KR101134340B1 - A eye-drop composition for preventing or treating ocular diseases - Google Patents

Abstract

PURPOSE: An ophthalmologic eye drop composition containing hyaluronic acid or salt thereof is provided to prevent or treat xerosis and cornea damage and to effectively suppress breeding of microorganism. CONSTITUTION: An ophthalmologic eye drop contains 0.15-0.2 wt% of hyaluronic acid or salt thereof, 0.25-0.55 mmol/L of magnesium ion, 50-80 mmol/L of sodium ion, 13-18 mmol/L of potassium ion, 60-75 mmol/L of chlorine ion, 0.8-8.5 mmol/L of amino caproic acid ion, 0.5-3.5 mmol/L of edetic acid ion, and 0.15-1.5 mmol/L of tetraborate ion. The composition further contains 0.5-5 mmol/L of phosphate ion.

Description

Eye drop composition for preventing or treating ophthalmic diseases

The present invention provides a composition for preventing or treating ophthalmic diseases that can be used for multiple uses, including hyaluronic acid or salts and ions thereof.

The cornea is a thin, transparent, blood vessel-free tissue with a thickness of about 1 mm, which is very important for vision, but is located at the front of the eye to prevent chemical invasion and biological invasion. The tear film is located on the epithelial layer of the cornea, which keeps the eyes wet at all times to prevent adhesion of the eyelids and conjunctiva, while maintaining the physiological state of the cornea or conjunctiva.

Since the cornea and conjunctiva are exposed to the outside, the cornea and the conjunctiva are easily damaged, and as a result, the corneal epithelial tissue is easily damaged by various external and endogenous factors, thereby causing a disorder. For example, disorders of the conjunctival epithelial tissue can be caused by external factors such as surgery, medication, trauma or contact lens wear, and also by endogenous diseases such as Sjögren's syndrome, Stevens-Johnson syndrome, and dry eye syndrome. Can be.

On the other hand, among the endogenous diseases that can cause corneal conjunctival epithelial disorders, dry eye syndrome is an ocular disease caused by chronic lack of sufficient lubrication and moisture in the eyes, and the amount and quality of tears that moisten the eyes are reduced or fluctuated. It refers to a complex of various symptoms caused by abnormalities of the tear layer, which can be caused by various causes, also known as dry keratoconjunctivitis. Dry eye syndrome occurs most often and disappears, but in some cases, eye irritation may cause pain and foreign body continuity. If not treated at the right time, corneal damage, ie corneal epithelial erosion, corneal epithelial disorder, corneal ulcer Or may cause vision loss.

To treat such keratoconjunctival epithelial disorders or dry eye, prior art used drugs such as emollients such as artificial tear formulations, topical steroids, topical retinoids (eg vitamin A), oral pilocarpine and topical cyclosporine. However, in general, palliative therapies may relieve some dry eye symptoms in a short period of time, but these products generally do not eliminate the physiological source of dry eye symptoms, It is necessary to administer it frequently. In addition, this limited efficacy of prior drug therapy generally prevents the drug from eliminating or reducing the underlying cause of dry eye, threatening the patient's overall eye health or poor patient compliance, as well as these factors. May cause side effects due to the combination of drugs.

In addition, the conventional compositions may contain eye preservatives and the like, and may cause eye damage. If such preservatives are not used, the compositions do not effectively inhibit the growth of microorganisms.

Accordingly, there is a need for the development of eye drop compositions that can effectively prevent or treat ophthalmic diseases such as keratoconjunctival epithelial disorders or dry eye, and at the same time effectively inhibit the generation of microorganisms and can be used for a long time.

KR 2008-0031195

It is an object of the present invention to provide a composition for preventing or treating ophthalmic diseases comprising hyaluronic acid or a salt thereof and a plurality of ions.

The present invention is a hyaluronic acid or a salt thereof having hydrophilic properties, the magnesium ions (Mg ^{2 +),} sodium ion (Na ^+), potassium ion (K ⁺⁾ and chloride ion (Cl ^-) eye drop composition for eye disease prevention or treatment include To provide.

