JP2009161456A - Ophthalmic composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an ophthalmic composition that relieves an irritating feeling at the time of instillation of glutathione and enhances compliance of a patient. <P>SOLUTION: The ophthalmic composition comprises a reduced glutathione and an irritation-relieving agent selected from among one or two or more terpenoid compounds selected from among l-menthol, dl-camphor, d-borneol, geraniol, cineole and linalool. Therefore, the ophthalmic composition containing glutathione can be instilled easily while hardly giving irritating feelings or itchy feelings at the time of instillation and enhances compliance of a patient. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an ophthalmic composition containing glutathione.

Glutathione is a peptidic thiol that exists universally from bacteria to humans, and plays a role as a major antioxidant in the cell and excretes toxins and the like outside the cell. Glutathione has a reduced form (GSH) and an oxidized form (glutathione disulfide, GSSG). In the present invention, unless otherwise noted, reduced glutathione is referred to as “glutathione”. Glutathione is abundant in eyes in the living body, particularly in the lens, and is said to be involved in maintaining tissue transparency. In ophthalmology, it is used for the treatment of early senile cataract and corneal disease, but has side effects such as eye irritation, pruritus, conjunctival hyperemia, and transient fog vision (15th revised Japanese Pharmacopoeia, C- 1187, Tokyo Yodogawa Shoten), improvement of patient compliance was desired.
JP-A-2-45420 Special table 2001-504132

  This invention is made | formed in view of the said situation, and it aims at providing the ophthalmic composition which eased the irritation | stimulation at the time of instillation of glutathione, and improved the patient's compliance.

  As a result of intensive studies, the present inventor can solve the above problems by blending one or more terpenoid compounds selected from 1-menthol, dl-camphor, d-borneol, geraniol, cineol, and linalool together with glutathione. The present invention has been completed.

That is, the present invention
<1> An ophthalmic composition comprising reduced glutathione and an irritation reducing agent.
<2> The ophthalmic composition according to <1>, wherein the stimulus relieving agent is one or more selected from l-menthol, dl-camphor, d-borneol, geraniol, cineol, and linalool.
<3> The ophthalmic composition according to <1> to <2>, containing one or more selected from boric acid, borate, and trometamol.
<4> Ophthalmology according to <1> to <3>, wherein the ophthalmic ophthalmic solution is an eye drop for wearing while wearing a soft contact lens, a disposable contact lens, an oxygen permeable hard contact lens, and a hard contact lens Composition.
I will provide a.

  According to the present invention, it is possible to provide an ophthalmic composition containing glutathione that has little irritation and pruritus during ophthalmic application, can be comfortably applied to an ophthalmic composition containing glutathione, and has high patient compliance. .

Hereinafter, the present invention will be described in more detail.
In the present invention, by adding an irritation reducing agent, preferably a specific terpenoid compound, to an ophthalmic composition containing glutathione, irritation and pruritus are alleviated and patient compliance is increased. Furthermore, in order to maintain the preservative efficacy of the composition, by blending one or more selected from boric acid, borate, and trometamol, the ophthalmic composition has a low irritation feeling while ensuring the preservative efficacy. Things are obtained. In addition, by using a preparation that can be instilled while wearing various contact lenses, the convenience is enhanced and the feeling of stimulation due to lens wearing is reduced, so that the sense of irritation is alleviated and the patient's compliance is further increased.

  The glutathione in the present invention refers to reduced glutathione, and the amount of the glutathione is not particularly limited. However, from the viewpoint of effectiveness and side effects, 0.01 to 4 g / 100 mL, preferably 0.04 to 2 g / 100 mL, more preferably 0.1 to 2 g / 100 mL, particularly preferably 0.5 to 1 g / 100 mL is desirable.

  Examples of the stimulant mitigating agent in the present invention include a terpenoid compound having a refreshing feeling, and more specifically, 1-menthol, dl-camphor, d-borneol, geraniol, cineol, linalool and the like. -Menthol, dl-camphor and d-borneol are preferred. These can be blended alone or in combination of two or more. In addition, the terpenoid compound may be compounded alone, or may be blended with essential oils such as mint oil, mint water, eucalyptus oil, bergamot oil containing these compounds.

