Composition containing lutein, zeaxanthin, astaxanthin, anthocyanins and proanthocyanidins

Abstract

A trace element supplement consisting of lutein, zeaxanthin, astaxanthin, anthocyanins, and proanthocyanidins is designed to improve retinal health in children and adolescents, relieve eye strain, and slow the progression of myopia. The daily dose is 1–20 mg lutein, 0.2–4 mg zeaxanthin, 0.5–8 mg astaxanthin, 10–700 mg taurine, and 0.5–8.5 mg zinc; the nighttime dose is 1–100 mg eyebright extract, 10–300 mg chamomile extract, 1–200 mg anthocyanins, and 1–500 mg proanthocyanidins.

Description

Summary

[0001] The present invention relates to a liquid composition containing lutein, zeaxanthin, astaxanthin, anthocyanins and proanthocyanidins, which was specifically developed to delay the development and progression of myopia in children and adolescents.

[0002] The formula is available in liquid strip packs, divided into two versions for daytime and nighttime use. The daytime formulation preferably contains 10 mg lutein, 2 mg zeaxanthin, 1 mg zinc, 50 mg taurine, and 0.5 mg astaxanthin; the nighttime formulation contains 30 mg eyebright extract, 100 mg chamomile extract, 10 mg anthocyanins (from blackcurrant extract, standardized to 36% anthocyanins, 25% anthocyanidins), and 10 mg proanthocyanidins (from grape seed extract, standardized to 95% proanthocyanidins).

[0003] The combination of these active ingredients works synergistically to reduce oxidative stress in the retina, protect visual function and support the structural integrity of the eye, thereby effectively delaying the progression of myopia in children and adolescents.

[0004] The present invention relates to the use of a composition containing lutein, zeaxanthin, astaxanthin, anthocyanins and proanthocyanidins as well as trace elements, for improving retinal health in children and adolescents, for relieving visual fatigue and for delaying the development of myopia. State of the art

[0005] The increasing prevalence of myopia among school-age children represents a significant global health problem. This is likely due to the fact that children spend a lot of time on activities that promote myopia, such as reading, computer use, or smartphone use. Such a high myopia prevalence places a considerable burden on the global population, particularly in developing countries where there is a great need for vision correction that is currently unmet.

[0006] Myopia is characterized by blurred distance vision, usually caused by an abnormal elongation of the eyeball. This results in the image formed by the cornea and lens being focused in front of the light-sensitive cells of the retina. People who perform close work for extended periods can develop pseudomyopia. Their distance vision is blurred due to overuse of the focusing mechanism. After prolonged close work, the eyes cannot immediately refocus sharply on distant objects. Clear distance vision usually returns after periods of rest. However, persistent visual stress can lead to a permanent decline in distance vision over time.

[0007] The exact biological causes of myopia are still unclear. Studies suggest that the following factors are possible triggers: 1. Intraocular pressure: In myopic patients with lower intraocular pressure, myopia appears to progress more slowly than in patients with higher intraocular pressure, suggesting a role for intraocular pressure in myopia progression. 2. Ciliary muscle contraction: Contraction of the ciliary muscle leads to an increase in axial length, while relaxation of the muscle reduces it, suggesting that the ciliary muscle could be a potential trigger of myopia. Prolonged close work can lead to sustained pressure on the ciliary muscle and thus promote the development of myopia in children. 3. Light damage: Epidemiological and experimental studies suggest that cumulative exposure to blue light can have short-term and long-term effects on the eye, such as blurred vision, visual fatigue, retinal damage, deterioration of visual function, and age-related eye diseases. 4. Scleral hypoxia: Prolonged close work can reduce the opening and blood flow of the choroidal capillaries, leading to hypoxia and nutrient deficiency in the adjacent scleral tissue. Hypoxic conditions in the scleral environment activate the HIF-1α signaling pathway, promote the differentiation of fibroblasts into myofibroblasts, reduce collagen synthesis, and lead to a remodeling of the scleral extracellular matrix, resulting in a thinning of the sclera and an elongation of its axial length. 5. Oxidative stress: In highly myopic patients, significant changes in the parameters TAC and total nitrite / nitrate in the aqueous humor were observed, which correlate strongly with the development of myopia. 6. Lack of outdoor activity: Outdoor light promotes the release of dopamine (DA). Activation of D1 receptors leads to hyperopia, while activation of D2 receptors leads to myopia. Strong outdoor sunlight activates dopamine D1 signaling pathways in the retina and shifts the refractive state towards hyperopia, thereby inhibiting myopia progression.

