CH640737A5 - EYE TREATMENT AGENTS. - Google Patents

Description

The present invention relates to agents for eye treatment, namely agents which can be used for the treatment of eye diseases, which are suitable for external use in the eye and which are either themselves a monetary preparation which contains the active ingredient for eye treatment, or which then form a gel after introduction into the eye, which slowly releases the active ingredient.

Many different active ingredients for eye treatment have been found to be therapeutically suitable for the treatment of diseases of the eye. Examples of such active ingredients are pilocarpine, epinephrine, tetracycline, coricosteroid and carbachol. When using active ingredients for eye treatment, it was previously a problem to get the active ingredient in contact with the surface of the

Eye for long enough to achieve the desired therapeutic effect.

Various methods have been proposed to increase the time of contact between the eye treatment agent and the eye. For example, U.S. Patent No. 3,828,777 to Ness describes an eye treatment device which results in the controlled and continuous administration of a predetermined dose of an active ingredient to the eye. This device described in the aforementioned US patent is a body of a microporous material 65 which releases an active ingredient at a certain rate, this material being insoluble in the tear fluid. The pores of this material are filled with a medium that is permeable to the passage of the

Active ingredient by diffusion. This body also contains a reservoir of an active ingredient formulation which is retained in the body, this formulation being of limited solubility in the medium and the device being of a form suitable for insertion into and retention in the conjunctival sac is. The body leads to a continuous and measured release of a therapeutically effective amount of the active ingredient to the eye and to the surrounding tissue, a set release rate being achieved over a long period of time.

Devices for introducing into the eye are known and are used to prolong the action time of an active ingredient which is contained in this device which can be introduced into the eye. U.S. Patent 3,811,444 to Teller et al. and in U.S. Patent No.

3,826,258 to Abraham et al. and further such devices are described in Neefe U.S. Patent No. 3,786,812. Haddad U.S. Patent No. 3,845,201 and Shell U.S. Patent No. 3,914,402 describe previously known solid dosage forms for active ingredients. Previously known ointments containing active ingredients were not effective because they are not clear or translucent and therefore obstruct the view, or they were not effective because they are quickly removed by the normal functions of the eye and thus one prolonged release of the active ingredient cannot be achieved. In U.S. Patent No.

4,003,991 to Krohn et al. describes an eye ointment which has a relatively low viscosity and which contains a water-soluble polymer material and a therapeutic agent.

The aim of the present invention is to develop a composition which can be used for the treatment of sick eyes.

Another object of the present invention is to develop a composition which is suitable for external use in the eye and which is a long-acting and well-retained gel preparation which contains the active ingredient for eye treatment.

Another object of the present invention is to develop a composition which is suitable for the treatment of a diseased eye, in which composition an active ingredient for eye treatment is reacted with a polymer material, a complex and / or a salt being formed, which is suitable for external use, ie for topical use, on the eye, the active ingredient for eye treatment being slowly released from the complex and / or from the salt. All of these objectives of the invention and also methods for using the agents for eye treatment according to the invention are explained in more detail below.

Generally speaking, the present invention relates to an aqueous dispersion of an eye treatment agent and a high molecular weight polymer material which forms highly viscous gels and which can be used to extend the duration of the activity of the active agent for eye treatment when the gel is in the conjunctival sac of the eye is introduced. The activity of the active ingredient for eye treatment is prolonged by slowly releasing the active ingredient from the gel framework and / or by slowly eroding the surface of the gel. The gel compositions according to the invention containing the active substance have an extended retention time in the eye and they remain in contact with the surface of the eye for long periods.

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The inventive eye treatment agent in the form of an aqueous gel which is introduced into the conjunctival sac of the eye is characterized in that the gel contains an active ingredient for eye treatment and a polymer material with a high molecular weight, the polymer material having carboxylic acid groups and / or carboxylic acid anhydride groups and a Has a molecular weight of over 1,000,000.

