GR1010095B - New hydrogels for the development of sterile contact lenses - Google Patents

Abstract

There is disclosed a method for the production of sterile pHEMA (HEMA = 2-Hydroxyethyl methacrylate) hydrogels (pHEMA) whose polymeric chains are crosslinked with EGDMA (= ethylene glycol dimethacrylate, crosslinker) and contain silver nanoparticles AgNPs prepared from extracts of natural willow, chamomile and oregano products. Furthermore, there is disclosed a method for the preparation of pHEMA hydrogels which contain low molecular weight bioactive compounds (Small Bioactive Molecules SBaM) of silver (I) with salicylic acid (AGSAL) and of antimony (V) with carvacrol (TPSC). The general type of new materials are pHEMA @ AgNPs and pHEMA @ SBaM. These new materials show antimicrobial activity against the bacteria P. aeruginosa, E. coli, S. epidermidis and S. aureus which are the most common bacteria of microbial keratitis.

Description

Technical description

"New hydrogels for the development of sterile contact lenses"

Technical Field

The present invention relates to the synthesis process of sterile pHEMA hydrogels (HEMA= 2-Hydroxyethyl methacrylate) (pHEMA) of which

the polymeric chains are cross-linked with EGDMA (= ethylene glycol dimethacrylate, crosslinker) and contain silver nanoparticles (silver Nanoparticle AgNPs) prepared from extracts of natural products. The general type of the new materials is pHEMA@AgNPs.

These new materials pHEMA@AgNPs show enhanced antimicrobial activity against Gram-negative bacteria P. aeruginosa and E. coli and against Gram-positive 5. epidermidis and 5. aureus which are the most common bacteria of microbial keratitis. As pHEMA hydrogel is used as a component material for manufacturing soft ophthalmic contact lenses, these new materials can be used in the development of sterile contact lenses.

Contact lenses are risk factors for the development of ocular complications such as microbial keratitis (MC) [Sci. Rep. 5 (2015) 14003, Br. J. Ophthalmol. 85 (2001) 842, Clin. Optom. 8 (2016) 1]. Although, the incidence of MK is quite low, compared to other microbial infections [Eye Contact Lens 35 (2009) 69], however, due to the large number of people who use contact lenses (e.g. 45 million in the United States [https ://www.cdc.gov/contactlenses/fast-facts.html]), there are thousands of cases of MK each year. Infections occur due to microbial contamination of contact lenses and contact lens care solution [Eye 26 (2012) 185, J. Mater. Chem. B 6 (2018) 2171.]. If MK develops it can even lead to corneal perforation [Clin. Optom. 8 (2016) 1]. Bacteria such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis and Staphylococcus aureus can adhere to and colonize contact lens materials [Br. J. Ophthalmol. 85 (2001) 842, Eye 26 (2012) 185]. Therefore, the use of ophthalmic contact lenses made of antimicrobial materials with long-term or permanent action is a research, technological and economic issue of great importance [J. Mater. Chem. B 6 (2018) 2171, Mater. Sci. Eng. C. 111 (2020) 110770],

Hydrogels based on pHEMA are hydrophilic biocompatible materials, permeable to water and oxygen. This makes them excellent ingredients for making contact lenses [Materials 12 (2019) 261, Nature 185 (1960) 117]. In addition, the dispersion of antimicrobial agents in hydrogels confers antibacterial properties to the polymeric material itself [J. Biol. Inorg. Chem. 23 (2018) 705, Mater. Sci. Eng. C 50 (2015) 332],

The present inventors, as a result of extensive research, synthesized and characterized new pHEMA@AgNPs materials for the development of sterile contact lenses. The materials contain silver nanoparticles from the treatment of silver nitrate with natural extracts (willow, chamomile, oregano, etc.) (AgNPs). The materials were characterized by X-ray Fluorescence (XRF) spectroscopy (Table 1). The new pHEMA@AgNPs materials show antibacterial properties against microbes that cause MK (Table 2).

Disclosure of Invention

In particular, the present invention is related to the synthesis of new sterile hydrogels with general type pHEMA@AgNPs. Silver nanoparticles from silver nitrate treatment with natural extracts (willow, chamomile, oregano, etc.) (AgNPs) are dispersed in pHEMA at a concentration of 1 or 2 mg/mL (AgNPs).

A preferred application of the present invention relates to the antibacterial activity of the new pHEMA@AgNPs materials in the development of sterile contact lenses.

Best mode of carrying out the invention

Silver nitrate (AgN03) is used for the synthesis of AgNPs due to its antibacterial properties. Aqueous extracts of natural products of willow, chamomile and oregano were also used for the synthesis of AgNPs.

For the preparation of soft contact lenses, the following were used: 2-hydroxyethyl methacrylate (pHEMA), ethylene glycol dimethacrylate (EGDMA), diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO), sodium chloride (NaCl) and hydrochloric acid ( HCI 37%).

The solvents used for the preparations are bi-distilled water.

Next, the present invention is described in detail and the process is not limited to the invention.

