WO2008014225A2 - Carotenoid coated substrates and substrates designed to mimic carotenoid coated substrates - Google Patents

Abstract

Structures including an optical substrate are disclosed where the optical substrate includes a macular pigment. The macular pigment includes a carotenoid. In an embodiment, the cartenoid includes lutein, zeaxanthin, and combinations thereof. The optical structure can include eyewear, lens, goggles, contact lenses, and windows. The macular pigment can be disposed on the surface of the optical structure or disposed with the material used to make the optical structure.

Description

CAROTENOID COATED SUBSTRATES AND SUBSTRATES DESIGNED TO MIMIC CAROTENOID COATED SUBSTRATES

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to U.S. provisional application entitled, "CAROTENOID COATED SUBSTRATES AND SUBSTRATES DESIGNED TO MIMIC CAROTENOID COATED SUBSTRATES," having serial number 60/832,811, filed on July 24, 2006, which is entirely incorporated herein by reference.

BACKGROUND

Human ocular tissues contain high concentrations of the dietary carotenoids lutein (L) and zeaxanthin (Z). These pigments are concentrated in the inner layers of the primate fovea and they are typically referred to as macular pigment (MP). It is generally assumed that the presence of these pigments is not incidental but rather that such high accumulation in functionally important areas (like the fovea) implies that MP serves some function. Probably the best known and studied function is based on the idea that the pigments protect the retina from oxidative damage that accrues with age. This protection is based on the fact that MP filters potentially actinic light (mostly within the visible range of 400-500 nm, a spectral region often referred to as the "blue light hazard) and L and Z are known to be active lipid-based antioxidants. By protecting the retina and, by extension, the retinal pigment epithelium, from degenerative change, it is thought that MP could retard or even prevent the development of age-related macular degeneration (AMD).

SUMMARY

Briefly described, embodiments of this disclosure include structures including optical substrates, where the optical substrates include a macular pigment. The macular pigment includes a carotenoid. In an embodiment, the cartenoid includes lutein, zeaxanthin, and combinations thereof. The optical structure can include eyewear, lens, goggles, contact lenses, and windows. The macular pigment can be disposed on the surface of the optical structure or disposed with the material used to make the optical structure. BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of this disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.

FIG. 1 illustrates data showing the relation between MP and disability glare and photostress recovery.

FIG. 2 is a graph of the spectral absorbance properties of MP as measured in vivo (symbols) and ex vivo (solid line).

FIG. 3 illustrates a filter cell that is filled with a solution of oil and L and Z and so artificially (and externally) mimics macular pigment in a precise way that we would like the glass to mimic MP.

FIG. 4 shows that the filter cell adds linearly to an individuals MP density.

FIG. 5 is a graph that shows that the filter cell decreases glare disability as a substantially linear function of increasing optical density.

FIG. 6 is graph that shows that the MP filter also enhances contrast in a substantially linear manner.

DESCRIPTION

Before the present disclosure is described in greater detail, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit (unless the context clearly dictates otherwise), between the upper and lower limit of that range, and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, the preferred methods and materials are now described.

All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. Further, the dates of publication provided could be different from the actual publication dates that may need to be independently confirmed.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure. Any recited method can be carried out in the order of events recited or in any other order that is logically possible.

Embodiments of the present disclosure will employ, unless otherwise indicated, techniques of chemistry, physics, biology, and the like, which are within the skill of the art. Such techniques are explained fully in the literature.

The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to perform the methods and use the compositions and compounds disclosed and claimed herein. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C, and pressure is at or near atmospheric. Standard temperature and pressure are defined as 20 °C and 1 atmosphere.

Before the embodiments of the present disclosure are described in detail, it is to be understood that, unless otherwise indicated, the present disclosure is not limited to particular materials, reagents, reaction materials, manufacturing processes, or the like, as such can vary. It is also to be understood that the terminology used herein is for purposes of describing particular embodiments only, and is not intended to be limiting. It is also possible in the present disclosure that steps can be executed in different sequence where this is logically possible.