  Although the compounding quantity of an irritation | stimulation relaxation agent is not restrict | limited in particular, 0.0005-0.1g / 100mL with respect to the whole composition, Preferably it is 0.001-0.05g / 100mL, More preferably, it is 0.001-0. It is desirable that the amount is 03 g / 100 mL, more preferably 0.002 to 0.02 g / 100 mL, and particularly preferably 0.003 to 0.01 g / 100 mL. Within this range, the stimulus alleviation effect is particularly good. In addition, when mix | blending in combination of 2 or more types, let the total amount be a compounding quantity.

  In the ophthalmic composition of the present invention, a compound selected from boric acid, borates (borax, etc.) and trometamol is preferably blended for the preservative effect of the composition. Particular preference is given to combining boric acid and / or borates and trometamol. These blending amounts are not particularly limited, but from the standpoint of antiseptic effect and osmotic pressure, 0.01 to 3 g / 100 mL, preferably 0.02 to 2 g / 100 mL, more preferably 0. It is desirable to set it as 05-2g / 100mL, More preferably, it is 0.1-1.5g / 100mL. In addition, when mix | blending in combination of 2 or more types, let the total amount be a compounding quantity.

  The ophthalmic composition in the present invention preferably contains no preservative selected from benzalkonium, benzethonium, chlorhexidine, polydronium, polyhexanide, and parabens from the viewpoint of reducing eye irritation.

  Various drugs can be blended in the ophthalmic composition of the present invention as long as the effects of the present invention are not impaired. The drug is not particularly limited, and more specifically, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, nafazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, neostigmine methyl sulfate, diphenhydramine hydrochloride, diphenhydramine, malein Chlorpheniramine acid, dipotassium glycyrrhizinate, epsilon-aminocaproic acid, allantoin, berberine chloride, berberine sulfate, sodium azulenesulfonate, zinc lactate, zinc sulfate, lysozyme chloride, pranoprofen, bromfenac sodium, cromoglycate sodium, Ketotifen fumarate, acitazanolast, amlexanox, ibudilast, pemirolast potassium, levocabastine hydrochloride, flavin adé Sodium dinucleotide, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, tocopherol acetate, potassium L-aspartate, magnesium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate Sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium, tropicamide, etc., and these drugs are ophthalmic preparations as long as the effects of the present invention are not impaired. Can be blended at an acceptable concentration.

  In addition to the ophthalmic composition of the present invention, additives such as buffering agents, tonicity agents, stabilizers, solubilizing agents, and viscosifying agents can be blended within a range that does not impair the effects of the present invention. . More specifically, pH adjusting agents and buffers such as phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, crystalline sodium phosphate, potassium dihydrogen phosphate, citric acid, sodium citrate, hydrochloric acid, sodium hydroxide, etc. Agents, sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, dry sodium carbonate, magnesium sulfate, glycerin, mannitol and other isotonic agents, ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid disodium (sodium edetate), etc. Stabilizer, dibutylhydroxytoluene (BHT), antioxidants such as ascorbic acid, propylene glycol, polyoxyethylene hydrogenated castor oil 60, polysorbate 80, solubilizing agents such as pluronic, methylcellulose, ethylcellulose, hydro Viscosity of Siethylcellulose, Hydroxypropylcellulose, Hydroxypropylmethylcellulose, Hydroxypropylethylcellulose, Carboxymethylcellulose, Polyvinyl alcohol, Polyvinylpyrrolidone, Hyaluronic acid, Sodium hyaluronate, Macrogol, Glucose, etc. Agents and the like.

  The pH of the composition of the present invention is not particularly limited, but is 3.0 to 9.0, more preferably 4.0 to 8.0, and still more preferably 5.0 to 7 from the viewpoint of irritation to mucous membranes. It is desirable to adjust to 5 (measurement condition: 20 ° C.).

