JP2003342166A - Pharmaceutical preparation for intraocular disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pharmaceutical preparation for intraocular diseases to be infused into the vitreous cavity for the treatment and prevention of intraocular diseases after vitrectomy operation and keeping the drug effect over a long period in the eye. <P>SOLUTION: A pharmaceutical preparation for intraocular diseases containing an aqueous medicine, especially a medicine containing an antibiotic substance is further incorporated with a viscoelastic material, preferably sodium hyaluronate to increase the viscosity of the preparation. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to treatment of intraocular diseases in the field of ophthalmology (medical treatment), particularly infectious intraocular diseases such as bacterial endophthalmitis (intraocular infection), or traumatic diseases. In order to prevent the onset of infectious intraocular disease after surgery in ophthalmic surgery (surgical treatment) for the purpose of closing perforated wounds and removing foreign objects in the eye to treat diseases such as endophthalmitis, The present invention relates to a preparation for intraocular disease which is injected into the vitreous cavity (posterior chamber) in a vitreous-free eye that has undergone surgery to remove the body.

[0002]

2. Description of the Related Art Generally, drugs such as antibiotics (antibacterial agents) are not directly or locally administered to the affected area but are orally or parenterally administered into the blood (systemic administration).
In many cases, it is carried into the affected area through a blood vessel.

However, nerve tissues such as the eyes and the brain have a defense function to prevent the entry of substances contained in blood. As a defense system that fulfills this defense function, the brain is equipped with a blood brain barrier, while the eye has a blood brain barrier equivalent to this.
d retinal barrier). Therefore, it is difficult for the drug to be carried into the eye from the blood vessel, and it is difficult for the systemically administered anti-infective agent to migrate. From this, in particular, the vitreous cavity has become a clinically extremely difficult site for drug treatment.

Therefore, when antibiotics for the treatment or prevention of infectious intraocular diseases such as bacterial endophthalmitis are systemically administered, the intraocular effects of the antibiotics have been unsatisfactory for a long time. The problem is that there are many cases in which significant visual impairment remains.

Therefore, in recent years, with the progress of vitreous surgery,
A method for treating endophthalmitis is performed, in which an operation for removing the vitreous is performed, and at the time, an intraocular perfusion solution mixed with an antibiotic is injected.

However, although this treatment method has slightly improved the treatment result of endophthalmitis, the satisfactory result has not been obtained yet.

In the current endophthalmitis surgery which is generally performed, first, the crystalline lens and the vitreous body are excised and sucked. As a result, as shown in FIG. 1B, the eyeball becomes an eyeball in a state where the inside of the eye cavity (anterior chamber and vitreous cavity) is entirely replaced with aqueous humor and intraocular perfusate. Next, an antibiotic is injected into the eyeball from which the vitreous body has been removed (hereinafter referred to as "vitreous-free eye").

[0008]

However, as in the above-mentioned conventional method, when an antibiotic is injected alone into the avitreous eye, it is clinically or experimentally observed that the effective concentration falls below about one and a half days. Became clear. That is, it was impossible to sustain the antibacterial action by simply injecting an antibiotic into the eye after the vitrectomy operation.

The reason for this is that, in the non-vitreous eye, the concentration of antibiotics in the vitreous cavity sharply decreases due to purification (clearance) in the eye by producing and discharging aqueous humor.

Under normal conditions, aqueous humor is always produced from the ciliary body at a constant rate and is discharged from the anterior segment of the eye. The flow of aqueous humor (intraocular fluid flow) produced by the ciliary body is the normal eyeball (hereinafter referred to as the “vitreous eye”) before the lens / vitrectomy surgery and the non-vitreous eye (lens lens).・ It is very different from (eyeball after vitrectomy). In the vitreous eye, since the gel-like vitreous body whose surface is covered with the membrane tissue occupies most of the posterior segment of the eye, as shown in FIG.
Most of the aqueous humor produced by the ciliary body is discharged from the anterior segment of the eye without moving to the vitreous cavity.

