AND DELIVERING OXYGEN TO THE EYES

FIELD OF THE INVENTION

The present invention relates to a contact lens product for extended wear, a process for producing a contact lens and a method for disinfecting a contact lens and simultaneously delivering oxygen to the eye.

BACKGROUND OF THE INVENTION

Leonardo da Vinci was first to predict the existence of contact lenses several hundred years ago. But not until 1887 the first contact lens was made by A.F. Mueller. They were made by fine polishing of glass and were very unpleasant and irritating.

Since then major improvements have been made. Even though contact lenses of today are pleasant to wear and have fine optical qualities, they still have some deficiencies.

Since contact lenses are a prolongation of the eyes they should imitate the properties of the eyes or interfere as little as possible with the metabolism of the cornea.

To compensate for the occurring interference most contact lenses must be taken out of the eyes with intervals to be disinfected, and further to give the eyes time for recon- stitution.

The disinfection of the contact lenses prevents growth of bacteria on the lenses which might lead to infection of the eyes making it impossible to wear contact lenses for a long

period of time. Disinfection agents, such as hydrogen peroxide, are widely used.

The reconstitution helps the eyes among other things to redress the metabolic disequilibrium which might have arisen during the period of wearing the lenses.

This need for reconstitution and disinfection makes extended wearing inexpedient, for the matter of the health aspect.

Some of the major problems that prevents extended wearing of contact lenses are the risk of infection of the eyes, caused by growth of microorganisms, and the lack of oxygen delivery to the eyes due to inadequate oxygen permeability of the contact lenses. Especially when the eyes are closed, e.g. during sleep at night, the lack of oxygen delivered to the eyes is imminent.

A plethora of more or less successful attempts to rectify the lack of oxygen delivered to the eyes have been made.. Some of the most successful attempts have been due to a selective choice of mostly monomeric, polymeric or co-polymeric compounds for the preparing of contact lenses. Although the choice of contact lens material have increased the oxygen permeability significant, the delivery of oxygen to the eyes is still critical.

US patent no. 4,757,014 discloses a composite article e.g. a container for contact lenses, comprising in sequence a fibrous polymeric support, which has been subjected to surface treat- ment to provide binding sites thereon, a layer of a protein immobilizer compound, and a biologically active protein. The protein can be catalase, which has use in decomposing hydrogen peroxide when disinfecting contact lenses. Further the enzyme can be Glucose oxidase and peroxidase. This patent does not discuss the problem concerning the lack of oxygen delivered to the eyes.

It has not been described earlier in prior art that it is possible to at the same time both disinfect the contact lenses sufficiently and deliver sufficient amounts of oxygen to the eyes, while wearing the contact lenses. 5 Also, the prior art does not render it possible to omit dis¬ infecting the contact lenses. The lenses need to be removed with short intervals, e.g. every day, to be disinfected.

0 Consequently it is not possible to wear contact lenses for a longer period of time without exposing the eyes to conditions which are not healthy.

The present invention makes it possible to wear contact lenses 15 for a longer period of time, in comparison to corresponding prior art contact lenses. The invention also makes it less costly for the contact lens wearer, since less amounts of disinfecting solution are needed.

_*

20

SUMMARY OF THE INVENTION

It is the object of the invention to overcome some of the disadvantages of the prior art contact lenses by providing a 25 contact lens product for extended wear, which solves the pro¬ blem concerning the lack of oxygen to the eye by increasing the delivery of oxygen to the eye and at the same time disinfect the contact lens. The contact lens product comprises

301) a contact lens, permeable to certain oxygen containing compounds,

2) at least one, on the outer surface of the contact lens, immobilized protein, capable of producing an oxygen containing 35 compound, and

3) at least one, on the inner surface of the contact lens,

1 immobilized protein, capable of producing 0 ₂ from certain oxygen containing compounds.

In a specific example of the contact lens product the immobi¬ lized protein, on the other surface of the contact lens, is Glucose oxidase (GOX) or Amino acid oxidaεe (AAO) and the immobilized protein on the inner surface is a catalase.

Another object of the invention is to provide a process for producing said contact lens product, comprising the steps of

1) immobilizing at least one protein, on the outer surface of the contact lens, capable of generating an oxygen containing compound,

2) immobilizing at least one protein or catalyst, on the inner surface of the contact lens, capable of generating 0 ₂ from the oxygen containing compound.