It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a support" includes a plurality of supports. In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings, unless a contrary intention is apparent.

Discussion

Embodiments of the present disclosure include optical structures including one or more carotenoids. Incorporation of the carotenoid into the optical structure may provide a level of eye protection (e.g., from radiation, age related macular degeneration, and the like) and/or vision enhancement (e.g., reduction of glare and the like). Although not intending to be bound by theory, the incorporation of the carotenoid into the optical structure may filter out certain wavelengths of light, which may provide eye protection and/or vision enhancement.

It should also be noted that lenses that filter light by reducing luminance vision tend to suffer. In general, especially at low or even moderate light levels, reducing light is deleterious to vision. However, it should be noted that most spatial vision occurs in the middle of the visible spectrum whereas embodiments of the present disclosure filter short-wave or blue light, which does not tend to contribute much to acuity. This may be one reason why green or red filters are not optimal. One advantage to yellow filters and embodiments of the present disclosure is that they actually enhance luminance sensitivity by increasing the activity of the magnocellular system (i.e., the luminance channel) and by causing the pupil to dilate more strongly. This is essentially why yellow filters tend to make everything look subjectively brighter. Although not intending to be bound by theory, macular pigment coated substrates or substrates that mimic macular pigments on a substrate may be expected to enhance sensitivity even more since the visual system compensates for filtering by macular pigment by also increasing sensitivity in the blue-yellow opponent channel.

The term "optical substrate" as used throughout the specification is to be understood to mean any substrate that has the capacity to transmit light. The term not only includes optical articles such as ophthalmic lenses and sunglass lenses, but other types of articles as described herein. The phrase "incorporation of the carotenoid into the optical structure" is to be understood to include embodiments where one or more carotenoids are disposed on the surface of an optical substrate, are disposed between two or more optical substrates, are disposed within the material of the optical substrate, and/or combinations thereof.

Embodiments of the optical structures can include, but are not limited to, eyewear (e.g., sun glasses, prescription glasses, non prescription glasses, and the like), lens (e.g., lens used in eyewear, goggles, contact lenses, and other lenses), goggles (e.g., protective goggles, swim goggles, and the like), contact lenses (e.g., hard and soft contact lenes), windows (e.g., an automotive windshield, an automotive window, an automotive sun/moon roof, a house window, and a building window), and other structures that are substantially transparent or transparent to light (e.g., visible light).

The optical substrate can be made of one or more materials. The optical substrate can have one or more layers of materials, where each layer may be the same or a different material. The optical substrate can be made of materials such as, but not limited to, a glass, a plastic, a polymer material, a hydrogel, and combinations thereof

In an embodiment, suitable materials for the lens include polyvinyl chloride (PVC), acrylics, polyester film, such as Mylar (commercially available from Dupont), and polystyrene including general-purpose polystyrene and high impact polystyrene. The lens material can be virtually any type of material that can be designed to fit and generally conform to the shape of the user's face and around the user's eye socket. The lens material is preferably a transparent, plastic material.

In another embodiment, contact lenses can be either hard or soft lenses. Soft contact lenses are preferably made from a soft contact lens material, such as a silicon or fluorine-containing hydro-gel or HEMA. It will be understood that any lens material can be used in the production of the contact lenses. hi another embodiment, an ultraviolet material (e.g., chromatophore) can be incorporated into embodiments of the present disclosure to shield from ultraviolet rays (UVA, UVA, and UVC). hi another embodiment, a glass or plastic substrate can be altered to mimic the spectral absorption characteristics of macular pigment at various optical density levels, hi an embodiment, the glass of plastic substrate can include four types of glass and/or plastic mimicking various levels of macular pigment (e.g., optical densities of 0.25, 0.50, 0.75 and 1.0). In particular, the glass or plastic is modified to mimic the internal macular pigments as closely as possible. In addition, the glass or plastic could be slightly dichroic (e.g., since about 5-10% of the pigment molecules are polarizing in nature).