On the other hand, in the non-vitreous eye, the aqueous humor produced in the ciliary body moves to the vitreous cavity and is discharged to the anterior segment as shown in FIG. 1 (b). The following three types are conceivable as the intraocular fluid flow at that time. Piston flow,
Bypass flow, fully mixed type. In the vitreous eye, it seems that all types of ,, and are complicatedly mixed (since the intraocular circulation of aqueous humor is greatly affected by the position and movement of the eyeball, head, and body, it constantly fluctuates, ,,, details about each of are unknown).

Due to the flow of the aqueous humor described above, in the non-vitreous eye, unlike the case of the vitreous eye (normal eyeball), the amount of aqueous humor in the vitreous cavity is zero immediately after the operation, but Is gradually filled with aqueous humor. As a result, the antibiotic injected into the vitreous cavity gradually elutes in the aqueous humor and its concentration decreases. The amount of aqueous humor produced by humans is about 2.5 μl / min,
The intraocular volume is 5.5 to 6 ml, and the daily production of aqueous humor is 60% of the intraocular volume. Therefore, the production, discharge, and circulation of aqueous humor have a great influence on the intraocular environment. Therefore,
In the vitreous eye, the concentration of antibiotics in the vitreous cavity drops sharply. This has been confirmed clinically. For example, when an antibiotic alone is injected into the vitreous cavity so that the intraocular concentration is 600 mg / dL, immediately after the operation,
As shown in FIG. 2 (a), a sufficient amount of the antibiotic is dispersed in the eye, but after 2 days from the operation, the antibiotic almost disappears as shown in FIG. 2 (b). Concentration of substance 3
less than mg / dL), below the effective concentration. Therefore, the time required to maintain the concentration of the antibiotic above the effective concentration is short, and the antibacterial effect is small.

[0013] A long-acting formulation prepared by mixing a viscous substance with an aqueous solution of a drug such as an antibiotic has been extensively studied as an eye drop to be externally administered to the surface of the cornea (see, for example, Japanese Patent Laid-Open Publication No. Sho. 62-215518, JP-A-3
-133925, JP-A-7-10776,
Japanese Patent Laid-Open No. 11-130697, Special Table 2000-50
4685 gazette, special table 2001-521885 gazette).

However, no attempt has been made to improve the sustainability of the drug effect in the preparation for intraocular disease which is continuously injected into the vitreous cavity of the vitreous-free eye, which is constantly diluted with aqueous humor.

The present invention has been made in view of the above-mentioned conventional problems, and an object thereof is to perform an operation for removing the vitreous body and then inject it into the vitreous cavity in order to treat or prevent intraocular disease. It is an object of the present invention to provide a preparation for intraocular disease, which is capable of sustaining the intraocular drug effect for a long period of time.

[0016]

In view of the above-mentioned conventional problems, the inventors of the present invention have more efficiently achieved the effect of an aqueous drug by the operation of injecting the intraocular disease preparation into the vitreous cavity after the vitreous removal operation. In order to exert the effect, the method of leaving the aqueous drug in the vitreous cavity for as long as possible was examined. As a result, by injecting a mixture of a viscoelastic substance as a base material and an aqueous drug such as an aqueous solution of an antibiotic into the vitreous cavity as a drug for intraocular disease, the drug effect in the eye can be prolonged. They have found that they can be maintained for a period of time and have completed the present invention.

In order to solve the above-mentioned problems, the preparation for intraocular disease according to the present invention is for treating or preventing intraocular disease after performing surgery for removing the vitreous on the eye of a vertebrate. In a formulation for intraocular diseases which is injected into the vitreous cavity, it is characterized in that it contains an aqueous drug and a viscoelastic substance for improving the viscosity.

According to the above construction, by mixing the aqueous drug with the viscoelastic substance, the rate of dilution of the aqueous drug by the perfusate such as aqueous humor after injection into the vitreous cavity can be delayed. This can extend the time during which the concentration of the drug in the vitreous cavity can be maintained above the effective concentration. As a result, the drug effect in the eye can be maintained for a long period of time.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION An embodiment of the present invention will be described below.

