KR20120046026A - Ophthalmic compositions for soft contact lens - Google Patents

Abstract

PURPOSE: An ophthalmic composition containing chlorpheniramine or salt thereof is provided to ensure good physical property of the lens and to suppress allergic symptom. CONSTITUTION: An ophthalmic composition for a soft lens contains 0.006-0.1g/100mL of chlorpheniramine maleate, 0.05-1.0g/100mL of glycyrrhizic acid 2 potassium, 0.05-1.0g/100mL of sodium chloride or potassium chloride, and 1.2-1.8g/100mL of boric acid or borax. The composition is an eye drop for a long-term user of the soft lens.

Description

Ophthalmic composition for soft contact lenses {OPHTHALMIC COMPOSITIONS FOR SOFT CONTACT LENS}

TECHNICAL FIELD This invention relates to the composition for soft ophthalmic ophthalmic ophthalmic use in which adsorption of chlorpheniramine or its salt to the soft contact lens was suppressed.

Soft contact lenses tend to dry the lens surface and easily adhere to pollen or house dust contaminants. Therefore, the eye wearing the soft contact lens is more likely to cause allergic symptoms such as itching than the naked eye. Therefore, an ophthalmic composition that is applied during the wearing of the soft contact lens to suppress the symptoms such as itching, redness, and inflammation is desired. It is becoming.

Although chlorpheniramine or its salts are known as antihistamine drugs that suppress itch, which is an allergic symptom, they are cationic and have soft contact lenses, especially soft contact lenses of Group IV with negative charge (FDA (American Food) It is easy to adsorb | suck to soft contact lens classification by the Pharmaceutical Affairs Bureau), and there exists a possibility of the side effect by accumulation, etc., or the influence on a lens property.

Therefore, in order to make an ophthalmic composition which can be used in soft contact lens wearing, it is necessary to suppress adsorption of chlorpheniramine or its salt to the soft contact lens.

Conventionally, as a method of suppressing the adsorption of drugs to soft contact lenses, a method of suppressing the adsorption of fat-soluble vitamins with a polymer and a nonionic surfactant (Japanese Patent Laid-Open No. 2001-158734) or pH is acidic and positive ( A method of suppressing the adsorption of a compound having secondary and tertiary amino groups by a compound, etc. (Japanese Patent Laid-Open No. 2009-161455) and the like are known. Means for suppressing adsorption to the lens are not yet known.

[Patent Document]

Patent Document 1: Japanese Patent Application Laid-Open No. 2001-158734

Patent Document 2: Japanese Patent Application Laid-Open No. 2009-161455

The present invention provides a means for suppressing adsorption of chlorpheniramine or a salt thereof to a soft contact lens, and a soft contact lens containing chlorpheniramine or a salt thereof using the means and having good lens properties of the soft contact lens. It is an object to provide an ophthalmic composition for enteric use.

MEANS TO SOLVE THE PROBLEM As a result of earnestly examining in order to achieve the said objective, when a glycaryrizine acid or its salt, chondroitin sulfate or its salt, sodium chloride or potassium chloride, boric acid, or borax are each mix | blended in specific concentration, the chlorpheniramine or its salt soft contact lens, It has been found that adsorption to is suppressed and the lens physical properties of the soft contact lens are also good.

The following invention is provided.

[1] (A) 0.006-0.1 g / 100 mL of chlorpheniramine maleate,

(B) 0.05 to 1.0 g / 100 mL of dipotassium glycyrrhizinate,

(C) 0.05 to 1.0 g / 100 mL sodium chondroitin sulfate,

(D) 0.2 to 1.5 g / 100 mL of one or two selected from sodium chloride and potassium chloride,

(E) Soft contact lens, containing 1.2 to 1.8 g / 100 mL of one or two selected from boric acid and borax, and containing no quaternary cationic preservative, parabens, chlorobutanol and sorbic acid, and having a pH of 6.6 to 7.3 Ophthalmic composition for enteric use.

[2] The ophthalmic composition according to claim 1, wherein the soft contact lens is Lens IV of the soft contact lens classification by the FDA (Food and Drug Administration).

[3] The ophthalmic composition according to claim 1 or 2, which is an eye drop for a soft contact lens wearer.

[4] The compounding quantity of (A) component is 0.015-0.03g / 100mL, the compounding quantity of (B) component is 0.25-0.3g / 100mL, the compounding quantity of (C) component is 0.4-0.5g / 100mL, (D The composition for ophthalmology of Claim 1 or 2 whose compounding quantity of a component is 0.3-0.5g / 100mL, and the compounding quantity of (E) component is 1.4-1.5g / 100mL.

