FOOD SUPPLEMENT FOR THE PREVENTION AND TREATMENT OF A DEGENERATIVE DISEASE OF THE RETINA

IT202400020518B1Active Publication Date: 2026-09-04OPHTAGON SRL
View PDF 0 Cites 0 Cited by

Patent Information

Application Number
IT102024000020518
Authority / Receiving Office
IT · IT
Patent Type
Patents
Current Assignee / Owner
Filing Date
2024-09-16
Publication Date
2026-09-04
Estimated Expiration
2044-09-16

AI Technical Summary

Technical Problem

Current food supplements for preventing and treating degenerative eye diseases like macular degeneration, particularly age-related macular degeneration (AMD), are limited in effectiveness due to potential side effects and do not adequately address local inflammation and excessive free radical production caused by exposure to ultraviolet rays and blue light from electronic devices.

Method used

A formulation combining quercetin and pyrroloquinoline quinone (PQQ) is developed for oral administration, exhibiting synergistic antioxidant and anti-inflammatory effects to reduce retinal damage from oxidative stress and inflammation, potentially slowing the progression of degenerative eye diseases.

Benefits of technology

The combination of quercetin and PQQ demonstrates enhanced protection against retinal degeneration by reducing inflammation and oxidative stress, offering a safer and more effective preventive and therapeutic option for conditions like AMD.

✦ Generated by Eureka AI based on patent content.
Patent Text Reader
Need to check novelty before this filing date? Find Prior Art