[0008] The factors mentioned above could serve as potential targets for the prevention and alleviation of myopia. Studies show that carotenoids such as lutein and zeaxanthin protect the macula against blue light damage and oxidative stress, while polyphenolic plant extracts (e.g., proanthocyanidins, anthocyanins) have antioxidant effects, reduce visual fatigue, and improve microcirculation.

[0009] DE202004010212U1 deals with the use of lutein, vitamins and minerals to combat oxidative damage to the macula caused by free radicals and to prevent age-related macular degeneration.

[0010] DE000020300305U1 deals with the use of lutein, vitamins and minerals for the prevention of nutrient deficiencies of the macula and for the treatment of existing age-related macular degeneration.

[0011] US20110268817A1 concerns the use of L-carnitine in combination with antioxidants such as vitamin E and inorganic elements such as manganese, zinc, sodium and potassium for the manufacture of a physiological dietary supplement or for the prevention or treatment of accommodative asthenopia.

[0012] US20160151437A1 concerns the use of bilberry fruit extract, lutein, zeaxanthin, β-carotene and omega-3 to improve visual impairments, such as improving eyesight, night vision and promoting recovery after long-term use of screen devices, and may theoretically prevent or treat age-related macular degeneration (AMD), cataracts and retinitis pigmentosa (RP).

[0013] In current technology, the documents refer either to the prevention of age-related macular degeneration or to the improvement of visual function. However, individual supplements do not simultaneously cover blue light protection, antioxidant effects, and the relief of visual fatigue, which are necessary for myopia prevention and the promotion of visual health in children and adolescents. Description of the invention

[0014] To solve the aforementioned problems, the present invention offers a trace element-nutrient combination containing both carotenoids and plant-based antioxidants, available in two separate formulations – one for day and one for night. The “daytime formulation” is taken during the day, and the “nighttime formulation” at night, to ensure comprehensive eye protection for children and adolescents.

[0015] Lutein and its stereoisomeric zeaxanthin forms, including meso-zeaxanthin, are the only carotenoids found in the human retina, with the highest concentration in the macula. Located in the center of the retina, at the back of the eye, the macula is responsible for central vision due to its high density of photoreceptors. These three carotenoids exhibit a regional distribution within the macula: lutein in the periphery, zeaxanthin in the mid-periphery, and meso-zeaxanthin in the center. Together, they form macular pigment, which is crucial for maintaining optimal visual function. With the increasing use of electronic devices, children's and adolescents' eyes are constantly exposed to potentially harmful blue light emitted from interactive whiteboards, smartphones, computers, tablets, and LED lighting. In children, approximately 15% of blue light at 400 nm and about 60–65% at 460–480 nm reach the retina. Children's retinas are particularly sensitive to short-wavelength radiation (UVA and blue light). Epidemiological and experimental studies show that cumulative blue light exposure can have short-term and long-term effects on the eye, including blurred vision, eye strain, retinal damage, and an increased risk of myopia. Since lutein has an absorption maximum at about 460 nm, it lies in the blue light range and can absorb 40-90% of the incident blue light (depending on the concentration), effectively reducing light damage.

[0016] Lutein is primarily synthesized in plants and microorganisms and is not produced by humans; therefore, it must be obtained through diet. Lutein can also remain in the human retina for extended periods. Supplementation increases both serum lutein concentration and macular pigment edema (MPOD). After discontinuation of supplementation, serum lutein concentration returns to baseline levels within 50 days to 3 months, while MPOD remains elevated, indicating a long-lasting protective effect on the macula.

[0017] In many regions of the world, fruit and vegetable intake is low, resulting in lutein and zeaxanthin consumption below recommended levels. Data from NHANES 2003-2004 show that children and adolescents (1-18 years) consume less than 0.6 mg of lutein + zeaxanthin per day. Therefore, additional supplementation is necessary. According to the FAO / WHO JECFA, the acceptable daily intake (ADI) of lutein and zeaxanthin from marigolds is 2 mg / kg body weight / day.