ADVANTAGE OF THE INVENTION According to this invention, the eyedrops etc. which can suppress the adsorption of chlorpheniramine or its salt to the soft contact lens, the lens physical property of a soft contact lens are favorable, and can be used when a soft contact lens wearer wears a soft contact lens, etc. The ophthalmic composition of the present invention can be provided to suppress allergic symptoms such as itching during soft contact lens wearing.

EMBODIMENT OF THE INVENTION Below, this invention is demonstrated in detail.

The present invention, (A) chlorpheniramine maleate 0.006 to 0.1 g / 100 mL,

(B) 0.05 to 1.0 g / 100 mL of dipotassium glycyrrhizinate,

(C) 0.05 to 1.0 g / 100 mL sodium chondroitin sulfate,

(D) 0.2 to 1.5 g / 100 mL of one or two selected from sodium chloride and potassium chloride,

(E) Soft contact lens, containing 1.2 to 1.8 g / 100 mL of one or two selected from boric acid and borax, and containing no quaternary cationic preservative, parabens, chlorobutanol and sorbic acid, and having a pH of 6.6 to 7.3 It is an ophthalmic composition for enteric use. In addition, the soft contact lens of the lens IV of the soft contact lens classification by FDA (United States Food and Drug Administration) of this invention contains ionic materials, such as methacrylic acid, and also has a high water content (50% water content). Say lens).

(A) chlorpheniramine maleate

In the present invention, chlorpheniramine maleate is used as chlorpheniramine or a salt thereof. The compounding quantity of (A) component is 0.006-0.1g / 100mL in an ophthalmic composition, Preferably it is 0.01-0.04g / 100mL, More preferably, it is 0.015-0.03g / 100mL. Below the lower limit, the antihistamine effect on the itch is not sufficient, and when the upper limit is higher than the upper limit, there is a fear of side effects and the inhibition of adsorption of chlorpheniramine or its salt to lens IV is insufficient.

(A) Adsorption suppression means for the soft contact lens of chlorpheniramine or its salt in this invention is 1 selected from (B) dipotassium glycyrrhizin, (C) sodium chondroitin sulfate, (D) sodium chloride, and potassium chloride It is obtained by using together 1 type (s) or 2 types chosen from species or 2 types, and (E) boric acid and borax.

(B) Dipotassium glycyrrhizin

The compounding quantity of (B) component is 0.05-1.0g / 100mL in an ophthalmic composition, Preferably it is 0.1-0.5g / 100mL, More preferably, it is 0.12-0.3g / 100mL, Especially preferably, 0.2-0.3g / 100 mL, most preferably 0.25 to 0.3 g / 100 mL. If it is less than the lower limit, the inhibition of adsorption of chlorpheniramine or its salt is not sufficient, and if it is more than the upper limit, side effects and influence on lens physical properties are feared.

(C) Sodium chondroitin sulfate (sodium chondroitin sulfate)

The compounding quantity of (C) component is 0.05-1.0g / 100mL in an ophthalmic composition, Preferably it is 0.2-0.7g / 100mL, More preferably, it is 0.3-0.6g / 100mL, Especially preferably, it is 0.4-0.5g / 100 mL. If it is less than the lower limit, the inhibition of adsorption of chlorpheniramine or its salt is not sufficient, and if too large, stickiness or blurring may occur.

(D) one or two selected from sodium chloride and potassium chloride

The compounding quantity of (D) component is 0.2-1.5 g / 100 mL in an ophthalmic composition, Preferably it is 0.25-1.0 g / 100 mL, More preferably, it is 0.3-0.5 g / 100 mL. If it is less than the lower limit, the effect of inhibiting adsorption of chlorpheniramine or its salt is not sufficient, and if it is more than the upper limit, the effect on the lens properties is feared.

(E) One or two selected from boric acid and borax.

The compounding quantity of (E) component is 1.2-1.8 g / 100 mL in an ophthalmic composition, Preferably it is 1.3-1.6 g / 100 mL, More preferably, it is 1.4-1.5 g / 100 mL. If it is less than the lower limit, the inhibition of adsorption of chlorpheniramine or its salt is not sufficient, and if it is more than the upper limit, the effect on the lens physical properties is feared. In particular, the combination of (D) sodium chloride and (E) boric acid is effective for inhibiting adsorption of chlorpheniramine or its salt.