The high molecular weight polymer materials which are contained in the eye treatment composition according to the invention have a molecular weight of more than 1,000,000 and preferably a molecular weight in the range of 1,000,000 to 6,000,000. These polymer materials are distinguished by the fact that they are functional Groups have carboxylic acid groups and / or carboxylic anhydride groups and preferably contain 2 to 7 carbon atoms per functional group. The gels formed in the preparation of the eye treatment polymer active ingredient dispersion preferably have a viscosity in the range of 40,000 to 300,000 cps at 20 revolutions per minute using a # 7 spindle and at a temperature of 25 ° C if an RVT Brookfield viscometer is used to determine this viscosity. In this determination, the viscosity of the monetary preparations described is preferably in the range from 75,000 to 20,000 cPs. The viscosity of the gels is too high to be measured with a # 3 spindle. The gels also have values for the flow limit, which are preferably to be found in the range from 5000 to 20,000 dynes / cm 2 or even higher, if the flow limit is determined at 25 ° C. using a Fer-ranti-Shirley viscometer.

The high molecular weight polymer materials contained in the eye treatment compositions of the present invention not only result in thickening of these compositions to provide a gel, but they also result in a certain type of viscosity or flow properties, namely plastic viscosity. The term “plastic viscosity” means that a material does not flow until a certain force or a certain stress value is exceeded. This value is called the "yield point" or "yield point" with the English term "yield value". Although the subject matter of the invention is not to be restricted to any theory, it can nevertheless be assumed that the prolonged duration of the activity of the active substance for eye treatment in the gel composition according to the invention is not only due to the ascertainable viscosity, that is to say the thickness of the gel, but also with it is related to the yield point. The gel compositions according to the invention also show the characteristic flow properties or theological parameters which are understood by the term “thixotropy”, that is to say a property which is associated with the breakdown and reconstruction of the gel structure. As soon as the gel compositions are subjected to shear forces that are above the yield point, these gel compositions begin to flow, i.e. the gel structure breaks down. When the shear forces or pushing forces no longer act, the gel structure forms again and it can even reach the initially high viscosity and the initially high yield point.

The high molecular weight polymer materials which are suitable as a component in the eye treatment compositions according to the invention are those which are capable of exhibiting the theological properties with regard to a high viscosity and a high yield point

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sen, within the limits given above.

Suitable polymer materials which can be contained as a component in the eye treatment compositions according to the invention are carboxypolymethylenes and carboxy vinyl polymer materials, for example those materials which are available under the brand name “Carbopol” from the BF Goodrich Company, and also polymer materials Ethylene and maleic anhydride, for example those products that are marketed by the Monsanto Company under the brand name “EMA”. The polymer materials are preferably used in the gel compositions in a concentration which is in the range from about 2 to about 8% by weight, based on the composition.

The agents for eye treatment according to the invention, i.e. Methods for formulating the eye treatment agents according to the invention are suitable for any active substances for eye treatment. Amine active substances which are known active substances for the treatment of eye diseases can be formulated particularly well. Examples of such active substances for eye treatment which can be contained in the eye treatment compositions according to the invention are the following: pilocarpine, epinephrine, tetracycline, phenylphrine, eserine, phospholine iodide, demecarium bromide, cyclopentolate, homatropin, scopolamine, chlorotetracycline, bacitracin, bacitracin Polymixin, gramicidin, oxytetracycline, chloramphenicol, gentamycin, penicillin, erythromycin, carbachol, sulfacetamide, pplymixin B, idoxuridine, isoflorophate, fluoromethalon, dexamethasone, hydrocortisone, hydrocortisone acetate, dexamethasononol-21-phosphonolol, -dolonisolonol-21-phosphonol, -phononolol, -phonidol, -phononolol, -phonidol, -phonidol, -phonidol, -phonidol, -phonizol-21-phosphonol, -phonidol, -phonizol-21-phosphonol , Prednisolone-21-phosphate, prednisolone acetate, betamethasone and triamcinolone.

The active substance for eye treatment is contained in the gel compositions according to the invention in such an amount that the desired purpose of the eye treatment agent is achieved. Usual active substance contents in agents for eye treatment can generally be found in the range from approximately 0.03 to approximately 15% by weight, based on the gel composition.

The agents for eye treatment according to the invention are particularly suitable for prolonging the activity of the active ingredient pilocarpine, which is a very strongly sought-after active ingredient for long-term treatment of the eyes. Accordingly, various special embodiments of the invention, which will be described in detail below, relate to those eye treatment compositions which contain pilocarpine as an active ingredient for eye treatment in these compositions according to the invention.

