Nanoparticles of Encapsulated Light-Absorbing Agent, Preparation Thereof and Ophthalmic Lens Comprising Said Nanoparticles

Abstract

The invention relates to nanoparticles of a composite material comprising a light absorbing agent dispersed in a matrix of a mineral oxide, to a method for the preparation of such nanoparticles, to the use of said method to modify the hue of nanoparticles of composite material comprising a light absorbing agent, and to an ophthalmic lens comprising such nanoparticles.

Claims

1. Nanoparticles of a composite material comprising at least one light absorbing agent LA dispersed in a matrix of a mineral oxide, wherein: the light absorbing agent LA is dispersed in said matrix in both a monomeric form LA.sub.m and an aggregated form LA.sub.A, said light absorbing agent LA has an absorbance ratio A=A.sub.A/A.sub.M ranging from 1.25 to 10, where A.sub.A is absorbance of LA measured at the wavelength of maximum absorption of LA.sub.A and A.sub.M is absorbance of LA measured at the wavelength of maximum absorption of LA.sub.M.

2. The nanoparticles of claim 1, wherein the mineral oxide is selected from the group comprising silicon dioxide, titanium oxide and zirconium oxide.

3. The nanoparticles of claim 1, wherein the light absorbing agent LA.sub.A is an aggregate of at least 2 light absorbing agents LA.sub.M.

4. The nanoparticles according to claim 1, wherein said light absorbing agent LA is selected from the group comprising, phenazines, phenoxazines, phenothiazine, porphyrins, and mixtures thereof.

5. The nanoparticles according to claim 4, wherein said light absorbing agent LA is a blue light absorbing agent selected from the group comprising methylene blue and Nile blue.

6. The nanoparticles according to claim 1, wherein the mineral oxide of the matrix is SiO.sub.2 and the light absorbing agent LA is methylene blue.

7. The nanoparticles according to claim 1, wherein said absorbance ratio A ranges from 1.3 to 5.

8. The nanoparticles according to claim 1, wherein said nanoparticles have a mean size ranging from 5 nm to 5000 nm.

9. The nanoparticles according to claim 1, wherein the amount of said absorbing agent ranges from 0.001 to 10 wt. %, relative to the total weight of said nanoparticles.

10. A method for the preparation of nanoparticles as defined in claim 1, wherein said method comprises at least the following steps, i) a step of preparing nanoparticles of a composite material comprising at least one light absorbing agent in a monomeric form LA.sub.M dispersed in a matrix of a mineral oxide, ii) a step of annealing the nanoparticles obtained in step i) at a temperature ranging from 80 to 300 C. for a period of time ranging from 5 min to 120 hours.

11. The method of claim 10, wherein the step of annealing is carried out at a temperature ranging from 80 to 180 C. for 30 min to 24 hours.

12. The use of the method as defined in claim 10, further defined as a method of modifying a hue of nanoparticules of a composite material comprising at least one light absorbing agent LA dispersed in a matrix of a mineral oxide.

13. An ophthalmic lens comprising nanoparticles as defined in claim 1.

14. The ophthalmic lens of claim 13, wherein said nanoparticles are dispersed in a polymer matrix.

15. The ophthalmic lens of claim 14, wherein the amount of said nanoparticles in the polymer matrix is 1000 ppm.

16. The ophthalmic lens of claim 15, wherein the amount of said nanoparticles in the polymer matrix is than 250 ppm.

17. The nanoparticles according to claim 8, wherein said nanoparticles have a mean size ranging from 100 to 200 nm.

18. The nanoparticles according to claim 9, wherein the amount of said absorbing agent ranges from 0.1 to 3 wt. %, relative to the total weight of said nanoparticles.

Description

EXAMPLES

[0117] Figures

[0118] FIG. 1a is a graph representing the absorption spectra of nanoparticles obtained by the Stber method and measured before the annealing step (0.03 wt. % of nanoparticles in CR-39) comprising different concentration of methylene blue as a function of Wavelength (nm). On this figure, the grey dotted line corresponds to nanoparticles prepared with a methylene blue solution at 1% w/w, the grey solid line corresponds to nanoparticles prepared with a methylene blue solution at 2% w/w, the black dotted line corresponds to nanoparticles prepared with a methylene blue solution at 3% w/w, and the black solid line corresponds to nanoparticles prepared with a methylene blue solution at 4% w/w. The experimental protocol is detailed in example 1 below.

[0119] FIG. 1b is a graph representing the absorption spectra of nanoparticles from FIG. 1a, but measured after annealing at 180 C. for 2 hours.