[0018] Lutein and zeaxanthin are unstable, easily oxidized, and poorly soluble. Their solubility and absorption can be improved by microencapsulation, which increases bioavailability.

[0019] Astaxanthin is a potent antioxidant. It has been reported to significantly improve blood flow to the retinal capillaries surrounding the optic disc. Therefore, by enhancing microcirculation, astaxanthin can restore ciliary body function, improve accommodation, and reduce visual fatigue. Microencapsulation may increase its water solubility and absorption.

[0020] Animal studies show that astaxanthin modulates dopamine D1 receptors and restores dopamine levels, thereby simulating the effects of external light to compensate for a lack of outdoor activity.

[0021] According to Regulation (EU) 2023 / 1581, the maximum astaxanthin dose for children and adolescents is: • 2.3 mg astaxanthin / day (23 mg oleoresin) for children aged 3 to <10 years • 5.7 mg astaxanthin / day (57 mg oleoresin) for adolescents aged 10 to <14 years • 8 mg astaxanthin / day for the general population aged 14 years and over

[0022] Zinc is an essential trace element that is important for the formation of visual pigments in the retina and supports vision in low light. Zinc protects retinal cells, especially the retinal pigment epithelium (RPE), from oxidative stress.

[0023] Taurine is an amino acid that is crucial for the healthy development and function of children's eyes, especially the retina. It acts as an antioxidant and protects retinal neurons. Studies show that taurine supplements can reduce visual fatigue and prevent damage caused by eye strain.

[0024] Eyebright (Euphrasia officinalis L.) is a traditional medicinal herb with diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, anticancer, antifungal, antiviral, antihypertensive, skin-protective, antiepileptic, and anticatarrhal properties. Eyebright can be used to treat eye inflammations such as ophthalmitis, blepharitis, cataracts, conjunctivitis, and congestion, as well as colds, sinusitis, and seasonal allergies.

[0025] Chamomile (Matricaria chamomilla L.) is one of the most widely used herbs worldwide. It has antioxidant and antibacterial properties and has demonstrated significant antiplatelet effects in vitro. Experiments have shown that eye drops containing chamomile extract have a positive effect on UVB-induced oxidative stress and inflammation in corneal cells.

[0026] Proanthocyanidins (PCs) are a class of polyphenolic compounds widely distributed in the plant kingdom. They possess strong antioxidant activity and are more effective free radical scavengers than vitamins C and E. Proanthocyanidins have diverse physiological functions, including antibacterial, antiviral, anticarcinogenic, anti-inflammatory, anti-allergic, vasodilatory, anti-edema, and neuroprotective effects. Cell experiments have shown that grape seed extract can protect against damage to retinal ganglion cells caused by oxidative stress.

[0027] Currently, various commercial sources of proanthocyanidins can be used to prepare the compositions within the scope of the present invention: grape seeds (Vitis vinifera) extracted with water or ethanol; and pine bark extract (Pinus pinaster) extracted with water or ethanol. A proanthocyanidin content of 95% is preferred.

[0028] Anthocyanidins are powerful antioxidants. Many fruits and vegetables are rich in anthocyanins and are frequently used as dietary supplements for eye health in Europe and East Asia. Anthocyanidins are believed to improve night vision. Clinical studies have shown that 12.5–50 mg of anthocyanidins from blackcurrants improved the dark adaptation threshold in subjects. This could be related to anthocyanidins stimulating rhodopsin regeneration. Anthocyanidins found in plants are O-glycosides composed of glycosides (cyanidins) and sugars. Glycosylation can improve the stability and water solubility of anthocyanidins.

[0029] Currently, several commercially available anthocyanidin sources can be used to prepare the compositions according to the present invention: bilberry extract (Vaccinium myrtillus), blackcurrant extract (Ribes nigrum L.), maqui berry extract (Aristotelia chilensis), blueberry extract (Vaccinium uliginosum L.), and aronia extract (Aronia melanocarpa). These plant extracts are generally extracted with water or ethanol, with an anthocyanin content of 36% and an anthocyanidin content of 25% being preferred.

