JPS6056684B2 - eye drops - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to a novel eye drop and a method for producing the same.

Conventionally, eye drops or eye ointments have been frequently used as eye drops.

The base of eye drops is usually purified water, which makes it difficult to spread on the cornea when instilled into the eye, and because it is diluted by lachrymal fluid, a large amount falls off from the eyelids, making it difficult to absorb the drug in the eye drops sufficiently. It was difficult to retain it in the eyelids or absorb it into the body. In addition, eye ointments are made from Vaseline or a mixture of liquid paraffin, purified lanolin, etc., and are not hydrophilic, so they tend to be flushed out of the eyelids by lachrymal fluid, which affects the cornea and ocular mucosa. It is not sufficiently attached to, therefore,
The drawback was that the medicine in the eye ointment was not released sufficiently and the amount that reached the affected area and was absorbed was small. In addition, the eye ointment had the disadvantage that after application, the eyelids became sticky due to the oily base, making it unpleasant. The present inventor has conducted intensive research to improve these drawbacks, to obtain eye drops that are sufficiently absorbed through the ocular mucosa, cornea, etc., and have excellent medicinal efficacy. The present invention was completed based on the discovery that extremely excellent effects can be obtained by preparing a formulation having a viscosity of .

That is, the present invention provides a carboxyvinyl polymer aqueous solution, a gel-like base obtained by adding a water-soluble basic substance to this, or a gel-like eye drop obtained by adding an ophthalmic drug to this, and sodium chloride or its like. A method for producing eye drops, which comprises adding an aqueous solution and thoroughly mixing to obtain a gel eye drop having a pH of 6 to 8 and a viscosity of 1,000 to 100,000 centipoise at 20°C, and its eye drops. The gist is the agent. The carboxyvinyl polymer used in the present invention is a hydrophilic polymer obtained by polymerizing acrylic acid as a main component. You can use what you have.

Carboxyvinyl polymer has free carboxy groups, and its aqueous solution is acidic.

When this is neutralized with a base, it becomes a viscous gel. In the present invention, the following organic amines are suitable as the water-soluble basic substance that neutralizes the carboxyvinyl polymer. Alkylamines such as methylamine, ethylamine, and propylamine; dialkylamines such as dimethylamine, diethylamine, and dipropylamine; trialkylamines such as trimethylamine, triethylamine, and tripropylamine; and alkanolamines such as methanolamine, ethanolamine, and propanolamine. , dialkanolamines such as dimethanolamine, diethanolamine, dipropanolamine, dibutanolamine, trialkanolamines such as trimethanolamine, triethanolamine, tripropanolamine, tributanolamine, and trimethylolaminomethane. Also,
Inorganic bases such as ammonia, aqueous solutions of alkali hydroxides, etc. can also be used. Regardless of the type of water-soluble basic substance used, when carboxyvinyl polymer is neutralized,
Gels of almost the same viscosity are obtained. Generally, it is preferable to neutralize carboxyvinyl polymer with a water-soluble basic substance so that the gel preparation has a pH of around neutrality, that is, pH 6 to 8. It is preferable to use the most preferable liquid type for stability. Therefore, the pH of the gel preparation in the present invention is adjusted within the range of 6 to 8. In the present invention, either water-soluble or water-insoluble eye drops can be used.

When a water-insoluble drug is used, the resulting gel preparation becomes cloudy, but it does not precipitate in the preparation and does not pose a problem for administration. However, a solubilizing agent may be used to make the preparation transparent or to promote absorption in the body, or the drug for eye drops may be prepared by dissolving it in a water-soluble organic solvent in advance. Examples of the water-soluble organic solvent include propylene glycol and polyethylene glycol having a molecular weight of 300 to 400. Among them, propylene glycol is the most versatile and suitable. Further, a water-soluble basic substance may also be used as a solvent. In addition, polyoxyethylene sorbitan monopalmitate,
Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, polyoxyethylenes such as polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, polyoxyethylene behenyl ether, etc. Examples include nonionic surfactants such as alkyl ethers, benzyl alcohol, and the like. The eye drops used in the present invention are stable in formulations, ie, in aqueous media, and are preferably nonionic.