[0120] FIG. 2 gives the graphs representing the correlation of h* (FIG. 2a) and C* (FIG. 2b) with silica nanoparticles prepared by the Stber method with methylene blue solutions at 0.5, 1, 2, 3 or 4 wt %. On these graphs, h*, respectively C* (in absolute value) is a function of methylene blue concentration (in % w/w).

[0121] FIG. 3 gives the results of the effects of the annealing temperature ( C.) of nanoparticles on the hue (h*) of clear lenses comprising silica nanoparticles obtained by the Stber method and prepared with a methylene blue solution at 2% w/w. On this figure, diamonds correspond to 30 ppm of nanoparticles in lenses, squares correspond to 70 ppm of nanoparticles in lenses and triangles correspond to 150 ppm nanoparticles in lenses.

[0122] FIG. 4 gives the results of the effects of the annealing temperature ( C.) of nanoparticles on the hue (h*) of clear lenses comprising silica nanoparticles obtained by the reverse emulsion method and prepared with a 2% w/w solution of methylene blue. On this figure, diamonds correspond to 80 ppm of nanoparticles in lenses, squares correspond to 120 ppm of nanoparticles in lenses and triangles correspond to 200 ppm of nanoparticles in lenses.

[0123] FIG. 5 is the transmission spectra from lenses comprising 70 ppm of silica nanoparticles obtained by the Stber method, prepared with a methylene blue solution at 2% w/w. and at different annealing temperatures (lenses represented by squares in FIG. 3). On this figure, the transmittance (% T) is a function of the wavelength (in nm) and the grey solid curve corresponds to annealing at 80 C. for 2 hours, the curve in close-up lines corresponds to annealing at 120 C. for 2 hours and the curve in spaced lines corresponds to annealing at 180 C. for 2 hours.

[0124] Materials

[0125] Chemicals used in the following examples are listed in Table 1 below:

TABLE-US-00001 TABLE 1 Component CAS Number Function CR-39 142-22-3 allyl monomer CR-39E Proprietary allyl monomer (as disclosed in U.S. Pat. No. 7,214,754) IPP 105-64-6 catalyst UV-9 000131-53-3 UV Absorber (benzophenone) Ammonium hydroxide 1336-21-6 Reagent solution (30%) Deionized Water (dH.sub.2O) Solvent Tetraethyl orthosilicate 78-10-4 Silica precursor (TEOS) Methylene blue 7720-79-3 Light absorbing agent Methanol 67-56-1 Solvent Triton X100 9002-93-1 Nonionic surfactant n-Hexanol 111-27-3 Solvent Cyclohexane 110-82-7 Solvent

[0126] Characterizations

[0127] Measure of the absorbance of nanoparticles: The absorbance measurement protocol consists in dispersing 0.03 wt. % of dried nanoparticles in CR-39, and measuring absorbance with a UV-Vis spectrophotometer (Cary), with reference to a blank made of CR-39 without particles in a 2 mm thick cuvette.

[0128] Color of nanoparticles: Colorimetric parameters of the nanoparticles of the invention are measured according to the international colorimetric system CIE L*a*b*, i.e. calculated between 380 and 780 nm, taking the standard illuminant D 65 at angle of incidence 15 and the observer into account (angle of 10). 0.03% of dried particles are dispersed in CR-39 and transmitted light through such material (in a 2 mm thick cuvette) is measured (with comparison to blank). Colorimetric parameters of this transmitted light are computed, yielding hue (h*) and chroma (C*) of nanoparticles.

[0129] Color of lenses: Color of lenses are measured according to the same principle as for nanoparticles, but on 2 mm thick lenses at center. Transmitted light of lenses comprising nanoparticles is measured and compared to the lens obtained with same polymerizable composition but without particles. Colorimetric parameters of this transmitted light are computed, yielding hue (h*) and chroma (C*).

[0130] Size of nanoparticles: The size of the nanoparticles is measured by standard Dynamic Light Scattering method. The technique measures the time-dependent fluctuations in the intensity of scattered light from a suspension of nanoparticles undergoing random Brownian motion. Analysis of these intensity fluctuations allows for the determination of the diffusion coefficients, which, using the Stokes-Einstein relationship can be expressed as the particle size.

Example 1

Preparation of Nanoparticles According to the Invention By the Stber Method

[0131] Preparation:

[0132] In this example silica nanoparticles comprising methylene blue as light absorbing agent were prepared by the Stber method.