[0030] According to the present invention, lutein and zeaxanthin in the daily formula can absorb blue light and scavenge free radicals; zinc is involved in rhodopsin metabolism and protects retinal epithelial cells; taurine promotes retinal neuroprotection; and astaxanthin possesses a high antioxidant capacity. This combination reduces photo-oxidative damage caused by ultraviolet and blue light during the day. Lutein, zeaxanthin, and astaxanthin are fat-soluble and have long half-lives: approximately 76 days for lutein and 32 hours for astaxanthin. Taking them with meals during the day increases their absorption rate.

[0031] According to the present invention, the plant-based active ingredients, such as anthocyanins and proanthocyanidins, in the nighttime formula can scavenge free radicals, inhibit inflammatory reactions, reduce ciliary muscle tension, improve the microcirculation of the eye, and alleviate symptoms such as dryness and fatigue. Anthocyanins and proanthocyanidins are water-soluble ingredients. Anthocyanin plasma concentrations reach their peak 30 minutes after ingestion and then decline rapidly within 4 hours. Taking the product in the evening can help to quickly alleviate daytime vision problems and eye inflammation, promote blood circulation, relax the ciliary muscle, and thus slow the progression of myopia.

[0032] As is known in the field, the appropriate dosage depends on various factors, such as height, weight, body surface area, age, sex, and the type and nature of the food consumed. The dosage regimen depends on the dosage, the patient's general health, and any other medications being taken. Therefore, based on the aforementioned factors, the appropriate dosage regimen for the combination described in the present invention can be determined by consulting a physician.

[0033] According to the present invention, the daily dose of the micronutrient combination product is 1 mg to 20 mg lutein, 0.2 mg to 4 mg zeaxanthin, 0.5 mg to 8 mg astaxanthin, 10 mg to 700 mg taurine, and 0.5 mg to 8.5 mg zinc. The nighttime dose of the micronutrient combination product is 1 mg to 100 mg eyebright extract, 10 mg to 300 mg chamomile extract, 1 mg to 200 mg anthocyanins, and 1 mg to 500 mg proanthocyanidins.

[0034] In a further embodiment according to the present invention, the daily dose of the micronutrient combination product is 6 mg to 12 mg lutein, 1.2 mg to 2.4 mg zeaxanthin, 0.3 mg to 8 mg astaxanthin, 20 mg to 500 mg taurine and 1 mg to 7 mg zinc; the nighttime dose of the micronutrient combination product is 20 mg to 80 mg eyebright extract, 30 mg to 200 mg chamomile extract, 1 mg to 100 mg anthocyanins and 1 mg to 200 mg proanthocyanidins.

[0035] In a further preferred embodiment according to the present invention, the daily dose of the micronutrient combination product is 8 mg to 10 mg lutein, 1.6 mg to 2 mg zeaxanthin, 0.5 mg to 2.3 mg astaxanthin, 50 mg to 200 mg taurine and 1 mg to 5 mg zinc; the nighttime dose of the micronutrient combination product is 30 mg to 50 mg eyebright extract, 50 mg to 100 mg chamomile extract, 1 mg to 50 mg anthocyanins and 1 mg to 100 mg proanthocyanidins.

[0036] In a further, more preferred embodiment according to the present invention, the daily dose of the micronutrient combination product is 10 mg lutein, 2 mg zeaxanthin, 0.5 mg astaxanthin, 50 mg taurine and 1 mg zinc; the nightly dose of the micronutrient combination product is 30 mg eyebright extract, 100 mg chamomile extract, 10 mg anthocyanins and 10 mg proanthocyanidins.

[0037] According to the present invention, lutein and zeaxanthin must be derived from natural sources such as marigolds and not from synthetic sources. Microencapsulated lutein and zeaxanthin are preferred.

[0038] According to the present invention, astaxanthin must be derived from Haematococcus pluvialis and not from synthetic sources. Microencapsulated astaxanthin is preferred.

[0039] According to the present invention, the zinc source is preferably an organic zinc source such as zinc gluconate, zinc glycinate or zinc citrate.