The preparation for intraocular diseases according to the present invention (hereinafter, abbreviated as "preparation" as appropriate) is used for treating intraocular diseases after performing surgery for removing the vitreous on vertebrate eyes. A formulation that is injected into the vitreous cavity to prevent
It contains an aqueous drug and a viscoelastic substance for improving the viscosity.

The aqueous drug is an aqueous solution containing an active ingredient effective for intraocular diseases. As the active ingredient, antibiotics; antifungal agents such as fluconazole (Diflucan (registered trademark));
Antiviral agents; antitumor agents; steroids; immunosuppressive agents and the like. Among these, the present invention is particularly effective against antiinfective agents such as antibiotics, antifungal agents, antiviral agents, among others, and particularly effective against antibiotics.

At present, there are many kinds of antibiotics that are individually injected into the vitreous cavity, and they can be used in the present invention. Specific examples of the antibiotics used in the present invention include polypeptide systems such as vancomycin and vancomycin hydrochloride; cephaloridine (Ceprolidine).
hafroidin, cefazolin, ceftazidime, ceftriaxone, and other cephams; imipenem and other carbapenems; gentamicin and amikacin
Aminoglycosides such as Ciprofloxacin (Ciprofl
oxan) and other pyridonecarboxylic acid compounds; clindamycin (Cl
Lincomycin-based compounds such as indamycin). Further, a plurality of kinds of these exemplified substances can be combined to make an antibiotic having a broader spectrum.
The type of the antibiotic may be appropriately selected according to the use and the type of the causative bacteria, but vancomycin or vancomycin hydrochloride is preferable because it has a strong antibacterial action against MRSA (methicillin-resistant Staphylococcus aureus). .

[0023] At present, the safe concentration of the antibiotic that is injected alone into the vitreous cavity has already been determined. Therefore, the concentration of the antibiotic in this preparation may be determined according to the safety concentration already determined. The concentrations of active ingredients other than antibiotics may also be determined according to the safe concentration. Thus, the concentration of the active ingredient in the aqueous drug is determined according to the safe concentration, but usually,
It is within the range of 0.05 to 10.0% by weight.

Any viscoelastic substance may be used as long as it is water-soluble and can improve the viscosity of the preparation as compared with the viscosity of the aqueous drug alone, and is a water-soluble synthetic polymer such as polyvinyl alcohol. However, a natural substance that is decomposed in the living body and absorbed by the living body is preferable so that the living body is not adversely affected. As such a natural viscoelastic substance that is decomposed and absorbed in a living body, specifically, hyaluronate such as sodium hyaluronate, hyaluronic acid, cellulose ester such as methylcellulose,
Alcoholic derivatives of cellulose esters such as hydroxypropylcellulose and hydroxypropylmethylcellulose, polysaccharides such as chitosan, xanthan gum, locust bean gum, gellan gum, carrageenan, furcellaran, tamarind gum; collagen, gelatin, sodium caseinate, albumin, etc. Examples include water-soluble proteins. Of these viscoelastic substances, polysaccharides, especially those having a weight average molecular weight of 10 are excellent in viscoelasticity.
High molecular weight polysaccharides of 20,000 or more are preferred. Among the polysaccharides, hyaluronate is preferred, and sodium hyaluronate is more preferred.

Sodium hyaluronate, particularly high molecular weight sodium hyaluronate, has a high viscosity in an aqueous solution. Therefore, since the viscosity of the preparation can be increased, the concentration of the active ingredient in the eye is not particularly affected by the production of aqueous humor. Therefore, the mixed aqueous solution containing sodium hyaluronate as a viscoelastic substance remains in the vitreous cavity without being discharged for 48 to 62 hours when injected into the eye. Therefore, when sodium hyaluronate is used as the viscoelastic substance, the concentration of the active ingredient in the vitreous cavity can be maintained above the effective concentration for a longer period of time.

