JP2000159659A - Artificial lachrymal fluid for ophthalmology - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare an artificial lachrymal fluid for ophthalmology, having excellent curing effect on dry eye by specifying both osmotic pressure and pH of the fluid through including metal ions which are included in a living body and comprise alkali metal ions as main ingredients and alkaline earth metal ions as auxiliary ingredients. SOLUTION: The objective artificial lachrymal fluid is prepared by including metal ions which are included in a living body and comprise (A) alkali metal ions as main ingredients and (B) alkaline earth metal ions as auxiliary ingredients so as for the osmotic pressure and pH value of the fluid to become respectively 220-295 OsmkgH2O (preferably 240-280 OsmkgH2O) and 6-8 (preferably 6.5-7.5). The ingredient A is e.g. Na+ or K+ and the ingredient B is e.g. Mg2+ or Ca2+. It is preferable that sodium chloride and potassium chloride are supply sources for Na+ and K+ respectively and that magnesium chloride and calcium chloride are supply sources for Mg2+ and Ca2+ respectively. The fluid may include Zn2+, caster oil or the like, if needed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an artificial ophthalmic tear suitable particularly for dry eye.

[0002] In the present specification, the osmotic pressure and the pH are values based on a measuring method when the following measuring instruments or equivalent measuring instruments are used.

Osmotic pressure: "Advanced osmometer 3W2"
(Advance) pH: "Castany LAB pH meter F-13" (Horiba, Ltd.)

[0004]

2. Description of the Related Art With the spread of information devices in recent years, the ratio of people who have faced a display device such as a CRT for a long time has been increasing. For this reason, the number of dry eye patients complaining of dryness on the surface of the eye is also increasing, and it is said that the number now accounts for about 20% of the population including potential patients.

[0005] The treatment of dry eye is a remedy such as water replenishment with isotonic artificial tears mainly composed of Na ⁺ and K ⁺ or suppression of water evaporation with viscous biopolymer eye drops such as chondroitin sulfate and hyaluronic acid. Is usually done. ("Clinical Ophthalmology, Vol. 51, No. 11, 1977 Special Issue" Yumkari, pp. 76-77, edited by Tsubota, "Diagnosis and Treatment of Ocular Surface-Dry Eye-" Medical Aoi Publishing, p. 16
4, p167, etc.) In addition, the dry eye caused by the wearing of the contact lens is almost completely recovered when the wearing of the lens is stopped. However, in such a case, it is necessary to continue life using eyeglasses for eyesight correction, and it is difficult to completely stop contact lenses in occupations that require contact lenses such as specific athletes and talents. It is.

Although not directly related to the invention of the present invention,
Prior art documents relating to dry eye treatment agents or artificial tears include the following.

JP-A-1-290623, "Eye drops for treating dry eye syndrome" JP-A-7-223966, "Ophthalmic artificial tears" JP-A-7-330604, "Therapeutic agent for dry eye" JP-A-7- No. 133967 "Therapeutic agent for dry eye" Japanese Patent Application Laid-Open No. Hei 9-136832 "A preventive / therapeutic agent for dry eye and diseases caused by dry eye" Japanese Patent Application Laid-Open No. Hei 10-218760 "A trace oil-added eye drop for dry eye treatment"

[0008]

However, as far as the present inventors know, there has not yet been put on the market any products which show an excellent improvement effect on dry eye.

In view of the above, it is an object of the present invention to provide an artificial tear having an excellent therapeutic effect on dry eye.

[0010]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have made intensive efforts for development and, during the course of the development, have rapidly supplied mineral ions required by eye surface tissues of dry eye patients. In addition, as a result of diligent efforts paying attention to the point of maintaining ion balance, the inventors came to an artificial tear having the following structure.

The artificial tear for ophthalmology of the present invention mainly contains an alkali metal ion as a biological ion, further contains an alkaline earth metal ion in an auxiliary manner, and has an osmotic pressure of 220 to 295 OsmkgH ₂ O. It is characterized by being prepared.

The above alkali metal ions are usually Na ⁺ and K ⁺ , and the alkaline earth metals are usually Mg ²⁺ and Ca
²⁺ .

It is desirable that Zn ²⁺ be contained as a minor auxiliary ion in addition to the alkali metal ion and the alkaline earth metal ion.

Furthermore, it is desirable that castor oil is dispersed and contained as an oil replenishing component.

[0015]

[Detailed Description of Means] Next, each component of the above means will be described in detail.

(1) The artificial tear for ophthalmology of the present invention has a high-level concept of containing a biological metal ion mainly composed of an alkali metal ion. And it further contains alkaline earth metal ions and has an osmotic pressure of 200 to 295 Osm.
kgH ₂ O (preferably 240~280 OsmkgH ₂ O), and, pH is 6-8 (preferably 6.5-7.5) and characteristic configuration that formed by dispersion so as to make.