Description

Food supplement for the prevention and treatment of a degenerative disease of the retina DESCRIPTION SECTOR OF INVENTION The present invention concerns a supplement food for the prevention and treatment of a retinal degenerative disease. This invention originates in the field of food supplements. In particular, a food supplement containing a formulation with combined anti-inflammatory and antioxidant suitable for preventing or treating degenerative eye diseases in particular retinal load such as degeneration macular, especially the senile form. FRONT TECHNIQUE Diseases affecting the eyes related to the age of the population represent one of the main causes of the progressive and irreversible loss of vision. Among these eye diseases include glaucoma, cataracts, and related macular degeneration to the age of the individual. The pathological processes underlying these pathologies are complex and in some cases difficult to diagnose, as it may depend on numerous factors factors such as, for example, inflammatory processes local, production of free radicals, aging of anatomical structures of the eye, exposure to ultraviolet rays and to the blue light. This last cause is gaining ground ever-increasing relevance being connected to the increasingly frequent use of devices electronic devices with a screen such as cell phones, computer monitor and television. These eye diseases, due to their slow and often silent progression, come often diagnosed when they are in one stage advanced in which the structures of the eye have suffered damage that makes it less effective the therapeutic treatment. Preventive activity, aimed at reducing the risk of disease progression, covers therefore a great importance in these diseases of the eye in particular in pathologies chronic course affecting the retina such as macular degeneration. In this pathology the macula, the central region of the retina where it has origin the image, is denatured as a result of the natural aging process, of the formation of free radicals and states of inflammation causing a reduction of the field visual and in general the ability to see. The most common form of this disease is senile type (DMS or AMD) and when it manifests itself it can cause loss of central vision. However, in recent times a significant increase in cases of degeneration of the macula in young subjects, mainly attributable to the prolonged exposure to short-wavelength rays produced by the LEDs present in the displays of the electronic devices. It has been observed that continuous exposure to blue rays increase the formation of reactive species of oxygen (ROS) in the pigmented epithelium retinal and inflammatory processes affecting of the eye which contribute to determining the macular degeneration which causes the appearance of clinical signs that negatively influence the view. The irreversibility of these effects has a long-lasting impact on visual acuity and in general about eye conditions. The main symptom associated with macular degeneration is the loss of the center of the field of vision, situation that determines the progressive blurring and / or loss of sight and blurred vision. Furthermore, in the form dry macular degeneration, the center of the retina deteriorates while in the wet form of macular degeneration blood vessels leaks grow under the retina. Notoriously, in the eye the levels of macular pigment are more represented in the central foveal area of ​​the retina, which is measured through the central foveal thickness. The macular pigment, composed of carotenoids lutein and zeaxanthin, is mainly present in the layers of nerve fibers and cells retinal ganglions, with concentrations maximums in the fovea. It is believed that this pigment acts as a filter for blue light and antioxidant agent that protects the retina from agents that play a role in pathogenesis of macular degeneration. For this reason it is believed that a diet integrated with antioxidants can be part of a defense strategy to reduce the damage oxidative in a vulnerable population such as the old one. These have been confirmed in some studies on age-related eye diseases (AREDS) in during which it was observed how the integration in the dietary regime of some vitamins and minerals can slow the progression of degeneration macular, especially in pathological forms that develop in middle to late adulthood (AMD). In light of this evidence, the demand for food supplements aimed at support eye health and prevent eye problems, especially those affecting to prevent macular degeneration especially in a vulnerable population such as that of subjects over 50 years of age. They are currently available on the market food supplements containing vitamins and minerals intended for the population affected by macular degeneration and other diseases that cause a reduction in vision or visual field. They are therefore known food supplements containing vitamin C and vitamin E as substances with antioxidant activity intended for prevention and treatment of forms of macular degeneration, especially of the type age-related. The use of supplements is also known foods containing high doses of beta- carotene, optionally in combination with minerals such as copper and zinc. It is However, it was observed that the administration of beta- carotene at doses considered therapeutically effective is not free from side effects too important, such as liver toxicity, tendency to yellowing of the skin, and for the higher dosages, an increased risk of develop lung cancer. Furthermore, recent studies have shown how the administration of oral supplements containing lutein and zeaxanthin play a role active in the prevention of degeneration macular, especially in the associated form at age (AMD). However, there is a need to have new preparations for oral administration suitable for preventing and treating diseases of the eyes in which they play a prominent role local inflammation together with excessive production of free radicals. One of the purposes of the invention is to provide a suitable formulation for the oral administration to reduce discomfort eyes resulting from prolonged exposure to external agents such as ultraviolet rays