Silver nanoparticles (AgNPs) are the active ingredients of the materials and are prepared as follows:

Preparation of silver nanoparticles (AgNPs) with willow, chamomile and oregano extracts: AgNPs were synthesized according to the following general protocol. 10 g of chopped willow bark, and 4 g of chamomile or oregano are placed in a Soxhlet apparatus and extracted with 50 ml of distilled water for 3 hours. The extract is then filtered. An amount of AgNO3170 mg (1 mmol) is added to 10 mL of extract. AgNPs are obtained by the effect of microwaves (700 W) for 2 min. The AgNPs solution is then placed in an ultrasonic bath for 10 minutes and then centrifuged at 6000 rpm for 20 minutes.

The materials were characterized by X-ray Fluorescence (XRF) spectroscopy (Table 1).

Synthesis of pHEMA@AgNPs: pHEMA hydrogels with integrated AgNPs were synthesized as follows: 2.7 mL of HEMA (57.4% v/v) were mixed with 2 mL of dd water (42.6%), which contained AgNPs, so that their final concentration was 1 or 2 mg/mL (0.02–0.04% w/v), and 10 μL EGDMA (0.002% v/v) (Figure 1).

Figure 1

The solution is then degassed by passing nitrogen gas for 15 minutes. TPO photo-activator (6 mg, 0.13%w/v) is added to the solution and stirred for 5 minutes. The solution is placed in a mold and then photo-polymerized with a mercury UV lamp λmax= 280 nm for 40 minutes. Unreacted monomers are removed from the hydrogel by washing in water for 15 minutes. 10 mm diameter discs are cut and washed by immersion in water, 0.9% NaCl, 0.1 M HCl and again in water for 5 minutes. Finally, the hydrogels are either stored in a saline solution of 0.9% NaCI or dried at 50°C until their weight stabilizes.

Table 1. Silver content (%) in the materials described in this invention

The materials were characterized by X-ray Fluorescence (XRF) spectroscopy (Table 1).

The viability (%) of the bacteria P. aeruginosa, E. coii, S. epidermidis and 5. aureus after their incubation for 20 hours at a temperature of 37°C in the presence of the pHEMA@AgNPs materials is significantly low compared to the reference experiment . The results from the study are given in Table 2.

Table 2. Bacterial survival rate (%) after incubation with the materials described in this invention

Claims (4)

1. A method of preparing a sterile soft ophthalmic contact lens comprising: (A) forming a degassed solution by mixing: (I) a colloidal solution of silver nanoparticles (AgNPs) from willow, chamomile or oregano bark extracts, (II) hydrophilic HEMA monomer ( = 2-Hydroxyethyl methacrylate), (III) crosslinker of polymeric chains EGDMA (= ethylene glycol dimethacrylate, crosslinker), (IV) bi-distilled water (ddw) and (V) photo-activator TPO (=2,4,6, -Trimethylbenzoyl-diphenyl-phosphineoxide) in the ratio of components: (I) 1-2 mg AgNPs (0.02-0.04% w/v), (II) 2.7 mL HEMA (57.4% v/v), (III) 10 μL EGDMA ( 0.002% v/v), (IV) 2 mL ddw (42.6%) and (V) 6 mg TPO (0.13%w/v) (B) exposure of this solution to UV radiation (λmax= 280 nm) for 40 min resulting in a polymerization reaction of the hydrophilic monomer HEMA and the cross-linking agent EGDMA in the presence of the photoactivator TPO and (C) receiving the product (D) The unreacted monomers, removing from the polymer product by washing sequentially in ddw for 15 min, NaCl 0.9%, HCl 0.1 M and again in ddw for 5 min. The synthesis of sterile soft ophthalmic contact lenses can be achieved with different amounts of reagents but in the same proportions and conditions as above. 2. A method of preparing a sterile soft ophthalmic contact lens comprising silver nanoparticles (AgNPs) from willow, chamomile or oregano bark extracts used in claim 1. The silver nanoparticles used in claim 1 are prepared from willow, chamomile or oregano bark extracts . Plant extracts are obtained by extraction in a Soxhlet apparatus. Amount of shredded willow bark (10 g) and chamomile or oregano (4 g) respectively are placed in a Soxhlet apparatus and extracted with bi-distilled water (50 ml) for 3 hours. The extract is then filtered. Amount of AgNO 3 (170 mg (1 mmol)) is added to extract solution (10 ml). AgNPs are formed by microwave exposure (700 W) for 2 min. The AgNPs solution is then placed in an ultrasonic bath for 10 minutes and then centrifuged at 6000 rpm for 20 minutes, when the AgNPs are collected. The synthesis of AgNPs can be achieved with different amounts of reagents in the same proportions and conditions as above. 3. Contact lens material prepared according to the method of claim 1, containing an amount of silver between 0.15-0.16% w/w for the lenses prepared by dispersing 1 mg AgNPs and 0.17-0.21% w/w for those prepared by dispersing 2 mg AgNPs to the total mass of the material. 4. Use of the sterile soft ophthalmic contact lenses prepared according to claims 1, 2 and 3, to prevent microbial infection by microbes causing microbial keratitis.