[0040] According to the present invention, the source of anthocyanidins can be one or more commercially available plant anthocyanin extracts, such as bilberry (Vaccinium myrtillus), blackcurrant (Ribes nigrum L.), maqui berry (Aristotelia chilensis), blueberry (Vaccinium uliginosum L.), and aronia (Aronia melanocarpa). The anthocyanin content is preferably 36% and the anthocyanidin content 25%.

[0041] According to the present invention, the source of proanthocyanidins can be one or more commercially available plant proanthocyanidin extracts, such as grape seeds (Vitis vinifera) and pine bark (Pinus pinaster). The purity of the proanthocyanidins must be at least 95%.

[0042] The micronutrient combination product of the present invention can preferably be provided in the form of a split day and night administration, or all trace elements can be provided in a single portion.

[0043] The micronutrient combination product of the present invention can be contained in various products. For example, in foods, food supplements, (supplementary) balanced diets, pharmaceutical products, solid, liquid or semi-solid preparations.

[0044] The micronutrient combination of the present invention can be provided in the form of hard capsules, soft capsules, drinks, capsule cups, vials, tablets, dragees, candies, jellies, powders, granules, etc.

[0045] The dosage form of the composition according to the present invention may, for example, contain formulation aids such as fillers (carriers), disintegrants, binders, flow regulators, lubricants, emulsifiers, solubilizers, wetting agents, defoamers, viscosity and consistency modifiers, gelling agents, solvents, solubilizers, adsorbents, plasticizers, release agents, humectants, absorbents, absorption enhancers, film formers, sweeteners such as sugars, sugar substitutes and artificial sweeteners, acidulants, flavorings, pigments, antioxidants, synergists, preservatives, and colorants. Other common excipients are described in "Remington's Pharmaceutical Science", 15.Edition, Mack Publishing Co., described.

[0046] Preferred embodiments are listed below: According to the present invention, the composition with lutein, zeaxanthin, anthocyanins, and proanthocyanidins preferably has the following dosage unit: a daily dose unit with 10 mg lutein, 2 mg zeaxanthin, 0.5 mg astaxanthin, 50 mg taurine, and 1 mg zinc (from zinc gluconate); a night dose unit with 30 mg eyebright extract, 100 mg chamomile extract, 10 mg anthocyanins (from blackcurrant extract, standardized to 36% anthocyanins and 25% anthocyanidins), and 10 mg proanthocyanidins (from grape seed extract, standardized to 95% proanthocyanidins). The composition is in the form of liquid single sticks. Quotes in the description

[0047] This list of documents provided by the applicant is automatically generated and is for informational purposes only. Cited patent documents DE202004010212U1

[0006] DE000020300305U1

[0007] US20110268817A1

[0008] US20160151437A1

[0009] Zitierte Nicht-Patentliteratur

[0048] Aggarwala KRG. Ocular Accommodation, Intraocular Pressure, Development of Myopia and Glaucoma: Role of Ciliary Muscle, Choroid and Metabolism. Med Hypothesis Discov Innov Ophthalmol. 2020;9(1):66-70. Epub 2020 Jan 5. PMID: 31976346; PMCID: PMC6969557.

[0004] Meng ZY, Yang L, Zhou P. Ciliary muscles contraction leads to axial length extension--The possible initiating factor for myopia. PLoS One. 2024 Apr 16;19(4):e0301844. doi: 10.1371 / journal.pone.0301844. PMID: 38626193; PMCID: PMC11020782.

[0004] Gazzolo D, Picone S, Gaiero A, Bellettato M, Montrone G, Riccobene F, Lista G, Pellegrini G. Early Pediatric Benefits of Lutein for Maturing Eyes and Brain-An Overview. Nutrients. 2021 Sep 17;13(9):3239. doi: 10.3390 / nu13093239. PMID: 34579116; PMCID: PMC8468336.

[0004] Wu H, Chen W, Zhao F, Zhou Q, Reinach PS, Deng L, Ma L, Luo S, Srinivasalu N, Pan M, Hu Y, Pei X, Sun J, Ren R, Xiong Y, Zhou Z, Zhang S, Tian G, Fang J, Zhang L, Lang J, Wu D, Zeng C, Qu J, Zhou X myopia control. Proc Natl Acad Sci US A. 2018 Jul 24;115(30):E7091-E7100. doi: 10.1073 / pnas.1721443115. Epub 2018 Jul 9. PMID: 29987045; PMCID: PMC6064999.