and / or blue light that promotes the development of processes local inflammation and / or the production of radicals free, antechamber of forms of degeneration macular. Another purpose is to provide a food supplement whose intake reduces the risk of progression of eye diseases which lead to a reduction in vision and visual acuity such as macular degeneration, in particular related macular degeneration at age. A further purpose is to provide a oral formulation for prevention or treatment of macular degeneration which intake reduces the risk of progression of this pathology. SUMMARY OF THE INVENTION As part of a research project aimed at determine the causes that contribute to development of degenerative diseases of the retina, in detail of the macula, and possible remedies, the inventors selected quercetin as promising molecule based on its ability to activate the expression of the factor Nrf2 transcription system that expresses genes repair and defense mechanisms such as HO-1. Quercetin It thus plays a restorative role in the damage cellular oxidative which represents one of the causes of degenerative eye diseases in particularly affecting the retina and macula. The invention originates from having observed how The activities found for quercetin are significantly increased when used, for the same purposes, in combination with pyrroloquinolinequinone. In vitro studies on combination of these two selected molecules they have in fact demonstrated a synergistic action, resulting from the combination of these two substances, on some biological mechanisms involved in the process of macular senescence. In particular, it was observed in a in vitro model that the combination of quercetin with PQQ activates the Nrf2 system pathway and It also exerts an inhibitory effect on NF-κB, as experimentally highlighted in the following Example 3 determining an antioxidant action and synergistic anti-inflammatory which makes it suitable for combination in prevention and / or treatment of macular degeneration in particular senile form and / or in the protection of the nerve optical. It therefore forms an object of the present invention a formulation containing a combination of quercetin with pyrroloquinolinequinone and a vehicle physiologically acceptable, for use in prevention or treatment of a disease degenerative eye disease. In some embodiments, the degenerative eye disease is a disease retinal degenerative disease, preferably of the retina macula or is it glaucoma. In accordance with preferred embodiments, the formulation and / or food supplement here described are for use in the treatment of macular degeneration, especially of the senile. According to some embodiments the formulation described here is suitable for the protection and / or trophism of the optic nerve and for the use in the prevention and / or treatment of degenerative forms of the eye such as glaucoma. The formulation described here contains pyrroloquinolinequinone and quercetin plays an antioxidant and anti-inflammatory action synergistic on the internal structures of the eye, in particular on the retina, which prevents and / or slows the progression of degeneration macular, especially in pathological forms that develop in middle to late adulthood (AMD). The combination of active ingredients here described exerts a synergistic action of inhibition of NF-κB ("nuclear factor kappa-light- chain-enhancer of activated B cells"), complex protein functioning as a transcription factor which markedly reduces inflammation at the of the retina and the macula. To this effect also adds synergistic antioxidant activity of the combination of pyrroloquinolinequinone with quercetin. In some embodiments the formulation or food supplement for uses doctors described here may contain vitamins, preferably vitamin A, vitamin C, vitamin E and possibly beta-carotene. In accordance with certain aspects of the invention the active ingredients are present in the formulation described here in a quantity pharmaceutically effective. In some embodiments, the formulation described here is contained in a food supplement or nutraceutical that can be introduced into the dietary regime of a individual affected by an eye disease such as described here. The present invention will be described in detailed below with reference to the figures included. BRIEF DESCRIPTION OF THE FIGURES - Figure 1 shows four bar graphs which are representative of the protective effect on senescent cells of the combination of compounds quercetin (QUER) and pyrroloquinoline quinone (PQQ) compared to the two compounds tested individually. black bar graph (Q+P) illustrates the effect synergistic effect found with respect to compounds (Q; P) tested individually, as described in the Example 2; - Figure 2 shows bar graphs that illustrate the cytoprotective effect on high glucose neurotoxicity in cultures retinal cells, of the compounds quercetin (Q) and pyrroloquinoline-quinone (P) tested individually and in combination (Q + P), according to Example 3. - figure 3 illustrates the reduction of the p65 DNA binding activity of NF-κB in ARPE cells exposed to high concentration of glucose according to Example 4 obtained with the two active ingredients QUER and PPQ alone and in synergistic combination according to the invention; - Figure 4 shows bar graphs representative of the activity of the tested compounds individually or in combination on the expression of IL-1β cytokines in ARPE cell culture high concentration of glucose according to Example 4. The bar graphs show that the combination of QUER + PQQ significantly reduces marked secretion of IL-1β, demonstrating the synergistic effect of combining the two compounds in inhibiting the production of cytokines inflammatory in cell cultures; - Figure 5 shows bar graphs representative of the effect on expression of Nrf2 protein in ARPE cell cultures exposed to quercetin and pyrroloquinoline-quinone individually and in combination (QUER + PQQ). bar graphs highlight the synergistic effect registered for the combination of the two ingredients active, as described in Example 5. DETAILED DESCRIPTION OF THE INVENTION It represents a primary aspect of the invention to have a