The carotenoids include, but are not limited to, macular pigments. The macular pigments include lutein, zeaxanthin, derivatives of each, and combinations thereof. The derivatives of lutein and/or zeaxanthin retain the properties and characteristics of lutein and zeaxanthin, respectively. Derivatives of lutein include, but are not limited to, lutein esters, and the like.

One or more types of carotenoids (or a composition including one or more types of carotenoid) can be disposed in a layer or in multiple layers disposed on a portion of the surface or on the entire surface the optical structure. In an embodiment, one or more layers of the carotenoids (or a composition including one or more types of carotenoid) can be disposed between two or more optical structures.

In an embodiment, one or more types of carotenoids can be incorporated into the material to form the optical structure. For example, the carotenoid could be included in a polymer that is subsequently formed into the optical structure or a portion of the optical structure. In an embodiment, the optical structure may include two or more polymer layers, and one or more of the polymer layers can include one or more types of carotenoids.

The amount of carotenoids used in the optical structure can vary depending on the desired results. For example, tests can be conducted to determine how much carotenoid should be included into a prescription lens to provide an adequate level of protection and/or visual enhancement for a particular person. In another example, a pre-determined amount of carotenoid is included in the optical structure to provide a certain level of protection and/or visual enhancement (e.g., a non-prescription lens, a window, and the like).

Example

Now having described the embodiments of the disclosure, in general, the example describes some additional embodiments. While embodiments of present disclosure are described in connection with the example and the corresponding text and figures, there is no intent to limit embodiments of the disclosure to these descriptions. On the contrary, the intent is to cover all alternatives, modifications, and equivalents included within the spirit and scope of embodiments of the present disclosure.

Example 1

Human ocular tissues contain high concentrations of the dietary carotenoids lutein (L) and zeaxanthin (Z). These pigments are concentrated in the inner layers of the primate fovea and they are typically referred to as macular pigment (MP).

It is generally assumed that the presence of these pigments is not incidental but rather that such high accumulation in functionally important areas (like the fovea) implies that MP serves some function. Probably the best known and studied function is based on the idea that the pigments protect the retina from oxidative damage that accrues with age. This protection is based on the fact that MP filters potentially actinic light (mostly within the visible range of 400-500 nm, a spectral region often referred to as the "blue light hazard) and L and Z are known to be active lipid-based antioxidants. By protecting the retina and, by extension, the retinal pigment epithelium, from degenerative change, it is thought that MP could retard or even prevent the development of age-related macular degeneration (AMD).

In addition to the protective hypothesis, a number of other ideas have been posited regarding MP function. These hypotheses largely focus on the possibility that MP improves visual performance by virtue of the fact that it filters short-wave light before it reaches the outer-segment of foveal cones. Fo veal cones, of course, have exaggerated importance to vision since this small area mediates fine resolution and color vision. The purely optical hypotheses for MP were originally summarized by Walls and Judd (1933), with reference to all intra-ocular yellow filters, and then later by Nussbaum et al. (1981), with specific reference to MP.

1. To increase visual acuity by reducing chromatic aberration.

2. To promote comfort by the reduction of glare and dazzle.

3. The enhancement of detail by the absorption of 'blue haze. '

4. The enhancement of contrast.

Walls and Judd argued that the ubiquity of intraocular yellow filters in nature (as opposed to retinal filters with other absorptive qualities, such as red filters) support the idea that yellow filters do play an important role in vision. In contrast to the protective hypothesis, however, most of the visual performance hypotheses have not been empirically studied. The possibility that MP improves the optical quality of images is important, of course, for a number of reasons. For example, supplementing L and Z could improve the visual performance of the elderly or individuals with AMD through optical means irrespective of whether these carotenoids actually effect underlying biological changes.