Suitable eye drops used in the gel preparation of the present invention include, for example, prednisolone, cortisone, hydrocortisone, hydrocortisone butyrate, methylprednisolone, cortisone acetate, cortisone caproate, dexamethasone, betamethasone, betamethasone Corticosteroids and their derivatives such as valerate, betamethasone benzoate, dexamethasone acetate, dexamethasone valerate, flumethasone, fluocinolone acetonide, fluocinonide, flumethasone, prednisolone acetate, methylprednisolone acetate, triamcinolone, triamcinolone acetonide , antibiotics such as chloramphenicol, tetracycline, oxytetracycline, chlortetracycline, penicillin, vitamins such as vitamin 8, vitamin B6, vitamin Bl2, vitamin A1 vitamin E1 vitamin D, and other boric acid, acrinol, azulene, and flapine. Various eye drops can be mentioned, such as adenine dinucleotide, allantoin, glutathione, and sulfa drugs. The method of the present invention involves dissolving or dispersing an ophthalmic drug in an aqueous solution of carboxyvinyl polymer, adding a water-soluble basic substance while stirring and mixing thoroughly, and adjusting the pH to 6 to 8. ,
Alternatively, a water-soluble basic substance is mixed and stirred into a carboxyvinyl polymer aqueous solution to form a gel, and an eye drop drug is added to this to form a gel preparation, and the resulting gel preparation has a viscosity of 1000 at 20°C. to 100,000 centipoise.

When the viscosity of the gel is below 1000 centipoise, it has strong fluidity like conventional aqueous eye drops and can be used as is after instillation.
Otherwise, it is undesirable because it may leak out of the body through lachrymal fluid. If it is 100,000 centipoise or more, the dosage form is too hard and the gel disintegrates insufficiently at the point of contact with the ocular mucosa, making it difficult for the ophthalmic drug to be released from the gel, adsorbed to the ocular mucosa, and absorbed into the body.

In the present invention, the viscosity range of the gel preparation includes a wide range from 1,000 centipoise to 100,000 centipoise, but a preparation with a relatively low viscosity of about 1,000 to 10,000 centipoise has high fluidity, so it directly adheres to the eyeball. It can be dripped on top.

On the other hand, relatively high viscosity formulations with a viscosity of about 10,000 to 100,000 centipoise have low fluidity and are paste-like, so they have an ointment-like consistency and can be applied to the eyelids in the same way as conventional eye ointments. Medicinal effects can be exerted by When applying the eye drops of the present invention,
The gel preparation is disintegrated and liquefied by lachrymal fluid, and is well adsorbed to the mucous membrane and cornea.

Even in gel formulations with high viscosity, the viscosity decreases rapidly after application and liquefies. Therefore, ophthalmic medicines in gel formulations are
It adheres closely to the ocular mucosa and cornea and is absorbed. Conventional eye drops are often washed away by lachrymal fluid, but in the eye drops of the present invention, the gel disintegrates and the eye drops are adsorbed to the ocular mucous membrane, etc., so they are washed away by lachrymal fluid. Since it is not washed away, it can exert its full medicinal effect. Furthermore, because conventional eye ointments use petrolatum, lanolin, and other lipophilic bases, they do not adhere closely to the ocular mucosa and tend to be washed away by lachrymal fluid, resulting in insufficient absorption of eye drops. , and the eyelids become sticky and unpleasant. On the other hand, even if the eye drops of the present invention have a high viscosity, they are extremely easily liquefied by lachrymal fluid and adhere well to the ocular mucosa. Furthermore, since no lipophilic base is used, it may cause discomfort to the patient. do not have. If the viscosity of the gel preparation is low, the ophthalmic drug will adhere to and absorb into the ocular mucosa quickly, but as the viscosity increases, it will take longer for the gel to disintegrate, slowing down the absorption of the ophthalmic drug, and therefore reducing its efficacy. It becomes sustainable. Therefore, when it is desired to quickly adhere to the ocular mucosa and maintain the medicinal effect, a relatively low viscosity gel preparation is preferable, whereas a relatively high viscosity gel preparation is preferable when the medicinal effect is to be maintained for a long period of time. Gel formulations are preferred. The viscosity is influenced somewhat by the added drug, but primarily by the concentration of the carboxyvinyl polymer. In order to obtain a gel preparation with a predetermined viscosity, the carboxyvinyl polymer is made into an aqueous solution containing 0.05 to 5.0% by weight. If the viscosity is lowered by the added eye drops, a gel having a predetermined viscosity can be obtained by using an aqueous solution with a high content of carboxyvinyl polymer in advance. When the eye drops of the present invention are applied, the viscosity rapidly decreases and the gel disintegrates, presumably due to the sodium chloride present in the tear fluid.