formulation for oral administration suitable for preventing and / or treat macular degeneration in particular of the age-related type. A formulation of is given here combination for use as defined in the enclosed Preferably the active ingredients synergists of the formulation described here are dispersed in a vehicle physiologically or pharmaceutically acceptable suitable for the oral administration. The administration to a subject of a combination of quercetin and pyrroloquinoline- quinone exerts anti-inflammatory effect, antioxidant and free radical scavenger resulting in a reduction in retinal damage induced by oxidative stress. A component or active ingredient of the formulation and supplement described here is consisting of pyrroloquinoline quinone, molecule also known as PQQ or pyrroloquinoline-quinone 3- oxidoreductase and having the following formula chemistry PQQ is an enzyme belonging to the class of oxidoreductases, which catalyzes the following reaction: quinate + pyrroloquinoline-quinone ⇄ 3- dehydroquinate + reduced pyrroloquinoline-quinone. In accordance with the uses described herein, the PQQ or its salt can be obtained as a product commercially available or can be produced by a method known in the art. Pyrroloquinoline quinone can be in free or salt form. Examples of salts pyrroloquinoline quinone include metal salts alkaline, alkaline earth metal salts and salts of ammonium pyrroloquinoline quinone. It is an alkali metal salt is preferable. Examples of alkali metal salts of pyrroloquinoline quinone used in the present invention are the salts of sodium, potassium, lithium, cesium and rubidium. Sodium or potassium salt is preferred because easily obtainable. The alkali metal salt of the pyrroloquinoline quinone may be a salt of alkali metal with a 1 to 3 substitution alkali metals and can be any of the monoalkali metal salts, metal salts dialkaline and trialkaline metal salts. for example, it could be a dialkali metal salt. In this case the disodium salt or salt dipotassium are preferred. The hydrated crystals of disodium salt are highly stable and suitable for the uses described here. According to some embodiments, PQQ present in the composition of the invention has a titre higher than 99.5%, higher than 99.9%. In some embodiments the composition of the invention contains PQQ in a quantity ranging from 50 to 5000mg, from 100 to 2000mg, 250 to 750mg. According to some embodiments the composition of the invention contains PQQ in a quantity ranging from 0.1 to 95% by weight, from 1 to 90% by weight, 10 to 85%, 30 to 80 by weight. Another ingredient of the composition or The supplement described here is quercetin, which combination with PQQ exerts the effect synergistic described here. Quercetin is a flavonoid typically found in plant origin and chemically defined as 3, 3',4',5,7-pentahydroxyflavone having the following structural formula: In the formulation quercetin can be in free form, e.g. as quercetin aglycone or of a derivative or metabolite such as 3- methylquercetin and / or salt or ester physiologically acceptable. Combining Quercetin with PQQ determines an anti-inflammatory effect and synergistic antioxidant. From a biological point of view, quercetin acts as a free radical scavenger, donating a pair of electrons through the moiety o- quinone / quinone methide. According to some embodiments the formulation or supplement described here contain quercetin in quantities ranging from 2 to 20% from 5 to 15, for example 10% by weight compared to the total weight of the composition in dosage unit form. For example, the composition in the form of units of dosage, for example of tablet, can contain 25 to 400 mg of quercetin optionally in ester or salt form. In some embodiments, the unit of dosage of the composition, e.g. in form of tablet or powder to be dissolved in water, includes at least the following active components: - PQQ in quantities ranging from 1 to 200mg, from 5 at 100mg, for example 20mg - Quercetin or its ester or physiological salt acceptable in a quantity ranging from 25 to 400 mg, 50 to 200 mg, e.g. 200 mg, according to any combination of the quantities of the two ingredients mentioned above. In accordance with certain embodiments the formulation described here contains PPQ and quercetin in the following weight ratios of 0.5:2 at 10:100, preferably from 1:10. In the context of the present invention with the combination term means that the components or active substances such as PQQ and quercetin are both present in composition without any interaction between them chemical reaction, for example with the formation of covalent bonds. Typically, in the formulation or in the supplement described here the components active ingredients are mixed and preferably dispersed in a physiologically acceptable vehicle. In this application, with the term "synergism or synergistic activity" means an activity that is greater than the sum of the activity of the single active ingredient. In In particular, synergy occurs when at least two active substances or ingredients interact in a way that enhances or increases one or more of their effects. Therefore, two substances or active ingredients that produce effects evidently similar will sometimes produce effects exaggerated or reduced when used at the same time and a quantitative evaluation is necessary to distinguish these cases from a simple additive action (Tallarida RJ. Drug Synergism: its detection and applications. J PharmacolExpTher. 