ES2212907B1 - OPHTHALMOLOGICAL PREPARATIONS BASED ON POVIDONA YODADA. - Google Patents

Abstract

New ophthalmological preparations based on povidone iodine, either in the form of eye drops or in gel form, with a composition of 5% or 2.5% of povidone in eye excipients and purified water, for the eye drops form, or in ophthalmic solution of 1-2% carbopol or carmellose sodium plus ocular excipients and purified water, for the gel form. These preparations, preferably presented in single-dose 0.4 ml, are effective antiseptics in eye surgery, being available at the optimal concentration to be used immediately and individually with each patient, without having to be previously manipulated.

Description

Povidone-based ophthalmic preparations iodized

The present invention relates to new ophthalmological preparations based on povidone iodine as effective antiseptics in eye surgery, preferably presented in single dose, in order to avoid excessive consumption and contamination of the product.

Prior art

Several studies have shown that 5% povidone iodine is effective in the background of conjunctival sac in the prevention of ocular infection, giving negative cultures of pathogens, and 2.5% in the prevention of ophthalmia neonatorum in particular.

Among these studies, we can mention Apt et al. (Apt L, Isenberg SJ, Yoshimori R, Spierer A. Outpatient topical use of povidone iodine in preparing the eye for surgery. Ophthamology 1989, 96: 289-292), which found that the application of povidone iodine at 5% before surgery reduced the conjunctival flora, and recommended its use associated with the instillation of a broad-spectrum antibiotic three days before surgery. These data were confirmed by other authors (Lagoutte F, Foie T, Jasinki M, et al. Polyvidona-iodee et prevention of L'infection posoperatoroir. J Fr Ophthalmol 1991; 15: 14-18.1991), who also found the preparation safe by the eye.

The study of Speaker and Menikoff (Speaker MG; Menikoff JA; Prophilaxis of endophalmitis with topical Povidone iodine Ophthalmology 1991; 98: 1769-1-1775) highlighted that the Povidone iodine decreases the incidence of endophthalmitis culture positive compared to the use of protein protein solution linked to saline irrigation, which has been classically the most used as an antiseptic in eye surgery, and there is synergism with the use of antibiotic therapy.

Other studies (Isenberg SJ, Apt L, Yoshimori R, et al . Chemical preparation of eye in ophthalmic surgery IV. Arch. Ophthalmol 1985; 103: 340.
1342.1985) demonstrated that a topical antibiotic combined with povidone iodine yielded a negative culture in 83% of cases.

Finally (Boes DA, Lindquist TD, Fritsche TR, Kalina RE. Effects of Povidone-Iodine chemical and Salive irrigation on perilimbar flora. Ophthalmology 1992; 99: 1569-1574) its use has been found effective in reduce bacteria collected from conjunctival perilimbar flora. The  Saline irrigation after preparation with povidone iodine does not have negative effect, despite studies that defended otherwise.

Currently, the pre-surgery use of dilutions of povidone iodine in the bottom of the conjunctival sac is usual and usually protocolized. In most of the protocols its use is established (unless there is an eye open or known allergy), both in the bottom of the bag (5%) and in skin (10%), although it must be irrigated carefully to avoid that gets into the eye.

In the Spanish market is the Povidona 10% iodized in different presentations, but all prepared for a use other than the prevention of eye infection, by the irritation that causes povidone in said eyes concentration. This is the case, for example, of the products of the "Betadine" brand: Betadine® Bucal, Betadine® Shampoo, Betadine® Gel, Betadine® Scrub, Betadine® Dermal Solution and Betadine® Vaginal; presentations all different from that of eye use.

In the United States there are ophthalmic solutions of 1.67% povidone (Alcon) and with 0.6% Polyvinil alcohol (Ross Products Pharmaceuticals) in the form of tears and agents moisturizers, but there are also no commercial eye preparations for antiseptic use.

Since the presentation of Povidona iodized to 5% or 2.5% in an eye vehicle currently does not exist, which usually done in surgery is to manipulate the product prior to its implementation. For example, in Spain and others countries it is usual to dilute the povidone in serum to these concentrations in the topical ocular application.

However, this way of using Povidone Iodized as an antiseptic in eye surgery gives rise to various and frequent problems, derived from: a) The dilution of the product with different sera and not with eye solutions; b) an inadequate product concentration, either by default or by excess, being in this second case harmful to the cornea; c) contamination of product; d) excessive consumption, with consequent waste; and) and, in general, a bad application of the product, not having Prepared in advance.

It would therefore be desirable to have some Preparations containing 5% povidone iodine for ocular use (or at 2.5% for certain cases), presented in an eye vehicle suitable, as in the form of eye drops or gel, for application directly on the bottom of the conjunctival sac and allow them to do so its effect In addition, since the previous instillation of a eye drops anesthetic is inevitable, because of the intense itching that povidone produces, optionally, a presentation that Take these two eye drops.

On the other hand, in order to avoid problems of pollution and excessive consumption, the product could come presented in single-dose, that is, in single-dose containers.