The present inventors have discovered that when a small amount of sodium chloride or its aqueous solution is added to the eye drops of the present invention, the viscosity of the eye drops rapidly decreases and the eye drops become liquefied. In view of this, as a result of further research, it was discovered that the eye drops produced by adding a small amount of sodium chloride to the eye drops of the present invention delay the disintegration of the gel when applied to the ocular mucosa. Ta. That is, eye drops containing sodium chloride are suitable as eye drops expected to have long-lasting medicinal effects. In this case, it is preferable to increase the content of carboxyvinyl polymer to prevent the viscosity from decreasing due to the addition of sodium chloride. The eye drops of the present invention vary depending on the eye drop medicine used, but for example, when steroids or antibiotics are used, the eye drops can be used to treat various inflammations such as keratitis, pharyngitis, blepharitis, and pharyngitis. In addition, it has a remarkable effect on eye strain (tired eyes), conjunctival congestion (red eyes), eye disease prevention (when dust or sweat gets into the eyes after swimming), and eye damage caused by ultraviolet rays and other light rays. Flame (snow eyes)
, lachrymal inflammation, eyelid erosion,
Widely used for bacterial conjunctivitis, tear replenishment, etc.

Examples of the present invention will be shown below.

The viscosity was measured using a C-type viscometer manufactured by Tokyo Keiki Co., Ltd.
This is a value measured at 0°C. Example 1 Carboxyvinyl polymer (Carbobol 940) 1y
was dissolved in 99 y of sterile purified water to obtain a 1% aqueous solution of carboxyvinyl polymer.

Add 90.5 y of sterile purified water to 7.5 f of the above 1% aqueous carboxyvinyl polymer solution and stir well. To this, gradually add 1.5 y of a solution of 2 y of sodium hydroxide dissolved in sterile purified water and stir. If this is continued, the solution becomes gel-like.

Add 0.5 y of chloramphenicol powder to this and stir vigorously to obtain a gel preparation in which chloramphenicol is uniformly dispersed. Chloramphenicol content 0.5%, P
H7. The viscosity is 2000 centipoise. Example 2 20 f of a 4% carboxyvinyl polymer aqueous solution was mixed with 74.8 f of sterile purified water, and while stirring, 10% sodium hydroxide and 3.2 f of an aqueous solution were added thereto and stirred thoroughly.
Form into a viscous gel.

Add chloramphenicol powder 2y to this and stir vigorously to obtain a gel preparation. Chloramphenicol content 2
%, PH6.9\viscosity 40,000 centipoise. Example 3 Water-soluble azulene (chamomile flower active ingredient) 0.02y
was dissolved in 87.98f of sterile purified water, add 10g of 1% carboxyvinyl polymer aqueous solution, and while stirring, add 2.0f of 2% sodium hydroxide aqueous solution.
to obtain a gel formulation.

PH7. OO, viscosity 4000 centipoise. Example 4 0.05' of acrinol was dissolved in 82.7' of sterile purified water by heating on a water bath, and after cooling, 14.3 f of a 1% aqueous solution of carboxyvinyl polymer was added and stirred, and then hydroxylated. Add 2.86y of 2% sodium aqueous solution and stir well to obtain a gel preparation.

PH6.5O, viscosity 3000 centipoise. Example 5 2fI of boric acid was dissolved in 80.84y of sterile purified water by heating on a water bath, and after cooling, 14.3y of a 1% aqueous solution of carboxyvinyl polymer was added thereto and stirred, and then 2fI of sodium hydroxide was added. % aqueous solution and stir well to obtain a gel preparation.

PH6.5O, viscosity 3000 centipoise. Example 6 20 y of propylene glycol is heated to about 70° C. on a water bath, 0.05 y of riboflavin butyrate is added thereto, dissolved, and then cooled.