2001 Sep:298(3):865-72). In some embodiments, the composition of the invention further comprises at least one additional active ingredient chosen from phosphatidylserine, nicotinamide, Coleus Forskolii e their mixtures whose presence, individually or in mixes together, contributes to the action antioxidant and anti-inflammatory, increasing the effectiveness of the composition in the treatment of macular degeneration, in particular senile form. In some embodiments, the composition of the invention may include further one or more micronutrients and / or minerals such as salts of Mg, K, Na, Zn, Fe, Cr, Se, Mn and others. The term "vehicle" as used in the present indicates a medium, excipient, diluent with in which the active ingredients are administered via Oral. The formulation described here can be in form of ophthalmic solution suitable for topical administration, typically for instillation. Any vehicle and / or excipient suitable for the desired form of preparation for the administration to humans and in general mammals is contemplated for use with the compounds described in the present invention. For the purposes of this application, the the term "physiologically acceptable" means indicate edible substances that are approved by health authorities for use in pharmaceutical, nutritional or food. The formulation described here can be contained in a product or food intended for animals, typically mammals. In the context of this application with the combination term means that one or more active ingredients are added or mixed with one or more ingredients. The term combination It should therefore not be understood in the sense that the active ingredients combine with each other with formation of chemical or other bonds. The formulations or compositions of this invention includes any composition achieved by administering the association of active ingredients of the present invention and a physiologically or pharmaceutically conveying acceptable. Such compositions are suitable for use food, nutritional, pharmaceutical or dietetic in mammals, particularly humans. The composition of the invention may take a wide variety of preparation forms, a depending on the desired route of administration. For example, for oral administration the composition can be in solid form for example of tablet, capsule, powder, granular, prolonged-release formulations of the principles active. The compositions in solid form, in especially in tablet form, are preferred compared to other types of preparations. Preparations in solid form can include one or more carriers such as starches, sugars, microcrystalline cellulose, and optionally diluents, granulating agents, lubricants, binders, disintegrating agents. Tablets, pills, capsules, granules They may also contain a binder such as rubber tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegration such as corn starch, starch potatoes, alginic acid; a lubricant such as magnesium stearate; a sweetening agent such as sucrose, lactose, or saccharin. If desired, The tablets can be coated with traditional techniques. When the pharmaceutical unit form is a capsule, it may contain in addition to materials of the above type a liquid vehicle such as a fatty oil. In the case of preparations in liquid form for oral administration, such as in case of suspensions, emulsions, solutions a suitable vehicle can be chosen between water, glycols, oils, alcohols and their mixtures. In some embodiments the composition of the invention is in liquid form, ready for hiring. The composition may also include contain flavouring agents, preservatives, dyes and the like. In some embodiments, the extracts plants or active ingredients contained in the composition of the present invention may be combined or mixed as active ingredients in intimate mixture with an edible vehicle suitable and / or an excipient according to the techniques pharmaceutical and food industry or traditional nutrition. Compositions for pharmaceutical use or nutritionally can be adequately presented in a single pharmaceutical form and prepared by any of the well-known methods known in pharmaceutical or food technology. In some embodiments the compositions or preparations of the invention may contain at least 0.1% of each bioactive principle / substance. The percentage of active ingredient in these compositions can obviously vary for example from about 1% to approximately 60% of the unit weight. The amount of active compound in such compositions is such that it is will get a dosage prophylactically or therapeutically effective. In some embodiments, the composition of the invention further comprises a or more additional components such as additives, fillers, stabilizers, emulsifiers, textured, film-forming, plasticizers, agents humectants and thickeners. Suitable excipients include one or more agents anti-caking agents preferably carbon dioxide silicon, magnesium salts of fatty acids. A preferred form of administration is in capsule, containing the ingredients and excipients according to any of the embodiments herein described. Various other materials may be present as coverings or to modify physical shape of the pharmaceutical unit. For example, tablets can be coated with shellac, sugar or both. To prevent disintegration during the transit through the upper part of the gastrointestinal tract, the composition can be an enteric-coated formulation. A syrup or elixir may contain in added to the active ingredient, sucrose as sweetening agent, methyl and propylparabens as preservatives, a colorant and a flavoring such as cherry or orange flavor. In some embodiments, in the compositions of the present invention, the principles active ingredients are normally formulated in units of dosage. The dosage unit can contain from 0.1 to 1,000 mg of active ingredient or extract plant containing the active ingredient per unit dosage for daily administration. In certain embodiments the composition of the invention the dosage unit is a sachet that can contain from 1 to 50 g, from 5 to 30g of composition. Alternatively the unit of dosage is one capsule or one tablet. In some embodiments, the formulation will contain quantitative principles active which will depend on the severity of the eye pathology, related symptoms, of the condition, of further therapies in course, from the individual health status and from the response to the association of active ingredients. In some embodiments the dose is in the range from 0.001% by weight to about 60% by weight weight of the formulation. According to some embodiments the formulation described here is contained or is a food supplement. The present invention is further illustrated in detail by the following examples. EXAMPLE 1 Food supplement in tablet form for prevention or treatment of macular degeneration retinal containing the following active ingredients: Active ingredient Quantity Quercetin 200mg PQQ 20mg