The invention

To meet this need, the purpose of the The present invention are ophthalmological preparations based on povidone iodine, either in the form of eye drops or in gel form, with a composition of 5% or 2.5% of povidone iodine in excipients eyepieces and purified water, for the eye drops form, or in solution 1-2% carbopol or sadistic carmelose ophthalmic more ocular excipients and purified water, for the gel form, although in the first case, in the eye drops presentation, they can also contain polyvinyl or hypromellose alcohol, or both compounds.

New developed preparations can presented in single doses as a preferred option, in an amount set around 0.4 ml, both for the eye drops form and For the gel form.

However, they can also be applied by any other clinically admitted means, such as in jars 15 ml dropper, both in isolation and in combination with others products.

In the single dose form of eye drops or gel  povidone iodine can include a single dose of eye drops anesthetic based on tetracaine hydrochloride and nafazoline, which would apply before povidone iodine. This two preparation Single-dose packaging allows a simpler application.

The fundamental advantage of this invention is the have an eye drops or eye antiseptic gel based on povidone iodized at the optimum concentration (5% or 2.5%), being prepared in each surgical operation to be used immediately and individual with each patient, without having to be previously manipulated.

Also, if you opt for your presentation in single-dose, through single-use single-dose containers, the invention involves a number of added advantages, such as the significantly reduce the cost of povidone iodized by the child consumption implied by this system (minimum quantity and individualized, without having to discard the excess) and minimize the product contamination risk, not being handled.

On the other hand, these new preparations ready to use allow to extend the treatment application antiseptic, thereby improving infection prevention eye surgery in a global way, and can be used even in other ocular processes, both in isolation and combined with other products.

The concentration of 5% povidone iodine, or 2.5%, is important in the prevention of ophthalmia neonatorum , because irritating keratoconjunctivitis is avoided, and it has been proven that at that concentration povidone is harmless to the eye.

The association of the product with a eye drops anesthetic for two-stage application, especially when product and anesthetic are presented in single doses, avoid stinging that produces the direct application of povidone iodine, at previously use the anesthetic.

The gel presentation is also novel, with the additional advantage that it allows a permanence of the most stable product at the bottom of the conjunctival sac (greater effectiveness in preventing premature elimination) and protection of epithelium during application. The gel on the eye surface improves hydration and product distribution on said surface.

Embodiment

As two preferred embodiments of the Preparations object of the present invention packages are proposed single dose with: a) 0.4 ml single dose of eye drops or povidone gel iodine at 5% or 2.5%; and b) Single dose of 0.4 ml of eye drops or gel of 5% or 2.5% iodinated povidone + 0.4 ml single dose Anesthetic.

In any case, eye drops, gel and anesthetic used may have the compositions and Presentations indicated below, which are examples that are not intended to be limiting of the multiple possibilities:

5% or 2.5% iodinated Povidone eye drops; three possibilities:

a) 15 ml eye drops, of composition 50 or 25 mg / ml of povidone iodine (International Common Denomination - DCI) in purified water with eye excipients.

b) 15 ml eye drops with polyvinyl alcohol, of composition 50 or 25 mg / ml of povidone iodine (INN) plus 14 mg / ml (variable) of polyvinyl alcohol (INN) in purified water with eye excipients

c) 15 ml eye drops with hypromellose, of composition 50 or 25 mg / ml of povidone iodine (INN) plus 3 mg / ml (variable) of hypromellose in purified water with excipients eyepieces

5% or 2.5% iodinated povidone gel; two possibilities:

a) Carmellose Sodium Ophthalmic Solution (INN) 1-2% (variable proportion) plus povidone iodine 5% or 2.5% (DCI) plus eye excipients and purified water.

b) Carbopol ophthalmic solution plus povidone 5% or 2.5% iodized (INN) plus eye excipients and water purified.

Anesthetic: 5 mg / ml tetracahyne hydrochloride plus 0.5 mg / ml nafazolin.

Single-dose preparations based on Povidone iodine illustrated above can be used in all types of  eye surgery, as powerful antiseptics. It would be indicated for topical use several minutes before surgery, to later produce a wash. They should not be used, however, in open eyes or with demonstrated sensitivity to their components. Also, because it contains iodine, caution should be taken in certain patients.

Industrial application

The new preparations for which it is requested patent are subject to application in the industry pharmaceutical, within what are pharmaceutical products or hygienic for medicine, and can be presented in the market for commercialization in the form of single-dose containers, although they can also be presented by any other means commonly admitted, as are the dropper bottles.

Claims (4)

1. Ophthalmological preparations based on povidone iodine in the form of eye drops or gel, essentially characterized by presenting a composition of 5% or 2.5% of povidone iodine in ocular excipients and purified water, for the eye drops form, or in ophthalmic solution of 1-2% carbopol or carmellose sodium plus ocular excipients and purified water, for the gel form. 2. Ophthalmological preparations based on povidone iodine in the form of eye drops or gel, according to claim characterized in that when they are presented in the form of eye drops, they also contain polyvinyl or hypromellose alcohol, or both compounds. 3. Monodose of ophthalmological preparations based on povidone iodine in the form of eye drops or gel, according to claims 1 and 2, characterized by being presented in single-dose containers, for single use, in a fixed amount around 0.4 ml, both for the eye drops form as for the gel form. 4. Use of ophthalmic preparations based on povidone iodine in the form of eye drops or gel, according to claims above, as components of other products intended to avoid eye infection