To this, 67.09 y of sterile purified water and 10 fI of a 1% carboxyvinyl polymer aqueous solution are added, and while stirring vigorously, 2.86 q of a 2% aqueous sodium hydroxide solution is added to obtain a gel preparation. PH8. Viscosity 5000 centipoise to O. Example 7 20y of propylene glycol is heated to about 700C on a water bath, and 0.1y of riboflavin butyrate is dissolved therein.

After cooling, 50.9 f of sterile purified water and 25 g of a 4% carboxyvinyl polymer aqueous solution are added and stirred, and further 4 y of a 10% sodium hydroxide aqueous solution is added and stirred to obtain a gel preparation. PH6.99, viscosity 50,000 centipoise. Example 8 25f of propylene glycol was heated to about 900C on a water bath, and 0.5f of prednisolone was added and dissolved.
Next, 60.1 g of sterile purified water and 12 f of a 1% carboxyvinyl polymer aqueous solution are mixed, and while stirring, 2.4 f of a 2% aqueous sodium hydroxide solution is added to obtain a gel preparation.

PH7. lO, viscosity 2200 centipoise. Example 9 20 da of propylene glycol was heated to about 90°C on a water bath, 0.5 f of prednisolone was added and dissolved,
To this are added 50.5 y of sterile purified water and 25 y of a 4% carboxyvinyl polymer aqueous solution, and the mixture is vigorously stirred.

Next, 4 g of a 10% aqueous sodium hydroxide solution is added to this and thoroughly stirred to obtain a gel preparation. Viscosity 43 to pH 6.8
000 centipoise. Example 10 25g of propylene glycol was heated to about 900C on a water bath, 0.5f of hydrocortisone was added thereto and dissolved, then 60.1f of sterile purified water and 12f of a 1% carboxyvinyl polymer aqueous solution were added and stirred. Then, 2.4 f of a 2% aqueous sodium hydroxide solution is added and stirred to obtain a gel preparation.

PH7. lO, viscosity 2200 centipoise. Example 11 20y of propylene glycol was heated to about 90°C on a water bath, 0.5y of hydrocortisone was added thereto and dissolved, and then 50.5y of sterile purified water and 25y of a 4% carboxyvinyl polymer aqueous solution were added. Stir and further add 4y of 10% sodium hydroxide aqueous solution and stir to obtain a gel preparation.

PH6.8Of divination 42000 centipoise. Example 1
Heat 25y of 2-propylene glycol to about 900C on a water bath, dissolve 0.1f of dexamethasone in it, then add 60.5V of sterile purified water and 12y of a 1% carboxyvinyl polymer aqueous solution and stir. Add 2.4 f of 2% sodium oxide aqueous solution and stir well to obtain a gel preparation.

PH7. O5. Viscosity 2200 centipoise. Example 13 0.1f of allantoin was dissolved in 76.7fI of sterile purified water while heating, and carboxyvinyl polymer 4
% aqueous solution is added and stirred, and further 3.2 y of a 10% sodium hydroxide aqueous solution is added and stirred to obtain a gel preparation.

PH6.9, viscosity 40,000 centipoise. Example 14 0.1y of allantoin was dissolved in 90.9f of sterile purified water while heating, and 1% of carboxyvinyl polymer was added to the solution.
7.5 y of aqueous solution is added and stirred, and further 1.5 f of 2% sodium hydroxide aqueous solution is added and stirred to obtain a gel preparation.

PH7. OO, viscosity 2000 centipoise. Example 15 20 y of propylene glycol was heated to about 70 y on a water bath, and 0.5 y of flapin adenine dinucleotide was added to this.
Add, dissolve, and cool.

Next, 67.09' of sterile purified water and 10 y of a 1% carboxyvinyl polymer aqueous solution were added and stirred, and while stirring, 2.86 y of a 2% sodium hydroxide aqueous solution was added.
to obtain a gel formulation. PH7. Viscosity 5000 centipoise to O. Example 16 20y of propylene glycol was heated to about 70'C on a water bath, and 0.1% of flavien adenine dinucleotide was added to it.
Add y and dissolve.