Phosphatidylserine 100mg Nicotinamide (niacin) 54mg Coleus Forskolii 50mg EXAMPLE 2 Experimental evidence: in vitro model of senescence mobile phone Fibroblast cultures were used primary humans; for crop production senescent, the cells were counted and a equal number of cells were seeded (4 × 10 cells / cm ) at each passage in continuous culture until the growth of the crop is slowed to less than 0.5 doublings of the population (PD) / week. Crop growth is slowed to a crawl of 0.5 population doublings (PD) / week. The cells were subjected to continuous culture until the onset of replicative senescence and to growth arrest in 3 replicates biological. First-passage fibroblasts PD = 24 and late-passage fibroblasts at PD = 84. Quantification of senescent cell burden. Cellular senescence was assessed in 3 biological replicates using the marker β-associated senescence biochemical galactosidase (SA-β-Gal) using a kit commercial (Sigma Aldrich, UK) according to the manufacturer's instructions, with a minimum of 100 cells evaluated per replicate. Primary fibroblast cultures were so considered senescent at PD84. This was verified by molecular characterization and biochemistry of growth kinetics of cultures; β-galactosidase staining associated with senescence (SA-βgal) has been shown a significant increase in the number of cells senescent, from 8% in first-grade cells passage to 36% in the last passage ones. SASP factors in conditioned media derived from senescent cells have shown levels altered for several key SASP proteins; are elevated levels of IL-8, MMP-3, were observed MMP-10 and TIMP2, but reduced levels of IL10. Passing fibroblasts were treated with quercetin (Q) 10 μM, pyrroloquinoline quinone (P) 1 μM or Q + P and viability were measured of senescent cells (SA-β-gal+ cells) and of total cells. The number of viable cells is calculated with respect to cells treated with the vehicle only (DMSO). n= 3 experiments independent, one-way ANOVA. EXAMPLE 3 Cytoprotective effects of quercetin and pyrroloquinoline quinone against neurotoxicity from high glucose in retinal cells cultivated. ARPE-19 cells were used (American Type Culture Collection, Manassas, VA, USA), a pigmented epithelial cell line human retinal effusion (RPE). ARPE cells were seeded at a density of 8 × 10 cells / well in a plate 96-well plates and cultured overnight. Then the cells were treated with 25 mM D- glucose (final concentration 30 mM because 5 mM of glucose are already present in the soils of cell culture) alone or together with quercetin (QUER) 10μM, pyrroloquinoline quinone (PQQ) 1μM or to the formulation containing QUER+PQQ at a concentration of 10μM for 24 hours or with medium empty (control). After washing gently with PBS, the cells were incubated with a solution of MTT at 0.5 mg / ml in the dark for 4 h. It was added DMSO to solubilize the formazan after the supernatant was removed. The absorbance at 570 nm was was measured with an ELISA reader (Multiskan MK3) for cell viability. EXAMPLE 4 QUER and PQQ reduce DNA binding activity of NF-kβ p65 in ARPE cells exposed to high glucose levels. Many studies have found that the NF-kB pathway plays a fundamental role in the etiogenesis of age-related eye diseases, including AMD. NF-kB family of transcription factors plays a critical role in regulating expression of a wide variety of genes, particularly in inflammatory process, including cytokines such as IL- 1β, IL-6 and TNF-α. To evaluate the ability of compounds which are the object of the invention to inhibit NF-kB activity in ARPE cell cultures (16-HBE) we used the NF-kB p65 DNA assay Binging Activity Assay by TransAM p65 transcription factor ELISA kit (Active Motif, Carlsbad, CA). Cells were treated with 25 mM D-glucose (final concentration 30 mM because 5 mM glucose was already present in the cell culture medium) in the presence and in absence of QUER 10 µm, PQQ 1 µm or QUER+PQQ, for 12 hours. Subsequently, it was determined the DNA binding activity of NF-kB p65. Each bar graph of the attached figure 3 represents the mean ± SD (n = 4). *p<0.001 vs. CSE, **p<0.001 vs. QUER or PQQ alone. 12 hours after stimulation. with GLU has markedly promoted the activity of DNA binding of NF-kB p65. However, a minor decrease was observed DNA binding activity in stimulation with GLU in the presence of QUER and PQQ. Surprisingly, the combination of QUER + PQQ reduced strongly the DNA binding activity of NF-kB p65, demonstrating a synergistic effect of the two compounds. Consistently, effects have been demonstrated similar in terms of cytokine expression. The ARPE cells were incubated with 25 mM D- glucose (final concentration 30 mM, since 5 mM of glucose were already present in the soil cell culture) and maintained in culture for another 7 days. The glucose concentration in control conditions was 5 mM. IL-1β is was detected with ELISA kits purchased from Abcam, Cambridge (MA) USA. Each sample was analyzed in duplicate using 100 μl of medium of culture per well. Prolonged exposure high glucose increases IL-1β expression in cultured ARPE cells. The treatment simultaneous with QUER 10µm or PQQ 1µm reduced significantly the secretion of cytokines stimulated by glucose. Surprisingly, as highlighted in Figure 4, the combination of QUER+PQQ dramatically reduced the secretion of IL-1β, demonstrating a synergistic effect of the two compounds in the inhibition of the production of cytokines. EXAMPLE 5 Activation of Nrf2 expression in cells HARPS ARPE cells were exposed to QUER, PQQ or a combination of the two compounds final concentration of 10 μM (10:1 ratio) for evaluate the expression of the Nrf2 protein in the time. As shown in Figure 5, the treatment with QUER caused an increase significant, time-dependent, of Nrf2 protein expression in nuclear extracts. Quantification of three Independent western blots showed that after 1 hour of exposure to 10 μM QUER, the expression of Nrf2 is significantly increased and is remained upregulated for up to 12 hours, while levels of the housekeeping transcription factor Sp1 were stable. PQQ 1 μM induced a minor increase of nuclear Nrf2. The combination of the two compounds QUER, PQQ has massively induced Nrf2 expression.