The eye drop compositions aminocaproic acid ion _{(NH 2 (CH 2) 5} COO -), ede acid ion _{(C 10 H 14 N 2 O} 8 2 -), tetraborate ions _{(tetrab orate ion, B 4 O} 7 2- ), And may further include a phosphate ion or a mixture thereof. The phosphate ion may be an ion represented by the formula PO ₄ ^3- , HPO ₄ ^2-, or H ₂ PO ₄ ⁻ , and preferably HPO ₄ ^{2 −} .

Hyaluronic acid is glycosaminoglycogen and is a biocompatible substance that is mainly attached to collagen and elastic body to form cartilage tissue and is also present in epithelial and neural tissues. It is also a substance that makes joints strong and flexible, and has been tested with rheumatoid arthritis and osteoarthritis. In addition, the hyaluronic acid is widely distributed in the intercellular matrix in connective tissue to form a sticky, elastic solution under physiological conditions, thereby mechanically protecting and buffering tissues such as iris and retina, corneal cells, vascular endothelial cells, and epithelial cells. It is biocompatible as the main component of the extracellular matrix known to provide it.

Since the composition containing such hyaluronic acid is biocompatible and has an appropriate viscosity, the residence time after instillation can be long to maintain the wet state of the eye for a long time.

The compositions of the present invention 0.15 to hyaluronic acid or its salt of 0.2% by weight, 0.25 to 0.55mmol / L of magnesium ions, (Mg ^{2 +)} 50-80mmol / sodium ions for ^{L (Na +), 13-18mmol /} L Potassium ions (K ⁺ ), 60-75 mmol / L chlorine ions (Cl ⁻ ), aminocaproic acid ions (NH ₂ (CH ₂ ) ₅ COO ⁻ ), edetic acid ions (C ₁₀ H ₁₄ N ₂ O ₈ ^2- ), tetraborate ions (B ₄ O ₇ ^2- ) and phosphate ions (PO ₄ ^3- , The medium) comprising at least one or more ^- HPO ₄ ^2- or H ₂ PO _4.

Eye drop preventing or treating ophthalmic diseases comprising hyaluronic acid or a salt thereof of the present invention while preventing or treating dry eye and corneal damage by appropriately adjusting the type and content of various ions together with the hyaluronic acid or a salt thereof. At the same time, it is possible to effectively suppress the production of microorganisms such as microorganisms, and as a result, it can be used not only for single use but also for multiple use over a period of time.

The composition of the present invention can effectively inhibit the inhibition of bacteria such as Aspergillus niger, Candida albican, Staphylococcos aureus, Pseudomonas aeruginosa or Escherichia colis, and in particular, can effectively inhibit the reproduction of Staphylococcos aureus, Pseudomonas aeruginosa or Escherichia colis.

In addition, the composition of the present invention does not occur precipitation for a long time, has a suitable viscosity of 15-24 dl / g is not easily volatilized and can remain for a long time to effectively control the water supply and the ion concentration of the eye.

In addition, it satisfies both the pH 7.2-7.4, the osmotic pressure of 140-160mOsm / L and the intrinsic viscosity of 15-24dL / g, which are required for the eye drop composition, and can be comfortably applied when instilling the eye drop composition. Excellent physical properties.

The eye drop composition of the present invention may exhibit the physical properties of pH 7.2-7.4 required for eye drops without the use of strong acids or strong bases such as hydrochloric acid or sodium hydroxide, and can effectively prevent eye soreness when applied to the eye.

The composition of the present invention comprises 0.15 to 0.2% by weight of hyaluronic acid or a salt thereof, 0.25 to 0.55 mmol / L magnesium ion, 50-80 mmol / L sodium ion 13-18 mmol / L potassium ion, 60-75 mmol / L Chlorine ions, aminocaproic acid ions up to 8.5 mmol / L (NH ₂ (CH ₂ ) ₅ COO ⁻ ), edetic acid ions up to 3.5 mmol / L and tetraborate ions up to 1.5 mmol / L (B ₄₎ 0 ₇ ^2- ).