Further, sodium hyaluronate has attracted attention due to its viscoelasticity, and in recent years, it is a substance gentle to the eye tissue, which is also used as an eye drop for stabilizing tear fluid against dry eye. Sodium hyaluronate is a substance that has been used by injection into the eye to maintain the shape of the eye and protect corneal endothelial cells during cataract surgery and corneal transplant surgery. Already proven.

For the above reasons, sodium hyaluronate is the most suitable viscoelastic substance (base) in this preparation, which is injected into the vitreous cavity when treating endophthalmitis.

The weight average molecular weight of sodium hyaluronate is preferably 600,000 or more, so that the viscosity of the preparation can be further increased and the sustained release of the preparation can be further improved.
It is more preferably at least, 000,000. The weight average molecular weight of sodium hyaluronate is preferably 10 million or less, more preferably 5 million or less so that the active ingredient is appropriately released and reaches the affected area. When an aqueous solution of sodium hyaluronate is used, the viscosity is 10,000 to 40,000 cps (25
Those in the range of ° C and a shear rate of 2 sec ^-1 are suitable. Further, when an aqueous solution of sodium hyaluronate is used, in order to optimize the viscosity of the preparation as described above, 5
More preferably, the concentration is within the range of 20 mg / ml.

The present preparation preferably has a viscosity adjusted so that the concentration of the active ingredient can be maintained above the effective concentration for a long period of time and the active ingredient is released appropriately.
Specifically, the viscosity of this preparation is preferably in the range of 1 to 5000 cps. The concentration of the viscoelastic substance in the preparation is preferably adjusted so that the viscosity of the preparation is within the above range.

The present preparation may contain components other than the aqueous drug and the viscoelastic substance.

Next, a method for preparing this preparation will be described.

As a method for preparing the present preparation, the active ingredient is dissolved in water to prepare an aqueous drug, and then the aqueous drug is mixed with an aqueous solution of a viscoelastic substance; the active ingredient is dissolved in water to prepare the aqueous drug. Method of mixing an aqueous drug with a viscoelastic substance; a method of mixing an active ingredient and an aqueous solution of the viscoelastic substance and then adding water; Examples include a method of dissolving the obtained mixture in water. When the active ingredient is mixed with the viscoelastic substance and then dissolved in water as in the third and fourth methods, the active ingredient is difficult to dissolve due to its high viscosity. Further, since the viscoelastic substance is commercially available in the form of an aqueous solution having a predetermined concentration, preparation using this commercially available product is easy. For these reasons, 1
The second method is the most preferable.

Next, an example of a method for preparing this preparation will be described. First, an active ingredient in powder form is dissolved in a perfusate at room temperature under vacuum to obtain an aqueous drug. Then, under vacuum, at room temperature, the obtained solution is poured into a container containing an aqueous solution of a viscoelastic substance. Then, the aqueous drug and the aqueous solution of the hi-viscoelastic substance are carefully mixed until a physically uniform state is reached.
This gives the formulation according to the invention.

Next, an example of the method of using the preparation of the present invention will be described.

First, a lens / vitrectomy operation is performed on a normal eyeball. After that, the intraocular perfusate is removed, the inside of the eye is replaced with air, and the entire eyeball is dried. Then, the above-mentioned intraocular disease preparation is injected so as to be in contact with the retina surface, and finally the air in the eye is replaced with a perfusate.

The use of the preparation according to the present invention is considered to be a use as a therapeutic agent after vitrectomy surgery and a use as a surgical adjuvant after an ophthalmic surgery including vitrectomy. In the former use, intraocular diseases represented by infectious intraocular diseases can be treated. In the latter application, ophthalmic surgery including vitreous removal for the purpose of closing perforation wounds and removing foreign objects in the eye to treat traumatic endophthalmitis (sterile endophthalmitis), etc. After surgery, it is possible to prevent the development of infectious intraocular disease due to infection during surgery. Further, for example, in these methods, when an aqueous solution of an antibiotic is used as an aqueous drug, bacterial endophthalmitis can be treated and prevented.