Claims

CLAIMS 1. A composition comprising pyrroloquinoline quinone in combination with quercetin or its salt or ester and a physiologically acceptable carrier for use in the prevention and / or treatment of a degenerative eye disease, particularly affecting the retina.

2. Composition for use according to claim 1, wherein the degenerative eye disease affecting the retina is age-related macular degeneration or glaucoma.

3. Composition for use according to claim 1 or 2 in the treatment or prevention of a degenerative eye disease with damage or injury to the retina.

4. A composition for use according to any of claims 1 to 3 further comprising an active ingredient selected from the group consisting of phosphatidylserine, nicotinamide, Coleus Forskolii and mixtures thereof.

5. Composition for use according to any of claims 1-4 further comprising at least one further active component selected from micronutrients, mineral salts, B177843 enzymes, vitamins and mixtures thereof.

6. Food supplement comprising a composition for use according to any of claims 1-5.

7. Food supplement for use according to claim 6 in solid form for oral administration.

8. Food supplement for use according to claim 7 in tablet or capsule form.

9. Food supplement for use according to any of claims 6-8 comprising Quercetin 200mg PQQ 20mg Phosphatidylserine 100mg Nicotinamide (niacin) 54mg Coleus Forskolii 50mg one or more physiologically acceptable excipients.

10. Food supplement for use according to any of claims 6-9 wherein said composition is contained in a B177843 capsule suitable for oral administration.