Various methods can be used to produce the agents according to the invention, which contain the active ingredient and the polymer material. A production process, which is referred to below as method A), preferably consists in dispersing the polymer in water and then adding a basic active ingredient for eye treatment in order to neutralize the polymer material. This neutralization is responsible for the formation of the hydrogel complex from the active ingredient for eye treatment and the polymer material. The final pH of the composition will depend on the basicity of the active ingredient for eye treatment and the amount in which it is added. If the active ingredient is not sufficiently basic, the pH of the hydrogel can be adjusted by adding a basic material, for example by adding ammonium hydroxide, sodium hydroxide, ethanolamine or other basic compounds, in order to achieve the desired pH. It is preferable to set a pH in the range of 4.5 to 8.5 in the formulations containing both the active ingredient for eye treatment and the polymer gel. It has also been found that any eye treatment agent can be added to a hydrogel by adding a basic non-pharmacological agent to the polymer to first make the gel, followed by the addition of the eye treatment agent at any concentration he follows.

In a second preferred method for producing the eye treatment compositions according to the invention, which is referred to here as method B), a salt is produced from the active ingredient for eye treatment and the polymer material. The active ingredient salt for eye treatment can be prepared by first dispersing the polymer material in an inert solvent, for example in hexane, benzene or chloroform, which forms a slurry. Subsequently, a solution of the active ingredient for eye treatment in a solvent is then usually added to the pulp thus obtained. The acid-base neutralization reaction takes place, in which the product of polymer material and active substance for eye treatment precipitates out of the solvent. As soon as the solvent is removed, a finely divided powdery solid remains. With some active ingredients for eye treatment, such as carbachol, a solid mass forms through the neutralization reaction. The solid mass can be broken down into small particles by grinding. A gel can then be produced by dispersing the finely divided powder in water.

The duration and the activity of gel formulations which contain an active ingredient for eye treatment, all of which can be prepared by the preferred three methods described here, are at least twice as long as the duration of action of previously known commercially available eye treatment compositions. An examination of formulations which contain a complex of pilocarpine with carboxymethylene and which were prepared by method A) shows that these gel formulations are unique because they remain in the conjunctival sac of a rabbit for a period of 4 to 8 hours. Previously known formulations, such as petrolatum ointments or suspensions of the easily soluble salts of pilocarpine, were flushed out of the rabbit's eye over a period of 15 to 30 minutes.

According to a further preferred embodiment for the preparation of the agent according to the invention, finely divided particles are produced from the salt of the active ingredient for eye treatment and the polymer material by working method B), and these particles are then suspended in a non-aqueous diluent, for example in a stabilized oil, for example one Mineral oil, a vegetable oil or a silicone liquid. The suspended particles can then be introduced directly into the eye. In this case, the gel forms directly in the eye, through the reaction of the particles with the tears of the eye. Pilocarpine salts of carboxypolymethylene containing 2 mg pilocarpine per dose resulted in pupil size, i.e. miosis, for 14 hours when this preparation was placed in a rabbit eye. In contrast, aqueous solutions of pilocarpine caused the pupils to shrink in size in only 4 to 6 hours.

According to a further embodiment of the invention, therefore, preparations can be made available at

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which salt particles of the active ingredient can be introduced directly into the eye in any suitable manner. These salt particles then form the gel in situ in the eye through reaction with the tears of the eye.

The invention will now be explained in more detail with reference to the following examples.

example 1

A salt form of carboxypolymethylene and pilocarpine is prepared according to method B) explained above, by stirring 6 g of carboxypolymethylene in 30 ml of hexane. The carboxypolymethylene used was the product that B. F. Goodrich Co. markets under the brand name “Carbopol 940”.

In this process, a total of 100 g of finished gel is then obtained, the working process being carried out by adding the benzalkonium chloride to 80 g of pure water. The solution of the benzal conium chloride thus obtained is then stirred while the powder of the salt form of the carboxypolymethylene and the pilocarpine is rapidly added. This solution is stirred vigorously so that as much of the powdered salt as possible is wetted with the water before gel formation occurs, which takes about 1 to 2 minutes. The stirring is then continued until no further hydration can be determined. A sufficient amount of sodium hydrochloride is then gradually added until the pH value given in Table I is finally reached. Finally, pure water is stirred into the gel until a total gel weight of 100 g is reached. The gel preparation obtained in this way is treated in an autoclave at 120 ° C. for 20 minutes, after which it is quickly emptied. The finished gel can contain air bubbles that can be removed by centrifugation.