Here, the alkali metal ions are usually Na ⁺ and K ⁺ , and the alkaline earth metal is usually Mg
²⁺ and Ca ²⁺ . As biometal ions, it is well known that these ions have a favorable effect on living cells.

The source of Na ⁺ and K ⁺ is not particularly limited as long as it does not adversely affect the living body and has high water solubility. Usually, their chlorides, ie, sodium chloride and potassium chloride, whose pH can be easily adjusted to 6 to 8 are used. In some cases, borates, phosphates, carbonates (normal salts, bicarbonates (bicarbonates, acid salts), carbonate hydroxide salts (basic salts), and sulfates, etc.) It is also possible to use in combination with or instead of chloride.

As described above, the source of Mg ²⁺ and Ca ²⁺ is not particularly limited as long as it does not adversely affect the living body and has high water solubility. Usually their chlorides, ie
Use magnesium chloride and calcium chloride. Of course,
Double salts such as magnesium potassium chloride and the like, and also bicarbonate, dihydrogen phosphate, sulfate and the like can be used in combination with or instead of the above chloride.

The reason for setting the osmotic pressure in the above range, that is, hypotonicity, is that in dry eye treatment, the role of hydration and the role of restoring the hypertonic eye surface due to excessive evaporation of tears to a normal state. Is strongly required. That is, if the osmotic pressure is too low, an unpleasant sensation tends to appear at the time of instillation, and if it is too high, a stimulating feeling tends to appear at the time of instillation.

It should be noted that the isotonic osmotic pressure is 27
0~310 OsmkgH ₂ O, preferably 280 to 300 Osm
Generally, it is kgH ₂ O.

When the biometal ion composition is Na ⁺ : 30.0 to 60.0 mM / L (preferably 40.0 mM / L)
K ⁺ : 10.0 to 40.0 mM / L (preferably 15 to 25 mM / L)
mM / L) Ca2 ⁺ : 1.0 to 5.0 mM / L (preferably 1.2 to 2.0 mM / L).
0 mM / L) Mg ²⁺ : 1.0 to 5.0 mM / L (1.5 to 3 mM / L) is preferable because a hypotonic type in the above range can be easily obtained.

Further, it is desirable that the present artificial tears contain Zn ²⁺ as a trace auxiliary component. This is because Zn ^{2+ is} also useful as a biological ion. As a Zn ²⁺ supply source, zinc chloride may be used, but zinc sulfate is more preferable. This is because it has an anti-inflammatory effect based on the local astringent action.

The content of Zn ²⁺ is 0.005 to 0.5.
mM / L (preferably 0.01 to 0.1 mM / L).

Further, it is desirable that the artificial tears further include castor oil dispersed and contained as an oil replenishing component, because the effect of treating dry eye is further increased.

Although vegetable oils other than castor oil can be expected to increase the effect of treating dry eye to some extent, castor oil is desirable from the viewpoint of compatibility with the ocular surface, especially irritation at the time of instillation.

The amount of the castor oil is usually 0.1 to 1
0 wt%, preferably 1-4 wt%. If the amount is too small, the effect of treating dry eye cannot be expected to increase, while if it is too large, a problem arises in dispersibility and the feeling of use becomes unfavorable.

Since castor oil cannot be dispersed in artificial tears as it is, it is usually emulsified and dispersed using a surfactant. The surfactant that can be used at this time is not particularly limited as long as it is nontoxic, but polyoxyethylene castor oil (HLB: 11 to 13) has a good dispersing effect on castor oil and is desirable from the viewpoint of maintaining clearness. The blending amount of polyoxyethylene castor oil with respect to 1 part by weight of castor oil is 1 to 3 parts by weight (preferably 1.5 to 5 parts by weight).
2.5 parts by weight).

Further, it is desirable to appropriately add boric acid and borax, which have a weak antibacterial and bactericidal effect and have a pH buffering action, so that the storage stability after opening the artificial tear fluid can be maintained to some extent.

The amount of the boric acid is usually 0.1 to 1.
0 wt%, preferably 0.3 to 0.7 wt%. The amount of borax per 1 part by weight of boric acid is １ ／.
0 to 1/5, preferably 1/15 to 1/7.

A non-toxic thickener is added to the artificial tear to increase the kinematic viscosity to 30.0 to 50.0 mm ² / s, preferably 35 to 45 mm ² / s. May be. When thickened, suppression of evaporation of tears can be expected. Here, the kinematic viscosity is a value measured at 20 ° C. using an “Ubbelohde viscometer” or an equivalent measuring instrument.

Examples of the thickener include synthetic water-soluble polymers such as 2-hydroxyethylcellulose, methylcellulose, polyvinyl alcohol and polyoxymethylene.
Thickening polysaccharides such as plant mucilage and plant gum can be used.

At this time, the amount of the thickening agent is appropriately determined depending on the viscosity of the ophthalmic solution. For example, 2-hydroxyethyl cellulose (hydroxyethoxyl group 3
(0-70% content), it is 0.3-0.6 wt%, preferably 0.4-0.5 wt%.

