JPH10109934A - Agents for inflammatory eye diseases - Google Patents

Abstract

(57) [Problem] To provide an agent for inflammatory eye diseases which is immediate and shows high anti-inflammatory effect. SOLUTION: The agent for inflammatory eye diseases comprising vitamin E and squalane. In particular, the content of vitamin E is more than 0.01% by weight and less than 99.99% by weight,
Squalane content exceeds 0.01% by weight and 99.99%
Less than 99% by weight, more preferably more than 0.05% by weight and less than 99.95% by weight, more preferably more than 0.05% by weight and less than 99.95% by weight, more preferably less than 99% by weight Contains 30% by weight of vitamin E
The agent for inflammatory eye diseases, wherein the content of squalane is more than 30% by weight and less than 70% by weight.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an agent for inflammatory eye diseases.

[0002]

2. Description of the Related Art Conventionally, in the treatment of inflammatory eye diseases, steroid drugs, nonsteroid drugs, antiallergic drugs,
Alternatively, treatment with eye drops or eye ointments containing an astringent is the mainstream. However, these agents for eye diseases have problems such that it takes a certain amount of time for the effect to appear, and the effect on itching is weak. In addition, steroids may cause side effects such as enhanced susceptibility to infection, rebound phenomenon and systemic side effects. Also, non-steroids can cause contact allergies. In addition, astringents may be accompanied by irritability, pruritus, eyelid redness and swelling. Therefore, development of a therapeutic agent that is immediate and safe for inflammatory eye diseases is desired. On the other hand, there has been proposed an ophthalmic agent containing vitamin E as an antioxidant (Japanese Patent Application Laid-Open No. 62-106018).
However, there has been no proposal on the application of vitamin E as an anti-inflammatory agent for eye diseases.

[0003]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide an agent for inflammatory eye diseases which has an immediate effect and a high anti-inflammatory effect.

[0004]

Means for Solving the Problems The agent for inflammatory eye diseases of the present invention is characterized by containing vitamin E and squalane.

[0005] The above-mentioned vitamin E refers to tocopherol (vitamin E) and derivatives thereof. Examples of those listed in the Japanese Pharmacopoeia include dl-α-tocopherol, tocopherol acetate (vitamin E acetate), and succinic acid. Acid tocopherol (vitamin E succinate) and the like. Other than those listed in the Japanese Pharmacopoeia, for example, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, tocopherol nicotinate (vitamin E nicotinate), tocopherol phosphate (vitamin E phosphate), Examples include, but are not limited to, natural vitamin E and the like, and include esters of tocopherol with monosaccharides and polysaccharides and water-soluble vitamin E.

The above-mentioned squalane is used to reduce squalene which is an unsaturated hydrocarbon present in deep-sea fish, particularly shark liver oil or vegetable oil, for example, olive oil, rice bran oil, wheat germ oil, sesame oil, and cottonseed oil. Is a saturated hydrocarbon. Further, a synthetic squalane obtained by using geranylacetone and an acetylene compound as raw materials is also included.

Vitamin E in the inflammatory eye disease preparation of the present invention
When the content is low, the effect of suppressing inflammation is not sufficient, and when it is large, the effect of suppressing inflammation does not significantly increase according to the content, and depending on the formulation, it becomes difficult to maintain the dosage form Therefore, the content is preferably more than 0.01% by weight and less than 99.99% by weight, more preferably 0.05 to 50% by weight.

[0008] When the content of squalane in the agent for inflammatory eye diseases of the present invention decreases, the effect of suppressing inflammation becomes insufficient, and even when the content of squalane increases, the effect of suppressing inflammation significantly increases depending on the content. However, depending on the formulation, it may be difficult to maintain the dosage form. Therefore, the content is preferably more than 0.01% by weight and less than 99.99% by weight, more preferably 0.05 to 50% by weight.