More preferably, the composition of the present invention is 0.15 to 0.2% by weight of hyaluronic acid or a salt thereof, 0.25 to 0.55 mmol / L magnesium ion, 50-80 mmol / L sodium ion 13-18 mmol / L potassium ion, 60- 75 mmol / L chlorine ion, 0.8-8.5 mmol / L aminocaproic acid ion, 0.5-3.5 mmol / L edetic acid ion and 0.15-1.5 mmol / L tetraborate ion, B ₄ O ₇ ^2- ) May be included.

Even more preferably, the composition of the present invention comprises 0.15 to 0.2% by weight of hyaluronic acid or a salt thereof, 0.25 to 0.55 mmol / L magnesium ion, 50-80 mmol / L sodium ion 13-18 mmol / L potassium ion, 60 -75 mmol / L chlorine ion, 0.8-8.5 mmol / L aminocaproic acid ion, 0.5-3.5 mmol / L edetic acid ion, 0.15-1.5 mmol / L tetraborate ion, B ₄ O ₇ ^{2 -} ) And 0.5-5 mmol / L of phosphate ions.

The above-described hyaluronic acid or a salt thereof and a composition containing the specific kind of ions in the amounts described above can effectively treat dry eye and corneal damage as well as effectively inhibit the reproduction of microorganisms and use them for multiple uses over a long period of time. It is particularly suitable for becoming.

In the composition of the present invention, the salt of hyaluronic acid is not particularly limited in kind, but may preferably be a sodium hyaluronate salt.

In addition, the weight average molecular weight of the hyaluronic acid or a salt thereof may be appropriately adjusted in a range capable of imparting an appropriate viscosity to the composition, but may preferably have a weight average molecular weight of 800,000 to 1,600,000.

The composition of the present invention can effectively treat a corneal epithelial disorder, dry eye syndrome or a wound occurring in the cornea which may occur in various causes.

For example, the compositions according to the invention may be caused by external factors such as surgery, medication, trauma or contact lens wear, or by endogenous diseases such as Sjögren's syndrome, Stevens-Johnson syndrome, or dry eye syndrome. It can be used as an adjuvant to prevent or treat epithelial tissue disorders.

The eye drop of the eye drop composition of the present invention can be appropriately adjusted according to the degree of symptoms, one to three drops once a day two to seven times a day, preferably 1 to 3 drops once a day It may be dispensed 3 to 6 times a day.

The present invention is a composition containing hyaluronic acid or salts and ions thereof can effectively treat dry eye and corneal wounds, and also can effectively suppress the growth of bacteria over a long period of time can be used for a period of time as well as disposable Suitable for multiple uses.

1 is a diagram showing divided areas of the right eye and the left eye of a subject in order to examine the degree of corneal staining.
2 is a diagram showing the satisfaction of the subjects after administration of the eye drop composition according to the present invention.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

In addition, the reagents and solvents mentioned below include sodium hyaluronate as LG Life Sciences-EP, magnesium chloride hydrate as large gold-USP, sodium chloride as Tomita Pharmaceutical-KP, potassium chloride as BMP, BULK Medicines Pharmacrutic-KP, sodium hydrogen phosphate Hydrate is purchased from Daejung Gold-USP, Sodium Citrate Hydrate, Hwawon Pharmaceutical-KP, Borax is Merck-KP, Aminocaproic Acid is Hwawon Pharmaceutical-KP, Sodium Edetate Hydrate is Samjeon Pure Chemical-KP. KP's product was used.