[0004] Merida S, Villar VM, Navea A, Desco C, Sancho-Tello M, Peris C, Bosch-Morell F. Imbalance between Oxidative Stress and Growth Factors in Human High Myopia. Front Physiol. 2020 May 14;11:463. doi: 10.3389 / fphys.2020.00463. PMID: 32477165; PMCID: PMC7240122.

[0004] Zhang S, Yang J, Reinach PS et al (2018) Dopamine receptor subtypes mediate opposing effects on form deprivation myopia in pigmented guinea pigs. Invest Ophthalmol Vis Sci 59:4441-4448

[0004] Chen S, Zhi Z, Ruan Q et al (2017) Bright light suppresses form-deprivation myopia development with activation of dopamine D1 receptor signaling in the ON pathway in retina. Invest Ophthalmol Vis Sci 58:2306-2316

[0004] Li LH, Lee JC, Leung HH, Lam WC, Fu Z, Lo ACY. Lutein Supplementation for Eye Diseases. Nutrients. 2020 Jun 9;12(6):1721. doi: 10.3390 / nu12061721. PMID: 32526861; PMCID: PMC7352796.

[0012]

[0013] Kizawa Y, Sekikawa T, Kageyama M, Tomobe H, Kobashi R, Yamada T. Effects of anthocyanin, astaxanthin, and lutein on eye functions: a randomized, double-blind, placebo-controlled study. J Clin Biochem Nutr. 2021 Jul;69(1):77-90. doi: 10.3164 / jcbn.20-149. Epub 2021 Feb 5. PMID: 34376917; PMCID: PMC8325772. Duan H, Song W, Guo J, Yan W. Taurine: A Source and Application for the Relief of Visual Fatigue. Nutrients. 2023 Apr 12;15(8):1843. doi: 10.3390 / nu15081843. PMID: 37111062; PMCID: PMC10142897.

[0020] Paduch R, Woźniak A, Niedziela P, Rejdak R. Assessment of eyebright (euphrasia officinalis L.) extract activity in relation to human corneal cells using in vitro tests. Balkan Med J. 2014 Mar;31(1):29-36. doi: 10.5152 / balkanmedj.2014.8377. Epub 2014 Mar 1. PMID: 25207164; PMCID: PMC4115993.

[0021] Bigagli E, Cinci L, D'Ambrosio M, Luceri C. Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells. J Photochem Photobiol B. 2017 Aug;173:618-625. doi: 10.1016 / j.jphotobiol.2017.06.031. Epub 2017 Jun 24. PMID: 28704790.

[0022] Wang H, Zhang C, Lu D, Shu X, Zhu L, Qi R, So KF, Lu D, Xu Y. Oligomeric proanthocyanidin protects retinal ganglion cells against oxidative stress-induced apoptosis. Neural Regen Res. 2013 Sep 5;8(25):2317-26. doi: 10.3969 / j.issn.1673-5374.2013.25.002. PMID: 25206541; PMCID: PMC4146041. Khayyal MT, Teaima MH, Marzouk HM, -Hazek RME, Behnam F, Behnam D. Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers. Eur J Drug Metab Pharmacokinet. 2024 Jul;49(4):467-475. doi: 10.1007 / s13318-024-00898-0. Epub 2024 May 15. PMID: 38748358; PMCID: PMC11199261.

[0025] Burri, B.J.; Park, J.Y.K. Compartmental models of vitamin a and β-carotene metabolism in women. Adv. Exp. Med. Biol. 1998, 445, 225-237.

[0027] Ohara K, Shibata Y, Matsumoto K, Hasegawa T, Akimoto M. Bioavailability of Anthocyanin Cyanidin-3-Glucoside from Black Rice (Oryza sativa L.) Extract after Co-Administration with Allyl Isothiocyanate in Rats. J Nutr Sci Vitaminol (Tokyo). 2024;70(6):514-520. doi: 10.3177 / jnsv.70.514. PMID: 39756973.