As the combination of the above-mentioned contents of vitamin E and squalane in an agent for inflammatory eye diseases, the content of vitamin E is preferably more than 0.01% by weight and 99.
Less than 99% by weight, squalane content is 0.01% by weight
More than 99.99% by weight, more preferably
When the content of vitamin E exceeds 0.05% by weight and 99.95
% By weight, the content of squalane is more than 0.05% by weight and less than 99.95% by weight, more preferably the content of vitamin E is more than 30% by weight and less than 70% by weight, and the content of squalane is More than 30% by weight and less than 70% by weight.

[0010] The dosage form of the agent for inflammatory eye diseases of the present invention is not particularly limited, and examples thereof include eye drops and eye ointments, such as liquid, paste, cream, jelly, It is a gel and an emulsion.

As the base of the above-mentioned dosage form, any pharmaceutically acceptable base may be used, and conventionally known bases such as a liquid preparation and an ophthalmic ointment may be used. For example, sodium alginate, gelatin , Corn starch, tragacanth gum, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, xanthan gum, carrageenan, mannan, agarose, polyvinyl alcohol, sodium polyacrylate, methoxyethylene
Polymers such as maleic anhydride copolymer, polyvinyl ether and polyvinyl pyrrolidone; beeswax, olive oil,
Fats and oils such as cocoa oil, sesame oil, soybean oil, camellia oil, peanut oil, beef oil, pork oil, chicken oil, lanolin; white petrolatum, yellow petrolatum; paraffin; hydrocarbon gels (for example, trade names Plastibase, Bristol-Myers Higher fatty acids such as stearic acid; higher alcohols such as cetyl alcohol, octyldodecanol, and stearyl alcohol; polyethylene glycol (for example, Macrogol 400, Macrogol 4)
Glycerin monostearate; polyoxyethylene cetyl ether; self-emulsifying propylene glycol monostearate; triethanolamine; monooleic acid ester; glyceride stearate; water, physiological saline, phosphate buffer and the like. However, the present invention is not limited to these.

Further, if necessary, polysorbate 8
0, surfactants such as polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, and lecithin; solubilizers such as polyvinylpyrrolidone; inorganic fillers such as kaolin, bentonite, zinc oxide, and titanium oxide; methyl paraoxybenzoate; Stabilizers such as propyl paraoxybenzoate;
Anti-aging agents; pH regulators; humectants such as glycerin and propylene glycol; preservatives such as benzalkonium chloride, benzethonium chloride, citric acid and its sodium salts, paraoxybenzoic acids, boric acid, borax, camphor; xanthan gum; Viscosity such as sodium chondroitin sulfate, liquid paraffin, glycerin, macrogol, polyvinylpyrrolidone, and a thickening agent; and the like may be added.

The amount of the inflammatory eye disease agent of the present invention is 1
1 to 4 times a day, 1 to 2 drops (about 50
５００500 μl), and 50 to 500 mg for an ointment.

The diseases to be treated by the agent for inflammatory eye diseases of the present invention include, for example, conjunctivitis, blepharitis, keratitis, superficial keratitis, spring catarrhal, scleritis, episcleritis, anterior segment Examples include, but are not limited to, uveitis, iritis, iridocyclitis, ocular trauma and subsequent postoperative inflammation.

[0015]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Examples of the present invention and comparative examples will be described. (Examples 1 to 4 and Comparative Examples 1 to 4) Tocopherol acetate (manufactured by BASF), squalane (manufactured by Maruha), azulene (manufactured by Wako Pure Chemical Industries) in a predetermined amount (% by weight) shown in Table 1,
Indomethacin (Sigma), Ketotifen fumarate (Sigma), Hydrocortisone acetate (Sigma)
And Plastibase (manufactured by Bristol-Myers Squibb) was supplied to a mortar and kneaded until the whole became uniform to obtain an eye ointment.

[0016]

[Table 1]

(Examples 5 to 11) A prescribed amount (g) of tocopherol acetate (manufactured by BASF) and squalane (manufactured by Maruha) shown in Table 2 in a formulation per 100 ml were mixed with polyoxyethylene hydrogenated castor oil 60 ( Nikko Chemicals, Polysorbate 80 (Nikko Chemicals) and polyvinylpyrrolidone K30 (PVP-40, Sigma) were added to and dissolved in purified water. Next, an appropriate amount of sodium hydroxide and dilute hydrochloric acid were added to adjust the pH to 6.5 to obtain an ophthalmic solution.