It is finally the object of the invention to provide a method for disinfecting the contact lenses and at the same time de¬ liver oxygen to the eye, comprising the steps of

1) generating an oxygen containing compound on the outer surface of the contact lens, '

2) transporting said compound through the matrix of the contact lens, and

3) transforming the oxygen containing compound to 0 ₂ .

A specific example comprises the steps of

1) generating H ₂ 0 ₂ on the outer surface of the contact lens,

2) transporting the H ₂ 0 ₂ through the matrix of the, contact

I lens, and

3) reducing the H ₂ 0 ₂ to 0 ₂ .

BRIEF DESCRIPTION OF THE DRAWING

Figure 1 shows the action of the contact lens disinfection and oxygen delivery system of the invention.

DETAILED DESCRIPTION OF THE INVENTION

It is the object of the invention to overcome some of the disadvantages of the prior art contact lenses by providing a contact lens product for extended wear, which simultaneously disinfect the contact lens and increase the amount of oxygen delivered to the eyes. The contact lens product comprises

1) a hydrogel soft contact lens, permeable to certain oxygen containing compounds,

2) at least one, on the outer surface of the contact lens, immobilized protein, capable of producing an oxygen containing compound, and

3) at least one, on the inner surface of the contact lens, im¬ mobilized protein or catalyst, capable of producing 0 ₂ , from certain oxygen containing compound.

All proteins or enzymes or mixtures thereof, capable of pro¬ ducing oxygen containing compounds, which are able to penetrate the contact lens, may be immobilized on the contact lens accor- ding to the invention.

In a preferred embodiment of the invention the contact lens comprises at least one immobilized H ₂ 0 ₂ generating protein on the outer surface, such as an oxidase or a mixture of oxidases.

Example of suitable oxidases are enzymes from the group E.C. 1.4.3 (Enzyme Nomenclature, Academic Press, Inc, 1992), com¬ prising D-/L-Aspartate oxidase, Amino acid oxidase, Glutamate oxidase, Amine oxidase Protein-lysine 6-oxidase, Lysine oxidase, and further enzymes from the group of E.C. 1.4.3, comprising Glucose oxidase, Hexose oxidase, Pyranose oxidase.

Suitable are also other oxidases capable of producing oxygen containing compounds from the air and tear film components.

Specific examples of oxidases are Glucose oxidase (GOX) and/or Amino acid oxidase (AAO) .

Glucose oxidase (GOX) or Amino acid oxidase (AAO) immobilized on the surface of the lens can utilise 0 ₂ from the tear film (and air) to generate H ₂ 0 ₂ .

Glucose oxidase (GOX) catalyses the general reaction:

Glucose oxidase

Glucose + 0 ₂ → Gluconic acid + H ₂ 0 ₂

Amino acid oxidase (AAO) catalyses the general reaction:

Amino acid oxidase

An amino acid + H ₂ 0 + 0 ₂ → a 2-oxo acid + NH ₃ + H ₂ 0 ₂

In an embodiment of the invention the contact lens comprises at least one immobilized protein or catalyst, capable of producing 0 ₂ from an oxygen containing compound, on the inner surface, preferable immobilized protein(s) or catalyst(s) or mixtures thereof, capable of reducing H ₂ 0 ₂ to 0 ₂ .

Examples of suitable immobilized proteins are enzymes, such as enzymes chosen from the groups of peroxidases (E.C. 1.11.1) and dismutases (SOD) (E.C. 1.15.1).

In a specific example said immobilized protein is catalase (E.C. 1.11.1.6), either alone or in combination with Superoxide dismutase (E.C. 1.15.1.1).

Alternatively the H ₂ 0 ₂ reducing compound is a catalyst, such as platinum or other metals, or alloys.

Other suitable proteins and catalysts are chemical compounds capable of transforming oxygen containing compounds to 0 ₂ .

The H ₂ 0 ₂ penetrate/diffuse through the lens and on the inner side of the lens it is reduced to 0 ₂ by e.g. a catalase. This will produce a supplementary source (flow) of oxygen to the eye. It is important that no or only little H ₂ 0 ₂ is released to the surface of the eye. This may be obtained by securing the presence of reducing compound (e.g. catalase) in an amount sufficient to ensure complete and fast conversion to oxygen.

Since the tear film contains glucose (25-100 mg/1) and amino acids (75 mg/1) (Iwata, S., International Ophthalmology Cli- nics. Vol. 13, 29-46,1973), the substrates of the oxidase(s) are available and continuously supplied from the tear film. At these concentrations H ₂ 0 ₂ will not be generated in concentra¬ tions harmful for the eyes. At the same time the by-product produced (ex. gluconic acids) is flushed away by the continuous production of tear fluid.

