WO2010011119A1

WO2010011119A1 - Ophthalmic solution for corneal enlargement

Info

Publication number: WO2010011119A1
Application number: PCT/MX2008/000095
Authority: WO
Inventors: Andrés Abelino CHOZA REMERO; Laura Elena Choza Romero
Original assignee: Choza Remero Andres Abelino; Laura Elena Choza Romero
Priority date: 2008-07-22
Filing date: 2008-07-22
Publication date: 2010-01-28

Abstract

The invention relates to an ophthalmic solution for corneal enlargement, combining riboflavin, collagen, methyl cellulose, balanced saline solution, bi-distilled water and a preservative. Said ophthalmic solution is intended for direct topical application to the eye of a patient suffering from keratoconus, post-LASIK ectasia, corneal ulcers or corneal thinning of any etiology.

Description

Ophthalmic solution for thickening cornets

TECHNICAL FIELD OF THE INVENTION

The present invention relates to the Science of Medicine, more specifically in Ophthalmology, since it provides an ophthalmological solution for thickening of the corneas, without the need to use ultraviolet light.

BACKGROUND OF THE INVENTION

The word keratoconus is formed by two other words of Greek origin: kerato, which means cornea and konos that means cone, is an uncommon condition where the cornea is affected by the thinning and protrusion of the same, this condition makes the Perception of images by the human eye is altered, causing poor vision progressively.

The cause of keratoconus so far remains unknown; However, at present there are various surgical treatments, mainly for the control of keratoconus, such as: corneal transplantation, the application of intrastromal rings, the application of radiofrequency pulses in certain places of the cornea to correct astigmatism generated by keratoconus, and application of riboflavin by ultraviolet light (corneal crosslinking) to favor the binding of the collagen fibers of the corneal stroma.

In US 4002758 a method is described for treating ophthalmic disorders of the cornea, where there is lysis of the collagen by the action of collagenous enzymes; said method comprises Ia oral aministrαción to a patient, once or four times a day, of a composition comprising: a compound selected from the group consisting of Cistine and Cysteine, from 200 to 1000 mg; and Pyridoxine (vitamin BÓ) in the form of a base or salt, from 50 to 300 mg. Where ophthalmological disorders can be, keratoconus, corneal damage, corneal herpes, among others. Additionally, the composition can be administered in tablets, so it is obvious the use of acceptable pharmaceutical excipients, such as sugars, carboxymethyl cellulose, talc, etc. In this case, the results are obtained in the long term, because the composition is administered orally.

For its part, the "crosslinking" method consists in saturating Riboflavin eye tissue (vitamin B2) to sensitize the collagen and stimulate the creation of new bridges or junctions between the long collagen chains; and with the irradiation of a special wavelength of ultraviolet light, for 30 min and at a certain distance. The disadvantages that this method presents, is that the epithelium of the cornea must be removed, exposing the patient's eye to ultra violet light; Because the patient is uncomfortable, it causes pain, vision is temporarily affected, it can cause photophobia and epiphora, and there is a risk of damage, when the amount of ultraviolet light to be applied is not well calibrated.

Regarding the application of intrastromal rings to stabilize the keratoconus, it is also a method that requires corneal incisions, and then makes semi-moons in order to apply pmma rings and correct astigmatism caused by the keratoconus, the recovery being taken and may have complications ranging from infections to corneal perforation. Therefore, to counteract the aforementioned drawbacks, an ophthalmic solution for corneal greasing was developed, which simply consists of the combination of Riboflavin and methylcellulose, without the application of ultraviolet light, which I describe below.

OBJECT OF THE INVENTION

The present invention aims to provide an ophthalmic solution for thickening corneas, which comprises a combination of Riboflavin Sodium Phosphate; Powdered collagen and 5% methyl cellulose.

The present invention also provides a method for preparing an ophthalmic solution for thickening corneas, which comprises a combination of Riboflavin Sodium Phosphate; Powdered collagen and 5% methyl cellulose

The invention also provides the use of a combination of Riboflavin, Powdered Collagen and 5% Methyl Cellulose, to develop an ophthalmic solution, to thicken the corneas of a patient suffering from keratoconus, Post Lasik Ectasia, corneal ulcers or corneal thinning of any etiology.