[0018]

[Table 2]

(Comparative Examples 5 to 8) A predetermined amount (g) of azulene (manufactured by Wako Pure Chemical Industries, Ltd.), indomethacin (manufactured by Sigma), and ketotifen fumarate (manufactured by Sigma) are shown in Table 3. And hydrocortisone acetate (manufactured by Sigma) were added to purified water in which polyoxyethylene hydrogenated castor oil 60 (manufactured by Nikko Chemicals) was dissolved, and mixed. Next, an appropriate amount of sodium hydroxide and dilute hydrochloric acid were added to adjust the pH to 6.5 to obtain an ophthalmic solution.

[0020]

[Table 3]

The following tests were carried out on the agents for inflammatory eye diseases obtained in Examples 1 to 7 and Comparative Examples 1 to 8. In the test, six rabbits were used in each group, and the obtained results are average values.

[Test Example] Effect on rabbit eye mucosal irritation Eye ointments obtained in the above Examples and Comparative Examples were placed in the membrane of the left eye of male Japanese white rabbits weighing 2.5 to 3.0 kg. 0.05 g of the preparation or 0.1 ml of ophthalmic solution was applied. 3
One minute later, the lower eyelid is pulled, and 2 (W / V)%
0.5 ml of saline solution containing sodium lauryl sulfate
Was closed after application, and lightly massaged for 15 seconds to irritate the ocular mucosa.

At 1, 3, 6, and 24 hours after the stimulation, Draize (Drugs and Cosmet)
ics, 46, 1959), mucosal redness (0-3), conjunctival edema (0-4), secretion (0-3)
3) was scored, and the irritation was evaluated.

As a control, the same operation as described above was carried out except that each ointment base or ophthalmic solution base was applied instead of the above-mentioned inflammatory eye disease preparation, and the evaluation was performed as above. did.

Using the obtained evaluation values as the average value of the drug-applied group as (B) and the average value of the control group as (C), the inhibition rate of each inflammatory eye disease agent was calculated by the following formula. A) (%) was determined and is shown in Tables 1 to 3. (A) (%) = [{(C)-(B)} / (C)] × 10
0

From the results shown in Tables 1 to 3, the agents for inflammatory eye diseases according to the present invention include steroids (hydrocortisone acetate), non-steroids (indomethacin), antiallergic agents (ketotifen fumarate) or astringents (azulene). Compared to an agent for eye diseases containing as a main component, an immediate and strong inflammation inhibitory action was observed, indicating that the preparation is effective for inflammatory eye diseases.

[0027]

As described above, the composition for inflammatory eye diseases according to claims 1 to 4 of the present invention contains squalane in addition to vitamin E. The agent has a quick-acting and strong anti-inflammatory effect as compared with an agent for an ophthalmic disease mainly containing a steroid, a non-steroid, an antiallergic agent or an astringent. Therefore, the agent for inflammatory eye diseases of the present invention has a high clinical effect on inflammatory eye diseases.

Claims (4)

[Claims] 1. An inflammatory eye disease agent comprising vitamin E and squalane. 2. The composition for inflammatory eye diseases has a vitamin E content of more than 0.01% by weight and less than 99.99% by weight, and a squalane content of more than 0.01% by weight and 99.99% by weight. 2. The agent for inflammatory eye diseases according to claim 1, which is less than the above. 3. The composition for inflammatory eye diseases has a vitamin E content of more than 0.05% by weight and less than 99.95% by weight, and a squalane content of more than 0.05% by weight and 99.95% by weight. 2. The agent for inflammatory eye diseases according to claim 1, which is less than the above. 4. The inflammatory eye disease agent according to claim 1, wherein the content of vitamin E is more than 30% by weight and less than 70% by weight, and the content of squalane is more than 30% by weight and less than 70% by weight.
The agent for inflammatory eye disease according to the above.