As described above, the formulation according to the present invention contains an aqueous drug and a viscoelastic substance for improving the viscosity, so that the aqueous solution containing perfusate such as aqueous humor after injection into the vitreous cavity can be used. The drug dilution rate can be slowed. Therefore, the concentration of the active ingredient on the retina surface can be maintained above the effective concentration for a long period of time. Therefore, it is possible to effectively treat and treat intraocular diseases such as intraretinal diseases such as retinal diseases without repeated administration.
Can be prevented.

[0038]

EXAMPLES Next, the present invention will be described in more detail based on Examples and Comparative Examples, but the present invention is not limited thereto. The inventors of the present application have conducted numerous studies on vitreous surgery using rabbits (for example, “Development of intraoperative fluorescent fundus imaging method using intraocular laser photocoagulation device”, Japan Ophthalmological Society). , 2001, Masatoshi Furushima, Souichi Matsumoto Celso, Kazuo Nakatsuka "and" Relationship between central retinal arterial pressure and blood pressure during surgery ", Neuro-Ophthalmological Society, 2001
"Takahiko Eto, Kazuo Nakatsuka, Masatoshi Furushima, Souichi Matsumoto Celso"). The following examples are made in that regard.

[Embodiment 1] In this embodiment, as an example,
Vancomycin, which is an antibiotic having a strong antibacterial action, was used as an active ingredient of an aqueous drug, and a sodium hyaluronate preparation (an aqueous solution of sodium hyaluronate) contained in a syringe was used as a viscoelastic substance.

First, 10 mg of powdered vancomycin was dissolved in 1 mL of perfusate at room temperature under vacuum,
A 10 mg / mL vancomycin solution was obtained. continue,
0.1m of obtained vancomycin solution under vacuum at room temperature
L (vancomycin content 1 mg) at a concentration of 10 mg /
0.4 mL of sodium hyaluronate solution (Pharma
"Healon (registered trademark)" manufactured by cia & Upjohn, weight average molecular weight of 190 to 3.9 million, intrinsic viscosity of 25 to 45 d
It was injected into a syringe containing L / g and a viscosity of 40,000 cps (25 ° C., shear rate 2 sec ⁻¹ ). afterwards,
The vancomycin solution and the sodium hyaluronate solution were carefully mixed until a physically uniform state was achieved.
Thereby, the preparation for intraocular disease according to the present invention was obtained. The obtained intraocular disease preparation was viscous.

Next, after performing a lens removing operation and a vitrectomy operation, the intraocular perfusate was removed, the inside of the eye was replaced with air, and the entire eyeball was dried. Then, the above-mentioned intraocular disease preparation (preparation containing sodium hyaluronate and antibiotics) was injected so as to contact the surface of the retina, and finally the air in the eye was replaced with a perfusate to complete the operation. As a result, as shown in FIG. 3 (a), the formulation adhering to the retinal surface immediately penetrated into the aqueous humor immediately after the operation, and even several days after the operation, as shown in FIG. 3 (b). A sufficient concentration of the formulation remained in the eye.

[Embodiment 2] In this embodiment, as an example,
Vancomycin hydrochloride (effective concentration 3 μg / dL), which is an antibiotic having a strong antibacterial action against MRSA, was used as an active ingredient of an aqueous drug.

First, 10 mg / mL vancomycin hydrochloride solution was obtained by dissolving 10 mg of powdered vancomycin hydrochloride in 1 mL of perfusate at room temperature under vacuum.
Then, under vacuum at room temperature, 0.1 mL of the obtained vancomycin hydrochloride solution (vancomycin hydrochloride content 1 mg)
Is a sodium hyaluronate solution having a concentration of 10 mg / mL (“Healon (registered trademark)” manufactured by Pharmacia & Upjohn, weight average molecular weight of 190 to 3.9 million, and intrinsic viscosity of 2).
5-45 dL / g, viscosity 40,000 cps (25 ° C,
Shear rate 2 sec ⁻¹ )) 0.4 mL. Then, the vancomycin hydrochloride solution and the sodium hyaluronate solution were carefully mixed until a physically uniform state was achieved. Thereby, the preparation for intraocular disease according to the present invention was obtained. The obtained intraocular disease preparation was viscous.