The pH of the ophthalmic composition (20 ° C.) is 6.6 to 7.3, preferably 6.6 to 7.0, more preferably 6.6 to 6.9, particularly preferably 6.7 to 6.8. If it is higher than the above range, the inhibition of adsorption of chlorpheniramine or its salt is insufficient. Moreover, there exists a possibility that the stimulus, such as feeling a pain, may arise outside the said range.

In the ophthalmic composition which can be used in soft contact lens entertaining, it is preferable not to mix | blend the cation type preservative etc. which adsorb | suck to a lens from a viewpoint of safety. The ophthalmic composition of the present invention does not contain quaternary cationic antiseptics, parabens, chlorobutanol, and sorbic acid, which may be affected by soft contact lenses. Examples of the quaternary cation-type preservatives include benzalkonium chloride, benzetonium chloride, polydronium chloride, polyhexamethylene biguanide, gluconate chlorhexidine, and the like, and methyl paraben and propyl paraben.

It is preferable to mix | blend 1 type, or 2 or more types chosen from l-menthol, dl-camphor, d-camphor, and d-borneneol as a refreshing agent to the ophthalmic composition of this invention. By mix | blending these refreshing agents, the improvement effect to the itch and inflammation of this invention becomes high. The compounding quantity of a refreshing agent is 0.001-0.03g / 100mL, Preferably it is 0.003-0.02g / 100mL, More preferably, it is 0.005-0.015g / 100mL. If it is less than the above range, there is no enhancement effect of the improvement effect by the cooling agent, and if it is more than the upper limit, heat feeling may be felt.

The ophthalmic composition of this invention can mix | blend the various components used for the eye drop in the range which does not impair the effect of this invention as needed. Preferable compounding components include drugs, buffers, stabilizers, isotonic agents, dissolution aids, antioxidants, viscous agents, pH adjusters and the like.

Examples of the drug include anti-inflammatory agents such as allantoin, berberine chloride, berberine sulfate, sodium azulene sulfonate, zinc sulfate, zinc lactate, and lysozyme chloride, sodium flavinatenin dinucleotides (active vitamin B ₂ ), and cya Vitamins such as nocobalamin (vitamin B ₁₂ ), pyridoxine hydrochloride (vitamin B ₆ ), vitamin E acetate, panthenol, calcium pantothenate, sodium pantothenate, retinol acetate, and parmitate retinol (vitamin A palmitto), amino Amino acids such as ethylsulfonic acid (taurine), L-aspartic acid and salts thereof, glucose, sugars such as D-mannitol xylitol, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, napazoline hydrochloride, napazoline hydrochloride, phenylephrine hydrochloride, Decongestion components such as hydrochloric acid tetrahydrozoline, sulfamethoxazole, sulfamethoxazole sodium, sulfapixazole, sulfapixazine sodium salts, chromoglylic acid, chromoglycol Sodium, tranilast, fumaric acid cake Totti may be mentioned antiallergic agent and the like, such as a pen.

Moreover, it is preferable to contain a vitamin or its derivative (s), an amino acid or its salt, an anti-inflammatory agent, and a tear fluid auxiliary component from the point of eye fatigue and inflammation suppression by contact lens wearing. The compounding quantity of a chemical | medical agent can select an effective suitability amount of each chemical | medical agent.

Examples of the buffer include citric acid, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, glacial acetic acid, tromethmol, sodium hydrogen carbonate, and the like. Particularly preferred buffer is tromethamol. In addition, the compounding quantity of the buffer is preferably 0.01 to 2 g / 100 mL in the ophthalmic composition, more preferably 0.05 to 1.5 g / 100 mL, and particularly preferably 0.1 to 1.0 g / 100 mL.

As a stabilizer, sodium etate hydrate etc. are mentioned, for example. As for the compounding quantity of a stabilizer, 0.01-1.0g / 100mL is preferable in an ophthalmic composition, More preferably, it is 0.02-0.5g / 100mL, Especially preferably, it is the range of 0.05-0.1g / 100mL.

As an isotonicity agent, glycerin etc. are mentioned, for example. It is preferable that the compounding quantity of an isotonic agent is the range of 0.1-2. 0g / 100mL in an ophthalmic composition.