[0028] QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] DE 202004010212U1 [0009, 0047] DE 000020300305U1 [0010, 0047] US 20110268817A1 [0011, 0047] US 20160151437A1 [0012, 0047] Cited non-patent literature

[0000] Aggarwala KRG. Ocular Accommodation, Intraocular Pressure, Development of Myopia and Glaucoma: Role of Ciliary Muscle, Choroid and Metabolism. Med Hypothesis Discov Innov Ophthalmol. 2020;9(1):66-70. Epub 2020 Jan 5. PMID: 31976346

[0048] Meng ZY, Yang L, Zhou P. Ciliary muscles contraction leads to axial length extension--The possible initiating factor for myopia. PLoS One. 2024 Apr 16;19(4):e0301844. doi: 10.1371 / journal.pone.0301844. PMID: 38626193

[0048] Gazzolo D, Picone S, Gaiero A, Bellettato M, Montrone G, Riccobene F, Lista G, Pellegrini G. Early Pediatric Benefit of Lutein for Maturing Eyes and Brain-An Overview. Nutrients. 2021 Sep 17;13(9):3239. doi: 10.3390 / nu13093239. PMID: 34579116

[0048] Wu H, Chen W, Zhao F, Zhou Q, Reinach PS, Deng L, Ma L, Luo S, Srinivasalu N, Pan M, Hu Y, Pei X, Sun J, Ren R, Xiong Y, Zhou Z, Zhang S, Tian G, Fang J, Zhang L, Lang J, Wu D, Zeng C, Qu J, Zhou X. Scleral hypoxia is a target for myopia control. Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7091-E7100. doi: 10.1073 / pnas.1721443115. Epub 2018 Jul 9. PMID: 29987045

[0048] Mérida S, Villar VM, Navea A, Desco C, Sancho-Tello M, Peris C, Bosch-Morell F. Imbalance Between Oxidative Stress and Growth Factors in Human High Myopia. Front Physiol. 2020 May 14;11:463. doi: 10.3389 / fphys.2020.00463. PMID: 32477165

[0048] Zhang S, Yang J, Reinach PS et al (2018) Dopamine receptor subtypes mediate opposing effects on form deprivation myopia in pigmented guinea pigs. Invest Ophthalmol Vis Sci 59:4441-4448

[0048] Chen S, Zhi Z, Ruan Q et al (2017) Bright light suppresses form-deprivation myopia development with activation of dopamine D1 receptor signaling in the ON pathway in retina. Invest Ophthalmol Vis Sci 58:2306-2316

[0048] Li LH, Lee JC, Leung HH, Lam WC, Fu Z, Lo ACY. Lutein Supplementation for Eye Diseases. Nutrients. 2020 Jun 9;12(6):1721. doi: 10.3390 / nu12061721. PMID: 32526861

[0048] Kizawa Y, Sekikawa T, Kageyama M, Tomobe H, Kobashi R, Yamada T. Effects of anthocyanin, astaxanthin, and lutein on eye functions: a randomized, double-blind, placebo-controlled study. J Clin Biochem Nutr. 2021 Jul;69(1):77-90. doi: 10.3164 / jcbn.20-149. Epub 2021 Feb 5. PMID: 34376917; PMCID: PMC8325772

[0048] Duan H, Song W, Guo J, Yan W. Taurine: A Source and Application for the Relief of Visual Fatigue. Nutrients. 2023 Apr 12;15(8):1843. doi: 10.3390 / nu15081843. PMID: 37111062

[0048] Paduch R, Woźniak A, Niedziela P, Rejdak R. Assessment of eyebright (euphrasia officinalis L.) extract activity in relation to human corneal cells using in vitro tests. Balkan Med J. 2014 Mar;31(1):29-36. doi: 10.5152 / balkanmedj.2014.8377. Epub 2014 Mar 1. PMID: 25207164; PMCID: PMC4115993

[0048] Bigagli E, Cinci L, D'Ambrosio M, Luceri C. Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells. J Photochem Photobiol B. 2017 Aug;173:618-625. doi: 10.1016 / j.jphotobiol.2017.06.031. Epub 2017 Jun 24. PMID: 28704790

[0048] Wang H, Zhang C, Lu D, Shu X, Zhu L, Qi R, So KF, Lu D, Xu Y. Oligomeric proanthocyanidin protects retinal ganglion cells against oxidative stress-induced apoptosis. Neural Regen Res. 2013 Sep 5;8(25):2317-26. doi: 10.3969 / j.issn.1673-5374.2013.25.002. PMID: 25206541