After cooling, 50.9 y of sterile purified water and 25 y of a 4% carboxyvinyl polymer aqueous solution were added and stirred, and with further stirring, 4 y of a 10% sodium hydroxide aqueous solution was added.
Add y to obtain a gel formulation. PH6.9λ viscosity 5000
0 centipoise. Example 17 While heating 64.4 y of sterile purified water on a water bath, 2 y of boric acid is added and dissolved therein. After cooling, 12 y of a 4% carboxyvinyl polymer aqueous solution is added and stirred.

Add 2% aqueous sodium hydroxide solution 9.
6V is added little by little to form a gel with uniform viscosity. The pH of this gel is 6.901 and the viscosity is 30,000 centipoise. When 12 fI of a 1% sodium chloride aqueous solution is added little by little to this while stirring, the viscosity is reduced.

Continue stirring until a uniform viscosity is achieved to obtain a gel formulation.
PH7. Viscosity 3000 centipoise to O. Example 18 25fI of propylene glycol is heated to about 90°C on a water bath, 0.5f1 of prednisolone is added thereto and dissolved, and 43y of sterile purified water and 11.5f of a 4% carboxyvinyl polymer aqueous solution are added and stirred.

Add 8 f of 2% sodium hydroxide aqueous solution to this while stirring.
to make a homogeneous gel (pH 6.9, viscosity 3
3000 centipoise). Next, a 1% aqueous solution of sodium chloride 12y is added little by little to this and stirred to obtain a uniform gel preparation.

PH7. Viscosity 2200 centipoise to O. Example 19 Add carboxyvinyl polymer to 61.7 y of sterile purified water.
A 4% aqueous solution 11y is added and stirred, and a 2% aqueous sodium hydroxide solution &8f is added little by little and stirred vigorously to obtain a gel base (PH 6.9O, viscosity 29,000 centipoise).

While stirring the above gel base, add 1 part of sodium chloride to it.
% aqueous solution 18f little by little to obtain a homogeneous gel.

The viscosity of the gel is significantly reduced by adding an aqueous sodium chloride solution. Next, 0.5 f of chloramphenicol powder is added to this and thoroughly stirred to obtain a uniform gel preparation. PH7. OO. Viscosity 2000 centipoise.
Example 20 Water-soluble azulene 0 in 47.28 y of sterile purified water
．． 02f1 was dissolved, 4% carboxyvinyl polymer aqueous solution 11f was added thereto and stirred, and while stirring, 29.7f1 of triethanolamine 2% aqueous solution was added little by little and stirred to form a uniform gel (PH6. 9O, viscosity 28,000 centipoise).

Add 12 y of 1% aqueous sodium chloride solution to this while stirring.
Add it little by little to obtain a uniform gel formulation.

PH7. Viscosity 3000 centipoise to OO. Example 21
Vitamin Bl2O. Dissolve O2' in 90.98 y of sterile purified water, and add 7 y of a 1% carboxyvinyl polymer aqueous solution to this.
．． After adding 5y and stirring, 1.5f of 2% sodium hydroxide aqueous solution was gradually added and stirred to obtain a uniform gel preparation.

PH7. Viscosity 2000 centipoise to O. Example n Vitamin Bl2O. Dissolve O2y in 89.28f of sterile purified water, and add 7.5% of carboxyvinyl polymer 4% aqueous solution to this.
After adding fI and stirring, add 3.2 y of 10% sodium hydroxide aqueous solution little by little and stir to obtain a uniform gel preparation.

PH7. Viscosity to O: 40,000 centipoise. Example 23
Dissolve 0.1 g of allantoin in 87.3 fI of sterile purified water while heating, and add 1% carboxyvinyl polymer.
Add 7.5 g of aqueous solution and stir, then gradually add 5.1' of 2% triethanolamine aqueous solution and stir to obtain a uniform gel preparation, pH 7. OO. Viscosity 2000 centipoise.

Example 24 0.1 y of allantoin was dissolved in 63.5 f of sterile purified water while heating, 20 y of a 4% carboxyvinyl polymer aqueous solution was added and stirred, and then 26.4 y of a 2% triethanolamine aqueous solution was gradually added. Add and stir to form a uniform gel formulation.