As the dissolution aid, for example, polyoxyethylene cured castor oil, polyoxyethylene castor oil, polyoxyethylene sorbitan monooleate (polysorbate 80, etc.), polyoxyethylene, in addition to propylene glycol, polyethylene glycol, ethanol and the like Nonionic surfactants, such as polyoxypropylene glycol, etc. are mentioned. Although the added mole number of polyoxyethylene and polyoxypropylene is not specifically limited, Polyoxyethylene hardened castor oil 60, polyoxyethylene hardened castor oil 40, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (200 The polyoxypropylene glycol 70 is particularly preferable in view of eye safety and adsorption inhibiting effect. It is preferable that the compounding quantity of a dissolution aid is the range of 0.01-50.0 g / 100 mL in an ophthalmic composition.

Examples of the antioxidant include dibutylhydroxytoluene (BHT), butyl hydroxyanisole (BHA), hydroquinone, molybdenum propyl, sodium hydrogen sulfite and the like. It is preferable that the compounding quantity of antioxidant is the range of 0.001-1.0g / 100mL in an ophthalmic composition.

Examples of the viscous agent include cellulose polymer compounds such as methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose and hydroxyethyl cellulose, polyvinyl polymer compounds such as polyvinylpyrrolidone and polyvinyl alcohol, liquid paraffin, Carboxyvinyl polymer, alginic acid, etc. are mentioned. It is preferable that the compounding quantity of a viscous agent is the range of 0.005-2. 0g / 100mL in an ophthalmic composition.

As a pH adjuster, dilute hydrochloric acid, sodium hydroxide, etc. are mentioned, for example.

The ophthalmic composition of this invention makes a remainder water, and can manufacture it by a well-known manufacturing method. For example, after dissolving each component in sterile purified water, purified water, ion-exchanged water, or a mixed solvent with alcohol such as ethanol, and the like, the pH and, if necessary, the penetration pressure may be appropriately adjusted with a pH adjuster or an isotonic agent. It can obtain by adjusting, sterile filtration, etc.

The obtained composition can be filled in a well-known eyedrop container (it is preferable that it contains a ultraviolet inhibitor or a pigment | dye in terms of stability of a content), and packaging, such as film packaging, can be provided as an ophthalmic composition with favorable storage stability.

The ophthalmic composition of the present invention can be used as an ophthalmic composition for soft contact lens enteric wear because it is an ophthalmic composition that can be used in soft contact lens entertaining because adsorption of chlorpheniramine or a salt thereof to the soft contact lens is suppressed. As an ophthalmic composition, the eyedrops for soft contact lens wearers which can be applied eyedrops in the state which wore the soft contact lens are suitable.

Soft contact lenses to which the ophthalmic composition of the present invention can be adapted are not limited to those described above, but in particular, chlorpheniramine or salts thereof (antihistamines) for lens IV of the soft contact lens classification by the FDA (Food and Drug Administration). About) has an excellent adsorption inhibitory effect. In addition, among the lens IV, the lens has a negative charge and is more effective for a lens having a moisture content of 55% or more. The kind of the soft contact lens is not particularly limited, and can be used for any one-time soft contact lens, regular exchange soft contact lens, conventional soft contact lens, silicone hydrogel contact lens, or color soft contact lens.

The present invention also provides the following invention. Moreover, also in the case of the following invention, a suitable component, its compounding quantity, etc. are as above-mentioned.

(A) An ophthalmic composition containing 0.006 to 0.1 g / 100 mL of chlorpheniramine maleate, (B) 0.05 to 1.0 g / 100 mL of dipotassium glycyrrhinate, (C) 0.05 to 1.0 g / 100 mL of sodium chondroitin sulfate, And (D) 0.2 to 1.5 g / 100 mL of one or two kinds selected from sodium chloride and potassium chloride, and 1.2 to 1.8 g / 100 mL of one or two kinds selected from (E) boric acid and borax, The method for suppressing adsorption of (A) chlorpheniramine maleate on a soft contact lens, wherein the pH of the composition is 6.6 to 7.3.

From (A) chlorpheniramine maleate, (B) dipotassium glycyrrhizin, (C) sodium chondroitin sulfate, (D) one or two selected from sodium chloride and potassium chloride, and (E) boric acid and borax As (A) adsorption inhibitor to the soft contact lens of (A) chlorpheniramine maleate which consists of 1 type or 2 types chosen, it does not contain a quaternary cationic type preservative, paraben, chlorobutanol, and sorbic acid, and is pH 6.6-7.3, In the ophthalmic composition for soft contact lens enteric wear, (A) component 0.006-0.1g / 100mL, (B) component 0.05-1.0g / 100mL, (C) component 0.05-1.0g / 100mL, (D) component 0.2-1.5 Adsorption inhibitor for the said ophthalmic composition mix | blended so that it may be g / 100 mL and (E) component 1.2-1.8 g / 100 mL.