The determination of the viscosity and the yield point was obtained by using a Ferranti-Shirley Viscometer under the following working conditions: switch position 3X, 60 second cycle, medium cone and spring constant of 100 revolutions per minute. The values given in Table II below for the viscosity and the yield point were obtained:

Table II

Formulation A Formulation B 25 ° C 37 = C 25 ° C 37 ° C

Plastic viscosity in cps 740 708 546 804

Yield point in dynes / cm2 11 421 10 778 13 351 11421

In humans, the results regarding the reduction in size of the pupil, i.e. the miosis, are obtained by using 50 microliters of formulation A) and the

4 g pilocarpine are dissolved in 30 ml hexane. The pilocarpine solution is then mixed with the suspension of carboxymethylene. An acid-base neutralization reaction takes place, the salt being formed from the pilocarpine and the carboxymethylene. This salt form from the carboxymethylene and the pilocarpine is obtained from the hexane serving as the carrier material in the form of a finely divided powder which contains about 35 to about 40% by weight of pilocarpine.

io Two gel formulations are prepared which contain the salt from the pilocarpine and the carboxypolymethylene. The gel formulations contain the constituents listed in Table I below in the amounts stated therein.

B

Formulation B) was placed in the left eye of 9 healthy volunteers who volunteered for this trial. The untreated right eye was used in these subjects for comparison purposes. Formulations A) and B) and also the formulation for comparison purposes, which was a standard pilocarpine solution, contained an amount of pilocarpine or pilo-35 carpine salt which corresponds to 2% by weight of pilocarpine. The following results were obtained, which are summarized in Table III, in which the diameter of the pupil of the eye treated with the pilocarpine preparation minus the diameter of the pupil of the 40 eye is given for comparison purposes.

Table III

Time in difference of the diameter of the pupils in mm

45 hours formulation A formulation B comparative test, 2% pilocarpine solution

1 2.42 2.33 2.50

50 3 2.44 2.56 1.83

6 2.56 2.44 1.19

9 1.81 1.89 0.72

12 1.39 1.17 0.64

24 0.17 0.06 -0.19

55 ''

From this table it can be seen that larger differences in the pupil diameter occur 1 hour after exposure when the composition A) or composition Bo zung B) is compared with the comparison solution. This shows that the compositions according to the invention have a longer duration of action.

65 Example 2

Three other formulations were made and used to determine the results of pupil constriction in rabbits. These phrases

Table I

Component weight%

Formulation A formulation

Salt from carboxypolymethylene and pilocarpine 5.15 5.15

Benzalkonium chloride (U.S.P.) 0.01 0.01

3 normal sodium hydroxide solution until a pH of 5.35 pH 6.0 is reached

Purified water until 100 100 is reached

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contain the specified ingredients in the specified amounts:

Table IV

component

Formulations A B

Pilocarpin, HCl, U.S.P. 2.0 g pilocarpine -

Salt from pilocarpine and carboxypolymethylene-carboxypolymethylene (the product Carbopol 940 from Goodrich)

Benzalkonium chloride (U.S.P.)

Abnormal sodium hydroxide solution until a pH of 5.4 pH 5.4 pH 5.4 is reached

3.38 g 0.01 g

1.7 g

3.38 g 0.01 g

5.15 g

0.01g

Purified water until a total of

100 g

100 g

100 g leads by adding 3 normal sodium hydroxide solution and mixing well after each portion of sodium hydroxide added. The gel is stored under refrigeration overnight to ensure that the pH reaches equilibrium. 5 The final pH is then adjusted to 5.4 and then purified water is added to the gel to reach the final weight of the formulation totaling 100 g. If the gel thus obtained contains air bubbles, these are removed by centrifugation.

Finally, the final pH of Formulation A and Formulation B was measured and found to be 5.35. A rheograph was made using a Visco'simeter, namely a Ferranti-Shirley Viscometer, under the following conditions: switch setting = 2X, 60 seconds flow, medium cone and spring constant of 100 revolutions per minute. All viscosity measurements given in Table V were carried out at 37 ° C.

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Table V

Formulation A Formulation B

Formulation C shown in Table IV was prepared as described in Example 1 above, and this formulation is therefore identical to Formulation A of Example 1.

Formulation A of Table IV above was prepared as follows:

Pilocarpine HCl and benzalkonium chloride are dissolved in 80 g of purified water. While stirring this solution vigorously, carboxypolymethylene is slowly added to the vigorously stirred solution. Stirring is continued until a cloudy solution without lumps is obtained.