PH6.95, viscosity 40,000 centipoise. Example 2
5. Heat 20y of propylene glycol to about 70'C on a water bath, add 0.05y of flapin adenine dinucleotide to this.
Add y and dissolve.

After cooling, 66.65 y of sterile purified water and 10 y of a 1% carboxyvinyl polymer aqueous solution are added and stirred to form a homogeneous solution. Next, add monoethanolamine 2 to this.
% aqueous solution was gradually added and stirred to obtain a uniform gel preparation. PH7. OO, viscosity 5000 centipoise. Example 26 Propylene glycol 20V was heated on a water bath to approx.
0.1y of flapin adenine dinucleotide is added and dissolved.

After cooling, 21.9 V of sterile purified water and 25' of a 4% carboxyvinyl polymer aqueous solution are added and stirred to form a uniform solution. Next, a 2% monoethanolamine aqueous solution 33y is gradually added to this and stirred to obtain a uniform gel preparation. PH6.9 viscosity 50,000 centipoise. Example 2
7 Dissolve 0.02y of water-soluble azulene in 83.23y of sterile purified water, and add 1% aqueous solution of carboxyvinyl polymer to this.
Add 0fI and stir, then add 2% triethanolamine.
Gradually add 6.75 f of aqueous solution and stir to obtain a uniform gel preparation.

PH7. OOs viscosity 4000 centipoise. Example 28 Propylene glycol 20f is heated to about 7C) on a water bath, 0.05fI of riboflavin butyrate is added and dissolved, and after cooling, 66.65f of sterile purified water and 1% carboxyvinyl polymer are added thereto. Add 10v of aqueous solution and stir, then add 3.2% monoethanolamine aqueous solution.
Gradually add 3V and stir to obtain a uniform gel formulation.

PH&00s viscosity 5200 centipoise. Example 29 Vitamin Bi2O. Dissolve O2y in 62.18y of sterile purified water, and add 11% carboxyvinyl polymer aqueous solution to this.
Add g and stir, then add 2% aqueous sodium hydroxide solution &
Add 8y little by little and stir to form a homogeneous gel (PH
6.9 to 29,000 centipoise).

While stirring further, add 1% aqueous solution of sodium chloride to this.
Add 8V little by little and stir to obtain a homogeneous gel formulation.
PH7. Viscosity 2000 centipoise to O. Example 30 Allantoin 0.1V was dissolved in 43.2f of sterile purified water while heating, 11y of 4% carboxyvinyl polymer aqueous solution was added and stirred, and 29.7g of 2% triethanolamine aqueous solution was gradually added thereto. and stir to form a uniform gel (PH6.9O, viscosity 28,000 centipoise).

While stirring the above gel, add 1% sodium chloride aqueous solution.
Add 6f little by little and stir to obtain a uniform gel formulation.

PH7. Viscosity 2000 centipoise to O. Example 31 Propylene glycol 20V is heated to about 70°C on a water bath, 0.05' of flapin adenine dinucleotide is added and dissolved, and after cooling, 41.95V of sterile purified water and carboxyvinyl polymer are added to it. Add 12f of a 4% aqueous solution and stir, and then gradually add 16fI of a 2% monoethanolamine aqueous solution to form a uniform gel (pH 6.
8Ol viscosity 34000 centipoise).

While stirring the above gel, add 1% sodium chloride to it.
10y of aqueous solution is gradually added and stirred to obtain a uniform gel preparation.

PH7. OOs viscosity 5000 centipoise. Example 32 83.96y of sterile purified water was heated on a water bath, 2f of boric acid was added thereto and dissolved, and after cooling, 4% carboxyvinyl polymer aqueous solution 12' was added and stirred. Add 1.92 f of 10% sodium hydroxide aqueous solution little by little to form a uniform gel.

When 0.12 f of sodium chloride is added little by little to this while stirring, the viscosity is significantly reduced. Stir until homogeneous to obtain a gel formulation. PH7. OO, viscosity 3000 centipoise. Example 33 25f of propylene glycol was heated to about 90°C on a water bath, 0.5f of prednisolone was dissolved therein, and then 61.28y of sterile purified water and carboxyvinyl polymer 4
% aqueous solution was added and stirred.