(A) one or two selected from (B) dipotassium glycyrrhizin, (C) sodium chondroitin sulfate, and (D) sodium chloride and potassium chloride for preparing an inhibitor of adsorption of chlorpheniramine maleate to a soft contact lens. Species and (E) one or two uses selected from boric acid and borax.

[Example]

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

[Examples 1 to 17 and Comparative Examples 1 to 9]

According to the composition table of Tables 1-3, after dissolving each component in the table in purified water according to the regular method, after adjusting pH, each solution was sterilely filtered and the ophthalmic composition was prepared. About each obtained formulation, the following test was done. (W / V%) is equal to g / 100 mL.

Adsorption inhibition test

From the four categories of soft contact lenses by the FDA (Food and Drug Administration), Group IV: AccuView (Johnson & Johnson Medical Co., Ltd.) is selected as a representative lens, and one lens is placed at 37 ° C in 5 mL of an ophthalmic composition. After infiltration for 7 days, the drug amount of the residue was quantified by HPLC. Using the ophthalmic composition which did not penetrate the lens similarly as a control, the adsorption rate for each lens was calculated from the ratio to the control.

The conditions of HPLC are shown below.

Detector: Ultraviolet absorption photometer (Measurement wavelength: 220nm)

Column: GI Science, Inc., Inertsil (trademark) ODS-3V (particle size 5㎛, inner diameter 4.6mm, length 150mm)

Column temperature: constant temperature around 40 ℃

Mobile phase: phosphate buffer / acetonitrile mixture

(Evaluation standard)

1: Average adsorption rate for the lens is less than 7%

2: average adsorption rate for the lens is 7% or more but less than 9%

3: Average adsorption rate for the lens is 9% or more but less than 11%

4: Average adsorption rate for the lens is 11% or more but less than 13%

5: The average adsorption rate for the lens is 13% or more

[Lens property test]

From the four categories of soft contact lenses by the FDA (Food and Drug Administration), Group IV: AccuView (Johnson & Johnson Medical Co., Ltd.) is selected as a representative lens, and one lens is placed at room temperature, 5 ml of an ophthalmic composition. After standing for 24 hours, the diameter of the contact lens was measured. The lens diameter of the unopened product was measured as a control.

(Evaluation standard)

1: less than ± 2% change in diameter compared to the control

2: Diameter change is more than ± 2% and less than ± 4% compared to the control

3: Diameter change is more than ± 4% and less than ± 6% compared to the control

4: Diameter change is more than ± 6% and less than ± 8% compared to the control

5: Diameter change more than ± 8% compared to the control

[Examples 18 to 30]

The ophthalmic composition of the composition shown in the following table was prepared like the said Example. The obtained ophthalmic composition obtained favorable results with respect to the adsorption inhibition effect and the physical properties of the lens.

Claims (4)

(A) 0.006 to 0.1 g / 100 mL of chlorpheniramine maleate,
(B) 0.05 to 1.0 g / 100 mL of dipotassium glycyrrhizinate,
(C) 0.05 to 1.0 g / 100 mL sodium chondroitin sulfate,
(D) 0.2 to 1.5 g / 100 mL of one or two selected from sodium chloride and potassium chloride,
(E) containing 1.2 or 1.8 g / 100 mL of one or two species selected from boric acid and borax, does not contain quaternary cationic preservatives, parabens, chlorobutanol and sorbic acid, and has a pH of 6.6 to 7.3 Soft contact lens ophthalmic composition for enteric use. The method of claim 1,
An ophthalmic composition, wherein the soft contact lens is Lens IV of the soft contact lens classification by the FDA (Food and Drug Administration). 3. The method according to claim 1 or 2,
An ophthalmic composition, which is an eye drop for an enteric contact with a soft contact lens. 3. The method according to claim 1 or 2,
The compounding quantity of (A) component is 0.015-0.03g / 100mL, The compounding quantity of (B) component is 0.25-0.3g / 100mL, The compounding quantity of (C) component is 0.4-0.5g / 100mL, The compounding quantity is 0.3-0.5g / 100mL, and the compounding quantity of (E) component is 1.4-1.5g / 100mL, The ophthalmic composition characterized by the above-mentioned.