The artificial tears of the present invention are obtained by adding and mixing the above-mentioned components to sterilized purified water which is usually used for eye drops, and filling the resulting sterilized eye drops container. The filling amount of this ophthalmic container is about one week (about 3 to 5 cc) or single use (about 0.5 cc), so that a cytotoxic and strong bactericidal preservative (preservative) is used. No addition is possible.

[0035]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will be described below with reference to the drawings.

Examples 1 and 2 shown in Tables 1 and 2 respectively
After preparing artificial tears of the formula described above, those that had been subjected to aseptic filtration with a 0.22 μm filter were instilled into 20 eyes of 10 dry eye patients who developed various causes (6 times a day). 1-2 drops).

The comparative example was carried out similarly using a commercially available artificial tear having the following formulation.

Comparative Example: 0.74% of sodium chloride (126.6 as Na ⁺ )
mM / L) Potassium chloride 0.13% (17.45 as K ⁺ )
mM / L) Osmotic pressure: 280 OsmkgH ₂ O, pH: 7.0 And before administration and 2 weeks after the start of administration, symptoms were observed for the following items, and the degree of improvement was evaluated.

(1) Subjective symptoms: Interview (2) Schirmer test: Schirmer test paper (3, manufactured by Showa Kako Co., Ltd.)
A 5 x 5 mm filter paper (Whatman No. 41) is bent at the tip 5 mm, placed in the lower eyelid conjunctiva and placed on the lid margin, performed in a sitting position, and the blinks are free. After 5 minutes, measure the outside of the tear from the inflection point. (Normal value: 10 to 30 mm, abnormal value: 5
mm or less) (Naoki Aikawa et al. “Dictionary of Medicine” published by Nanzando, 19
(3) BUT (Break Up Time) measurement test: Fluorocene was instilled into the subject's eye, observed with cobalt blue, and the time (seconds) from eyelid opening to tear film destruction was measured five times. The average value was defined as BUT (tear layer breakage time). Here, the time until tear film destruction is the time until the preconialfilm that has spread to the cornea gradually becomes thinner as the eyelids open and a dry spot is observed. The normal value is 15 to 34 seconds, and the abnormal value is 10 seconds or less. (Refer to Nishi-Shin Mototsuji et al., "Ophthalmology Dictionary" Medical Aoi Publishing, 1991, p. 16) The results of the above observations are shown in Tables 3, 4, and 5.

It can be seen that each of the examples is superior to the comparative example in treating dry eye. In particular, Example 2 in which castor oil is dispersed and blended has a more remarkable dry eye treatment effect.

[0041]

[Table 1]

[0042]

[Table 2]

[0043]

[Table 3]

[0044]

[Table 4]

[0045]

[Table 5]

[0046]

According to the present invention, the ophthalmic artificial tear according to the present invention has an excellent dry eye treatment effect as supported by the above embodiments.

Particularly, when castor oil is dispersed and blended, the effect of treating dry eye is more remarkable.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Taihei Shibasaki 6-192 Shineicho, Toyoake-shi, Aichi F-term (reference) 4C076 AA12 BB24 CC10 DD22 DD24 DD29 EE53 4C086 AA01 AA02 GA17 HA02 HA04 HA21 HA24 MA03 MA05 MA17 NA14 ZA33

Claims (8)

[Claims] 1. An artificial ophthalmic tear containing a biometal ion mainly composed of an alkali metal ion, further comprising an alkaline earth metal ion as an auxiliary, having an osmotic pressure of 220 to 295 OsmkgH ₂ O and a pH of 6 An artificial ophthalmic tear fluid characterized by being prepared so as to be ~ 8. 2. The osmotic pressure is from 240 to 280 OsmkgH ₂ O.
The artificial tear for ophthalmology according to claim 1, wherein: 3. The artificial ophthalmic tear according to claim 1, wherein the alkali metal ions are Na ⁺ and K ⁺ , and the alkaline earth metals are Mg ²⁺ and Ca ^2+. liquid. 4. The ophthalmic artificial tear according to claim 3, wherein the metal ion composition further contains Zn ²⁺ as a minor auxiliary component. 5. The artificial ophthalmic tear according to claim 4, further comprising castor oil dispersed as an oil supplement component. 6. An ophthalmic artificial tear comprising a living metal ion mainly containing an alkali metal ion, wherein the metal ion composition is Na ⁺ : 30.0 to 60.0 mM / L,
K ⁺ : 10.0 to 40.0 mM / L, Ca ²⁺ : 1.0 to 5.
Ophthalmic artificial tears containing 0 mM / L, Mg ²⁺ : 1.0 to 5.0 mM / L, and prepared to have a pH of 6 to 8. 7. The biometal ion composition further comprises Zn
The ophthalmic artificial tear according to claim 6, characterized in that it contains ²⁺ : 0.1 to 2.0 mM / L. 8. The artificial ophthalmic tear according to claim 6, further comprising 0.5-10 wt% of castor oil dispersed therein.