While further stirring, 1.6 y of a 10% aqueous solution of sodium hydroxide is gradually added to the mixture to form a uniform gel. next,
Add 0.12y of sodium chloride little by little to this and stir to obtain a uniform gel preparation. PH7. OON viscosity 2200
centipoise. Example 34 86.56y of sterile purified water,
Mixing 4% carboxyvinyl polymer aqueous solution 11y,
While stirring, add 1.76y of 10% aqueous sodium hydroxide solution.
Add little by little to make a uniform gel.

Then, while stirring, add 0.18y of sodium chloride.
Add a little bit at a time to reduce the viscosity. Add 0.5 y of chloramphenicol powder to this and stir thoroughly to obtain a uniform gel preparation. PH7. OOl viscosity 2000 centipoise. Example 35 Water-soluble azulene 0.02V was dissolved in 87.1y of sterile purified water, 11' of a 4% carboxyvinyl polymer aqueous solution was added and stirred, and a small amount of 1.76y of a 10% sodium hydroxide aqueous solution was added thereto. Add one by one and stir to form a homogeneous gel.

Furthermore, while stirring, add 0.12y of sodium chloride.
is added little by little to reduce the viscosity and obtain a uniform gel formulation.

PH7. OOl viscosity 4000 centipoise. Example 36 Allantoin was dissolved in 86.46V of sterile purified water while heating, and 1% of a 4% carboxyvinyl polymer aqueous solution was added to this.
Add 1y of sodium hydroxide and add 10y of sodium hydroxide to this while stirring.
% aqueous solution little by little and stir thoroughly to form a uniform gel.

Further, while stirring, 0.18y of sodium chloride is added little by little to reduce the viscosity and obtain a uniform gel preparation. P.H.
7. OOs viscosity 2000 centipoise. Example 37 20y of propylene glycol was heated to about 70C on a water bath, and 0.05f of flapin adenine dinucleotide was added to it.
After cooling, add 66.06 y of sterile purified water and 12 f of a 4% carboxyvinyl polymer aqueous solution,
While stirring, add 1.8 y of 10% sodium hydroxide aqueous solution little by little to form a uniform gel.

Next, add 0.09y of sodium chloride little by little and stir thoroughly to obtain a uniform gel preparation.PH7.
Viscosity 5000 centipoise to O. Example: Heat 25 y of feather propylene glycol to about 9 CfC on a water bath, add 0.05 y of fluocinonide and dissolve it, add 60.55 y of sterile purified water and 12 ml of a 1% carboxyvinyl polymer aqueous solution, and stir vigorously. do.

Next, 2.4 f of a 2% aqueous sodium hydroxide solution is added to this and thoroughly stirred to obtain a gel preparation. Viscosity 3 to pH 6.7
400 centipoise. Example 39 25y of propylene glycol was heated to about 900C on a water bath, 0.05f of fluocinonide was added and dissolved, and 44g of sterile purified water was added.
Add 3.45y and 11.5y of a 4% carboxyvinyl polymer aqueous solution and stir.

Add 8 f of 2% sodium hydroxide aqueous solution to this while stirring.
is gradually added to form a uniform gel (PH 6.92, viscosity 33,000 centipoise). Next, 12 g of a 1% aqueous sodium chloride solution is added little by little and stirred to obtain a uniform gel preparation.

PH6.9f)s viscosity 2200 centipoise. Example 4
0 Heat 25 g of propylene glycol to about 9 C) on a water bath, add 0.05 y of fluocinonide and dissolve it, add 45.95 f of sterile purified water and 25 f of a 4% carboxyvinyl polymer aqueous solution, and stir vigorously. do.

Claims (1)

[Claims] 1. A water-soluble basic substance and an ophthalmic drug are mixed in a carboxyvinyl polymer aqueous solution, the pH is 6 to 8, and the pH is 1000 centipoise to 10 at 20°C.
An eye drop characterized in that it is a gel preparation having a viscosity of 0,000 centipoise. 2. The eye drops according to claim 1, wherein sodium chloride is added. 3. The eye drops according to claim 1 or 2, wherein the carboxyvinyl polymer aqueous solution is an aqueous solution containing 0.05 to 5.0% by weight of carboxyvinyl polymer.