  The osmotic pressure ratio of the composition of the present invention is not particularly limited, but it is 0.5 to 3.0, more preferably 0.8 to 2.0 from the viewpoint of irritation to mucous membranes and influence on physical properties of soft contact lenses. More preferably, it is desirable to adjust to 0.85 to 1.5.

  The viscosity of the composition of the present invention is not particularly limited, but is 0.8 to 50 mPa · s, more preferably 0.8 to 20 mPa · s, and still more preferably 0.8 from the standpoint of sustained effectiveness, blurring, and stickiness. It is desirable to adjust to 10 mPa · s (measurement conditions: 25 ° C., E-type viscometer).

  The composition of this invention can be manufactured according to the manufacturing method of a normal ophthalmic composition, and can perform heating, cooling, emulsification, high-pressure emulsification, sterilization, filtration etc. as needed.

  The composition of the present invention can be filled in both multi-dose containers and single-dose containers, and can also be provided in the form of tablets and dissolved solutions. Moreover, as a material of a container, although polyethylene, a polyethylene terephthalate, a polyethylene naphthalate, and a polypropylene are mentioned, it is not limited to these.

  The ophthalmic composition of the present invention is a preparation that is widely applied to the eye, such as eye drops, eye wash, eye drops for contact, contact mounting liquid, contact desorption liquid, contact lens disinfectant, contact lens care agent, and the like. Can do.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.

<Experimental example 1>
Ophthalmic compositions having compositions 1 to 7 shown in Table 1 were prepared by a conventional method, and the feeling of irritation at the time of instillation was evaluated.
<Method for evaluating irritation>
Ten professional panelists sensitive to the feeling of irritation evaluated the degree of blotting when instilled according to the following criteria, and the irritation rating score was determined from the average score. Composition 6 was evaluated with a soft contact lens worn.

Criterion 5: No stain at all 4: Slightly look at 3: Slightly look at 2: Smudge 1: Slightly look at

Grade ◎: Average score is 4.0 or more ○: Average score is 3.0 or more and less than 4.0 Δ: Average score is 2.0 or more and less than 3.0 ×: Average score is less than 2.0

<Experimental example 2>
The ophthalmic compositions of the present invention shown in Table 2 as Examples 1 to 7 were prepared, and the irritation sensation at the time of instillation was measured using various contact lenses (Menicon Z: 2 oxygen permeable type hardware, seed S-1: 3 software) , One Day Accuview: Disposable software 5) Evaluation was performed under wearing conditions. (Evaluation criteria and scores are the same as in Experimental Example 1)
(Example 1) 0.3 g of boric acid, 0.05 g of trometamol, and 0.05 g of sodium edetate are added to an appropriate amount of purified water, mixed and dissolved, and heated to 75 ° C. Retinol palmitate 10,000 I.V. U. A solution prepared by premixing 0.05 g of d-α-tocopherol acetate, 0.005 g of dibutylhydroxytoluene and 0.13 g of polyoxyethylene hydrogenated castor oil 60 at 50 ° C. is added to the previous solution and mixed and dissolved. After cooling to room temperature, a solution in which a terpenoid compound (1-menthol 0.005 g) is dissolved in 2.0 g of glutathione and 0.5 g of propylene glycol in advance is added and mixed and dissolved. The pH was adjusted to 7.0 with dilute hydrochloric acid or sodium hydroxide, and the volume was adjusted to 100 mL with purified water.

  According to Example 1, ophthalmic compositions shown in Table 2 were prepared.

Claims (4)

An ophthalmic composition comprising reduced glutathione and an irritation reducing agent. The ophthalmic composition according to claim 1, wherein the stimulant mitigating agent is one or more selected from l-menthol, dl-camphor, d-borneol, geraniol, cineol, and linalool. The ophthalmic composition according to claim 1, comprising one or more selected from boric acid, borate, and trometamol. The ophthalmic composition according to claim 1, wherein the ophthalmic composition is an eye drop for eye drops while wearing a soft contact lens, a disposable contact lens, an oxygen permeable hard contact lens, or a hard contact lens.