≪ Example 1 >

Sterile purified water 80mL weight average molecular weight of 1,000,000, the sodium hyaluronate, magnesium chloride hydrate in the _{(MgCl 2? 6H 2 O)} , sodium chloride (NaCl), potassium chloride (KCl), sodium hydrogen phosphate hydrate _{(Na 2 HPO 4? 12H 2} O) , Borax (Na ₂ B ₄ O ₇ -10H ₂ O), aminocaproic acid (C ₆ H ₁₃ NO ₂ ), sodium edetate hydrate (C ₁₀ H ₁₄ N ₂ Na ₂ O ₈ -2H ₂ O) Table 1 After stirring completely according to the content of Example 1 described in the following, sterile purified water was further added so that the total volume was 100 mL, and filtered through a 0.2 μm membrane filter to obtain an eye drop composition 1.

<Example 2>

Eyedropper composition 2 was obtained in the same manner as in Example 1, except that each substance was added as described in Example 2 in Table 1.

<Example 3>

Eyedropper composition 3 was obtained in the same manner as in Example 1, except that each substance was added as described in Example 3 in Table 1.

<Example 4>

Eye drop composition in the same manner as in Example 1 except that sodium hydrogen phosphate hydrate (Na ₂ HPO ₄ ˜12H ₂ O) was not used and each substance was added in the amount described in Example 4 of Table 1 below. 4 was obtained.

Example 5

The eye drop composition 5 was obtained in the same manner as in Example 1, except that each substance was added as described in Example 5 in Table 1.

Comparative Example

Comparative eye drop compositions were prepared as described below to include the same materials and concentrations as Bismed Eye Drops (DupamaConstruction).

Sodium hyaluronate, magnesium chloride hydrate (MgCl ₂ ~ 6H ₂ O), calcium chloride hydrate (CaCl ₂ ~ 2H ₂ 0), sodium chloride (NaCl), potassium chloride (KCl), sodium hydrogen phosphate with a weight average molecular weight of 1,000,000 in 80 mL of sterile purified water _{(Na 2 HPO 4? 12H 2} O), sodium citrate monohydrate _{(C 6 H 5 Na 3 O} 7? 2H 2 O) was completely dissolved with stirring according to the content of the comparative example shown in Table 1, and then the total volume so that the 100mL Sterile purified water was further added and filtered through a 0.2 μm membrane filter to obtain a comparative eye drop composition.

[Table 1]

Experimental Example 1

The eye drops composition 1 to 5 prepared in Examples 1 to 5 were stored for 6 months at room temperature conditions of 25 ± 2 ℃ and relative humidity 60 ± 5% and harsh conditions 40 ± 2 ℃ and relative humidity 75 ± 5% It was observed whether precipitation occurred in the compositions 1 to 5 and the results are shown in Table 2 below.

TABLE 2

As can be seen in Table 2, the eye drop composition according to Examples 1 to 5 did not occur precipitation for 6 months under severe conditions of high temperature and humidity as well as room temperature conditions. From this it was found that the eye drop composition of the present invention can maintain high stability for a long time.

Experimental Example 2

The pH, osmotic pressure and extreme viscosity of the eye drop compositions 1 to 5 prepared according to Examples 1 to 5 were measured and the results are shown in Table 3. Seven-meter (Mettle Toledo) was used as the pH-meter and Osmomat 030-D (Gonotec) was used for the osmotic pressure test. The ultimate viscosity was measured by the first method, the capillary viscometer method of Viscosity Test.

[Table 3]

As can be seen in Table 3, the eye drop compositions 1 to 5 of Examples 1 to 5 all satisfied the standard conditions of the eye drop composition, pH, osmotic pressure and intrinsic viscosity.

This shows that the eye drop composition of the present invention has suitable physical properties as eye drops.

On the other hand, in the case of the comparative example, the pH shows a basicity of 8.6, it was found that it is necessary to adjust the pH by adding an acidic material in order to adjust the appropriate pH.

Experimental Example 3

The eyedrop compositions 1 to 5 and the comparative eye drop compositions prepared according to Examples 1 to 5 were examined for inhibition of growth or growth of microorganisms through comparison of microbiological characteristics for a predetermined time.