DETAILED DESCRIPTION OF THE INVENTION

The characteristic details of the present ophthalmic solution for thickening corneas are clearly shown in the following description and in the figures included, to demonstrate its effectiveness. -A- Brief description of the figures:

Figure 1 is a graph where the topography of a cornea of a patient suffering from keratoconus is illustrated. Figure 2 illustrates the topography of the cornea of Figure 1, but with 10 days of treatment with the ophthalmic solution of the present invention. Figure 3 illustrates the topography of the cornea shown in Figures 1 and

2, but with 8 months of treatment. Figure 4 shows the topography of a cornea with thinning caused by the application of laser beams to correct myopic astigmatism (Ectasia Post-Lasik). Figure 5 shows the cornea referenced in Figure 4 with 34 days of treatment with the ophthalmic solution of the present invention.

In Figure 6, the greasing of the cornea of Figures 4 and 5 is observed, with 4 months of treatment with the solution of this invention. Figure 7 illustrates the topography of a thinned cornea of a patient. Figure 8 illustrates the improvement of the cornea of Figure 7, with 35 days of application of the ophthalmic solution of the present invention.

The present invention proposes an ophthalmic solution for thickening corneas, which is constituted of: Riboflavin phosphate Sodium; Powdered collagen; 5% methyl cellulose; Balanced saline solution; bidistilled water; And a conservative.

One of the modalities of the ophthalmic solution of the present invention is that the ingredients that constitute it are in the following amounts: Riboflavin phosphate Sodium in 0.05%; 0.05% powdered collagen; 5% methylcellulose in 39.96%; The saline solution balanced by 19.98%; bi-distilled water by 29.97%; and the conservative at 9.99%.

However, the amount of Riboflavin can be increased up to 0.1%, when the patient has severe keratoconus problems and the Saline Solution can vary from 9.99 to 19.98%.

Because the stroma covers approximately 90% of the thickness of the cornea, hence it has a direct relationship with the origin of the keratoconus. Since the stroma of the cornea is mainly formed by collagen fibers, keratocytes and fundamental substance, we think of the direct and non-aggressive application of the nutrients generating these elements ophthalmic route. So that Riboflavin stimulates, through sunlight, the generation of new collagen fibers; The cellulose to nourish the Fundamental Substance and the hydrolyzed Collagen to nourish the stromal cell that is the keratocyte. The saline solution used in this formulation is the conventional ones, where its function is to irrigate the eye.

The way to prepare the ophthalmic solution, in question, is the following: To prepare 10.01 mL of ophthalmic solution, we dilute 5 mg of collagen spray in 2 mL of the balanced saline solution and 2 mL of double-distilled water. Said dilution is made with the help of a thermo-agitator, for 15 min at 40 ⁰ C, until homogenization of the mixture is achieved and allowed to cool from 20 to 22 ⁰ C. On the other hand, we mix 5 mg of Riboflavin Sodium Phosphate, in 1 mL of double distilled water and 4 mL of 5% methylcellulose. The mixture was stirred at 9000 rpm for 20 min; then we filter in a conventional manner; and we stirred it again at 9000 rpm for 10 more minutes.

After mixing both mixtures, stirring for 20 min at 9000 rpm and add 1 mL of a conventional preservative; then it is left to rest for 1 h, so that it reaches a temperature of 20 to 22 ⁰ C and finally it is packaged in a sterile environment in a container, preferably that does not allow the passage of light, suitable to be applied to the eye of a patient.

It should be noted that the entire process of preparing the ophthalmic solution is done under indirect light, since Riboflavin is highly sensitive to light. In addition, it should be adjusted to a pH of 7.1 to 7.3.

In this way we obtain an ophthalmic solution to thicken ocular corneas, topically applied, where it is recommended to apply a drop of the described solution, every 4 hours, for at least 6 months, to the eye of a patient with keratoconus problems, patients with Ectasia Post Lasik, with corneal ulcers, with corneal thinning of any etiology.

In the following examples, it is shown that the ophthalmic solution of the present invention actually greases the corneas that suffered from thinning caused by any factor.

Example!. Treatment of a patient with corneas suffering from keratoconus.

To a patient with keratoconus problems in his corneas, a corneal topography was done with a device called ORSCAN to measure the thickness of its corneas (Figure 1), where it can be seen that the cornea had very thin areas, from 245 microns and 335 microns in the center of said cornea, this worn area is the one that has the red color in Figure 1. From that day, a drop was applied on the cornea, a drop every 4 h, of the ophthalmic solution to thicken corneas, of the present invention and after 10 days of continuous application, a second corneal topography was taken (Figure 2), where it was observed that the thin areas of the comet increased in thickness to 373 and 494, respectively.