[0133] 24 mL of methanol, 6 mL of ammonium hydroxide solution (30%), 0.4 mL of Methylene blue solutions (respectively at 1, 2, 3 and 4% w/w) and TEOS (0.2 mL) were mixed for 2 hours at a speed of about 800 rpm. After reaction finished, the nanoparticles were collected by centrifugation and washed with methanol. The nanoparticles were then dried at room temperature until a constant weight was attained. The nanoparticles were then annealed at 80, 120 or 180 C. for 2 hours.

[0134] These nanoparticles can thereafter be used for the manufacture of ophthalmic lenses after dispersion at 0.3 wt. % in CR-39 (masterbatch).

[0135] Characterization

[0136] The effects of the concentration of methylene blue contained in silica nanoparticles on their color have been determined by measuring the absorbance of the nanoparticles measured before performing annealing step (i.e. nanoparticules dried at ambient temperature) and after performing the annealing step 180 C. for 2 hours.

[0137] The absorption spectra of 0.03 wt. % nanoparticles in CR-39 as a function of Wavelength (nm), measured before performing the annealing step, is represented on FIG. 1a annexed. On this figure, the grey dotted line corresponds to nanoparticles prepared with a methylene blue solution at 1% w/w, the grey solid line corresponds to nanoparticles prepared with a methylene blue solution at 2% w/w, the black dotted line corresponds to nanoparticles prepared with a methylene blue solution at 3% w/w, and the black solid line corresponds to nanoparticles prepared with a methylene blue solution at 4% w/w.

[0138] As it can be seen on FIG. 1a, the variation of methylene blue concentration in nanoparticles varied the color of encapsulated material. Absorption peak of methylene blue show different dimer/monomer ratio. At high concentration of methylene blue solution, big dimer peak at 608 nm is dominant while monomer peak at 670 nm arises after lowering concentration of methylene blue solution.

[0139] FIG. 1b shows the absorption spectra of the same particles, after annealing at 180 C. for 2 hours. These results show that the absorbance of monomeric form of methylene blue (above 650 nm) has almost disappeared. Methylene blue is present in form of agglomerates predominantly after such annealing step.

[0140] FIG. 2 gives the graphs representing the correlation of h* (FIG. 2a) and C* (FIG. 2b) with nanoparticles prepared with methylene solutions at 0.5, 1, 2, 3 or 4 wt %. On these graphs, h*, respectively C* (in absolute value) is a function of methylene blue concentration (in % w/w).

[0141] These results show that C* increases with methylene blue concentration, and more interesting h* roughly linearly increases with methylene blue concentration too. These results demonstrate that a change in light absorbing agent content in nanoparticle mineral oxide matrix makes it possible to finely adjust the actual hue of the light absorbing agent to reach optimum color, rather than just increasing intensity (C*) of a color at a given hue. This effect can be attributed to dimerization that occurs increasingly when methylene blue is encapsulated in higher concentration in the particles.

Example 2

Preparation of Nanoparticles According to the Invention By the Reverse Emulsion Method

[0142] Preparation

[0143] In this example silica nanoparticles comprising methylene blue as light absorbing agent were prepared by the reverse emulsion method.

[0144] In 100 ml Duran bottle, 7.56 g of Triton X-100, 5.86 g of n-hexanol, and 23.46 g of cyclohexane were mixed by magnetic stirrer at a speed of 400 rpm for 15 min. After that, 1.6 ml demineralized water was added dropwise, and stirring was continued for a further 15 min. 0.32 ml of methylene blue solution (2% w/w) were added dropwise. Stirring was continued for 15 min, 0.4 ml of TEOS were then added dropwise and stirring continued for 15 min. Last addition was ammonium hydroxide 30% w/w, dropwise 0.24 ml and the mixture was stirred at a speed of 400 rpm for 24 h. Then 50 ml of acetone was added and the nanoparticles were collected by centrifugation, washed with acetone and dried at room temperature. The nanoparticles were then annealed at 80, 120 or 180 C. for 2 hours.

[0145] These nanoparticles can thereafter be used for the manufacture of ophthalmic lenses after dispersion at 0.3 wt. % in CR-39 (masterbatch).

Example 3

Preparation of Ophthalmic Lenses Comprising Silica Nanoparticules Comprising a Light Absorbing Agent

[0146] Masterbatches (MB) of nanoparticules (NP) prepared according to example 1 with the methylene blue solution at 2% w/w and example 2 above (also obtained with a methylene blue solution at 2% w/w) were used to prepare ophthalmic lenses.