Removing oxygen from the tear film will lower the partial pressure of oxygen in the liquid, and this will ensure further up-take of oxygen from the air.

According to the invention the contact lens may be, further coated with a coating, such as a mucin layer, either as separate consecutive coating or as a mixed coatings.

The low concentration of H ₂ 0 ₂ produced at the surface of the lens can, besides being used as a generator for 0 ₂ for the eye, also be used for disinfection of the contact lenses by utiliz¬ ing one of the natural defence systems of the tear film. The disinfection system so to speak optimize the well known natural antimicrobial system of the mammalian eyes.

It is further believed that the continuous production of H ₂ 0 ₂ will trigger peroxidase, present in the tear film, to oxidize thiocyanate into hypothiocyanite by the following reaction: Peroxidase

SCN ^" + H ₂ 0 ₂ → OSCN ^" + H ₂ 0

Hypothiocyanite (OSCN") have antimicrobial properties.

Although it might not be effective enough to kill all microor¬ ganisms present in a contact lens container, when the lens is removed from the eye to be cleaned, it will be satisfactory if the lens stays on the eye to complement the natural defence systems.

According to the invention the disinfection and oxygen delivery can be used in context with most soft hydrogel contact lenses.

Preferably the hydrogel contact lens is prepared from monomers or polymers, chosen from the group of collagen, N,N-dimethyl acylamide, 2-hydroxyethyl methacrylate, hydroxyethylmethyl methacrylate, N-vinyl pyrrolidone, poly vinyl pyrrolidone, vinyl acetate, glyceryl methacrylate, flour silicon methacry¬ late, butyl methacrylate, isobutyl methacrylate, 3-methoxy-2- hydroxypropyl methacrylate, pentyl methacrylate, cyclohexyl methacrylate, alkyl methacrylate, glycerol methacrylate, methyl

methacrylic acid, methacrylic acid or methacrylic aci,d ester,

1 and the like, or chemical modifications thereof.

Another object of the invention is to provide a process for producing the said contact lens product comprising the steps of

1) immobilizing at least one protein, on the outer surface of the contact lens, capable of generating an oxygen containing compound,

2) immobilizing at least one protein or catalyst, on the inner surface of the contact lens, capable of generating 0 ₂ from the oxygen containing compound.

In a preferred embodiment of the invention the process com¬ prises the steps whereby

1) at least one protein, capable of generating H ₂ 0 _2ι is im¬ mobilised on the outer surface of the contact lens, and

2) at least one protein or catalyst, capable of reducing H ₂ 0 ₂ to 0 ₂ is immobilised on the inner surface of the contact lens.

In a specific embodiment of the invention said H ₂ 0 ₂ generating protein is an oxidase or mixtures thereof, as defines above, preferable a Glucose oxidase (GOX) and/or an Amino acid oxidase (AAO) .

In an embodiment of the invention said protein capable of reducing H ₂ 0 ₂ to 0 ₂ is a catalase or may alternatively be a catalyst, such as a platinum metal.

According to the invention mixtures of said enzyme(s) and catalyst(s) are also contemplated. Mixtures of catalase and Superoxide dismutase are also contemplated.

Preferably said contact lens, on which the protein(s) ,

I enzyme(s) or catalyst(s) are immobilized, is a soft hydrogel contact lens as defined above.

Methods of immobilizing the enzymes on the surface are avail¬ able for a person skilled in the art of immobilization. E.g. the method described in PCT/91/00107 (Novo Nordisk A/S) can be used.

A final object of the invention is to provide a method for disinfecting contact lenses and delivering oxygen to the eye, comprising the steps of

1) generating an oxygen containing compound on the outer surface of the contact lens,

2) transporting said compound through the matrix of the contact lens, and

3) reducing the oxygen containing compound to 0 ₂ .

Said transport may be either active or passive.

In a specific example the method comprises the steps of

1) generating H ₂ 0 ₂ on the outer surface of the contact lens

2) transporting the H ₂ 0 ₂ through the matrix of the contact lens, and

3) reducing the H ₂ 0 ₂ to 0 ₂ .

As will be apparent to those skilled in the art in the light of the foregoing disclosure, many alterations and modifications are possible in practice of this invention without departing from the spirit or scope thereof. Accordingly, the scope of the

invention is to be construed in accordance with the substance defined by the following claims.