Next, after performing lens removal surgery and vitrectomy surgery on both eyes of 10 white rabbits, the intraocular perfusate was removed and the inside of the eye was replaced with air to remove the entire eyeball. Allowed to dry.

Then, for 10 white rabbits (body weight: 2.5 to 3.5 kg) surgically excised from the lens and vitreous body, one eye was contacted with the intraocular disease preparation on the retina surface. While injecting into the other eye, the concentration in the other eye is 10 mg / m
Only L sodium hyaluronate solution was injected. Finally, the air in the eye was replaced with a perfusate to complete the surgery.

After the operation, the change in the concentration of vancomycin hydrochloride in the vitreous cavity (near the retina) was measured. as a result,
In the intraocular disease preparation of the present example based on sodium hyaluronate, the concentration of vancomycin hydrochloride gradually decreased as shown in FIG. 4, and the concentration of vancomycin hydrochloride was 6 and 7 days after the operation. Effective concentration (3μ
g / dL or more) could be maintained.

Comparative Example 1 In this comparative example, physiological saline was used in place of the sodium hyaluronate preparation, and 0.1 mL of a 10 mg / mL vancomycin hydrochloride solution (containing vancomycin hydrochloride was added to 0.4 mL of physiological saline). Quantity 1m
g) were mixed. As a result, a vancomycin hydrochloride solution (hereinafter, referred to as a comparative formulation) was obtained as a control.

Next, this comparative preparation was used in place of the preparation for intraocular diseases of Example 2, and surgery was performed in the same manner as in Example 1.

After the operation, the change in the concentration of vancomycin hydrochloride in the vitreous cavity (near the retina) was measured. as a result,
In the comparative preparation, as shown in FIG. 4, the concentration of vancomycin hydrochloride decreased rapidly, and the concentration of vancomycin hydrochloride was below the effective concentration about 1.5 days after the injection.

[Evaluation of Retinal Toxicity] Regarding the retinal toxicity of the white rabbits of Example 2, that is, the presence or absence of functional impairment of the retina,
The examination was performed using a full-field stimulating electroretinogram (ERG) of the rod system and the cone system.

The rods and cones are photoreceptor cells in the outer layer of the retina, and play an important role in controlling electrical signals generated from the retina in response to light. The full-field stimulation electroretinogram is
This test can evaluate not only the reaction of rods and cone cells, but also the functions of bipolar cells, amacrine cells, and retinal pigment cells in the inner layer of the retina, which are responsible for the transmission of electrical signals and the maintenance of metabolism and function of photoreceptors.

Here, on the 14th day after the operation of Example 2,
A full-field-stimulated electroretinogram of the rod system, a full-field-stimulated electroretinogram of the rod system and the cone system, and a full-field-stimulated electroretinogram of the cone system were recorded. The results are shown in FIGS. 5 (a), (b), and (c), respectively. In addition, as a control, Comparative Example 1
On the 14th day after surgery,
The full-field-stimulated electroretinogram of the rod system and the cone system and the full-field-stimulated electroretinogram of the cone system were recorded. The results are shown in Figure 5.
Shown in each of (a), (b), and (c).

As can be seen from the results shown in FIG. 5, the total visual field-type electroretinogram of the rod system, the total visual field-type electroretinogram of the rod system and the cone system, and the total visual field-type electroretinogram of the cone system No retinal dysfunction was seen in all records.

[Measurement of increase in intraocular pressure] The presence or absence of increase in intraocular pressure (intraocular pressure) of the white rabbit in Example 2 was examined. This is because it was feared that sodium hyaluronate remaining in the eye would cause an increase in intraocular pressure. The intraocular pressure was measured every 24 hours until the 6th day after the operation.

[0055]

[Table 1]

As shown in Table 1, a slight increase in intraocular pressure was observed on the first and second days after the operation. However, 30m
There were no cases of elevated intraocular pressure exceeding mHg. Therefore, it is considered that there is little or no damage to the eye tissue due to the increase in intraocular pressure.