[0147] Monomer Formulations

[0148] Different monomer formulations (MF) were prepared. Their compositions (in wt. %) are detailed in Table 2 below:

TABLE-US-00002 TABLE 2 Annealing NP of NP of temp. Ex. 1 Ex. 2 MF ( C.) CR-39 CR-39E (MB) (MB) UV-9 IPP 1 80 94.03 2.00 1.00 0.05 2.92 2 80 92.70 2.00 2.33 0.05 2.92 3 80 90.03 2.00 5.00 0.05 2.92 4 120 94.03 2.00 1.00 0.05 2.92 5 120 92.70 2.00 2.33 0.05 2.92 6 120 90.03 2.00 5.00 0.05 2.92 7 180 94.03 2.00 1.00 0.05 2.92 8 180 92.70 2.00 2.33 0.05 2.92 9 180 90.03 2.00 5.00 0.05 2.92 10 80 92.36 2.00 2.67 0.05 2.92 11 80 91.03 2.00 4.00 0.05 2.92 12 80 88.36 2.00 6.67 0.05 2.92 13 120 92.36 2.00 2.67 0.05 2.92 14 120 91.03 2.00 4.00 0.05 2.92 15 120 88.36 2.00 6.67 0.05 2.92 16 180 92.36 2.00 2.67 0.05 2.92 17 180 91.03 2.00 4.00 0.05 2.92 18 180 88.36 2.00 6.67 0.05 2.92

[0149] Each monomer formulation was prepared by weighing and mixing the different ingredients in a beaker. CR-39, CR-39E and masterbatch containing nanoparticles were first mixed. Once homogeneous, UV9 was added and then the beaker content was mixed again until full dissolution. Finally, IPP was added and the mixture was stirred thoroughly, then degassed and filtered.

[0150] Lens Manufacturing

[0151] Each monomer formulation was used to prepare ophthalmic lenses according to a casting and polymerization process.

[0152] Plano glass molds were filled with each monomer formulations using a cleaned syringe, and the polymerization was carried out in a regulated oven in which the temperature was gradually increased from 45 to 85 C. in 15 hours and maintained at 85 C. during 2 hours. The molds were then disassembled and the resulting lenses had a 2 mm thickness at their center.

[0153] Characterization

[0154] FIG. 3 gives the results of the effects of the annealing temperature ( C.) of nanoparticles on the hue (h*) of clear lenses comprising silica nanoparticles obtained by the Stber method and prepared with a methylene blue solution at 2% w/w. On this figure, diamonds correspond to 30 ppm of nanoparticles in lenses (MF1, MF4 and MF7), squares correspond to 70 ppm of nanoparticles in lenses (MF2, MF5 and MF8) and triangles correspond to 150 ppm nanoparticles in lenses (MF3, MF6 and MF9).

[0155] These results show that increasing annealing temperature leads to increasing in h*.

[0156] FIG. 4 gives the results of the effects of the annealing temperature ( C.) of nanoparticles on the hue (h*) of clear lenses comprising silica nanoparticles obtained by the reverse emulsion method and prepared with a 2% w/w solution of methylene blue. On this figure, diamonds correspond to 80 ppm of nanoparticles in lenses (MF10, MF13 and MF16), squares correspond to 120 ppm of nanoparticles in lenses (MF11, MF14 and MF17) and triangles correspond to 200 ppm of nanoparticles in lenses (MF12, MF15 and MF18).

[0157] These results show that increasing annealing temperature leads to increasing in h*.

[0158] FIG. 5 is the transmission spectra from lenses comprising 70 ppm of silica nanoparticles obtained by the Stber method, prepared with a methylene blue solution at 2% w/w. and at different annealing temperatures (lenses represented by squares in FIG. 3, MF2, MF5 and MF8). On this figure, the transmittance (% T) is a function of the wavelength (in nm) and the grey solid curve corresponds to annealing at 80 C. for 2 hours, the curve in close-up lines corresponds to annealing at 120 C. for 2 hours and the curve in spaced lines corresponds to annealing at 180 C. for 2 hours.

[0159] These results show that adding nanoparticles obtained after performing io the annealing step at a temperature of 80 C. brings the transmission downward.

[0160] Moreover, varying annealing temperature enhances changing in absorption spectra which leads to change of color tones of lenses.

[0161] This example illustrates that lenses comprising a light absorbing agent encapsulated in a mineral oxide matrix can be adjusted to get the optimum color. The color generated can be modified by selecting a type of encapsulation method, adding various amounts of light absorbing agent at synthesis steps and varying the annealing temperature. The color is then stable during the lens fabrication process.