The stirring is then interrupted and the trapped air is allowed to escape. Then 10 g of a solution containing about 95% of the molar amount of sodium hydroxide are slowly added to the cloudy solution with stirring. A gel quickly forms while stirring is continued for 10 to 20 minutes. The gel is stored in a refrigerator overnight to complete the hydration and to allow the pH to reach equilibrium. The final pH of the finished gel is adjusted by dropwise adding 3 normal sodium hydroxide solution and mixing well after each drop of added sodium hydroxide solution. Subsequently, purified water is stirred into the gel in order to bring the weight of the gel to a final weight of 100 g. If the finished gel contains air bubbles, these are removed by centrifugation.

Formulation B of Table IV above is prepared as follows:

The benzalkonium chloride is dissolved in 80 g of purified water. The solution is stirred vigorously and carboxypolymethylene is slowly added to the stirred solution. Then continue stirring until a cloudy suspension is reached without any lumps.

The stirring is then interrupted in order to allow any trapped air to escape. 10 g of a solution containing the pilocarpine is prepared and this solution is slowly added to the carboxypolymethylene solution with stirring. A gel quickly forms. The mixture is then stirred for a further 10 to 20 minutes. The pH value of the gel is brought to a value which is in the range from 0.1 to 0.2 pH value units of the desired pH value, specifically by adjusting the pH value.

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Plastic viscosity in cPs 784

Yield point in dynes / cm2 11 480

910 14 560

30 The pupil reduction results were obtained using 6 albino rabbits, for this test the formulations A, B and C listed in Table IV were used and also a solution of 2% 35 pilocarpine for comparison purposes. The tests were carried out in the same manner as described in Example 1. The pupil reduction results are summarized in Table VI below, with pupil diameters given in mm.

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Table VI

Time in pupil diameter in mm 45 hours A B C

2%

Pilocarpine solution (comparison)

50

55

60

0

5.29

5.35

5.18

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0.5

3.46

3.43

3.62

3.21

1.0

3.44

3.40

3.46

3.42

2.5

3.22

3.46

3.60

4.20

3.5

3.61

3.56

3.77

4.66

4.5

3.85

3.72

4.04

5.32

5.5

4.35

4.33

4.08

-

7.5

4.79

5.08

4.69

-

8.5

5.02

4.57

4.54

-

9.5

5.15

4.90

4.70

-

10.5

-

5.0

4.65

-

11.5

-

5.1

5.25

-

The topically applied gels for eye treatment according to the invention are therapeutic compositions with prolonged retention and slow release of the active ingredient. The agents for eye treatment according to the invention can therefore be used to combat various pathological conditions in the eye, in particular glaucoma when the active Be

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is part of the agent pilocarpine, epinephrine or carbachol. The previously known eye treatment agents with the properties of a slow release are either fixed inserts or flakes or different compositions and shapes or suspensions, which are either steroid preparations or ointment-like dosage forms. Ointment-like dosage forms primarily contain petrolatum and small amounts of lanolin or its derivatives. Another known ointment-like dosage form consists of polyethylene, which contains liquid petrolatum, which is incorporated into the basic structure. The ointment-like dosage forms described so far are mainly oily and cosmetically unsatisfactory because they are greasy, and they also obstruct vision. Furthermore, it has been shown that, with such formulations, the therapeutic activity or pharmacological activity can in the best case be extended by 25% compared to aqueous preparations. In contrast to this, the eye treatment compositions according to the invention based on an active ingredient for eye treatment combined with the polymer mergers have an extension of the effectiveness by two to three times if they are also compared with corresponding aqueous solutions. In addition, the gel compositions of the invention typically contain about 95% by weight of water included in the polymer matrix, and are non-greasy and also clear so that visibility is not obstructed, and furthermore their refractive index is similar to that of tears .

Example 3

According to working method C), the acid salt form of pilocarpine is poured into a gel which was produced from ethyl maleic anhydride, which is marketed by Monsanto under the brand name EMA-91. Two gel preparations were made and contained the ingredients listed in Table VII below.

Table VII

Component amount in% by weight

Formulation A Formulation B

Ethylene maleic acid

anhydride

3.38

5.0

Pilocarpine hydrochloride

(U.S.P.)

1.90

2.0

28% ammonium

hydroxide

2.27

3.5

Mannit, N.F.

1.9

2.0

Benzalkonium chloride

(U.S.P.)