[0057]

INDUSTRIAL APPLICABILITY As described above, according to the present invention, an intraocular drug containing an aqueous drug injected into the vitreous cavity for treating or preventing intraocular disease after surgery for removing the vitreous body is performed. Since a viscoelastic substance for improving the viscosity of the aqueous preparation is added to the disease preparation, the effect of maintaining the drug effect in the eye can be maintained for a long period of time.

Therefore, the present invention enables epoch-making treatment of intractable infectious endophthalmitis. That is, in the conventional treatment of infectious endophthalmitis by injecting an antibiotic alone, there were quite a lot of cases where the visual dysfunction remained strong due to poor effect. On the other hand, by injecting the preparation of the present invention containing an antibiotic as an active ingredient into the vitreous cavity after vitrectomy surgery, it becomes possible to leave an effective concentration of the antibiotic in the eye for a long period of time, and the pathogen It can be expected to reduce the pathogenicity of E. coli and successfully cure infectious endophthalmitis.

[Brief description of drawings]

FIG. 1 is a view for explaining that the flow of aqueous humor changes due to vitreous surgery, where (a) shows the structure of a normal eyeball and the flow of aqueous humor in this eyeball, and (b) shows ,
1 shows the structure of the eyeball and the flow of aqueous humor in the eyeball after surgery to remove the lens and vitreous.

FIG. 2 is a diagram showing a change in antibiotic concentration when an antibiotic is injected alone into an eyeball from which the lens and vitreous have been removed, (a) an eyeball immediately after surgery (antibiotic injection), b) shows an eyeball 2 days after the operation.

FIG. 3 is an eyeball from which the lens and vitreous have been removed,
It is a figure which shows a mode that the preparation moves when the preparation containing the sodium hyaluronate according to the present invention and an antibiotic is injected, (a) is an eyeball immediately after surgery (antibiotic injection), (b) is the number of operations. The eyeball after day is shown.

FIG. 4 is a graph showing changes in the antibiotic concentration in the eye after injecting the formulation according to one example of the present invention and the comparative formulation into an eyeball from which the lens and vitreous have been removed.

FIG. 5 is a full-field stimulus electroretinogram recorded on day 14 after surgery for injecting the formulation according to one embodiment of the present invention and the formulation for comparison to an eye from which the lens and vitreous have been removed. Yes, (a) is a full-field stimulating electroretinogram of the rod system,
(B) is a full-field-stimulating electroretinogram of the rod and cone systems,
(C) is a full-field-stimulating electroretinogram of the cone system.

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[Procedure amendment]

[Submission date] February 12, 2003 (2003.2.1
2)

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0033

[Correction method] Change

[Correction content]

Next, an example of a method for preparing this preparation will be described. First, an active ingredient in powder form is dissolved in a perfusate at room temperature under vacuum to obtain an aqueous drug. Then, under vacuum, at room temperature, the obtained solution is poured into a container containing an aqueous solution of a viscoelastic substance. Thereafter, an aqueous solution of aqueous pharmaceutical and viscoelastic material,
Mix thoroughly until physically uniform. This gives the formulation according to the invention.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Takahiko Eto             483-6 Otsubo, Kamisokata Oita City, Oita Prefecture F-term (reference) 4C076 AA12 BB24 CC32 EE30G

Claims (4)

[Claims] 1. A preparation for intraocular disease, which is injected into the vitreous cavity to treat or prevent intraocular disease after performing surgery for removing the vitreous on the eye of a vertebrate, with an aqueous drug. And a viscoelastic substance for increasing the viscosity, and a formulation for intraocular diseases. 2. The preparation for intraocular disease according to claim 1, wherein the viscoelastic substance is a polysaccharide. 3. The preparation for intraocular diseases according to claim 1, wherein the viscoelastic substance is sodium hyaluronate. 4. The preparation for intraocular diseases according to any one of claims 1 to 3, wherein the aqueous drug contains an antibiotic.