[0048] Khayyal MT, Teaima MH, Marzouk HM, -Hazek RME, Behnam F, Behnam D. Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers. Eur J Drug Metab Pharmacokinet. 2024 Jul;49(4):467-475. doi: 10.1007 / s13318-024-00898-0. Epub 2024 May 15. PMID: 38748358

[0048] Burri, B.J.; Park, J.Y.K. Compartmental models of vitamin a and β-carotene metabolism in women. Adv. Exp. Med. Biol. 1998, 445, 225-237

[0048] Ohara K, Shibata Y, Matsumoto K, Hasegawa T, Akimoto M. Bioavailability of Anthocyanin Cyanidin-3-Glucoside from Black Rice (Oryza sativa L.) Extract after Co-Administration with Allyl Isothiocyanate in Rats. J Nutr Sci Vitaminol (Tokyo). 2024;70(6):514-520. doi: 10.3177 / jnsv.70.514. PMID: 39756973

[0048]

Claims

[1] A trace element supplement consisting of lutein, zeaxanthin, astaxanthin, anthocyanins, and proanthocyanidins is used to improve retinal health in children and adolescents, relieve eye fatigue, and delay the progression of myopia. The daily dose is 1–20 mg lutein, 0.2–4 mg zeaxanthin, 0.5–8 mg astaxanthin, 10–700 mg taurine, and 0.5–8.5 mg zinc; the nighttime dose is 1–100 mg eyebright extract, 10–300 mg chamomile extract, 1–200 mg anthocyanins, and 1–500 mg proanthocyanidins. [2] The composition according to claim 1, wherein the daily dose is 6 mg to 12 mg lutein, 1.2 mg to 2.4 mg zeaxanthin, 0.3 mg to 8 mg astaxanthin, 20 mg to 500 mg taurine and 1 mg to 7 mg zinc; and the night dose is 20 mg to 80 mg eyebright extract, 30 mg to 200 mg chamomile extract, 1 mg to 100 mg anthocyanins and 1 mg to 200 mg proanthocyanidins. [3] The composition according to any of the preceding claims, wherein the daily dose is 8 mg to 10 mg lutein, 1.6 mg to 2 mg zeaxanthin, 0.5 mg to 2.3 mg astaxanthin, 50 mg to 200 mg taurine and 1 mg to 5 mg zinc; and the nightly dose is 30 mg to 50 mg eyebright extract, 50 mg to 100 mg chamomile extract, 1 mg to 50 mg anthocyanins and 1 mg to 100 mg proanthocyanidins. [4] Composition according to any of the preceding claims, wherein the daily dose is 10 mg lutein, 2 mg zeaxanthin, 0.5 mg astaxanthin, 50 mg taurine and 1 mg zinc; the night dose is 30 mg eyebright extract, 100 mg chamomile extract, 10 mg anthocyanins and 10 mg proanthocyanidins. [5] Composition according to any of the preceding claims, wherein lutein and zeaxanthin are derived from natural sources such as marigolds and not from synthetic sources and are preferably microencapsulated. [6] Composition according to any of the preceding claims, wherein the astaxanthin is derived from Haematococcus pluvialis and not from synthetic sources and is preferably microencapsulated. [7] Composition according to any of the preceding claims, wherein the zinc source is preferably an organic zinc source such as zinc gluconate, zinc glycinate or zinc citrate. [8] Composition according to any one of the preceding claims, wherein the anthocyanin source may be one or more commercially available plant anthocyanin extracts such as bilberry (Vaccinium myrtillus), blackcurrant (Ribes nigrum L.), maqui berry (Aristotelia chilensis), blueberry (Vaccinium uliginosum L.) and aronia (Aronia melanocarpa). The anthocyanin content is preferably 36% and the anthocyanin content is preferably 25%. [9] Composition according to any one of the preceding claims, wherein the proanthocyanidin source may be one or more commercially available plant proanthocyanidin extracts such as grape seeds (Vitis vinifera) and pine bark (Pinus pinaster). The purity of the proanthocyanidin must be at least 95%.