Of the optical hypotheses, the acuity hypothesis (#1) has been the most studied yet seems the least plausible. Although quantitative modeling suggested the hypothesis was feasible, empirical data have not supported the hypothesis. Wooten and Hammond (2001) also quantitatively modeled the visibility hypothesis (#3 and 4) and argued that the MP could improve vision through the atmosphere by absorbing short-wave dominant air light (blue haze) that produces a veiling luminance over spectrally flat objects viewed at a distance.

The optical hypothesis that has received the least attention is referred to here as the glare hypothesis (#2). Implicit to this hypothesis is the idea that SW light is a strong contributor to the visual discomfort associated with exposure to a strong glare source. This possibility was confirmed recently by Stringham. Stringham showed that visual discomfort resulting from a glare source was much higher for SW light than for mid-or-long wave light. Subjects with higher MP density were shown to be able to handle more short-wave light before an aversive response (quantified by EMG recordings of squinting) was elicited. This effect was not found in the parafovea where MP density is optically negligible. Although these studies suggest that MP reduces visual discomfort due to glare/dazzle (i.e., discomfort glare), they do not address whether subjects can actually see better under glare conditions (i.e., disability glare). We have preliminary data that strongly support this function. Decrements in visual performance could result from both veiling light that reduces the contrast between an object and its background and photopigment depletion and regeneration rates. To test these possibilities, we measured visibility thresholds under veiling conditions and photostress recovery times. We found that MP density is directly and strongly related to grating visibility and reductions in photostress recovery.

FIG. 1 illustrates data showing the relation between MP and disability glare and photostress recovery. The left panel shows the relation between MP and grating visibility under veiling glare conditions. These data show that MP directly and strongly improves vision when exposed to glare. The right panel shows that MP shields the retina in such a way as to shorten photostress recovery times. Photostress is determined by the ability of rhodoposin to regenerate. MP screens the retina so that less rhodopsin is depleted when exposed to glaring light.

Taken together, it is clear that MP does lead to enhanced visual performance through the optical mechanism of filtering short-wave light (ca. 400-520 urn). This interpretation is consistent with studies that have found that supplementation with the MP carotenoids lutein and zeaxanthin leads to improvements in visual performance. For example, in a recent double-blind placebo controlled study, Richer found that, after 12 months of lOmg lutein or lOmg lutein + antioxidant supplementation, visual acuity in 56 patients with atrophic AMD improved by 5.4 and 3.5 letters, respectively, on the Snellen chart. Those receiving a placebo showed no improvement in acuity. Furthermore, a similar result was reported by Olmedilla who supplemented cataract patients with 15mg of lutein, three times a week for up to 2 years and found that the lutein -supplemented patients' visual acuity improved nearly 1 line on the Snellen visual acuity chart compared to placebo controls.

Theoretically, the mechanism by which MP improves visual performance is entirely optical, i.e., due to the pigment's spectral absorption properties. These properties are shown in the FIG. 2.

FIG. 2 is a graph of the spectral absorbance properties of MP as measured in vivo (symbols) and ex vivo (solid line). FIG. 3 illustrates a filter cell 10 that is filled with a solution of oil and L and Z 16 and so artificially (and externally) mimics macular pigment in a precise way that we would like the glass to mimic MP. Movement of the first optical structure 12 towards a second optical structure 14 adjusts the amount of solution 16 (e.g., L and Z) so that the effect of differing amounts of L and/or Z 16 can be determined. FIG. 2 shows the actual measured spectrum and shows that it has the precise shape of the internal macular pigments. The advantage of the filter cell is that it allows us to vary optical density on a continuous scale thereby testing the effects of varying density levels on visual performance.