Five kinds of test bacteria were tested. The five kinds of test bacteria include two kinds of fungi of Aspergillus niger (ATCC 16404), Candida albicans (ATCC 10231) and three kinds of bacteria of Staphylococcos aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 9027) and Escherichia colis (ATCC 8739). Used. The five kinds of test bacteria were inoculated into the eye drop compositions 1 to 5 so that the high concentration test group contained 10 ⁵ to 10 ⁶ bacteria per 1 mL, and the low concentration test group was inoculated to contain 10 ³ bacteria per mL. Store at 25 ° C. After 1, 2, 3, 6, and 7 days of inoculation, 1 ml of each sample is diluted to make about 100 cfu / mL, and 1 ml of diluted sample is inoculated onto the plate, and about 20-25 mL of predetermined medium (bacteria is TSA (Tryptic soybean) agar) medium and fungi were cultured with SDA (Sabour name dextrose agar) medium. Fungal inoculated plates were incubated at 20-25 ° C. for 5 days and bacteria inoculated plates were incubated at 30-35 ° C. for 3 days.

The number of bacteria expressed after the culture was visually confirmed by cfu / mL (cony (colony forming unit)), and the results are shown in Tables 4 to 8 below.

[Table 4]

TABLE 5

TABLE 6

TABLE 7

[Table 8]

TABLE 9

As can be seen in Tables 4 to 9, the eye drop compositions 1 to 5 prepared according to Examples 1 to 5 were reduced or almost constant during the 7 days after inoculation, whereas in the case of comparative eye drop compositions The population increased significantly. In the case of Pseudomonas aeruginosa cells, the number of bacteria increased more than 10 times from 1.9 ± 10 ⁶ to 6.8 ± 10 ⁷ in the high concentration test group, and the number of bacteria increased more than 10,000 times from 9.0 ± 10 ² to 8.4 ± 10 ⁶ in the low concentration test group. .

From this, the eye drop composition of the present invention can be effectively inhibited the growth of microorganisms for a certain period of time can be prevented from being contaminated with bacteria for a long time, it can be seen that it can be used for multi-use as well as disposable.

Experimental Example 4

Eye drop test for 20 normal (10 males, 10 females) of the composition of the comparative example prepared in accordance with the eye drops composition 1 and 2 and hydrochloric acid prepared according to Examples 1 and 2 and pH 7.3 of the eye drop reference conditions Eye drops, sore, foreign body, etc.) to determine the score according to the score criteria and the results are shown in Table 10 to Table 12.

TABLE 10

Eye drops

As can be seen in Table 10, in the case of the eye drops composition 1 and 2 of Examples 1 and 2, 90% or more in both sexes is easy and convenient to give three or more points, while in the case of comparative eye drops composition 30 Eye drops were not good because more than% scored 2 points or less.

From this, it was found that the eye drop composition of the present invention can be comfortably instilled and has excellent eye drop.

TABLE 11

soreness

As can be seen in Table 11, in the case of the eye drops composition 1 and 2 of Examples 1 and 2, more than 90% of both men and women give a score of at least 3 points, while the eye drops almost no eye drops, In both cases, more than 40% of both men and women were given a score of 2 or less, indicating a bitter phenomenon.

From this, it can be seen that the composition of the present invention is a composition having excellent physical properties without bitter phenomenon.

TABLE 12

Foreign body

As can be seen in Table 12, in the case of the eye drops composition 1 and 2 of Examples 1 and 2 100% of both men and women gave a score of 3 or more, there was no foreign object at all, but in the composition of the comparative example 10% or less 2 points or less By giving a score of it was found that there is a foreign object.

From this, it can be seen that the composition of the present invention is a composition having excellent physical properties that do not feel any foreign body when instilled in the eye.