0.01

0.01

Purified water

until achievement

a total

100

100

The working procedure for the preparation of 100 g of the finished gel was carried out by adding the ethylene maleic anhydride to 25 ml of vigorously stirred water using a high-speed mixer. A mixing time of 1 minute was sufficient to completely wet and disperse the polymer. Ammonium hydroxide was added to the dispersion and mixed for 1 or 2 minutes until a solid gel was formed. The pilocarpine hydrochloride, mannitol and benzalkonium chloride were dissolved in 15 ml of pure water and this solution was then added to the gel. This mixture was stirred for 4 minutes. When determining the pH, a pH of 5.1 was obtained.

Using a viscometer, a Brookfield RVT viscometer at 20 rpm equipped with a # 7 spindle, and also using a Ferranti-Shirley viscometer used under the following operating conditions: switch position 3X, 60 seconds Run, average level and spring constant of 100 revolutions per minute, the following values for the viscosity were obtained:

Table VIII Values for formulation A in Table VII:

24 ° C 25 ° C; 37 ° C

Brookfield viscosity in cPs 123 000 - -

Ferranti-Shirley Plastic

Viscosity in cps - 434 384

Ferranti-Shirley yield point in dynes / cm2 - 7 614 7 077

Values for formulation B in Table VII:

24 ° C 25 ° C 37 ° C

Brookfield viscosity in cPs 109,000 - -

Ferranti-Shirley Plastic

Viscosity in cPs - 692 558

Ferranti-Shirley yield point in dynes / cm2 - 10 081 11 046

The pupil reduction results were determined by using 6 albino rabbits and administering formulations A) and B) of Table VII to them and also a comparative formulation which was a solution of pilocarpine hydrochloride. It had an active ingredient concentration of 2% pilocarpine. The data obtained for pupil narrowing are summarized in Table IX. Dosages of 50 microliters were administered.

Table IX

Time in pupil diameter in mm hours Formulation A Formulation B Comparison test, 2% pilocarpine solution

0

4.92

5.06

5.08

0.5

3.72

3.53

3.43

1.0

3.23

3.27

3.55

2.0

3.37

3.32

4.05

3.0

3.57

3.13

4.63

3.5

3.55

3.38

4.73

4.5

3.67

3.58

4.98

5.5

3.77

3.77

5.20

6.5

4.00

4.03

-

7.5

4.47

4.12

-

8.5

4.57

4.40

-

9.5

-

4.78

-

10.5

-

5.12

-

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Example 4

In order to illustrate the dependence of the retention time on the increased durability of the gel compositions according to the invention, two studies were carried out and summarized as follows:

a) Three groups of rabbits, each group comprising 6 animals, were administered 50 μl of a carboxypolymethylene gel which contained 1.7% of pilocarpine, which was prepared according to procedure B). Using a saline-saturated cotton swab, the gel was removed from the two groups of rabbit eyes 60 minutes and 120 minutes after administration, respectively, and the results were compared to a control group in which the gel formulation was left in the rabbit eye. The control group in rabbits gave 8.06 hours of pupil narrowing, while the test group gave 5.18 hours pupil narrowing when the gel was removed 60 minutes after insertion, or 5.28 hours. when the gel is removed 120 minutes after it is inserted. Accordingly, the removal of the gel from the rabbit eye significantly reduced the duration of the effect even if it was carried out only 2 hours after the introduction.

b) Triturated pilocarpine was used to prepare the salt from carboxypolymethylene and pilocarpine according to method B). The triturated pilocarpine was also incorporated into the petrolatum. Each formulation used contained 1.7% pilocarpine and was administered to the right eye of rabbits in a volume of 50 μl

enough. A group of rabbits, 6 animals per group, was killed at certain times. The entire conjunctival sac of each rabbit was removed and the levels of tritiated pilocarpine in each connective tissue sac were determined. 2 hours after the introduction, 30% of the originally introduced amount of the formulation of pilocarpine and carboxypolymethylene remained. back to the rabbit eye. In contrast, only 15% of the original amount remained in the rabbit eye 15 minutes after the introduction when the formulation of pilocarpine and petrolatum was used. Over 60% of the amount of the pilocarpine and petrolatum formulation was removed from the rabbit eye after only 5 minutes, whereas in contrast, after 5 minutes, nothing had been removed from the rabbit eye formulation of pilocarpine and carboxypolymethylene.