Since the visual enhancement produced by MP is due to its specific filtering properties, theoretically, these properties can be easily reproduced with engineered glass. Such glass can be used externally in glasses or goggles in order to mimic increases in natural macular pigment. Of course, the use of yellow filters to improve vision has been proposed for a long time. "The use of yellow filters to enhance visual performance has been proposed for more than 75 years. Many users, including some military aircrew members, are absolutely convinced that the yellow filters improves target acquisition performance; yet others are just as certain that they provide no improvement or even degrade performance." (Provines et al., 1992)

Pro vines' study was designed to determine whether yellow ophthalmic lenses enhanced visual threshold acquisition performance when viewing approaching aircraft. The study had a null outcome, but the individual variability in results was large. Yellow filters apparently helped some individuals, harmed some, and did nothing for others. Importantly, however, all of the past studies that have explored the relation between short-wave absorption and acuity or contrast sensitivity have used various yellow filters that resemble MP, i.e., none has actually duplicated its spectral absorption. It is likely that some of these yellow filters were close enough to effectively mimic MP and it is likely that others were not. Proper design based on effectively mimicking MP would, of course, be necessary to achieve the visual performance enhancement predicted for MP. Such glasses could dramatically improve vision. For example, when viewing a series of parallel ridges covered with vegetation, ridges nearby will appear green. With each successive ridge, however, air light reduces contrast, until distant ridges are lost in a milky bluish haze, even on a clear day (e.g., Green River Area, Wyoming, average visual range in June = 108 miles). Based on the analysis by Wooten and Hammond (2002), an individual with high MP would be able to distinguish such ridges up to 27 miles further than individuals with little or no MP, but equal Snellen acuity. These increases are easily achievable using glass engineered to mimic increases in MP density.

FIG. 4 shows that the filter cell adds linearly to an individuals MP density. Thus, it appears that the use of embodiments of the present disclosure would resemble increasing MP density. FIG. 5 is a graph that shows that the filter cell decreases glare disability as a substantially linear function of increasing optical density. FIG. 6 is graph that shows that the MP filter also enhances contrast in a substantially linear manner.

It should be noted that ratios, concentrations, amounts, and other numerical data may be expressed herein in a range format. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub- ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a concentration range of "about 0.1% to about 5%" should be interpreted to include not only the explicitly recited concentration of about 0.1 wt% to about 5 wt%, but also include individual concentrations (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.5%, 1.1%, 2.2%, 3.3%, and 4.4%) within the indicated range. The term "about" can include ±1%, ±2%, ±3%, ±4%, ±5%, ±6%, ±7%, ±8%, ±9%, or ±10%, or more of the numerical value(s) being modified. In addition, the phrase "about 'x' to 'y'" includes "about 'x' to about 'y"\

Many variations and modifications may be made to the above-described embodiments. All such modifications and variations are intended to be included herein within the scope of this disclosure and protected by the following claims.

Claims

CLAIMS At least the following is claimed:

1. A structure, comprising: an optical substrate including a macular pigment.

2. The structure of claim 1, wherein the optical substrate includes a coating, wherein the coating includes the macular pigment.

3. The structure of claim 1, wherein the macular pigment includes a carotenoid.

4. The structure of claim 3, wherein the cartenoid is selected from lutein, zeaxanthin, and combinations thereof.

5. The structure of claim 1, wherein the optical structure is selected from: eyewear, lens, goggles, contact lenses, and windows.

6. The structure of claim 5, wherein the eyewear is selected from: sun glasses, prescription glasses, non prescription glasses.

7. The structure of claim 5, wherein the contact lenses is selected from: hard contact lenses and soft contact lenses.

8. The structure of claim 5, wherein the window is selected from: an automotive windshield, an automotive window, an automotive sun/moon roof, a house window, and a building window.

9. The structure of claim 5, wherein the lens includes lens used in eyewear, goggles, and contact lenses.

10. The structure of claim 1, wherein the optical substrate is a material selected from: a glass, a plastic, a polymer material, a hydrogel, and combinations thereof.

11. The structure of claim 10, wherein the macular pigment is mixed with the material made to form the optical substrate.

12. The structure of claim 1, wherein the optical substrate include at least two layers, wherein the macular pigment is disposed between the two of the layers.