the cooling agent is easily adsorbed to soft contact lenses It was not possible to instill eye drops. In order to solve this problem, JP-A-11-130667 discloses a method containing a polyoxysorbitan ester and adjusting the pH to 5.5 or more. JP-A-11-180858 discloses a nonionic interface. Although an eye drop containing an active agent or the like is disclosed, its effect is not always sufficient, and when it is repeatedly used frequently, there is a concern that the nonionic surfactant may affect a soft contact lens or a cornea.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0003

[Correction method] Change

[Correction contents]

[0003] Accordingly, an object of the present invention is to mix a soft contact lens with a cooling agent having an effect of improving eye fatigue and the like, which is peculiar to the wearing of a soft contact lens, and to suppress adsorption to the soft contact lens. It is an object of the present invention to provide an ophthalmic composition which can be instilled as it is, and a method for suppressing adsorption of a cooling agent to a soft contact lens.

[Procedure amendment 5]

[Document name to be amended] Statement

[Correction target item name] 0004

[Correction method] Change

[Correction contents]

[0004]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that the ophthalmic composition for a soft contact lens containing a cooling agent is frequently used. By simultaneously admixing polyhydric alcohols, it was found that the adsorption of the cooling agent to the soft contact lens was suppressed, and at the same time, problems such as eye fatigue and dryness due to the soft contact lens could be alleviated.
The present invention has been completed. That is, the present invention provides a cooling agent of 0.0001 to 0.1 g / 100 mL and polyhydric alcohols (excluding high molecular compounds) of 0.01 to 10
g / 100 mL, provided is an ophthalmic composition for soft contact lenses. Further, the present invention provides a method for suppressing adsorption of a cooling agent to a soft contact lens, characterized in that a polyhydric alcohol other than a polymer compound is added to a composition containing the cooling agent.

[Procedure amendment 6]

[Document name to be amended] Statement

[Correction target item name] 0005

[Correction method] Change

[Correction contents]

[0005] The first essential component of the present invention is a cooling agent such as fennel oil, d-camphor, dl-camphor and Coolmint No. 71212, geraniol, peppermint water, peppermint oil, bergamot oil, d-borneol, dl-borneol (ryuno), l-menthol, dl-menthol, eucalyptus oil, linalool, N-
Ethyl-p-menthan-3-carboxyamide (for example, WS-3, Takasago International Corporation) and the like,
It is not limited to these. These may be used alone or in combination of two or more, and it is more preferable to use them in combination of two or more. Among them, menthol, camphor and borneol are particularly preferable from the viewpoint of effect and feeling of use. The amount of the cooling agent in the ophthalmic composition of the present invention is 0.0001 to 0.1 g / 100 mL.
And 0.0005 to 0.08 g / 100 mL is particularly preferable. Most preferably, 0.001 to 0.02 g
/ 100 mL range. When the content is in the above range, a particularly good reduction in dry feeling and a cool feeling can be obtained.

[Procedure amendment 7]

[Document name to be amended] Statement

[Correction target item name] 0006

[Correction method] Change

[Correction contents]

[0006] The polyhydric alcohols as the second essential component of the present invention are polyhydric alcohols excluding high molecular compounds. Examples of such polyhydric alcohols include ethylene glycol, propylene glycol, and 1,3. -Butylene glycol, glycerin and the like, but are not limited thereto. In particular, propylene glycol,
Glycerin is preferred because of its high adsorption suppressing effect. The blending amount of the polyhydric alcohol in the ophthalmic composition of the present invention is 0.1.
01 to 10 g / 100 mL, more preferably 0.1 to 0.1 g / 100 mL.
02 to 2 g / 100 mL. Moreover, it is preferable that it is 0.1-100,000 times amount (weight) with respect to a cooling agent, More preferably, it is 1-1000 time. In this range, the effect of suppressing the adsorption of the cooling agent to the soft contact lens is particularly good.