From these results it can be seen that the retention of the gel formulation in the rabbit eye is better than the retention of a formulation using petrolatum. On the other hand, according to the publication by Fraunhofer and Hanna, in Survey of Ophth., 18, 292 (1974), a formulation using petrolatum is retained better than one in which the carrier material is methyl cellulose or polyvinyl alcohol.

In the investigations carried out here, pilocarpine was partly used as a pleasant tracer substance, and the results with regard to retention can also be qualitatively applied to other active substances for eye treatment.

Claims (10)

640737 2 PATENT CLAIMS 1. means for eye treatment in the form of an aqueous active ingredient for eye treatment contains pilocarpine, and gels which are introduced into the conjunctival sac of the eye in that the high molecular weight polymer is carb-characterized in that the gel is an active ingredient in oxypolymethylene, the Gel has a viscosity, eye treatment and a high-viscosity polymer material which is in the range from 75,000 to 200,000 cps and has a molecular weight, the polymer material having a carbon yield point which is in the range from about 5000 to about acid groups and / or carboxylic anhydride groups can be found to 20,000 dynes / cm 2. and has a molecular weight of over 1,000,000. 11. Agent for eye treatment that is able to 2. Means for eye treatment according to claim claim to form an aqueous gel when it is in the conjunctiva-1, characterized in that the is introduced into the aqueous gel io sack of the eye, characterized in that the polymer material contains a molecular weight in that the Has particles of a drug to the eye area of 1,000,000 to 6,000,000. act and a polymer material with high molecular weight 3. means for eye treatment according to claim 1 contains important, wherein the polymer material carboxylic acid group or 2, characterized in that the gel has a viscosity pen and / or carboxylic acid anhydride groups and has in the range of 75,000 to 200,000 cps. 15 has a molecular weight of over 1,000,000. 4. Means for eye treatment according to claim 3, 12. Means for eye treatment according to claim, characterized in that the gel has a viscosity in the loading 11, characterized in that the pore rich contained therein has from 90,000 to 150,000 cps. Lymermaterial has a molecular weight in the range 5. Agent for eye treatment according to one of the patent from 1 000 000 to 6 000 000 can be found. Claims 1 to 4, characterized in that the gel is a 13 th 13 means for eye treatment according to claim Yield point in the range of 5000 to 20,000 dynes / cm2 to 11 or 12, characterized in that it shows as an active ingredient. for eye treatment idoxuridine, pilocarpine, carbachol 6. Agent for eye treatment according to one of the patent claims or a mixture of two or more of these active ingredient claims 1 to 5, characterized in that it contains a fe. Contains active ingredient from the group Idoxuridine, Pilocar 25 14. Agent for eye treatment according to one of the patent pin and its acceptable salts as well as carbachol claims 11 to 13, characterized in that it is chosen as. Active ingredient for eye treatment an for eye treatment 7. Agent for eye treatment according to one of the patent-suitable antibiotics which contains neomycin, poly claims 1 to 6, characterized in that it contains a steroid for eye treatment as active myxin, chloramphenicol, erythromycin, gentamycin or substance, which consists of 30 Mixture of two or more such antibiotics is selected from the following group: hydrocortisone, Hy- ist. drocortisone acetate, dexamethasone, dexamethasone-21-phos-15. Agent for eye treatment according to one of the pa phat, fluorcinolone, medrysone, prednisolone, methyl claims 11 to 14, characterized in that it contains, as solon, prednisolone-21-phosphate, prednisolone acetate, fluorine active ingredient for eye treatment pilocarpine, and metholone, betamethasone and triamcinolone. 35 that the high molecular weight polymer is a carb 8. is an eye treatment agent according to one of the patent oxypolymethylene. Claims 1 to 7, characterized in that it contains 16. As an active agent for eye treatment according to one of the patent substances for eye treatment an eye treatment claims 11 to 15, characterized in that the par-suitable antibiotic, which consists of the following article group suspended in a non-aqueous carrier material is selected: neomycin, polymyxin, chlorine-40. amphenicol, erythromycin, tobramycin and gentamycin. 17. Agent for eye treatment according to claim 9.Means for eye treatment according to one of the patent 16, characterized in that it contains 1 to 8 as carrier material, characterized in that the gel contains egg-stabilized oil which has a mineral oil, a plant pH value, the is in the range from 4.5 to 8.5. zen oil, a silicone liquid or a mixture of such 10. Is an agent for eye treatment according to one of the 45 carrier materials. claims 1 to 9, characterized in that it as