The treatment was continued until 8 months were completed and a third topography was taken again (Figure 3) to measure the behavior of the cornea thickness; observing that the reference areas increased their thickness to 590 and 510 microns, respectively, disappearing the red coloration. In this way it is demonstrated that the ophthalmic solution described does increase the thickness of the corneas, due to the presence of collagen.

Example 2. Treatment of a patient with corneas affected by Ectasia Post-Lasik.

In Figure 4 the corneal topography of a cornea that has a thickness of from 327 microns can be observed, said wear was caused by the application of laser beam to the cornea, to correct myopic astigmatism, an operation commonly called Post-Lasik Ectasia. From that day on, a drop was applied to the cornea, one drop every 4 h, of the ophthalmic solution in question, for 34 days, and then to make a second corneal topography (Figure 5), where a surprising increase in the thickness of the Ia is observed cornea at 520 microns and after 4 months, third topography (Figure 6), there was only an increase in 522 microns Once again proving that the ophthalmic solution of the present invention causes a thickening of the corneal tissue, which can be a good solution to recover the corneas when they are subjected to a Post-Lasik Ectasia.

Example 3. Treatment of a patient with thinning of corneas, of any etiology.

Figure 7 shows a topography of a cornea that suffers a thinning of any etiology, where the center has a thickness of 498 microns, starting the treatment already described, for 35 days, when a second corneal topography was made (Figure 8) , where it is appreciated that the central area of said cornea increased its thickness to 564 microns. Once again it is reaffirmed that the application of the present solution restores the corneal tissues.

Claims

CLAIMS Having sufficiently described my invention, which I consider new, which implies an inventive activity and that has industrial application, it is my desire to claim as exclusive property, the matter contained in the following clauses:

1. An ophthalmic solution to thicken corneas, characterized in that it comprises a combination of Riboflavin Sodium Phosphate, Powdered Collagen and 5% Methyl Cellulose.

2. The ophthalmic solution for thickening corneas, according to claim 1, characterized in that the Sodium Riboflavin Phosphate is in an amount of 0.05 to 0.1%; the collagen sprayed in 0.05%; and 5% methylcellulose in 39.96%.

3. The ophthalmic solution for thickening corneas, according to claim 2, characterized in that the Sodium Riboflavin Phosphate is in an amount of 0.05%.

4. The ophthalmic solution for thickening corneas, according to claims 1, 2 and 3, characterized in that it also contains a balanced salt solution in an amount of 9.99 to 19.98%; bi-distilled water in 29.97% and a conservative in 9.99%.

5. The ophthalmic solution for thickening corneas, according to claim 4, wherein the balanced saline solution is in an amount of 19.98%.

6. A method for preparing the ophthalmic solution referred to in claims 1, 2, 3, 4 and 5; characterized by the following stages:

i) Prepare a first dilution, diluting the powdered Collagen in the balanced saline solution and half of the double distilled water.

Such dilution is done with the aid of a thermo-shaker for 15 min at 40 ⁰ C until homogenization is achieved Ia

And the mixture is allowed to cool to 20 to 22 ⁰ C; ii) prepare a second dilution, mixing the Riboflavin Sodium Phosphate, in the other half of the double-distilled water and the Methyl-cellulose 5

%; stir at 9000 rpm for 20 min; then filter in a conventional manner; and stir again at 9000 rpm for 10 more minutes; iii) join the dilutions of stages i) and ii), stirring for 20 min at

9000 rpm and 1 mL of a conventional preservative is added; then let stand 1 h until it reaches a temperature of 20 to 22 ⁰ C; iv) adjust to a pH of 7.1 to 7.3; and v) packaging under sterile conditions in a container, preferably, that does not allow the passage of light.

7. The method of claim 6, characterized in that it is carried out with indirect light.

8. The use of a combination of Riboflavin, Powdered Collagen and 5% Methyl Cellulose, to develop an ophthalmic solution, to thicken the corneas of a patient suffering from keratoconus, Post Lasik Ectasia, corneal ulcers or corneal thinning of any etiology; applying in each eye, a drop of said ophthalmic solution, every 4 h, for at least 6 months.