[Procedure amendment 8]

[Document name to be amended] Statement

[Correction target item name] 0011

[Correction method] Change

[Correction contents]

For example, dipotassium glycyrrhizinate,
Runtoin, berberine chloride, berberine sulfate, Azure
Sodium sulfonate, zinc sulfate, zinc lactate,
Anti-inflammatory agents such as zozyme, flavin adenine dinucleotide
Sodium Tide (Activated Vitamin B_Two), Pyridoki hydrochloride
Syn (vitamin B₆), Cyanocobalamin (vitamin B)
₁₂), Vitamin E acetate, panthenol, pantothe
Calcium phosphate, sodium pantothenate, retino acetate
, Retinol palmitate (vitamin A palmitate)
Vi), epinephrine, epinephrine hydrochloride
, Ephedrine hydrochloride, naphazoline hydrochloride, nafa nitrate
Zoline, phenylephrine hydrochloride, tetrahydrozoline hydrochloride
Decongestant components such as diphenhydramine hydrochloride, malein
Antihistamines such as chlorpheniramine acid, sulfa
Methoxazole, sulfamethoxazole sodium,
Sulfisoxazole, sulfisomidine sodium
Which sulfa drugs, cromoglycic acid, cromoglycate nato
Anti-lium, tranilast, pemirolast potassium, etc.
Effective ingredients such as allergic drugs and neostigmine methyl sulfate
Min, and boric acid, borax, phosphoric acid, sodium hydrogen phosphate
System, sodium dihydrogen phosphate, crystalline sodium phosphate,
Potassium dihydrogen phosphate, citric acid, sodium citrate
PH adjusters and buffers such as
Agent, sodium chloride, potassium chloride, calcium chloride,
Sodium bicarbonate, sodium carbonate, dried sodium carbonate
Inorganic salts such as sodium and magnesium sulfate, glycerin
Which tonicity agent, ethylenediaminetetraacetic acid, ethylenedia
Disodium mintetraacetate (sodium edetate), α-
Cyclodextrin, β-cyclodextrin, γ-cy
Stabilizers such as clodextrin, polyoxyethylene
Hardened castor oil 60 (eg HCO-60, Nikko Chemical
Co., Ltd.), polyoxyethylene sorbitan monoolee
(For example, TO-10, Nikko Chemicals Co., Ltd.)
Nonionic surfactant (compounding amount is soft contact
0.5g / 100mL
It is preferable that the content is not more than 0.2 g / particularly.
100 mL or less, most preferably 0.05 g / 100 m
L or less. ), Polyoxyethylene polyoxypro
Pyrene block copolymers (eg Poloxamer 40
7, a polymer solubilizer such as NOF Corporation, dibutyl
Hydroxytoluene (BHT), ascorbic acid, etc.
Antioxidants, sorbic acid, potassium sorbate, glucone
Chlorhexidine acid, benzalkonium chloride, ben chloride
Zethonium, alkyl polyaminoethyl glycine (eg
For example, Tego-51, KOTOBUKI CO. LTD. )
Which preservatives, methylcellulose, ethylcellulose,
Droxyethyl cellulose, hydroxypropyl cellulose
Glucose, hydroxypropyl methylcellulose, hydroxy
Cypropylethylcellulose, polyvinyl alcohol,
Polyvinyl pyrrolidone, hyaluronic acid, hyaluronic acid
Thickeners such as thorium and glucose, chlorobutanol
Which additives such as local anesthetics do not impair the effect of the present invention
It can be blended within the range. Eye drops of the present invention, eyewash
Ophthalmic compositions such as preparations can be prepared by conventional methods.

Claims (5)

[Claims] 1. An ophthalmic composition for a soft contact lens, comprising a cooling agent and a polyhydric alcohol. 2. The ophthalmic composition for soft contact lenses according to claim 1, wherein the polyhydric alcohol is propylene glycol and / or glycerin. 3. The ophthalmic composition for soft contact lenses according to claim 1, wherein the cooling agent is at least one selected from the group consisting of menthol, borneol and camphor. 4. The content of the nonionic surfactant is 0.5%.
The ophthalmic composition for a soft contact lens according to any one of claims 1 to 3, wherein: 5. A method for suppressing adsorption of a cooling agent to a soft contact lens, comprising a method of containing a polyhydric alcohol.