Since the composition of the present invention contains the etate ions to adjust the pH to a range of 7.2 to 7.4, which is a reference pH, it can be seen that the composition is excellent in eyedrops when the eye is instilled in the eye and there is no soreness and foreign body.

Experimental Example 5 Evaluation of Dry Eye Relief

The eye drop composition 1 prepared according to Example 1 was administered to 14 males and 39 females with mild to moderate dry eye symptoms for 4 weeks to examine the therapeutic effect of the eye drop composition of the present invention.

One. Subjects  Eye condition assessment

Before administration of the eye drop composition of the present invention, the eye condition of the subjects was evaluated as follows.

(1) tear film break time measurement

The tear break up time (TBUT) of the subjects was measured by the following method.

The subject's head was supported by the headrest and the sitting body was taken. The slit lamp microscope was set at 10x magnification and the illumination and microscope were positioned at an angle of 60 degrees. The slit lamp was adjusted to 3 mm at maximum illumination and tear film break time was observed using a cobalt filter.

5 μl of 2% sodium fluorescein (NaFI) containing no preservative was applied to the subject's eyes using an Eppendorf pipette. Immediately after instillation, the subject's head was placed on the headrest of the slit lamp apparatus, and the subject was blinked three times, and then stared at the front without blinking.

The tear film located on the subject's cornea was monitored with a slit lamp microscope to measure the time from the last blink of the eye to the appearance of one or more black spots on the tear film.

It was measured twice for each eye and the average is shown in Table 13 below.

Table 13 Tears breakdown time of subjects

(2) tear measurement

The tear amount of the subjects was measured as follows using the Schirmer test.

The filter paper was placed under the eyelids for 5 minutes and then the length of the paper wet by tears was measured and the results are shown in Table 14 below.

Table 14: Tears of Subjects according to Schirmer Test

(3) Evaluation of symptoms according to dry eye syndrome

The degree of burning, foreign body sensation, itching, redness, eye pain, photophobia, and blurred vision during dry eye symptoms No symptoms) to 5 (very severe) to give a score, the average value was obtained and the values are shown in Table 15 below.

[Table 15] Dry Eye Symptom Evaluation

(4) corneal wound evaluation

In order to evaluate the degree of corneal wounds of the subjects, corneal staining was performed as follows to measure corneal staining.

The head of the subject was supported by the headrest and the sitting position was taken. The slit lamp microscope was set at 10x magnification and the illumination and microscope were positioned at an angle of 60 degrees. The slit lamp was adjusted to 3 mm at maximum illumination and tear film break time was performed through a cobalt filter.

5 μl of 2% sodium fluorescein (NaFI) containing no preservative was applied to the subject's eyes using an Eppendorf pipette. Immediately after instillation, the subject's head was placed on the headrest of the slit lamp apparatus.

After 5 minutes of instillation with NaFI, the corneas of the left and right eyes, as shown in FIG. 1, are divided into five regions, such as C (central), T (Temporal), N (nasal), S (superior), and I (inferior). Divided according to the degree of dyeing according to the following Table 16 for each part divided by 0 (not dyed) to 3 (strongly dyed) points and the average value for each part is shown in Table 17 below.

TABLE 16

[Table 17] Evaluation of Corneal Staining

(5) Evaluation of previously used eye drops

In order to evaluate the satisfaction with the eye drops that have been used individually by the subjects, the following questions were given a score from 0 to 9 points from very negative to very positive, and then the averages were obtained. It was like

[Table 18] Evaluation of Satisfaction with Eye Drops

2. Evaluation of the effect of eye drops on dry eye

The eye drop composition prepared in Example 1 was administered to the subjects to confirm that various symptoms of dry eye symptoms were improved.

The composition of Example 1 was administered to the subjects in a 1-2 drop dose four times a day for 4 weeks, and at the beginning of the experiment, at 1 week after administration and 4 weeks after administration, tear film break time, eyes We measured the volume, dry eye symptom, corneal wound and satisfaction with eye drops. Evaluation of tear film break time, tear amount measurement, dry eye symptoms, corneal wound degree and eye drops satisfaction was performed in the same manner as described in section 1. The results are shown in Table 19 to Table 23 .

In addition, FIG. 2 shows the proportion of people who answered that they did not feel dry eye symptoms, burning sensation, foreign body sensation, itching, eye pain, glare and dimness in the whole subject. The ratio was tested for significance at the p-value level described in FIG. 2 using a generalized estimating equation.

TABLE 19 Tear Film Break Time of Subjects After Administration of Composition of Example 1

The tear film break time in Table 19 was subjected to a significance test at the p value level described in Table 19 above using a repeat measurement assay.

TABLE 20 Tears of Subjects Following Administration of Composition of Example 1

In Table 20, the tear amount was performed at the p-value level described in Table 20 above using a repeated measurement assay.

TABLE 21 Assessment of Dry Eye Symptoms After Administration of the Composition of Example 1

The scores set by the subjects in Table 21 were subjected to a significance test at the p-value levels described in Table 21 using repeated measures analysis.

Table 22.Evaluation of Corneal Staining after Administration of the Composition of Example 1

In Table 22, corneal staining was performed at the p-value level shown in Table 22 using a repeated measurement assay.

Table 23. Satisfaction assessment after administration of the composition of Example 1

The scores set by the subjects in Table 23 were subjected to a significance test at the p-value levels described in Table 23 using repeated measures analysis.

As can be seen in Table 19 to Table 23, the tear film break time and tear amount increased when the composition of Example 1 was administered, burning sensation, foreign body feeling, itching, hyperemia, eye pain, glare and severity in dry eye These symptoms were markedly improved and corneal staining was significantly reduced, indicating that corneal wounds were markedly improved. In addition, the use of eye drops significantly improved the swiftness of action, sustained effect, and improvement of dry eye syndrome, and the frequency of use of eye drops was significantly reduced. In particular, the administration of the composition of the embodiments of the present invention only for one week showed the therapeutic effect for the dry eye as described above was found to exhibit a fairly rapid effect.

From the experimental examples, it was found that the mucosal agent compositions of the present invention can effectively treat dry eye syndrome, and can be used for multiple times by inhibiting the growth and growth of microorganisms for a long time.

Claims (13)

0.15 to 0.2 wt% hyaluronic acid or a salt thereof;
0.25 to 0.55 mmol / L magnesium ions;
50-80 mmol / L sodium ion;
13-18 mmol / L potassium ion;
60-75 mmol / L chlorine ion;
0.8-8.5 mmol / L aminocaproic acid ions;
0.5-3.5 mmol / L of edetic acid ion; And
0.15-1.5 mmol / L tetraborate ion
Eyedrop composition for preventing or treating dry eye syndrome comprising a. delete delete delete According to claim 1, wherein the composition further comprises 0.5-5mmol / L of phosphate ions eye drops for preventing or treating dry eye composition. The eye drop composition according to claim 1, wherein the hyaluronic acid salt is sodium hyaluronate. According to claim 1, wherein the hyaluronic acid or a salt thereof is a weight average molecular weight of 800,000 to 1,600,000 eye dryness prevention or treatment eye drop composition for. delete delete According to claim 1, wherein the composition is used as an artificial tear eyedrop composition for preventing or treating dry eye. The eye drop composition according to claim 1, wherein the composition is multi-use. 0.15 to 0.2% by weight of hyaluronic acid or its sodium salt;
0.25 to 0.55 mmol / L magnesium ions;
50-80 mmol / L sodium ion;
13-18 mmol / L potassium ion;
60-75 mmol / L chlorine ion;
0.8-8.5 mmol / L aminocaproic acid ions;
0.5-3.5 mmol / L of edetic acid ion;
0.15-1.5 mmol / L tetraborate ion; And
An eye drop composition for preventing or treating dry eye syndrome containing 0.5-5 mmol / L of phosphate ions. delete

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